Soybean Seeds (Glycine max L.) Extract Against Cytokine Storm in ARDS Rat Model through Inhibiting Inflammation Marker

Several studies have suggested that "cytokine storms" are significant causes of the severity of COVID-19. Controlling and inhibiting the cytokine storm in COVID-19 could prevent the spread of COVID-19 and saves patient lives. Soybean (Glycine max L.) is known to have various biological activities. This study aims to examine bioactive compounds in SSE and the effect of SSE on the ARDS rats model. A total of 25 Sprague Dawley Lipopolysaccharide-induced rats were used. Determination of serum IL-1β, IL-12, and lung TNF-α levels was performed by ELISA method. NF-κB and IFN-γ expression were determined by the qRTPCR method. IL-6 expressions were analyzed by immunohistochemistry assay. The bleeding, inflammation, and alveolus collapse score were analyzed using the HE staining method. The results showed that SSE could decrease the level of IL-1β, IL-12, TNF-α, IL-6, NF-kB, and IFN-γ and improve the bleeding, inflammation, and alveolus score in the lung. SSE could decrease the pro-inflammatory cytokines and improve lung condition in ARDS rats model. © 2023, Bogor Agricultural University. All rights reserved.

Pathogenetic therapy of COVID-19: focus on glucocorticoids

The problem of preventing excessive production of pro-inflammatory cytokines in the case of COVID-19 remains unre-solved. The use of steroids in the treatment of coronavirus pneumonia remains controversial. To date, there is insufficient literature data for the routine use of steroids in COVID-19 intensive care programs, and this issue remains the subject of continuous research and endless debate. The review of the scientific literature focuses on one of the areas of pathogenetic therapy for COVID-19 — the pre- vention and elimination of hyperproduction of pro-inflammatory cytokines using glucocorticoid drugs. The review presents modern international recommendations on the use of glucocorticoid drugs in severe COVID-19, examines the pathogenetic mechanisms of their action and side effects. © 2022. The Authors. This is an open access article under the terms of the Creative Commons Attribution 4.0 International License, CC BY, which allows others to freely distribute the published article, with the obligatory reference to the authors of original works and original publication in this journal.

Prolonged T-cell activation and long COVID symptoms independently associate with severe COVID-19 at 3 months.

Coronavirus disease-19 (COVID-19) causes immune perturbations which may persist long term, and patients frequently report ongoing symptoms for months after recovery. We assessed immune activation at 3-12 months post hospital admission in 187 samples from 63 patients with mild, moderate, or severe disease and investigated whether it associates with long COVID. At 3 months, patients with severe disease displayed persistent activation of CD4+ and CD8+ T-cells, based on expression of HLA-DR, CD38, Ki67, and granzyme B, and elevated plasma levels of interleukin-4 (IL-4), IL-7, IL-17, and tumor necrosis factor-alpha (TNF-α) compared to mild and/or moderate patients. Plasma from severe patients at 3 months caused T-cells from healthy donors to upregulate IL-15Rα, suggesting that plasma factors in severe patients may increase T-cell responsiveness to IL-15-driven bystander activation. Patients with severe disease reported a higher number of long COVID symptoms which did not however correlate with cellular immune activation/pro-inflammatory cytokines after adjusting for age, sex, and disease severity. Our data suggests that long COVID and persistent immune activation may correlate independently with severe disease.

Prognostic Significance of the Coagulation and Complement Systems in Critical COVID-19 Infection.

Infection with the SARS-CoV-2 virus (COVID-19 disease) can cause a wide range of clinical situations - from an asymptomatic state to fatal outcomes. In cases of serious clinical manifestations, the underlying mechanisms involve a number of immune cells and stromal cells as well as their products such as pro-inflammatory interleukin-6 and tumour necrosis factor-alpha that ultimately cause the cytokine storm. The situation of overproduction of pro-inflammatory cytokines is somewhat similar to, though in a mild form, health conditions in obesity and related metabolic disorders like type-2 diabetes, which are also considered important risk factors for severe illness in COVID-19. Interestingly, neutrophils perhaps play a significant role in this pathogenesis. On the other hand, it is thought that COVID-19-related critical illness is associated with pathological hyperactivity of the complement system and coagulopathy. Although the precise molecular interactions between the complement and coagulation systems are not clear, we observe an intimate cross-talk between these two systems in critically ill COVID-19 patients. It is believed that both of these biological systems are connected with the cytokine storm in severe COVID-19 disease and actively participate in this vicious cycle. In order to hinder the pathological progression of COVID-19, a number of anticoagulation agents and complement inhibitors have been used with varying success. Among these drugs, low molecular weight heparin enoxaparin, factor Xa inhibitor apixaban, and complement C5 inhibitor eculizumab have been commonly used in patients with COVID-19. Our overall experience might help us in the future to tackle any such conditions.

INTERRELATIONS BETWEEN VIRAL LOAD AND CELLULAR IMMUNITY IN PATIENTS WITH COVID-19 OF VARYING SEVERITY.

Assessment of viral load levels in various biological samples taken from the respiratory tract can be an indicator of an ongoing process of active viral replication and may be used to monitor severe respiratory viral infections. The study of the relationship between SARS-CoV-2 viral load and immunological laboratory parameters is an important step in the search for clinical markers of COVID-19. The aim of this research was to quantify viral load in patients with COVID-19 and to identify the relationship between viral load and changes in the parameters of the cellular component of the immune system. A laboratory examination was carried out on 74 patients diagnosed with COVID-19, they were divided into 3 groups based on the severity of the disease: mild, moderate, severe. Total viral load in clinical samples was determined by the number of SARS-CoV-2 RNA copies per 100 copies of the reference RNaseP gene. A comprehensive assessment of the cellular component of the immune system was performed using flow cytometry and direct monoclonal antibodies, and the IL-6, and C-reactive protein concentrations were determined. We revealed a relationship between the development of serious clinical conditions in the patients with COVID-19, and the levels of viral load. High levels of viral RNA in biological samples correlate with main indicators of the T cell component of the immune system associated with disease severity. In a subgroup of patients with an extremely high viral load, strong positive correlations were found between the relative numbers of cytotoxic lymphocytes (CD3+CD8+), activated T lymphocytes (CD3+HLA-DR+), as well as absolute and relative numbers of activated B lymphocytes and NK cells (CD3-CD25+). Laboratory monitoring of the cellular component of the immune system, along with the assessment of viral loads, should improve early assessment of clinical condition in the patients with COVID-19. Changes in expression levels of activation markers on immune cells can be potentially viewed as indicators of recovery during COVID-19.Copyright © Nikitin Yu.V. et al., 2023 The article can be used under the Creative Commons Attribution 4.0 License.

Aqueous cannabidiol ß-cyclodextrin complexed polymeric micelle nasal spray to attenuate in vitro and ex vivo SARS-CoV-2-induced cytokine storms.

Cannabidiol (CBD) has a number of biological effects by acting on the cannabinoid receptors CB1 and CB2. CBD may be involved in anti-inflammatory processes via CB1 and CB2 receptors, resulting in a decrease of pro-inflammatory cytokines. However, CBD's poor aqueous solubility is a major issue in pharmaceutical applications. The aim of the present study was to develop and evaluate a CBD nasal spray solution. A water-soluble CBD was prepared by complexation with ß-cyclodextrin (ß-CD) at a stoichiometric ratio of 1:1 and forming polymeric micelles using poloxamer 407. The mixture was then lyophilized and characterized using FT-IR, DSC, and TGA. CBD-ß-CD complex-polymeric micelles were formulated for nasal spray drug delivery. The physicochemical properties of the CBD-ß-CD complex-polymeric micelle nasal spray solution (CBD-ß-CDPM-NS) were assessed. The results showed that the CBD content in the CBD-ß-CD complex polymeric micelle powder was 102.1 ± 0.5% labeled claim. The CBD-ß-CDPM-NS was a clear colorless isotonic solution. The particle size, zeta potential, pH value, and viscosity were 111.9 ± 0.7 nm, 0.8 ± 0.1 mV, 6.02 ± 0.02, and 12.04 ± 2.64 cP, respectively. This formulation was stable over six months at ambient temperature. The CBD from CBD-ß-CDPM-NS rapidly released to 100% within 1 min. Ex vivo permeation studies of CBD-ß-CDPM-NS through porcine nasal mucosa revealed a permeation rate of 4.8 µg/cm2/min, which indicated that CBD was effective in penetrating nasal epithelial cells. CBD-ß-CDPM-NS was tested for its efficacy and safety in terms of cytokine production from nasal immune cells and toxicity to nasal epithelial cells. The CBD-ß-CDPM-NS was not toxic to nasal epithelial at the concentration of CBD equivalent to 3.125-50 µg/mL. When the formulation was subjected to bioactivity testing against monocyte-like macrophage cells, it proved that the CBD-ß-CDPM-NS has the potential to inhibit inflammatory cytokines. CBD-ß-CDPM-NS demonstrated the formulation's ability to reduce the cytokine produced by S-RBD stimulation in ex vivo porcine nasal mucosa in both preventative and therapeutic modes.

Transcriptome in Human Mycoses

Mycoses are infectious diseases caused by fungi, which incidence has increased in recent decades due to the increasing number of immunocompromised patients and improved diagnostic tests. As eukaryotes, fungi share many similarities with human cells, making it difficult to design drugs without side effects. Commercially available drugs act on a limited number of targets and have been reported fungal resistance to commonly used antifungal drugs. Therefore, elucidating the pathogenesis of fungal infections, the fungal strategies to overcome the hostile environment of the host, and the action of antifungal drugs is essential for developing new therapeutic approaches and diagnostic tests. Large-scale transcriptional analyses using microarrays and RNA sequencing (RNA-seq), combined with improvements in molecular biology techniques, have improved the study of fungal pathogenicity. Such techniques have provided insights into the infective process by identifying molecular strategies used by the host and pathogen during the course of human mycoses. This chapter will explore the latest discoveries regarding the transcriptome of major human fungal pathogens. Further we will highlight genes essential for host–pathogen interactions, immune response, invasion, infection, antifungal drug response, and resistance. Finally, we will discuss their importance to the discovery of new molecular targets for antifungal drugs. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2014, 2022.

INTERRELATIONS BETWEEN VIRAL LOAD AND CELLULAR IMMUNITY IN PATIENTS WITH COVID-19 OF VARYING SEVERITY.

Assessment of viral load levels in various biological samples taken from the respiratory tract can be an indicator of an ongoing process of active viral replication and may be used to monitor severe respiratory viral infections. The study of the relationship between SARS-CoV-2 viral load and immunological laboratory parameters is an important step in the search for clinical markers of COVID-19. The aim of this research was to quantify viral load in patients with COVID-19 and to identify the relationship between viral load and changes in the parameters of the cellular component of the immune system. A laboratory examination was carried out on 74 patients diagnosed with COVID-19, they were divided into 3 groups based on the severity of the disease: mild, moderate, severe. Total viral load in clinical samples was determined by the number of SARS-CoV-2 RNA copies per 100 copies of the reference RNaseP gene. A comprehensive assessment of the cellular component of the immune system was performed using flow cytometry and direct monoclonal antibodies, and the IL-6, and C-reactive protein concentrations were determined. We revealed a relationship between the development of serious clinical conditions in the patients with COVID-19, and the levels of viral load. High levels of viral RNA in biological samples correlate with main indicators of the T cell component of the immune system associated with disease severity. In a subgroup of patients with an extremely high viral load, strong positive correlations were found between the relative numbers of cytotoxic lymphocytes (CD3+CD8+), activated T lymphocytes (CD3+HLA-DR+), as well as absolute and relative numbers of activated B lymphocytes and NK cells (CD3-CD25+). Laboratory monitoring of the cellular component of the immune system, along with the assessment of viral loads, should improve early assessment of clinical condition in the patients with COVID-19. Changes in expression levels of activation markers on immune cells can be potentially viewed as indicators of recovery during COVID-19.Copyright © Nikitin Yu.V. et al., 2023 The article can be used under the Creative Commons Attribution 4.0 License.

The potential role of scavenger receptor B type I (SR-BI) in SARS-CoV-2 infection.

Scavenger receptor type B I (SR-BI), the major receptor for high-density lipoprotein (HDL) mediates the delivery of cholesterol ester and cholesterol from HDL to the cell membrane. SR-BI is implicated as a receptor for entry of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). SR-BI is colocalized with the angiotensin-converting enzyme 2 (ACE2) increasing the binding and affinity of SARS-CoV-2 to ACE2 with subsequent viral internalization. SR-BI regulates lymphocyte proliferation and the release of pro-inflammatory cytokines from activated macrophages and lymphocytes. SR-BI is reduced during COVID-19 due to consumption by SARS-CoV-2 infection. COVID-19-associated inflammatory changes and high angiotensin II (AngII) might be possible causes of repression of SR-BI in SARS-CoV-2 infection. In conclusion, the downregulation of SR-BI in COVID-19 could be due to direct invasion by SARS-CoV-2 or through upregulation of pro-inflammatory cytokines, inflammatory signaling pathways, and high circulating AngII. Reduction of SR-BI in COVID-19 look like ACE2 may provoke COVID-19 severity through exaggeration of the immune response. Further studies are invoked to clarify the potential role of SR-BI in the pathogenesis of COVID-19 that could be protective rather than detrimental.

Rare Cases of Polymyalgia Rheumatica After Receiving COVID-19 Vaccinations.

Polymyalgia rheumatica (PMR) is a systemic rheumatic inflammatory disease of adults presenting with symmetrical proximal muscle stiffness and pain predominantly involving the shoulders, neck, and pelvic girdle. The coronavirus disease of 2019 (COVID-19) presented as a pandemic causing worldwide morbidity and mortality in large numbers. Rapid scientific research expedited preventative vaccine development and has helped tremendously in cutting down severe illness, hospitalizations, and death from COVID-19, with the messenger ribonucleic acid (mRNA) vaccines outperforming the others. We present two cases that showcase the incidence of polymyalgia rheumatica after receiving COVID-19 vaccination. Patient 1 is a 69-year-old female who developed arm and thigh stiffness a week before the second dose while receiving her primary Moderna vaccine series. She had an elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), so she was started on low-dose steroids, which were weaned down over a five-month period. Three weeks after receiving her Moderna booster, she had a recurrence of the classic polymyalgia rheumatica symptoms and elevated ESR. She responded to prednisone 15 mg with a successful taper over eight months. Patient 2 is a 74-year-old male who received his primary series and booster through Pfizer-BioNTech. Prior to the booster, he was treated for COVID-19 with monoclonal antibody therapy. He presented to the office with hip and shoulder pain and stiffness along with an elevated C-reactive protein. Consequently, he received 20 mg of prednisone but needed to increase his dose to 25 mg total to help with the control of his inflammation. The goal of this article is to prompt physicians about the possibility of PMR incidence after patients receive vaccinations for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PMR can be debilitating to the quality of life of patients. Knowing this association allows for more timely and competent treatment. PMR following SARS-CoV-2 vaccinations is continuously being observed in the medical field. Increased knowledge may help prevent the recurrence with subsequent doses. Further studies on the follow-up of such cases and the effect on subsequent immunization would be helpful.

A review of fibroblast-like synoviocytes in the pathogenesis of Rheumatoid arthritis: Their activation and the inhibition of their apoptosis

Rheumatoid Arthritis (RA) is a systemic, autoimmune, inflammatory disease characterized by synovial hyperplasia, inflammatory cell infiltration in the synovial tissues, and progressive destruction of cartilage and bones. This disease often leads to chronic disability. More recently, activation of synovial fibroblasts (SFs) has been linked to innate immune responses and several cellular signalingpathways that ultimately result in the aggressive and invasive stages of RA. SFs are the major sources of pro-inflammatory cytokines in RA synovium. They participate in maintaining the inflammatory state that leads to synovial hyperplasia and angiogenesis in the inflamed synovium. The altered apoptotic response of synovial and inflammatory cells has been connected to these alterations of inflamed synovium. RA synovial fibroblasts (RASFs) have the ability to inhibit several apoptotic proteins that cause their abnormal proliferation. This proliferation leads to synovial hyperplasia. Apoptotic pathway proteins have thus been identified as possible targets for modifying the pathophysiology of RA. This review summarizes current knowledge of SF activation and its roles in the inhibition of apoptosis in the synovium, which is involved in joint damage during the effector phase of RA development.Copyright © 2022 Biomedpress.

Effect of miRNAs, Proinflammatory Cytokines and ACE2 in COVID-19 Pathophysiology

Background: Angiotensin-converting enzyme 2 (ACE2) is the main cellular receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and acts as a pro-inflammatory mediator of Coronavirus disease (COVID-19). The clinical outcome of SARS-CoV-2 infection is influenced by the pro-inflammatory mediators. The specific microRNAs (miRNAs) influence the ACE2 expression and are accountable for the increased circulatory pro-inflammatory mediator levels. Thus, host factors play a crucial role in COVID-19 pathophysiology. The pathogenesis of COVID-19 disease is not well understood. Hence we comprehended the role of miRNAs, pro-inflammatory cytokines, and ACE2 genes in COVID-19 pathophysiology. Method(s): We utilized multiple databases, specifically EMBASE, PubMed (Medline), and Google Scholar, for our search. Discussion(s): SARS-CoV-2 genes could be the target of host miRNAs. The miRNAs regulate the expression of ACE2 in various organs, including the kidney, heart, blood vessels, and lung. ACE2 acts as a pro-inflammatory mediator of SARS-CoV-2 associated disease. Pro-inflammatory cytokines (IL-6, IL-1beta, and TNF) have been associated with severe COVID-19 disease. Hence variation in expression of miRNAs would influence the regulation of COVID-19 pathophysiology. The clinical outcomes of COVID-19 are variable which could be linked with the difference in binding of host miRNA to the target genes. Conclusion(s): Correlation of these genes with severe or critical stages of patients will provide bio-markers for the severity of lung inflammation which would be useful in the rapid identification of patients in need of hospital admission. Analysis of the relationship between the miRNAs and ACE2 will be helpful in designing anti-miR therapy for ACE2-related SARS-CoV-2 infection.Copyright © 2021 Bentham Science Publishers.

Lung mesenchymal cells from patients with COVID-19 driven lung fibrosis: Several features with CTD-ILD derived cells but with higher response to fibrogenic signals and might be more pro-inflammatory.

A subset of severe COVID19 patients develop pulmonary fibrosis, but the pathophysiology of this complication is still unclear. We previously described the possibility to isolate lung mesenchymal cells (LMC) by culturing broncho-alveolar lavage (BAL) cells from patients with pulmonary fibrosis or chronic lung allograft dysfunction. Aim of this study was to investigate the possibility to isolate and characterize LMC from BAL of patients that, two months after discharge for severe COVID19, show CT signs of post-COVID19 fibrosis (Post-COVID) and in some cases has been considered transplant indication. Results were compared with those from BAL of patients with collagen tissue disease-associated interstitial fibrosis (CTD-ILD). BAL fluid levels of TGFß, VEGF, TIMP2, RANTES, IL6, IL8, and PAI1 were assessed. LMC were cultured and expanded, phenotyped by flow cytometry, and tested for osteogenic and adipogenic differentiation. Finally, we tested immunomodulatory and proliferative capabilities, collagen I production + /- TGF-beta stimulation. BAL cytokine and growth factor levels were comparable in the two groups. Efficiency of isolation from BAL was 100% in post-COVID compared to 63% in CTD-ILD. LMC from post-COVID were positive for CD105, CD73, CD90, and negative for CD45, CD34, CD19 and HLA-DR as in CTD-ILD samples. Post-COVID LMC displayed higher collagen production with respect to CTD-ILD LMC. Immunomodulatory capacity towards lymphocytes was very low, while Post-COVID LMC significantly upregulated pro-inflammatory cytokine production by healthy PBMCs. Our preliminary data suggest that LMC from post-COVID19 fibrosis patients share several features with CTD-ILD ones but might have a higher response to fibrogenic signals and pro-inflammatory profile.

Resistin, a Multipotential Therapeutic Target

Being overweight and obese are risk factors that have increased during the COVID-19 pandemic;these factors increase the white adipose tissue (WAT) that increases the release of adipokines (adiponectin, leptin, and resistin). So, obesity provokes the expansion of adipose tissue;it induces changes in their macrophages of pro-inflammatory cytokines (M2 to M1). These changes increase the resistin levels with effects on the metabolism, inflammation process, glucose homeostasis, and insulin resistance, promote cell proliferation and migration, and even serve as a biomarker for tumorigenesis. Therefore, resistin is proposed as a multipotential therapeutic target to treat different diseases, between chronic-degenerative and some types of cancer, because resistin has characteristics that give it a high probability to be a therapeutic target to attend to and prevent various diseases. In different ways, developing new drugs by molecular docking to use molecules with pharmacological characteristics capable of interacting in the regions of resistin to hinder/block the interaction between resistin and their receptors (Δ-DCN, TLR4, and CAP-1) and by promoting health to reduce overweight and obesity, and this could generate lower plasma serum resistin values, so this review remarks the potential of resistin as multipotential therapeutic target. © 2022 by the authors.

Herbal Substances with Antiviral Effects: Features and Prospects for the Treatment of Viral Diseases with Emphasis on Pro-Inflammatory Cytokines.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the coronavirus family and could induce the viral disease named coronavirus disease 2019 (COVID-19). The disease became a pandemic after the reported first case in December 2019. In this review, we highlighted the herbal substances with antiviral effects. To examine peer-review publications dealing with the features and prospects for COVID-19 treatment with an emphasis on pro-inflammatory cytokines, we conducted electronic and full-text searches of Science Direct, CABI Direct, Web of Science, PubMed, and Scopus databases. Cytokine storm mechanisms are factors that induce a pro-inflammatory response, including the expression of cytokines and chemokines. The subsequent leukocyte recruitment and antiviral effect or functions contribute to the first line of defense against viruses. There have been numerous investigations with herbal medicine candidates used as immunomodulators or antivirals. However, cytokine-storm-targeted therapy was recommended to SARS-CoV patients with acute respiratory distress syndrome leading to severe pulmonary failure. These reviews showed that herbal formulations as alternative medicine might significantly reduce complicated viral infections and hold promising specific antiviral on experimental animal models.

Study of D-Dimer and Serum Ferritin Levels as Prognostic Biomarkers in Covid-19 Patients

Objective: Coronavirus disease 2019 (COVID-19) is primarily a respiratory illness causing thrombotic disorders. Pro-inflammatory cytokines are one of the responsible causes of cytokine storm syndrome in patients with COVID-19. Coagulopathy and inflammation are associated with COVID-19 severity. The coronavirus spike protein facilitates the entry of the virus into the target cells causing coagulopathy and inflammation.Other infections include direct viral toxicity, endothelial cell damage, inflammation, and deregulation of the immune response and renin-angiotensinaldosterone system. The study aims to estimate levels of D-Dimer and Serum Ferritin in symptomatic and asymptomatic COVID-19 patients and its comparison with healthy controls. Method(s): The study includes 30 healthy control and 30 symptomatic and 30 asymptomatic COVID-19 patients of both sexes. Analysis of serum ferritin was done on a fully automated immunology analyzer-SIEMENS based on the principle of chemiluminescence. D-dimer was estimated on mLab which is cartridge-based. Result(s): We observed that the levels of D-Dimer and Serum Ferritin significantly increased in symptomatic COVID-19 patients as compared to asymptomatic COVID-19 positive patients and healthy non-COVID-19 controls. Conclusion(s): The elevated serum ferritin and D-dimer were associated with a poor outcome and poor prognosis and could predict the worsening of COVID-19 patients. The significant increase showed that D-Dimer and serum ferritin accurately predicts patients developing severe COVID- infection. Copyright © 2022 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Nitazoxanide and COVID-19: A review.

Coronavirus disease 2019 (COVID-19) is a current global illness triggered by severe acute respiratory coronavirus 2 (SARS-CoV-2) leading to acute viral pneumonia, acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and cytokine storm in severe cases. In the COVID-19 era, different unexpected old drugs are repurposed to find out effective and cheap therapies against SARS-CoV-2. One of these elected drugs is nitazoxanide (NTZ) which is an anti-parasitic drug with potent antiviral activity. It is effectively used in the treatment of protozoa and various types of helminths in addition to various viral infections. Thus, we aimed to elucidate the probable effect of NTZ on SARS-CoV-2 infections. Findings of the present study illustrated that NTZ can reduce SARS-CoV-2-induced inflammatory reactions through activation of interferon (IFN), restoration of innate immunity, inhibition of the release of pro-inflammatory cytokines, suppression of the mammalian target of rapamycin (mTOR), and induction of autophagic cell death. Moreover, it can inhibit the induction of oxidative stress which causes cytokine storm and is associated with ALI, ARDS, and multi-organ damage (MOD). This study concluded that NTZ has important anti-inflammatory and immunological properties that may mitigate SARS-CoV-2 infection-induced inflammatory disorders. Despite broad-spectrum antiviral properties of NTZ, the direct anti-SARS-CoV-2 effect was not evident and documented in recent studies. Then, in silico and in vitro studies in addition to clinical trials and prospective studies are needed to confirm the beneficial impact of NTZ on the pathogenesis of SARS-CoV-2 infection.

Resistin, a Multipotential Therapeutic Target

Being overweight and obese are risk factors that have increased during the COVID-19 pandemic;these factors increase the white adipose tissue (WAT) that increases the release of adipokines (adiponectin, leptin, and resistin). So, obesity provokes the expansion of adipose tissue;it induces changes in their macrophages of pro-inflammatory cytokines (M2 to M1). These changes increase the resistin levels with effects on the metabolism, inflammation process, glucose homeostasis, and insulin resistance, promote cell proliferation and migration, and even serve as a biomarker for tumorigenesis. Therefore, resistin is proposed as a multipotential therapeutic target to treat different diseases, between chronic-degenerative and some types of cancer, because resistin has characteristics that give it a high probability to be a therapeutic target to attend to and prevent various diseases. In different ways, developing new drugs by molecular docking to use molecules with pharmacological characteristics capable of interacting in the regions of resistin to hinder/block the interaction between resistin and their receptors (Δ-DCN, TLR4, and CAP-1) and by promoting health to reduce overweight and obesity, and this could generate lower plasma serum resistin values, so this review remarks the potential of resistin as multipotential therapeutic target. © 2022 by the authors.

Adult-Onset Still's Disease-A Complex Disease, a Challenging Treatment.

Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder with an unknown cause characterized by high-spiking fever, lymphadenopathy, hepatosplenomegaly, hyperferritinemia, and leukocytosis. The clinical course can be divided into three significant patterns, each with a different prognosis: Self-limited or monophasic, intermittent or polycyclic systemic, and chronic articular. Two criteria sets have been validated. The Yamaguchi criteria are the most generally used, although the Fautrel criteria offer the benefit of adding ferritin and glycosylated ferritin values. AOSD's pathogenesis is not yet completely understood. Chemokines and pro-inflammatory cytokines, including interferon (IFN)-γ, tumor necrosis factor α (TNFα), interleukin (IL)-1, IL-6, IL-8, and IL-18, play a crucial role in the progression of illness, resulting in the development of innovative targeted therapeutics. There are no treatment guidelines for AOSD due to its rarity, absence of controlled research, and lack of a standard definition for remission and therapy objectives. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids (CS), and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are used in AOSD treatment. Biological therapy, including IL-1, IL-6, IL-18, and IL-17 inhibitors, as well as TNFα or Janus-kinases (JAKs) inhibitors, is administered to patients who do not react to CS and csDMARDs or achieve an inadequate response.

Inhibition of Pseudomonas aeruginosa LPS-Induced airway inflammation by RIPK3 in human airway.

Although the physiological function of receptor-interacting protein kinase (RIPK) 3 has emerged as a critical mediator of programmed necrosis/necroptosis, the intracellular role it plays as an attenuator in human lungs and human bronchial epithelia remains unclear. Here, we show that the expression of RIPK3 dramatically decreased in the inflamed tissues of human lungs, and moved from the nucleus to the cytoplasm. The overexpression of RIPK3 dramatically increased F-actin formation and decreased the expression of genes for pro-inflammatory cytokines (IL-6 and IL-1ß), but not siRNA-RIPK3. Interestingly, whereas RIPK3 was bound to histone 1b without LPS stimulation, the interaction between them was disrupted after 15 min of LPS treatment. Histone methylation could not maintain the binding of RIPK3 and activated movement towards the cytoplasm. In the cytoplasm, overexpressed RIPK3 continuously attenuated pro-inflammatory cytokine gene expression by inhibiting NF-κB activation, preventing the progression of inflammation during Pseudomonas aeruginosa infection. Our data indicated that RIPK3 is critical for the regulation of the LPS-induced inflammatory microenvironment. Therefore, we suggest that RIPK3 is a potential therapeutic candidate for bacterial infection-induced pulmonary inflammation.