3.2.2. Microbiological Content

Antimicrobial capacity of different extract was also proved in fish products elaborated from thawed hake. Consequently, microbiological results of fish patties at days 0, 4, 7 and 11 from elaboration, are shown in Table 5.

**Table 5.** Microbiological results (cfu/g) of fish patties analysis at days 0, 4, 7 and 11 under refrigerated storage.

TVC: Total Viable Count; TCC: Total Coliform Count P: Pomegranate extract, RA: Rosemary extract rich in Rosmarinic Acid; NOS: Rosemary extract rich in diterpenes; NOVS: Rosemary extract rich in diterpenes and with lecitin as emulsifier; HYT-L: Hydroxytyrosol extract obtained from olive leaf; HYT-F: Hydroxytyrosol extract obtained from olive fruit.

As it can be appreciated, TVC results after 11 days of refrigerated storage were lower in samples that incorporated HYT-F and HYT-L in their formula, followed by P, control sample, NOVS, NOS and RA. While, TCC results showed as both pomegranate and rosemary extracs, diterpens rich extracts (NOS and NOVS) and rosmarinic acid rich extract (RA) obtained the lowest results in comparison with the control sample, or samples that incorporated HYT to their formulas. These last results can be related with antimicrobial activity of all the extracts against *E. Coli* O157:H7ATCC 25922 CECT 434. On the other hand, results obtained from analysis of *E. Coli* and *L. monocytogenes* did not present significant differences (*p* < 0.05) among incorporation of natural extracts. In addition, it must be taken into account that only samples enriched with HYT, both from fruit or leaf, did not exceed the limit stablished by European legislation regarding to TVC in fish products (5,000,000 cfu/g). In parallell, only P and rosemary extracts (RA, NOS, and NOVS) kept fish product samples below legal microbiological safety limits of TCC (50,000 cfu/g). However, all the natural extracts, including the control sample prevented against microbiological growth of *E. Coli* and *L. monocytogenes.*


**1. Introduction**

[8] American Society for Testing and Materials (ASTM). Web page www.astm.org.con‐

[9] Centro Multidisciplinar de Innovación y Tecnología. Caracterización de Biodiesel. Bi‐ odiesel en Sustitución del Gasoil-Biodiesel de Calidad. Publicaciones Técnicas. CE‐

[10] Komers K, Stloukal R, Machek J, Skopal F. Biodiesel from rapeseed oil, methanol and KOH. 3. Analysis of composition of actual mixture. Eur J Lipid Sci Technol

[11] Agudelo SJR, Benjumea R, Gómez ME, Pérez BJF. Biodiesel. Una revisión del desem‐ peño mecánico y ambiental. Ingeniería & Desarrollo. Universidad del Norte. Medel‐

[12] Canakci M, Sanli H. Biodiesel production from various feedstocks and their effects on the fuel properties. J Ind Microbiol Biotechnol 2008;35(5):431–441. doi: 10.1007/

[13] Landa, Itziar. Caracterización de biodiesel principales parámetros de calidad. CEMI‐

[14] Park JY, Kim DK, Lee JP, Park SC, Kim YJ, Lee JS. Blending effects of biodiesels on oxidation stability and low temperature flow properties. Bioresour Technol

[15] Sharma Y, Singh B, Upadhyay S. Advancements in development and characteriza‐ tion of biodiesel: a review. Fuel 2008;87(12):2355–2373. doi: 10.1016/j. fuel.2008.01.014.

[16] Ramos M. J., Fernández C. M, Casas A., Rodríguez L., & Pérez Á. Influence of fatty acid composition of raw materials on biodiesel properties. Bioresour Technol

[17] Universiteit Utrecht. Copernicus Institute of Sustainable Development. Energy and Resource. Potential indirect land use change (ILUC). Available online: http:// www.uu.nl/en/research/copernicus-institute-of-sustainabledevelopment/ research/

[18] INTN (Instituto Nacional de Tecnología y Normalización). Normas Paraguayas. Leg‐ islación alimentaria y Resoluciones MERCOSUR internalizadas. INTN Asunción,

[19] Proc Kenneth RL, McCormick KK, Chandler B, Buchhler B. Operating Experience and Teardown Analysis for Engines Operated on Biodiesel Blends (B20), NREL/

[20] IDIADA Automotive Technology. Technical Report: Comparison of vehicle emis‐ sions at European Union annual average temperatures from E0 and E5 petrol. PEP‐

2008;99(5):1196–1203. doi: 10.1016/j.biortech.2007.02.017.

2009;100(1):261–268. doi: 10.1016/j.biortech. 2008.06.039.

energy-and-resources/potential-indirect-land-use-change-iluc

SOL, YPF, Abengoa Bioenergía, CEPSA, Ebro Puleva. 2003.

sulted in November 2009.

2001;103:363–71.

286 Biofuels - Status and Perspective

s10295-008-0337-6.

Paraguay. 2008.

CP-540-38509, 2005-01-3641.

MITEC-Navarra- España. 2007.

lín-Colombia 2003;13:1–14.

TEC, Navarra, España. 2006.

Biodiesel is a source of energy derived from renewable sources, which can be a substitute for diesel fuel. It is biodegradable, and it has limited greenhouse gas emissions because of the closed CO2 cycle and a lower combustion emission profile (especially SOx). Biodiesel consists of fatty acid alkyl esters (usually methyl esters, FAME) derived from either the transesterifi‐ cation of triglycerides and/or the esterification of free fatty acids (FFAs) with low molecular weight alcohols [1-3].

Traditionally, the production of biodiesel is carried out in the presence of a homogeneous base catalyst; however, effluent disposal leads to environmental problems and economical incon‐ veniences. These problems can be overcome by the use of heterogeneous catalysts. Another problem with commercial production of biodiesel is the high cost of raw materials. In order to overcome this problem, waste oils and fats can be used as feedstocks [4-7]. However, waste cooking oils contain a high amount of free fatty acids, which is a problem for biodiesel production by the traditional process (homogeneous alkali-catalyzed transesterification) [8,9]. Different solid acids such as resins with sulfonic acid groups [10-14], zeolites [15-17], solid super acid catalysts [18] and carbonaceous catalysts [19] have been used as catalysts in the conversion of waste cooking oil containing a high amount of free fatty acids into biodiesel.

Heteropolyacids (HPAs) have several advantages as catalysts, which make them economically and environmentally attractive. On the one hand, HPAs have a very strong Bronsted acidity, approaching the superacid region; on the other, they are efficient oxidants, exhibiting fast reversible multielectron redox transformations under rather mild conditions. Their acid-base and redox properties can be varied over a wide range by changing the chemical composition.

© 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Solid HPAs possess a discrete ionic structure, comprising fairly mobile basic structural units, e.g., heteropolyanions and counter cations (H+ , H3O+ , H5O2 + , etc.) unlike the network structure of, e.g., zeolites and metal oxides [20-22]. HPAs have low specific surface areas (1–10 m2 /g). In order to increase the specific area of HPAs or, even better, to increase the number of accessible acid sites of the HPAs, a variety of supports like activated carbon [23-26], silica [27-32], zeolite [33-38] and polymeric matrix [39-43] have been used as support to immobilize HPAs.

HPAs and HPAs supported on different supports have been used as acid catalysts for biodiesel production [44-48].

Transesterification of waste cooking oil with high acid value and high water content was performed using heteropolyacid H3PW12O40.6H2O (PW) as homogeneous catalyst. PW was found to be the most promising catalyst, which exhibited the highest ester yield (87%) for transesterification of waste cooking oil and an ester yield of 97% for esterification of long-chain palmitic acid. The PW acid catalyst showed higher activity under the optimized reaction conditions compared with the conventional homogeneous catalyst sulfuric acid, and it can easily be separated from the products by distillation of the excess methanol and can be reused several times [45].

Biodiesel production in the presence of 20 wt% myristic acid from soybean oil was carried out over heteropolyacid immobilized on mesoporous Ta2O5 materials. Different catalysts were prepared. The network structures of the hybrid materials and the functions of the incorporated alkyl groups on the catalytic activity of the materials have been put forward [46].

Biodiesel synthesis from waste cooking oil was carried out over 12-tungstosilicic acid on SBA-15. The heteropolyacid was prepared using impregnation method. The effect of different reaction parameters like percentage loading, catalyst amount, mole ratio, time and tempera‐ ture were studied for the supreme conversion. The catalyst was recycled up to four times after simple workup without notable loss in the activity [48].

In this work, we report the transesterification of waste cooking oil with different alcohols over heteropolyacids immobilized on SBA-15. We also studied the effect of free fatty acid addition into waste cooking oil. A kinetic model is proposed.


**4. Conclusions**

Exhausted woods represent a largely available waste product of the tannin extraction process, whose practical exploitation has not yet been duly considered. As reported in the present paper, these materials exhibit good antioxidant properties in the DPPH and superoxide scavenging assay, and are also able to efficiently adsorb pollutants such as toxic gases, organic dyes and heavy metals. In particular, chestnut woods, containing mainly hydrolyzable tannins, were particularly active as antioxidants, whereas quebracho woods, characterized by the presence of condensed tannins, were found to be more effective as adsorbent materials, especially toward NOx fumes. Of particular interest is the enhancement of the antioxidant properties of exhausted woods and chestnut wood fiber following hydrolytic treatment, a methodology that had already been applied to materials containing lignins like spent coffee grounds [4] and the black sesame seed pigment [25], but also ellagitannins like pomegranate wastes [26]. An interpretation of such effects at a molecular level invoke aromatization and dehydration processes enhancing the hydrogen donor ability of the OH functionalities stemming from delocalization of the resulting phenoxyl radical over a more conjugated molecular backbone [4,8]. On the other hand, from consideration of the moderate weight loss further to the hydrolytic treatment it cannot be argued that the observed activation effects may simply be ascribed to removal of cellulosic or other inactive components of the materials.

Overall, these results would point to exhausted woods as novel potential functional additives to be used for example in active packaging, as food stabilizers against oxidative deterioration, or in filtering devices as pollutant removal agents.

**Author Contributions:** Conceptualization and writing—original draft preparation, L.P.; methodology and data curation, L.P. and M.T. (Marco Trifuoggi); investigation, F.M. and M.T. (Maria Toscanesi); resources and supervision, S.G.; writing—review and editing, A.N.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The authors declare no conflict of interest.


As scientists continue to explore the potential applications of epigenetic reprogramming, the possibilities are endless. This research could transform the way a disease is treated and prevent it from occurring in the first place. There is much to learn about this process, but the medical and scientific communities are excited to explore the potential of these organisms. Epigenetic detection has been an important advance in cancer research. By shedding light on how cancer develops and progresses, new treatments have been developed on the basis of these findings. In spite of many challenges like aberrant promoter methylation, inactivated mutations, tumor microenvironment, and external factors, these developments could have a significant impact on the fight against cancer. Epigenetic therapies are a promising new field of medicine that has the potential to revolutionize healthcare. Epigenetic drugs and other therapies are being studied for their potential to treat a wide range of diseases, including cancer. The gut microbiome can be used to manage and treat cancer and gut-related diseases. The bioactive metabolites produced by beneficial probiotic microbes affect the epigenome and the differentiation and functioning of various immune cells, enterocytes, and pancreatic cells. Modifying the intestinal microbiome by repairing dysbiosis through diet intervention or fecal transplants would be a promising approach to treating metabolic syndromes. Additionally, several clinical trials of

*Perspective Chapter: Epigenetic Therapy – The Future Treatment for Cancer DOI: http://dx.doi.org/10.5772/intechopen.110641*

epigenetic therapy are currently underway and could offer insight into the potential of epigenetic therapies. A new generation of epigenetic therapies could revolutionize healthcare care and change the way we live in the near future.

#### **Acknowledgements**

The authors are grateful to the editors for invitation of the book chapter. The authors SCR and SPR sincerely thank the founder of SVR BioScience Research Services, Dr. Sundru Manjulata Devi for giving an opportunity to contribute to the review.

#### **Conflict of interest**

The authors declare no conflict of interest.

#### **Authorship criteria**

Concept and design of the book chapter was conceived by SMD. The epigenetic changes and therapy was contributed by SMD. SCR contributed and formulated the for role of CRISR-Cas9 and SPR promoted the role of gut microbiota and probiotics in epigenetic changes. Editing, revision and final approval was made by SMD, SCR and SPR.

#### **Author details**

Surya Chandra Rao Thumu1 , Shobha Rani Papanna2 and Sundru Manjulata Devi3 \*

1 Centre for Neuroscience, Indian Institute of Science, Bangalore, Karnataka, India

2 Genespy Research Services Private Limited, Mysuru, Karnataka, India

3 SVR BioScience Research Services, Mysuru, Karnataka, India

\*Address all correspondence to<EMAIL_ADDRESS><EMAIL_ADDRESS>
© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

### **References**

[1] Morovic W, Budinoff CR. Epigenetics: A new frontier in probiotic research. Trends in Microbiology. 2021;**29**:117-126. DOI: 10.1016/j.tim.2020.04.008

[2] Nakamura M, Gao Y, Dominguez AA, Qi LS. CRISPR technologies for precise epigenome editing. Nature Cell Biology. 2021;**23**:11-22. DOI: 10.1038/ s41556-020-00620-7

[3] Keung AJ, Joung JK, Khalil AS, Collins JJ. Chromatin regulation at the frontier of synthetic biology. Nature Reviews. Genetics. 2015;**16**:159-171. DOI: 10.1038/nrg3900

[4] Holtzman L, Gersbach CA. Editing the epigenome: Reshaping the genomic landscape. Annual Review of Genomics and Human Genetics. 2018;**19**:43-71. DOI: 10.1146/ annurev-genom-083117-021632

[5] Gasperini M, Tome JM, Shendure J. Towards a comprehensive catalogue of validated and target-linked human enhancers. Nature Reviews. Genetics. 2020;**21**:292-310. DOI: 10.1038/ s41576-019-0209-0

[6] Kumar M, Hemalatha R, Kumar R, Nagpal R, Devraj JP, Verma V, et al. Probiotics, prebiotics and synbiotics—A review. Cell. 2021;**8**:93-95. DOI: 10.4049/ jimmunol.1001864

[7] Jones PA, Issa J-PJ, Baylin S. Targeting the cancer epigenome for therapy. Nature Reviews. Genetics. 2016;**17**:630-641. DOI: 10.1038/nrg.2016.93

[8] Wang Y, Yan L, Zhang Z, Prado E, Fu L, Xu X, et al. Epigenetic regulation and its therapeutic potential in pulmonary hypertension. Frontiers in

Pharmacology. 2018;**9**:241. DOI: 10.3389/ fphar.2018.00241

[9] Roberti A, Valdes AF, Torrecillas R, Fraga MF, Fernandez AF. Epigenetics in cancer therapy and nanomedicine. Clinical Epigenetics. 2019;**11**:81. DOI: 10.1186/s13148-019-0675-4

[10] Kesika P, Sivamaruthi BS, Chaiyasut C. Do probiotics improve the health status of individuals with diabetes mellitus? A review on outcomes of clinical trials. BioMed Research International. 2019;**2019**:1531567. DOI: 10.1155/2019/1531567

[11] Xiong X, Chen M, Lim WA, Zhao D, Qi LS. CRISPR/Cas9 for human genome engineering and disease research. Annual Review of Genomics and Human Genetics. 2016;**17**:131-154. DOI: 10.1146/ annurev-genom-083115-022258

[12] Qi LS, Larson MH, Gilbert LA, Doudna JA, Weissman JS, Arkin AP, et al. Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell. 2013;**152**:1173- 1183. DOI: 10.1016/j.cell.2013.02.022

[13] Morton AR, Dogan-Artun N, Faber ZJ, MacLeod G, Bartels CF, Piazza MS, et al. Functional enhancers shape extrachromosomal oncogene amplifications. Cell. 2019;**179**:1330-1341. e13. DOI: 10.1016/j.cell.2019.10.039

[14] Mirabella AC, Foster BM, Bartke T. Chromatin deregulation in disease. Chromosoma. 2016;**125**:75-93. DOI: 10.1007/s00412-015-0530-0

[15] Franzago M, Fraticelli F, Nicolucci A, Celentano C, Liberati M, Stuppia L, et al. Molecular analysis of a genetic variants panel related to

*Perspective Chapter: Epigenetic Therapy – The Future Treatment for Cancer DOI: http://dx.doi.org/10.5772/intechopen.110641*

nutrients and metabolism: Association with susceptibility to gestational diabetes and Cardiometabolic risk in affected women. Journal Diabetes Research. 2017;**2017**:4612623. DOI: 10.1155/2017/4612623

[16] Hidalgo-Cantabrana C, O'Flaherty S, Barrangou R. CRISPR-based engineering of next-generation lactic acid bacteria. Current Opinion in Microbiology. 2017;**37**:79-87. DOI: 10.1016/j. mib.2017.05.015

[17] Pan M, Barrangou R. Combining omics technologies with CRISPR-based genome editing to study food microbes. Current Opinion in Biotechnology. 2020;**61**:198-208. DOI: 10.1016/j. copbio.2019.12.027

[18] Canani RB, di Costanzo M, Leone L, Bedogni G, Brambilla P, Cianfarani S, et al. Epigenetic mechanisms elicited by nutrition in early life. Nutrition Research Reviews. 2011;**24**:198-205. DOI: 10.1017/ s0954422411000102

[19] Delgado S, Sánchez B, Margolles A, Ruas-Madiedo P, Ruiz L. Molecules produced by probiotics and intestinal microorganisms with immunomodulatory activity. Nutrients. 2020;**12**:391. DOI: 10.3390/nu12020391

[20] Adli M. The CRISPR tool kit for genome editing and beyond. Nature Communications. 2018;**9**:1911. DOI: 10.1038/s41467-018-04252-2

[21] Tadić V, Josipović G, Zoldoš V, Vojta A. CRISPR/Cas9-based epigenome editing: An overview of dCas9-based tools with special emphasis on off-target activity. Methods. 2019;**164-165**:109-119. DOI: 10.1016/j.ymeth.2019.05.003

[22] Gilbert LA, Larson MH, Morsut L, Liu Z, Brar GA, Torres SE, et al. CRISPRmediated modular RNA-guided

regulation of transcription in eukaryotes. Cell. 2013;**154**:442-451. DOI: 10.1016/j. cell.2013.06.044

[23] Kiani S, Chavez A, Tuttle M, Hall RN, Chari R, Ter-Ovanesyan D, et al. Cas9 gRNA engineering for genome editing, activation and repression. Nature Methods. 2015;**12**:1051-1054. DOI: 10.1038/nmeth.3580

[24] Konermann S, Brigham MD, Trevino A, Hsu PD, Heidenreich M, Cong L, et al. Optical control of mammalian endogenous transcription and epigenetic states. Nature. 2013;**500**:472-476. DOI: 10.1038/ nature12466

[25] Tanenbaum ME, Gilbert LA, Qi LS, Weissman JS, Vale RD. A protein-tagging system for signal amplification in gene expression and fluorescence imaging. Cell. 2014;**159**:635-646. DOI: 10.1016/j. cell.2014.09.039

[26] Konermann S, Brigham MD, Trevino AE, Joung J, Abudayyeh OO, Barcena C, et al. Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature. 2015;**517**:583-588. DOI: 10.1038/ nature14136

[27] Polstein LR, Gersbach CA. Lightinducible spatiotemporal control of gene activation by customizable zinc finger transcription factors. Journal of the American Chemical Society. 2012;**134**:16480-16483. DOI: 10.1021/ ja3065667

[28] Margolin JF, Friedman JR, Meyer WK, Vissing H, Thiesen HJ, Rauscher FJ 3rd. Krüppel-associated boxes are potent transcriptional repression domains. Proceedings of the National Academy of Sciences of the United States of America. 1994;**91**:4509- 4513. DOI: 10.1073/pnas.91.10.4509

[29] Fritsch L, Robin P, Mathieu JRR, Souidi M, Hinaux H, Rougeulle C, et al. A subset of the histone H3 lysine 9 methyltransferases Suv39h1, G9a, GLP, and SETDB1 participate in a multimeric complex. Molecular Cell. 2010;**37**:46-56. DOI: 10.1016/j.molcel.2009.12.017

[30] Lu Y, Chan Y-T, Tan H-Y, Li S, Wang N, Feng Y. Epigenetic regulation in human cancer: The potential role of epi-drug in cancer therapy. Molecular Cancer. 2020;**19**:79. DOI: 10.1186/ s12943-020-01197-3

[31] Morita S, Noguchi H, Horii T, Nakabayashi K, Kimura M, Okamura K, et al. Targeted DNA demethylation in vivo using dCas9–peptide repeat and scFv–TET1 catalytic domain fusions. Nature Biotechnology. 2016;**34**:1060- 1065. DOI: 10.1038/nbt.3658

[32] Amabile A, Migliara A, Capasso P, Biffi M, Cittaro D, Naldini L, et al. Inheritable silencing of endogenous genes by hit-and-run targeted epigenetic editing. Cell. 2016;**167**:219-232.e14. DOI: 10.1016/j.cell.2016.09.006

[33] Vojta A, Dobrinić P, Tadić V, Bočkor L, Korać P, Julg B, et al. Repurposing the CRISPR-Cas9 system for targeted DNA methylation. Nucleic Acids Research. 2016;**44**:5615-5628. DOI: 10.1093/nar/gkw159

[34] Lei Y, Zhang X, Su J, Jeong M, Gundry MC, Huang Y-H, et al. Targeted DNA methylation in vivo using an engineered dCas9-MQ1 fusion protein. Nature Communications. 2017;**8**:16026. DOI: 10.1038/ncomms16026

[35] Liu J, Yue Y, Han D, Wang X, Fu Y, Zhang L, et al. A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nature Chemical Biology. 2014;**10**:93-95. DOI: 10.1038/nchembio.1432

[36] Xu X, Tao Y, Gao X, Zhang L, Li X, Zou W, et al. A CRISPR-based approach for targeted DNA demethylation. Cell Discovery. 2016;**2**:16009. DOI: 10.1038/ celldisc.2016.9

[37] Choudhury SR, Cui Y, Lubecka K, Stefanska B, Irudayaraj J. CRISPR-dCas9 mediated TET1 targeting for selective DNA demethylation at BRCA1 promoter. Oncotarget. 2016;**7**:46545-46556. DOI: 10.18632/oncotarget.10234

[38] Kearns NA, Pham H, Tabak B, Genga RM, Silverstein NJ, Garber M, et al. Functional annotation of native enhancers with a Cas9-histone demethylase fusion. Nature Methods. 2015;**12**:401-403. DOI: 10.1038/ nmeth.3325

[39] Hilton IB, D'Ippolito AM, Vockley CM, Thakore PI, Crawford GE, Reddy TE, et al. Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nature Biotechnology. 2015;**33**:510-517. DOI: 10.1038/nbt.3199

[40] Kwon DY, Zhao Y-T, Lamonica JM, Zhou Z. Locus-specific histone deacetylation using a synthetic CRISPR-Cas9-based HDAC. Nature Communications. 2017;**8**:15315. DOI: 10.1038/ncomms15315

#### [41] Paul B, Barnes S,

Demark-Wahnefried W, Morrow C, Salvador C, Skibola C, et al. Influences of diet and the gut microbiome on epigenetic modulation in cancer and other diseases. Clinical Epigenetics. 2015;**7**:112. DOI: 10.1186/ s13148-015-0144-7

[42] Hollister EB, Gao C, Versalovic J. Compositional and functional features of the gastrointestinal microbiome and their effects on human health. Gastroenterology. 2014;**146**:1449-1458. DOI: 10.1053/j.gastro.2014.01.052

*Perspective Chapter: Epigenetic Therapy – The Future Treatment for Cancer DOI: http://dx.doi.org/10.5772/intechopen.110641*

[43] Rinninella E, Raoul P, Cintoni M, Franceschi F, Miggiano GAD, Gasbarrini A, et al. What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms. 2019;**7**:14. DOI: 10.3390/microorganisms7010014

[44] Sharma M, Li Y, Stoll ML, Tollefsbol TO. The epigenetic connection between the gut microbiome in obesity and diabetes. Frontiers in Genetics. 2020;**10**:1329. DOI: 10.3389/ fgene.2019.01329

[45] Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. The international scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews Gastroenterology & Hepatology. 2014;**11**:506-514. DOI: 10.1038/ nrgastro.2014.66

[46] Pandey KR, Naik SR, Vakil B. Probiotics, prebiotics and synbiotics—A review. Journal of Food Science and Technology. 2015;**52**:7577-7587. DOI: 10.1007/s13197-015-1921-1

[47] Moludi J, Maleki V, Jafari-Vayghyan H, Vaghef-Mehrabany E, Alizadeh M. Metabolic endotoxemia and cardiovascular disease: A systematic review about potential roles of prebiotics and probiotics. Clinical and Experimental Pharmacology & Physiology. 2020;**47**:927-939. DOI: 10.1111/1440-1681.13250

[48] Cani PD, Everard A, Duparc T. Gut microbiota, enteroendocrine functions and metabolism. Current Opinion in Pharmacology. 2013;**13**:935-940. DOI: 10.1016/j.coph.2013.09.008

[49] Louis P, Hold GL, Flint HJ. The gut microbiota, bacterial metabolites and colorectal cancer. Nature Reviews. Microbiology. 2014;**12**:661-672. DOI: 10.1038/nrmicro3344

[50] Ansari I, Raddatz G, Gutekunst J, Ridnik M, Cohen D, Abu-Remaileh M, et al. The microbiota programs DNA methylation to control intestinal homeostasis and inflammation. Nature Microbiology. 2020;**5**:610-619. DOI: 10.1038/s41564-019-0659-3

[51] Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis. 2010;**31**:27-36. DOI: 10.1093/carcin/ bgp220

[52] Woo V, Alenghat T. Epigenetic regulation by gut microbiota. Gut Microbes. 2022;**14**:2022407. DOI: 10.1080/19490976.2021.2022407

[53] Wang Y, Kuang Z, Yu X, Ruhn KA, Kubo M, Hooper L, et al. The intestinal microbiota regulates body composition through NFIL3 and the circadian clock. Science. 2017;**357**:912-916. DOI: 10.1126/ science.aan0677

[54] Cervantes-Barragan L, Chai JN, MaD T, di Luccia B, Ahern PP, Merriman J, et al. *Lactobacillus reuteri* induces gut intraepithelial CD4 + CD8αα + T cells. Science. 1979;**2017**(357):806-810. DOI: 10.1126/science.aah5825

[55] Miro-Blanch J, Yanes O. Epigenetic regulation at the interplay between gut microbiota and host metabolism. Frontiers in Genetics. 2019;**10**:638. DOI: 10.3389/fgene.2019.00638

[56] Shock T, Badang L, Ferguson B, Martinez-Guryn K. The interplay between diet, gut microbes, and host epigenetics in health and disease. The Journal of Nutritional Biochemistry. 2021;**95**:108631. DOI: 10.1016/j. jnutbio.2021.108631

[57] Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;**504**:451- 455. DOI: 10.1038/nature12726

[58] Chang P, v, Hao L, Offermanns S, Medzhitov R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proceedings of the National Academy of Sciences of the United States of America. 2014;**111**:2247-2252. DOI: 10.1073/pnas.1322269111

[59] Jabs S, Biton A, Bécavin C, Nahori M-A, Ghozlane A, Pagliuso A, et al. Impact of the gut microbiota on the m(6) a epitranscriptome of mouse cecum and liver. Nature Communications. 2020;**11**:1344. DOI: 10.1038/ s41467-020-15126-x

[60] Dalmasso G, Nguyen HTT, Yan Y, Laroui H, Charania MA, Ayyadurai S, et al. Microbiota modulate host gene expression via microRNAs. PLoS One. 2011;**6**:e19293-e19293. DOI: 10.1371/ journal.pone.0019293

[61] Xue X, Cao AT, Cao X, Yao S, Carlsen ED, Soong L, et al. Downregulation of microRNA-107 in intestinal CD11c(+) myeloid cells in response to microbiota and proinflammatory cytokines increases IL-23p19 expression. European Journal of Immunology. 2014;**44**:673-682. DOI: 10.1002/eji.201343717

[62] Zununi Vahed S, Barzegari A, Rahbar Saadat Y, Goreyshi A, Omidi Y. Leuconostoc mesenteroides-derived anticancer pharmaceuticals hinder inflammation and cell survival in colon cancer cells by modulating NF-κB/AKT/ PTEN/MAPK pathways. Biomedicine & Pharmacotherapy. 2017;**94**:1094-1100. DOI: 10.1016/j.biopha.2017.08.033

[63] Hullar MAJ, Fu BC. Diet, the gut microbiome, and epigenetics. Cancer Journal. 2014;**20**:170-175. DOI: 10.1097/ PPO.0000000000000053

[64] Endesfelder D, Zu Castell W, Ardissone A, Davis-Richardson AG, Achenbach P, Hagen M, et al. Compromised gut microbiota networks in children with anti-islet cell autoimmunity. Diabetes. 2014;**63**:2006- 2014. DOI: 10.2337/db13-1676

[65] Waldecker M, Kautenburger T, Daumann H, Busch C, Schrenk D. Inhibition of histone-deacetylase activity by short-chain fatty acids and some polyphenol metabolites formed in the colon. The Journal of Nutritional Biochemistry. 2008;**19**:587-593. DOI: 10.1016/j.jnutbio.2007.08.002

[66] Marks PA, Richon VM, Miller T, Kelly WK. Histone deacetylase inhibitors. Adv Cancer Res. 2004;**91**:137-168. DOI: 10.1016/ S0065-230X(04)91004-4

[67] Acharya MR, Sparreboom A, Venitz J, Figg WD. Rational development of histone deacetylase inhibitors as anticancer agents: A review. Molecular Pharmacology. 2005;**68**:917-932. DOI: 10.1124/mol.105.014167

[68] Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009;**461**:1282-1286. DOI: 10.1038/nature08530

[69] Lan A, Lagadic-Gossmann D, Lemaire C, Brenner C, Jan G. Acidic extracellular pH shifts colorectal cancer cell death from apoptosis to necrosis upon exposure to propionate and acetate, major end-products of the human probiotic propionibacteria. Apoptosis. 2006;**12**:573-591. DOI: 10.1007/ s10495-006-0010-3

*Perspective Chapter: Epigenetic Therapy – The Future Treatment for Cancer DOI: http://dx.doi.org/10.5772/intechopen.110641*

[70] Wieërs G, Belkhir L, Enaud R, Leclercq S, Philippart de Foy J-M, Dequenne I, et al. How probiotics affect the microbiota. Frontiers in Cellular and Infection Microbiology. 2020;**9**:454. DOI: 10.3389/fcimb.2019.00454

[71] Yu T, Guo F, Yu Y, Sun T, Ma D, Han J, et al. Fusobacterium nucleatum promotes Chemoresistance to colorectal cancer by modulating autophagy. Cell. 2017;**170**:548-563.e16. DOI: 10.1016/j. cell.2017.07.008

[72] Calcinaro F, Dionisi S, Marinaro M, Candeloro P, Bonato V, Marzotti S, et al. Oral probiotic administration induces interleukin-10 production and prevents spontaneous autoimmune diabetes in the non-obese diabetic mouse. Diabetologia. 2005;**48**:1565-1575. DOI: 10.1007/ s00125-005-1831-2

[73] Lau K, Benitez P, Ardissone A, Wilson TD, Collins EL, Lorca G, et al. Inhibition of type 1 diabetes correlated to a *lactobacillus johnsonii* N6.2-mediated Th17 bias. The Journal of Immunology. 2011;**186**:3538-3546. DOI: 10.4049/ jimmunol.1001864

[74] Takiishi T, Korf H, van Belle TL, Robert S, Grieco FA, Caluwaerts S, et al. Reversal of autoimmune diabetes by restoration of antigen-specific tolerance using genetically modified Lactococcus lactis in mice. The Journal of Clinical Investigation. 2012;**122**:1717-1725. DOI: 10.1172/JCI60530

[75] Le TKC, Hosaka T, Nguyen TT, Kassu A, Dang TO, Tran HB, et al. Bifidobacterium species lower serum glucose, increase expressions of insulin signaling proteins, and improve adipokine profile in diabetic mice. Biomedical Research. 2015;**36**:63-70. DOI: 10.2220/biomedres.36.63

[76] Zhang J, Motyl KJ, Irwin R, MacDougald OA, Britton RA,

McCabe LR. Loss of bone and Wnt10b expression in male type 1 diabetic mice is blocked by the probiotic *lactobacillus reuteri*. Endocrinology. 2015;**156**:3169- 3182. DOI: 10.1210/EN.2015-1308

[77] Wei S-H, Chen Y-P, Chen M-J. Selecting probiotics with the abilities of enhancing GLP-1 to mitigate the progression of type 1 diabetes in vitro and in vivo. Journal of Functional Foods. 2015;**18**:473-486. DOI: 10.1016/j. jff.2015.08.016

[78] Abdelazez A, Abdelmotaal H, Evivie SE, Melak S, Jia F-F, Khoso MH, et al. Screening potential probiotic characteristics of lactobacillus brevis strains in vitro and intervention effect on type I diabetes in vivo. BioMed Research International. 2018;**2018**:7356173. DOI: 10.1155/2018/7356173

[79] Marcial GE, Ford AL, Haller MJ, Gezan SA, Harrison NA, Cai D, et al. Lactobacillus johnsonii N6.2 modulates the host immune responses: A doubleblind, randomized trial in healthy adults. Frontiers in Immunology. 2017;**8**:655. DOI: 10.3389/fimmu.2017.00655

[80] Groele L, Szajewska H, Szypowska A. Effects of lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed type 1 diabetes: Protocol of a randomised controlled trial. BMJ Open. 2017;**7**:e017178-e017178. DOI: 10.1136/ bmjopen-2017-017178

[81] Sokol H, Seksik P, Furet JP, Firmesse O, Nion-Larmurier I, Beaugerie L, et al. Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflammatory Bowel Diseases. 2009;**15**:1183-1189. DOI: 10.1002/ibd.20903

[82] Cui J, Li F, Shi Z-L. Origin and evolution of pathogenic coronaviruses. Nature Reviews. Microbiology. 2019;**17**:181-192. DOI: 10.1038/ s41579-018-0118-9

[83] Kibe R, Kurihara S, Sakai Y, Suzuki H, Ooga T, Sawaki E, et al. Upregulation of colonic luminal polyamines produced by intestinal microbiota delays senescence in mice. Scientific Reports. 2014;**4**:4548. DOI: 10.1038/srep04548

[84] Dai Z, Zhang J, Wu Q, Chen J, Liu J, Wang L, et al. The role of microbiota in the development of colorectal cancer. International Journal of Cancer. 2019;**145**:2032-2041. DOI: 10.1002/ ijc.32017

[85] Ryan FJ, Ahern AM, Fitzgerald RS, Laserna-Mendieta EJ, Power EM, Clooney AG, et al. Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease. Nature Communications. 2020;**11**:1512. DOI: 10.1038/ s41467-020-15342-5

[86] Nör C, Sassi FA, de Farias CB, Schwartsmann G, Abujamra AL, Lenz G, et al. The histone deacetylase inhibitor sodium butyrate promotes cell death and differentiation and reduces Neurosphere formation in human Medulloblastoma cells. Molecular Neurobiology. 2013;**48**:533-543. DOI: 10.1007/ s12035-013-8441-7

[87] Canale M, Casadei-Gardini A, Ulivi P, Arechederra M, Berasain C, Lollini P-L, et al. Epigenetic mechanisms in gastric cancer: Potential new therapeutic opportunities. International Journal of Molecular Sciences. 2020;**21**:5500. DOI: 10.3390/ijms21155500

[88] Ding S-Z, Goldberg JB, Hatakeyama M. Helicobacter pylori infection, oncogenic pathways and epigenetic mechanisms in gastric

carcinogenesis. Future Oncology. 2010;**6**:851-862. DOI: 10.2217/fon.10.37

[89] Zhou Z, Li H-Q, Liu F. DNA methyltransferase inhibitors and their therapeutic potential. Current Topics in Medicinal Chemistry. 2019;**18**:2448-2457. DOI: 10.2174/1568026619666181120150122

[90] Schneider BJ, Shah MA, Klute K, Ocean A, Popa E, Altorki N, et al. Phase I study of epigenetic priming with Azacitidine prior to standard neoadjuvant chemotherapy for patients with Resectable gastric and esophageal adenocarcinoma: Evidence of tumor Hypomethylation as an indicator of major histopathologic response. Clinical Cancer Research. 2017;**23**:2673-2680. DOI: 10.1158/1078-0432.CCR-16-1896

[91] Sun D, Chen Y, Fang J-Y. Influence of the microbiota on epigenetics in colorectal cancer. National Science Review. 2019;**6**:1138-1148. DOI: 10.1093/ nsr/nwy160

[92] Lao VV, Grady WM. Epigenetics and colorectal cancer. Nature Reviews. Gastroenterology & Hepatology. 2011;**8**:686-700. DOI: 10.1038/ nrgastro.2011.173

[93] Poupeau A, Garde C, Sulek K, Citirikkaya K, Treebak JT, Arumugam M, et al. Genes controlling the activation of natural killer lymphocytes are epigenetically remodeled in intestinal cells from germ-free mice. The FASEB Journal. 2019;**33**:2719-2731. DOI: 10.1096/fj.201800787R

[94] Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: A meta-analysis. Gut. 2001;**48**:526-535. DOI: 10.1136/ gut.48.4.526

[95] Tahara T, Hirata I, Nakano N, Tahara S, Horiguchi N, Kawamura T, et al. *Perspective Chapter: Epigenetic Therapy – The Future Treatment for Cancer DOI: http://dx.doi.org/10.5772/intechopen.110641*

Potential link between fusobacterium enrichment and DNA methylation accumulation in the inflammatory colonic mucosa in ulcerative colitis. Oncotarget. 2017;**8**:61917-61926. DOI: 10.18632/oncotarget.18716

[96] Linson EA, Hanauer SB. Epidemiology of colorectal cancer in inflammatory bowel disease—The evolving landscape. Current Gastroenterology Reports. 2021;**23**(9):1-16. DOI: 10.1007/ s11894-021-00816-3

[97] Ohigashi S, Sudo K,

Kobayashi D, Takahashi O, Takahashi T, Asahara T, et al. Changes of the intestinal microbiota, short chain fatty acids, and fecal pH in patients with colorectal cancer. Digestive Diseases and Sciences. 2013;**58**:1717-1726. DOI: 10.1007/ s10620-012-2526-4

[98] Weir TL, Manter DK, Sheflin AM, Barnett BA, Heuberger AL, Ryan EP. Stool microbiome and metabolome differences between colorectal cancer patients and healthy adults. PLoS One. 2013;**8**:e70803-e70803. DOI: 10.1371/ journal.pone.0070803

[99] Hýžd'alová M, Hofmanová J, Pacherník J, Vaculová A, Kozubík A. The interaction of butyrate with TNF-α during differentiation and apoptosis of colon epithelial cells: Role of NF-κB activation. Cytokine. 2008;**44**:33-43. DOI: 10.1016/j.cyto.2008.06.003

[100] Hu S, Dong TS, Dalal SR, Wu F, Bissonnette M, Kwon JH, et al. The microbe-derived short chain fatty acid butyrate targets miRNA-dependent p21 gene expression in human colon cancer. PLoS One. 2011;**6**:e16221-e16221. DOI: 10.1371/journal.pone.0016221

[101] Walsh T, Casadei S, Lee MK, Pennil CC, Nord AS, Thornton AM, et al. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proceedings of the National Academy of Sciences of the United States of America. 2011;**108**:18032-18037. DOI: 10.1073/ pnas.1115052108

[102] Kroeger PT Jr, Drapkin R. Pathogenesis and heterogeneity of ovarian cancer. Current Opinion in Obstetrics & Gynecology. 2017;**29**:26-34. DOI: 10.1097/GCO.0000000000000340

[103] Jelinic P, Ricca J, van Oudenhove E, Olvera N, Merghoub T, Levine DA, et al. Immune-active microenvironment in small cell carcinoma of the ovary, hypercalcemic type: Rationale for immune checkpoint blockade. Journal of the National Cancer Institute. 2018;**110**:787-790. DOI: 10.1093/jnci/ djx277

[104] Ahluwalia A, Yan P, Hurteau JA, Bigsby RM, Jung SH, Huang TH-M, et al. DNA methylation and ovarian cancer. Gynecologic Oncology. 2001;**82**:261-268. DOI: 10.1006/gyno.2001.6291

[105] Stone ML, Chiappinelli KB, Li H, Murphy LM, Travers ME, Topper MJ, et al. Epigenetic therapy activates type I interferon signaling in murine ovarian cancer to reduce immunosuppression and tumor burden. Proceedings of the National Academy of Sciences of the United States of America. 2017;**114**:E10981-E10990. DOI: 10.1073/ pnas.1712514114

[106] Moufarrij S, Dandapani M, Arthofer E, Gomez S, Srivastava A, Lopez-Acevedo M, et al. Epigenetic therapy for ovarian cancer: Promise and progress. Clinical Epigenetics. 2019;**11**:7. DOI: 10.1186/s13148-018-0602-0

[107] Cicek MS, Koestler DC, Fridley BL, Kalli KR, Armasu SM, Larson MC,

et al. Epigenome-wide ovarian cancer analysis identifies a methylation profile differentiating clear-cell histology with epigenetic silencing of the HERG K+ channel. Human Molecular Genetics. 2013;**22**:3038-3047. DOI: 10.1093/hmg/ ddt160

[108] Fuhrman BJ, Feigelson HS, Flores R, Gail MH, Xu X, Ravel J, et al. Associations of the fecal microbiome with urinary estrogens and estrogen metabolites in postmenopausal women. The Journal of Clinical Endocrinology and Metabolism. 2014;**99**:4632-4640. DOI: 10.1210/jc.2014-2222

[109] Shimizu K, Muranaka Y, Fujimura R, Ishida H, Tazume S, Shimamura T. Normalization of reproductive function in germfree mice following bacterial contamination. Experimental Animals. 1998;**47**:151-158. DOI: 10.1538/expanim.47.151

[110] Plottel CS, Blaser MJ. Microbiome and malignancy. Cell Host & Microbe. 2011;**10**:324-335. DOI: 10.1016/j. chom.2011.10.003

[111] Rowland IR, Wiseman H, Sanders TAB, Adlercreutz H, Bowey EA. Interindividual variation in metabolism of soy Isoflavones and Lignans: Influence of habitual diet on Equol production by the gut microflora. Nutrition and Cancer. 2000;**36**:27-32. DOI: 10.1207/ s15327914nc3601\_5

[112] Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nature Reviews. Genetics. 2002;**3**:415-428. DOI: 10.1038/nrg816

[113] Brock M, Hooker CM, Ota-Machida E, Han Y, Guo M, Ames S, et al. DNA methylation markers and early recurrence in stage I lung cancer. New England Journal of Medicine. 2008;**358**:1118-1128. DOI: 10.1056/ nejmoa0706550

[114] Momparler RL, Ayoub J. Potential of 5-aza-2′-deoxycytidine (Decitabine) a potent inhibitor of DNA methylation for therapy of advanced non-small cell lung cancer. Lung Cancer. 2001;**34**:111-115. DOI: 10.1016/s0169-5002(01)00397-x

[115] Schrump DS, Fischette MR, Nguyen DM, Zhao M, Li X, Kunst TF, et al. Phase I study of decitabinemediated gene expression in patients with cancers involving the lungs, esophagus, or pleura. Clinical Cancer Research. 2006;**12**:5777-5785. DOI: 10.1158/1078-0432.ccr-06-0669

[116] Ansari J, Shackelford RE, El-Osta H. Epigenetics in non-small cell lung cancer: From basics to therapeutics. Translational Lung Cancer Research. 2016;**5**:155-171. DOI: 10.21037/ tlcr.2016.02.02

[117] Yao H, Rahman I. Current concepts on the role of inflammation in COPD and lung cancer. Current Opinion in Pharmacology. 2009;**9**:375-383. DOI: 10.1016/j.coph.2009.06.009

[118] Shin JI, Brusselle GG. Mechanistic links between COPD and lung cancer: A role of microRNA let-7? Nature Reviews. Cancer. 2013;**14**:70. DOI: 10.1038/ nrc3477-c1

Section 3


**5. Transmission of COVID-19**

It is universally acknowledged that people-to-people transmission of SARS-CoV-2 occurs in the community, family settings, and health care. Substantial dissemination methods involve droplets from the respiratory duct and indirectly through fomites and aerosols. Some circumstantial evidence shows that PCR and culture are two important laboratory tests used to separate the virus from saliva and identify its feces [30–33]. It has also been observed that the virus appears differently in both blood and urine [34, 35]. If the COVID-19 is mild, the virus shedding in respiratory samples remains for a long period in the case of children; the virus having RNA is obtained in higher magnitude (83.3%) in feces with lasting shedding for a fortnight, whereas it lasts for more than one month in children [27]. Diverse research suggests that the spread of the virus can be seen during incubation on the day or the day before the signs are set forth and spread from very mild asymptomatic infections [36–40]. From the day of his admission, positive samples were collected from the nasopharynx of a half-year-old baby with a high viral load;

#### *Origin and Impact of COVID-19 on Socioeconomic Status DOI: http://dx.doi.org/10.5772/intechopen.98893*

these specimens were positive for several days [41]. Therefore, multiple instances may remain undetected and pose a sustainable challenge for virus transmission [42]. The replication number (Ro) is usually considered to be in the range of 2.0 and 2.8 [37–40]; in case higher multiplication numbers are recommended, the serial interlude remains within a span of 5 to 7 days [43–45]. The mean incubation period is between 4.75 and 7 days [46, 47], ranging from 3 to 14 days. Information about the virus load is increasing simultaneously with an increase in our understanding of the virus. In another instance, patients with higher viral loads were identified; the viral droplets in the nose were higher than those in the throat. The intensity of viral droplets was alike in the case of a single symptomatic patient and an asymptomatic patient [32]. On another occasion, for a comprehensive study, the assessment of the virus load was conducted in a pair of patients with a series of samples collected from swabs, throat, urine, stool, and sputum over consecutive days from admission to hospitalization. The viral loads peaked with 104 to107 copies/mL at approximately 5 to 6 days after the onset of symptoms. Similar samples of viral droplets from other patients were examined by the writers, who found the viral loads to be nearly 1011 copies/mL in the throat sample, but the sputum samples had a median of 7.99 × 194, 7.52 ×105. Additionally, the virus was examined using RT-PCR in feces from 9 out of 17 established studies [24]. An examination of nine pregnant women infected with the virus did not provide substantial proof of ureteral transmission to the fetus [48].

As a positive-stranded RNA virus, SARS-CoV-2 was discovered, which is said to belong to the genus beta coronavirus, having a crown-like spike composed of glycoproteins enveloping the surface (**Figure 2**) [18]. There are six categories of coronaviruses found in human beings along with SARS-CoV-2; they are MERS-CoV, HCoV-HKU1, HCoV-OC43, HCoV-229E, SARS-CoV, and HCoV-NL63 [22]. Evaluation of phylogenetics demonstrated that ARS-CoV-2 was nearly related to SARS, with 88–89% similarity; it is also deemed to be derived from bat-SL-CoVZXC21 (unique identifier: MG772934.1) and bat-SL-CoVZC45 (unique identifier: MG772933.1); however, it has a comparatively distant relationship with SARS-CoV and MERS-CoV being 79% and 50% similar, respectively [23–25]. SARS-CoV-2 is covered with a wrapper; it is circular, elliptic, and often

#### **Figure 2.**

*The main stockpile and medium of transmission of coronaviruses (presumed stocks of SARS-CoV-2 are circled red); the alpha and beta members of coronaviruses have the potential to afflict human beings; the devouring of animals, infected with the virus as an origin of food, is the prime reason of virus spreading from beasts to human beings. Owing to being in contact with a virus-infected person, finally, the virus spread to sound individuals. Arrow with dotted black lines demonstrates the likelihood of virus spread from the bat, whereas the arrow with solid black lines represents the accurate transferal. Reference: [49]. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).*

polymorphic elements have a radius ranging between 30 nm and 70 nm [26]. The phylogenetic reports and additional research on entire genome sequencing have shown that COVID-19 is inconsistent with SARS-CoV. It can thus be considered the latest beta-coronavirus damaging human organs [27]. The genesis of the 2019-nCoV has been mysterious ever since, but the rising surge is deemed to be connected to the Seafood Market of Huanan in South China [28]. Researchers have been striving to discover the sources in animals to do away with the spread of this novel coronavirus, but none are certain until now. The maximum number of hosts is consistent with the prospective sources of the 2019-nCoV that it belongs to seafood, pangolins, or even bats [3, 4, 26]. The immediate work is to track down the transitory source instrumental in transmitting the coronavirus to human beings. Therefore, determining the source of the virus must bear the potential to help discover the zoonotic transmission method [26]. SARS-CoV-2 demonstrates the risk of high pathogenicity and communicability [29]. It is likely to be transferred from one person to another by the viral loads of infected persons who are directly in contact with the surfaces already contaminated by the respiratory droplets through sneezing, coughing, and physical contact with infected patients [29]. According to several reports, symptomatic individuals are the most recurring sources of COVID-19 escalation [27]. Furthermore, there are opinions that asymptomatic individuals can also transmit the virus as intensely as symptomatic individuals. Besides, more studies are required to understand and explain the durability of infectiveness, the procedures of transmission, and the incubation period of the virus. As HCoV-19 is the latest phenomenon among human beings, much effort is needed to be acquainted with the sources of this virus. Based on a twisted explanation or inappropriate delineation of the early released and restricted amount of data on the HCoV-19 genome, different suppositions or hypotheses are prevalent in that HCoV-19 was artificially produced in mysterious circumstances [50, 51] Specifically, the installation of a polybasic (furin) at the cleavage site of the spike protein was discovered in betacoronaviruses for the first time (48). Based on the comprehension and information collected from the MERS-CoV and SARS-CoV outbreaks, SARS (Bat-CoVRaTG13) in *Rhinolophus* affinis was successfully detected and separated; it was 95% similar to HCoV-19. It could be propounded that the COVID-19 virus possibly belongs to bats with a higher degree of conviction [52]. Additionally, phenylacetic acid amide on the cleavage region of S1 and S2 has recently been observed in the coronavirus genetic arrangement detected in a different *Rhinolophus malayanus* [52]. These outcomes imply that there are nearly two bat types: *Rhinolophus malayanus* and *Rhinolophus* affinis. They are presumed to be the native sources of HCoV-19. Bats are believed to be a possible animal pool for HCoV-19- and SARS-like [53] coronaviruses. Presently, non-comprehensive evidence is found to show the bats responsible for directly spreading HCoV-19-like coronaviruses to human beings. Recent research shows that the Malayan pangolin (Manisjavanica) has been considered a potential natural storehouse or transitional source of HCoV-19 [54–56]. In another study, community genomic sequencing of blood, intestine, and lung samples from Malayan pangolins was examined by Lam et al. [54, 57]. They detected virus sequences with a connection with a pair of subcategories of HCoV-19 like coronaviruses. Specifically, five analytical remnants of the pangolin virus, which play a significant role in human receptor binding, are similar in every detail to HCoV-19 [57]. Based on a re-evaluation conducted on a formerly announced virus metagenomics dataset of Malayan pangolins [58], it is recommended that there is a prospective pangolin origin of HCoV-19 [59]. The all-inclusive feature of HCoV-19 concerning Pangolin-CoV in pangolins has repeatedly suggested that Malayan pangolin could be a prospective transitional source for HCoV-19 [55]. It is believed that HCoV-19 could spring from a probable intermingling of the aforementioned

*Origin and Impact of COVID-19 on Socioeconomic Status DOI: http://dx.doi.org/10.5772/intechopen.98893*

Bat-CoV-RaTG13-like virus [52] and Pangolin-CoV-like virus [55]. Malayan pangolins are reported to have been spotted in the natural habitat across Southeast Asia. However, it has never been considered to belong to China, where HCoV-19 was confirmed for the first time [3, 27, 45, 52] because it was significant as an origin of food and herbal treatment.

Irrespective of its whereabouts still not being identified, multiple cases of COVID-19 have been referred to those who have visited the Seafood Wholesale Market of Huanan, situated in the city of Wuhan, China. On February 11, 2020, the WHO came up with COVID-19, a shortened form for COVID 2019. The virus responsible for this flare-up is recognized as SARS-CoV-2; recently, it has been unearthed and is closely related to bat coronaviruses, SARS-Cov, and pangolin coronaviruses.


**Mary Anne Melo**

Mary Anne Melo (DDS, MSc, Ph.D., Fellow ADM) is a Clinical Professor at the University of Maryland School of Dentistry and currently serving as Chair of the Department of General Dentistry. Dr. Melo applies her experience as a dentist and dental materials researcher to advance the development of smart and bioactive restorative materials. Her clinical areas of interest include minimally invasive dentistry, the management of high-caries-risk patients, and esthetic dentistry. Her research has focused chiefly on anticaries approaches for caries-inhibiting, antibacterial, or remineralization functionalities. Her research group has pioneered the investigations of antibacterial and remineralizing dental adhesives and resin composites. Dr. Melo is a current member of the Academy of Operative Dentistry; the International Association for Dental Research; the American Academy of Cariology, and the American Academy of Cosmetic Dentistry. Dr. Melo is a co-inventor on two patents, has edited three books, and has published more than 200 papers in the area of dental materials. Several grants support her research. She lectures nationally and internationally on diverse topics of restorative dentistry.


**2. Bryophytes and the environmental changes**

Climate change is affecting the group very deeply, in particular because they are very dependent on water, including for their sexual reproduction, as they have flagellated antherozoids. Even in environments where they are the dominant flora, such as in maritime Antarctica, species may have their occurrence threatened in the face of climate change. This is also the case of boreal areas and high mountains ecosystems [7]. Bryophytes can even be used for monitoring and as an indication of the effects of climate change on living organisms. They have even been indicated as "canaries in the coal mine" with regard to their behavior in relation to the external environment [8]. As a result, they are symbols of eternity in some cultures.

This group has very simple thalli, with leaves generally formed by only one layer of cells, stems without conductive tissues and rhizoids only one cell thick, which obtain

their nourishment directly from atmospheric humidity, from the soil or substrate where they are fixed. Many react quickly in the presence of pollutants and can be used to monitor and control them. Morphological and even genetic modifications in relation to the toxicity of polluting metals or even the stress caused by their presence can be followed, making them first-class bioindicators [9, 10]. Many species are extremely sensitive to pollutants, suffering some injuries or even resulting in the death of the entire thallus, while others are very resistant, even managing to retain pollutants, preventing them from affecting other species in the environment [11]. The reduction of pollutants in large urban centers is already being done using bryophytes in systems that filter and purify the atmospheric air with great efficiency.

There are even species that live submerged in water and that can collaborate in the removal of pollutants from these systems without suffering damage, as is the case of *Leptodyction riparium*, *Fontinalis antipyretica,* and *Scapania undulata*, among others [12, 13]. Some aquatic species are even reported as accumulating very rare chemical elements in nature such as Nd, Gd, Ho, Er, Tm, Lu, La, Ce, Sm, Eu, Tb, and Dy [14].


**4.2 Relationship with WTP**

Many studies have suggested that WTP judgments are based on activation in the medial OFC. Because this area is not on the brain surface, it is difficult to monitor this activation with NIRS. We have shown that brain activation in the right superior frontal and the left and right parietal lobes was related to WTU. Because of the limitations of NIRS measurements, it is unclear whether the medial OFC was activated in the current experiments and related to WTU judgments.

#### **4.3 Difference by race**

Participants with different nationalities and different cultural backgrounds are expected to have different styles of thinking. A number of studies have suggested that people from different cultures have different cognitive processing styles (e.g., North Americans attend to focal objects more than do East Asians). Although these cultural differences may cause the correlations between brain activations and subjective ratings to differ among cultures, our results indicate the operation of a common brain mechanism in this regard. However, culture may nonetheless influence impressions, WTU, WTB, and brain activation related to these judgments. The cultural differences involved in-store shopping behaviors need to be understood given that such differences carry important implications for both academic and commercial domains.

#### **4.4 Advantage of NIRS for studying everyday situations**

The participants in the current study moved their arms and hands to apply a facial cream and touched jar. These actions are not permitted in magnetic resonance imaging scanners, and they also cause strong electroencephalogram artifacts due to muscle potentials. Thus, brain monitoring with NIRS is the only acceptable technique to use in situations in which participants move with relative freedom.


**Chapter 7**

Group III-Nitrides and Their Hybrid Structures for Next-Generation Photodetectors *by Deependra Kumar Singh, Basanta Kumar Roul, Karuna Kar Nanda and Saluru Baba Krupanidhi*

#### **Chapter 8**

Studying a LW-VCSEL-Based Resonant Cavity Enhanced Photodetector and Its Application in Microwave Photonics Circuits *by Mikhail E. Belkin, Leonid I. Zhukov, Dmitriy A. Fofanov, Mikhail G. Vasil'ev and Alexander S. Sigov*

Preface

French scientist P. Aigrain introduced the term "photonics" in 1967. This term encompasses light generation (lasers or light-emitting diodes [LEDs]), organic LEDs (OLEDs), light transmission (through free space or guided structures), processing (modulation, switching, etc.), and detection of both light and images.

Section 1, "Light-Emitting Diodes and Organic Light-Emitting Diodes," includes three chapters discussing recent reviews and important modernizations in evaluating lighting systems. Chapter 1 discusses the operation and mechanisms of OLEDs. Chapter 2 presents an overview of LEDs, including information on their economic benefits and ratings of outdoor high-intensity discharge (HID) lights, smart control of road lighting, and intelligent design of indoor LED lights in industrial buildings. Chapter 3 evaluates LED driver circuits based on different supply sources and

Section 2, "Photodetectors," includes five chapters presenting recent developments in the photo-detection field. Photodetectors (PDs) are devices able to convert light into a measurable electrical signal, mainly taking advantage of two approaches: 1) the use of the incident photon flux to generate excitons within specific materials and 2) the use of materials characterised by strongly temperature-dependent properties. Chapter 4 reports on silicon (Si) PDs, which have been widely developed in the visible spectrum for the realisation of high-performance complementary metaloxide semiconductor (CMOS) sensors. Nowadays, Si is becoming an ideal platform for detecting the short-wavelength infrared (SWIR) spectral band thanks to the integration of Si with 2D materials. Chapter 5 discusses 2D materials like transition metal dichalcogenides (TMDs), black phosphorous, silicene, and graphene. It also presents the advances of PDs based on 2D materials and the main heterostructures. Chapter 6 introduces a new type of group-10 noble TMDs (NTMDs) that demonstrate the capability to realize PDs characterized by ultra-broad detection waveband (200 nm to 10.6 μm), fast response time, high responsivity and detectivity, and polarization sensitivity. Chapter 7 describes the evolution in the field of III-nitride semiconductors and their employment to the realization of structures for next-generation PDs. Finally, Chapter 8 presents a comparative study of a long-wavelength vertical cavity surface-emitting laser (LW-VCSEL) adapted to work as a PD and the

This book provides readers with a detailed overview of the most recent advances in the fascinating world of both LEDs and PDs as well as explores some possible future directions in the field. This book is for students and scientists working in the field of

We thank all the contributors to this book as well as Anja Filipovic and Mia Vulovic at IntechOpen for their valuable assistance during the preparation and publication

This book examines LEDs/OLEDs and photodetectors (PDs).

power requests.

standard PIN PDs.

of this book.

photonics and advanced technologies.

**175**


**1. Introduction**

Vector-borne diseases and many zoonotic diseases remain significantly relevant in tropical areas, such as Latin America. In the specific case of those caused by viruses, arboviruses, this region, as well as Asia, are particularly affected over time, primarily due to the widespread of competent vectors, as is the case of *Aedes aegypti*, but also *A. albopictus*, and more recently *A. vittatus* [1, 2]. Then, as expected, an integrated One Health approach, considering the environment, and animal and human health, is needed for vector-borne diseases [3].

Over the last decades, multiple arboviral diseases caused by alphaviruses and flaviviruses have been a concern in Latin America [4]. However, since the introduction of yellow fever and dengue, the epidemiological landscape in the region has significantly changed [5]. Dutch slave traders brought yellow fever (YFV) to the America from Africa during the mid-seventeenth century.

For the next two and a half centuries, the disease terrorized seaports throughout the America [6]. Reports describe the possible first introduction in 1648 in Mexico [5, 7–9]. Although some studies suggest dengue (DENV) was introduced in the America, through the Caribbean islands in 1635 [5, 10, 11], before 1981, dengue was considered a public health problem only in Asia and posed little or no threat to the region of the America [11, 12]. This scenario shifted with the 1981 Cuban epidemic,

the first significant dengue epidemic in the area. For the following decade, sporadic cases of dengue were observed. Then, in 1990, Venezuela experienced the second major epidemic in the region. These events marked dengue as an emerging disease in the America [11, 12]. As observed, flaviviruses, such as dengue and yellow fever, have been significant concerns regarding morbidity and mortality in the region [4, 13–27]. Additionally, many of them, as observed with Zika (ZIKV) and chikungunya (CHIKV), lead to chronic consequences, such as central nervous system (CNS) compromise (including congenital microcephaly and other complications of congenital Zika syndrome) [28–32], as well as chronic rheumatic and non-rheumatic diseases (CHIKV) [33–39].

Taxonomically speaking, the essential arboviruses are included in the genus alphavirus, family Togaviridae (**Figure 1**), which consists of a total of 32 species; and in the genus flavivirus, family Flaviviridae (**Figure 2**), where 53 species are currently included.

**Figure 1.**

*Taxonomical classification of viruses belonging to the genus alphavirus (family Togaviridae, order martellivirales, class alsuviricetes). (https://ictv.global/taxonomy).*

## **Figure 2.**

*Taxonomical classification of viruses belonging to the genus flavivirus (family Flaviviridae, order amarillovirales, class flasuviricetes). (https://ictv.global/taxonomy).*

Alphaviruses, originally endemic in Latin America, such as the Venezuelan equine encephalitis (VEE) and the eastern equine encephalitis; were described in 1920 in Venezuela and 1972 in Trinidad and Tobago, respectively [5]. Mayaro virus, another

**Figure 3.**

*The number of articles published about arboviruses (alphaviruses, flaviviruses, and orthobunyaviruses) in Latin America, cumulated until November 1, 2022, in PubMed-indexed journals. (https://pubmed.ncbi.nlm.nih.gov/).*

alphavirus from Trinidad and Tobago, was described in 1954. In Trinidad and Tobago, an endemic orthobunyavirus, the Oropouche virus, was described in 1955 [5].

Then, as observed in the number of published articles available in PubMed (**Figure 3**), many of these arboviruses in Latin America, such as Mayaro (MAYV), Madariaga (MADV), Saint Louis encephalitis (SLEV), Rocio (ROCV), and Oropuche (OROV) are neglected. Nevertheless, according to the World Health Organization (WHO), only DENV and CHIKV are formally included as neglected tropical diseases (https://www.who.int/health-topics/neglected-tropical-diseases).

Even the total of articles of them (1364) is much lower than the total of DENV (20.5 times higher), ZIKV (8 times), YFV (6 times), CHIKV (5 times), or VEE (1.4 times) (**Figure 3**). So then, MAYV, MADV, SLEV, ROCV, and OROV may be considered neglected. As a consequence, such arboviruses will be analyzed in the current chapter.