Notes

Curiosity aids: Growth in need for knowledge bidirectionally forecasts long term lowering of anxiety and depression signs and symptoms throughout Decade.
Paeoniflorin also inhibited mRNA and protein expression of MDP-NOD2 pathway components and decreased the levels of related inflammatory cytokines. In vitro experiments showed that MDP strongly stimulated RAW264.7 cells to secrete tumor necrosis factor α (TNF-α), and induced translocation of nuclear factor-kappa B (NF-κB p65) from the cytoplasm to nucleus using immunofluorescence co-localization experiments. Overall, the results indicated that Gram-positive bacteria promote the occurrence of colitis via up-regulation of MDP-NOD2 pathway, and paeoniflorin is able to decrease the infiltration of Gram-positive bacteria in intestine and inhibit Gram-positive bacteria-dependent MDP-NOD2 pathway to alleviate mice colitis.The disease caused by viral pneumonia called severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) declared by the World Health Organization is a global pandemic that the world has witnessed since the last Ebola epidemic, SARS and MERS viruses. Many chemical compounds with antiviral activity are currently undergoing clinical investigation in order to find treatments for SARS-CoV-2 infected patients. On-going drug-drug interaction examinations on new, existing, and repurposed antiviral drugs are yet to provide adequate safety, toxicological, and effective monitoring protocols. This review presents an overview of direct and indirect antiviral drugs, antibiotics, and immune-stimulants used in the management of SARS-CoV-2. It also seeks to outline the recent development of drugs with anti-coronavirus effects; their mono and combination therapy in managing the disease vis-à-vis their biological sources and chemistry. Co-administration of these drugs and their interactions were discussed to provide significant insight into how adequate monitoring of patients towards effective health management could be achieved.Since the very beginning of the COVID-19 pandemic, different treatment strategies have been explored. These mainly involve the development of antimicrobial, antiviral, and/or anti-inflammatory agents as well as vaccine production. However, other potential options should be more avidly investigated since vaccine production on a worldwide level, and the anti-vaccination movement, also known as anti-vax or vaccine hesitancy by many communities, are still real obstacles without a ready solution. This review presents recent findings on the potential therapeutic advantages of heterologous serotherapy for the treatment of COVID-19. We present not only the effective use in animal models of hyperimmune sera against this coronavirus but also strategies, and protocols for the production of anti-SARS-CoV-2 sera. Promising antigens are also indicated such as the receptor-binding domain (RBD) in SARS-CoV-2 S protein, which is already in phase 2/3 clinical trial, and the trimeric protein S, which was shown to be up to 150 times more potent than the serum from convalescent donors. Due to the high death rate, the treatment for those currently infected with coronavirus cannot be ignored. Therefore, the potential use of anti-SARS-CoV-2 hyperimmune sera should be carefully but urgently evaluated in phase 2/3 clinical studies.COVID-19 caused by the SARS-CoV-2 virus, accompanies an unprecedented spike in cytokines levels termed cytokines release syndrome (CRS), in critically ill patients. Clinicians claim that the surge demonstrates a deregulated immune defence in host, as infected cell expression analysis depicts a delay in type-I (interferon-I) and type-III IFNs expression, along with a limited Interferon-Stimulated Gene (ISG) response, which later resume and culminates in elicitation of several cytokines including- IL-6, IL-8, IL-12, TNFα, IL-17, MCP-1, IP-10 and IL-10 etc. Although cytokines are messenger molecules of the immune system, but their increased concentration results in inflammation, infiltration of macrophages, neutrophils and lung injury in patients. This inflammatory response results in the precarious pathogenesis of COVID-19; thus, a complete estimation of the immune response against SARS-CoV-2 is vital in designing a harmless and effective vaccine. In pathogenesis analysis, it emerges that a timely forceful type-I IFN production (18-24hrs post infection) promotes innate and acquired immune responses, while a delay in IFNs production (3-4 days post infection) actually renders both innate and acquired responses ineffective in fighting infection. Further, underlying conditions including hypertension, obesity, cardio-vascular disease etc may increase the chances of putting people in risk groups, which end up having critical form of infection. This review summarizes the events starting from viral entry, its struggle with the immune system and failure of host immunological parameters to obliterate the infections, which finally culminate into massive release of CRS and inflammation in gravely ill patients.
Extracellular vesicles (EVs) are vital mediators of transferring microRNAs (miRNAs). We focused on effect of miR-185-3p that mediated by macrophages-derived EVs on atherosclerosis (AS) by targeting small mothers against decapentaplegic 7 (Smad7).

EVs were extracted from M1 macrophages and identified. ApoE
mice were treated with EVs, EVs containing miR-185-3p inhibitor or mimic, then the pathological changes of mouse aorta were observed. The levels of blood lipid, cell adhesion molecules, oxidative stress factors, inflammatory factors, and proliferation and apoptosis of vascular endothelial cells were assessed. Expression of miR-185-3p and Smad7 was detected and the targeting relationship between miR-185-3p and Smad7 was validated.

MiR-185-3p was upregulated while Smad7 was downregulated in atherosclerotic mouse aorta. M1 macrophages-derived EVs elevated miR-185-3p to promote development of AS pathology and levels of blood lipid, endothelial cellular adhesion, oxidative stress factors and inflammatory factors, suppressed cell proliferation and promoted cell apoptosis of vascular endothelial cells in atherosclerotic mice through downregulating Smad7. Smad7 was a target gene of miR-185-3p and miR-185-3p could inhibit expression of Smad7.

M1 macrophages-derived EVs and upregulated miR-185-3p aggravated the development of AS in ApoE
mice by negatively regulating Smad7. This research may further the understanding of AS mechanism.
M1 macrophages-derived EVs and upregulated miR-185-3p aggravated the development of AS in ApoE-/- mice by negatively regulating Smad7. read more This research may further the understanding of AS mechanism.
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