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Home pharmacological therapy in early COVID-19 to prevent hospitalization and reduce mortality: Time for a suitable proposal.
Pandolfi, S, Chirumbolo, S, Ricevuti, G, Valdenassi, L, Bjørklund, G, Lysiuk, R, Doşa, MD, Lenchyk, L, Fazio, S
Basic & clinical pharmacology & toxicology. 2022;(2):225-239
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Abstract
The COVID-19 pandemic is a highly dramatic concern for mankind. In Italy, the pandemic exerted its major impact throughout the period of February to June 2020. To date, the awkward amount of more than 134,000 deaths has been reported. Yet, post-mortem autopsy was performed on a very modest number of patients who died from COVID-19 infection, leading to a first confirmation of an immune-thrombosis of the lungs as the major COVID-19 pathogenesis, likewise for SARS. Since then (June-August 2020), no targeted early therapy considering this pathogenetic issue was approached. The patients treated with early anti-inflammatory, anti-platelet, anticoagulant and antibiotic therapy confirmed that COVID-19 was an endothelial inflammation with immuno-thrombosis. Patients not treated or scarcely treated with the most proper and appropriate therapy and in the earliest, increased the hospitalization rate in the intensive care units and also mortality, due to immune-thrombosis from the pulmonary capillary district and alveoli. The disease causes widespread endothelial inflammation, which can induce damage to various organs and systems. Therapy must be targeted in this consideration, and in this review, we demonstrate how early anti-inflammatory therapy may treat endothelia inflammation and immune-thrombosis caused by COVID-19, by using drugs we are going to recommend in this paper.
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Nutraceuticals: Transformation of Conventional Foods into Health Promoters/Disease Preventers and Safety Considerations.
AlAli, M, Alqubaisy, M, Aljaafari, MN, AlAli, AO, Baqais, L, Molouki, A, Abushelaibi, A, Lai, KS, Lim, SE
Molecules (Basel, Switzerland). 2021;(9)
Abstract
Nutraceuticals are essential food constituents that provide nutritional benefits as well as medicinal effects. The benefits of these foods are due to the presence of active compounds such as carotenoids, collagen hydrolysate, and dietary fibers. Nutraceuticals have been found to positively affect cardiovascular and immune system health and have a role in infection and cancer prevention. Nutraceuticals can be categorized into different classes based on their nature and mode of action. In this review, different classifications of nutraceuticals and their potential therapeutic activity, such as anti-cancer, antioxidant, anti-inflammatory and anti-lipid activity in disease will be reviewed. Moreover, the different mechanisms of action of these products, applications, and safety upon consumers including current trends and future prospect of nutraceuticals will be included.
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Bitter Taste Receptor as a Therapeutic Target in Orthopaedic Disorders.
Cheng, W, Yao, M, Liu, F
Drug design, development and therapy. 2021;:895-903
Abstract
Non-gustatory, extraoral bitter taste receptors (T2Rs) are G-protein coupled receptors that are expressed throughout the body and have various functional responses when stimulated by bitter agonists. Presently, T2Rs have been found to be expressed in osteoclasts and osteocytes where osteoclasts were capable of detecting bacterial quorum-sensing molecules through the T2R38 isoform. In the innate immune system, stimulating T2Rs induces anti-inflammatory and anti-pathogenic effects through the phospholipase C/inositol triphosphate pathway, which leads to intracellular calcium release from the endoplasmic reticulum. The immune cells with functional responses to T2R activation also play a role in bone inflammation and orthopaedic disorders. Furthermore, increasing intracellular calcium levels in bone cells through T2R activation can potentially influence bone formation and resorption. With recent studies finding T2R expression in bone cells, we examine the potential of targeting this receptor to treat bone inflammation and to promote bone anabolism.
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Obesity-Associated Inflammation: Does Curcumin Exert a Beneficial Role?
Varì, R, Scazzocchio, B, Silenzi, A, Giovannini, C, Masella, R
Nutrients. 2021;(3)
Abstract
Curcumin is a lipophilic polyphenol, isolated from the plant turmeric of Curcuma longa. Curcuma longa has always been used in traditional medicine in Asian countries because it is believed to have numerous health benefits. Nowadays it is widely used as spice component and in emerging nutraceutical food worldwide. Numerous studies have shown that curcumin possesses, among others, potential anti-inflammatory properties. Obesity represents a main risk factor for several chronic diseases, including type 2 diabetes, cardiovascular disease, and some types of cancer. The establishment of a low-grade chronic inflammation, both systemically and locally in adipose tissue, occurring in obesity most likely represents a main factor in the pathogenesis of chronic diseases. The molecular mechanisms responsible for the onset of the obesity-associated inflammation are different from those involved in the classic inflammatory response caused by infections and involves different signaling pathways. The inflammatory process in obese people is triggered by an inadequate intake of nutrients that produces quantitative and qualitative alterations of adipose tissue lipid content, as well as of various molecules that act as endogenous ligands to activate immune cells. In particular, dysfunctional adipocytes secrete inflammatory cytokines and chemokines, the adipocytokines, able to recruit immune cells into adipose tissue, amplifying the inflammatory response also at systemic level. This review summarizes the most recent studies focused at elucidating the molecular targets of curcumin activity responsible for its anti-inflammatory properties in obesity-associated inflammation and related pathologies.
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Impact of Dietary Flavanols on Microbiota, Immunity and Inflammation in Metabolic Diseases.
Martín, MÁ, Ramos, S
Nutrients. 2021;(3)
Abstract
Flavanols are natural occurring polyphenols abundant in fruits and vegetables to which have been attributed to beneficial effects on health, and also against metabolic diseases, such as diabetes, obesity and metabolic syndrome. These positive properties have been associated to the modulation of different molecular pathways, and importantly, to the regulation of immunological reactions (pro-inflammatory cytokines, chemokines, adhesion molecules, nuclear factor-κB [NF-κB], inducible enzymes), and the activity of cells of the immune system. In addition, flavanols can modulate the composition and function of gut microbiome in a prebiotic-like manner, resulting in the positive regulation of metabolic pathways and immune responses, and reduction of low-grade chronic inflammation. Moreover, the biotransformation of flavanols by gut bacteria increases their bioavailability generating a number of metabolites with potential to affect human metabolism, including during metabolic diseases. However, the exact mechanisms by which flavanols act on the microbiota and immune system to influence health and disease remain unclear, especially in humans where these connections have been scarcely explored. This review seeks to summarize recent advances on the complex interaction of flavanols with gut microbiota, immunity and inflammation focus on metabolic diseases.
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Redox and Anti-Inflammatory Properties from Hop Components in Beer-Related to Neuroprotection.
Vazquez-Cervantes, GI, Ortega, DR, Blanco Ayala, T, Pérez de la Cruz, V, Esquivel, DFG, Salazar, A, Pineda, B
Nutrients. 2021;(6)
Abstract
Beer is a fermented beverage widely consumed worldwide with high nutritional and biological value due to its bioactive components. It has been described that both alcoholic and non-alcoholic beer have several nutrients derived from their ingredients including vitamins, minerals, proteins, carbohydrates, and antioxidants that make beer a potential functional supplement. Some of these compounds possess redox, anti-inflammatory and anticarcinogenic properties making the benefits of moderate beer consumption an attractive way to improve human health. Specifically, the hop cones used for beer brewing provide essential oils, bitter acids and flavonoids that are potent antioxidants and immune response modulators. This review focuses on the redox and anti-inflammatory properties of hop derivatives and summarizes the current knowledge of their neuroprotective effects.
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Steroid-Induced Diabetes Ketoacidosis in an Immune Thrombocytopenia Patient: A Case Report and Literature Review.
Alakkas, Z, Alzaedi, OA, Somannavar, SS, Alfaifi, A
The American journal of case reports. 2020;:e923372
Abstract
BACKGROUND Steroids are used as anti-inflammatory agents, administered for a variety of medical conditions, either as short- or long-term treatment. Steroid use is associated with many adverse effects, including hyperglycemia, but ketoacidosis is rare. CASE REPORT We present the case of a 53-year-old woman who developed diabetic ketoacidosis after administration of methylprednisolone during treatment of immune thrombocytopenic purpura. She did not have diabetes or a family history of diabetes. Steroid-induced hyperglycemia with insulin resistance, lipolysis, and ketogenesis occurred and were likely to have precipitated the ketoacidosis. Blood glucose, blood gases, and urine test results were diagnostic for ketoacidosis. CONCLUSIONS The risk of ketoacidosis and hyperglycemia should be considered in the course of steroid therapy, even without a diagnosis of diabetes, especially in patients who have risk factors for diabetes mellitus including obesity and long-term use of steroids, so that early identification of diabetic ketoacidosis can prevent further morbidity and mortality in chronic patients.
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Evaluation of mechanisms of action of re-purposed drugs for treatment of COVID-19.
Rajaiah, R, Abhilasha, KV, Shekar, MA, Vogel, SN, Vishwanath, BS
Cellular immunology. 2020;:104240
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Abstract
Coronavirus disease 2019 (COVID-19) is a global health emergency caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The rapid worldwide spread of SARS-CoV-2 infection has necessitated a global effort to identify effective therapeutic strategies in the absence of vaccine. Among the re-purposed drugs being tested currently, hydroxychloroquine (HCQ), without or with zinc ion (Zn++) and the antibiotic azithromycin (AZM), has been administered to prevent or treat patients with COVID-19. The outcome of multiple clinical studies on HCQ has been mixed. Zn++ interferes with viral replication by inhibiting replicative enzymes and its entry into cells may be facilitated by HCQ. Another immunomodulatory drug, methotrexate (MTX), is well known for its ability to mitigate overactive immune system by upregulating the anti-inflammatory protein, A20. However, its beneficial effect in treating COVID-19 has not drawn much attention. This review provides an overview of the virology of SARS-CoV-2 and an analysis of the mechanisms by which these anti-inflammatory agents may act in the treatment of COVID-19 patients. We propose a rationale for the combinatorial use of these re-purposed drugs that may help to combat this ongoing pandemic health emergency.
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Targeting immunometabolism as an anti-inflammatory strategy.
Pålsson-McDermott, EM, O'Neill, LAJ
Cell research. 2020;(4):300-314
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Abstract
The growing field of immunometabolism has taught us how metabolic cellular reactions and processes not only provide a means to generate ATP and biosynthetic precursors, but are also a way of controlling immunity and inflammation. Metabolic reprogramming of immune cells is essential for both inflammatory as well as anti-inflammatory responses. Four anti-inflammatory therapies, DMF, Metformin, Methotrexate and Rapamycin all work by affecting metabolism and/or regulating or mimicking endogenous metabolites with anti-inflammatory effects. Evidence is emerging for the targeting of specific metabolic events as a strategy to limit inflammation in different contexts. Here we discuss these recent developments and speculate on the prospect of targeting immunometabolism in the effort to develop novel anti-inflammatory therapeutics. As accumulating evidence for roles of an intricate and elaborate network of metabolic processes, including lipid, amino acid and nucleotide metabolism provides key focal points for developing new therapies, we here turn our attention to glycolysis and the TCA cycle to provide examples of how metabolic intermediates and enzymes can provide potential novel therapeutic targets.
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Lactoferrin as potential preventative and adjunct treatment for COVID-19.
Chang, R, Ng, TB, Sun, WZ
International journal of antimicrobial agents. 2020;(3):106118
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Abstract
The coronavirus disease 2019 (COVID-19) pandemic is rapidly advancing across the globe despite drastic public and personal health measures. Antivirals and nutritional supplements have been proposed as potentially useful against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that causes COVID-19, but few have been clinically established. Lactoferrin (Lf) is a naturally occurring, non-toxic glycoprotein that is orally available as a nutritional supplement and has established in vitro antiviral efficacy against a wide range of viruses, including SARS-CoV, a closely related coronavirus to SARS-CoV-2. Furthermore, Lf possesses unique immunomodulatory and anti-inflammatory effects that may be especially relevant to the pathophysiology of severe COVID-19 cases. Here we review the underlying biological mechanisms of Lf as an antiviral and immune regulator, and propose its unique potential as a preventative and adjunct treatment for COVID-19. We hope that further research and development of Lf nutritional supplementation would establish its role for COVID-19.