Diversity and location of the most consumed edible insects in the world.
\r\n\tThe Japanese were revolutionizing quality improvement. As a result, Japan adopted a "total quality" approach to its strategies. In the United States, Total Quality Management (TQM) encompasses not only statistics but also approaches that encompass the entire organization. There were several subsequent quality-management initiatives.
\r\n\tIn 1986, Motorola developed Six Sigma to improve its business processes by minimizing defects. A philosophy that views all work as a process, which can be identified, measured, analyzed, improved, and controlled. Generally, "Six Sigma quality" is an indicator that a process is well controlled.
\r\n\tLean manufacturing (1988), also known as just-in-time manufacturing, derives from Toyota's 1930 operating model "The Toyota Way." Lean describes a set of management practices that reduce waste and increase productivity.
\r\n\tThe ISO 9000 series of quality-control standards appeared in 1987. ISO 9001 integrates a process-oriented approach into enterprise management based on the plan-do-check-act method. The quality movement has matured as we enter the 21st century. ISO 9000 was revised in 2000 to emphasize customer satisfaction. The fifth edition of ISO 9001, published in 2015, emphasizes risk-based thinking to improve the application of the process approach. In addition to the manufacturing sector, quality has moved into service, healthcare, education, and government. For example, through standards such as ISO/IEC 17025 for testing and calibration laboratories and ISO 15189 for medical laboratories.
\r\n\tMore recently, it has been recognized that the Fourth Industrial Revolution, Industry 4.0, best defines the present industry model. As its part, "Quality 4.0" refers to the future of quality and organizational excellence.
\r\n\tThe book will aim to introduce a comprehensive overview of the up-to-date models used in quality management systems by experts in the field.
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Insects have played an important part in the history of human nutrition in Africa, Europe, Asia, and Latin America. Over 1900 species of insects are known worldwide to be part of human diets; some important groups include grasshoppers, caterpillars, beetle grubs, wringed termites, bees, worms, ant brood, cicadas, and a variety of aquatic insects [2]. It is interesting to know that more than two billion people consume insects on a regular basis, and insect eating provides a significant proportion of the animal proteins consumed in some regions [3]. Because entomophagy is widely practiced, and because it compares favorably with nutrient and environmental aspects of conventional livestock rearing, it has the potential to contribute substantially to reducing undernutrition among an expanding global population [3].
Insects have been in existence for at least 400 million years, making them among the earliest land animals. They diverged as members of one of the largest subphyla in arthropods more than 390 million years ago experiencing a rapid evolution and radiation that is considered faster than any other group [4]. The class insects are the largest animal group on earth and constitute as much as 80% of the animal kingdom. Because of the nutritional importance of edible insects and their huge availability, this has attracted their consumption by more than two billion people on a daily basis [5].
\nOver 1900 species of edible insects in 300 ethnic groups in 113 countries worldwide have been recorded by various authors to be part of human diet (Table 1) [6]. According to Van Huis et al. [3], 246 species of edible insects have been reported in 27 countries in Africa. Another study carried out 2 years later by Ramos-Elorduy noted that Africa is one of the most important hot spots of edible insect biodiversity in the world with 524 species recorded from 34 African countries [7]. These species are mostly of the orders Orthoptera, Lepidoptera, Coleoptera, Hymenoptera, and Isoptera. Below is a checklist of the most consumed edible insect species in the world and their orders and locations (Figure 1).
Order | Species | Location |
---|---|---|
Lepidoptera | DRC, Zambia, Cameroon, Congo, CA Republic, Zimbabwe, Nigeria, Tanzania | |
DRC, Zambia, South Africa, Botswana, Burkina Faso, Nigeria, Mozambique, Namibia, Ghana, Togo, Chad | ||
DRC, Zambia, South Africa, Botswana, Burkina Faso, Nigeria, Mozambique, Namibia, Ghana, Togo, Chad | ||
DRC, Zambia, South Africa, Botswana, Burkina Faso | ||
Zambia, Nigeria, Ivory Coast, Sierra Leone, Guinea, Liberia, Guinea Bissau | ||
Orthoptera | DRC, Zambia, South Africa, Botswana, Burkina Faso, Nigeria, Mozambique, Namibia, Ghana, Togo, Chad | |
DRC, Zambia, South Africa, Cameroon, Congo, CA Republic, Zimbabwe, Burkina Faso, Malawi, Mali | ||
DRC, Zambia, South Africa, Cameroon, Zimbabwe, Kenya, Uganda, Tanzania, Malawi | ||
Coleoptera | DRC, Cameroon, Congo, CA Republic, Nigeria, Ivory Coast, Sao Tomé, Guinea, Ghana, Liberia | |
Thailand, Australia, Nigeria, Ivory Coast, Sierra Leone, Guinea, Liberia, Guinea Bissau DRC, Congo, Botswana | ||
Hymenoptera | Mexico, Cameroon, Congo, CA Republic, Nigeria, Angola, Ivory Coast, Niger, Sao Tomé, Guinea | |
DRC, Zambia, South Africa, Zimbabwe, Botswana, Malawi, Sudan, Kenya, South Sudan | ||
Zambia, South Africa, Zimbabwe, Botswana, Sudan, Mozambique, Namibia, South Sudan | ||
Isoptera | Zambia, Angola, Kenya, Togo, Burundi, Ivory Coast, Canada, the USA | |
Zambia, Zimbabwe, Burkina Faso, Burundi, Benin, Australia, the Netherlands | ||
DRC, Cameroon, Congo, CA Republic, Nigeria, Burundi, South Africa, Zimbabwe, Nigeria, Malawi |
Recorded number of edible insect species, by country. Source: Centre for Geo Information, Wageningen University, based on data compiled by Jongema, 2012 [
Hunger and malnutrition is a serious problem in the ever-expanding human population. With the high rate at which the world population is growing, the world food supply should grow at the same rate, if not faster. Therefore, the search for new food sources including the identification and development of localized ethnic ones continues [3].
\nIn most part of the world, particularly in Africa and Latin America, food resources are becoming increasingly scarce and the importing of foods is becoming more expensive. It is thus imperative to identify and develop indigenous food resources. To effectively respond not just to rapid population growth but also to other pressing challenges, researchers have turned their attention to insects not only because of their abundance, enormous biomass, and high-quality protein but also because of the time-honored practice among many culturally diverse peoples of Africa and Latin America of consuming live, roasted, and fried insects, providing them with a nutritious protein of good quality and high digestibility [12, 13]. The choice of insects as food is further strengthened by the fact that they also constituted rich sources of fat, vitamins, and minerals, especially iron and zinc [14].
Insects are the most abundant and most diverse multicellular organisms on planet earth and are thought to account for about 80% of all species [15]. Numerous crops rely on them for pollination, and their importance extends into their other agricultural and human health benefit [16].
\nOver 1900 species of insects are known to be part of human diets, more than 2 billion people consume insects on a regular basis, and insect eating provides a significant proportion of the animal protein consumed in some regions [3, 17]. In fact, in many developing countries and among various cultures scattered throughout the world, insects remain a vital and preferred food and an essential source of protein, fat, minerals, and vitamins [18]. This is because some edible insects have been shown to have nutritional value that can be compared with meat and fish, while others have higher proportion of proteins, fat, and energy value [19]. This has become especially important as the need for alternative protein sources increases due to rapid urbanization in developing countries and the shifts in the composition of global food demand. Among the most important orders of insects consumed in the world are the Coleoptera, Hymenoptera, Isoptera, Lepidoptera, Odonata, and Orthoptera, and they are highly priced (Figure 2) [20]. Notable examples of these are the locusts, termites, worms, grasshoppers, caterpillars, palm weevils, and beetle grubs, among others.
Number of insect species, by order, consumed worldwide. Source: Jongema [
Although insects were mainly recognized as pests affecting humans, plants, and animal health, insects play an essential role in minimizing food insecurity in addition to provide ecosystem services (such as pollination, waste degradation, and biological control). Insects also represent an important food source for a wide variety of animal species. Van Huis et al. outlined the important role of insects in assuring food and feed security. Below is a list of pictures showing the various edible insects consumed around the world (Figure 3) [3].
Examples of edible insects.
Scientific validation of traditional wisdom in bioprospecting has assured greater significance. Edible insects have long been a significant dietary factor and remedy for illnesses in many regions of the world [22]. Traditional healers have used insects as medicine to treat various diseases in human beings and animals successfully. Some of these diseases include common fever, scabies, epilepsy, violent headaches, bronchitis, hemorrhage, and dog bite. Insects are also used to treat wound, to prevent gangrene, and to increase milk flow in lactating women, among others [23]. This treatment is finding modern usage in many hospitals. Also, chemicals produced by edible insects against self-defense have also been exploited by many researchers for the production of antibacterial and anticancer drugs. For instance, pierisin, a protein purified from pupa of cabbage butterfly, exhibits cytotoxic effects against human gastric cancer. Cecropin has also been reported to be cytotoxic against mammalian lymphoma and leukemia cells [22]. Despite the fact that edible insects have a high nutritional, economic, and medicinal value, they are often neglected. It is high time that scientists recognize this fact and begin to build on it given the benefits of these creatures to the environment and to human health.
Many rural communities like those in Africa, Asia, and South America know that eating insects provides a valuable source of protein, minerals, and vitamins as well as a tasty snack and therefore must be in high demand. Crickets, grasshoppers, and locusts, for example, are a seasonal delicacy, while the giant water beetles are used in salads [22].
\nConsidering the popularity of edible insects, it is not surprising that scores of species have been and are prominent items of commerce in the town and village markets of Africa and tropical and semitropical regions of the world [24]. In several areas in Africa, particularly in Zimbabwe, Nigeria, South Africa, Ivory Coast, and Zambia, many families make fairly good living from selling insects [25, 26]. These insects are mostly gathered from bushes and farmland by women and children (Figure 4), processed, and eaten or sold in school premises and local and urban markets. Some of these insects are also processed and exported to shops and restaurants in cities in and out of the country [20, 27]. The commercialization of edible insects therefore provides significant income to many households in Africa. However, poorly understood and poorly organized market chains severely limit agribusiness in Africa. The market constraints encountered by farmers when attempting to diversify the production of edible insect business should therefore be documented.
A picture showing women and children selling edible insects in local markets.
The part played by insects in human nutrition cannot be underestimated [28]. Substantial evidence suggests that insects are a highly nutritious and healthy food source with high content of nutrients such as fats, proteins, amino acids, carbohydrates, vitamins, fibers, and minerals required by humans and animals [3]. However, the nutritional compositions of edible insects between and within species are highly variable depending upon the metamorphic stage, habitat, and diet of the insect as well as the preparation and processing methods applied before consumption [29]. Although the nutritional composition of some edible insects has previously been investigated in a number of countries, for example, India, the USA, Mexico, and Thailand, very few authors have reported a compiled nutritional composition of edible insects in the world. The lack of nutritional data on most edible insects may result in a reduction in consumer confidence and limits integration of insect consumption with other food sources. Hence, this work seeks to compile nutritional data of edible insects consumed in the world.
\nWith the growing world population, there are now more than 3.7 billion people suffering from malnutrition, mainly due to lack of protein and energy from food [30]. Also, new agricultural land is scarce to produce food for humans, and as such a greater proportion of people are eating resource-intensive animal protein than ever before. Livestock production is very expensive because it requires a large input of energy compared to the energy output [31]. These livestock also compete for nutrients and energy with humans.
\nUtilization of insects as a protein source could benefit insect conservation through habitat protection [32]. Insects are essential agents because they are able to exploit all organic sources in nature and are able to recycle organic waste and provide nutrients to farm animals and humans [33, 34]. Furthermore, edible insects have high quantities of polyunsaturated fat which provides majority of the energy for sustaining life. The energy contents of edible insects vary according to the species and region found and have also been found to be significantly higher than those of livestock and vegetables [19, 35]. Hence, edible insects may efficiently provide the necessary energy for the vital functions and survival of organisms.
\nRamos Elorduy et al. [36] analyzed 78 insects from Oaxaca State, Mexico, and determined that caloric content was 293–762 kcal per 100 g of dry matter as shown in Table 2.
Location | Common name | Scientific name | Energy content kcal/100 g fresh weight |
---|---|---|---|
Australia | Australia plague locust, raw | 499 | |
Australia | Green (weaver) ant, raw | 1272 | |
Canada, Quebec | Red-legged grasshopper, whole, raw | 160 | |
The USA, Illinois | Yellow mealworm, larva, raw | 206 | |
The USA, Illinois | Yellow mealworm, adult, raw | 138 | |
Ivory Coast | Termite, adult, dewinged, dried, flour | 535 | |
Mexico Veracruz State | Leaf-cutter ant, adult, raw | 404 | |
Mexico Hidalgo State | Honey ant, adult, raw | 116 | |
Thailand | Field cricket, raw | 120 | |
Thailand | Giant water bug, raw | 165 | |
Thailand | Rice grasshopper, raw | 149 | |
Thailand | Grasshopper, raw | 89 | |
Thailand | Domestic silkworm, pupa, raw | 94 | |
The Netherlands | Migratory locust, adult, raw | 179 |
Examples of energy content of different processed insect species, by regions.
Source: FAO [37].
Proteins are organic compounds consisting amino acids which are the building blocks and could be either essential or nonessential. Protein is the basis of all organism activity and constitutes many important materials such as enzyme, hormones, and hemoglobin. Proteins are the most abundant biological macromolecules, occurring in all cells and all parts of cells. Proteins also occur in great variety; thousands of different kinds, ranging in size from relatively small peptides to huge polymers with molecular weights in the millions, may be found in a single cell. Moreover, proteins exhibit enormous diversity of biological function and are the most important final products of the information pathways. Proteins are the molecular instruments through which genetic information is expressed. Therefore, ensuring a steady source of protein is very important in providing energy for humans and animals.
\nInsects are potentially an important energy efficient source of protein in humans (Table 3), either through a direct consumption or as food supplements for stock [17]. Many local communities in the world, particularly in the Amazon region, attain about 8–70% of their dietary protein from insects [39]. The highest amount of crude protein is found in insects in the order Lepidoptera followed by Coleoptera, while the order Hymenoptera has the least. The high protein content is an indication that edible insects can be of value to man and animal ration and can eventually replace higher animal protein usually absent in the diet of rural dwellers in developing countries [8].
Insect order | Stage | Range (% protein) |
---|---|---|
Coleoptera | Adults and larvae | 23–66 |
Lepidoptera | Pupae and larvae | 14–68 |
Hemiptera | Adults and larvae | 42–74 |
Homoptera | Adults, larvae, and eggs | 45–57 |
Hymenoptera | Adults, pupae, larvae, and eggs | 13–77 |
Odonata | Adults and naiad | 46–65 |
Orthoptera | Adult and nymph | 23–65 |
Xiaoming et al. [40] evaluated the protein content of 100 species from a number of insect orders. He showed that protein content was high and in the range of 13–77% of dry matter and that there was a large variation between and within the insect orders.
\nEdible insects have also been shown to have higher protein content, on a mass basis, than other animal and plant foods such as beef, chicken, fish, soybeans, and maize [41]. FAO compared protein content of insects, reptiles, cattle, and fish (Table 4) [42]. Results showed that the protein content of the selected insect species had higher protein contents than the fish and mammals. This strongly suggests that insects are an important source of protein and as such their consumption should be encouraged.
Animal group | Species and common name | Edible product | Protein content (g/100 g fresh weight) |
---|---|---|---|
Insect (raw) | Locusts and grasshoppers: | Larva | 14–18 |
Locusts and grasshoppers: | Adult | 13–28 | |
Adult | 35–48 | ||
Silkworm ( | Caterpillar | 10–17 | |
Palm worm beetles: | Larva | 7–36 | |
Yellow mealworm ( | Larva | 14–25 | |
Crickets | Adult | 8–25 | |
Termites | Adult | 13–28 | |
Cattles | Turtles: | Flesh | 25–27 |
Intestine | 18 | ||
Liver | 11 | ||
Heart | 17–23 | ||
Liver | 12–27 | ||
Fish (raw) | Finfish | Tilapia | 16–19 |
Mackerel | 16–28 | ||
Catfish | 17–28 | ||
Crustaceans | Lobster | 17–19 | |
Prawn (Malaysia) | 16–19 | ||
Shrimp | 13–27 | ||
Mollusks | Cuttlefish | 15–18 |
Many studies have also shown that edible insects are important source of amino acids (tryptophan and lysine). The inclusion of these insect species in diets could be of immense benefit in complementing lysine-poor staple cereals [43–45], and a host of others were able to demonstrate that an insect species
Amino acid | Beef g/kg dry matter | |
---|---|---|
Essential | ||
Isoleucine | 24.7 | 16 |
Leucine | 52.2 | 42 |
Lysine | 26.8 | 45 |
Methionine | 6.3 | 16 |
Phenylalanine | 17.3 | 24 |
Threonine | 20.2 | 25 |
Tryptophan | 3.9 | - |
Valine | 28.9 | 20 |
Semi-essential | ||
Arginine | 25.5 | 33 |
Histidine | 15.5 | 20 |
Methionine + cysteine | 10.5 | 22 |
Tyrosine | 36.0 | 22 |
Nonessential | ||
Alanine | 40.4 | 30 |
Aspartic acid | 40.0 | 52 |
Cysteine | 4.2 | 5.9 |
Glycine | 27.3 | 24 |
Glutamic acid | 55.4 | 90 |
Proline | 34.1 | 28 |
Serine | 25.2 | 27 |
Taurine | 210 | - |
Fats and carbohydrates are important nutritive elements in the human body. They are the main energy source in the body, can reduce consumption of proteins, and help for detoxification [38].
\nEdible insects are also a good source of carbohydrates. In fact, the carbohydrate content of edible insects ranged from 6.71% in sting bug to 15.98% in cicada [47]. Carbohydrates in insects are formed mainly by chitin. Chitin is a macromolecular compound that has a high nutritional and health value. This chitin reduces serum cholesterol [48]. Also, recent report showed that considerable amounts of polysaccharide in edible insects might improve immune functioning of human body [49].
\nFat is the most energy-dense macronutrient in food. It consists of triglycerides and three fatty acid molecules which are the backbone. Fatty acid can either be saturated, unsaturated, or essential. Dietary intervention and epidemiological studies showed that fatty acid intake played a key role in human health. Reduction in dietary saturated fatty acids can decrease factor VII coagulant activity, which was implicated as a risk factor of cardiovascular disease [50]. Scientific literature has shown that consumption of PUFAs has several health benefits to humans such as reduction of glucose tolerance, thus reducing risk of diabetes and blood pressure [51], and prevention of insulin resistance [52], decreasing thrombotic tendency by inhibition of thromboxane A2 formation [53] and lowering blood pressure [51, 54]. Womeni et al. [55] investigated the content and composition of fat extracted from several insects (Table 6). They showed that their oils are rich in polyunsaturated fatty acids and frequently contain the essential linoleic and α-linolenic acids. The nutritional importance of these two essential fatty acids is well recognized, mainly for the healthy development of children and infants [56].
Edible insect species | Fat content (% of dry matter) | Composition of main fatty acids (% of oil content) | Type of fatty acid |
---|---|---|---|
African palm weevil ( | 54% | Palmitoleic acid 38% | MUFA |
Linoleic acid 45% | PUFA | ||
Edible grasshopper ( | 67% | Palmitoleic acid 28% | MUFA |
Linoleic acid 46% | PUFA | ||
a-Linolenic acid | PUFA | ||
Termites ( | 49% | Palmitic acid | SFA |
Oleic acid | MUFA | ||
Stearic acid 9% | SFA | ||
Saturniid caterpillar ( | 24% | Palmitic acid 8% | SFA |
Oleic acid 9% | MUFA | ||
Linoleic acid 7% | PUFA | ||
a-Linolenic acid 38% | PUFA | ||
Variegates grasshopper ( | 9% | Palmitoleic acid 24% | MUFA |
Oleic acid 11% | MUFA | ||
Linoleic acid 21% | PUFA | ||
a-Linolenic acid 15% | PUFA | ||
g-Linolenic acid 23% | PUFA |
Fat content and randomly selected fatty acids of several edible insect species consumed in Cameroon.
Source: Womeni et al. [55]. PUFA= Polyunsaturated Fatty Acids; MUFA= Monounsaturated Fatty Acids; SFA= Saturated Fatty Acids.
Many recent studies have shown that edible insects are a rich source of fatty acids, particularly polyunsaturated fat [19, 57]. These fatty acids differ and depend on many factors such as species reproduction stages [58, 59] and season or life stage [59].
Minerals are known to play important metabolic and physiologic roles in the living system. Iron, zinc, copper, and manganese strengthen the immune system as antioxidant and cofactors of enzyme [60]. Similarly, magnesium, zinc, and selenium prevent cardiomyopathy, muscle degeneration, growth retardation, impaired spermatogenesis, immunologic dysfunction, and bleeding disorder [61]. Iron deficiency is a major problem in women’s diets in the developing world, particularly among pregnant women, and especially in Africa [62]. Magnesium is needed for more than 300 biochemical reactions in the body. It helps to maintain normal muscle and nerve function, keeps the heart rhythm steady, and regulates blood sugar levels [63].
\nAnalysis of normal elements showed that edible insects are rich in nutritious elements such as potassium and sodium (cricket nymph), calcium (adult cricket), copper (mealworm), iron (axayacatl), zinc (cricket), manganese (cricket), and phosphorus [3]. Therefore, edible insects can supply the necessary nutritive elements for human body functions and could be consumed along with other food and animals rich in other essential minerals to further complement the diet of these insects. The mineral contents of some edible insects in Nigeria are shown in Table 7.
Insect species | Ca | P | Fe | Mg | Ash |
---|---|---|---|---|---|
1.00* | 14.90* | 9.56* | 60.96* | 7.60* | |
21 | 136 | 27 | 0.15 | 2.90 | |
18 | 114 | 29 | 0.26 | 1.90 | |
9.21 | 126.9 | 0.68 | 0.13 | 1.82 | |
4.40 | 100.2 | 0.35 | 0.09 | 2.10 | |
42.40 | 131.2 | 1.96 | 8.21 | 1.20 | |
61.28 | 136.4 | 18.2 | 6.14 | 4.21 | |
8.56 | 111.3 | 1.78 | 1.01 | 1.60 | |
10.52 | 102.4 | 2.24 | 2.56 | 2.50 | |
12.00 | 9.00 | 19.50 | 0.50 | 4.30 | |
8.57 | 100.5 | 2.01 | 1.56 | 3.20 | |
8.24 | 111.0 | 1.79 | 1.87 | 1.50 | |
15.4 | 125.5 | 25.2 | 5.23 | 2.20 | |
45.68 | 130.2 | 2.31 | 6.62 | 1.50 | |
NA | NA | 85.00 | 175.00 | 10.50 | |
NA | NA | NA | NA | 6.40 | |
54.1 | 685.0 | 30.80 | 131.8 | 2.70 | |
42.16 | 131.2 | 30.82 | 11.72 | 2.74 |
Vitamins are a group of organic compounds that are necessary for metabolism in human bodies. Vitamins cannot be synthesized in the human body; they must be supplied constantly by food [38]. Vitamin C, also called ascorbic acid, serves as a reducing agent (an antioxidant), while vitamin B comprises of components of coenzymes. Vitamins K and A are required for normal blood clotting and proper vision, respectively. Many studies have shown that edible insects contain appreciable amounts of vitamins [9, 44]. The high vitamin content of edible insects presents them as a highly potentially good source of food supplement for malnourished people and animals. The vitamin contents of some insect orders are shown in Table 8. Each of the orders contains appreciably high amounts of vitamins A, B2, and C.
Order | N | Vitamin A | Vitamin B2 | Vitamin C | |||
---|---|---|---|---|---|---|---|
Range | Mean | Range | Mean | Range | Mean | ||
Isoptera | 3 | 0.026–0.05 | 0.14 | 1.54–1.98 | 1.69 | 3.01–17.76 | 8.06 |
Coleoptera | 3 | 0.086–0.125 | 0.11 | 0.08–2.62 | 1.64 | 4.25–7.59 | 5.75 |
Orthoptera | 3 | 0.0–0.068 | 0.03 | 0.03–0.08 | 0.06 | 0.0–8.64 | 3.21 |
Lepidoptera | 5 | 0.028–0.034 | 0.09 | 0.09–2.21 | 1.50 | 1.95–4.52 | 2.83 |
Hymenoptera | 1 | 3.24 | 10.25 |
Land, water, and energy resources are declining, so these resources need to be conserved and managed to produce more food [68]. Also, animal husbandry competes for these vital resources, as the land is occupied by the production of feed and cannot be used to produce more food for humans [32]. It is very expensive to carry out livestock farming. This is because they consume large amounts of energy than they produce [68]. For example, livestock consume 77 million tons of protein in feedstuff that is potential for human nutrition to produce 58 million tons of protein [69]. Insect culture, on the other hand, requires little areas [70]. Also, many of the edible insect species do not compete with human beings for food resources. Equally, insect farming requires little water, which is significant because water shortages already exist throughout the world and are likely to increase. Hence, insects are nick named “minilivestock” [71].
Insects deliver a host of ecological services fundamental to the survival of humankind. Utilization of insects as a protein source could benefit insect conservation through habitat protection [32]. Insects are essential agents feeding on organic matter in nature, and they efficiently exploit all organic sources. Insects also recycle organic waste and provide nutrients for farm animals [33, 34]. Many insect species are absolutely necessary to improve soil fertility. This is because insects play an important role in breaking down waste products until it is fit to be consumed by fungi and bacteria, thus releasing minerals and nutrients which become readily available in the soil for plant uptake, hence improving soil fertility. Animal carcasses, for example, are consumed by fly maggots and beetle larvae. Dung beetles—of which there are about 400 known species—also play a significant role in decomposing manure. Hence, insects could be used as efficient bio-transformers to convert abundant, low-cost organic wastes into animal biomass rich in proteins and suitable for use in animal nutrition [72].
Besides serving as sources of food, edible insects provide humans with a variety of other valuable products. A huge variety of insect species are known to have remarkable commercial and pharmaceutical values. For example, bees and silkworm have been shown to produce massive tons of honey and silk, respectively. These products can be sold in the local as well as in the international markets [72], while silkworms produce more than 90,000 tons of silk [73]. Also carmine, a red dye produced by scale insects of the order Hemiptera, is used to color foods, textiles, and pharmaceuticals. Resilin, a rubberlike protein that enables insects to jump, has been used in medicine to repair arteries because of its elastic properties [74]. In addition to this, other products produced by edible insects such as honey, propolis, royal jelly, and venom have been used in treating traumatic and infected wounds and burns [75]. Furthermore, insect products have also been used in engineering methods in the production of biomaterials [76].
Sustainably meeting global food demands is one of humanity’s greatest challenges and has attracted considerable attention in the past few years [77]. There is general consensus on agriculture’s positive contribution to food security through its role in increasing availability of affordable food and the incomes of the poor. Within the context of sustainable diet, the use of insects as food and feed has a significant role to play in assuring food security and improving livelihood of the African people. Edible insects are rich in protein and amino acids, especially essential amino acids which are necessary for the human body. They can also supply unsaturated fatty acids, minerals, vitamins, and carbohydrates, which have an excellent nutritive value. They are also of valuable importance medically, commercially, and ecologically. These edible insects should therefore be taken into consideration for a world in which human nutrition has been a huge problem.
Recent studies have identified four important challenges that must be addressed in order to tap the huge potentials that edible insects offer for enhancing food and feed security.
\nTo begin with, more work on the nutritional values of edible insects is needed in order to establish insects as food. Also, insect farming should be compared with livestock farming in order to determine which one of them is more environmentally damaging or environmentally friendly. Furthermore, there should be a further clarification on the socioeconomic importance of edible insects in enhancing food security. Lastly, clear comprehensive legal framework at (inter)national levels is needed to pave the way for more investment, leading to the full development of production and international trade in insect products as food and feed sources.
In the beginning of last century, the first antimicrobial protein, lysozyme, was reported. A few years later, the best known antimicrobial compound, called penicillin, was discovered, which made research into natural antimicrobial proteins/peptides (AMPs) a very important research domain for therapeutic molecules that can be used against bacterial infections [1]. AMPs are naturally occurring small proteins (or peptides) in different organisms and are produced by many tissues and different cell types, acting as host defense molecules against bacteria, but with some also showing a fast antifungal, antiviral, antiparasitic and antitumor response [1, 2, 3].
The largest part of AMPs consists of antibacterial peptides with an inhibitory activity towards bacteria, both Gram-positive and Gram-negative [2]. Studies have revealed that AMPs exhibit an overall positive charge, allowing electrostatic interactions with negatively charged phospholipid groups in the bacterial membrane. By this attribute, pores can be formed by AMPs to disrupt the membrane integrity. Some AMPs are able to cross the lipid bilayer, followed by disruption of intracellular functions such as blocking enzyme activity or inhibition of protein synthesis, both resulting in bacterial cell lysis [1]. For this reason, AMPs are often referred to ‘natural antibiotics’.
AMP activity is not restricted to antimicrobial mechanisms, also AMP activity against parasites has been observed: a few AMPs are reported as antimalarial peptides and can possibly serve as new future drug targets against the malaria parasite. For example, cecropins have been shown to block the development of oocysts into sporozoites, while dermaseptins (and some derivatives) have been found to be able to permeabilize the host cell membrane [4].
Furthermore, a subset of AMPs have shown antifungal characteristics against some fungi commonly found in food and agriculture, but also against the common
AMPs are considered key components of the innate immune system, as shortly after an infection, these are promptly synthesized to neutralize a wide variety of pathogens, but through another mechanism compared to that of cytokines or phagocytes [10]. High concentrations of AMPs are usually required to exert an optimal pathogen killing activity, but
The best studied AMPs include the human defensins and cathelicidins and both have been shown to be chemotactic: β defensins (hBD) recruit (memory) T cells and immature dendritic cells through their chemotactic activity, suggesting they promote cellular immune responses via interactions with the G protein-coupled receptor CCR6 [11]. Another example of direct AMP chemotaxis includes cathelicidin LL-37, an AMP that has been proven to be chemotactic for neutrophils, monocytes and T cells, but not dendritic cells [11]. Additionally, an indirect chemotactic effect is possible by AMPs through inducing the release of pro-inflammatory cytokines and chemokines, to further refine and activate the innate, and eventually the adaptive, immune response [1, 11]. In synergy with particular immune mediators, LL-37 has been shown to enhance IL-6 and IL-10 cytokine production, even as the production of macrophage chemoattractant proteins (MCP-1 and MCP-3) chemokines, resulting in an strengthened (innate) immune response [12]. Toll-like receptors (TLR) are key players in innate immunity by recognizing microbe-associated molecular patterns (MAMPs). TLR activation leads to secretion of AMPs, but some AMPs, including cathelicidins, can modulate TLR-mediated inflammatory responses by strongly reducing LPS-induced TLR activation, mostly by inhibiting TLR4 [11, 13]. Lastly, AMPs, e.g. cathelicidins and β defensins, also exert a regenerative function by affecting wound healing, by stimulating migration, proliferation and tube formation of endothelial cells, through a cascade of activated pathways [11].
Overall, AMPs are important key players in host protection. Due to increasing antibiotic resistance, several AMPs have good potential therapeutic purposes, ranging from antimicrobial, anti-inflammatory and immunomodulatory properties. Also co-administration of AMPs with existing therapies can have good clinical outcomes [14]. Recently, the ACP LTX-315 which has been described earlier, demonstrated in phase I human clinical studies to be an effective drug, due to its immunostimulatory effect resulting in tumor necrosis [9]. Currently, a phase I clinical trial for transdermally accessible tumors is ongoing to evaluate the efficacy of LTX-315 monotherapy or in combination with immune checkpoint inhibitor immunotherapy [9]. Still, some limitations for the therapeutic use of AMPs need to be resolved: high proteolytic degradation of AMPs (i.e. susceptibility to proteases) is commonly observed, unpredicted toxicity is known to occur, chemical synthesis is costly and delivery of AMP targets to the site of infection can be very difficult [9, 14, 15]. As an example, LL-37 has proven to be very effective against Ebola virus infection, but its use as therapeutic molecule is limited as LL-37 is rapidly degraded and can lose its activity under certain conditions. These limitations were overcome with the design of an engineered LL-37 which prevents cell entry of the virus. The therapeutic outcome of these AMPs in animal models is ongoing, possibly combined with other small molecules that interfere with viral replication or together with virus-neutralizing antibodies [16].
AMPs mostly consist of 10 to 60 amino acids, including mainly basic and hydrophobic residues, resulting in positively charged molecules [1, 2]. They can be classified, based on their structure, into four categories; 1) linear extension structure, 2) α-helical AMPs, 3) AMPs consisting of β-strands stabilized by disulfide bonds and 4) both α-helical and β-sheet structures [2]. Due to their cationic properties, AMPs are easily detectable by mass spectrometric analysis. In addition, structural information of AMPs can be obtained by tandem mass spectrometry in which fragmentation spectra are obtained. Based upon this, the corresponding amino acid sequence can be determined and the precursor ion can be identified [17]. Even if the AMPs have a cyclic nature, due to their cysteine bond formation, mass spectrometry can be used as an identification tool, although a specific approach is needed [18, 19, 20, 21]. The added benefit of using proteomic approaches to study AMPs is the fact that the majority of AMPs are post- or co-translational proteolytically processed from their large polyprotein precursor, resulting in the release of the active AMP. This is important as it allows for the identification of the active AMP in physiological conditions. It overcomes the limitations of a genomics approach, as it can be complicated to predict the configuration of the exact active peptide from genomic sequences alone [22, 23]. In addition, due to their high positive charge, distribution of the AMP in a tissue can be analyzed using mass spectrometry imaging (MSI). MALDI MSI is a multiplexed analysis that allows the screening of hundreds of analytes simultaneously in a single tissue section without
Overall, mass spectrometry (imaging) is an useful approach for the detection and identification of AMPs in their native and active form.
In the search for positive response patterns towards immune checkpoint inhibitors in non-small cell lung cancer (NSCLC) patients, we recently applied matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) on pretreatment tumor tissue biopsies. Since no prior knowledge of the molecules is required for MSI analysis, new unknown response patterns and biomarkers can be revealed. An additional advantage of using this visualization technique is that new, unknown biomolecules can be detected in their active and native state.
Using this approach, three peptides
Average MALDI MSI spectra obtained with mass spectrometry imaging (MSI) analysis of whole formalin-fixed paraffin-embedded (FFPE) tumor biopsies of NSCLC patients. (A) an example of a resulting average mass spectrum with three peptides m/z 3369.5, m/z 3440.6 and m/z 3484.6 of interest. (B) Average MSI spectra of 25 pretreatment tumor FFPE biopsies from NSCLC patients that received anti-PD-(L)1 immunotherapy. From this small patient cohort, nine patients received clinical benefit from the therapy (responders), from which seven patients showed expression of the three interesting peptides. The other 16 NSCLC patients did not derive any clinical benefit from immunotherapy treatment (non-responders), from which 14 show no (or very low) peptide expression. From the nonresponding patients, two NSCLC patients showed interesting peptide expression. Figure adapted from [
A major bottleneck of the direct analysis of tissues with MALDI-based MSI is the lack of a reliable identification of the visualized molecules, but it has been proven earlier that peptide/protein identification can be performed by using top-down proteomics. This is a major challenge for identification of cyclic proteins or peptides, due to their intramolecular cysteine bridges.
Mass spectrometry followed by
Identification of the cyclic peptides (shown in Figure 1) by collision-induced dissociation (either with CID or HCD), a routine approach in top-down peptidome analysis, is mostly not successful as fragmentation of the peptide backbone will not result in multiple fragments of different lengths. Rather, a long fragment with a mass close to the mass of the original parent (minus the loss of H2O) will be generated, irrespective of where the fragmentation occurred. Hence, these MS/MS spectra cannot be used to deduce a sequence tag that can be used to identify the peptide [31]. However, it has been shown that electron-transfer dissociation (ETD) can be used successfully for the identification of naturally occurring peptides [32], so, ETD has been applied as a fragmentation technique instead of HCD. Rather than generating fragments of the peptides by colliding them with an inert gas in CID, ETD induces fragmentation of large, multiply-charged cations by transferring electrons to them. ETD can be used effectively not only to break the peptide backbone (typically into C and Z ions), but also to reduce any cysteine bridges in the peptide [18, 19, 20]. This is nicely demonstrated in Figure 2B. An extract of the NSCLC tissue was prepared and analyzed with LC–MS/MS on a LTQ Velos Orbitrap (Thermo Fisher, Waltham, MA, USA) equipped with ETD. This type of instrument combines a dual stage linear ion trap with an orbitrap analyzer, an HCD cell and an ETD source. This allows for a very flexible use of different fragmentation techniques in the ion trap. In this case, the peptide is fragmented by using ETD and the resulting fragments were measured in the Orbitrap. The fragmentation of any of the three target peptides showed a neutral loss of 3 Da in each peptide (Figure 2B), corresponding to a reduction of three disulfide bridges between 6 cysteine residues [21].
Mass spectra and annotated sequence of synthetic peptide corresponding for human neutrophil peptide 1 (HNP1). A) Full MS spectrum of intact HNP1, in three different charge states. The five charged ion with m/z 689.31 (mass 3441.6 Da) is selected for reduction of the three internal disulfide bridges with ETD; B) the resulting intact peptide m/z 1722.77 after reduction of three disulfide bridges. This reduced peptide is immediately selected for fragmentation with CID; C) the resulting fragmentation spectrum with c, y and z type ions; D) annotated sequence of human neutrophil peptide 1. Figure adapted from [
The reduction of the disulfide bonds in effect turns the circular peptide into a linear one (Figure 2A and B). In a subsequent experiment, the resulting reduced and thus no longer circular peptide is selected and trapped in the ion trap for an additional fragmentation with CID (Figure 2C). In this way, multiple fragments are generated, measured this time in the ion trap, from which an amino acid sequence can be deduced. This leads to the identification of the peptide with mass 3440.6 as human neutrophil peptide 1 (HNP1), presented in Figure 2D. The two other peptides of interest were analyzed in a similar way and identified as human neutrophil peptides 2 and 3. These three peptides have an almost identical amino acid sequence, only differing in the first amino acid residue [21].
To conclude, the combined approach of MSI and top-down proteomics using both ETD and CID has revealed human neutrophil peptide 1, 2 and 3, also known as neutrophil defensin 1, 2 and 3, as putative discriminative markers between a responding and a nonresponding NSCLC patient towards immunotherapy [21], highlighting a possible broader role for these AMPs than just a function as antimicrobial peptides. Additionally, these results were verified with immunohistochemical (IHC) analyses on the same pretreatment biopsies with a defensin 1/3 polyclonal antibody. In Figure 3, it is illustrated that IHC is feasible on FFPE tissue sections, previously MSI analyzed, without an apparent change in staining intensity [21].
Distribution of human neutrophil peptides 1-3 in FFPE tissues after MSI and IHC analyses. A) Distribution of HNP1-3 obtained with MSI and the corresponding mass spectrum; B) validation of the presence of HNP1-3 in the same FFPE tissue, prior MSI analyzed, with IHC. The region indicated with the box in the MSI result was compared with the same tissue region after IHC analysis with a defensin 1/3 antibody. Figure adapted from [
This combined approach has been proven to be very useful in the detection and identification of interesting AMPs, especially in their native, processed form in a clinical context [21].
The previously described observations were a starting point to explore the possible role of neutrophil defensins in cancer immunology.
Defensins, together with cathelicidins, are widely studied, as they were early recognized as important components of the antimicrobial mechanisms of leukocytes. The defensins can be classified in human α-defensins, which are composed of β-strands, and human β-defensins, consisting of both α-helical and β-strands structures [33]. The sequences of these two defensin types include six cysteine residues and their cyclic structure is stabilized by formation of three intramolecular disulfide bonds, from which the cysteine bonding pattern makes a differentiation between α-defensins and β-defensins [33]. These cysteine residues are of major importance for their cationic antimicrobial characteristics [22]. A third class of defensins is also reported, called θ-defensins, and although mRNA expression of θ-defensins has been observed in humans, no functional AMPs from the θ-defensin family are reported to be produced in humans [22].
Currently, 31 β-defensins have been identified and are being studied. They are mainly expressed by epithelial cells and keratinocytes, but can also be secreted from macrophages, neutrophils and lymphocytes, suggesting a broader role in immune responses besides antimicrobial activity [22]. More importantly for this review part are the α-defensin family, more specifically the human neutrophil peptides 1, 2 and 3 (HNP1-3), as previously described. As the name suggests, these AMPs are predominantly produced by neutrophils, but they have also been detected in macrophages, natural killer (NK) cells, immature monocyte-derived dendritic cells and some classes of T and B cells. The fourth α-defensin is also found in these cell types, while α-defensins 5 (HD5) and 6 (HD6) are secreted by intestinal Paneth cells, with the main function to provide intestinal host defense towards pathogens and to control and maintain homeostasis of the intestinal microbiome [22, 34]. HD5 and HD6 deficiency is associated with Crohn’s disease, possibly due to the reduced antimicrobial defense capacity by lower HD5 and HD6 expression, leading to an altered microbiome composition [1, 35].
HNP1-3 have an almost identical amino acid sequence, only differing in a single amino acid residue, while this does not hold true for HNP4, HD5 and HD6 (Figure 4), although all six α-defensins are characterized by the same cysteine residues [36]. HNP1 and HNP2 (the same is true for HNP2 and HNP3) are released from the same precursor, which is cleaved by a signal peptidase at position 19 leaving a propeptide, which will be further processed by proteolysis in the developing granulocyte. The resulting mature peptide is then packaged into azurophilic granules of the neutrophils, with the HNPs representing more than 30% of the total protein content in these granules [37]. Neutrophils are first-line defense immune cells against different pathogens and are directly recruited to sites of infection, followed by engulfment of the pathogen. Upon neutrophil activation, degranulation of azurophilic granules takes place, thus leading to abundant HNP release as a first-line of response to invading organisms [37, 38, 39]. These HNP1-3 have been shown to have antibacterial, antiviral, anticancer and even immunomodulatory activities, which will be discussed further in more detail.
Alignment of the amino acid sequences of all 6 human α defensins. Conserved cysteine residues are presented in green and their corresponding cysteine bonding pattern is indicated.
HNP1-3 have a well described antibacterial activity, with demonstrated effectivity towards
HNP1-3 have not only proven an effective response towards both Gram-positive and Gram-negative bacteria, but antiviral activity is also a well-known characteristic of HNPs, including human immunodeficiency virus (HIV), human papilloma virus (HPV), herpes virus and influenza A virus (IAV) [2]. These HNPs have also been reported as anti-HIV peptides: high production of HNP1-3 by immature dendritic cells have a host protective role against progression of HIV-1, due to the direct HNP damage capability towards the virions, followed by the virion internalization by the immature dendritic cell, leading to viral processing and presentation to HIV-specific CD4+ T cells [43]. In addition, HNP1-3 are identified in the female genital tract acting as host defense forming a natural barrier to HPV [44]. HNP1-3 can inhibit herpes simplex virus (HSV) entry by directly binding to its target receptor and these defensins even exhibit post entry antiviral activity, leading to reduced viral replication after HSV infection [22]. As a last example worth mentioning, these HNPs have an anti-IAV activity by direct interaction with the virus, leading to destabilization of the viral envelope and thus leading to virus inactivation. HNP1 has also been suggested to bind the protein kinase C (PKC) receptor, in this way avoiding both IAV entry and replication [45, 46].
Already a direct antitumor effect has been described for human neutrophil peptides in a variety of tumor cells [47]. Furthermore, HNP1 has been reported as a potential prognostic biomarker in cancer [48, 49, 50]. In addition, the HNPs are suggested to induce tumor necrosis [48, 49]. Although, despite the reported anticancer activity, defensins HD5 and HD6 are known markers of development and contribution to colorectal tumor growth [51].
In the same study in which we showed an association of the presence of HNPs and a response towards anti-PD-(L)1 immunotherapy in NSCLC, a possible immune stimulatory effect of HNPs towards lung cancer cells has been reported, while no such activity could be shown against non-tumoral cells [21].
Although earlier studies suggest a direct cytotoxic anticancer activity of the human neutrophil peptides [47, 48, 49], in this study, a possible immune–stimulatory effect of HNP1-3 towards lung cancer is suggested. The question raised by these findings is how these HNPs can act as immune-stimulatory effector, not directly on tumor cells nor on the immune cells, while leaving non-tumoral cells intact. A hypothesis is that α-defensins specifically target tumor cells by interaction with phosphatidylserine (PS) exposure. This interaction has been shown in a recent
PS exposure by the tumor cells have been driven in
It is conceivable that HNPs play an immune-stimulatory role towards (lung) cancer cells. Due to their direct antimicrobial activity characteristics, HNPs are considered to be part of the innate immune response, just as neutrophils, their main cellular source, as approximately 9% of the neutrophil protein content includes HNPs [56]. Neutrophils have Jekyll and Hyde properties in relation to cancer, as they have been shown to elicit both antitumoral as protumoral activities [57, 58]. Tumor-associated neutrophils (TANs) have been linked with poor prognosis in late-stage tumorigenesis [58, 59]. Although, recent findings indicate antitumor properties of neutrophils in early-stage human tumors; neutrophils have been shown to present antigens, resulting in T cell interaction leading to a proper T cell activation and response. Furthermore, neutrophils are able to attract and activate these T cells through cytokine secretion [60]. It has also been proven that HNPs enhances adaptive immunity, however, their mechanisms remain largely unknown. Nevertheless, studies have shown that HNPs have immunostimulatory characteristics through chemoattraction of naïve T cells [61], CD8+ T cells [37], monocytes [37], maturation and differentiation of immature dendritic cells [43, 61] and by inducing pro-inflammatory chemokine and cytokine production, such as IFN-γ, IL-8 and IL-2 [62].
Chemoattraction of monocytes by HNP has been proven by De Yang
Monocyte-derived dendritic cells seem to play an important role in this HNP-driven immunity: moDCs can internalize and process antigens in their immature state, followed by maturation of moDCs by upregulating MHC class II molecules that react with naive CD4 and CD8 T cells to induce their activation, leading to induction of adaptive immunity [43, 56]. HNPs are thus thought to form a link between innate and adaptive immunity, by serving as chemoattractants and immune cell activators [37]. It is demonstrated that HNP-driven DC activation leads to an increased DC capacity to stimulate T cells, explaining the possible HNP interplay in adaptive immunity [61, 64, 65]. Also in an
During the last decades, it became more clear that antimicrobial peptides (AMPs) are not restricted in characteristics as being antibacterial, but that AMPs are also serving as a first-line of defense against fungi, viruses, and even tumor cells. Furthermore, these small cationic molecules have been shown to exhibit potent immune regulatory activities, including chemoattraction, activation and differentiation of leukocytes and monocytes to initiate and further enhance adaptive immunity. Combined, we believe that AMPs may hold great potential to be used as lead for new (co-)therapeutic agents.
With proteomic approaches, more in particular mass spectrometry, it is feasible to identify (cyclic) AMPs in their active form after their corresponding proteolysis. While emphasis has been put strongly on HNP identification in a tumorimmunology-related context, it is also important to stress out that mass spectrometric analyses allows for the detection and identification of native AMPs in different specimens, even when present at low concentrations. These unbiased analyses can lead to the detection and identification of new AMPs, important for future drug development.
In this way, human neutrophil peptide (HNP) 1, 2 and 3 were identified in a non-small cell lung cancer (NSCLC) related context, of which the presence have been shown to be discriminative between a responding and a nonresponding NSCLC patient towards anti-PD-(L)1 immunotherapeutics. Although the biological activity of HNPs is well described against bacteria and viruses, little is known about their antitumor characteristics. Some studies suggest a direct antitumoral activity of HNP1-3, while it has also been proven that these HNPs do not show a direct cytolytic activity towards NSCLC, but a reduced NSCLC proliferation was observed in the presence of HNP and peripheral blood mononuclear cells (PBMC)
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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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