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1.
Antibiotic-Resistant ESKAPE Pathogens and COVID-19: The Pandemic beyond the Pandemic.
Catalano, A, Iacopetta, D, Ceramella, J, Pellegrino, M, Giuzio, F, Marra, M, Rosano, C, Saturnino, C, Sinicropi, MS, Aquaro, S
Viruses. 2023;(9)
Abstract
Antibacterial resistance is a renewed public health plague in modern times, and the COVID-19 pandemic has rekindled this problem. Changes in antibiotic prescribing behavior, misinformation, financial hardship, environmental impact, and governance gaps have generally enhanced the misuse and improper access to antibiotics during the COVID-19 pandemic. These determinants, intersected with antibacterial resistance in the current pandemic, may amplify the potential for a future antibacterial resistance pandemic. The occurrence of infections with multidrug-resistant (MDR), extensively drug-resistant (XDR), difficult-to-treat drug-resistant (DTR), carbapenem-resistant (CR), and pan-drug-resistant (PDR) bacteria is still increasing. The aim of this review is to highlight the state of the art of antibacterial resistance worldwide, focusing on the most important pathogens, namely Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae, and their resistance to the most common antibiotics.
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2.
An updated review on distribution, biosynthesis and pharmacological effects of artemisinin: A wonder drug.
Nabi, N, Singh, S, Saffeullah, P
Phytochemistry. 2023;:113798
Abstract
Plant-based drugs have been used for centuries for treating different ailments. Malaria, one of the prevalent threats in many parts of the world, is treated mainly by artemisinin-based drugs derived from plants of genus Artemisia. However, the distribution of artemisinin is restricted to a few species of the genus; besides, its yield depends on ontogeny and the plant's geographical location. Here, we review the studies focusing on biosynthesis and distributional pattern of artemisinin production in species of the genus Artemisia. We also discussed various agronomic and in vitro methods and molecular approaches to increase the yield of artemisinin. We have summarized different mechanisms of artemisinin involved in its anti-malarial, anti-cancer, anti-inflammatory and anti-viral activities (like against Covid-19). Overall the current review provides a synopsis of a global view of the distribution of artemisinin, its biosynthesis, and pharmacological potential in treating various diseases like malaria, cancer, and coronavirus, which may provoke future research efforts in drug development. Nevertheless, long-term trials and molecular approaches, like CRISPR-Cas, are required for in-depth research.
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Disorders of gut-brain interaction in post-acute COVID-19 syndrome.
Golla, R, Vuyyuru, SK, Kante, B, Kedia, S, Ahuja, V
Postgraduate medical journal. 2023;(1174):834-843
Abstract
The novel coronavirus SARS-CoV-2 is responsible for the devastating pandemic which has caused more than 5 million deaths across the world until today. Apart from causing acute respiratory illness and multiorgan dysfunction, there can be long-term multiorgan sequalae after recovery, which is termed 'long COVID-19' or 'post-acute COVID-19 syndrome'. Little is known about long-term gastrointestinal (GI) consequences, occurrence of post-infection functional gastrointestinal disorders and impact the virus may have on overall intestinal health. In this review, we put forth the various mechanisms which may lead to this entity and possible ways to diagnose and manage this disorder. Hence, making physicians aware of this spectrum of disease is of utmost importance in the present pandemic and this review will help clinicians understand and suspect the occurrence of functional GI disease post recovery from COVID-19 and manage it accordingly, avoiding unnecessary misconceptions and delay in treatment.
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4.
Potential Benefit of Vitamin D Supplementation in COVID-19.
Stafford, A, White, ND
American journal of lifestyle medicine. 2023;(2):202-205
Abstract
Vitamin D is an important nutrient in the body that plays a vital role in immune system function. Several epidemiologic studies have shown that low vitamin D levels are found in a large percentage of COVID-19 patients with acute respiratory failure and that vitamin D levels may predict mortality in COVID-19 infection. Based on these findings, vitamin D supplementation may be an effective approach to preventing and/or treating COVID-19. Potential underlying mechanisms and clinical trial data evaluating the impact of supplementation in humans are described below.
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5.
The SLC6A15-SLC6A20 Neutral Amino Acid Transporter Subfamily: Functions, Diseases, and Their Therapeutic Relevance.
Kukułowicz, J, Pietrzak-Lichwa, K, Klimończyk, K, Idlin, N, Bajda, M
Pharmacological reviews. 2023;(1):142-193
Abstract
The neutral amino acid transporter subfamily that consists of six members, consecutively SLC6A15-SLC620, also called orphan transporters, represents membrane, sodium-dependent symporter proteins that belong to the family of solute carrier 6 (SLC6). Primarily, they mediate the transport of neutral amino acids from the extracellular milieu toward cell or storage vesicles utilizing an electric membrane potential as the driving force. Orphan transporters are widely distributed throughout the body, covering many systems; for instance, the central nervous, renal, or intestinal system, supplying cells into molecules used in biochemical, signaling, and building pathways afterward. They are responsible for intestinal absorption and renal reabsorption of amino acids. In the central nervous system, orphan transporters constitute a significant medium for the provision of neurotransmitter precursors. Diseases related with aforementioned transporters highlight their significance; SLC6A19 mutations are associated with metabolic Hartnup disorder, whereas altered expression of SLC6A15 has been associated with a depression/stress-related disorders. Mutations of SLC6A18-SLCA20 cause iminoglycinuria and/or hyperglycinuria. SLC6A18-SLC6A20 to reach the cellular membrane require an ancillary unit ACE2 that is a molecular target for the spike protein of the SARS-CoV-2 virus. SLC6A19 has been proposed as a molecular target for the treatment of metabolic disorders resembling gastric surgery bypass. Inhibition of SLC6A15 appears to have a promising outcome in the treatment of psychiatric disorders. SLC6A19 and SLC6A20 have been suggested as potential targets in the treatment of COVID-19. In this review, we gathered recent advances on orphan transporters, their structure, functions, related disorders, and diseases, and in particular their relevance as therapeutic targets. SIGNIFICANCE STATEMENT The following review systematizes current knowledge about the SLC6A15-SLCA20 neutral amino acid transporter subfamily and their therapeutic relevance in the treatment of different diseases.
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6.
Mechanistic Insight into the role of Vitamin D and Zinc in Modulating Immunity Against COVID-19: A View from an Immunological Standpoint.
Ahsan, N, Imran, M, Mohammed, Y, Al Anouti, F, Khan, MI, Banerjee, T, Adnan, M, Ashfaq, F, Kieliszek, M, Ashraf, SA, et al
Biological trace element research. 2023;(12):5546-5560
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Abstract
The pathophysiology of coronavirus disease-19 (COVID-19) is characterized by worsened inflammation because of weakened immunity, causing the infiltration of immune cells, followed by necrosis. Consequently, these pathophysiological changes may lead to a life-threatening decline in perfusion due to hyperplasia of the lungs, instigating severe pneumonia, and causing fatalities. Additionally, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause mortality due to viral septic shock, resulting from unrestrained and backfiring immune reactions to the pathogen. Sepsis can cause premature organ failure in COVID-19 patients, as well. Notably, vitamin D and its derivatives and minerals, such as zinc and magnesium, have been reported to improve the immune system against respiratory illnesses. This comprehensive review aims to provide updated mechanistic details of vitamin D and zinc as immunomodulators. Additionally, this review also focuses on their role in respiratory illnesses, while specifically delineating the plausibility of employing them as a preventive and therapeutic agent against current and future pandemics from an immunological perspective. Furthermore, this comprehensive review will attract the attention of health professionals, nutritionists, pharmaceuticals, and scientific communities, as it encourages the use of such micronutrients for therapeutic purposes, as well as promoting their health benefits for a healthy lifestyle and wellbeing.
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Neurological Sequelae of COVID-19: A Biochemical Perspective.
Zhang, X, Zhang, Y, Wen, L, Ouyang, JL, Zhang, W, Zhang, J, Wang, Y, Liu, Q
ACS omega. 2023;(31):27812-27818
Abstract
Exogenous factors can induce protein expression and modify the proteome which sustains for a certain period of time. The proteins of SARS-CoV-2 are high in valine plus glycine, which possess potent affinity to divalent cations such as calcium. Calcium buildup changes the protein expression profile by enabling the efficient synthesis of proteins rich in amino acids with calcium affinity. Subsequent formation of insoluble and stiff calcium oxalate and aggregates confers cellular stress and causes cell senescence. This scenario accounts for sequelae seen in some patients following recovery from COVID-19.
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Acute and post-acute sequelae of SARS-CoV-2 infection: a review of risk factors and social determinants.
Wang, C, Ramasamy, A, Verduzco-Gutierrez, M, Brode, WM, Melamed, E
Virology journal. 2023;(1):124
Abstract
SARS-CoV-2 infection leading to Coronavirus Disease 2019 (COVID-19) has caused more than 762 million infections worldwide, with 10-30% of patients suffering from post-acute sequelae of SARS-CoV-2 infections (PASC). Initially thought to primarily affect the respiratory system, it is now known that SARS-CoV-2 infection and PASC can cause dysfunction in multiple organs, both during the acute and chronic stages of infection. There are also multiple risk factors that may predispose patients to worse outcomes from acute SARS-CoV-2 infection and contribute to PASC, including genetics, sex differences, age, reactivation of chronic viruses such as Epstein Barr Virus (EBV), gut microbiome dysbiosis, and behavioral and lifestyle factors, including patients' diet, alcohol use, smoking, exercise, and sleep patterns. In addition, there are important social determinants of health, such as race and ethnicity, barriers to health equity, differential cultural perspectives and biases that influence patients' access to health services and disease outcomes from acute COVID-19 and PASC. Here, we review risk factors in acute SARS-CoV-2 infection and PASC and highlight social determinants of health and their impact on patients affected with acute and chronic sequelae of COVID-19.
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9.
New Insights into the Link between SARS-CoV-2 Infection and Renal Cancer.
Rago, V, Bossio, S, Lofaro, D, Perri, A, Di Agostino, S
Life (Basel, Switzerland). 2023;(1)
Abstract
Cancer has been described as a risk factor for greater susceptibility to SARS-CoV-2 infection and severe COVID-19, mainly for patients with metastatic disease. Conversely, to that reported for most solid and hematological malignancies, the few available clinical studies reported that the infection did not increase the risk of death in renal cancer patients. The expression on proximal tubular renal cells of the key players in cellular viral uptake, ACE2, TMPRSS2, and NRP1, seems to be the mechanism for the direct kidney injury seen in patients with COVID-19. Interestingly, data from The Cancer Genome Atlas and experimental analyses on various renal cancer cell lines demonstrated that the above-reported receptors/cofactors are maintained by renal cancer cells. However, whether SARS-CoV-2 infection directly kills renal cancer cells or generates enhanced immunogenicity is a question worth investigating. In addition, some researchers have further addressed the topic by studying the expression and prognostic significance of gene signatures related to SARS-CoV-2 infection in renal cancer patients. The emerging data highlights the importance of better understanding the existence of a link between renal cancer and COVID-19 since it could lead to the identification of new prognostic factors and the development of new therapeutic targets in the management of renal cancer patients.
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10.
Phytocompounds and their molecular targets in immunomodulation: a review.
Cherian, A, Vadivel, V, Thiruganasambandham, S, Madhavankutty, S
Journal of basic and clinical physiology and pharmacology. 2023;(5):577-590
Abstract
Immune cells are important for the healthy function of every organ. The homeostasis of the immune system is selfregulated by T-cells, B-cells, and natural killer cells. The immunomodulation process of immune cells is part of the immunotherapy. According to therapeutic methods of immune responses are categorized as inducing (immunostimulant), amplification (immune booster), attenuation (immunomodulation), and prevention (immunosuppressive) actions. The prevalence of chronic immunological diseases like viral infections, allergies, and cancer is mainly due to the over-activation of the immune system. Further, immunomodulators are reported to manage the severity of chronic immunological disorders. Moreover, these immunomodulator-acting proteins are identified as potential molecular targets for the regulation of the immune system. Moreover, natural compound like phytocompounds are known to bind these targets and modulates the immune system. The specialized phytocompounds like curcumin, quercetin, stilbenes, flavonoids, and lignans are shown the immunomodulatory actions and ameliorate the immunological disorders. The present scenario of a COVID-19 pandemic situation has taught us the need to focus on strengthening the immune system and the development of the most promising immunotherapeutics. This review is focused on an overview of various phytocompounds and their molecular targets for the management of immunological disorders via immunosuppressants and immunostimulants actions.