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2022
Qiu, Y., X. Gao, R. Chen, S. Lu, X. Wan, M. A. Farag, and C. Zhao, "Metabolomics and biochemical insights on the regulation of aging-related diabetes by a low-molecular-weight polysaccharide from green microalga .", Food chemistry: X, vol. 14, pp. 100316, 2022. Abstract

Globally, aging and diabetes are considered prevalent threats to human health. polysaccharide (CPP) is a natural active ingredient with multiple health benefits including antioxidant and hypolipidemic activities. In this study, the aging-related diabetic (AD) mice model was established to investigate the underlying hypoglycemic and antioxidant mechanisms of CPP. It improved superoxide dismutase, catalase (CAT), glutathione peroxidase (GSH-px), and malondialdehyde activities in liver and insulin secretion. CAT and GSH-px activity in the brain increased after CPP administration. In addition, through histopathological examinations, it was evident that injuries in the liver, brain, jejunum, and pancreas were restored by CPP. This restoration was likely mediated via the activation of glucagon-like peptide-1 receptor/FOXO-1 (forkhead box O1) pathway concurrent with the inhibition of interleukin-6 receptor/FOXO-1 pathway. Furthermore, metabolomics and correlation analysis revealed that CPP possibly relived AD through changes in insulin levels and declined oxidative stress as regulated by phenylpyruvic acid. These findings suggested that CPP exerted antioxidant and hypoglycemic roles in an AD mice model, thereby providing a sound scientific foundation for further development and utilization of CPP.

Baky, M. H., H. Fahmy, and M. A. Farag, "Recent Advances in Nutraceuticals in Relation to Its Hydroxy Citric Acid Level. A Comprehensive Review of Its Bioactive Production, Formulation, and Analysis with Future Perspectives.", ACS omega, vol. 7, issue 30, pp. 25948-25957, 2022. Abstract

(Gaertn.) Desr. (known as Malabar tamarind) is a popular traditional herbal medicine and is one of the well-known folk medicines reported for the treatment of obesity and incorporated in several nutraceuticals worldwide. These effects are mediated by a myriad of bioactive compounds with most effects attributed to its hydroxy citric acid (HCA) content. This review aims to present a holistic overview on novel trends in the production of . bioactive components and how extraction optimization is important to ensure best product quality with its reported nanoformulations with particular emphasis on HCA content. Further, an overview of the different analytical approaches used for quality control assessment of . plant and its nutraceuticals is presented highlighting both advantages and limitations. Moreover, analytical approaches for detecting . metabolites in biological fluids with emphasis on HCA level to determine its pharmacokinetics and proof of efficacy are presented for the first time.

Chen, Y., W. Wu, X. Ni, M. A. Farag, E. Capanoglu, and C. Zhao, "Regulatory mechanisms of the green alga oligosaccharide via the metabolomics and gut microbiome in diabetic mice.", Current research in food science, vol. 5, pp. 1127-1139, 2022. Abstract

Type 2 diabetes (T2D) has emerged as one of the most acute public health diseases of the present time, which increases with the population ageing. This study aimed to evaluate the hypoglycaemic activity of oligosaccharide (ULO) under ageing-related diabetes conditions in an animal model. The results demonstrated that ULO can promote hypoglycaemia and delay senescence as mediated GLP-1/GLP-1R pathway to mobilize the intercommunication between the brain and gut. In addition, twenty-six different metabolites and eight different bacteria were screened in the brain and the gut, respectively. A network relationship displayed that all-trans-retinoic acid has positive relationships with and , suggesting that plays a potential key role in maintaining the hypoglycaemic and anti-ageing activities of ULO. Based on these findings, ULO might be an efficient therapy for restoring blood glucose metabolism and delaying brain senescence in elderly T2D patients.

Eid, S. M., M. A. Farag, and S. Bawazeer, "Underivatized Amino Acid Chromatographic Separation: Optimized Conditions for HPLC-UV Simultaneous Quantification of Isoleucine, Leucine, Lysine, Threonine, Histidine, Valine, Methionine, Phenylalanine, Tryptophan, and Tyrosine in Dietary Supplements.", ACS omega, vol. 7, issue 35, pp. 31106-31114, 2022. Abstract

Amino acids (AAs) are considered as the building blocks of life. Unlike nonessential AAs, the human body cannot synthesize essential AAs and should be supplied in food or dietary supplements. The aim of the work is simultaneous HPLC-UV determination of 10 structurally related AAs without pre- or postderivatization in powdered dietary supplements (PDSs). This was challenging, especially because PDS has no standardized procedures for its quality control. HPLC-UV chromatograms of the 10 AAs were recorded using a gradient elution of the mobile phase on a CLC-C18 column at 225 nm. The elution started with 100% of phosphate buffer (pH 7.4, 10 mM) for 10 min; then, the concentration of acetonitrile increased linearly to reach 50% for another 15 min at room temperature. Good separation was achieved within a 25 min run time without pre- or postderivatization. The method was carefully validated according to the ICH guidelines over the linearity range of 100-200, 50-200, 20-150, 50-400, 20-250, 75-175, 50-250, 50-250, 50-300, and 5-100 μg/mL for l-lysine, l-threonine, l-histidine, l-valine, l-methionine, l-isoleucine, l-leucine, l-tyrosine, l-phenylalanine, and l-tryptophan, respectively, with mean recoveries ranges between 98.91 and 100.77. The method was found to be precise, and the relative standard deviation (RSD) was found to be between 0.28 and 1.92 with recoveries between 97.91 and 101.11. The method was found to be robust that resists deliberate changes in pH, flow rate, and mobile-phase percentages. It was successfully applied for the analysis of PDSs. The proposed method could be very useful for the quality control of the 10 structurally related AAs during their synthesis and for testing raw materials and pharmaceutical preparations.

El-Kersh, D. M., R. F. Abou El-Ezz, M. Fouad, and M. A. Farag, "Unveiling Natural and Semisynthetic Acylated Flavonoids: Chemistry and Biological Actions in the Context of Molecular Docking.", Molecules (Basel, Switzerland), vol. 27, issue 17, 2022. Abstract

Acylated flavonoids are widely distributed natural metabolites in medicinal plants and foods with several health attributes. A large diversity of chemical structures of acylated flavonoids with interesting biological effects was reported from several plant species. Of these, 123 compounds with potential antimicrobial, antiparasitic, anti-inflammatory, anti-nociceptive, analgesic, and anti-complementary effects were selected from several databases including SCI-Finder, Scopus, Google Scholar, Science Direct, PubMed, and others. Some selected reported biologically active flavonoids were docked in the active binding sites of some natural enzymes, namely acetylcholinesterase, butyrylcholinesterase, α-amylase, α-glucosidase, aldose reductase, and HIV integrase, in an attempt to underline the key interactions that might be responsible for their biological activities.

Farag, M. A., M. M. Rezk, M. Hamdi Elashal, M. El-Araby, S. A. M. Khalifa, and H. R. El-Seedi, "An updated multifaceted overview of sweet proteins and dipeptides as sugar substitutes; the chemistry, health benefits, gut interactions, and safety.", Food research international (Ottawa, Ont.), vol. 162, issue Pt A, pp. 111853, 2022. Abstract

Artificial sweeteners have become increasingly popular worldwide owing to their lower calorie content in addition to the claims of health benefits such as weight control, blood glucose level regulation in diabetics, and protection against dental caries. Nevertheless, there is still controversy regarding their safety, especially when administered over the long term, taking into account that most of the safety studies are based on animal models and only a few human studies. This review focuses on low-calorie protein/peptide sweeteners. These include artificial sweeteners, i.e. aspartame, advantame, neotame, and alitame which are synthetic, versus those of natural origin such as thaumatin, monellin, brazzein, pentadin, mabinlin, curculin, and egg white lysozyme. We conducted a systematic literature survey to ensure the accuracy of the data regarding the chemical properties, synthesis, and industrial applications. The health benefits and safety of these sweeteners in humans are presented for the first time in context to their metabolic profiles and gut interaction.

Sayed, A. E. M., F. A. Omar, M. M. A. - A. Emam, and M. A. Farag, "UPLC-MS/MS and GC-MS based metabolites profiling of seed with its anti- and anti-inflammatory activities.", Natural product research, vol. 36, issue 24, pp. 6433-6438, 2022. Abstract

Compared to its leaf, few studies have been reported on the seeds of Lam. Metabolites profiling analysis of seed methanolic extract (ME) and its fixed oil (MO) was attempted LC/MS and GC/MS. LC/MS analysis of seeds annotated 84 peaks of which glucosinolates and their corresponding acetyl isomers were abundant. GC/MS of seed oil revealed the abundance of fatty acids with oleic acid at 34.3%. ME exhibited significant anti- activity with MIC 0.92 µg/mL, nearly one-half that of Clarithromycin. Fixed oil (MO) showed a nonselective anti-inflammatory effect with IC= 24.4 ± 0.8 µg/mL correlated to Ibuprofen. To unravel the mechanism of the anti- activity a molecular docking study of the principal components of the ME has been performed, using H. pylori urease enzyme. Interactions with Ni ions and amino acid residue in the active site, which are crucial for the enzyme's biochemical role, are evidenced.

Farag, M. A., M. Sheashea, C. Zhao, and A. A. Maamoun, "UV Fingerprinting Approaches for Quality Control Analyses of Food and Functional Food Coupled to Chemometrics: A Comprehensive Analysis of Novel Trends and Applications.", Foods (Basel, Switzerland), vol. 11, issue 18, 2022. Abstract

(1) Background: Ultraviolet-visible (UV-Vis) spectroscopy is a common analytical tool to detect chromophore in compounds by monitoring absorbance spectral wavelengths. Further, it could provide spectral information about complex conjugated systems in mixtures aided by chemometric tools to visualize large UV-Vis datasets as typical in food samples. This review provides novel insight on UV-Vis applications in the last 20 years, as an advanced analytical tool in the quality control of food and dietary supplements, as well as several other applications, including chemotaxonomy, authentication, fingerprinting, and stability studies. (2) Conclusions: A critical assessment of the value of UV application and its novel trends in the quality control (QC) of nutraceuticals reveals the advantages and limitations, focusing on areas where future advancements are in need. Although simple, UV and its novel trends present potential analytical tools with an acceptable error for QC applications from a non-targeted perspective compared to other expensive spectral tools.

Farag, M. A., A. Bahaa Eldin, and I. Khalifa, "Valorization and extraction optimization of Prunus seeds for food and functional food applications: A review with further perspectives.", Food chemistry, vol. 388, pp. 132955, 2022. Abstract

Valorization of byproducts generated during food processing has recently attracted considerable attention, especially processes with high wastage rates. In this review we present a detailed analysis of the phytochemical composition of Prunus seed oil and extracts as potential sources of unsaturated fatty acids, phenolics, and phytosterols. Besides their nutritional value these seeds, especially apricot and peach seeds, could be exploited to produce value-added products such as food enhancers, and antioxidants. Optimum extraction methods of Prunus seeds are discussed to improve yield and lessen environmental hazards associated with typical solvent extraction-based methods. This review presents the best valorization practices for one of the largest cultivated fruit seeds worldwide and its different applications in food and functional food industries.

2021
Farag, M. A., A. Meyer, and S. E. Ali, "Bleaching effect in Sarcophyton spp. soft corals-is there a correlation to their diterpene content?", Environmental science and pollution research international, vol. 28, issue 20, pp. 25594-25602, 2021. Abstract

Rising seawater temperature is one of the greatest threats to the persistence of coral reefs. While great efforts have been made to understand the metabolic costs of thermal acclimation, the exact roles of many secondary metabolites involved in the immediate response exhibited by soft corals remain largely unknown. Herein, an untargeted metabolomics approach using ultra-performance liquid chromatography coupled to high-resolution mass spectrometry (UPLC-MS) was employed to investigate thermal stress-induced modifications to the de novo synthesis of secondary metabolites in two soft coral species, Sarcophyton ehrenbergi and S. glaucum. Exposure to elevated temperature resulted in symbiont photoinhibition primarily via either damage to photosystem II (PSII) or the loss of algal symbionts during coral bleaching. This was suggested by a decrease in pulse amplitude modulated (PAM) measurements of corals incubated at different temperatures. Thermal stress was also found to impair the production of diterpenoid secondary metabolites in soft corals. Principally, reduction in the levels of a number of diterpenes, viz. sarcophytoxide and deoxysarcophytoxide, in heat stressed S. ehrenbergi and S. glaucum was observed indicative that thermal acclimation is energetically costly and will necessitate downstream changes in secondary metabolic pathways. Our data suggest that, while the host controls the production of ecologically important terpenes, when energetic contribution from the algal symbiont is reduced or absent as a result of a bleaching event, energy reserves may be insufficient to maintain the production of such energetically cost chemicals. This study provides for the first time a holistic assessment of secondary metabolite changes imposed in soft corals during exposure and acclimation to elevated temperatures.

Bakry, I. A., L. Yang, M. A. Farag, S. A. Korma, I. Khalifa, I. Cacciotti, N. I. Ziedan, J. Jin, Q. Jin, W. Wei, et al., "A Comprehensive Review of the Composition, Nutritional Value, and Functional Properties of Camel Milk Fat.", Foods (Basel, Switzerland), vol. 10, issue 9, 2021. Abstract

Recently, camel milk (CM) has been considered as a health-promoting icon due to its medicinal and nutritional benefits. CM fat globule membrane has numerous health-promoting properties, such as anti-adhesion and anti-bacterial properties, which are suitable for people who are allergic to cow's milk. CM contains milk fat globules with a small size, which accounts for their rapid digestion. Moreover, it also comprises lower amounts of cholesterol and saturated fatty acids concurrent with higher levels of essential fatty acids than cow milk, with an improved lipid profile manifested by reducing cholesterol levels in the blood. In addition, it is rich in phospholipids, especially plasmalogens and sphingomyelin, suggesting that CM fat may meet the daily nutritional requirements of adults and infants. Thus, CM and its dairy products have become more attractive for consumers. In view of this, we performed a comprehensive review of CM fat's composition and nutritional properties. The overall goal is to increase knowledge related to CM fat characteristics and modify its unfavorable perception. Future studies are expected to be directed toward a better understanding of CM fat, which appears to be promising in the design and formulation of new products with significant health-promoting benefits.

Ibrahim, H., A. Serag, and M. A. Farag, "Emerging analytical tools for the detection of the third gasotransmitter HS, a comprehensive review.", Journal of advanced research, vol. 27, pp. 137-153, 2021. Abstract

Background: Hydrogen sulfide (HS) is currently considered among the endogenously produced gaseous molecules that exert various signaling effects in mammalian species. It is the third physiological gasotransmitter discovered so far after NO and CO. HS was originally ranked among the toxic gases at elevated levels to humans. Currently, it is well-known that, in the cardiovascular system, HS exerts several cardioprotective effects including vasodilation, antioxidant regulation, inhibition of inflammation, and activation of anti-apoptosis. With an increasing interest in monitoring HS, the development of analysis methods should now follow.

Aim of review: This review stages special emphasis on the several analytical technologies used for its determination including spectroscopic, chromatographic, and electrochemical methods. Advantages and limitations with regards to the application of each technique are highlighted with special emphasis on its employment for HS measurement ., biofluids, tissues.

Key Scientific Concepts and important findings of Review: Fluorescence methods applied for HS measurement offer an attractive non-invasive and promising approach in addition to its selectivity, however they cannot be considered as H2S-specific probes. On the other hand, colorimetric assays are among the most common methods used for HS detection, albeit their employment HS measurement has not yet been possible . Separation techniques such as gas or liquid chromatography offer higher selectivity compared to direct spectrophotometric or fluorescence methods especially for suitable for endpoint HS measurements . plasma or tissue samples. Despite all the developed analytical procedures used for HS determination, the need for highly selective, much work should be devoted to resolve all the pitfalls of the current methods.

Ibrahim, H., A. Serag, and M. A. Farag, "Emerging analytical tools for the detection of the third gasotransmitter HS, a comprehensive review.", Journal of advanced research, vol. 27, pp. 137-153, 2021. Abstract

BACKGROUND: Hydrogen sulfide (HS) is currently considered among the endogenously produced gaseous molecules that exert various signaling effects in mammalian species. It is the third physiological gasotransmitter discovered so far after NO and CO. HS was originally ranked among the toxic gases at elevated levels to humans. Currently, it is well-known that, in the cardiovascular system, HS exerts several cardioprotective effects including vasodilation, antioxidant regulation, inhibition of inflammation, and activation of anti-apoptosis. With an increasing interest in monitoring HS, the development of analysis methods should now follow.

AIM OF REVIEW: This review stages special emphasis on the several analytical technologies used for its determination including spectroscopic, chromatographic, and electrochemical methods. Advantages and limitations with regards to the application of each technique are highlighted with special emphasis on its employment for HS measurement ., biofluids, tissues.

KEY SCIENTIFIC CONCEPTS AND IMPORTANT FINDINGS OF REVIEW: Fluorescence methods applied for HS measurement offer an attractive non-invasive and promising approach in addition to its selectivity, however they cannot be considered as H2S-specific probes. On the other hand, colorimetric assays are among the most common methods used for HS detection, albeit their employment HS measurement has not yet been possible . Separation techniques such as gas or liquid chromatography offer higher selectivity compared to direct spectrophotometric or fluorescence methods especially for suitable for endpoint HS measurements . plasma or tissue samples. Despite all the developed analytical procedures used for HS determination, the need for highly selective, much work should be devoted to resolve all the pitfalls of the current methods.

Yao, P., Y. Gao, J. Simal-Gandara, M. A. Farag, W. Chen, D. Yao, D. Delmas, Z. Chen, K. Liu, H. Hu, et al., "Litchi ( Sonn.): a comprehensive review of phytochemistry, medicinal properties, and product development.", Food & function, vol. 12, issue 20, pp. 9527-9548, 2021. Abstract

Since ancient times, litchi has been well recognized as a functional food for the management of various ailments. Many bioactives, including flavanoids, anthocyanins, phenolics, sesquiterpenes, triterpenes, and lignans, have been identified from litchi with a myriad of biological properties both and . In spite of the extensive research progress, systemic reviews regarding the bioactives of litchi are rather scarce. Therefore, it is crucial to comprehensively analyze the pharmacological activities and the structure-activity relationships of the abundant bioactives of litchi. Besides, more and more studies have focused on litchi preservation and development of its by-products, which is significant for enhancing the economic value of litchi. Based on the analysis of published articles and patents, this review aims to reveal the development trends of litchi in the healthcare field by providing a systematic summary of the pharmacological activities of its extracts, its phytochemical composition, and the nutritional and potential health benefits of litchi seed, pulp and pericarp with structure-activity relationship analysis. In addition, its by-products also exhibited promising development potential in the field of material science and environmental protection. Furthermore, this study also provides an overview of the strategies of the postharvest storage and processing of litchi.

Sheashea, M., J. Xiao, and M. A. Farag, "MUFA in metabolic syndrome and associated risk factors: is MUFA the opposite side of the PUFA coin?", Food & function, vol. 12, issue 24, pp. 12221-12234, 2021. Abstract

Omega-9 fatty acids represent some of the main mono-unsaturated fatty acids (MUFA) found in plant and animal sources. They can be synthesized endogenously in the human body, but they do not fully provide all the body's requirements. Consequently, they are considered as partially essential fatty acids. MUFA represent a healthier alternative to saturated animal fats and have several health benefits, including the prevention of metabolic syndrome (MetS) and its complications. This review concentrates on the major MUFA pharmacological activities in the context of MetS management, including alleviating cardiovascular disease (CVD) and dyslipidemia, central obesity, non-alcoholic fatty liver disease (NAFLD), and type 2 diabetes mellitus (T2DM). The beneficial effects of MUFA for CVD were found to be consistent with those of polyunsaturated fatty acids (PUFA) for the alleviation of systolic and diastolic blood pressure and high low density lipoprotein cholesterol (LDLc) and triacylglcerol (TAG) levels, albeit MUFA had a more favorable effect on decreasing night systolic blood pressure (SBP). To reduce the obesity profile, the use of MUFA was found to induce a higher oxidation rate with a higher energy expenditure, compared with PUFA. For NAFLD, PUFA was found to be a better potential drug candidate for the improvement of liver steatosis in children than MUFA. Any advantageous outcomes from using MUFA for diabetes and insulin resistance (IR) compared to using PUFA were found to be either non-significant or resulted from a small number of meta-analyses. Such an increase in the number of studies of the mechanisms of action require more clinical and epidemiological studies to confirm the beneficial outcomes, especially over a long-term treatment period.

Chen, Z., M. A. Farag, Z. Zhong, C. Zhang, Y. Yang, S. Wang, and Y. Wang, "Multifaceted role of phyto-derived polyphenols in nanodrug delivery systems.", Advanced drug delivery reviews, vol. 176, pp. 113870, 2021. Abstract

As naturally occurring bioactive products, several lines of evidence have shown the potential of polyphenols in the medical intervention of various diseases, including tumors, inflammatory diseases, and cardiovascular diseases. Notably, owing to the particular molecular structure, polyphenols can combine with proteins, metal ions, polymers, and nucleic acids providing better strategies for polyphenol-delivery strategies. This contributes to the inherent advantages of polyphenols as important functional components for other drug delivery strategies, e.g., protecting nanodrugs from oxidation as a protective layer, improving the physicochemical properties of carbohydrate polymer carriers, or being used to synthesize innovative functional delivery vehicles. Polyphenols have emerged as a multifaceted player in novel drug delivery systems, both as therapeutic agents delivered to intervene in disease progression and as essential components of drug carriers. Although an increasing number of studies have focused on polyphenol-based nanodrug delivery including epigallocatechin-3-gallate, curcumin, resveratrol, tannic acid, and polyphenol-related innovative preparations, these molecules are not without inherent shortcomings. The active biochemical characteristics of polyphenols constitute a prerequisite to their high-frequency use in drug delivery systems and likewise to provoke new challenges for the design and development of novel polyphenol drug delivery systems of improved efficacies. In this review, we focus on both the targeted delivery of polyphenols and the application of polyphenols as components of drug delivery carriers, and comprehensively elaborate on the application of polyphenols in new types of drug delivery systems. According to the different roles played by polyphenols in innovative drug delivery strategies, potential limitations and risks are discussed in detail including the influences on the physical and chemical properties of nanodrug delivery systems, and their influence on normal physiological functions inside the organism.

El-Shamy, S., and M. A. Farag, "Novel trends in extraction and optimization methods of bioactives recovery from pomegranate fruit biowastes: Valorization purposes for industrial applications.", Food chemistry, vol. 365, pp. 130465, 2021. Abstract

Pomegranate biowastes present potential economic value worldwide owing to their several health benefits mediated by a complex mixture of unique bioactives. The exploitation of these bioactives has motivated the exploration of eco-friendly, efficient, and cost-effective extraction techniques to maximize their recovery. The current review aims to provide updated technical information about bioactives extraction mechanisms from pomegranate wastes (seeds and peel), their advantages and disadvantages, and factors towards optimization. A comparative overview of the modern green extraction techniques viz., supercritical fluid extraction, ultrasound-assisted extraction, microwave-assisted extraction, pressurized liquid extraction, and eutectic solvent mixture as alternatives to conventional extraction methods for seeds and peel is presented. Approaches focused on biowastes modification for properties improvement are also discussed. Such comprehensive review shall provide the best valorization practices of pomegranate biowastes and its application in food and non-food areas focusing on original methods, innovation, protocols, and development to be considered for other fruit biowastes.

Elshahed, M. S., A. Miron, A. C. Aprotosoaie, and M. A. Farag, "Pectin in diet: Interactions with the human microbiome, role in gut homeostasis, and nutrient-drug interactions.", Carbohydrate polymers, vol. 255, pp. 117388, 2021. Abstract

Pectins are a part of daily diet as well as food additives that are indigestible polysaccharides by human enzymes, however, they can be easily degraded by gut bacteria with the production of short chain fatty acids (SCFAs). Knowledge of pectin gut homeostasis and further how pectin affect gut bacterial communities is insufficient and limited. This review focuses on providing the whole story of how pectin functions as prebiotics in the gut. Understanding the interplay between functional and immunological responses inside animal or human gut as influenced by pectin in diets is provided. The interaction between pectin and gut microbiota is presented from both sides, in terms of how pectin affects gut microbiome and or the fermentation products produced in response by gut bacteria. This knowledge can be used to define preferred dietary pectins, targeting beneficial bacteria, and favoring balanced microbiota communities in the gut to maximize pectins' health benefits.

Serag, A., Z. Shakkour, A. M. Halboup, F. Kobeissy, and M. A. Farag, "Sweat metabolome and proteome: Recent trends in analytical advances and potential biological functions.", Journal of proteomics, vol. 246, pp. 104310, 2021. Abstract

Metabolome and proteome profiling of biofluids, e.g., urine, plasma, has generated vast and ever-increasing amounts of knowledge over the last few decades. Paradoxically, omics analyses of sweat, one of the most readily available human biofluids, have lagged behind. This review capitalizes on the current knowledge and state of the art analytical advances of sweat metabolomics and proteomics. Moreover, current applications of sweat omics such as the discovery of disease biomarkers and monitoring athletic performance are also presented in this review. Another area of emerging knowledge that has been highlighted herein lies in the role of skin host-microbiome interactions in shaping the sweat metabolite-protein profiles. Discussion of future research directions describes the need to have a better grasp of sweat chemicals and to better understand how they function as aided by advances in omics tools. Overall, the role of sweat as an information-rich biofluid that could complement the exploration of the skin metabolome/proteome is emphasized.

Zayed, A., M. T. Badawy, and M. A. Farag, "Valorization and extraction optimization of Citrus seeds for food and functional food applications.", Food chemistry, vol. 355, pp. 129609, 2021. Abstract

Valorization of food byproducts has attracted recently considerable attention. Citrus fruits provide considerable non-edible residues reach 80% in juice production. They are considered agri-wastes to comprise peel, pulp and seeds. Previous investigations have focused on peel and pulp to recover value-added products. The review presents for the first-time phytochemical composition of Citrus seeds' products, i.e., oil and extracts. Fatty acids, phytosterols and tocopherols amounted as the major bioactives in Citrus seeds, in addition to limonoids, dietary fibers and flavonoids. Besides their nutritional values, these chemicals have promising applications including production of biodiesel, food enhancers and antioxidants, especially from mandarin and grapefruit seeds. Optimum conditions of the different Citrus seeds' valorization are discussed to improve extraction yield and lessen environmental hazards of solvent extraction. This review presents the best utilization practices for one of the largest cultivated fruit seeds worldwide and its different applications.

2020
Emad, A. M., S. F. Ali, E. A. Abdel-Rahman, M. R. Meselhy, M. A. Farag, S. S. Ali, and E. A. Abdel-Sattar, "Anti-inflammatory and antioxidant effects of Apium graveolens L. extracts mitigate against fatal acetaminophen-induced acute liver toxicity.", Journal of food biochemistry, pp. e13399, 2020. Abstract

In the present work, antioxidant activity, total phenolics (TP), and total flavonoids (TF) contents of aqueous and methanol extracts of celery were determined, in addition to untargeted metabolites profiling its methanol celery root extract (MCRE) via UPLC-MS. Although MCRE exhibited the lowest TPC and TFC levels, it presented the most potential hydroxyl radical quenching effect using electron paramagnetic resonance spin trapping technique. Treatment of Acetaminophen-induced hepatotoxicity (AAH) rats with MCRE lowered serum levels of AST, ALT, ALP, TNF-α, and IL-1β significantly. Additionally, MCRE significantly increased total antioxidant capacity (TAC) and glutathione (GSH) levels relative to AAH rats. Strikingly, Kaplan-Meier survival analysis of all groups revealed a 100% prevention of acetaminophen-induced mortality of rats by MCRE pretreatment (100 mg/kg/day). MCRE prevented AAH-associated severe weight loss and elicited normal behavior in the rescued rats. Our results suggest that pretreatment with MCRE can mitigate against overdosed acetaminophen-induced acute liver failure and warrant further investigations on the potential of postinjury intervention. PRACTICAL APPLICATIONS: Acetaminophen-induced hepatotoxicity (AAH) accounts for alerting numbers of overdose-related acute liver failure and liver transplant cases with increased morbidity and mortality rates. Currently proposed mechanisms implicate mitochondria-mediated oxidative stress and inflammation in the pathogenesis of AAH, which underline current interventions employing antioxidants to combat liver damage by over-dosed acetaminophen. The present work uncovers potent protective effects of some celery extracts (and their fractions) against acetaminophen-induced oxidative stress and inflammation. Treatment of rats with fatal liver injury with methanol extract of celery root significantly reduced secretion of liver enzymes and markedly decreased inflammatory as well as oxidative stress markers in these animals. This, in turn, rescued challenged rats exposed to fatal doses of acetaminophen completely, which establishes methanol extracts of celery roots as effective therapeutic intervention against AAH. The antioxidant capacity of the extracts was determined using EPR technique, and the secondary metabolites related to antioxidant activity were characterized via UPLC-MS.

Farag, M. A., N. Hegazi, E. Dokhalahy, and A. R. Khattab, "Chemometrics based GC-MS aroma profiling for revealing freshness, origin and roasting indices in saffron spice and its adulteration.", Food chemistry, vol. 331, pp. 127358, 2020. Abstract

Saffron, stigmas of Crocus sativus, is one of the most precious spices used as food colorant and flavoring agent. Due to its scarce source and high cost, it is liable to fraudulent admixture with allied plants "safflower and calendula". In this study, gas chromatography-mass spectrometry (GC-MS) was employed to determine authenticity, adulterants detection, and to assess the roasting impact on its aroma. A total of 93 volatiles were identified belonging to different classes viz. aldehydes, alcohols, ketones, aliphatic hydrocarbons, aromatics, mono-and sesquiterpenes, oxides/ethers and pyrans/furans. Principle component analysis (PCA) identified safranal and 2-caren-10-al as discriminatory volatile markers of saffron from its allied flowers, later found enriched in estragole, β-caryophyllene and eugenol. PCA model also revealed markers for freshly dried versus long-stored saffron, with ketoisophorone as freshness marker versus safranal as an ageing indicator. Safranal was further identified as a marker to distinguish saffron from safflower, whereas calendula aroma was predominated by monoterpene hydrocarbons.

Khattab, A. R., and M. A. Farag, "Current status and perspectives of xanthones production using cultured plant biocatalyst models aided by tools for its optimization.", Critical reviews in biotechnology, vol. 40, issue 3, pp. 415-431, 2020. Abstract

With an increasing interest in exploring the biocatalyst potential for the production of natural products (NP), research in NP biotechnology now follows. Xanthones constitute an important class of phytochemicals exhibiting a myriad of bioactivities and potential for interacting with multimolecular targets, and xanthones are considered to be privileged phytochemical scaffolds in medicinal chemistry. Recent advances in xanthones biosynthetic pathways are outlined and their metabolic engineering. This review summarizes the state-of-the-art processes for the biotechnological production of xanthones, its limitations, and potential improvements. The tissue culturing methods employed for the production of xanthones from different species of plant are reviewed addressing differences in xanthone classes. This review sheds the light of computational approaches, , response surface methodology (RSM) and artificial neural networks (ANN), for optimizing the culture performance and improving xanthones production.

Shakour, Z. A. T., N. m Fayek, and M. A. Farag, "How do biocatalysis and biotransformation affect dietary flavonoids chemistry and bioactivity? A review.", Critical reviews in biotechnology, vol. 40, issue 5, pp. 689-714, 2020. Abstract

Flavonoids, especially flavanones, flavones and polymethoxyflavones (PMFs) are distinctive bioactive compounds of fruits. peel and juice by-products potentially represent rich sources of these flavonoids that exhibit a myriad of biological activities both in and systems. Recently, much attention has been made toward biotransformation processes as a promising tool for the structural modification of natural products to be used in the drug and food industries along with its role in solving pollution problems related to by-products disposal. In this article, we present a state of the art review on both and biotransformation processes of juice and waste carried out by microorganisms, plant cell cultures, animal and human liver microsomes targeting its flavonoids composition. Such review highlights the main metabolic pathways for enzymatic and microbial reactions involved in these processes and suggest for reactions that need to be more capitalized for a wider application in industrial bioprocesses of by-products. Biotransformation and biocatalysis applications included employment of citrus by-products enriched in flavonoids as a low-cost, economical and natural sources of sugar substitutes, antifungal, anticancer drugs, hydrolyzable enzymes, probiotics and flavonoid aglycones. Further, biological effects of the biotransformed metabolites are discussed in relation to its parent compound highlighting potentials and or any limitations for each reaction type. Applications covered in biotransformation include for nutraceutical/food and cosmetics industries.

Farag, M. A., S. A. Jomaa, A. Abd El-Wahed, and A. H. R. El-Seedi, "The Many Faces of Kefir Fermented Dairy Products: Quality Characteristics, Flavour Chemistry, Nutritional Value, Health Benefits, and Safety.", Nutrients, vol. 12, issue 2, 2020. Abstract

Kefir is a dairy product that can be prepared from different milk types, such as goat, buffalo, sheep, camel, or cow via microbial fermentation (inoculating milk with kefir grains). As such, kefir contains various bacteria and yeasts which influence its chemical and sensory characteristics. A mixture of two kinds of milk promotes kefir sensory and rheological properties aside from improving its nutritional value. Additives such as inulin can also enrich kefir's health qualities and organoleptic characters. Several metabolic products are generated during kefir production and account for its distinct flavour and aroma: Lactic acid, ethanol, carbon dioxide, and aroma compounds such as acetoin and acetaldehyde. During the storage process, microbiological, physicochemical, and sensory characteristics of kefir can further undergo changes, some of which improve its shelf life. Kefir exhibits many health benefits owing to its antimicrobial, anticancer, gastrointestinal tract effects, gut microbiota modulation and anti-diabetic effects. The current review presents the state of the art relating to the role of probiotics, prebiotics, additives, and different manufacturing practices in the context of kefir's physicochemical, sensory, and chemical properties. A review of kefir's many nutritional and health benefits, underlying chemistry and limitations for usage is presented.