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1.
Developmental Impacts of Epigenetics and Metabolism in COVID-19.
Naik, N, Patel, M, Sen, R
Journal of developmental biology. 2024;(1)
Abstract
Developmental biology is intricately regulated by epigenetics and metabolism but the mechanisms are not completely understood. The situation becomes even more complicated during diseases where all three phenomena are dysregulated. A salient example is COVID-19, where the death toll exceeded 6.96 million in 4 years, while the virus continues to mutate into different variants and infect people. Early evidence during the pandemic showed that the host's immune and inflammatory responses to COVID-19 (like the cytokine storm) impacted the host's metabolism, causing damage to the host's organs and overall physiology. The involvement of angiotensin-converting enzyme 2 (ACE2), the pivotal host receptor for the SARS-CoV-2 virus, was identified and linked to epigenetic abnormalities along with other contributing factors. Recently, studies have revealed stronger connections between epigenetics and metabolism in COVID-19 that impact development and accelerate aging. Patients manifest systemic toxicity, immune dysfunction and multi-organ failure. Single-cell multiomics and other state-of-the-art high-throughput studies are only just beginning to demonstrate the extent of dysregulation and damage. As epigenetics and metabolism directly impact development, there is a crucial need for research implementing cutting-edge technology, next-generation sequencing, bioinformatics analysis, the identification of biomarkers and clinical trials to help with prevention and therapeutic interventions against similar threats in the future.
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Nanogels: Smart tools to enlarge the therapeutic window of gene therapy.
Espuche, B, Moya, SE, Calderón, M
International journal of pharmaceutics. 2024;:123864
Abstract
Gene therapy can potentially treat a great number of diseases, from cancer to rare genetic disorders. Very recently, the development and emergency approval of nucleic acid-based COVID-19 vaccines confirmed its strength and versatility. However, gene therapy encounters limitations due to the lack of suitable carriers to vectorize therapeutic genetic material inside target cells. Nanogels are highly hydrated nano-size crosslinked polymeric networks that have been used in many biomedical applications, from drug delivery to tissue engineering and diagnostics. Due to their easy production, tunability, and swelling properties they have called the attention as promising vectors for gene delivery. In this review, nanogels are discussed as vectors for nucleic acid delivery aiming to enlarge gene therapy's therapeutic window. Recent works highlighting the optimization of inherent transfection efficiency and biocompatibility are reviewed here. The importance of the monomer choice, along with the internal structure, surface decoration, and responsive features are outlined for the different transfection modalities. The possible sources of toxicological endpoints in nanogels are analyzed, and the strategies to limit them are compared. Finally, perspectives are discussed to identify the remining challenges for the nanogels before their translation to the market as transfection agents.
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3.
COVID-19, Possible Hepatic Pathways and Alcohol Abuse-What Do We Know up to 2023?
Michalak, A, Lach, T, Szczygieł, K, Cichoż-Lach, H
International journal of molecular sciences. 2024;(4)
Abstract
The pandemic period due to coronavirus disease 2019 (COVID-19) revolutionized all possible areas of global health. Significant consequences were also related to diverse extrapulmonary manifestations of this pathology. The liver was found to be a relatively common organ, beyond the respiratory tract, affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple studies revealed the essential role of chronic liver disease (CLD) in the general outcome of coronavirus infection. Present concerns in this field are related to the direct hepatic consequences caused by COVID-19 and pre-existing liver disorders as risk factors for the severe course of the infection. Which mechanism has a key role in this phenomenon-previously existing hepatic disorder or acute liver failure due to SARS-CoV-2-is still not fully clarified. Alcoholic liver disease (ALD) constitutes another not fully elucidated context of coronavirus infection. Should the toxic effects of ethanol or already developed liver cirrhosis and its consequences be perceived as a causative or triggering factor of hepatic impairment in COVID-19 patients? In the face of these discrepancies, we decided to summarize the role of the liver in the whole picture of coronavirus infection, paying special attention to ALD and focusing on the pathological pathways related to COVID-19, ethanol toxicity and liver cirrhosis.
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4.
Honey infused with herbs: A boon to cure pathological diseases.
Kumar, S, Verma, M, Hajam, YA, Kumar, R
Heliyon. 2024;(1):e23302
Abstract
Healing with herbs has been a common practice for ages. Nowadays, various infectious diseases like malaria, flu, hepatitis B; COVID-19, etc. are commonly spreading around the world as a consequence of environmental pollution and related consequences. These diseases are not well controlled by the present drug treatment. Antibiotics are failing because of bacterial resistance. Although people believe that herbal medicines are more effective and safer. Therefore, traditional herbal remedies have been recommended for treatment purposes throughout the world. They are often used in combination, fused with honey, or alone for curing different types of ailments. Today, modern formulations of these medicines exist in the form of capsules, tablets, powders, and granules. In several traditional systems, 'Honey' is recommended as a natural medicine that improves several health conditions. In 'Ayurveda', honey is considered a most precious and miraculous product of nature and is used to treat various diseases either alone or after its infusion with herbs. It is a natural, antioxidant-rich, and highly nutritious food that is widely used as a natural sweetener without any side effects. It has antibacterial, antiviral, antifungal, and antioxidant properties. It also proves fruitful in managing/curing various disorders like colds, coughs, cancer, diabetes, wound healing, and cardiovascular disorders. Honey infused with herbs is also used to repair wounds, diabetes, lymphedema, and the prevention of chronic venomous diseases as a part of the folk medicinal system. The current article aims to analyse the medicinal efficiency of honey infused with herbs for curing/managing/treating various types of ailments.
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Antiviral Effects and Mechanisms of Green Tea Catechins on Influenza: A Perception on Combating Symptoms from COVID-19.
Man, GCW, Zheng, X, Hung, SW, Chan, LKY, Zhang, T, Chen, X, Chu, KO, Huen, ICY, Lui, DWY, Wong, AD, et al
Current topics in medicinal chemistry. 2024;(1):60-73
Abstract
Over the centuries, influenza and its associated epidemics have been a serious public health problem. Although vaccination and medications (such as neuraminidase inhibitors) are the mainstay of pharmacological approaches to prevent and treat influenza, however, frequent mutations in the influenza genome often result in treatment failure and resistance to standard medications which limit their effectiveness. In recent years, green tea catechins have been evaluated as potential anti-influenza agents. Herein, in this review, we highlighted the effects and mechanisms underlying the inhibitory effects of epigallocatechin 3-gallate (EGCG), the most abundant ingredient in green tea, against different influenza viral infections, and their clinical benefits toward prevention and treatment. In addition, as the severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) causes the outbreak of COVID-19 pandemic, our review also delineates the current perspective on SARS-CoV-2 and future insights as to the potential application of EGCG on suppressing the flu-like symptoms caused by COVID-19.
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Obesity and Leukemia: Biological Mechanisms, Perspectives, and Challenges.
Tsilingiris, D, Vallianou, NG, Spyrou, N, Kounatidis, D, Christodoulatos, GS, Karampela, I, Dalamaga, M
Current obesity reports. 2024;(1):1-34
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Abstract
PURPOSE OF REVIEW To examine the epidemiological data on obesity and leukemia; evaluate the effect of obesity on leukemia outcomes in childhood acute lymphoblastic leukemia (ALL) survivors; assess the potential mechanisms through which obesity may increase the risk of leukemia; and provide the effects of obesity management on leukemia. Preventive (diet, physical exercise, obesity pharmacotherapy, bariatric surgery) measures, repurposing drugs, candidate therapeutic agents targeting oncogenic pathways of obesity and insulin resistance in leukemia as well as challenges of the COVID-19 pandemic are also discussed. RECENT FINDINGS Obesity has been implicated in the development of 13 cancers, such as breast, endometrial, colon, renal, esophageal cancers, and multiple myeloma. Leukemia is estimated to account for approximately 2.5% and 3.1% of all new cancer incidence and mortality, respectively, while it represents the most frequent cancer in children younger than 5 years. Current evidence indicates that obesity may have an impact on the risk of leukemia. Increased birthweight may be associated with the development of childhood leukemia. Obesity is also associated with worse outcomes and increased mortality in leukemic patients. However, there are several limitations and challenges in meta-analyses and epidemiological studies. In addition, weight gain may occur in a substantial number of childhood ALL survivors while the majority of studies have documented an increased risk of relapse and mortality among patients with childhood ALL and obesity. The main pathophysiological pathways linking obesity to leukemia include bone marrow adipose tissue; hormones such as insulin and the insulin-like growth factor system as well as sex hormones; pro-inflammatory cytokines, such as IL-6 and TNF-α; adipocytokines, such as adiponectin, leptin, resistin, and visfatin; dyslipidemia and lipid signaling; chronic low-grade inflammation and oxidative stress; and other emerging mechanisms. Obesity represents a risk factor for leukemia, being among the only known risk factors that could be prevented or modified through weight loss, healthy diet, and physical exercise. Pharmacological interventions, repurposing drugs used for cardiometabolic comorbidities, and bariatric surgery may be recommended for leukemia and obesity-related cancer prevention.
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Cholesterol and COVID-19-therapeutic opportunities at the host/virus interface during cell entry.
Grewal, T, Nguyen, MKL, Buechler, C
Life science alliance. 2024;(5)
Abstract
The rapid development of vaccines to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has been critical to reduce the severity of COVID-19. However, the continuous emergence of new SARS-CoV-2 subtypes highlights the need to develop additional approaches that oppose viral infections. Targeting host factors that support virus entry, replication, and propagation provide opportunities to lower SARS-CoV-2 infection rates and improve COVID-19 outcome. This includes cellular cholesterol, which is critical for viral spike proteins to capture the host machinery for SARS-CoV-2 cell entry. Once endocytosed, exit of SARS-CoV-2 from the late endosomal/lysosomal compartment occurs in a cholesterol-sensitive manner. In addition, effective release of new viral particles also requires cholesterol. Hence, cholesterol-lowering statins, proprotein convertase subtilisin/kexin type 9 antibodies, and ezetimibe have revealed potential to protect against COVID-19. In addition, pharmacological inhibition of cholesterol exiting late endosomes/lysosomes identified drug candidates, including antifungals, to block SARS-CoV-2 infection. This review describes the multiple roles of cholesterol at the cell surface and endolysosomes for SARS-CoV-2 entry and the potential of drugs targeting cholesterol homeostasis to reduce SARS-CoV-2 infectivity and COVID-19 disease severity.
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Effect and mechanism of quercetin or quercetin-containing formulas against COVID-19: From bench to bedside.
Chen, JY, Huang, TR, Hsu, SY, Huang, CC, Wang, HS, Chang, JS
Phytotherapy research : PTR. 2024
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global coronavirus disease 2019 (COVID-19) pandemic since 2019. Immunopathogenesis and thromboembolic events are central to its pathogenesis. Quercetin exhibits several beneficial activities against COVID-19, including antiviral, anti-inflammatory, immunomodulatory, antioxidative, and antithrombotic effects. Although several reviews have been published, these reviews are incomplete from the viewpoint of translational medicine. The authors comprehensively evaluated the evidence of quercetin against COVID-19, both basically and clinically, to apply quercetin and/or its derivatives in the future. The authors searched the PubMed, Embase, and the Cochrane Library databases without any restrictions. The search terms included COVID-19, SARS-CoV-2, quercetin, antiviral, anti-inflammatory, immunomodulatory, thrombosis, embolism, oxidative, and microbiota. The references of relevant articles were also reviewed. All authors independently screened and reviewed the quality of each included manuscript. The Cochrane Risk of Bias Tool, version 2 (RoB 2) was used to assess the quality of the included randomized controlled trials (RCTs). All selected studies were discussed monthly. The effectiveness of quercetin against COVID-19 is not solid due to methodological flaws in the clinical trials. High-quality studies are also required for quercetin-containing traditional Chinese medicines. The low bioavailability and highly variable pharmacokinetics of quercetin hinder its clinical applications. Its positive impact on immunomodulation through reverting dysbiosis of gut microbiota still lacks robust evidence. Quercetin against COVID-19 does not have tough clinical evidence. Strategies to improve its bioavailability and/or to develop its effective derivatives are needed. Well-designed RCTs are also crucial to confirm their effectiveness in the future.
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Immune Mechanisms Underpinning Long COVID: Collegium Internationale Allergologicum Update 2024.
Untersmayr, E, Venter, C, Smith, P, Rohrhofer, J, Ndwandwe, C, Schwarze, J, Shannon, E, Sokolowska, M, Sadlier, C, O'Mahony, L
International archives of allergy and immunology. 2024;:1-14
Abstract
BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in a prolonged multisystem disorder termed long COVID, which may affect up to 10% of people following coronavirus disease 2019 (COVID-19). It is currently unclear why certain individuals do not fully recover following SARS-CoV-2 infection. SUMMARY In this review, we examine immunological mechanisms that may underpin the pathophysiology of long COVID. These mechanisms include an inappropriate immune response to acute SARS-CoV-2 infection, immune cell exhaustion, immune cell metabolic reprogramming, a persistent SARS-CoV-2 reservoir, reactivation of other viruses, inflammatory responses impacting the central nervous system, autoimmunity, microbiome dysbiosis, and dietary factors. KEY MESSAGES Unfortunately, the currently available diagnostic and treatment options for long COVID are inadequate, and more clinical trials are needed that match experimental interventions to underlying immunological mechanisms.
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Field based research in the era of the pandemic in resource limited settings: challenges and lessons for the future.
Mulchandani, R, Lyngdoh, T, Gandotra, S, Isser, HS, Dhamija, RK, Kakkar, AK
Frontiers in public health. 2024;:1309089
Abstract
The coronavirus pandemic that began in December 2019, has had an unprecedented impact on the global economy, health systems and infrastructure, in addition to being responsible for significant mortality and morbidity worldwide. The "new normal" has brought along, unforeseen challenges for the scientific community, owing to obstructions in conducting field-based research in lieu of minimizing exposure through in-person contact. This has had greater ramifications for the LMICs, adding to the already existing concerns. As a response to COVID-19 related movement restrictions, public health researchers across countries had to switch to remote data collections methods. However, impediments like lack of awareness and skepticism among participants, dependence on paper-based prescriptions, dearth of digitized patient records, gaps in connectivity, reliance on smart phones, concerns with participant privacy at home and greater loss to follow-up act as hurdles to carrying out a research study virtually, especially in resource-limited settings. Promoting health literacy through science communication, ensuring digitization of health records in hospitals, and employing measures to encourage research participation among the general public are some steps to tackle barriers to remote research in the long term. COVID-19 may not be a health emergency anymore, but we are not immune to future pandemics. A more holistic approach to research by turning obstacles into opportunities will not just ensure a more comprehensive public health response in the coming time, but also bolster the existing infrastructure for a stronger healthcare system for countries.