The vineyard area, grape production, and wine production in China.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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A fermented beverage of rice, honey, and fruit (hawthorn fruit and/or grape) absorbed into pottery jars from the early Neolithic village of Jiahu in China’s Henan province indicate the beverage’s earlier existence, dated back to 7000 B.C [1]. The viticulture and enology history in China could be traced back to the Han dynasty (138 B.C.). Zhang Qian was the first to introduce vines and winemaking techniques into China through the Silk Road. Since then, wine has been made in all of ancient China’s dynasties [2], although it did not become popular until the Tang dynasty (618–907 A.D.). As a symbol of Chinese wine culture, many famous poetries were written and spread for thousands of years. During the Yuan dynasty (1271–1368 A.D.), the government instructed wine and other fruit beverages to be a replacement for cereal grain beverages. Moreover, an agricultural science literature known as ‘Nong Sang Ji Yao’ also recorded viticultural and winemaking practices in detail, which formed the most prosperous period of the wine industry in ancient China’s history. The modern Chinese wine industry began at the end of the 19th Century when a high-ranking official brought more than 100
Summary of the history and development of China wine industry.
In the past decades, the area used for grape cultivation and the total wine production and consumption in China has rapidly expanded. Relevant statistics regarding the grape and wine industry since the birth of the People’s Republic of China are shown in Table 1.
Year | Vineyard area (kha) | Grape production (mt) | Wine production (mhl) | Year | Vineyard area (kha) | Grape production (mt) | Wine production (mhl) |
---|---|---|---|---|---|---|---|
1950 | 3.2 | 0.04 | 0.83(khl) | 2000 | 283 | 3.28 | 2.02 |
1959 | 18 | 0.09 | 0.08 | 2005 | 408 | 5.79 | 4.34 |
1965 | 11.5 | 0.1 | 0.12 | 2010 | 513 | 8.14 | 10.89 |
1970 | / | 0.09 | 0.2 | 2012 | 613 | 10.01 | 13.82 |
1975 | 64 | 0.12 | 0.35 | 2014 | 689 | 11.73 | 11.61 |
1980 | 32 | 0.11 | 0.78 | 2016 | 713 | 12.63 | 11.37 |
1985 | 87 | 0.36 | 2.33 | 2018 | 820 | 13.67 | 6.29 |
1990 | 121 | 0.86 | 2.54 | 2020 | 785 | 14.2 | 6.6 |
1995 | 149 | 1.74 | 2.29 |
The vineyard area, grape production, and wine production in China.
As can be seen from Table 1 below, China has accomplished great success in the grape and wine industry with unprecedented speed, both in terms of vineyard area, wine production, and consumption. According to the latest International Organization of Vine and Wine (OIV) report on the world Viti vinicultural situation (2019 and 2020) [4, 5], the size of the total world area under vines (regardless of the final destination of the grapes and including vineyards not yet in production) remained stable at 7.3 mha (millions of hectares) in 2020. With 961 kha, Spain remains the clear leader in terms of cultivated vine area, followed by France (797 kha) and China (785kha).
The world wine production (excluding juice and musts) in 2020 was estimated at 258 mhl as Italy (49.10 mhl) maintained its position as the world’s leading producer, followed by France (46.60 mhl) and Spain (40.70 mhl). China, on the other hand, produced 6.60 mhl. The data shows a slight drop in global wine consumption (estimated at around 234 mhl) in 2020 because of the COVID-19 outbreak. The United States (33.0 mhl), France (24.7mhl), and Italy (24.5 mhl) maintained their top three positions as the world’s largest consuming countries with China ranking sixth with 12.4 mhl consumption in the world.
In China, Red varieties account for nearly 80% of the total vineyard area, while the white varieties proportion was only 20% [3]. Red wine is also far more popular in the Chinese market than other types of wine, and a large section of the population refers to such wine as “红酒” (Hóngjiǔ), because of its red color.
According to administrative division and the meteorological and geographical regionalization, China wine producing regions have been widely categorized into 11 recognized regions [6], including the Northeast, the Eastern Region of Helan Mountain, Beijing-Tianjin-Hebei (also known as Jing-Jin-Ji), Shandong (also known as Jiaodong Peninsula), Old Course of the Yellow River, Loess Plateau, Inner Mongolia, Hexi Corridor, Southwest Alpine, Xinjiang and Others (Figure 2).
Chinese wine production regions.
As can be seen from Figure 2, viticulture and enology are widely distributed in China, from 24 to 47°N, 76–132°E. The majority of vineyards are located in northern China, where they are affected by the continental monsoon climate with cold, dry winters and extremely low temperatures of −15°C during the winter. The fatal flaw for grape varieties is not only extremely low temperatures but also large amounts of water evaporation caused by extreme droughts in spring and winter, often known as ‘drought-freezing’. As a result, measures have been adopted to protect vines from the cold and drought during the winter months. One of the most effective methods is to bury the vine in the soil, which is also known as buried viticulture.
In addition, some sub-areas in China’s south and southwest have been identified as wine producing regions. These regions are generally located at a high altitude with a complex ecological condition, also suitable for the cultivation of
Regions | Producing area | Latitude & Longitude | Vineyard area (kha) | Main variety | Wine production (mhl) | Frost-free period (d) | Rainfall mm | Drought index | Climatic subdivisions | Active accumulated temperature (>10°C) | Extreme low temperature °C | Altitude (m) | Agrotype | ||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Range | Average value | Range | Average value | ||||||||||||
Northeast | Jilin, Liaoning, Heilongjiang | 39°18′-45°45′N, 118°50′-133°30′E | 8.25 | Shuang, Hong, Shuang You, Zuo You Hong, Bei Bing Hong, Gong Zhu Bai, Vidal | 1.15 | 147–222 | 171 | 400–1000 | 0.67–1.61 | Cold temperate and mid-temperate semi-humid region | 2567–2779 | −33.7 ∼ −15 | 12.2–422 | 207.15 | Chernozems |
Beijing-Tianjin-Heibei | Changli, Tianjin, Huaizhuo Basin | 36°03′-42°40′N, 113°27′-119°50′ E | 17.01 | Cabernet Sauvignon, Cabernet Gernischt, Melort, Muscat Hamburg, Chardonnay, Italian Riesling, Longyan | 0.72 | 162–228 | 206 | 350 ∼ 770 | 0.85–2.26 | Warm-temperate semi-arid to semi-humid region | 3800–4200 | −23.4 ∼ −14.2 | 1.30–629.30 | 190.78 | Cinnamon soil, Fluvo-aquic soil, Brown earth |
Shangdong | Jiaodong Peninsula, Central Shandong, Northwestern Shandong, Southern Shangdong | 34°22′-38°23′ N, 114°47′-122°43′ E | 16.75 | Cabernet Sauvignon, Cabernet Gernischt, Melort, Cabernet Franc, Chardonnay, Italian Riesling | 3.84 | 212–241 | 230 | 550–950 | 0.81–1.55 | Warm-temperate semi-humid region | 3800–4600 | −15.3 ∼ −10.2 | 4.80–171.5 | 68.6 | Brown earth |
Old Course of the Yellow River | Henan, Anhui, Jiangsu | 33°36′-34°56′N, 114°49′-117°12′ E | 1.5 | Cabernet Sauvignon, Melort, Cabernet Franc, Chardonnay, Italian Riesling, Rkatsiteli, Bacco Noir | 1.88 | 228–245 | 238 | 600 ∼ 900 | 0.91–1.25 | Warm-temperate semi-humid region | 4000 | −11.6 ∼ −9.78 | 34.7–110.4 | 57.8 | Yellow moist soil |
Loess Plateau | Shanbei plateau, Kuan-Chung Plain, Qinling-Daba Mountain, Central Shanxi, Southern Shangxi | 33°21′-39°35′ N, 107°59′-113°01′E | 3.74 | Cabernet Sauvignon, Melort, Cabernet Gernischt, Yan 73, Meili, Chardonnay, Ugni Blanc, Italian Riesling, Ecolly Bei Bing Hong, Hu Tai | 0.34 | 165–254 | 213 | 300 ∼ 700 | 1.19–2.09 | Mid-temperate and warm-temperate semi-arid to semi-humid region | 3000–4500 | −23.5 ∼ −8.6 | 402.9–1134.6 | 654.2 | Black loessial soil, Cultivated loessial soil, Yellow-brown earth, Cinnamon soil |
Inner Mongolia | Wuhai | 39°15′-39°52′ N, 106°36′-107°06′ E | 6.14 | Cabernet Sauvignon, | 0.03 | 143–184 | 169 | 50–450 | 1.50–6.91 | Cold and mid-temperate arid to semi-arid region | 2800–3600 | −26.0 ∼ −20.2 | 178.7–1561.4 | 911.6 | Sandy loam soil, Loamy soil, Gravelly soil |
Eastern Region of Ningxia Helan Mountain | Yinchuan, Qingtongxia, Hongsibu, Yongning, Helen | 37°28′-39°05′ N, 105°21′-106°80′ E | 34 | Cabernet Sauvignon, Melort, Cabernet Gernischt, Cabernet Franc, Pinot Noir Chardonnay, Italian Riesling, Riesling | 0.34 | 172–190 | 183 | 200–700 | 4.31–5.22 | Cold and mid-temperate arid region | 3100–3500 | −21.2 ∼ −18.9 | 1092.5–1128.8 | 1110.9 | Sierozems, Eolian sandy soil, Cumulated irrigated soil |
Hexi Corridor | Wuwei, Zhangye, Jiayuguan | 36°46′-40°12′ N, 93°99′-104°43′ E | 20.55 | Cabernet Sauvignon, Pinot Noir, Melort, Cabernet Gernischt, Chardonnay, Italian Riesling, Vidal | 0.82 | 141–213 | 173 | 37.3–230 | 2.22–31.42 | Cold temperate arid to semi-arid region | 3200 | −22.7 ∼ −14.4 | 11390–2311.8 | 1517 | Gravelly soil, Sandy loam soil |
Xinjiang | North Slope of Tianshan Mountains, Lli Valley, Yanqi Basin, Turpan-Hami Basin | 39°30′-44°10′ N, 80°28′-96°23′ E | 36.7 | Cabernet Sauvignon, Melort, Yan 73,Marselan, Syrah Chardonnay, Riesling, Pitit manseng, | 0.52 | 176–242 | 199 | 50 ∼ 300 | 3.91–246.45 | Mid-temperate arid region | 3500–4000 | −31.9 ∼ −13.6 | 1.0–1422.0 | 837.6 | Brown desery soil, Gray desery soil, Fluvo-aquic soil |
Southwest Alpine | Southwest Sichuan, Western Sichuan Plateau, Shangri-La region, Southeast Yunnan | 23°50′-31°43′N, 99°70′-103°49′ E | 5.45 | Cabernet Sauvignon, Melort, Cabernet Gernischt, Fa-guoye,Rose Honey,Crystal | 0.31 | 278–353 | 273 | 500 ∼ 800 | 0.66–1.92 | Subtropical semi-humid region | 3000–5000 | −10.6 ∼ −0.3 | 1254.1–3319.0 | 1986.3 | Gravelly sandy loam, Cinnamon soil, Red earth, Lime soil, Brown earth, Red clay soil, Cinnamon soil, Torrid red soil, Sandy soil |
Others | Northern Hunan, Southeastern Hunan, Hechi | 23°47′-29°57′ N, 108°47′-113°77′ E | 13.3 | Vitis Xiangniang No.1, Vitis Yeniang No.1, Yenaing No.2 | 0.07 | 277–365 | 314 | 0.44–0.72 | Subtropical humid region | >5000 | −5.0 ∼ −3.6 | 40.2–355.5 | 218.6 | Red earth, Yellow earth, Lateritic red earth, Humid-thermo ferralitic |
The vineyard area for wine grape in each region can be seen from Table 2, with a total of 163.39 kha, however, the CADA report (2018) shows that the wine grape area in China was only 85.19 kha, which could be due to some table grapes that are also used for winemaking being counted in Table 2.
In China, the main cultivated grape varieties in most regions are similar. The red grape varieties play a dominant role which occupies more than 80% [3], and among them, Cabernet Sauvignon is the most widely planted variety, followed by Merlot and Cabernet Gernischt (Table 2).
Recently, a new red variety,
White grape varieties only represent a small quantity of about 20% in China. Among them, Chardonnay, Italian Riesling, and Riesling are the commonly cultivated varieties in the various regions (Table 2). A traditional white grape variety known as Longyan, has the potential to be utilized as both a table grape and a wine grape. As a late-harvested variety, the Longyan grape has been widely cultivated in Beijing-Tianjin-Heibei, Shandong, and Loess Plateau regions for the development of wine characterized by a green to yellow color, fresh fruity flavor, and good taste [8].
China has very abundant
Since the 1950s, significant progress has been made in understanding and utilizing wild
Elite clones and hybrids varieties of
As a wine grape, the
When Bei Bing Hong (a variety of
Lan [11] studied the evolution of free and glycosidically bound volatile compounds in ‘Beibinghong’ grape berries during on-vine, over-ripening, and freezing processes. The results showed that the aroma profiles of ‘Beibinghong’ icewine berries were characterized by C6 compounds, higher alcohols, and terpenoids in free fractions as well as carbonyl compounds, higher alcohols, C6 alcohols, and terpenoids in bound fractions. A striking alteration of the volatile profile of C6 alcohols, higher alcohols, and oxidative terpene derivatives occurred at sub-zero temperatures. These changes were attributed to a series of reactions (biotransformation, oxidation, and anaerobic metabolism) induced by water loss and particularly, freeze–thaw cycles [11].
Anthocyanins are responsible for the color of grapes and wine. Zhao [10] analyzed the anthocyanin profiles of grape berries of
Additionally, Li [9] also revealed that
Spine grape was used as table grape years ago, because of its larger berry size compared to other wild species, with an average fruit weight between 3.0–4.5 grams, and a total soluble solid range of 14.5%–16.0% [20]. Recently, with the rapid increase of cultivated area, only a small quantity of spine grapes was made available as fresh edible fruit and a major portion tend to be abandoned each year. Researchers have found that the intense process of converting the Spine grape to wine not only prevents the wastage of grape fruits but also brings high economic benefits to local growers [21]. More so, the development of new cultivars also promotes Spine wine production.
Meng analyzed the physicochemical parameters and aromatic components of nine clones of spine grape from Zhongfang County (Hunan Province, China) [22]. The berry weight, total soluble solids, titratable acids (expressed as equivalent of tartaric acid), and pH were found to be in the ranges of 2.08–3.88 g, 9.5–15.4 Brix, 1.99–3.93 g/L, and 3.16–3.77, respectively, indicating that the clones are more suitable for winemaking compared to the wild spine grape.
Flavor compounds are important quality indexes for wine production, which are mainly derived from grape berries, and can be affected by soil, altitude, slope, and cultivation management among others. In two different studies, Meng [22] and Zhao [18] respectively evaluated the free aromatic components and the influence of different altitudes on flavor compounds of Spine grape clones, ‘Ziqiu‘, ‘Seputao’,’ Miputao’,’ Xiangzhenzhu’, ‘Tianputao’, and’ Baiputao’. According to the findings, C6 compounds were the most abundant aromatic components in various spine grape clones, accounting for 71–94% of the total aromatic compounds identified. The most predominant compounds were (E,E)-2,4-hexadienal and (E)-2-hexenal [22]. At the height of 700 meters above sea level, the contents of anthocyanins, non-anthocyanin phenolic compounds, and aroma compounds in ‘Seputao’ were significantly higher than those at 240 meters and 600 meters altitudes. However, at the altitude of 240 meters, the contents of reducing sugars, anthocyanins, non-anthocyanin phenolic compounds, and aroma compounds in‘Ziqiu’were the highest among three altitudes 240, 600, and 700 meters [18].
Meng [19] also investigated the phenolic profiles and antioxidant activity of four spine grapes cultivars (Junzi #1, Junzi #2, Liantang, and Baiyu) from Chongyi County, Jiangxi Province, China. It was revealed that Junzi #1 had the highest phenolic content and the strongest antioxidant capacity, HPLC analysis also showed that the (+)-catechin was the most abundant phenolics while hydroxycinnamic acids were the major phenolic acids [19]. Regarding some individual phenolic compounds, JZ-1 contained the highest p-coumaric acid, coumarin, trans-resveratrol, and (+)-catechin contents, while BY had the highest rutin and quercetin contents.
The same researcher also characterized the phenolic profile of young wines made from spine grape. Like most vinifera wines, flavan-3-ols were the major class of phenolic compounds present in spine grape wines while quercetin-3-rhamnoside was the main singular flavonol [21]. In addition, syringetin-3-glucoside and dihydroquercetin-3-hexoside were the characteristic flavonols of red and white spine grape wines, respectively, while coutaric acid and fertaric acid were the dominant phenolic acids [21].
Organic acids play a key role in grape and wine quality. The acid component of grape berries mainly consists of tartaric acid, malic acid, lactic acid, acetic acid, citric acid, and oxalic acid. The total acidity in
The effect of deacidification reagents (KHCO3 and CaCO3) on the aroma compounds of spine wine was studied by Li [23]. The results showed that the OAVs of compounds with flavors of fruit, cheese, caramel, and chemical were reduced. However, sensory evaluation revealed that the mouthfeel and aroma characteristics of spine wine were improved after deacidification.
Due to the relatively low sugar content in Spine grapes, ranging from 12.3 to 15.9°Brix, an early winemaking study showed that sugar addition was required for red Spine wine production to improve wine quality [24]. Conversely, this neutral grape characterized by low sugar levels and high acidity is suitable for making distilled spirit-based beverages [25].
Currently, high quality Spine grape spirits are produced by several local wineries and are welcomed by local consumers. Xiang [26] identified the key odor-active volatile compounds in the head, heart, and tail fractions of freshly distilled spirits from Spine grape (
Selection studies have also been conducted on
Also, the grape berries of
Fang examined the effects of different processes on the flavor components of wild
Liu also proved that carbonic maceration increased the contents of esters, acids, and phenols as well as the species and contents of volatile compounds in wines [31]. The combination of carbonic maceration and malolactic fermentation could result in more volatile compounds in wines, giving such wines a unique taste distinct from traditional wines [31]. Similar results were reported in
In China, most of the viticulture regions are distributed in cold and mid-temperate regions (Table 2), these regions are typically affected by the continental monsoon climate with cold, dry winters, and frequent early spring frosts, which can result in severe freezing injury and dehydration risks to branches and roots [32, 33]. It has been acknowledged that, as the main cultivated wine grape variety, the grape and wine quality of
In order to choose suitable measures for overwintering, interspecific hybrid breeding, rootstock grafting, wind dispersing cold air, adjusting plant load, soil or material covering, delaying pruning, and other technics were implemented by numerous of researchers all over the world [34, 35]. However, after years of experiments, burying the vines into the soil is still the most effective way to protect vines over winter. In general, the vines are taken down off the trellis after pruning and then buried into the soil (more than 30 cm underground) in the winter, and the soil is removed before the sprouting in the next spring. Both artificial and mechanical methods are used to complete the burying and unearthing of the vines, and this work should be done very carefully to prevent damage to branches and buds. To aid buried viticulture, several cover materials and methods, such as film mulching, industrial cotton, straw mattress, and plastic have been devised and used. Additionally, various types of vine burying and soil removing equipment (or digging machines) have been designed and employed [36].
Because buried management exposes the soil surface in winter and early spring, there is an increased danger of wind erosion and sandstorms, which may cause ecological problems in viticulture regions in northern China. Recently, a new viticultural procedure was reported during winter pruning to ameliorate this phenomenon, by clutching the vine shoots on the wires until next spring. Also, a windbreak was built as a protective function to reduce wind speed, and the dangers of sand storms as well [37].
In conclusion, buried viticulture is labor intensive, costly, and has the potential to cause damage and diseases to branches while also destroying the ecological environment. Buried viticulture further limits mechanized production and all these challenges are serious impediments to China’s wine development [34].
Nowadays, with a decrease in wine consumption and an increase in imported wines, there is no mention of competition from Chinese liquor -Baijiu, Chinese rice wine, and beer, and domestic wine production in China has decreased year by year since 2012. It is now a common phenomenon in the global wine industry where total wine production exceeds demand and as such, China’s wine manufacturers will continue to face great pressure in the coming years. To preserve the wine market, enologists and researchers must improve wine quality, increase shelf life, and produce new products.
In this chapter, some useful pretreatment techniques, such as berry heterogeneity, cold maceration, carbonic maceration, flash evaporation, saignée, pulsed electric field, high hydrostatic pressure, and withering procedure are further reviewed (Table 3).
Technics | Treatment | Mechanism | Major impacts on wine composition | Reference |
---|---|---|---|---|
Berry heterogeneity | Berry classification | Heterogeneity influence fruits weight, diameter, berry density, and soluble solids content | Smaller fruits reduced the contents of malic acid and pH value, increased wine color, phenolic substances, varied the aroma substances and titratable acids contents | [38] |
Cold maceration | Temperature below 10°C for 3-7 days | Lower temperature improved the maceration time and substance from grape skins | Improving wine color and aroma | [39] |
Carbonic Maceration | Sealed tank with CO2 at 30–35°C for 8–15 days | Anaerobic metabolism by berry enzymes | Reducing acid, color, and tannin, improving aroma quality | [40] |
Flash evaporation | Heat must to 85–91°C by steam at −0.9 Pa | Break down the skins at high temperature with decompression condition | Increasing the extraction of total phenols, anthocyanidin, and aroma compounds | [41] |
Saignée | 30% of juice was released after 12 hours | Removing juice to increase skin ratio of red wine | Simultaneous production of dry-red and rose wines, increase the color, aroma intensity, and antioxidant properties of red wine | [42] |
Pulsed electric field | 3000 Hz, 10 pulse, with 6.5-35kv/cm electric field intensity | Electrical breakdown, electroporation perforated theory | Increasing phenolic profile and wine color | [43] |
High hydrostatic pressure | Grapes were subjected to HHP treatments(200-550Mpa) for 10 min | Provide the activation energy for extraction chemical compounds at low temperature without break covalent bonds | Controlled microbial populations, increased phenolic compounds, and anthocyanin extraction, returned higher aromatic quality and color scores in wine | [44] |
Withering | Loss of water by 20–40% | Concentrated the grape substance by dehydration | Increased alcohol, residual sugar, and acidity content, improved, phenols, antioxidant activity, brightness, yellow tone, aroma, and taste | [45] |
Pretreatment techniques before fermentation.
China has become one of the most important wine countries in the world, the history and current situation of Chinese grape and wine industry were reported. According to the meteorological and geographical regionalization, China wine producing area have been categorized into 11 regions, the detailed information of these regions was listed.
In many parts of China, Vitis wild species such as
The authors would like to thank Sam Faisal Eudes for the language correction. Huo Xingsan from China Alcoholic Drinks Association, and Sun Zhijun from winechina.com for providing wine data in China.
This work was supported by the National Key Research and Development Project (Item No. 2019YFD1002500). The Horticulturists, enologists, and sommeliers training and monograph writing in Gansu Hexi Corridor (Grant No. Ganshangcaiwufa 2017–466).
Chronic myelogenous leukemia (CML) is a clonal hematopoietic stem cell disorder associated with the activity of
The free radical scavengers like alpha-tocopherol may be effective against cancer-associated oxidative stress. The mean serum vitamin E level significantly decreased in CML patients that seems to be quite in agreement with free radical involvement in CML progression [9]. In contrast to antioxidant function of vitamin E in CML, we suggest new modulation mechanisms of vitamin E that could be operative in prevention of CML progression. In particular, we analyzed the modulation function of vitamin E for molecular unblocking of myeloid differentiation potential in CML cells via vitamin E-dependent induction of pivotal transcription factor CEBP alpha (CCAAT/enhancer-binding protein) as myeloid master regulator of myelopoiesis/granulopoiesis and consequently G-CSFR (granulocyte-colony stimulation factor receptor) [10]. Moreover, we have found that vitamin E could be involved in targeting epithelial-mesenchymal transition (EMT) mechanism in CML cells via SNAIL as EMT inducer [11, 12]. Therefore, we propose that vitamin E could be a therapeutic option when CML progresses in setting of imatinib therapy. Finally, since alkaline phosphatase is considered as a marker of stem cells [13], we studied the aberrant expression of placental-like alkaline phosphatase (PLAP) and discovered the potential of vitamin E in remodeling of CML-associated aberrant expression of this enzyme [14]. Vitamin E-dependent induction of tissue non-specific alkaline phosphatase (TNAP) is paralleled by restored CEBP alpha expression as myeloid master regulator in CML cells [14].
Taken together, these findings suggest that vitamin E shows ability of remodeling leukemic stem cell (LSC) phenotype in CML cells to hematopoietic stem cell (HSC) phenotype with myeloid differentiation potential development.
C/EBPα is mainly involved in cell fate decisions for myeloid differentiation [15]. The progression of CML to blast crisis is correlated with down-modulation of C/EBP-alpha contributing to the differentiation block, enhanced proliferation, and development of acute myelogenous leukemia [16, 17]. The level of C/EBPα expression is significantly declined in CML patients [18]. Currently, the deregulation of C/EBP alpha is considered as a paradigm of leukemogenesis [19]. Therefore, C/EBPα is a critical regulator of myeloid development guiding granulocyte and monocyte differentiation.
We have studied the modulating potential of vitamin E as the possible inducer of C/EBP-alpha expression in BCR-ABL-positive CML K562 cells. K562 cell line originated from a CML patient in blast crisis progression is recognized as a model for leukemia research. We studied the effects of vitamin E in K562 cells in comparison with valproic acid with known differentiation properties towards myeloid cells [20, 21, 22].
Valproic acid in a concentration of 4 mM for 48 h reduced the growth rate and cell viability and induced apoptosis in a fraction of K562 cells (up to 30%). As to vitamin E, in the series of our preliminary experiments, no evidence of toxicity has been demonstrated when K562 cells were cultured with vitamin E in a concentration of 100 μM for 48 h. These concentrations were further used in the experiments for assaying the expression of C/EBP-alpha and G-CSFR mRNA. Figure 1A demonstrates that valproic acid did not change significantly the level of mRNA C/EBP expression in K562 cells. On the contrary, vitamin E proved to be an effective inducer of mRNA C/EBP with about 10-fold increase in expression as compared with non-treated K562 cells. When mRNA G-CSFR expression in K562 cells was assessed, both valproic acid and vitamin E induced mRNA of this receptor, with effect of vitamin E surpassed that of VA (Figure 1A and Table 1).
mRNA expression in CML cells modified by vitamin E. (A) The relative levels of mRNA C/EBP-alpha and G-CSFR expression in K562 cells exposed to valproic acid (2 mM) or vitamin E (100 μM) for 48 h. (B) The aberrant AP mRNA detected by qRT-PCR in leukemic cells of the patient with CML blast crisis: 1 – control without primers; 2 – primers to PAP; 3 – primers to TNAP; 4 – primers to IAP. (C) Ectopic gene expression of embryonic PLAP mRNA in peripheral blood cells of the patient with CML, acute myeloid leukemia (AML), and polycytemia vera (PV): 1 – GAPDH, reference gene; 2 – aberrant PLAP. (D) The relative levels of mRNA expression of PLAP, TNAP, and CCAAT-enhancer binding protein alpha (C/EBPα) in K562 cells exposed to vitamin E (100 μM) for 48 h by real time RT-PCR 2¯(ΔCt) method. (E) Relative mRNA expression level of transcription factor Snail and transcription factor CEBPα in CML blast crisis K562 cells exposed to vitamin E (100 μM) and metformin (4 mM) for 48 h. The relative levels of mRNA expression were analyzed by qRT-PCR and calculated by 2¯(ΔCt) method.
N (n = 3) | C/EBP alpha | G-CSFR | ||
---|---|---|---|---|
Fold increase | Standard Deviation, σ | Fold increase | Standard Deviation, σ | |
1 | 8.395 ± 1.481 | 1.219 | 3.930 ± 1.843 | 1.988 |
2 | 9.854 ± 0.023 | 4.626 ± 0.853 | ||
3 | 11.381 ± 1.506 | 5.134 ± 1.357 |
Fold increase C/EBP alpha and G-CSFR mRNA expression (analyzed in triplicates) in gene expression in K562 cells line culture under 48-h vitamin E exposure (100 μM) calculated by 2−(∆∆Ct) method. Note: σ = √ 1/n ∑(xi – x¯)2.
Thease findings are quite confirmed by Tavor et al. [23] have first shown that the restoration of C/EBP-alpha expression in BCR-ABL-positive KCL22 blast cell line provided by transfection with C/EBPα plasmid vector caused a block in the G2/M phase of the cell cycle with gradual increase in apoptosis suggesting that C/EBP-alpha may be considered as a putative target in differentiation therapies in acute myeloid leukemia. C/EBPα directly activates G-CSFR transcription in lineage committing activation of common myeloid progenitor [24, 25, 26]. Therefore, C/EBPα loss is causally connected with early block in myeloid maturation suggesting that C/EBPα is a master regulator of hematopoietic differentiation. The transcription factor C/EBPα is known as a critical regulator of myeloid development, directing granulocyte, and monocyte differentiation [27].
Our findings gave evidence of C/EBP alpha-dependent activation to granulocytic differentiation via targeted increase in G-CSFR expression in vitamin E treated K562 cells. It should be further elucidated whether such effects of vitamin E on myeloid transcription factor C/EBP-alpha are direct or mediated indirectly due to the antioxidant properties of vitamin E. Nevertheless, our data suggest vitamin E-associated hematopoietic differentiation-like potential associated with C/EBPα and G-CSFR up-regulation. Our findings might be very important for future studies of imatinib resistance in CML clinical setting taking into account the recent report by S. Kagita et al. demonstrating correlation of C/EBPα expression with response and resistance to imatinib in CML [28].
LSCs in CML do not depend on BCR-ABL signaling for their survival [29, 30], and their persistence remains a major obstacle to curing CML [31, 32]. The search for new biological markers of LSC phenotype is still relevant today. Placental-like alkaline phosphatase (PLAP) is expressed by many tumors. Its aberrant expression has been considered to be potentially useful as tumor marker [33]. However, the biological background of the role of this aberrant alkaline phosphatase (AP) in cancer is still unclear. The AP activity in blood serum known as nonspecific marker of bone metastasis [33] is also of potential significance for the identification of stem cell phenotype [13, 34]. Moreover, AP activity is a widely accepted marker of stem cells associated with embryonic stem cell pluripotency [35]. The expression of various forms of AP in CML cells has not yet been studied. Therefore, we aimed to analyze the expression patterns of various AP forms in cells originated from CML patients in blast crisis and to modify their expression by vitamin E (100 μM) in K562 cells. We used the primers to three known tissue AP, namely placental AP (PAP), non-specific AP (TNAP) (expressed in bone, kidney, liver) and intestinal AP (IAP) [36] to analyze the mRNA expression of these APs in CML cells by qRT-PCR. We have observed the aberrant expression of mRNA IAP in cells of CML patient in blast crisis (Figure 1B) that upon sequencing (data not shown) demonstrated the significant alignment with known cancer-associated PLAP sequence, while no gene homology with tissue PAP was detected. This fact gave reason to consider revealed PLAP as embryonic-like placental AP (ELAP), to be more precise, the aberrant PLAP in blast cells of CML patients (Figure 1C). Indeed, such PLAP is expressed in early embryo pre-implantation period as was detected in studying mouse embryonic cell development, while tissue TNAP begins to express in post-implantation period [35]. We have not detected TNAP in cells of CML patients. Only the embryonic-like PLAP was detected, which expression also increased in acute myeloid leukemia (Figure 1C). Recently, TNAP recognized ultimately as mesenchymal stromal cell antigen-1 (MSCA-1) [13] was described as a biomarker associated with normal hematopoiesis as well as with terminal myeloid differentiation [37]. The decreased TNAP synthesis is a classical feature of CML used as one of diagnostic cytochemical markers in differential diagnosis [2]. We have observed vitamin E targeted decrease in aberrant embryonic-like PLAP expression at mRNA level with increased TNAP mRNA expression. Moreover, along with down-regulation of aberrant PLAP the up-regulation of C/EBP alpha mRNA expression was restored by vitamin E in exposed K562 cells as we founded (Figure 1D and Table 2).
N(n=3) | Fold decreasing | Standard deviation, σ | Fold increasing | Standard deviation, σ | Fold increasing | Standard deviation, σ |
---|---|---|---|---|---|---|
PLAP(M ± m) | CEBPα(M ± m) | TNAP (M ± m) | ||||
1 | 4.088 ± 0.322 | 1.42 | 2.972 ± 1.594 | 1.35 | 6.023 ± 2.809 | 1.98 |
2 | 6.292 ± 1.883 | 4.377 ± 0.117 | 1.690 ± 1.524 | |||
3 | 2.848 ± 1.561 | 6.207 ± 1.713 | 1.931 ± 1.283 |
The relative fold decreasing PLAP corresponding to fold increasing CEBP α and TNAP mRNA expression (analyzed in triplicates) in gene expression in K562 cells line culture under 48-h vitamin E exposure (100 μM) calculated by 2−(∆∆Ct) method. Note: σ = √ 1/n ∑(xi – x¯)2.
Taken together, we have concluded that the loss of TNAP and CEBP alpha in CML may contribute to pathogenesis of this disease whereas aberrant embryonic-like PLAP may be considered as a new CML biomarker of LSC pluripotent phenotype in CML progression. Therefore, aberrant embryonic-like PLAP may be considered as a putative target in differentiation therapies in myeloid neoplasms. Our findings suggest the biomodulation role of vitamin E as the available inducer of differentiation potential of CML leukemic cells. The ectopic PLAP expression in leukemic cells of different myeloid neoplasms suggests its importance in biology of these malignancies.
Conclusivelly, to analyze whether ectopic PLAP expression in CMLcells
To sum up, we have demonstrated increased aberrant PLAP expression in leukemic cells of myeloid origin (CML) in the setting of the decreased TNAP expression. The aberrant expression of embryonic PLAP may be considered as one of the putative markers of myeloid cell undifferentiated state. On the other hand, potential of PLAP as one of the possible target for controlling LSC phenotype should be further explored. More attention is needed to explore the potential of the bioactive molecules such as vitamin E that may induce granulopoiesis reprogramming.
The persistence of LSC remains a major obstacle to cure CML [38, 39]. Epithelial mesenchymal transition (EMT) mechanism is known to contribute to tumor stem cell progression [40, 41]. Although EMT has been studied in relation to epithelium-derived tumors, there is increasing evidence implicating the involvement of EMT activators in hematopoietic malignancies [42, 43]. The expression of some EMT modulators has been demonstrated in Ph + leukemia cells [44]. EMT inducer Snail if of most important role in maintaining stemness properties in tumor progression [45, 46]. It was shown that Snail also drives LSC phenotype in leukemia progression [44, 47]. Earlier, we revealed that alpha-tocopherol might be an effective inducer of mRNA CEBP alpha in K562 cells
We have determined the relationship between EMT-Snail suppression and restored CEBP alpha myeloid differentiation potential in CML blast crisis K562 cells exposed to vitamin E. Metformin as known substance mediating EMT reversal [49] was used to compare EMT suppression effect of vitamin E in K562 cells.
We have found highly detectable Snail1 mRNA expression and down-regulated CEBP alpha in K562 cells (Figure 1E). Vitamin E suppressed EMT-Snail mRNA expression and up-regulated myeloid master regulator CEBP alpha mRNA expression (Figure 1E and Tables 3, 4). Such reactivation of CEBP alpha is enhanced by metformin pointing to the possible synergistic effect with alpha-tocopherol. We observed that vitamin E is a modulator of gene expression that affects Snail1 and CEBP alpha mRNA expression in K562 cells in opposite directions. One could suggest the causal relationship between EMT-Snail1 suppression and restoration of CEBP alpha expression that seems to contribute to recover myeloid differentiation potential of CML blast cells. As seen in Figure 1E, myelopoietic master regulator C/EBPα is also restored upon metformin treatment, although the effect of vitamin E is more pronounced (Table 4).
N(n=3) | Fold decreasing | Standard deviation, σ | Fold decreasing | Standard deviation, σ |
---|---|---|---|---|
Vitamin E/Snail M ± m | Metformin/Snail M ± m | |||
1 | 14.160 ± 0.437 | 0.408 | 1.579 ± 0.110 | 0.086 |
2 | 13.176 ± 0.547 | 1.366 ± 0.103 | ||
3 | 13.833 ± 0.110 | 1.464 ± 0.005 |
Fold increase EMT-inducer transcription factor SNAIL mRNA expression (analyzed in triplicates) in gene expression in K562 cells line culture under 48-h vitamin E exposure (100 μM) calculated by 2−(∆∆Ct) method. Note: σ = √ 1/n ∑(xi – x¯)2.
N(n=3) | Fold increasing | Standard deviation, σ | Fold increasing | Standard deviation, σ | Fold increasing | Standard deviation, σ |
---|---|---|---|---|---|---|
Vitamin E M ± m | Vitamin E + Metformin M ± m | Metformin M ± m | ||||
1 | 5.156 ± 0.328 | 0.232 | 5.564 ± 0.075 | 0.371 | 2.841 ± 0.007 | 0.272 |
2 | 4.634 ± 0.194 | 5.00 ± 0.489 | 3.164 ± 0.330 | |||
3 | 4.696 ± 0.132 | 5.902 ± 0.413 | 2.498 ± 0.336 |
The fold increase of relative levels of the transcription factor CEBP alpha mRNA expression compared with metformin (4 mM) under decreasing of relative levels of the transcription factor Snail mRNA expression by vitamin E (analyzed in triplicates) in K562 cells line culture under 48-h vitamin E exposure (100 μM) calculated by 2−(∆∆Ct) method. Note: σ = √ 1/n ∑(xi – x¯)2.
Taken together, schematic model of the Vitamin E modulation effects in CML blast crisis progression with Snail-EMT phenotype is presented (Figure 2).
Schematic model of the vitamin E modulation in CML progression with EMT phenotype.
CML is characterized by an accelerated and unregulated proliferation of predominantly myeloid cells in the bone marrow with their accumulation in the blood. CML develops as a result of malignant transformation and clonal proliferation of pluripotent hematopoietic stem cells (HSCs), leading to overproduction of immature myeloid progenitor cells that results in blast cell crisis. The CML blast crisis resembles acute leukemia. Because the preeminent mutation driving CML is Bcr-ABL thyrosine kinase oncogene, the use of Bcr-Abl kinase inhibitors (TKIs), such as imatinib, dasatinib, and nilotinib, significantly improves treatment outcomes and extends the life expectancy of CML patients. However, imatinib resistance drives blast crisis progression. The persistence of LSCs remains a major obstacle to cure CML. The clinical CML blast crisis progression with LSC phenotype is practically incurable. Therefore, the blocking of terminal myeloid differentiation and LSC phenotype development defines a putatively new strategy for CML prevention.
The potential of vitamin E in regulation of these interdependent mechanisms in CML progression was hinted by several observations that were reported earlier. Sangodkar et al. [50] showed that vitamin E activates PP2A phosphatase resulting in Bcr-Abl thyrosine kinase inhibition and re-activation of myeloid differentiation pathway. In BCR/ABL transformed cells and CML blast crisis hematopoietic progenitors, the PP2A activity is strongly inhibited, while the pharmacological activation of PP2A suppresses BCL/ABL activity and induces BCR/ABL degradation [51]. The pharmacological modulation of PP2A activity is becoming an attractive strategy for cancer treatment. The substances of several different classes are known as PP2A activating compounds, vitamin E (α-tocopherol) and its analogues having been reported among such compounds [50, 52].
Nevertheless, the effects of vitamin E on differentiation pathways in cells of blast crisis CML, in particular those involving restoration of the expression of CCAAT-enhancer binding protein alpha (C/EBPα) and granulocyte colony-stimulating factor receptor (G-CSFR) have not been yet studied. The expression of these proteins decreases drastically in chronic phase and blast crisis of CML [53, 54]. In this regard, we evaluated the effect of vitamin E on RNA expression of crucial factors of myeloid differentiation, C/EBRα and G-CSFR, in BCR-ABL-positive CML blast crisis K562 cells. Our data demonstrate that vitamin E restores the expression of C/EBPα and concequently G-CSFR. Our results are consistent with Tavor et al. [23] who demonstrated that the restoration of C/EBPα expression in BCR-ABL-positive KCL22 blast cell line triggered a proliferative arrest, a block in the G2/M phase of the cell cycle and a gradual increase in apoptosis suggesting the activation of differentiation. Therefore, C/EBPα stimulated by vitamin E may be considered as a putative target in differentiation therapies in myeloid leukemias.
The second effect of vitamin E potentially useful for CML treatment was reported by Nieborowska-Skorska et al. [55] who demonstrated that vitamin E prevents accumulation of imatinib-resistant BCR-ABL1 kinase mutations in mice CML xenografts. The authors stressed anti-oxidant function of vitamin E in this processes. We use vitamin E as modulating factor in CML that involves vitamin E-dependent EMT mechanism of repression taking into account the pivotal role of EMT in the development of LSC phenotype. In this connection, we observed Snail1 overexpression suggesting some features of EMT phenotype in K562 cells seemingly contributing to CML pathogenesis. Furthermore, we have determined down-regulation of CEBP alpha transcription factor representing the master regulator of myelopoiesis in CML cells coinciding with Snail1 overexpression. Our findings are quite consistent with the recent report by Lourenço et al. [43] who suggest that C/EBP α is crucial determinant of epithelial maintenance by preventing EMT. Indeed, we have found that CEBP alpha is repressed by overexpression of EMT-inducer Snail in CML blast crisis K562 cells. Consequently, the reactivation of CEBP alpha by vitamin E is paralleled by suppression of Snail.
Therefore, our findings make deeper understanding of the role of vitamin E in suppression of CML LSC phenotype. In addition, we have revealed a new marker – aberrant placental-like alkaline phosphatase (PLAP) that expressed ectopically in CML progression. Moreover, its suppression by vitamin E consequently re-activates CEBP alpha and TNAP as myeloid differentiation factors. Taken together, our findings presented in this Chapter stress the role of vitamin E in modifying expression profile of CML cells towards restoration of myeloid differentiation potential.
Vitamin E is a complex group of lipid-soluble antioxidants comprising four tocopherols and four tocotrienols. It prevents production of reactive oxygen species (ROS) that are elevated in majority of tumor cells leading to lipid peroxydation, changing signaling pathways that control cell proliferation and apoptosis, expression of several transcription factors, epigenetic modulators, resistance to treatment, etc. We have suggested the causal relationship between EMT-Snail1 suppression and restoration of CEBP-alpha myeloid master regulator expression that seems to contribute to recover myeloid differentiation potential of CML blast cells by vitamin E. We first observed that vitamin E is an effective modulator of down-regulation of transcription factor Snail EMT-inducer and up-regulation of pivotal myelopoietic transcription factor CEBP alpha resulting in restoration of TNAP expression. Taken into account the data of literature and our findings, we can postulate that vitamin E might be used as a potential pharmacopoeian biological modulator capable of preventing the onset of blast crisis development, ameliorating disease progression and possibly overcoming drug resistance of leukemic cells in CML patients.
All authors of chapter are Laureates of the National Award of the Cabinet of Ministers of Ukraine for the development and implementation of innovative technologies in the field of Biomedicine (N289.p from May 10, 2018).
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\\n\\nOur mission is to support Authors in publishing their research and making an impact within the scientific community. Currently, 14% of Authors receive full waivers and 6% receive partial waivers.
\\n\\nWhile providing support and advice to all our international Authors, waiver priority will be given to those Authors who reside in countries that are classified by the World Bank as low-income economies. In this way, we can help ensure that the scientific work being carried out can make an impact within the worldwide scientific community, no matter where an Author might live.
\\n\\nThe application process is open after your submitted manuscript has been accepted for publication. To apply, please fill out a Waiver Request Form and send it to your Author Service Manager. If you have an official letter from your university or institution showing that funds for your OA publication are unavailable, please attach that as well. The Waiver Request will normally be addressed within one week from the application date. All chapters that receive waivers or partial waivers will be designated as such online.
\\n\\nDownload Waiver Request Form
\\n\\nFeel free to contact us at funders@intechopen.com if you have any questions about Funding options or our Waiver program. If you have already begun the process and require further assistance, please contact your Author Service Manager, who is there to assist you!
\\n\\nNote: All data represented above was collected by IntechOpen from 2013 to 2017.
\\n"}]'},components:[{type:"htmlEditorComponent",content:'At IntechOpen, the majority of OAPFs are paid by an Author’s institution or funding agency - Institutions (73%) vs. Authors (23%).
\n\nThe first step in obtaining funds for your Open Access publication begins with your institution or library. IntechOpen’s publishing standards align with most institutional funding programs. Our advice is to petition your institution for help in financing your Open Access publication.
\n\nHowever, as Open Access becomes a more commonly used publishing option for the dissemination of scientific and scholarly content, in addition to institutions, there are a growing number of funders who allow the use of grants for covering OA publication costs, or have established separate funds for the same purpose.
\n\nPlease consult our Open Access Funding page to explore some of these funding opportunities and learn more about how you could finance your IntechOpen publication. Keep in mind that this list is not definitive, and while we are constantly updating and informing our Authors of new funding opportunities, we recommend that you always check with your institution first.
\n\nFor Authors who are unable to obtain funding from their institution or research funding bodies and still need help in covering publication costs, IntechOpen offers the possibility of applying for a Waiver.
\n\nOur mission is to support Authors in publishing their research and making an impact within the scientific community. Currently, 14% of Authors receive full waivers and 6% receive partial waivers.
\n\nWhile providing support and advice to all our international Authors, waiver priority will be given to those Authors who reside in countries that are classified by the World Bank as low-income economies. In this way, we can help ensure that the scientific work being carried out can make an impact within the worldwide scientific community, no matter where an Author might live.
\n\nThe application process is open after your submitted manuscript has been accepted for publication. To apply, please fill out a Waiver Request Form and send it to your Author Service Manager. If you have an official letter from your university or institution showing that funds for your OA publication are unavailable, please attach that as well. The Waiver Request will normally be addressed within one week from the application date. All chapters that receive waivers or partial waivers will be designated as such online.
\n\nDownload Waiver Request Form
\n\nFeel free to contact us at funders@intechopen.com if you have any questions about Funding options or our Waiver program. If you have already begun the process and require further assistance, please contact your Author Service Manager, who is there to assist you!
\n\nNote: All data represented above was collected by IntechOpen from 2013 to 2017.
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Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:"Shenzhen Technology University",institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda R.",middleName:"R.",surname:"Gharieb",fullName:"Reda R. Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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