Summary of the articles with time series methods (individual or hybrid) for solar radiation/power forecasting.
\r\n\tAn update on clinical manifestations, their assessment, monitoring, and imagiology, including peripheral arthritis, enthesopathy, and extra-articular findings, and, the differential diagnosis with other diseases which evolves with axial and peripheral calcifications will be provided.
\r\n\r\n\t
\r\n\tAn important component of this book must be dedicated to the more recent treatments namely with biologic therapies but focusing also on new small molecule inhibitors and experimental therapies.
Power generation forecasting is the fundamental basis in managing existing and newly constructed power systems. Without having accurate predictions for the generated power, serious implications such as inappropriate operational practices and inadequate energy transactions are inevitable. High penetrations of intermittent renewable energy sources such as wind and solar significantly increase uncertainties of power systems which in turn, complicate the system operation and planning. Accurate forecasting of these intermittent energy sources provides a valuable tool to ease the complication and enable independent system operators (ISOSs) to more efficiently and reliably run power systems.
\nThere are three major methods for wind and solar forecasting; classical statistical techniques, computational intelligent methods, and hybrid algorithms. Each category includes several methods.
\nTime series methods are one of the most commonly used statistical techniques for forecasting. Time series can be defined as “the evolution of a set of observations sampled at regular intervals along time. The specificity of time series models, compared to other statistic methods, is that it introduces ‘time’ as one of its explicative variables” [1]. Time series develop mathematical models that can forecast future observations on the basis of available data. Section below provides definitions and explanations for time series methods commonly in use for forecasting.
\nThis section provides an overview of the most commonly used time series methods for solar and wind forecasting. A brief description is provided for each method along with its mathematical representation.
\nThe autoregressive (AR) model presents a process whose current value can be represented as a linear combination of the past values and a signal noise
where
Unlike the AR model that uses a weighted sum of past values (\n
where
The autoregressive moving average (ARMA) model is developed by combining AR and MA terms to provide a parsimonious parametrization for a process. The ARMA model of orders
where
The auto regressive moving average model with exogenous variables (ARMAX) provides a multivariate time-series representation to enhance the accuracy of the univariate ARMA model by including relevant information in addition to the time-series under consideration. For example, climate information such as cloud cover, humidity, wind speed and direction can be included as exogenous variables in an ARMA model to develop an ARMAX for more accurate forecasting of solar radiation time series. The ARMAX model of orders
where
The autoregressive integrated moving average (ARIMA) model is used for non-stationary time series. Despite representing differences in local trend or level, different sections of non-stationary processes exhibit certain levels of similarity. A stationary ARMA (
where
The autoregressive fractionally integrated moving average (ARFIMA) model is used for long-memory forecasting. ARFIMA generalizes ARIMA by allowing the differencing to take fractional values. An ARFIMA model is given by [5]:
\nwhere powers of
The autoregressive integrated moving average with exogenous variables (ARIMAX) includes the previous values of an exogenous time-series in the ARIMA to enhance its performance and accuracy. It is more applicable to time-series with sudden changes in trends. An ARIMA (
where
The vector autoregressive (VAR) model characterizes linear dependences between two or more time-series. VAR model uses multiple variables to generalize the univariate autoregressive model (AR model). A
where
The autoregressive conditional heteroscedasticity (ARCH) is used for time series with specific variances for the error terms [7].
\nEstimated values are calculated using the following equations [8]:
\nwhere
The generalized ARCH (GARCH) model estimates the values by:
\nBy setting
The performance of the forecast methods is measured by various metrics related to the forecast error. Higher values of errors correspond to less forecast accuracies. This section provides the definitions and equations for performance metrics which are commonly used to calculate the forecast error. Note that
Mean square error (MSE) is calculated by:
\nNormalized mean square error (NMSE) is calculated by normalizing the MSE as:
\nRoot mean square error is given by calculating the square root of the MSE as:
Normalized root mean square error (NRMSE) is calculated by normalizing the RMSE as:
Mean absolute error is calculated by:
Normalized mean absolute error (NMAE) is calculated by normalizing the MAE as:
Mean relative error (MRE) is calculated by:
Mean bias error (MBE) is calculated by:
Mean absolute percentage error is calculated by:
Mean absolute scaled error is calculated by:
Mean square percentage error is calculated by:
Time series methods have been extensively used to forecast solar radiation/power and wind speed/power. Typically, solar and wind data exhibit features such as non-linearity and non-stationarity which cannot be captured by most of the time series methods. To address this limitation, these methods are used in combination with other computational intelligent or data processing methods to take advantage of their capabilities to better characterize wind and solar data for more accurate forecasting. These combinations are referred to as hybrid methods which are proven effective for renewables forecasting.
\nThis section provides a review of the articles that use time series methods individually or in hybrid algorithms for solar radiation/power forecasting. The literature review provides a summary of the solar-related variable that is predicted, the horizon for which the variable is predicted, the performance metrics in use to calculate the forecast error, the time series methods and data in use, and the research findings of each article. Table 1 provides the summary.
\nReferences | \nForecast variable | \nForecast horizon | \nError metric | \nTime series method | \nData | \nFinding | \n
---|---|---|---|---|---|---|
[9] | \n5, 15, 30, and 60 min averaged global horizontal irradiance (GHI) | \n5 min to several hours | \nMAPE | \nRegressions in logs, ARIMA, and hybrid (ARIMA and ANN) | \n4 years of hourly GHI data for three locations in USA | \nARIMA can obtain better results if used in logs with time varying coefficients | \n
[10] | \nDaily GHI | \n1 day | \nRMSE, NRMSE, MAE, and MBE | \nAR, ARMA | \n19 years of daily GHI from the metrological station of Ajaccio, France | \nAR and ANN models perform better than other prediction methods (ARMA, k-Nearest Neighbors, Markov Chains, etc.), if the time-series data is not pre-processed | \n
[11] | \nHourly GHI | \n1 h | \nMBE and RMSE | \nARIMA | \nMeteorological data including GHI, diffuse horizontal irradiance (DHI), direct normal irradiance (DNI) and cloud cover from two weather stations in USA (Miami and Orlando) | \nCloud cover information yields to more accurate forecasting | \n
[12] | \nHalf daily values of GHI | \nUp to 3 days | \nNRMSE | \nAR | \nHourly GHI measurements from stations of the Spanish National Radiometric Network | \nNeural network models obtain better results for almost all stations except for Lerida station where the clearness index-based models outperform | \n
[13] | \nHourly solar irradiance | \n1 h | \nRMSE, and NRMSE | \nNaive, ARMA | \n144 months of hourly solar irradiance of the Paris suburb of Alfortville | \nARMA model has competitive results as compared to similarity method (SIM), support vector machine (SVM) and neural network (NN) | \n
[14] | \nHourly solar radiation | \n1 h | \nRMSE, and NRMSE | \nHybrid (ARMA and time delay neural network (TDNN)) | \n10 months of solar radiation data from the observation station in Nanyang Technological University | \nThe combination of the ARMA and TDNN provides more accurate results than each individual forecaster | \n
[15] | \nDaily average of solar irradiance | \n1–15 h | \nMAPE | \nARIMA | \nSolar irradiance data from a 4.0 kW PV panel in the city of Awali, Kingdom of Bahrain | \nARIMA models are proved to effectively capture the auto-correlative structure of the solar irradiance | \n
[16] | \nDaily solar irradiance and surface air temperature | \n1 day | \nNA | \nARIMA | \nSolar irradiance and surface air temperature data from 10 meteorological stations in Europe and 4 stations in Asia | \nVarious climate time series are dependent on long-range variability of solar irradiance | \n
[17] | \nHourly solar power from PV systems | \n1 h up to 36 h | \nRMSE | \nAR, AR with exogenous input (ARX), RX (regressive model with no endogenous variables) | \n1 year of solar power observations from 21 PV systems in Denmark | \nARX model with both solar power observations and numerical weather predictions (NWPs) as the input outperforms the AR model for forecast horizons longer than 2 h ahead | \n
[18] | \nHourly GHI, DHI and DNI | \n1 h | \nRMSE, and MBE | \nAR | \n5 min GHI data from Jeddah, Saudi Arabia for a five-year interval | \nUsing sunshine duration, relative humidity and air temperature as the inputs result in the most accurate forecast by the developed adaptive model | \n
[19] | \nMonthly average solar radiation | \n1 month | \nRMSE | \nLinear regression (LR) | \nDaily GHI and meteorological data in Darwin, Australia from 2000 to 2011 | \nLR obtains the best predictions compared to Angstrom-Prescott-Page (APP) and ANN models | \n
[20] | \nHourly PV power | \n1 and 2 h | \nMAE, MBE, RMSE, and NRMSE | \nARIMA | \nHourly average power of a 1 MW PV power plant located in Merced, California collected between November 2009 and August 2011 | \nANN-based forecasting models including the ANN and GA-optimized ANN obtain better predictions than Persistent, ARIMA and k-NN models | \n
[21] | \nHourly GHI | \n1 h | \nNRMSE | \nHybrid (ARMA and ANN) | \n6 years of hourly solar radiation and meteorological data from five locations in the Mediterranean area in France | \nCombining ARMA and ANN enhances the forecast accuracy | \n
[22] | \nHourly solar irradiation | \n24 h | \nNRMSE | \nARMA | \n2 years of meteorological data from Ajaccio, France | \nANN outperforms the ARMA by 1.3 points reduction in the error estimate | \n
[23] | \nDaily GHI | \n1 day | \nRMSE, NRMSE, MAE, and MBE | \nAR, ARIMA | \n30 min global solar radiation data in Corsica Island, France from January 1998 to December 2007 | \nAn ANN with exogenous and endogenous data outperforms univariate forecasters such as ARMA models | \n
[24] | \nSolar irradiance | \n12 h | \nRMSE, and MASE | \nHybrid (ARIMA-Back Propagation) | \nHourly solar irradiance observations from National Solar Radiation Data Base (NSRDB) site between 2008 and 2009 | \nThe hybrid ARIMA-BP does not outperform ARIMA | \n
[25] | \nSolar power | \n1 min | \nMAE, MSE, and MAXE | \nHybrid (Wavelet, ARMA, and Nonlinear Autoregressive model with exogenous variables (NARX)) | \n1 min solar power data from the solar panel at UCLA for nearly 200,000 observations | \nCapability of the ARMA process to model the linear features of the data and the NARX advantage to compensate the error of Wavelet-ARMA enhances the forecast accuracy of the hybrid Wavelet-ARMA-NARX method | \n
[26] | \nSolar generation | \n1–5 h | \nMAE, and MSE | \nARMA | \n14 years of hourly solar radiation data from SolarAnywhere | \nARMA outperforms the persistence model for short and medium term solar predictions | \n
[27] | \nHourly solar irradiance | \n1 h and 3 h | \nRMAE | \nHybrid (non-linear regression and PR) | \nSolar radiation data from sensors, and National Digital Forecast Database, as well as the meteorological measurements from local airports in Los Angeles region | \nThe hybrid method excels the benchmark methods including the regression, ARIMA and ANN by 40% and 33.33% for 1-h and 3-h ahead, respectively | \n
Summary of the articles with time series methods (individual or hybrid) for solar radiation/power forecasting.
This section provides a review of the articles that use time series methods individually or in hybrid algorithms for wind speed/power forecasting. The literature review provides a summary of the wind variable that is predicted, the horizon for which the variable is predicted, the performance metrics in use to calculate the forecast error, the time series methods and data in use, and the research findings of each article. Table 2 provides the summary.
\nReferences | \nForecast variable | \nForecast horizon | \nError metric | \nTime series method | \nData | \nFinding | \n
---|---|---|---|---|---|---|
[28] | \nHourly average wind Speed | \n1 h | \nNA | \nARMA | \n2 years of wind speed data from Quetta in Pakistan | \nARMA is more appropriate for prediction intervals and probability forecasts | \n
[29] | \nWind power density | \n1–10 days | \nMAE, and RMSE | \nAR-GARCH, ARFI-GARCH | \nDaily midday wind speed measurements from 1995 to 2004, as well as weather ensemble predictions from 1997 to 2004 for five wind farms in UK | \nWeather ensemble-based forecasters are shown to perform better than time series models and atmospheric-based models | \n
[30] | \nMean hourly wind speed | \n1 h | \nRMSE | \nAR, and ARIMA | \n744 hours of wind speed measurements in Odigitria of the Greek island of Crete in March 1996 | \nThe neural logic-based models perform better than the time series methods | \n
[15] | \nDaily average of wind speed | \n1–15 h | \nMAPE | \nARIMA | \nWind speed data from a 1.7 kW wind turbine in the city of Awali, Kingdom of Bahrain | \nARIMA models are proved to effectively capture the auto-correlative structure of the wind speed | \n
[31] | \nWind speed | \n3 h | \nRMSE | \nAR | \nWind speed data measured every 3-h in three Mediterranean sites in Corsica | \nAR is sufficient to simulate 3-h wind speeds | \n
[32] | \nWind speed | \n1, 2 and 3-step(s) | \nMAE, MAPE and MSE | \nHybrid (Wavelet Packet-ARIMA-BFGS (Broyden-Fletcher-Goldfarb-Shanno)) | \nHalf-hourly wind speed measurements from 20 December 2011 to 5 January 2012 in Chinese Qinghai wind farm | \nThe ARIMA models have better time performance than the ANN models in approximating wind speed time series while providing a little lower accuracy | \n
[33] | \nHourly mean wind speed and direction | \n1 h | \nMAE | \nARMA, and VAR | \nHourly average wind data from May 1 to October 21, 2002 in two wind sites in North Dakota, USA | \nARMA forecasts the wind speed better than the component model whereas the opposite is observed for wind direction forecasting | \n
[34] | \nWind power | \n3 h | \nMAPE, and NMAE | \nARIMA | \nWind power data in Portugal | \nThe ARIMA model is used as a benchmark to evaluate the performance of the proposed hybrid Wavelet-PSO-ANFIS forecasting method | \n
[35] | \nWind speed | \n1–24 h | \nMAE, and RMSE | \nAR, ARX, ARX-GARCH, Hybrid (ARX-TN (truncated normal), ARX-GARCH-TN) | \n3 years of hourly wind speed observations from a meteorological station in Denmark, as well as wind speed predictions based on a NWP model from the Danish Meteorological Institute | \nThe time series models are used as benchmark methods to evaluate the performance of the developed stochastic differential equation for probabilistic wind speed forecasting | \n
[36] | \nWind speed/power | \n1–24 h | \nMAE, MBE, RMSE, MASE NMBE, NMAE, and NRMSE | \nAR, ARMA, and ARIMA | \nWind speed, wind direction, humidity, solar radiation, temperature, atmospheric pressure, and heat radiation data from two anemometric measuring towers in La Ventosa, Mexico | \nResults show that the developed method based on support vector regression is more accurate than the persistence and autoregressive models | \n
[37] | \nWind speed/power | \n1 and 2 day(s) | \nDaily mean error (DME) | \nfractional-ARIMA ( | \n4 weeks of hourly average wind speed data from four wind monitoring sites in North Dakota | \nThe proposed | \n
[38] | \nAverage hourly wind speed | \n1 h | \nME, MSE, and MAE | \nHybrid (ARIMA-ANN) | \n1 month of wind speed measurements in three regions of Mexico | \nThe combination of ARIMA and ANN predicts the wind speed with more accuracy than the individual ARIMA and ANN | \n
[39] | \nWind speed | \n1 day | \nMAPE | \nHybrid (KF-ANN model based on ARIMA) | \nDaily wind speed observations from two meteorological stations in Mosul, Iraq and Johor, Malaysia | \nThe ARIMA model provides inaccurate wind speed forecasts due to its limitation to capture the nonlinearity of the wind speed patterns | \n
[40] | \nWind speed | \n1, 2 and 3-step(s) | \nMAE, MSE, and MAPE | \nHybrid (ARIMA-ANN and ARIMA-Kalman) | \nHourly wind speed measurements from a station | \nBoth hybrid methods can obtain accurate forecasts and are appropriate for non-stationary wind speed datasets | \n
[41] | \nWind speed | \n1 h | \nNA | \nARMA-GARCH | \n7 years of hourly wind speed data from an observation site in Colorado, USA | \nThe ARMA-GARCH model is proved efficient in capturing the trend change of wind speed mean and volatility over time | \n
[42] | \nHourly average wind speed | \n1 h up to 10 h | \nRMSE | \nARMA | \n9 years of hourly wind speed data of five locations in Navarre, Spain | \nFor longer term forecasting, the ARMA models with transformed and standardized data perform better than the persistence model | \n
[43] | \nWind speed | \n1 month | \nMSE, MAE, and MAPE | \nARIMA | \n7 years of wind speed measurements from the South Coast of Oaxaca, Mexico | \nARIAM models provide more sensitivity than the ANN methods to the adjustment and prediction of the wind speed | \n
[44] | \nWin speed | \n1–6 min(s), and 1–6 hour(s) | \nMAE, and MAPE | \nHybrid (Empirical mode decomposition (EMD)-Least squares support vector machines (LSSVM)-AR) | \n1 year of wind speed data measurements in Beloit, Kansas, USA | \nThe proposed hybrid approach is proved more accurate than the existing forecasting approaches | \n
[45] | \nWind speed/power generation | \n1 h | \nMAE, and RMSE | \nHybrid (ARIMA-ANN/SVR) | \n2 years of hourly wind data from a 1.5 MW wind turbine in North Dakota, USA | \nThe hybrid approaches are practical for both wind speed and power forecasting but not the best for all the forecasting time horizons | \n
[46] | \nWind speed | \n15 min | \nMAPE, MSPE, and MAE | \nUnivariate and multivariable ARIMA | \nWind speed data from the Wind Engineering Research Field Laboratory (WERFL) at five different heights at Texas Tech University | \nMultivariate models are more accurate than the univariate models and they are both less accurate than the recurrent neural network models | \n
Summary of the articles with time series methods (individual or hybrid) for wind speed/power forecasting.
This chapter provides a comprehensive literature review to demonstrate the application of time-series methods for renewable energy forecasting. In spite of recent developments in intelligent methods and their extensive applications for more accurate solar energy/wind power forecasting, our literature review concludes that time-series methods, individually or in combination with intelligent methods, are still viable options for short-term forecasting of intermittent renewable energy sources due to their less computational complexities.
\nNon-alcoholic fatty liver disease (NAFLD) is currently the most prevalent chronic liver disease worldwide [1]. A subset of NAFLD patients have the progressive form of NAFLD termed non-alcoholic steatohepatitis (NASH). NASH is typically characterized by a specific pattern on liver histology, including steatosis, lobular inflammation, and ballooning with or without perisinusoidal fibrosis [2]. It can progress to advanced fibrosis, cirrhosis, hepatocellular carcinoma, and liver-related morbidity and mortality. Liver disease is only the third leading cause of death in patients with NAFLD, following cardiovascular disease and malignancy [3].
Precise histological diagnosis of NAFLD is commonly based on liver biopsy [4]; however, biopsies present several potential problems [5]. Thus, there is a need for reliable and cost-effective noninvasive biomarkers to avoid the invasiveness of biopsy [6].
Although there are some clinical strategies to ameliorate NAFLD progression, such as treatments for obesity or type 2 diabetes mellitus (T2DM), there is no medication proven to be effective as a treatment for NASH [7]. Therefore, it is necessary to improve the research on possible therapeutic targets for NASH due to the severity of this pathological condition.
Previous evidences have linked gut dysbiosis with obesity, insulin resistance (IR), metabolic syndrome (MS), and NAFLD [8, 9]. The impact of the GM on NAFLD/NASH has been attributed to increased gut permeability, intestinal endotoxemia, endogenous alcohol production, upregulation of hepatic de novo lipogenesis and triglyceride synthesis, reduction in choline metabolism, and aggravation of IR [10]. The increased permeability of the intestinal barrier results in the release of substances such as lipopolysaccharides (LPS), bacterial components, short-chain fatty acids (SCFAs), bile acids (BAs), choline metabolites, and endogenous ethanol that reach the liver and seem to contribute to the pathogenesis of NAFLD (Figure 1) [11, 12]. It is important to note that some of these substances could perhaps be employed as potential noninvasive biomarkers of NAFLD progression.
Implication of intestinal dysbiosis in NAFLD pathogenesis. Short-chain fatty acids (SCFAs), bile acids (BAs), lipopolysaccharides (LPS), trimethylamine-N-oxide (TMAO), ethanol (EtOH), non-alcoholic fatty liver (NAFL), and non-alcoholic fatty liver disease (NAFLD).
Manipulation of the microbiota through probiotics, prebiotics, and antibiotic treatment yields encouraging results for the treatment of obesity, T2DM, and NASH in animal models, but data in humans are scarce. In regard to NAFLD, this therapeutic strategy seeks to prevent the endotoxicity produced by the microbiota-derived metabolites that reach the liver and promote the progression of the disease [13]. Thus, there is a need to focus research on the GM as a therapeutic target to ameliorate NASH.
To provide a broad overview of the relationship between intestinal dysbiosis and NAFLD, we have elaborated on this subject in this book chapter. In this sense, this narrative chapter will explain (a) non-alcoholic fatty liver disease, (b) the gut microbiota, (c) gut microbiota-derived mediators involved in NAFLD, and (d) the gut microbiota as a therapeutic target in NAFLD.
NAFLD has emerged as the most common form of chronic liver disease worldwide. The incidence of NAFLD has drastically increased in parallel with obesity in recent years. Currently, the global prevalence of NAFLD is approximately 25% [1], but it can increase to 58% in individuals who are overweight or as high as 98% in individuals with nondiabetic morbid obesity [14].
NAFLD comprises a spectrum of disorders extending from simple steatosis (SS) to NASH, fibrosis, and cirrhosis [2, 15]. This pathology has potentially serious sequelae [16]. Although SS tends to develop into a favorable clinical course [3], NASH can develop into liver cirrhosis and hepatocellular carcinoma [15]. Thus, liver-related mortality increases exponentially with an advance in the fibrosis stage [17]. In this regard, NASH is a very common cause of liver transplant worldwide [1]. Although the most common cause of death in patients with NAFLD is cardiovascular disease, independent of other metabolic comorbidities, NAFLD is becoming a major cause of liver disease-related morbidity (e.g., cirrhosis, end-stage liver disease, hepatocellular carcinoma, and liver transplantation).
NAFLD is characterized by significant lipid deposition in the hepatocytes of the liver parenchyma [18]. Obesity, T2DM, dyslipidemia, MS, and IR are the main risk factors for NAFLD [19]. Most NAFLD patients are asymptomatic, and the evidence of hepatic steatosis should be detected via a routine blood test, showing a deregulation in liver enzymes. Currently, it is not possible to diagnose NAFLD with only a blood test, but the aspartate aminotransferase (AST)-alanine aminotransferase ratio (ALT) can be used as a first step [20, 21, 22]. However, the ALT level correlation with histological findings has poor sensitivity and specificity for the diagnosis of NASH [23]. Then, it is necessary to rule out other causes of liver damage, such as alcoholic fatty liver disease, drug-induced liver injury, viral hepatitis, autoimmune liver disease, hemochromatosis, celiac disease, and Wilson’s disease [1]. Finally, ultrasonography is the most common noninvasive tool used to detect NAFLD. There are also other imaging techniques used to detect liver steatosis, such as computer tomography or magnetic resonance imaging, but ultrasound is the technique that provides the most information without irradiation [24, 25].
One-third of the NAFLD-affected subjects progress to NASH. This condition is characterized by the presence of hepatocellular ballooning and inflammation and has a prevalence of 2–3% worldwide [2]. Key issues in NAFLD patients are the differentiation of NASH from SS and the identification of advanced hepatic fibrosis. To date, liver biopsy has been the
Regarding NAFLD therapeutics, all forms of treatment of metabolic disorders are able to modify liver damage. Diet and lifestyle modification and insulin-sensitizing agents appear to be promisingly effective against NAFLD progression. However, these approaches may not be effective in some patients. Many other drugs are currently being studied to establish treatments for NAFLD. At present, no accepted drug treatment for NASH has been stated [24]. In this sense, it is very important to improve the knowledge of NAFLD physiopathology. Actually, the underlying precise mechanisms of NAFLD pathogenesis have just begun to be understood. The classic “multiple hit” theory states that lipid accumulation initiates hepatic steatosis and subsequently triggers multiple insults acting together (hormones/adipokines from adipose tissue, inflammation, deregulated fat metabolism, lipotoxicity, oxidative stress, mitochondrial dysfunction, and genetic and epigenetic factors), ultimately inducing NASH and cirrhosis [27]. Progression to NASH is linked to systemic inflammation, and it is associated with other pathological processes, such as innate immunity alterations, endoplasmic-reticulum stress, toll-like receptor (TLR) signaling, mitochondrial dysfunction, and intestinal dysbiosis [6, 28, 29, 30, 31, 32]. Regarding this last process, approximately 70–75% of blood that reaches the liver comes from the portal vein circulation that communicates the liver with the intestine [33]. The liver is continually exposed to GM-derived mediators, including bacteria and bacterial components, such as LPS, promoting an inflammatory response that contributes to liver injury [13].
Millions of symbiotic microorganisms live on and within human beings and play an important role in human health and disease. Initial colonization occurs at the time of birth, and humans progressively acquire ∼1014 bacterial cells at equilibrium, which remain for life [13].
The human microbiota, especially the GM, has even been considered to be an “essential organ,” carrying approximately 150 times more genes than the human genome [34]. The GM is composed of an immense number of microorganisms (bacteria, viruses, and fungi) with several functions, such as host nutrition, bone mineralization, immune system regulation, xenobiotic metabolism, proliferation of intestinal cells, and protection against pathogens [35, 36]. This bacterial community is dominated by anaerobic bacteria and includes 500–1000 species [37].
The duodenum and proximal jejunum normally contain small numbers of bacteria, usually lactobacilli and enterococci, which are facultative anaerobes. The distal ileum is a transition zone between sparse populations of aerobic bacteria of the proximal small intestine and very dense populations of anaerobic microorganisms in the large bowel. Occasional groups of bacteria can be found in low concentrations within the lumen of the small intestine. Bacteria do not form clusters, and the luminal contents are separated from the mucosa by a mucus layer [13].
The GM is specific to an individual and highly resilient to changes. However, it can be affected by several factors, intrinsic and extrinsic to the host, such as the subject’s genetic makeup, dietary habits, antibiotic use, and environmental changes [13, 39, 40]. A disruption in the composition of the normal GM is known as intestinal dysbiosis [41, 42]. Generally, this process includes an unfavorable change in the bacterial composition, with a reduction in autochthonous bacteria and growth of others that prejudice host health [43].
Intestinal dysbiosis is a process that may adversely impact metabolism and produce immune responses, favoring NAFLD progression. Important studies on the relationship of the GM with obesity have identified profound changes in the composition and metabolic function of the GM in subjects with obesity. Moreover, these studies demonstrated that the GM interacts with host epithelial cells to indirectly control energy expenditure and storage and activate inflammatory responses in NASH pathogenesis [44]. Qualitative or quantitative imbalances in the GM might have serious health consequences for the host, including small intestinal bacterial overgrowth (SIBO) syndrome [13]. Due to gut dysbiosis, there is an elevated production of toxic bacterial components and metabolic mediators, which consequently accumulate in the intestine. In addition, an increase in intestinal permeability and further disruption of the epithelial barrier lead to the release of these GM-derived mediators [42], which could reach the liver through portal circulation, favoring hepatic inflammation and the development of NAFLD [45, 46]. After disruption of the gut epithelial barrier, the liver is exposed to microbial products and metabolites resulting from bacterial metabolism [47, 48]. In this sense, it has been demonstrated that patients with NAFLD have gut dysbiosis, gut epithelial barrier dysfunction, and increased translocation of bacterial components to the liver [49]. For this reason, mediators derived from gut dysbiosis might also be related to the pathogenesis of the disease. Several previous studies in clinical settings have associated intestinal dysbiosis with the occurrence of NAFLD [50, 51, 52] and with the progression to NASH [10, 53].
Among the various factors, dietary habits are considered to be most influential on the gut microbiome in subjects with obesity and NAFLD patients. It is well-known that a high-fat diet causes gut dysbiosis characterized by lowered species richness and changes in microbial composition, such as decreased
GM-derived mediators resulting from intestinal dysbiosis could play a key role in NAFLD progression through several mechanisms: (1) enhanced energy extraction from food nutrients by formation of SCFAs; (2) modulation of BA synthesis, which is crucial for fat absorption and affects metabolism of glucose via farnesoid X receptor (FXR); (3) innate immune system activation by bacterial component translocation; (4) endogenous ethanol production; and (5) reduction in choline metabolism, which reduces efflux of very-low-density lipoprotein (VLDL) from hepatocytes, promoting inflammation. These mechanisms involve translocation of these mediators, such as SCFAs, BAs, endogenous ethanol, and choline metabolites, which may be potentially evaluated as noninvasive blood markers of NAFLD progression [59].
SCFAs are molecules with seven carbon atoms or less, for example, acetic, propionic, and butyric acids, that are produced by the gut bacterial fermentation of cellulose, xylans, resistant starch, or inulin since humans lack enzymes that digest fibers. These substances can strongly regulate host metabolism [60]. In general, these SCFAs have several effects on energy metabolism, the immune response, and adipose tissue expansion and act as signaling molecules between the GM and the host. SCFAs provide not only important sources of nutrients and energy for the intestinal epithelium but also serve as precursors for lipogenesis and gluconeogenesis [61, 62]. SCFAs can directly act as lipid precursors in the liver and mediate other effects as ligands for G protein-coupled receptors, specifically the subtypes GPR41 and GPR43 [59]. Experimental studies have demonstrated that these SCFAs can modulate regulatory T-cell expansion and enhance neutrophil chemotaxis, promoting inflammation in mouse models [63, 64, 65, 66]. Furthermore, SCFAs modulate the production of several inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin 2 (IL-2), interleukin 6 (IL-6), and interleukin 10 (IL-10) [67]. Recently, some studies found that high concentrations of intestinal SCFAs as a result of dysbiosis and their G-protein coupled receptors play an important role in NAFLD progression [68, 69]. Activation of GPR41 and GPR43 stimulates secretion of peptide-YY, inhibits gut motility, and slows intestinal transit. Therefore, nutrient absorption and energy capture from the diet increase and may promote hepatic lipogenesis [56, 70]. Additionally, activation of GPR41 and GPR43 induces secretion of glucagon-like peptide-1 (GLP-1), which activates genes in hepatocytes that regulate fatty acid β-oxidation and insulin sensitivity [56, 71], promoting NAFLD occurrence and progression. Furthermore, clinical studies have demonstrated SCFA enrichment in fecal samples of children and adults with NAFLD [72, 73].
However, other previously published studies have reported that SCFAs could be beneficial in the progression of NAFLD. In this regard, butyrate activates AMP-activated protein kinase (AMPK) in the liver and accelerates the assembly of tight junction proteins [74, 75], improving intestinal barrier dysfunction and reducing metabolic endotoxemia. In addition, butyrate is able to modulate regulatory T-cell activity, suppressing the immune response and reducing liver inflammation [76].
The close relationship between intestinal dysbiosis and SCFA production, according to the results of previous experimental and clinical studies, provides evidence of their potential use as markers of NAFLD progression. In this sense, in a recent study, we studied this possibility, but we failed to demonstrate any relationship between circulating SCFA levels and histological degrees of NAFLD in a cohort of patients with morbid obesity [6]. However, additional studies are necessary to accurately determine the specific role of SCFAs in NAFLD.
As previously mentioned, the gut-liver axis, which involves gut hormone release and the immune response, is essential to regulate systemic metabolism. BAs participate in communication along this axis. They are steroid-derivative components of bile synthesized after cholesterol oxidation by enzymes present in hepatocytes, and they are involved in the absorption of lipids and vitamins in bile salt-dependent flow regulation. BAs participate in the digestion and solubilization of lipids and regulate hepatic glucose and inflammation [59, 60]. Moreover, they are capable of controlling their own synthesis through the activation of FXR [77, 78]. In addition, BAs act as signaling molecules that modulate several physiological processes, and GM dysbiosis can change BA pool characteristics through its effects on BA metabolism [78, 79].
The GM is a critical modulator of BA pool size and composition, and the process of dysbiosis could substantially alter concentrations of conjugated and/or secondary bile acids, as well as increase their synthesis.
Unmodified BAs, also called primary BAs (cholic acid (CA) and chenodeoxycholic acid (CDCA)), undergo a deconjugation process by GM components after reaching the colon and become secondary BAs, such as deoxycholic acid (DCA) and lithocholic acid (LCA); they can be transported again to the liver via the portal vein in a mechanism called “enterohepatic circulation.” BAs prevent the overgrowth of bacteria in the gut to maintain gut homeostasis. This protective effect is mediated by their detergent properties and the activation of FXR, which protects the distal small intestine from bacterial proliferation. It is recognized that these circulating BAs, in addition to the abovementioned functions, can coordinate a wide number of pathways mediated by specific nuclear receptors (NRs) [60].
The increased intestinal permeability associated with BA modifications has been linked to metabolic endotoxemia, IR, and inflammatory cytokine release with enhanced proinflammatory signaling cascades, which are common findings in patients with NAFLD [59]. An increased level of BAs causes activation of the cell death pathway mediated by inflammatory and oxidative stress cascades in liver tissue [80, 81].
Regarding hepatic lipid metabolism, Watanabe et al. demonstrated that hepatic FXR activation mediated by BAs could induce the expression of the atypical NR small heterodimer partner (SHP), which promotes the inhibition of sterol-regulatory element-binding protein-1c (SREBP-1c), thus reducing hepatic synthesis of triglycerides. In addition, FXR can limit lipid accumulation in the liver by promoting fatty acid oxidation after the activation of peroxisome proliferator-activated receptor alpha (PPARα) and by the induction of plasma VLDL-triglyceride clearance [82, 83, 84, 85]. FXR activation in the liver was also demonstrated to coordinate glucose homeostasis via the inhibition of gluconeogenesis and glycolysis. Interestingly, the activation of FXR in the intestine can generate crucial endocrine feedback regulation [86]. Experimental studies have demonstrated that intestinal dysbiosis can modulate the activity of FXR in the intestine, affecting lipid metabolism in the liver [4]. Specifically, FXR not only plays an important role in maintaining BA levels but also regulates glucose and lipid metabolism via different mechanisms, such as increasing insulin sensitivity, repressing hepatic gluconeogenic genes, and increasing hepatic glycogen synthesis [87, 88].
Previous investigations have demonstrated a BA level increase in the biological fluids of patients with NASH compared to that in the biological fluids of subjects with healthy livers and an evident association with intestinal dysbiosis [89, 90, 91]. Additionally, the levels of BAs have been correlated with histopathological features, such as the degree of hepatic steatosis, the presence of cellular ballooning, and the severity of fibrosis in patients with NASH [92]. These studies confirmed the disruption in BA homeostasis in NASH physiopathology [65] and the correlation of BAs with NASH severity parameters (portal inflammation, lobular inflammation, and hepatocyte ballooning) [93]. In children with NAFLD, changes in the circulating BA profile have also been reported. Troisi et al. demonstrated that serum BA levels decrease in early NAFLD and increase during progression to fibrosis in obese children. These authors postulated that BAs may have value as a noninvasive biomarker in pediatric NAFLD progression [83, 94]. In a previous study by our research group, we found that FXR jejunal expression was lower in NASH patients than in normal liver (NL) subjects; in regard to BAs, we also found that levels of glycolic acid (GCA), a primary BA, and DCA, a secondary BA, were significantly higher in NAFLD patients than in NL subjects [6].
Considering the numerous published experimental and clinical studies associating gut dysbiosis, BAs and NAFLD, it is expected that BAs could be proposed as potential noninvasive markers of the disease. For example, Svegliati-Baroni et al. specifically proposed DCA and LCA, which can only be produced by bacterial fermentation [95].
The liver is exposed to potentially harmful substances derived from the gut, considered pathogen-associated molecular patterns (PAMPs), that include translocated bacteria, LPS, bacterial DNA, bacterial RNA, and endotoxins, which are potent inducers of tissue inflammation [41, 96]. These PAMPs might contribute to the pathogenesis of NAFLD by activating the innate immune system via TLRs, which recognize these gut-derived bacterial components. The healthy liver expresses low mRNA levels of TLRs (TLR1, TLR2, TLR4, TLR6, TLR7, TLR8, TLR9, and TLR10), implying a high tolerance of the liver to TLR ligands from the microbiota. The translocation of these bacterial components from the gut into the portal system is facilitated by intestinal barrier disruption due to GM dysbiosis [13, 96]. In this sense, there is evidence that dysbiosis causes permeability changes that increase portal levels of gut-derived TLR ligands (LPS or endotoxin), which further activate TLR4 on hepatic Kupffer and stellate cells [97]. LPS is the major structural component of gram-negative bacteria and the major component of endotoxin. LPS may be recognized by LPS-binding protein (LBP) in serum and is the major activator of the innate immune response [98]. Ruiz et al. indicated that the serum levels of LBP were increased in patients with obesity and NASH compared to those in patients with obesity and SS and the increased serum LBP level was correlated to an upregulated expression of TNF-α in liver tissue [99].
During TLR4 activation, the adaptor molecule myeloid differentiation factor 88 (MyD88) is activated, and the downstream signaling MyD88-dependent pathway results in the activation of necrosis factor kappa beta (NF-κB), leading to the expression of proinflammatory cytokines (TNF-α, IL-6, IL-8 and IL-12) and chemokines (interferon γ (IFN-γ) and monocyte chemotactic protein-1 (MCP-1)), promoting inflammation [68, 97]. There are several intracellular cascades involved in this process, generating oxidative stress, low-grade systemic inflammation, and hepatic injury [100]. In addition, TLR signaling can also lead to the production of inflammasomes in peripheral and parenchymal cells, which activate a variety of processes, including activation of caspase-1, resulting in cell death [101].
The inflammasome, which is a multimeric signaling platform that leads to the production of IL-18 and IL-1β through the NOD-like receptors pyrin domain-containing (NLRP3 and NLRP6), is activated by LPS derived from intestinal dysbiosis via TLR4 and TLR9 responses. Reports have associated inflammasome activation with the development of liver steatosis, inflammation, and fibrosis in NAFLD patients [102, 103].
It has been shown that TLR2, TLR4, and TLR9 play an important role in the development of NASH [104]. In addition, other studies have established that the increase in endotoxin levels is related to IL-1α and TNF-α production [105, 106]. In patients with NAFLD, gut permeability and SIBO due to intestinal dysbiosis have been associated with the severity of steatosis [107]. In biopsy-proven human NASH, plasma levels of IgG against endotoxin were found to be increased with NASH grade severity, suggesting the deleterious effect of chronic endotoxin exposure [108]. In our previous GM-derived metabolite study, we found overexpression of TLR9 jejunal expression in NAFLD subjects, which suggested the activation of the immune system during NAFLD progression [6]. Additionally, enhanced expression of TLR4, the release of IL-8, and high levels of LPS have been demonstrated in NAFLD patients [109, 110]. However, other reports did not reveal an association between endotoxemia and NAFLD progression, suggesting that endotoxemia may not be the only driver of disease development in all patients [111].
Multiple experimental studies have demonstrated that a high-fat diet can increase the proportion of LPS derived from the GM, and administration of endotoxin has been shown to induce IR and weight gain [99, 112]. On the other hand, some authors have recently proposed that the small intestine shields the liver from otherwise toxic fructose exposure via the GM [113].
There is a clear relation between gut dysbiosis, bacterial-derived components, the inflammatory response, and NAFLD; therefore, these bacterial mediators, especially circulating TLRs, might be used as potential noninvasive markers of disease progression.
Intestinal dysbiosis increases endogenous ethanol production [111], which also affects gut permeability, disrupting intestinal tight junctions. This process allows endotoxins and ethanol to reach the liver and trigger the TLR response and inflammasome activation, contributing to liver damage [114]. In addition to the proinflammatory response, ethanol promotes oxidative stress and hepatocyte necrosis because of the formation of reactive oxygen and nitrogen species [94]. Endogenous ethanol inhibits the tricarboxylic acid cycle, thus increasing levels of acetate and thereby promoting triglyceride accumulation in hepatocytes [64]. Ethanol can also increase the activity of the enzyme cytochrome P450 2E1 (CYP2E1), which catalyzes the oxidation of ethanol but produces free radicals favoring oxidative damage, mitochondrial dysfunction, and liver inflammation [94, 115, 116].
Several studies have detected increased levels of non-dietary ethanol derived from bacteria in patients with obesity [111, 117] and in patients with NASH [111, 118, 119]. In this sense, Zhu et al. proposed that microbiomes rich in ethanol-producing
Furthermore, Zhu et al. showed an increased abundance of alcohol-producing bacteria in NASH microbiomes, elevated blood-ethanol concentration in NASH patients, and the well-established role of alcohol metabolism in oxidative stress and liver inflammation [56]. In our previous GM-derived metabolite study, we found an interesting result about the higher circulating endogenous ethanol levels in NASH patients than in patients with SS. This fact suggested that circulating ethanol levels could distinguish between different degrees of liver damage. Moreover, in the same study, we evaluated the diagnostic efficacy of a biomarker panel including circulating ethanol, betaine, GCA, and DCA levels as markers of NASH in a group of patients with liver histology indicative of NASH. A cutoff point and area under the curve were determined so that NASH could be diagnosed. The accuracy with which this panel discriminates NASH subjects from non-NASH subjects showed an area under the ROC curve (AUROC) of approximately 0.776 (0.632–0.921). Therefore, we concluded that the levels of certain circulating microbiota-related metabolites are associated with NAFLD severity and could be used as a “liquid biopsy” in the noninvasive diagnosis of NASH [6].
In summary, proinflammatory and prooxidative damage has been demonstrated as a result of endogenous ethanol in the liver, which might contribute to the pathogenesis of NAFLD, and previous reports may support its use as a noninvasive biomarker of disease progression.
Choline is an essential nutrient obtained through both dietary intake and endogenous synthesis and is an important constituent of the phospholipid membrane. The human GM actively metabolizes dietary components, including choline. Alterations in choline and phosphatidylcholine metabolism due to intestinal dysbiosis may have an impact on several physiological pathways, which could induce NAFLD. Choline deficiency prevents the synthesis and excretion of VLDL, leading to hepatic triglyceride accumulation and liver steatosis [122, 123]. In fact, the link between choline deficiency and the accumulation of hepatic lipids has been recognized for more than 50 years [124], leading to the establishment of choline-deficient diets to induce models of NAFLD in animals.
In addition, choline can be metabolized to its derivative trimethylamine (TMA) by the GM. TMA reaches the liver via portal circulation and is subsequently oxidized by hepatic flavin-containing monooxygenases in the liver, forming trimethylamine-N-oxide (TMAO), which is then released into blood circulation [125, 126]. Previous studies have revealed that TMAO may affect lipid absorption and cholesterol homeostasis and modulate glucose and lipid metabolism by decreasing the total BA pool size [122]. TMAO modulates glucose metabolism and increases IR in mice fed a high-fat diet [127]. TMAO also affects lipid absorption and cholesterol homeostasis by reducing the conversion of cholesterol into BAs [122].
A small number of human studies have shown that the consumption of a low-choline diet promotes fatty liver and liver damage [123, 128]. Other studies have pointed out that plasma-free choline levels are positively related to the severity of NAFLD, fibrosis, and NASH [129, 130].
On the other hand, in our previous research, we analyzed circulating levels of these choline metabolites according to hepatic histology and observed that levels of TMAO were significantly higher in NAFLD patients than in NL subjects [6], which correlates with the previous statement that serum TMAO levels are significantly higher in patients with NAFLD than in healthy people and correlates with the development and severity of NAFLD through different mechanisms: modulating glucose metabolism, promoting inflammation in adipose tissue, and influencing lipid absorption and cholesterol homeostasis [125, 129, 131].
In summary, the evidence has demonstrated that choline and TMAO are associated with the progression of NAFLD, indicating the potential use of these GM-derived mediators as markers of disease progression.
Although there are no treatments to directly reverse steatosis, fibrosis, or liver damage, lifestyle changes and therapeutic strategies to treat other MS-related diseases, such as obesity, T2DM, or IR, could ameliorate NAFLD, avoiding its progression to NASH. Lifestyle intervention (diet and exercise), bariatric surgery, antidiabetic drugs, lipid-altering agents, and antihypertensive drugs can improve all of the features of NASH by ameliorating MS-related diseases [4]. Nevertheless, there is currently no specific treatment proven to be effective in treating NASH. Clarifying NAFLD risk factors could lead to more accurate prediction of disease progression and more effective treatments based on individualized drivers of disease [132]. The search for a possible therapy for NASH is focused on different pathways: metabolic targets, cell stress and apoptosis, immune targets, fibrosis, and GM modulation.
Currently, there are different mechanisms to manage NAFLD/NASH with metabolic targets focused on ameliorating other related diseases but also involved in NAFLD progression. Moreover, vitamin E acts as an antioxidant and hepatoprotective agent used to treat NASH (Figure 2).
Current and future treatment strategies to manage and treat NAFLD and NASH. Peroxisome proliferator-activated receptor (PPAR), farnesoid X receptor (FXR), farnesoid growth factor-19 (FGF-19), farnesoid growth factor-21 (FGF-21), acetyl-CoA carboxylase (ACC), glucagon-like peptide-1 receptor (GLP-1R), dipeptidyl peptidase-4 (DPP-4), sodium-glucose cotransporter 1/2 (SGLT-1/2), apoptosis signal-regulating kinase-1 (ASK-1), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and lysyl oxidase-like 2 (LXL-2).
On the other hand, there are many active studies and clinical trials focused on new therapeutic strategies with different pharmacological targets to avoid NAFLD and NASH progression. In this regard, PPAR agonists, antidiabetic drugs, FXR ligands, and anti-inflammatory and antiapoptotic agents can act as insulin sensitizers and improve the proinflammatory chronic state characteristic of NASH; antifibrotic agents can avoid NASH progression to fibrosis; and GM modulation can prevent the intestinal dysbiosis involved in NAFLD pathogenesis (Figure 2) [4, 7, 24, 133].
The key role that the GM plays in the progression of the disease opens the door to new ways of thinking about NASH prevention and treatment. The possibility of modulating the GM to treat NAFLD and NASH has gained interest in the potential use of probiotics, prebiotics, and antibiotics as effective treatments.
Probiotics are defined as viable microorganisms that when administered in adequate amounts, confer a health benefit to the host [134]. There are many mechanisms by which probiotics improve the GM and consequently ensure liver health (inhibition of intestinal bacterial enzymes, stimulation of host immunity, competition for limited nutrients, inhibition of bacterial mucosal adherence and epithelial invasion, protection against intestinal permeability, and control of bacterial translocation from the gut to the portal vein circulation). The biological activity of probiotics depends on delivering anti-inflammatory mediators that downregulate proinflammatory cytokines [104]. Therefore, probiotic therapy offers an interesting approach to control hepatic injury and a low-grade proinflammatory state.
Another alternative is the use of prebiotic fiber, which is defined as an amount of nondigestible food ingredients that beneficially affect the host, by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon [135]. The health effects of prebiotic fiber are related to improved glucoregulation and modified lipid metabolism as well as selective modulation of the GM. Some mechanisms have been proposed to explain the beneficial effects of prebiotics on the accumulation of triglycerides in the liver observed in animals, including reduced de novo fatty acid synthesis and SCFA production, body weight and fat loss, and improved glycemic control, GM modulation, and anti-inflammatory effects [13, 104]. These promising preliminary results strongly indicate the potential use of probiotics and prebiotics for the prevention or treatment of NASH.
Prophylactic use of antibiotics in patients with chronic liver diseases is an established method of preventing infections or innate immune dysfunction in acute liver failure (ALF) [13]. In addition, it has been demonstrated in animal and human models that the positive effect of polymyxin B and metronidazole in reducing the severity of NAFLD during total parenteral nutrition or after intestinal bypass could be interesting for their use to treat NAFLD [136, 137]. However, direct evidence is currently lacking, and thus, antibiotics cannot be routinely recommended to treat NASH, although further research is needed.
Overall, to date, there have been only a few studies concerning the use of probiotics, prebiotics, and antibiotics in humans; therefore, large-scale randomized controlled trials with histological endpoints are indicated.
Intestinal dysbiosis can trigger gut inflammation and increase the permeability of the intestinal epithelial barrier, exposing the gut-liver axis to GM-derived mediators of dysbiosis, such as bacterial components or metabolites, which may induce hepatotoxicity, inflammation, and consequently NAFLD progression. Gut-derived mediators of dysbiosis contribute to NAFLD progression by activating the immune system, inducing oxidative stress, enhancing inflammation, and finally promoting fibrogenesis.
Despite the evident association between GM dysbiosis, obesity, and NAFLD derived from several experimental studies, few studies have been conducted in patients with NAFLD to explore the role of GM-derived mediators of dysbiosis in the occurrence and progression of the disease. Additionally, few studies have focused on gut-derived mediators of dysbiosis as noninvasive markers of disease progression. The study of these mediators may provide an opportunity to develop a specific diagnostic and prognostic biomarker for NAFLD and NASH. In this sense, we propose the metabolomic study of these mediators and other metabolites involved to achieve a metabolomic profile that could be used as biomarkers for evaluating the status of NAFLD. On the other hand, some previous evidence has focused on GM modulation using probiotics, prebiotics, and antibiotics as therapeutic strategies to prevent or treat NAFLD and NASH, which is more uncertain and requires future research. In this sense, it remains important to promote study of GM targeting to find an effective treatment for NAFLD and overall for NASH.
This study was supported by the
The authors declare no conflict of interest.
NAFLD | non-alcoholic fatty liver disease |
NASH | non-alcoholic steatohepatitis |
GM | gut microbiota |
T2DM | type 2 diabetes mellitus |
IR | insulin resistance |
MS | metabolic syndrome |
LPS | lipopolysaccharides |
SCFAs | short-chain fatty acids |
BAs | bile acids |
TMAO | trimethylamine-N-oxide |
EtOH | ethanol |
NAFL | non-alcoholic fatty liver |
SS | simple steatosis |
AST | aspartate aminotransferase |
ALT | alanine aminotransferase |
TLRs | toll-like receptors |
SIBO | small intestinal bacterial overgrowth syndrome |
FXR | farnesoid X receptor |
VLDL | very-low density lipoprotein |
GPR | G-protein coupled receptors |
TNF-α | tumor necrosis factor alpha |
IL | interleukin |
GLP-1 | glucagon-like peptide-1 |
AMPK | AMP-activated protein kinase |
CA | cholic acid |
CDCA | chenodeoxycholic acid |
DCA | deoxycholic acid |
LCA | lithocholic acid |
NRs | nuclear receptors |
SHP | small heterodimer partner |
SREBP-1c | sterol-regulatory element-binding protein-1c |
PPARα | proliferator-activated receptor alpha |
NL | normal liver |
GCA | glycolic acid |
PAMPs | pathogen-associated molecular patterns |
LPB | LPS-binding protein |
NF-κB | necrosis factor-kappa beta |
INF-γ | interferon gamma |
MCP-1 | monocyte chemotactic protein-1 |
NLRP | NOD-like receptors pyrin domain |
CYP2E1 | enzyme cytochrome P450 2E1 |
AUROC | area under the ROC curve |
TMA | trimethylamine |
FGF | farnesoid growth factor |
ACC | acetyl-CoA carboxylase |
DPP-4 | dipeptidyl peptidase-4 |
SGLT-1/2 | sodium-glucose cotransporter-1/2 |
ASK-1 | apoptosis signal-regulating kinase-1 |
LXL-2 | lysyl oxidase-like-2 |
ALF | acute liver failure |
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Mahruf C. Shohel",coverURL:"https://cdn.intechopen.com/books/images_new/9974.jpg",editedByType:"Edited by",publishedDate:"May 18th 2022",editors:[{id:"94099",title:"Dr.",name:"M. Mahruf C.",middleName:null,surname:"Shohel",slug:"m.-mahruf-c.-shohel",fullName:"M. Mahruf C. Shohel"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"499",title:"Organometallic Chemistry",slug:"organic-chemistry-organometallic-chemistry",parent:{id:"85",title:"Organic Chemistry",slug:"organic-chemistry"},numberOfBooks:3,numberOfSeries:0,numberOfAuthorsAndEditors:80,numberOfWosCitations:56,numberOfCrossrefCitations:27,numberOfDimensionsCitations:69,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"499",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"7345",title:"BODIPY Dyes",subtitle:"A Privilege Molecular Scaffold with Tunable Properties",isOpenForSubmission:!1,hash:"5fb7c298ddb4308893451f964a28c422",slug:"bodipy-dyes-a-privilege-molecular-scaffold-with-tunable-properties",bookSignature:"Jorge Bañuelos-Prieto and Rebeca Sola Llano",coverURL:"https://cdn.intechopen.com/books/images_new/7345.jpg",editedByType:"Edited by",editors:[{id:"227055",title:"Dr.",name:"Jorge",middleName:null,surname:"Bañuelos-Prieto",slug:"jorge-banuelos-prieto",fullName:"Jorge Bañuelos-Prieto"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5822",title:"Alkenes",subtitle:null,isOpenForSubmission:!1,hash:"2f4b128e24e2481364cf3587a3bc75e1",slug:"alkenes",bookSignature:"Reza Davarnejad and Baharak Sajjadi",coverURL:"https://cdn.intechopen.com/books/images_new/5822.jpg",editedByType:"Edited by",editors:[{id:"88069",title:"Associate Prof.",name:"Reza",middleName:null,surname:"Davarnejad",slug:"reza-davarnejad",fullName:"Reza Davarnejad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5426",title:"New Advances in Hydrogenation Processes",subtitle:"Fundamentals and Applications",isOpenForSubmission:!1,hash:"8297cc5b2f32051885f1f73009e69a7e",slug:"new-advances-in-hydrogenation-processes-fundamentals-and-applications",bookSignature:"Maryam Takht Ravanchi",coverURL:"https://cdn.intechopen.com/books/images_new/5426.jpg",editedByType:"Edited by",editors:[{id:"2416",title:"Dr.",name:"Maryam",middleName:null,surname:"Takht Ravanchi",slug:"maryam-takht-ravanchi",fullName:"Maryam Takht Ravanchi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:3,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"53189",doi:"10.5772/66108",title:"Production of Biofuel via Hydrogenation of Lignin from Biomass",slug:"production-of-biofuel-via-hydrogenation-of-lignin-from-biomass",totalDownloads:2816,totalCrossrefCites:5,totalDimensionsCites:13,abstract:"Historically, humans have been harnessing biomass as a source of energy since the time they knew to make a fire from woods. Even today, some countries still depend on woods as a main source of energy. Biologically, biomass contains carbon-, hydrogen- and oxygen-based matters that unify in a solid material and that are potentially to be converted to fuel. Lignin is one of the components present in lignocellulosic biomass and has been actively examined to be used for biofuel production. Issues arise with the chemical characteristic and rigidity of its structure, which a setback for its viability for biofuel conversion. However, such setbacks have been counteracted with the advances of lignin-based knowledge on its conversion to chemical precursors for biofuel conversion. Recently, investigations on hydrogenation as one of the chemical processes used can be potentially utilised for efficient and viable means for biofuel production.",book:{id:"5426",slug:"new-advances-in-hydrogenation-processes-fundamentals-and-applications",title:"New Advances in Hydrogenation Processes",fullTitle:"New Advances in Hydrogenation Processes - Fundamentals and Applications"},signatures:"Bawadi Abdullah, Syed Anuar Faua Ad Syed Muhammad and Nik\nAzmi Nik Mahmood",authors:[{id:"188743",title:"Dr.",name:"Bawadi",middleName:null,surname:"Abdullah",slug:"bawadi-abdullah",fullName:"Bawadi Abdullah"},{id:"188839",title:"MSc.",name:"Nik Azmi",middleName:null,surname:"Nik Mahmood",slug:"nik-azmi-nik-mahmood",fullName:"Nik Azmi Nik Mahmood"},{id:"189820",title:"Dr.",name:"Syed Anuar Faua Ad",middleName:null,surname:"Syed Muhammad",slug:"syed-anuar-faua-ad-syed-muhammad",fullName:"Syed Anuar Faua Ad Syed Muhammad"}]},{id:"52449",doi:"10.5772/65407",title:"Recent Advances in Heterogeneous Catalytic Hydrogenation of CO2 to Methane",slug:"recent-advances-in-heterogeneous-catalytic-hydrogenation-of-co2-to-methane",totalDownloads:2867,totalCrossrefCites:4,totalDimensionsCites:8,abstract:"With the accelerating industrialization, urbanization process, and continuously upgrading of consumption structures, the CO2 from combustion of coal, oil, natural gas, and other hydrocarbon fuels is unbelievably increased over the past decade. As an important carbon resource, CO2 gained more and more attention because of its converting properties to lower hydrocarbon, such as methane, methanol, and formic acid. Among them, CO2 methanation is considered to be an extremely efficient method due to its high CO2 conversion and CH4 selectivity. However, the CO2 methanation process requires high reaction temperatures (300–400°C), which limits the theoretical yield of methane. Thus, it is desirable to find a new strategy for the efficient conversion of CO2 to methane at relatively low reaction temperature, and the key issue is using the catalysts in the process. The advances in the noble metal catalysts, Ni-based catalysts, and Co-based catalysts, for catalytic hydrogenation CO2 to methane are reviewed in this paper, and the effects of the supports and the addition of second metal on CO2 methanation as well as the reaction mechanisms are focused.",book:{id:"5426",slug:"new-advances-in-hydrogenation-processes-fundamentals-and-applications",title:"New Advances in Hydrogenation Processes",fullTitle:"New Advances in Hydrogenation Processes - Fundamentals and Applications"},signatures:"Zuzeng Qin, Yuwen Zhou, Yuexiu Jiang, Zili Liu and Hongbing Ji",authors:[{id:"5795",title:"Dr.",name:"Hongbing",middleName:null,surname:"Ji",slug:"hongbing-ji",fullName:"Hongbing Ji"},{id:"188601",title:"Dr.",name:"Zuzeng",middleName:null,surname:"Qin",slug:"zuzeng-qin",fullName:"Zuzeng Qin"},{id:"194474",title:"Mr.",name:"Yuwen",middleName:null,surname:"Zhou",slug:"yuwen-zhou",fullName:"Yuwen Zhou"},{id:"194475",title:"Prof.",name:"Zili",middleName:null,surname:"Liu",slug:"zili-liu",fullName:"Zili Liu"}]},{id:"53666",doi:"10.5772/66967",title:"Supported Nickel-Based Catalysts for Partial Hydrogenation of Edible Oils",slug:"supported-nickel-based-catalysts-for-partial-hydrogenation-of-edible-oils",totalDownloads:2370,totalCrossrefCites:1,totalDimensionsCites:7,abstract:"Nickel-based catalysts, supported on diatomite, silica gel and perlite, with high nickel loadings, have been prepared by precipitation-deposition method. Various nickel precursor salts were used for the preparation of catalyst precursors. In the precursor state, the catalysts were characterized using nitrogen physisorption, mercury porosimetry, infrared, and X-ray diffraction spectroscopy. The reducibility of catalyst precursors was evaluated using hydrogen temperature programmed reduction. Hydrogen chemisorption and X-ray photoelectron spectroscopy measurements were performed with the aim of characterizing the chemical state of the catalyst precursors. This research was focused on the study of some major factors on the state, dispersion and reducibility of a deposited Ni2+ phase by the combined use of mentioned experimental techniques. We have examined the influence of the nature of support and the use of modifiers on activity of nickel-based catalysts in the partial hydrogenation of sunflower and soybean oils. Nitrogen physisorption and mercury porosimetry data showed that synthesis operating conditions and pore structure of supports have a profound effect on the textural properties of catalyst precursors. The analysis of infrared and X-ray diffraction spectra showed the existence of chemical species and phases which indicate the different extent of interaction between the support and the active metal. Temperature programmed reduction study revealed that the reduction features depend on the identity of the nickel precursor salt and its interaction with the support. A stronger interaction of the supported Ni2+ phase with support hinders the reduction of catalyst precursors. Hydrogen chemisorption results showed the presence of nickel crystallites varying from 5 to 47 nm in size. The X-ray photoelectron spectroscopy data confirmed the formation surface species with different strength of interaction and different nickel crystallite sizes. The hydrogenation results showed significant differences, depending on the support and the modifier, as well as structural characteristics of reduced catalyst precursors. The results show the importance of modifiers in the control of the activity and selectivity of the partial hydrogenation process. The developed kinetic models of the hydrogenation of soybean and sunflower oils over studied catalytic systems were found useful in the prediction of the rate of reactions, product selectivity and catalytic activity.",book:{id:"5426",slug:"new-advances-in-hydrogenation-processes-fundamentals-and-applications",title:"New Advances in Hydrogenation Processes",fullTitle:"New Advances in Hydrogenation Processes - Fundamentals and Applications"},signatures:"Miroslav Stanković, Jugoslav Krstić, Margarita Gabrovska, Vojkan\nRadonjić, Dimitrinka Nikolova, Davor Lončarević and Dušan\nJovanović",authors:[{id:"189814",title:"Dr.",name:"Miroslav",middleName:null,surname:"Stanković",slug:"miroslav-stankovic",fullName:"Miroslav Stanković"}]},{id:"52488",doi:"10.5772/65448",title:"Hydrogenation Catalysis in Biobased Ionic Liquids",slug:"hydrogenation-catalysis-in-biobased-ionic-liquids",totalDownloads:1728,totalCrossrefCites:1,totalDimensionsCites:6,abstract:"This chapter is dedicated to hydrogenation procedures of (poly)-alkenes or unsaturated ketones in various biobased and not-biobased ionic liquids. The first part of this chapter defines the concept of biobased ionic liquids and their preparation. In the second part, hydrogenation processes performed in non-biobased ionic liquids are described. Finally, in the last part, the two themes are mixed and recent examples of hydrogenation procedures of alkenes, polyalkenes or unsaturated ketones in biobased ionic liquids are developed.",book:{id:"5426",slug:"new-advances-in-hydrogenation-processes-fundamentals-and-applications",title:"New Advances in Hydrogenation Processes",fullTitle:"New Advances in Hydrogenation Processes - Fundamentals and Applications"},signatures:"Safa Hayouni, Nadège Ferlin and Sandrine Bouquillon",authors:[{id:"188732",title:"Prof.",name:"Sandrine",middleName:null,surname:"Bouquillon",slug:"sandrine-bouquillon",fullName:"Sandrine Bouquillon"},{id:"189857",title:"Dr.",name:"Nadège",middleName:null,surname:"Ferlin",slug:"nadege-ferlin",fullName:"Nadège Ferlin"},{id:"189858",title:"MSc.",name:"Safa",middleName:null,surname:"Hayouni",slug:"safa-hayouni",fullName:"Safa Hayouni"}]},{id:"53136",doi:"10.5772/65518",title:"Recent Developments in the Use of Flow Hydrogenation in the Field of Medicinal Chemistry",slug:"recent-developments-in-the-use-of-flow-hydrogenation-in-the-field-of-medicinal-chemistry",totalDownloads:2371,totalCrossrefCites:3,totalDimensionsCites:5,abstract:"This chapter focuses on recent applications of flow hydrogenation in medicinal chemistry. Flow reactors can enhance laboratory safety, reducing the risks associated with pyrophoric catalysts, due to their containment in catalyst cartridges or omnifit columns. Flow hydrogenation reduces the risks arising from hydrogen gas, with either hydrogen generated in situ from water, or precise management of the gas flow rate through tube-in-tube reactors. There is an increasing body of evidence that flow hydrogenation enhances reduction outcomes across nitro, imine, nitrile, amide, azide, and azo reductions, together with de-aromatisation and hydrodehalogenation. In addition, olefin, alkyne, carbonyl, and benzyl reductions have been widely examined. Further, protocols involving multistage flow reactions involving hydrogenation are highlighted.",book:{id:"5426",slug:"new-advances-in-hydrogenation-processes-fundamentals-and-applications",title:"New Advances in Hydrogenation Processes",fullTitle:"New Advances in Hydrogenation Processes - Fundamentals and Applications"},signatures:"Cecilia C. Russell, Jennifer R. Baker, Peter J. Cossar and Adam\nMcCluskey",authors:[{id:"44482",title:"Prof.",name:"Adam",middleName:null,surname:"McCluskey",slug:"adam-mccluskey",fullName:"Adam McCluskey"}]}],mostDownloadedChaptersLast30Days:[{id:"55862",title:"Olefin Metathesis by Group VI (Mo, W) Metal Compounds",slug:"olefin-metathesis-by-group-vi-mo-w-metal-compounds",totalDownloads:1766,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Olefin metathesis is an important reaction not only in petroleum chemistry but also in fine chemistry. Professors Grubbs, Schrock, and Chauvin obtained the Nobel Prize in 2005 for the development of this reaction (determination of the mechanism and synthesis of homogeneous catalysts). This reaction can be described as the redistribution of carbon chains of olefins via a breaking of their C═C double bonds. It is catalyzed by metal carbenes and the catalytic cycle passes through a metallacyclobutane. The purpose of this chapter is to give an overview of catalysts based on tungsten or molybdenum active for this reaction. Numerous tungsten and molybdenum organometallic complexes displaying a carbene functionality were synthesized. Some of them are highly active in olefin metathesis. Industrially, tungsten oxide on silica is used as a precursor of the propene production by olefin metathesis of but-2-ene and ethylene. However, the active sites are not well known but they can be modeled by grafting, via surface organometallic chemistry, perhydrocarbyl complexes of molybdenum or tungsten on oxide surfaces. After a review of the complexes used in homogeneous catalysis, a review of the industrial catalysts and their models will be given.",book:{id:"5822",slug:"alkenes",title:"Alkenes",fullTitle:"Alkenes"},signatures:"Frédéric Lefebvre, Yassine Bouhoute, Kai C. Szeto, Nicolas Merle,\nAimery de Mallmann, Régis Gauvin and Mostafa Taoufik",authors:[{id:"198132",title:"Dr.",name:"Frederic",middleName:null,surname:"Lefebvre",slug:"frederic-lefebvre",fullName:"Frederic Lefebvre"},{id:"205605",title:"Dr.",name:"Yassine",middleName:null,surname:"Bouhoute",slug:"yassine-bouhoute",fullName:"Yassine Bouhoute"},{id:"205606",title:"Dr.",name:"Kai",middleName:null,surname:"Szeto",slug:"kai-szeto",fullName:"Kai Szeto"},{id:"205607",title:"Dr.",name:"Nicolas",middleName:null,surname:"Merle",slug:"nicolas-merle",fullName:"Nicolas Merle"},{id:"205608",title:"Dr.",name:"Aimery",middleName:null,surname:"De Mallmann",slug:"aimery-de-mallmann",fullName:"Aimery De Mallmann"},{id:"205609",title:"Dr.",name:"Régis",middleName:null,surname:"Gauvin",slug:"regis-gauvin",fullName:"Régis Gauvin"},{id:"205610",title:"Dr.",name:"Mostafa",middleName:null,surname:"Taoufik",slug:"mostafa-taoufik",fullName:"Mostafa Taoufik"}]},{id:"53512",title:"Catalytic Hydrogenation of Benzoic Acid",slug:"catalytic-hydrogenation-of-benzoic-acid",totalDownloads:2240,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Hydrogenation of benzoic acid using mono- and bimetallic catalyst of Ru, Pd, Co, and Re yielded different products. It was observed that 5% Ru/C was an active catalyst for hydrogenation of both aromatic ring and carboxylic group, while Pd/C catalyst hydrogenated only aromatic ring. Ru-Sn/Al2O3 is a chemoselective catalyst for hydrogenation of –COOH group of benzoic acid.",book:{id:"5426",slug:"new-advances-in-hydrogenation-processes-fundamentals-and-applications",title:"New Advances in Hydrogenation Processes",fullTitle:"New Advances in Hydrogenation Processes - Fundamentals and Applications"},signatures:"Sunil B. Shinde and Raj M. Deshpande",authors:[{id:"188266",title:"Dr.",name:"Sunil",middleName:"Babaji",surname:"Shinde",slug:"sunil-shinde",fullName:"Sunil Shinde"},{id:"189343",title:"Dr.",name:"Raj",middleName:null,surname:"Deshpande",slug:"raj-deshpande",fullName:"Raj Deshpande"}]},{id:"65034",title:"Decomposition Mechanisms of BODIPY Dyes",slug:"decomposition-mechanisms-of-bodipy-dyes",totalDownloads:1208,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"The stability of metal complexes in both thermodynamic and kinetic aspects always was a matter of interest in the field of coordination chemistry. Practical implementation of a fluorophores in a field of molecular biology also is essentially constrained by their solvolytic and protolytic stability. The aforementioned emphasizes interest in a search for factors of quantitative stability-based discrimination on a row of BODIPY derivatives. This chapter shows that thermodynamic stability of a dipyrrinates varies to a large extent from a mostly undestructable solvolytically BODIPYs to a very volatile in the same aspect rare-earth element complexes.",book:{id:"7345",slug:"bodipy-dyes-a-privilege-molecular-scaffold-with-tunable-properties",title:"BODIPY Dyes",fullTitle:"BODIPY Dyes - A Privilege Molecular Scaffold with Tunable Properties"},signatures:"Yuriy S. Marfin, Sergey D. Usoltsev and Evgeniy V. Rumyantsev",authors:null},{id:"56012",title:"Alkene and Olefin Functionalization by Organoaluminum Compounds, Catalyzed with Zirconocenes: Mechanisms and Prospects",slug:"alkene-and-olefin-functionalization-by-organoaluminum-compounds-catalyzed-with-zirconocenes-mechanis",totalDownloads:1385,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Alkene and olefin functionalization via addition of electro‐ or nucleophilic reagents is one of the convenient synthetic methods for the insertion of heteroatoms into organic molecules. The use of organometallic reagents in these reactions in combination with the specific catalysts provides high substrate conversion and process selectivity. The introduction of this approach into the chemistry of organoaluminum compounds leads to the development of chemo‐, regio‐ and stereoselective catalytic methods of alkene and olefin functionalization. The chapter focuses on the modern concepts of the alkene hydro‐, carbo‐ and cycloalumination mechanisms, that is, the experimental and theoretical data on the intermediate structures involved in the product formation, the effects of the catalyst and organoaluminum compound structure, reaction conditions on the activity and selectivity of the bimetallic systems. The prospects of the development of enantioselective methods using these catalytic systems for the alkene and olefin transformations are considered.",book:{id:"5822",slug:"alkenes",title:"Alkenes",fullTitle:"Alkenes"},signatures:"Lyudmila V. Parfenova, Pavel V. Kovyazin, Tatyana V. Tyumkina,\nLeonard M. Khalilov and Usein M. 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He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNVJQA4/Profile_Picture_2022-03-07T13:23:04.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. His research interests include biochemistry, oxidative stress, reactive species, antioxidants, lipid peroxidation, inflammation, reproductive hormones, phenolic compounds, female infertility.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Associate Prof.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/15648_n.jpg",biography:"Dr. Mohd Aftab Siddiqui is currently working as Assistant Professor in the Faculty of Pharmacy, Integral University, Lucknow for the last 6 years. He has completed his Doctor in Philosophy (Pharmacology) in 2020 from Integral University, Lucknow. He completed his Bachelor in Pharmacy in 2013 and Master in Pharmacy (Pharmacology) in 2015 from Integral University, Lucknow. He is the gold medalist in Bachelor and Master degree. He qualified GPAT -2013, GPAT -2014, and GPAT 2015. His area of research is Pharmacological screening of herbal drugs/ natural products in liver and cardiac diseases. He has guided many M. Pharm. research projects. He has many national and international publications.",institutionString:"Integral University",institution:null},{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. degree from Integral University. Currently, he’s working as an Assistant Professor of Pharmaceutics in the Faculty of Pharmacy, Integral University. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than 32 original articles published in reputed journals, 3 edited books, 5 book chapters, and a number of scientific articles published in ‘Ingredients South Asia Magazine’ and ‘QualPharma Magazine’. He is a member of the American Association for Cancer Research, International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs that aim to provide practical solutions to current healthcare problems.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}},{id:"297507",title:"Dr.",name:"Charles",middleName:"Elias",surname:"Assmann",slug:"charles-assmann",fullName:"Charles Assmann",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/297507/images/system/297507.jpg",biography:"Charles Elias Assmann is a biologist from Federal University of Santa Maria (UFSM, Brazil), who spent some time abroad at the Ludwig-Maximilians-Universität München (LMU, Germany). He has Masters Degree in Biochemistry (UFSM), and is currently a PhD student at Biochemistry at the Department of Biochemistry and Molecular Biology of the UFSM. His areas of expertise include: Biochemistry, Molecular Biology, Enzymology, Genetics and Toxicology. He is currently working on the following subjects: Aluminium toxicity, Neuroinflammation, Oxidative stress and Purinergic system. Since 2011 he has presented more than 80 abstracts in scientific proceedings of national and international meetings. Since 2014, he has published more than 20 peer reviewed papers (including 4 reviews, 3 in Portuguese) and 2 book chapters. He has also been a reviewer of international journals and ad hoc reviewer of scientific committees from Brazilian Universities.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",country:{name:"Brazil"}}},{id:"217850",title:"Dr.",name:"Margarete Dulce",middleName:null,surname:"Bagatini",slug:"margarete-dulce-bagatini",fullName:"Margarete Dulce Bagatini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217850/images/system/217850.jpeg",biography:"Dr. Margarete Dulce Bagatini is an associate professor at the Federal University of Fronteira Sul/Brazil. She has a degree in Pharmacy and a PhD in Biological Sciences: Toxicological Biochemistry. She is a member of the UFFS Research Advisory Committee\nand a member of the Biovitta Research Institute. She is currently:\nthe leader of the research group: Biological and Clinical Studies\nin Human Pathologies, professor of postgraduate program in\nBiochemistry at UFSC and postgraduate program in Science and Food Technology at\nUFFS. She has experience in the area of pharmacy and clinical analysis, acting mainly\non the following topics: oxidative stress, the purinergic system and human pathologies, being a reviewer of several international journals and books.",institutionString:"Universidade Federal da Fronteira Sul",institution:{name:"Universidade Federal da Fronteira Sul",country:{name:"Brazil"}}},{id:"226275",title:"Ph.D.",name:"Metin",middleName:null,surname:"Budak",slug:"metin-budak",fullName:"Metin Budak",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226275/images/system/226275.jfif",biography:"Metin Budak, MSc, PhD is an Assistant Professor at Trakya University, Faculty of Medicine. He has been Head of the Molecular Research Lab at Prof. Mirko Tos Ear and Hearing Research Center since 2018. His specializations are biophysics, epigenetics, genetics, and methylation mechanisms. He has published around 25 peer-reviewed papers, 2 book chapters, and 28 abstracts. He is a member of the Clinical Research Ethics Committee and Quantification and Consideration Committee of Medicine Faculty. His research area is the role of methylation during gene transcription, chromatin packages DNA within the cell and DNA repair, replication, recombination, and gene transcription. His research focuses on how the cell overcomes chromatin structure and methylation to allow access to the underlying DNA and enable normal cellular function.",institutionString:"Trakya University",institution:{name:"Trakya University",country:{name:"Turkey"}}},{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",slug:"anca-pantea-stoian",fullName:"Anca Pantea Stoian",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",biography:"Anca Pantea Stoian is a specialist in diabetes, nutrition, and metabolic diseases as well as health food hygiene. She also has competency in general ultrasonography.\n\nShe is an associate professor in the Diabetes, Nutrition and Metabolic Diseases Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. She has been chief of the Hygiene Department, Faculty of Dentistry, at the same university since 2019. Her interests include micro and macrovascular complications in diabetes and new therapies. Her research activities focus on nutritional intervention in chronic pathology, as well as cardio-renal-metabolic risk assessment, and diabetes in cancer. She is currently engaged in developing new therapies and technological tools for screening, prevention, and patient education in diabetes. \n\nShe is a member of the European Association for the Study of Diabetes, Cardiometabolic Academy, CEDA, Romanian Society of Diabetes, Nutrition and Metabolic Diseases, Romanian Diabetes Federation, and Association for Renal Metabolic and Nutrition studies. She has authored or co-authored 160 papers in national and international peer-reviewed journals.",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",country:{name:"Romania"}}},{id:"279792",title:"Dr.",name:"João",middleName:null,surname:"Cotas",slug:"joao-cotas",fullName:"João Cotas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279792/images/system/279792.jpg",biography:"Graduate and master in Biology from the University of Coimbra.\n\nI am a research fellow at the Macroalgae Laboratory Unit, in the MARE-UC – Marine and Environmental Sciences Centre of the University of Coimbra. My principal function is the collection, extraction and purification of macroalgae compounds, chemical and bioactive characterization of the compounds and algae extracts and development of new methodologies in marine biotechnology area. \nI am associated in two projects: one consists on discovery of natural compounds for oncobiology. The other project is the about the natural compounds/products for agricultural area.\n\nPublications:\nCotas, J.; Figueirinha, A.; Pereira, L.; Batista, T. 2018. An analysis of the effects of salinity on Fucus ceranoides (Ochrophyta, Phaeophyceae), in the Mondego River (Portugal). Journal of Oceanology and Limnology. in press. DOI: 10.1007/s00343-019-8111-3",institutionString:"Faculty of Sciences and Technology of University of Coimbra",institution:null},{id:"279788",title:"Dr.",name:"Leonel",middleName:null,surname:"Pereira",slug:"leonel-pereira",fullName:"Leonel Pereira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279788/images/system/279788.jpg",biography:"Leonel Pereira has an undergraduate degree in Biology, a Ph.D. in Biology (specialty in Cell Biology), and a Habilitation degree in Biosciences (specialization in Biotechnology) from the Faculty of Science and Technology, University of Coimbra, Portugal, where he is currently a professor. In addition to teaching at this university, he is an integrated researcher at the Marine and Environmental Sciences Center (MARE), Portugal. His interests include marine biodiversity (algae), marine biotechnology (algae bioactive compounds), and marine ecology (environmental assessment). Since 2008, he has been the author and editor of the electronic publication MACOI – Portuguese Seaweeds Website (www.seaweeds.uc.pt). He is also a member of the editorial boards of several scientific journals. Dr. Pereira has edited or authored more than 20 books, 100 journal articles, and 45 book chapters. He has given more than 100 lectures and oral communications at various national and international scientific events. He is the coordinator of several national and international research projects. In 1998, he received the Francisco de Holanda Award (Honorable Mention) and, more recently, the Mar Rei D. Carlos award (18th edition). He is also a winner of the 2016 CHOICE Award for an outstanding academic title for his book Edible Seaweeds of the World. In 2020, Dr. Pereira received an Honorable Mention for the Impact of International Publications from the Web of Science",institutionString:"University of Coimbra",institution:{name:"University of Coimbra",country:{name:"Portugal"}}},{id:"61946",title:"Dr.",name:"Carol",middleName:null,surname:"Bernstein",slug:"carol-bernstein",fullName:"Carol Bernstein",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61946/images/system/61946.jpg",biography:"Carol Bernstein received her PhD in Genetics from the University of California (Davis). She was a faculty member at the University of Arizona College of Medicine for 43 years, retiring in 2011. Her research interests focus on DNA damage and its underlying role in sex, aging and in the early steps of initiation and progression to cancer. In her research, she had used organisms including bacteriophage T4, Neurospora crassa, Schizosaccharomyces pombe and mice, as well as human cells and tissues. She authored or co-authored more than 140 scientific publications, including articles in major peer reviewed journals, book chapters, invited reviews and one book.",institutionString:"University of Arizona",institution:{name:"University of Arizona",country:{name:"United States of America"}}},{id:"182258",title:"Dr.",name:"Ademar",middleName:"Pereira",surname:"Serra",slug:"ademar-serra",fullName:"Ademar Serra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/182258/images/system/182258.jpeg",biography:"Dr. Serra studied Agronomy on Universidade Federal de Mato Grosso do Sul (UFMS) (2005). He received master degree in Agronomy, Crop Science (Soil fertility and plant nutrition) (2007) by Universidade Federal da Grande Dourados (UFGD), and PhD in agronomy (Soil fertility and plant nutrition) (2011) from Universidade Federal da Grande Dourados / Escola Superior de Agricultura Luiz de Queiroz (UFGD/ESALQ-USP). Dr. Serra is currently working at Brazilian Agricultural Research Corporation (EMBRAPA). His research focus is on mineral nutrition of plants, crop science and soil science. 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Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,series:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983"},editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",slug:"ana-isabel-flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",slug:"christian-palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},onlineFirstChapters:{paginationCount:0,paginationItems:[]},publishedBooks:{paginationCount:9,paginationItems:[{type:"book",id:"9959",title:"Biomedical Signal and Image Processing",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/9959.jpg",slug:"biomedical-signal-and-image-processing",publishedDate:"April 14th 2021",editedByType:"Edited by",bookSignature:"Yongxia Zhou",hash:"22b87a09bd6df065d78c175235d367c8",volumeInSeries:10,fullTitle:"Biomedical Signal and Image Processing",editors:[{id:"259308",title:"Dr.",name:"Yongxia",middleName:null,surname:"Zhou",slug:"yongxia-zhou",fullName:"Yongxia Zhou",profilePictureURL:"https://mts.intechopen.com/storage/users/259308/images/system/259308.jpeg",institutionString:"University of Southern California",institution:{name:"University of Southern California",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9973",title:"Data Acquisition",subtitle:"Recent Advances and Applications in Biomedical Engineering",coverURL:"https://cdn.intechopen.com/books/images_new/9973.jpg",slug:"data-acquisition-recent-advances-and-applications-in-biomedical-engineering",publishedDate:"March 17th 2021",editedByType:"Edited by",bookSignature:"Bartłomiej Płaczek",hash:"75ea6cdd241216c9db28aa734ab34446",volumeInSeries:9,fullTitle:"Data Acquisition - Recent Advances and Applications in Biomedical Engineering",editors:[{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",institutionString:"University of Silesia",institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"9905",title:"Biometric Systems",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/9905.jpg",slug:"biometric-systems",publishedDate:"February 10th 2021",editedByType:"Edited by",bookSignature:"Muhammad Sarfraz",hash:"c730560dd2e3837a03407b3a86b0ef2a",volumeInSeries:8,fullTitle:"Biometric Systems",editors:[{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",institutionString:"Kuwait University",institution:{name:"Kuwait University",institutionURL:null,country:{name:"Kuwait"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"8622",title:"Peptide Synthesis",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/8622.jpg",slug:"peptide-synthesis",publishedDate:"December 18th 2019",editedByType:"Edited by",bookSignature:"Jaya T. 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