Pro- and Anti-Inflammatory Prostaglandins and Cytokines in Humans: A Mini Review.

Inflammation has been described for two millennia, but cellular aspects and the paradigm involving different mediators have been identified in the recent century. Two main groups of molecules, the prostaglandins (PG) and the cytokines, have been discovered and play a major role in inflammatory processes. The activation of prostaglandins PGE2, PGD2 and PGI2 results in prominent symptoms during cardiovascular and rheumatoid diseases. The balance between pro- and anti-inflammatory compounds is nowadays a challenge for more targeted therapeutic approaches. The first cytokine was described more than a century ago and is now a part of different families of cytokines (38 interleukins), including the IL-1 and IL-6 families and TNF and TGFß families. Cytokines can perform a dual role, being growth promotors or inhibitors and having pro- and anti-inflammatory properties. The complex interactions between cytokines, vascular cells and immune cells are responsible for dramatic conditions and lead to the concept of cytokine storm observed during sepsis, multi-organ failure and, recently, in some cases of COVID-19 infection. Cytokines such as interferon and hematopoietic growth factor have been used as therapy. Alternatively, the inhibition of cytokine functions has been largely developed using anti-interleukin or anti-TNF monoclonal antibodies in the treatment of sepsis or chronic inflammation.

Comparison of Vitamin D and Resveratrol Performances in COVID-19.

Over the last few years, we have experienced the infection generated by severe respiratory syndrome coronavirus 2 (SARS-CoV-2) often resulting in an exaggerated immune reaction and systemic inflammation. The preferred treatments against SARS-CoV-2 were those that mitigated immunological/inflammatory dysfunction. A variety of observational epidemiological studies have reported that vitamin D deficiency is often a crucial factor in many inflammatory diseases and autoimmune diseases, as well as the susceptibility to contract infectious diseases, including acute respiratory infections. Similarly, resveratrol regulates immunity, modifying the gene expression and the release of proinflammatory cytokines in the immune cells. Therefore, it plays an immunomodulatory role that can be beneficial in the prevention and development of non-communicable diseases associated with inflammation. Since both vitamin D and resveratrol also act as immunomodulators in inflammatory pathologies, many studies have paid particular attention to an integrated treatment of either vitamin D or resveratrol in the immune reaction against SARS-CoV-2 infections. This article offers a critical evaluation of published clinical trials that have examined the use of vitamin D or resveratrol as adjuncts in COVID-19 management. Furthermore, we aimed to compare the anti-inflammatory and antioxidant properties linked to the modulation of the immune system, along with antiviral properties of both vitamin D and resveratrol.

Interrelationship between COVID-19 and Coagulopathy: Pathophysiological and Clinical Evidence.

Since the first description of COVID-19 infection, among clinical manifestations of the disease, including fever, dyspnea, cough, and fatigue, it was observed a high incidence of thromboembolic events potentially evolving towards acute respiratory distress syndrome (ARDS) and COVID-19-associated-coagulopathy (CAC). The hypercoagulation state is based on an interaction between thrombosis and inflammation. The so-called CAC represents a key aspect in the genesis of organ damage from SARS-CoV-2. The prothrombotic status of COVID-19 can be explained by the increase in coagulation levels of D-dimer, lymphocytes, fibrinogen, interleukin 6 (IL-6), and prothrombin time. Several mechanisms have been hypothesized to explain this hypercoagulable process such as inflammatory cytokine storm, platelet activation, endothelial dysfunction, and stasis for a long time. The purpose of this narrative review is to provide an overview of the current knowledge on the pathogenic mechanisms of coagulopathy that may characterize COVID-19 infection and inform on new areas of research. New vascular therapeutic strategies are also reviewed.

Inflammation inhibitory activity of green tea, soybean, and guava extracts during Sars-Cov-2 infection through TNF protein in cytokine storm.

Coronavirus disease is caused by the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) known as COVID-19. COVID-19 has caused the deaths of 6,541,936 people worldwide as of September 27th, 2022. SARS-CoV-2 severity is determined by a cytokine storm condition, in which the innate immune system creates an unregulated and excessive production of pro-inflammatory such IL-1, IL-6, NF Kappa B, and TNF alpha signaling molecules known as cytokines. The patient died due to respiratory organ failure and an acute complication because of the hyper-inflammation phenomenon. Green tea, soybean, and guava bioactive substances are well-known to act as anti-inflammation, and antioxidants become prospective COVID-19 illness candidates to overcome the cytokine storm. Our research aims to discover the bioactivity, bioavailability, and protein targets of green tea, soybean, and guava bioactive compounds as anti-inflammatory agents via the TNF inhibition pathway. The experiment uses in silico methods and harnesses the accessible datasets. Samples of 3D structure and SMILE identity of bioactive compounds were retrieved from the KNApSAck and Dr Duke databases. The QSAR analysis was done by WAY2DRUG web server, while the ADME prediction was performed using SWISSADME web server, following the Lipinsky rules of drugs. The target protein and protein-protein interaction were analyzed using STRING DB and Cytoscape software. Lastly, molecular docking was performed using Autodock 4.2 and visualization with BioVia Discovery Studio 2019. The identified study showed the potential of green tea, soybean, and guava's bioactive compounds have played an important role as anti-inflammation agents through TNF inhibitor pathway.

SARS-CoV-2 induces cardiomyocyte apoptosis and inflammation but can be ameliorated by ACE inhibitor Captopril.

Although the clinical manifestation of COVID-19 is mainly respiratory symptoms, approximately 20% of patients suffer from cardiac complications. COVID-19 patients with cardiovascular disease have higher severity of myocardial injury and poor outcomes. The underlying mechanism of myocardial injury caused by SARS-CoV-2 infection remains unclear. Using a non-transgenic mouse model infected with Beta variant (B.1.351), we found that the viral RNA could be detected in lungs and hearts of infected mice. Pathological analysis showed thinner ventricular wall, disorganized and ruptured myocardial fiber, mild inflammatory infiltration, and mild epicardia or interstitial fibrosis in hearts of infected mice. We also found that SARS-CoV-2 could infect cardiomyocytes and produce infectious progeny viruses in human pluripotent stem cell-derived cardiomyocyte-like cells (hPSC-CMs). SARS-CoV-2 infection caused apoptosis, reduction of mitochondrial integrity and quantity, and cessation of beating in hPSC-CMs. In order to dissect the mechanism of myocardial injury caused by SARS-CoV-2 infection, we employed transcriptome sequencing of hPSC-CMs at different time points after viral infection. Transcriptome analysis showed robust induction of inflammatory cytokines and chemokines, up-regulation of MHC class I molecules, activation of apoptosis signaling and cell cycle arresting. These may cause aggravate inflammation, immune cell infiltration, and cell death. Furthermore, we found that Captopril (hypotensive drugs targeting ACE) treatment could alleviate SARS-CoV-2 induced inflammatory response and apoptosis in cardiomyocytes via inactivating TNF signaling pathways, suggesting Captopril may be beneficial for reducing COVID-19 associated cardiomyopathy. These findings preliminarily explain the molecular mechanism of pathological cardiac injury caused by SARS-CoV-2 infection, providing new perspectives for the discovery of antiviral therapeutics.

Mitigation of influenza-mediated inflammation by immunomodulatory matrix-bound nanovesicles.

Cytokine storm describes a life-threatening, systemic inflammatory syndrome characterized by elevated levels of proinflammatory cytokines and immune cell hyperactivation associated with multi-organ dysfunction. Matrix-bound nanovesicles (MBV) are a subclass of extracellular vesicle shown to down-regulate proinflammatory immune responses. The objective of this study was to assess the efficacy of MBV in mediating influenza-induced acute respiratory distress syndrome and cytokine storm in a murine model. Intravenous administration of MBV decreased influenza-mediated total lung inflammatory cell density, proinflammatory macrophage frequencies, and proinflammatory cytokines at 7 and 21 days following viral inoculation. MBV decreased long-lasting alveolitis and the proportion of lung undergoing inflammatory tissue repair at day 21. MBV increased the proportion of activated anti-viral CD4+ and CD8+ T cells at day 7 and memory-like CD62L+ CD44+, CD4+, and CD8+ T cells at day 21. These results show immunomodulatory properties of MBV that may benefit the treatment of viral-mediated pulmonary inflammation with applicability to other viral diseases such as SARS-CoV-2.

A peptide derived from HSP60 reduces proinflammatory cytokines and soluble mediators: a therapeutic approach to inflammation.

Cytokines are secretion proteins that mediate and regulate immunity and inflammation. They are crucial in the progress of acute inflammatory diseases and autoimmunity. In fact, the inhibition of proinflammatory cytokines has been widely tested in the treatment of rheumatoid arthritis (RA). Some of these inhibitors have been used in the treatment of COVID-19 patients to improve survival rates. However, controlling the extent of inflammation with cytokine inhibitors is still a challenge because these molecules are redundant and pleiotropic. Here we review a novel therapeutic approach based on the use of the HSP60-derived Altered Peptide Ligand (APL) designed for RA and repositioned for the treatment of COVID-19 patients with hyperinflammation. HSP60 is a molecular chaperone found in all cells. It is involved in a wide diversity of cellular events including protein folding and trafficking. HSP60 concentration increases during cellular stress, for example inflammation. This protein has a dual role in immunity. Some HSP60-derived soluble epitopes induce inflammation, while others are immunoregulatory. Our HSP60-derived APL decreases the concentration of cytokines and induces the increase of FOXP3+ regulatory T cells (Treg) in various experimental systems. Furthermore, it decreases several cytokines and soluble mediators that are raised in RA, as well as decreases the excessive inflammatory response induced by SARS-CoV-2. This approach can be extended to other inflammatory diseases.

Resveratrol regulates inflammation and improves oxidative stress via Nrf2 signaling pathway: Therapeutic and biotechnological prospects.

Usually, in aerobic metabolism, natural materials including nucleic acids, proteins, and lipids can experience auxiliary injury by oxidative responses. This damage produced by reactive oxygen/nitrogen species has been identified as "oxidative stress." As a natural polyphenol got from red wine and peanuts, resveratrol is one of the most eminent anti-aging mixtures. Based on many studies', resveratrol hinders destructive effects of inflammatory causes and reactive oxygen radicals in several tissues. The nuclear erythroid 2-related factor 2 is a factor related to transcription with anti-inflammatory, antioxidant possessions which is complicated by enzyme biotransformation and biosynthesis of lipids and carbohydrates. This review provides current understanding and information about the character of resveratrol against oxidative stress and regulation of inflammation via Nrf2 signaling pathway.

The F/B ratio as a biomarker for inflammation in COVID-19 and T2D: Impact of metformin.

The pandemic of COVID-19 has highlighted the intricate relationship between gut microbiome and overall health. Recent studies have shown that the Firmicutes/Bacteroidetes ratio in the gut microbiome may be linked to various diseases including COVID-19 and type 2 diabetes (T2D). Understanding the link between gut microbiome and these diseases is essential for developing strategies for prevention and treatment. In this study, 115 participants were recruited and divided into three groups: 1st group: T2D patients and healthy controls, 2nd group: COVID-19 patients with and without T2D, 3rd group: T2D patients with COVID-19 treated with or without metformin. Gut microbial composition at the phylum level was assessed using qRT-PCR with universal primers targeting the bacterial 16 S rRNA gene and specific primers for Firmicutes and Bacteroidetes. Data was analyzed using one-way ANOVA, logistic regression, and Spearman's rank correlation coefficient. The study found that the ratio of Firmicutes to Bacteroidetes (F/B) was higher in patients with both T2D and COVID-19 compared to those with only T2D or COVID-19. Additionally, the F/B ratio was positively correlated with C-reactive protein (CRP) in T2D and COVID-19 patients. The study also suggests that metformin treatment may affect this correlation. Logistic regression analysis showed that the F/B ratio was significantly associated with CRP. These findings suggest that the F/B ratio may be a potential biomarker for inflammation in T2D and COVID-19 patients and metformin treatment may have an effect on the correlation between F/B and CRP levels.

Inflammaging, Immunosenescence, and Anti-Inflammatory Medications Used in Psychiatry: A Brief Overview.

The immune system is central to brain health and longevity, yet with age, infection, injury, or chronic stress, the immune system can trigger persistent central nervous system inflammation that impairs brain functioning. This brief review investigates psychopharmacological treatments that have anti-inflammatory effects in the context of immune system dysregulation in the aging brain. [Journal of Psychosocial Nursing and Mental Health Services, 61(5), 7-10.].

Cost and community acceptability of enhanced antibiotic distribution approaches for trachoma in the Republic of South Sudan: enhancing the A in SAFE (ETAS) study protocol.

BACKGROUND: The World Health Organization targeted trachoma for global elimination as a public health problem by 2030. Reaching elimination thresholds by the year 2030 in the Republic of South Sudan will be a considerable challenge, as the country currently has many counties considered hyper-endemic (> 30% trachomatous inflammation-follicular [TF]) that have yet to receive interventions. Evidence from randomized trials, modeling, and population-based surveys suggests that enhancements may be needed to the standard-of-care annual mass drug administration (MDA) to reach elimination thresholds in a timely manner within highly endemic areas. We describe a protocol for a study to determine the cost and community acceptability of enhanced antibiotic strategies for trachoma in South Sudan. METHODS: The Enhancing the A in SAFE (ETAS) study is a community randomized intervention costing and community acceptability study. Following a population-based trachoma prevalence survey in 1 county, 30 communities will be randomized 1:1 to receive 1 of 2 enhanced MDA interventions, with the remaining communities receiving standard-of-care annual MDA. The first intervention strategy will consist of a community-wide MDA followed by 2 rounds of targeted treatment to children ages 6 months to 9 years, 2 weeks and 4 weeks after the community MDA. The second strategy will consist of a community-wide biannual MDA approximately 6 to 8 months apart. The costing analysis will use a payer perspective and identify the total cost of the enhanced interventions and annual MDA. Community acceptability will be assessed through MDA coverage monitoring and mixed-methods research involving community stakeholders. A second trachoma-specific survey will be conducted 12 months following the original survey. DISCUSSION: ETAS has received ethical clearance and is expected to be conducted between 2022 and 2023. Results will be shared through subsequent manuscripts. The study's results will provide information to trachoma programs on whether enhanced interventions are affordable and acceptable to communities. These results will further help in the design of future trachoma-specific antibiotic efficacy trials. Enhanced MDA approaches could help countries recover from delays caused by conflict or humanitarian emergencies and could also assist countries such as South Sudan in reaching trachoma elimination as a public health problem by 2030. TRIAL REGISTRATION: This trial was registered on December 1st, 2022 (clinicaltrails.org: NCT05634759).

Myricetin possesses the potency against SARS-CoV-2 infection through blocking viral-entry facilitators and suppressing inflammation in rats and mice.

BACKGROUND: Myricetin (3,5,7-trihydroxy-2-(3,4,5-tri hydroxyphenyl)-4-benzopyrone) is a common flavonol extracted from many natural plants and Chinese herb medicines and has been demonstrated to have multiple pharmacological activities, such as anti-microbial, anti-thrombotic, neuroprotective, and anti-inflammatory effects. Previously, myricetin was reported to target Mpro and 3CL-Pro-enzymatic activity to SARS-CoV-2. However, the protective value of myricetin on SARS-Cov-2 infection through viral-entry facilitators has not yet been comprehensively understood. PURPOSE: The aim of the current study was to evaluate the pharmacological efficacy and the mechanisms of action of myricetin against SARS-CoV-2 infection both in vitro and in vivo. METHODS: The inhibitory effects of myricetin on SARS-CoV-2 infection and replication were assessed on Vero E6 cells. Molecular docking analysis and bilayer interferometry (BLI) assays, immunocytochemistry (ICC), and pseudoviruses assays were performed to evaluate the roles of myricetin in the intermolecular interaction between the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein and angiotensin-converting enzyme 2 (ACE2). The anti-inflammatory potency and mechanisms of myricetin were examined in THP1 macrophages in vitro, as well as in carrageenan-induced paw edema, delayed-type hypersensitivity (DTH) induced auricle edema, and LPS-induced acute lung injury (ALI) animal models. RESULTS: The results showed that myricetin was able to inhibit binding between the RBD of the SARS-CoV-2 S protein and ACE2 through molecular docking analysis and BLI assay, demonstrating its potential as a viral-entry facilitator blocker. Myricetin could also significantly inhibit SASR-CoV-2 infection and replication in Vero E6 cells (EC50 55.18 µM), which was further validated with pseudoviruses containing the RBD (wild-type, N501Y, N439K, Y453F) and an S1 glycoprotein mutant (S-D614G). Moreover, myricetin exhibited a marked suppressive action on the receptor-interacting serine/threonine protein kinase 1 (RIPK1)-driven inflammation and NF-kappa B signaling in THP1 macrophages. In animal model studies, myricetin notably ameliorated carrageenan-induced paw edema in rats, DTH induced auricle edema in mice, and LPS-induced ALI in mice. CONCLUSION: Our findings showed that myricetin inhibited HCoV-229E and SARS-CoV-2 replication in vitro, blocked SARS-CoV-2 virus entry facilitators and relieved inflammation through the RIPK1/NF-κB pathway, suggesting that this flavonol has the potential to be developed as a therapeutic agent against COVID-19.

Intravenous immunoglobulins (IVIG) in severe/critical COVID-19 adult patients.

The coronavirus disease 2019 (COVID-19) pandemic has become a huge obstacle to the health system due to the high rate of contagion. It is postulated that intravenous immunoglobulins (IVIG) can lower the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related inflammation and prevent the development of acute respiratory distress syndrome (ARDS). The main advantages of IVIG treatment might be targeting cytokine storm in severe and critical COVID-19 by influences on complement, innate immune cells, effector T-cells, and Tregs. Randomized clinical trials (RCTs) and non-RCTs evaluating the safety and efficacy of IVIG in patients with severe/critical COVID-19 were performed. It seems that early administration of high-dose IVIG (in the acceleration phase of the disease) in severe or especially critical COVID-19 may be an effective therapeutic option, but there are no strong data to use it routinely. The results regarding mortality reduction are inconclusive. Additionally, IVIG treatment carries a risk of complications that should be considered when initiating treatment. However, given the COVID-19 mortality rate and limited therapeutic options, the use of IVIG is worth considering. This review summarizes the development and highlights recent advances in treatment with IVIG of severe/critically ill COVID-19 patients.

Elderberry Extracts: Characterization of the Polyphenolic Chemical Composition, Quality Consistency, Safety, Adulteration, and Attenuation of Oxidative Stress- and Inflammation-Induced Health Disorders.

Elderberry is highly reputed for its health-improving effects. Multiple pieces of evidence indicate that the consumption of berries is linked to enhancing human health and preventing or delaying the onset of chronic medical conditions. Compared with other fruit, elderberry is a very rich source of anthocyanins (approximately 80% of the polyphenol content). These polyphenols are the principals that essentially contribute to the high antioxidant and anti-inflammatory capacities and the health benefits of elderberry fruit extract. These health effects include attenuation of cardiovascular, neurodegenerative, and inflammatory disorders, as well as anti-diabetic, anticancer, antiviral, and immuno-stimulatory effects. Sales of elderberry supplements skyrocketed to $320 million over the year 2020, according to an American Botanical Council (ABC) report, which is attributable to the purported immune-enhancing effects of elderberry. In the current review, the chemical composition of the polyphenolic content of the European elderberry (Sambucus nigra) and the American elderberry (Sambucus canadensis), as well as the analytical techniques employed to analyze, characterize, and ascertain the chemical consistency will be addressed. Further, the factors that influence the consistency of the polyphenolic chemical composition, and hence, the consistency of the health benefits of elderberry extracts will be presented. Additionally, adulteration and safety as factors contributing to consistency will be covered. The role of elderberry in enhancing human health alone with the pharmacological basis, the cellular pathways, and the molecular mechanisms underlying the observed health benefits of elderberry fruit extracts will be also reviewed.

Repurposing of RAS-Pathway Mediated Drugs for Intestinal Inflammation Related Diseases for Treating SARS-CoV-2 Infection.

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is an emerging zoonotic virus, which causes Coronavirus Disease 2019 (COVID-19). Entry of coronaviruses into the cell depends on binding of the viral spike (S) proteins to cellular receptors Angiotensin-converting enzyme 2 (ACE2). The virus-mediated reduction of ACE2/Ang1-7 causes flooding of inflammatory cytokines. A similar scenario of hyper immunologic reaction has been witnessed in the context of Intestinal Inflammatory Diseases (IIDs) with the deregulation of ACE2. This review summarizes several IIDs that lead to such susceptible conditions. It discusses suitable mechanisms of how ACE2, being a crucial regulator of the Renin-Angiotensin System (RAS) signaling pathway, can affect the physiology of intestine as well as lungs, the primary site of SARS-CoV-2 infection. ACE2, as a SARS-CoV-2 receptor, establishes a critical link between COVID-19 and IIDs. Intercessional studies targeting the RAS signaling pathway in patients may provide a novel strategy for addressing the COVID-19 crisis. Hence, the modulation of these key RAS pathway members can be beneficial in both instances. However, it's difficult to say how beneficial are the ACE inhibitors (ACEI)/ Angiotensin II type-1 receptor blockers (ARBs) during COVID-19. As a result, much more research is needed to better understand the relationship between the RAS and SARS-CoV-2 infection.

Recuperative herbal formula Jing Si maintains vasculature permeability balance, regulates inflammation and assuages concomitants of "Long-Covid".

Coronavirus disease 2019 (COVID-19) is a worldwide health threat that has long-term effects on the patients and there is currently no efficient cure prescribed for the treatment and the prolonging effects. Traditional Chinese medicines (TCMs) have been reported to exert therapeutic effect against COVID-19. In this study, the therapeutic effects of Jing Si herbal tea (JSHT) against COVID-19 infection and associated long-term effects were evaluated in different in vitro and in vivo models. The anti-inflammatory effects of JSHT were studied in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and in Omicron pseudotyped virus-induced acute lung injury model. The effect of JSHT on cellular stress was determined in HK-2 proximal tubular cells and H9c2 cardiomyoblasts. The therapeutic benefits of JSHT on anhedonia and depression symptoms associated with long COVID were evaluated in mice models for unpredictable chronic mild stress (UCMS). JSHT inhibited the NF-ƙB activities, and significantly reduced LPS-induced expression of TNFα, COX-2, NLRP3 inflammasome, and HMGB1. JSHT was also found to significantly suppress the production of NO by reducing iNOS expression in LPS-stimulated RAW 264.7 cells. Further, the protective effects of JSHT on lung tissue were confirmed based on mitigation of lung injury, repression in TMRRSS2 and HMGB-1 expression and reduction of cytokine storm in the Omicron pseudotyped virus-induced acute lung injury model. JSHT treatment in UCMS models also relieved chronic stress and combated depression symptoms. The results therefore show that JSHT attenuates the cytokine storm by repressing NF-κB cascades and provides the protective functions against symptoms associated with long COVID-19 infection.

Oridonin inhibits inflammation of epithelial cells via dual-targeting of CD31 Keap1 to ameliorate acute lung injury.

Introdcution: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of COVID-19 mortality. However, drug delivery to lung tissues is impeded by endothelial cell barriers, limiting the efficacy of existing treatments. A prompt and aggressive treatment strategy is therefore necessary. Methods: We assessed the ability of anti-CD31-ORI-NPs to penetrate endothelial cell barriers and specifically accumulate in lung tissues using an animal model. We also compared the efficacy of anti-CD31-ORI-NPs to that of free oridonin in ameliorating acute lung injury and evaluated the cytotoxicity of both treatments on endothelial cells. Results: Compared to free ORI, the amount of anti-CD31-ORI-NPs accumulated in lung tissues increase at least three times. Accordingly, anti-CD31-ORI-NPs improve the efficacy three times on suppressing IL-6 and TNF-a secretion, ROS production, eventually ameliorating acute lung injury in animal model. Importantly, anti-CD31-ORI-NPs significantly decrease the cytotoxicity at least two times than free oridonin on endothelial cells. Discussion: Our results from this study will not only offer a novel therapeutic strategy with high efficacy and low toxicity, but also provide the rational design of nanomaterials of a potential drug for acute lung injury therapy.

Role of antimicrobial peptide cathelicidin in thrombosis and thromboinflammation.

Thrombosis is a frequent cause of cardiovascular mortality and hospitalization. Current antithrombotic strategies, however, target both thrombosis and physiological hemostasis and thereby increase bleeding risk. In recent years the pathophysiological understanding of thrombus formation has significantly advanced and inflammation has become a crucial element. Neutrophils as most frequent immune cells in the blood and their released mediators play a key role herein. Neutrophil-derived cathelicidin next to its strong antimicrobial properties has also shown to modulates thrombosis and thus presents a potential therapeutic target. In this article we review direct and indirect (immune- and endothelial cell-mediated) effects of cathelicidin on platelets and the coagulation system. Further we discuss its implications for large vessel thrombosis and consecutive thromboinflammation as well as immunothrombosis in sepsis and COVID-19 and give an outlook for potential therapeutic prospects.

A comprehensive overview of juvenile idiopathic arthritis: From pathophysiology to management.

Rheumatoid Arthritis (RA) is a progressive autoimmune disease. It is among the most widespread chronic illnesses in children, with an annual incidence of 1.6 to 23 new instances per 100,000 adolescents. About 1 child in every 1000 develops Juvenile Idiopathic Arthritis (JIA) type of chronic arthritis. The cause of JIA is not well known but what known is that it involves inflammation of the synovium and destruction of tissues in joints which can cause early-onset of oligo articular JIA. It is challenging to diagnose the condition in some children who initially complain of pain and joint swelling as there is no blood test discovered that can confirm the diagnoses of JIA. As JIA patients are immunosuppressed due to the use of drugs, making them vulnerable to catch infections like COVID-19 which can lead to cardiovascular diseases having high rate of morbidity and mortality. The comorbidity like Diabetes has higher incidence in these patients resulting in synergistic effect on inflammation. Currently, the connection of genetics in JIA provides evidence that HLA Class I and II alleles have a role in the pathophysiology of various subtypes of JIA which includes inflammation in the axial skeletal. The primary objective of therapy in juvenile idiopathic arthritis is the suppression of clinical symptoms. The pharmacological approach includes use of medications like DMARDs, NSAIDs etc. and non-pharmacological approach includes physiotherapy, which helps in restoring normal joint function and herbs as adjuvants which has the benefit of no side effects.

Natural Products Against COVID-19 Inflammation: A Mini-Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is a virus whose genetic material is positive single-stranded RNA, being responsible for coronavirus disease 2019 (COVID- 19), an infection that compromises the lungs and consequently the respiratory capacity of the infected individual, according to the WHO in November 2021, 249,743,428 cases were confirmed, of which 5,047,652 individuals died due to complications resulting from the infection caused by SARSCOV- 2. As the infection progresses, the individual may experience loss of smell and taste, as well as breathing difficulties, severe respiratory failure, multiple organ failure, and death. Due to this new epidemiological agent in March 2020 it was announced by the director general of the World Health Organization (WHO) a pandemic status, and with that, many research groups are looking for new therapeutic alternatives through synthetic and natural bioactives. This research is a literature review of some in silico studies involving natural products against COVID-19 inflammation published in 2020 and 2021. Work like this presents relevant information to the scientific community, boosting future research and encouraging the use of natural products for the search for new antivirals against COVID-19.