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1.
Potential Resistance of SARS-CoV-2 Main Protease (Mpro) against Protease Inhibitors: Lessons Learned from HIV-1 Protease.
Mótyán, JA, Mahdi, M, Hoffka, G, Tőzsér, J
International journal of molecular sciences. 2022;(7)
Abstract
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome 2 (SARS-CoV-2), has been one of the most devastating pandemics of recent times. The lack of potent novel antivirals had led to global health crises; however, emergence and approval of potent inhibitors of the viral main protease (Mpro), such as Pfizer's newly approved nirmatrelvir, offers hope not only in the therapeutic front but also in the context of prophylaxis against the infection. By their nature, RNA viruses including human immunodeficiency virus (HIV) have inherently high mutation rates, and lessons learnt from previous and currently ongoing pandemics have taught us that these viruses can easily escape selection pressure through mutation of vital target amino acid residues in monotherapeutic settings. In this paper, we review nirmatrelvir and its binding to SARS-CoV-2 Mpro and draw a comparison to inhibitors of HIV protease that were rendered obsolete by emergence of resistance mutations, emphasizing potential pitfalls in the design of inhibitors that may be of important relevance to the long-term use of novel inhibitors against SARS-CoV-2.
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2.
Implication of food insecurity on the gut microbiota and its potential relevance to a multi-ethnic population in Malaysia.
Shafiee, NH, Razalli, NH, Muhammad Nawawi, KN, Mohd Mokhtar, N, Raja Ali, RA
JGH open : an open access journal of gastroenterology and hepatology. 2022;(2):112-119
Abstract
Food insecurity (FI) has an impact on food intake, and it can make it difficult for people to eat enough nutritious food at all times to sustain an active and healthy lifestyle. The COVID-19 outbreak has hampered people's capacity to obtain nutritious and affordable food. Although FI has been studied in Malaysia, the extent to which it is linked to gut microbiota has yet to be discovered. This review aimed to compile evidence of the relationship between FI and gut microbial changes and their potential relevance to a multi-ethnic population in Malaysia. FI is typically associated with cheaper and calorie-dense foods because of the high cost of quality food and financial constraints that hinder food-insecure people from adopting healthier dietary choices. As a result, they have started eating low-quality food such as simple carbohydrates, fats, and processed foods. These poor eating habits can reduce microbial diversity and influence changes in the composition and function of the gut microbiota. This review also explores the impact of ethnicity on the variation in composition of gut microbiota. In conclusion, the findings of this review may be utilized to develop and implement diet-related intervention programs to ensure that Malaysians get enough nutritious food to maintain a healthy gut microbiota and improve overall health.
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3.
Insights into the modulation of the interferon response and NAD+ in the context of COVID-19.
Habeichi, NJ, Tannous, C, Yabluchanskiy, A, Altara, R, Mericskay, M, Booz, GW, Zouein, FA
International reviews of immunology. 2022;(4):464-474
Abstract
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in dramatic worldwide mortality. Along with developing vaccines, the medical profession is exploring new strategies to curb this pandemic. A better understanding of the molecular consequences of SARS-CoV-2 cellular infection could lead to more effective and safer treatments. This review discusses the potential underlying impact of SARS-CoV-2 in modulating interferon (IFN) secretion and in causing mitochondrial NAD+ depletion that could be directly linked to COVID-19's deadly manifestations. What is known or surmised about an imbalanced innate immune response and mitochondrial dysfunction post-SARS-CoV-2 infection, and the potential benefits of well-timed IFN treatments and NAD+ boosting therapies in the context of the COVID-19 pandemic are discussed.
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4.
Nutrition, Epigenetics, and Major Depressive Disorder: Understanding the Connection.
Ortega, MA, Fraile-Martínez, Ó, García-Montero, C, Alvarez-Mon, MA, Lahera, G, Monserrat, J, Llavero-Valero, M, Mora, F, Rodríguez-Jiménez, R, Fernandez-Rojo, S, et al
Frontiers in nutrition. 2022;:867150
Abstract
Major depressive disorder (MDD) is a complex, multifactorial disorder of rising prevalence and incidence worldwide. Nearly, 280 million of people suffer from this leading cause of disability in the world. Moreover, patients with this condition are frequently co-affected by essential nutrient deficiency. The typical scene with stress and hustle in developed countries tends to be accompanied by eating disorders implying overnutrition from high-carbohydrates and high-fat diets with low micronutrients intake. In fact, currently, coronavirus disease 2019 (COVID-19) pandemic has drawn more attention to this underdiagnosed condition, besides the importance of the nutritional status in shaping immunomodulation, in which minerals, vitamins, or omega 3 polyunsaturated fatty acids (ω-3 PUFA) play an important role. The awareness of nutritional assessment is greater and greater in the patients with depression since antidepressant treatments have such a significant probability of failing. As diet is considered a crucial environmental factor, underlying epigenetic mechanisms that experience an adaptation or consequence on their signaling and expression mechanisms are reviewed. In this study, we included metabolic changes derived from an impairment in cellular processes due to lacking some essential nutrients in diet and therefore in the organism. Finally, aspects related to nutritional interventions and recommendations are also addressed.
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5.
Metabolic engineering in food crops to enhance ascorbic acid production: crop biofortification perspectives for human health.
Chaturvedi, S, Khan, S, Bhunia, RK, Kaur, K, Tiwari, S
Physiology and molecular biology of plants : an international journal of functional plant biology. 2022;(4):871-884
Abstract
Ascorbic acid (AsA) also known as vitamin C is considered as an essential micronutrient in the diet of humans. The human body is unable to synthesize AsA, thus solely dependent on exogenous sources to accomplish the nutritional requirement. AsA plays a crucial role in different physiological aspects of human health like bone formation, iron absorption, maintenance and development of connective tissues, conversion of cholesterol to bile acid and production of serotonin. It carries antioxidant properties and is involved in curing various clinical disorders such as scurvy, viral infection, neurodegenerative diseases, cardiovascular diseases, anemia, and diabetes. It also plays a significant role in COVID-19 prevention and recovery by improving the oxygen index and enhancing the production of natural killer cells and T-lymphocytes. In plants, AsA plays important role in floral induction, seed germination, senescence, ROS regulation and photosynthesis. AsA is an essential counterpart of the antioxidant system and helps to defend the plants against abiotic and biotic stresses. Surprisingly, the deficiencies of AsA are spreading in both developed and developing countries. The amount of AsA in the major food crops such as wheat, rice, maize, and other raw natural plant foods is inadequate to fulfill its dietary requirements. Hence, the biofortification of AsA in staple crops would be feasible and cost-effective means of delivering AsA to populations that may have limited access to diverse diets and other interventions. In this review, we endeavor to provide information on the role of AsA in plants and human health, and also perused various biotechnological and agronomical approaches for elevating AsA content in food crops.
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6.
The Role of Psychobiotics to Ensure Mental Health during the COVID-19 Pandemic-A Current State of Knowledge.
Zielińska, D, Karbowiak, M, Brzezicka, A
International journal of environmental research and public health. 2022;(17)
Abstract
Psychobiotics are defined as probiotics, mainly of the genus Lactobacillus and Bifidobacterium, that confer mental health benefits to the host when consumed in a particular quantity through the interaction with commensal gut microbiota. The gut microbiota, which means a diverse and dynamic population of microorganisms harboring the gastrointestinal tract, communicates with the brain and vice versa through the brain-gut axis. The mechanisms of action of psychobiotics may be divided into four groups: synthesis of neurotransmitters and neurochemicals, regulation of the HPA axis, influence on the immune system, and synthesis of metabolites. Recent years showed that the COVID-19 pandemic affected not only physical, but also mental health. Social isolation, fear of infection, the lack of adequate vaccine, disinformation, increased number of deaths, financial loss, quarantine, and lockdown are all factors can cause psychiatric problems. The aim of this review was to discuss the potential role of psychobiotic in light of the current problems, based on in vitro and in vivo studies, meta-analyses, clinical trials evidence, and registered studies assessing probiotics' therapeutic administration in the prevention or treatment of symptoms or side effects of COVID-19.
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7.
Thyroid Dysfunction and COVID-19: The Emerging Role of Selenium in This Intermingled Relationship.
Gorini, F, Sabatino, L, Coi, A, Iervasi, G, Vassalle, C
International journal of environmental research and public health. 2022;(11)
Abstract
COVID-19 represents a worldwide public health emergency, and, beyond the respiratory symptoms characterizing the classic viral disease, growing evidence has highlighted a possible reciprocal relationship between SARS-CoV-2 infection and thyroid dysfunction. The updated data discussed in this review suggests a role of SARS-CoV-2 infection on the thyroid gland, with multiple thyroid pictures described. Conversely, no conclusion can be drawn on the association between pre-existing thyroid disease and increased risk of SARS-CoV-2 infection. In this scenario, selenium (Se), an essential trace element critical for thyroid function and known as an effective agent against viral infections, is emerging as a potential novel therapeutic option for the treatment of COVID-19. Large multicentre cohort studies are required to elucidate the mechanisms underlying thyroid dysfunction during or following recovery from COVID-19, including Se status. Meanwhile, clinical trials should be performed to evaluate whether adequate intake of Se can help address COVID-19 in Se-deficient patients, also avoiding thyroid complications that can contribute to worsening outcomes during infection.
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8.
Advances in muscle health and nutrition: A toolkit for healthcare professionals.
Prado, CM, Landi, F, Chew, STH, Atherton, PJ, Molinger, J, Ruck, T, Gonzalez, MC
Clinical nutrition (Edinburgh, Scotland). 2022;(10):2244-2263
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Abstract
Low muscle mass and malnutrition are prevalent conditions among adults of all ages, with any body weight or body mass index, and with acute or chronic conditions, including COVID-19. This article synthesizes the latest research advancements in muscle health and malnutrition, and their impact on immune function, and clinical outcomes. We provide a toolkit of illustrations and scientific information that healthcare professionals can use for knowledge translation, educating patients about the importance of identifying and treating low muscle mass and malnutrition. We focus on the emerging evidence of mitochondrial dysfunction in the context of aging and disease, as well as the cross-talk between skeletal muscle and the immune system. We address the importance of myosteatosis as a component of muscle composition, and discuss direct, indirect and surrogate assessments of muscle mass including ultrasound, computerized tomography, deuterated creatine dilution, and calf circumference. Assessments of muscle function are also included (handgrip strength, and physical performance tests). Finally, we address nutrition interventions to support anabolism, reduce catabolism, and improve patient outcomes. These include protein and amino acids, branched-chain amino acids, with a focus on leucine; β-hydroxy-β-methylbutyrate (HMB), vitamin D; n-3 polyunsaturated fatty acids (n-3 PUFA), polyphenols, and oral nutritional supplements. We concluded with recommendations for clinical practice and a call for action on research focusing on evaluating the impact of body composition assessments on targeted nutrition interventions, and consequently their ability to improve patient outcomes.
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9.
Histidine-enhanced gene delivery systems: The state of the art.
Hooshmand, SE, Jahanpeimay Sabet, M, Hasanzadeh, A, Kamrani Mousavi, SM, Haeri Moghaddam, N, Hooshmand, SA, Rabiee, N, Liu, Y, Hamblin, MR, Karimi, M
The journal of gene medicine. 2022;(5):e3415
Abstract
Gene therapy has emerged as a promising tool for treating different intractable diseases, particularly cancer or even viral diseases such as COVID-19 (coronavirus disease 2019). In this context, various non-viral gene carriers are being explored to transfer DNA or RNA sequences into target cells. Here, we review the applications of the naturally occurring amino acid histidine in the delivery of nucleic acids into cells. The biocompatibility of histidine-enhanced gene delivery systems has encouraged their wider use in gene therapy. Histidine-based gene carriers can involve the modification of peptides, dendrimers, lipids or nanocomposites. Several linear polymers, such as polyethylenimine, poly-l-lysine (synthetic) or dextran and chitosan (natural), have been conjugated with histidine residues to form complexes with nucleic acids for intracellular delivery. The challenges, opportunities and future research trends of histidine-based gene deliveries are investigated.
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10.
Neurological Complications of Malaria.
Trivedi, S, Chakravarty, A
Current neurology and neuroscience reports. 2022;(8):499-513
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Abstract
PURPOSE OF REVIEW To discuss the neurological complications and pathophysiology of organ damage following malaria infection. RECENT FINDINGS The principal advancement made in malaria research has been a better understanding of the pathogenesis of cerebral malaria (CM), the most dreaded neurological complication generally caused by Plasmodium falciparum infection. However, no definitive treatment has yet been evolved other than the use of antimalarial drugs and supportive care. The development of severe cerebral edema in CM results from two distinct pathophysiologic mechanisms. First, the development of "sticky" red blood cells (RBCs) leads to cytoadherence, where red blood cells (RBCs) get stuck to the endothelial walls and between themselves, resulting in clogging of the brain microvasculature with resultant hypoxemia and cerebral edema. In addition, the P. falciparum-infected erythrocyte membrane protein 1 (PfEMP1) molecules protrude from the raised knob structures on the RBCs walls and are in themselves made of a combination of human and parasite proteins in a tight complex. Antibodies to surfins, rifins, and stevors from the parasite are also located in the RBC membrane. On the human microvascular side, a range of molecules involved in host-parasite interactions, including CD36 and intracellular adhesion molecule 1, is activated during interaction with other molecules such as endothelial protein C receptor and thrombospondin. As a result, an inflammatory response occurs with the dysregulated release of cytokines (TNF, interleukins 1 and 10) which damage the blood-brain barrier (BBB), causing plasma leakage and brain edema. This second mechanism of CNS injury often involves multiple organs in adult patients in endemic areas but remains localized only to the central nervous system (CNS) among African children. Neurological sequelae may follow both P. falciparum and P. vivax infections. The major brain pathology of CM is brain edema with diffuse brain swelling resulting from the combined effects of reduced perfusion and hypoxemia of cerebral neurons due to blockage of the microvasculature by parasitized RBCs as well as the neurotoxic effect of released cytokines from a hyper-acute immune host reaction. A plethora of additional neurological manifestations have been associated with malaria, including posterior reversible encephalopathy syndrome (PRES), reversible cerebral vasoconstriction syndrome (RCVS), malarial retinopathy, post-malarial neurological syndrome (PMNS), acute disseminated encephalomyelitis (ADEM), Guillain-Barré syndrome (GBS), and cerebellar ataxia. Lastly, the impact of the COVID-19 pandemic on worldwide malaria control programs and the possible threat from co-infections is briefly discussed.
