HPLC analyzed results of
\r\n\tFourth, the effects of digitalization on economic and sustainable development and the benefits of digitization for public services, including e-governance, e-payments, e-democracy, e-health, e-learning, e-payments, and so on, are also presented.
\r\n\r\n\tAt the fifth stage, we will try to highlight the imperative role of blockchain technology, artificial intelligence, and machine learning in the digitization process.
\r\n\r\n\tLast but not least, the main threats of a digital economy are presented under the form of cybercrime and “surveillance capitalism”, including the impact of financial crimes referring to card frauds, online frauds, digital frauds, digital shadow economy, black market, money laundering, etc.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"45ca4a969c50d02d2bab6894218c7ef8",bookSignature:"Prof. Monica Violeta Achim and Dr. Nawazish Mirza",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10918.jpg",keywords:"Definition, Digital Transactions, Innovative Financial Services, Cryptocurrency, E-governance, E-payments, Spiral Transformation of Knowledge, Financial Education, Artificial Intelligence, Machine Learning, Money Laundering Surveillance Capitalism Economy, the General Data Protection Regulation (GDPR)",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 25th 2021",dateEndSecondStepPublish:"September 17th 2021",dateEndThirdStepPublish:"November 16th 2021",dateEndFourthStepPublish:"February 4th 2022",dateEndFifthStepPublish:"April 5th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"9 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:"In February 2020, Ph.D. Achim won the Prize for Excellence in Scientific Research, at Babeș-Bolyai University, Cluj-Napoca, Romania. Since 2020, she became a member of the Romanian Ministery of Education and Research, as a representative in the panel of Economic Sciences.",coeditorOneBiosketch:"Prof.Mirza obtained a Ph.D. from the University of Paris Dauphine and has over 18 years of research, teaching, and consulting experience across Western Europe, Middle East, Asia Pacific, and Australia.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"236659",title:"Prof.",name:"Monica Violeta",middleName:null,surname:"Achim",slug:"monica-violeta-achim",fullName:"Monica Violeta Achim",profilePictureURL:"https://mts.intechopen.com/storage/users/236659/images/system/236659.jpg",biography:"Monica Violeta Achim is is currently full professor and doctoral supervisor in the field of Finance at the Faculty of Economic Sciences and Business Administration, Babeş-Bolyai University, Cluj-Napoca. She teaches the disciplines 'Diagnosis and Financial Analysis”, 'Financial analysis in banks” and 'Economic and financial crime” at the same faculty. She has many research concerns in the area of financial analysis, business performances, corporate governance, economic and financial crimes and public finance. With over 22 years of experience in academia, she has published as author and co-author, over 130 scientific articles and 25 books. Among the main targeted top journals, the following can be mentioned: The European Journal of Health Economics, Technological and Economic Development of Economy, Population Health Management, Social Indicators Research, Apply Research in Quality Life, Journal of Business Economics and Management, E+M Ekonomie and Management, Economic Research-Ekonomska Istraživanja, Sustainability, Entrepreneurship Research Journal, Singapore Economic Review. Her most recent reference work is the book Economic and financial crime. Corruption, Shadow economy and Money laundering, published as co-authored at Springer. She is also reviewer and board member for many international journals.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Babeș-Bolyai University",institutionURL:null,country:{name:"Romania"}}}],coeditorOne:{id:"420517",title:"Dr.",name:"Nawazish",middleName:null,surname:"Mirza",slug:"nawazish-mirza",fullName:"Nawazish Mirza",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000039UrYIQA0/Profile_Picture_1622035121865",biography:"Nawazish Mirza is a professor of finance at the Excelia Business School, La Rochelle, France. He obtained a Ph.D. from the University of Paris Dauphine and has over 18 years of research, teaching, and consulting experience across Western Europe, Middle East, Asia Pacific, and Australia. His research interests include financial technology, credit ratings, risk management, financial intermediation, and valuations. He has extensive professional and consulting experience in credit ratings, investment banking, and the valuation of new technologies. His recent research has been published in the Resources Policy, Journal of Environmental Management, International Review of Economics and Finance, Economic Modelling, Pacific-Basin Finance, Technology, and Social Forecasting, Finance Research Letters, among others. He is associate editor of the Journal of Economic and Administrative Sciences and Economic Research. He is guest editor of Climate Change Economics.",institutionString:"Excelia Business School",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"7",title:"Business, Management and Economics",slug:"business-management-and-economics"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"418641",firstName:"Iva",lastName:"Ribic",middleName:null,title:"M.Sc.",imageUrl:"https://mts.intechopen.com/storage/users/418641/images/16830_n.png",email:"iva.r@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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The crop is also being used to make diesel biofuel from the oil extracted from the seed. Today, the world’s top producers of soybean are the United States (90 million ton), Brazil (68 million tons), Argentina (52 million tons), China (15 million tons) and India. These countries’ production represents more than 90% of global soybean production. In the 2009/2010 harvest the world produced 261.57 million tons of soybean grain on 102.38 million hectares define this by [1]. Also, according to [1], over a period of 50 years, soybean production area increased 330%, rising from 23.81 million in 1961 to the current production area.
Currently with a world population of 7.0 billion people, which is projected to increase to more than 9.0 billion by 2050 and 10 billion by 2100 [2], there is a concern to maintain food. To achieve a gradual increase in world production of soybeans, two alternatives are possible: increased production area and/or increased productivity. Because planted area has increased 37% between 2000 to 2011 [1] and productivity has increased only 17.8%, the second solution looks to be the better option
Among all the factors inherent in agricultural production, the climate are the most difficult to control and it exercises greater limiting action in the maximum yield. It worsens according to the difficult to predict occurrences of adverse weather, the main risk factors in the exploration of major crops. Stress non biotic such as drought, excessive rain, extreme temperatures and low light can significantly reduce yields of crops and restrict the locations, times and soils, where the species most important commercially, can or not be cultivated.
In general, soybean production potential and risk is controlled by prevailing climatic conditions and genotypic performance. The basic source for crop production is solar radiation which acts as an energy source for photosynthesis. Light quality also acts to influence plant height and phenological development [3].
The light spectrum duration and quality besides the radiation intensity are determinants of morphological and phenotypic responses striking in soybean, such as plant height, induction of flowering and ontogeny [4]. The final yield of dry matter from the plant depends on the solar radiation absorbed by the leaves and the efficiency with which these convert radiant energy into chemical energy through photosynthesis.
Soybean is a qualitative short-day plant and must receive a certain day length or less so that developmental timing is optimal for the location [5]. This means that adaptability of each cultivar varies with latitude [6]. Movement of soybean to the central and northern regions of the country from the original southern region has faced the challenge of adaptation to shorter day lengths occurring in these regions (from Tropic of Capricorn to Equator Line). To deal with this challenge Brazilian agricultural scientists have sought to introduce the ‘long juvenile period’. This characteristic gives soybean a longer developmental period under short days so that it can accrue enough dry matter for optimal yield [7].
Each variety has its critical photoperiod above which flowering is delayed. Flowering occurs anyway, but more rapidly as the days become shorter. It slows progressively, as the photoperiod exceeds the critical period for each genotype.
In addition to photoperiod, temperature also influences growth and developmental timing in soybean. This occurs due to the effect of temperature on the rate of metabolic reactions, the diffusion rate of gases through aqueous media and the solubility of nutrients in the plant. Soybean grows best at temperatures between 20oC and 30oC. Greatest number of pods per plant is obtained under mild temperature conditions having a day/night temperature combination of 26/14oC [8]. Temperatures above 40oC during the vegetative stage (emergence to first flower) reduce growth and hastens flowering. High temperatures during the reproductive phase can cause reductions in seed number and seed weight, thus reducing grain quality and yield. If the high temperature is associated with a drought, the losses on grain production are even higher [7]. On the other hand, cold regions where the temperature is equal or below to 10C is not properly to soybean cultivation, because in these places, the vegetative growth and the development become small or null.
Ninety % of the total soybean fresh weight (biomass) is water and water acts in all physiological and biochemical processes in the plant, working as a solvent, carrying gases, minerals and other plant solutes and acting as a thermal regulator to cool and maintain plant temperature [9].Water availability is important in three periods of soybean development: germination, emergence and flowering-grain filling. During the first period, both: excess or lack of water is detrimental to crop establishment and obtaining a good uniformity of the plant population and the surplus water more limiting than the deficit. Soybean seeds need to absorb at least 50% of its weight in water to ensure a good germination. At this stage, the water content in soil must not exceed 85% of the total maximum available, or must not be less than 50% [10]. The roots can reach over 1.5 m deep, however heavy and compacted soils hinder root penetration, further reducing the effective depth of the root system of soybean plants.
Another serious risk in Brazilian soybean production is drought stress. The problem is more pronounced in tropical and subtropical, semiarid and arid climates where up to 8mm/day may be lost by evapotranspiration.
The necessity of water needs by soybean gradually increase with plant development, peaking at 7 to 8mm/day during flowering through grain filling [11]. The negative effect of water deficiency on yield depends on the phenological stage in which soybean is affected by drought stress. For example, if drought occurs during the germination and emergence stages, plant stand is reduced. In the flowering period it can cause flower abortion and prevents anthesis while in the grain filling stage drought affects seed weight [12]. The lack of water induces these effects through reducing the efficiency of the photosynthesis [13].
An abundance of water is also harmful to yield by causing water logging of the soil. A very wet soil results in low aeration which reduces root growth, can cause nutritional deficiency and promotes the attack of root diseases.
The climate exerts the greatest limiting effect on yield. Thus, proper management of the soybean crop depends on climate information at the site of interest. Agroclimatic zoning is used to provide climate data to the agricultural community [14].
Cardoso et al. [15] verified that in general the precipitation climate forecasts contribution to the improvement of estimated soybean productivity, primarily in periods when the crop is more sensitive to water deficit. The improvement of estimated soybean productivity may give a contribution to agribusiness sector, in order to turn more realistic expectations available and assist on the strategic planning for the decisions maker.
Knowledge of favorable periods for soybean culture, such as timing of the rainy season and duration of intermittent dry wet spells is very important for planning various agronomic operations such as preparing a seedbed, proper maturity, sowing, weeding, harvesting, threshing and drying. This minimizes crop risk and optimizes use of resources such as water, labor, fertilizer, herbicides and insecticides. Knowledge of the critical periods for crop development in conjunction with knowledge of climatic factors is very helpful for adjusting management practices for best crop yield and quality.
As already highlighted climate stresses such as drought, excessive rain, extreme temperatures and low irradiance can significantly reduce yields of crops and restrict areas and timings of production. The most important factors useful to know for soybean production are air temperature, photoperiod and water supply [10].
In Brazil, a system has been developed for identification of suitable areas for planting soybean. The Agricultural Zoning Program has been coordinated by the Ministry of Agriculture and EMBRAPA since 1996. This program has the objective of defining planting seasons guarantee at least an 80% probability of having an adequate water supply for the growing season. The planting periods were defined through the simulation of a climatic water balance that gives an index of water supply called by the Portuguese initials as ISNA (Water Necessity Satisfaction Index) using historical rainfall data, potential evapotranspiration, physiological characteristics of each crop and water retention by the soil [16].
Since 1988, agricultural scientists have been studying climate change mainly according to the rules of IPCC (Intergovernmental Panel on Climate Change). In recent years global studies have shown consistent changes in air temperature and rainfall in many places of the world [17, 18]. The Earth\'s average temperature can rise between 1.8ºC and 4.0ºC in the next 100 years [19] with more significant increases for minimum than maximum air temperature. However, in the case of South America temperature trends may not be consistent [20]. Contemporary scientific studies have warned of anomalies in temperature and precipitation patterns indicating the occurrence of global change, with direct consequences on human activities, especially those related to agricultural production [18].
Globally, agriculture accounts for 23% of all emissions of greenhouse gases (GHG) that come from human activity. Parts of these (15%) are derived from agricultural practices and the other part (8%) is from changes in land use [21]. However, in Brazil a greater proportion of agriculture’s contribution to GHG comes from agricultural practices [22]. Soil is also an important source of carbon emission and sequestration [23]. Soil management practices affect to what degree these processes go on. Conventional tillage operations tend to increase carbon release to the atmosphere, whereas conservation tillage and crop rotation with their increased contribution of crop organic matter to the soil tend to increase carbon sequestration [24]. These practices also improve the physical, chemical, and biological balances in the soil. Current agriculture through its production of fiber, bioenergy and food reduces pollution and mitigates GHG emissions [25].
A good example are the results of a research carried out at Embrapa Soja (Londrina, PR, Brazil) for levels of Carbon (C) and Nitrogen (N) in soil under no-tillage (NT) and conventional sowing (CT). [26] found that the biggest difference in results between NT and CT systems occurs in the first 30 cm of the soil profile with a 29% increase in total C content of soil in NT vs. CT. Still, disputing claims of U.S. researchers [27], the survey confirmed significant increases in carbon sequestration in the 0-60cm soil layer. They determined that in NT vs. CT there was 18% and 16% increase in the C and N contents, respectively, of the soil organic matter. Within the same 0-60 cm profile, C and N content of the microbial mass increased 35% and 23%, respectively. Over the 20 years of the research, C and N rates of accumulation within the 0-60cm layer of soil were 800 kg C ha-1 year-1 and 70 kg N ha-1 year-1, respectively, in NT vs. CT. According to the Agricultural Census [28], in 2006 the total no-tillage area for crops in Brazil was 15.6 million hectares.
Because of the rising temperatures associated with global warming, the adaptability of certain crops to an area may change. In particular, drought problems may become worse and yield potential reduced. Because of this, agricultural scientists have been developing strategies to avoid potential adverse climatic changes, especially those related to drought stress.
Problems with drought and temperature stress have to be resolved with research for adaptation like developing new soybean genotypes and cultivars with heat and water loss tolerance.
In Brazil, the southeast region, which accounts for 40% of soybean production, has suffered severe losses due to the occurrence of droughts. Growing seasons in the years 2003 and 2004 for example, showed yield losses due to drought close to 24% and 44%, respectively. In 2004/05 growing season, Rio Grande do Sul state alone, lost an average 70% of its production. In the last 10 seasons, the direct losses can be estimated by more than $18 billion due to the occurrence of drought [29].
The search for commercial cultivars more drought tolerant through classical breeding are relatively difficult because of the complex mechanisms developed by plants to ameliorate this stress. Biotechnology is also an important ally in the breeding for drought tolerant cultivars. With the sequencing of the soybean genome it becomes possible to understand the function of a specific gene and how it interacts with other genes. This allows for breeding new cultivars with greater resistance to environmental stresses.
Currently inside the world agriculture, the increases of yields and the reduces of the costs and risks from failure, have become the basic requirements of competitive. Besides, in terms of economic activity with narrow profit margins, there is no room for risk.
Immense progress has been achieved, adapting the soybeans to obtain high levels of incomes in areas of lower latitudes. The photoperiod limitation was eliminated by the careful selection and also the development of the germoplasma less sensitive to photoperiod. The yields are extremely dependent of the water available and probably are also necessary to increase it to meet the crop transpiration and the productivity enhancement.
Environmental forecasts signaling the increase of the temperatures in the upcoming decades which mean the climate change. The difficulty to feed the world population, (which is in growing fast) using only traditional technologies will be immense shortly. The development of variety tolerant to adverse climatic conditions such as drought and high temperatures, it will be essential, as well as the development of new research tools in the areas of plant biotechnology and ecophysiology. It will enable us to understand the details of the processes involved in physiological and agronomic crops. Only with the development and continued growing in agricultural research, you can ensure food quality and quantity for future generations.
Diabetes is a metabolic disease characterized by hyperglycemia resulting from defects in insulin secretion or function, and is associated with the long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels [1]. One of the main consequences of diabetes is the impairment of self-repairing abilities [2]. Various studies have indicated that diets high in saturated fat and cholesterol contribute to hypercholesterolemia and metabolic disturbances, which may cause hyperglycemic condition in humans and animals [3]. Hyperglycemia can rapidly become severe hyperglycemia and/or ketoacidosis in the presence of infection or other types of stress. The inducing stress can result from the presence of excessive counter regulatory hormones (glucagon, growth hormone, catecholamine, and glucocorticoid; either endogenous or exogenous) and high circulating or tissue levels of inflammatory cytokine [1, 4]. As many reports have shown, a wound healing is an intricate regulation mechanism, which involves many cell populations and molecular mediators, and is one of the key mechanisms that ensures the barrier functions of the skin and the maintenance of body homeostasis. The efficiency of this process is largely determined by the balance of proinflammatory and proregenerative signals, which are mediated by cytokines [5, 6]. But in patients who suffer from diabetes mellitus, chronic wounds occur often due to the impairment of wound healing; major complications of diabetes lead to inflammation and oxidative stress, delayed wound healing, and persistent ulcers. The impaired healing in diabetes is the result of a complex pathophysiology involving vascular, neuropathic, immune, and biochemical components. Hyperglycemia correlates with stiffer blood vessels, which cause slower circulation and microvascular dysfunction, causing reduced tissue oxygenation. Blood vessel alterations observed in diabetic patients also account for reduced leukocyte migration into the wound, which becomes more vulnerable to infections. The hyperglycemic environment itself can compromise leucocyte function. In addition, peripheral neuropathy can lead to numbness of the area and reduced ability to feel pain, which can lead to chronicization of wounds that are not immediately noticed and properly treated [7].
In this chapter, two immunomodulatory extracts (β-glucan and triterpenes) from popular medicinal mushroom were assessed by scientific experiments to examine the functions for treating poorly healing wounds. These immunomodulatory extracts have been studied for its biological effects in mammals widely, and reported to possess antitumor and immunomodulating activities with anti-inflammatory effects and the ability to control tissue cytokines [8, 9, 10]. Here, the scientific experiment results of wound healing were consolidated and the novel application of derivative compounds from traditional medicinal mushroom can be used for treatment of diabetic foot in the future.
Glucan is a polysaccharide structure which is constructed by D-glucose, linked by glycosidic bonds. It is now a common product usually obtained by extracting its components from fungi [11] (such as mushrooms) or yeast cell walls and it has been known in recent studies to effectively stimulate immune cells; it not only can enhance specific immune responses of the organism, but also enhance the nonspecific immune response, and is a good immune regulator. One group of the glucan, the beta-glucans (β-glucans), is a heterogeneous group of glucose polymers consisting of β-(1,3)-linked β-d-glucopyranosyl units with a β-(1,6)-linked side chain of varying distribution and lengths. These polysaccharides are of different chemical compositions, with most belonging to the group of β-glucans; these have β-(1 → 3) linkages in the primary chain of the glucan and additional β-(1 → 6) branch points that are needed for their bioactive response [12, 13]. Many species of mushroom can produce glucan, such as
Research on β-glucans application has indicated that this bioactive immunomodulating substance not only enhances the organism’s ability to resist infection by bacteria, fungi, viruses, and parasites, but even has the effect of inhibiting tumor growth [15]. This novel immunomodulating substance is thought to mediate effects through activation of various immune system components including macrophages, neutrophils, natural killer (NK) cells, and lymphocytes. Moreover, they are demonstrated to possess immunostimulatory activity and enhance wound healing especially by increasing macrophage infiltration into the injury sites and stimulating tissue regeneration [16].
In the field of wound healing, it has been pointed out by many related studies that by activating macrophages, β-glucan can stimulate the regeneration of collagen and help wound healing [17]. In 2001, Kougias and others found that in addition to the receptors on immune cells, (1-3)-β-D-glucans receptors were also found on human dermal fibroblasts. Making fibroblasts directly receive messages from glucans represents a factor that promotes wound healing not only by activating macrophages, but also by stimulating fibroblasts [18]. In study of the mechanism between fibroblasts and wound healing, we can find that after being stimulated by β-glucan, fibroblasts activate two translation factors (transcription factors)-AP-1 (activator protein-1), SP1 (specific protein-1), and two signaling pathways-NF-κB (nuclear factor-κB), NF-1 (nuclear factor-1), can strengthen the immune response at the wound site and promote the hyperplasia and the expression of collagen precursor genes (procollagen genes), thereby generating collagen, to achieve the effect of wound healing [18, 19]. The results from a reference illustrated that mushroom polysaccharides derived from Schizophyllum (1-3),(1-6)-β-D-glucans, were mixed with gelatin to make artificial skin, either by in vitro cell culture or transplanted into mice, which led to the observation of the growth of new tissues and finding that they all have the effect of promoting epidermal cellization [20]. Mushroom β-glucan’s (MBG) role has also been confirmed in tests on the recovery of liver cuts in fish and skin wounds in rats. By stimulating the mechanism of Wnt/β catenin signaling signal transmission, liver cell hyperplasia, and cellular activity, it promotes wound healing [13]. In the application of β-D-glucans in wound healing, it has a reduced chance of infection after surgery [21]; the synthesis of polysaccharides and collagen matrix can promote the recovery of local deep scald skin also has a medical effect for the relief of patients’ pain [22].
In 2018, we carried out a study on mushroom β-glucan (MBG) from
Mushroom β-glucan-containing bio-fiber sponge dressing. (a) Appearance of mushroom β-glucan-containing bio-fiber sponge dressing; (b) mushroom β-glucan-containing particles dispersed in the fiber sponge structure (1000×).
The prepared fiber sponge substrate has a high magnification of moisture absorption and swelling ratio and an appropriate structural stability that causes the release of mushroom β-glucan (MBG) in the substrate slowly. It is expected that it will have an extended-release ability to produce immunostimulatory polysaccharides, which can improve the shortcomings of commercially available sponge dressing products.
In an experiment using three diabetic model pigs, we explored whether mushroom β-glucan (MBG) sponge dressing can accelerate wound healing rate when applied to man-cut wounds. For the present study, all the mammal experiments were performed in accordance with protocol by the Institutional Animal Care and Use Committee (IACUC) of Agricultural Technology Research Institute (ATRI, in Taiwan). Type I diabetes pigs were manual Streptozotocin-induced (to generate chronic wound healing), housed, and surgery was operated in SPF animal room facilities by ATRI Animal Technology Laboratories. Six square wounds (2 ± 0.5 cm × 2 ± 0.5 cm) with full skin layer on the back of one pig were formed by manual operation, three on each side, L1, L2, L3 on the left;R1, R2, R3 on the right (schematic diagram in Figure 2), and randomly apply the test mushroom β-glucan (MBG) sponge dressing or control dressing to the wound in the above. Then, the wound healing of each test substance was continuously observed, and the effect of the test substance on wound healing was explored based on pathological interpretation. During the test period, the test substances in each group did not affect the growth of the pigs and also did not cause death.
Wounds with full skin layer on the diabetic pig. Six square wounds (2 ± 0.5 cm × 2 ± 0.5 cm) with full skin layer on pigs were formed by manual operation, randomly apply the test mushroom β-glucan (MBG) sponge dressing or control dressing to the wound in the above (three pigs, each test dressing N = 4 or 5).
In data calculation, the average value (mean) and standard error of the mean (SEM) of each test group were calculated by Microsoft Excel, and finally presented in the report as mean ± SEM. In statistical analysis, one-way ANOVA was performed with IBM SPSS Statistics 20 analysis software, and the Scheffe’s post-mortem analysis method was used. The lowercase letter labels in figures mean that there is a significant difference between those who do not have the same letter at the observation time point (p < 0.05). In the experimental results, on the 10th day of the experiment, the secretion of tissue fluid of each test group decreased, and it was observed that the granulation tissue had grown to fill the entire wound, forming a bright red and smooth appearance, and the neonatal epithelial tissue could be observed at the edge of the wound, the wound area was significantly reduced, for example in Figure 3. The degree of wound healing speed was group B: 51.1% > group D: 49.2% > group C: 44.3% > group A: 41.0%. In statistical analysis results: group A and group B, group A and group C, group A and group D reach statistical significance p < 0.05. The statistical significance of group B and C was not more than p > 0.05, and the statistical significance of group B and D was not more than p > 0.05. Group C and D did not reach statistical significance p > 0.05. The test mushroom β-glucan (MBG) sponge dressing showed better wound healing performance than vehicle control (Figure 4).
Ten days’ observation result at the edge of the wound. The performance of wound healing appearance at 10th day, the granulation tissue had grown to fill the entire wound, forming a bright red and smooth appearance, and the neonatal epithelial tissue could be observed at the edge of the wound.
Wound healing ratio.
In the histopathological examination result, the thickness of the skin dermal layer and epidermal layer were measured to evaluate the wound healing. In the diabetic pig model, the thickness of the skin dermal layer of the animals in each test group was not different from each other (Figure 5). The analysis of the thickness of the epidermal layer showed that the thickness of the test group A is significantly higher than that of mushroom β-glucan (MBG) sponge dressing (test group B) (p < 0.01) (Figure 6). Epidermal cell layer tissue formation (epithelization) showed that the wound healing of each group of animals in the diabetic pig model was good, and there was no statistical difference between the test groups in the evaluation of epithelial cell formation response (Figure 7).
The thickness of the skin dermal layer of the animals in each test group.
The thickness of the epidermal layer of the animals in each test group.
The evaluation of epithelial cell formation response of the animals in each test group.
The results of wound healing tissue react evaluation showed that the inflammatory reaction of animal skin in test group B and test group D was significantly higher than that in control group (test group A) with statistical difference (p < 0.01). In addition, the degree of inflammatory response stimulation in test group C was significantly slowed down compared with the positive control group (test group D), indicating that test group B and test group D stimulated local skin inflammation and accelerated skin wound healing, but significantly slowed down in the experimental group C (Figure 8). After assay of the degree of skin blood capillary, the experimental group B (M1P1 0.5%) can be observed that the response is statistically different from the control group (test group A), showing that the new blood capillary of test substance is more effective than the control group (test group A) in wound healing (Figure 9). Moreover, section slices of recovered wound indicated that mushroom β-glucan (MBG) sponge dressing treatment revealed better wound tissue flatness effects than untreated group and positive control (Figure 10(a)–(d)).
The degree of inflammatory response stimulation of the animals in each test group.
The degree of skin new blood capillary in each test group.
Section slices of recovered wound in each test group. (a) Animal ID: 068-L1 H&E staining, 50×. Group A; (b) animal ID: 069-L3 H&E staining, 50×. Group B; (c) animal ID: 070-R1 H&E staining, 50×. Group C; (d) animal ID: 069-L2 H&E staining, 50×. Group D. Mushroom β-glucan (MBG) sponge dressing treatment (b and c) reveals better wound tissue flatness effects than untreated group and positive control.
In conclusion, based on the results of epidermal layer, dermal layer thickness and the local tissue reaction of wound healing, the mushroom β-glucan (MBG) sponge dressing M1P1 0.5% treatment group (test group B) is more effective in wound healing than the test substance treatment group C (M1P1 1%) and the positive control group (test group D). When the mushroom β-glucan was applied on diabetic pigs wound, we expected the bioactive immunomodulation from mushroom β-glucan (MBG) occurred in chronic wound microenvironment, and promote wound healing.
Since antiquity, mushrooms have been valued by humankind as a culinary wonder and folk medicine in Oriental practice. In recent years, mushrooms have emerged as a source of dietary supplements, antioxidants, anticancer, prebiotic, immunomodulating, anti-inflammatory, cardiovascular, antimicrobial, and antidiabetic functions [23]. Among the different types of mushrooms,
Several plant derivatives, such as secondary metabolites, are capable of promoting wound healing in various animal models. A group of secondary metabolites attracting much attention is the pentacyclic triterpenes [27, 28]. Triterpenes, a large and structurally diverse group of natural products derived from squalene or related acyclic 30-carbon precursors, are uniquely abundant with well-characterized biological activities of modulation on the immune cells [29]. In surgical wounds, the triterpenes induced a reduction in time to closure, and this effect was reported in virtually all wound types. In references, triterpenes also modulate the production of ROS in the wound microenvironment, accelerating the process of tissue repair through inducing cell migration, cell proliferation, and collagen deposition [27].
According to these findings and hypotheses, we used triterpenes extracted from
The
HPLC identification of
Retention time | Predicted triterpenes species | Height (mAU) | Area (mAU × min) |
---|---|---|---|
38.59 | Antcin H | 0.06 | 0.01 |
43.01 | Dehydrosulphurenic acid, | 2.41 | 0.95 |
50.50 | Eburicoic acid | 1.44 | 0.73 |
59.65 | Methyl antcinate B | 2.01 | 0.65 |
74.07 | Dehydroeburicoic acid | 1.22 | 0.53 |
HPLC analyzed results of
Diabetes mouse skin wound healing examination was carried out following the wound healing model assay procedure [13, 31]. All study procedures were performed in accordance with protocol approved by the National Taiwan University Animal and Use Committee (NTUAUC). We used 15 of 6-week-old male ICR (N = 3, purchased from Laboratory Animal Center, National Taiwan University College of Medicine) for this experiment, and animals were housed in the Animal Housing Facility of National Taiwan University, College of Life Science. At the beginning, manual incision wound (one of 1.5 × 0.5 cm2 full thickness) was made on mice skin. Each wound was cleaned by the 3 M Cavilon™ No Rinse-Skin Cleanser and then sprayed with 3 M Cavilon™ No Sting Barrier Film solution with or without
Five experiment groups, including: 1. control mice, sprayed with 3 M Cavilon™ No Sting Barrier Film, 2. diabetic mice, sprayed with 3 M Cavilon™ No Sting Barrier Film, 3. diabetes mice, sprayed with 5 mg/kg triterpenes with 3 M Cavilon™ No Sting Barrier Film, 4. diabetic mice sprayed with 10 mg/kg triterpenes with 3MCavilon™ No Sting Barrier Film, and 5. diabetic mice sprayed with 20 mg/kg triterpenes with 3MCavilon™ No Sting Barrier Film. The wound recovery assay was observed by area change of wound healing appearance. The surgical wound area observation of the five groups was as shown in Figure 12 (on the left). The presented result as shown in the control group (without diabetes), respectively, comparing with the diabetes mice, sprayed with 5, 10, and 20 mg/kg triterpenes is significantly different in the Days 1–17 after the surgery. In the observation of Day 1 to the Day 5, the presented data has shown that the recovery of the wounded area is markedly in the control and sprayed with 20 mg/kg triterpenes group but not in the diabetes and other treatment groups. In the control group, the recovery process is significantly observed in the Day 5 followed the surgery but the diabetes group has not shown the wound recovery situation in the Day 5. In the Day 7 observation, the wound was initiated to be contacted in the control and 20 mg/kg triterpenes group, other treatment groups were not significant presented with recovery especially the diabetes group. The long-term observation of the wound healing process can be found that the control group completely healing in the Day 17. The 20 mg/kg triterpenes group was not completely wound healing (criteria was presented as hair totally overlapped on the wound) however, the wound exactly has been gradually recovery compared to the diabetes group Figure 12 (right).
Long-term observation of the wound healing process. (Left) The performance of wound healing appearance on mice; (Right) recovery effectiveness compared to the diabetes group.
In this study, serum biological analysis was also carried out in the five groups. After administration of different concentrations of
Serum circulating thrombopoietin (TPO) after administration of different concentrations of
Serum CCL1 after administration of different concentration
As the result, the diabetic mice with skin wound examination, the detection of inflammatory factors such as CCL1 and TPO expression were found to induce than control mice, the hyperglycemia does cause an inflammatory response. Moreover, to the best of our knowledge, hyperglycemia impairs the tissue healing associated with an increased and prolonged inflammatory response. An investigation of the anti-inflammatory response in wound healing as affected by the triterpenes verified the promotion of wound recovery.
As the microenvironment of inflammation related to cellular transdifferentiation, migration, proliferation, survival, and extracellular matrix formation. And many factors are clearly involved in maintaining the balance between appropriate fibroblast activation and the fibrosis resulting from their continued activation for wound healing. We suggest the mechanism that the extracted triterpenes may bind to the glucocorticoid responsive elements (GREs) of target genes to regulate gene expression by mechanisms such as suppressing the expression of proinflammatory proteins and enhancing the expression of anti-inflammatory proteins. Furthermore, oleanolic acid is a triterpene that can increase insulin secretion by activating muscarinic M3 receptors in pancreatic β-cells through the Ach released from cholinergic nerve terminals. According to these findings, we suggest that the extracted triterpenes from
The proposed mechanism of triterpenes is involved in the diabetic mice with anti-inflammation. Figure description: The mechanism of triterpenes was speculated as binding to the glucocorticoid responsive elements (GREs) of target genes to regulate gene expression such as by suppressing the expression of proinflammatory proteins and enhancing the expression of anti-inflammatory proteins. Furthermore, oleanolic acid is a triterpene that can increase insulin secretion by activating muscarinic M3 receptors in pancreatic β-cells through the Ach released from cholinergic nerve terminals. According to these findings, we suggest that the extracted triterpenes could directly permeate the cell to bind with the GRE or indirectly combine with the M3 receptor, resulting in an anti-inflammatory effect and thereby inducing wound healing in the diabetic mice.
Frequent and uncontrolled hyperglycemic state from type II diabetes mellitus (T2DM) can result in peripheral neuropathy in later stages of the disease. Patients who suffer from peripheral neuropathy will often suffer from a diabetic foot that results directly from peripheral arterial disease (PAD) and/or sensory neuropathy. It is a chronic complication of T2DM. If control measures such as infections and blood glucose controls are not properly implemented, a diabetic foot can often lead to ulcers or gangrene, which eventually result in amputations.
In 2018, a patient who suffered from T2DM volunteered to be included in this case study. During the study, as shown in Figure 16a and b, the patient suffered from advanced stage of PAD, which resulted in ulcers and gangrenes on the foot’s lateral and anterior sides. While the patient followed the primary physician’s instructions for lifestyle alteration, routine blood glucose management as well as performing a graft surgery for the affected area, under the physician’s discretion, a topical test article containing β-glucan isolated from
The severe ulcers on diabetic patient’s feet and treated with β-glucan (MBG) and triterpenes. (a, b) Gangrene resulted from peripheral arterial disease and infections. (c, d) After the test article containing
A progress for diabetic patient’s feet wound healing. (a–h) The healing progress of gangrenes on a T2DM patient’s feet, treated by test article containing
The authors thank the technical services provided by the ATRI Animal Technology Laboratories to carry out wound repairing efficacy experiments on large mammals (ordinary or diabetic pigs) and the Council of Agriculture, Taiwan for funding support.
The authors declare no conflict of interest.
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In Section 1, the problems caused by greenhouse gas emissions are addressed, and different technologies used in CO2 capture are briefly introduced. The aim of this chapter is to provide a comprehensive overview of CO2 adsorption on solid materials with special focus on an emerging class of materials called metal organic frameworks owing to their unique characteristics comprising extraordinary surface areas, high porosity, and the readiness for systematic tailoring of their porous structure. Recent literature on CO2 capture using MOFs is reviewed, and the assessment of CO2 uptake, selectivity, and heat of adsorption of different MOFs is summarized, particularly the performance at low pressures which is relevant to post-combustion capture applications. Different strategies employed to improve the performance of MOFs are summarized along with major challenges facing the application of MOFs in CO2 capture. 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Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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