ABSTRACT
Objective To explore the potential common mechanism and active ingredients of Reduning Injection against SARS, MERS and COVID-19 through network pharmacology and molecular docking technology. Methods The TCMSP database was used to retrieve the chemical components and targets of Artemisiae Annuae Herba, Lonicerae Japonicae Flos and Gardeniae Fructus in Reduning Injection. The gene corresponding to the target was searched by UniProt database, and Cytoscape 3.8.2 was used to build a medicinal material-compound-target (gene) network. Three coronavirus-related targets were collected in the Gene Cards database with the key words of "SARS""MERS" and "COVID-19", and common target of three coronavirus infection diseases were screened out through Venny 2.1.0 database. The common targets of SARS, MERS and COVID-19 were intersected with the targets of Reduning Injection, and the common targets were selected as research targets. Protein-protein interaction (PPI) network map were constructed by Cytoscape3.8.2 software after importing the common targets into the STRING database to obtain data. R language was used to carry out GO biological function enrichment analysis and KEGG signaling pathway enrichment analysis, histograms and bubble charts were drew, and component-target-pathway network diagrams was constructed. The key compounds in the component-target-pathway network were selected for molecular docking with important target proteins, novel coronavirus (SARS-CoV-2) 3CL hydrolase, and angiotensin-converting enzyme II (ACE2). Results 31 active compounds and 207 corresponding targets were obtained from Reduning Injection. 2 453 SARS-related targets, 805 MERS-related targets, 2 571 COVID-19-related targets, and 786 targets for the three diseases. 11 common targets with Reduning Injection: HSPA5, CRP, MAPK1, HMOX1, TGFB1, HSP90AA1, TP53, DPP4, CXCL10, PLAT, PRKACA. GO function enrichment analysis revealed 995 biological processes (BP), 71 molecular functions (MF), and 31 cellular components (CC). KEGG pathway enrichment analysis screened 99 signal pathways (P < 0.05), mainly related to prostate cancer, fluid shear stress and atherosclerosis, hepatocellular carcinoma, proteoglycans in cancer, lipid and atherosclerosis, human T-cell leukemia virus 1 infection, MAPK signaling pathway, etc. The molecular docking results showed that the three core active flavonoids of quercetin, luteolin, and kaempferol in Reduning Injection had good affinity with key targets MAPK1, PRKACA, and HSP90AA1, and the combination of the three active compounds with SARS-CoV-2 3CL hydrolase and ACE2 was less than the recommended chemical drugs. Conclusion Reduning Injection has potential common effects on the three diseases of SARS, MERS and COVID-19. This effect may be related to those active compounds such as quercetin, luteolin, and kaempferol acting on targets such as MAPK1, PRKACA, HSP90AA1 to regulate multiple signal pathways and exert anti-virus, suppression of inflammatory storm, and regulation of immune function.Copyright © 2022 Drug Evaluation Research. All rights reserved.
ABSTRACT
Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (COVID-19) pandemic. It is the final outcome of the acute respiratory distress syndrome (ARDS), characterized by an initial exacerbated inflammatory response and ultimate tissue scarring. Energy balance may be crucial for the recovery of clinical COVID-19. Hence, we asked if two key pathways involved in energy generation, AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling and fatty acid oxidation (FAO) could be beneficial. We tested the drugs Metformin (AMPk activator) and Baicalin (Cpt1A activator) in different experimental models mimicking COVID-19 associated inflammation in lung and kidney. We also studied two different cohorts of COVID19 patients that had been previously treated with Metformin. These drugs ameliorated lung damage in an ARDS animal model, while activation of AMPK/ACC signaling increased mitochondrial function and decreased TGF-beta-induced fibrosis, apoptosis and inflammation markers in lung epithelial cells. Similar results were observed with two new indole derivatives IND6 and IND8 with AMPK activating capacity. Consistently, a reduced stay in the intensive care unit was observed in COVID-19 patients previously exposed to Metformin. Baicalin also reduced kidney fibrosis in two animal models of kidney injury, another key target of COVID-19, while in vitro both drugs improved mitochondrial function and prevented TGF-beta-induced renal epithelial cell dedifferentiation. Our results support that strategies based on energy supply may prove useful in the prevention of COVID-19-induced lung and renal damage.Copyright © 2023
ABSTRACT
Background: Although our understanding of immunopathology in the risk and severity of COVID-19 disease is evolving, a detail of immune response in long-term consequences of COVID-19 infection remains unclear. Recently, few studies have detailed the immune and cytokine profiles associated with PASC. However, dysregulation of immune system driving pulmonary PASC is still largely unknown. Method(s): To characterize the immunological features of PPASC, we performed droplet-based scRNA-sequencing using 10X genomics to study the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from participants naive to SARS-CoV-2 (NP, n=2) and infected with SARS-CoV-2 with chronic pulmonary symptoms (PPASC, n=2). Result(s): Analysis of more than 34,000 PBMCs by integrating our dataset with previously reported control datasets generated cell distribution and identified 11 immune cell types based on canonical gene expression. The proportion of myeloid-lineage cells (CD14+monocyte, CD16+monocyte, and dendritic cells) and platelets were increased in PPASC compared with those of NP. Specifically, PPASC displayed up-regulation of VEGFA and transcription factors, such as ATF2, ELK, and SMAD in myeloid-lineage cells. Also, TGF-beta and WNT signaling pathways were up-regulated in these cell population. Cell-cell interaction analysis identified that myeloid-lineage cells in PPASC participated in regulation of fibrosis and immune response, such as VEGFA (increased) and MIF (decreased) interactions. Conclusion(s): Together, this study provides high-resolution insights into immune landscape in PPASC. Our results emphasize differences in myeloid lineage-mediated fibrosis and immunity between PPASC and NP, suggesting they could act as potential pathological drivers of PPASC. (Figure Presented).
ABSTRACT
Background: The CoV-2 envelope (E) protein plays an important role in virus assembly, budding, immunopathogenesis and disease severity. E protein has ion channel activity, is located in Golgi and ER membranes of infected cells and is associated with inflammasome activation and immune dysregulation. Here we report that BIT225, an investigational HIV clinical compound, inhibits E ion channel activity and prevents body weight loss and mortality and reduces inflammation in lethally infected K18-hACE2 transgenic mice. BIT225 efficacy was observed when dosing was initiated before or 24 h or 48 h after infection. Method(s): SARS-CoV-2 E protein ion channel activity and Xenopus TMEM16A were measured in Xenopus oocytes. K18-hACE2 transgenic mice were infected intranasally with 104 pfu SARS CoV 2 (US-WA1/2020) and dosed orally twice daily with BIT225 for up to 12 Days. Dosing was initiated 12 h pre-infection or 24 h or 48 h post-infection. Disease parameters measured were survival, body weight, viral RNA by qPCR and infectious virus titre (plaque assay) in lung tissue homogenates and serum. In addition, levels of pro-inflammatory cytokines (IL-6, IL-1alpha, IL-1beta, TNFalpha & TGFbeta, MCP-1) were measured in lung and serum samples. Result(s): BIT225 inhibited ion channel activity of E-protein, but not that of TMEM16A in Xenopus oocytes. BIT225 dosed at 300mg/kg BID for 12 days starting 12 h pre-infection completely prevented body weight loss and mortality in SARS-CoV-2 infected K18 mice (n=12), while all vehicle-dosed animals reached a mortality endpoint by day 9 across two studies (n=12). Figure 1 shows results from a time of addition study: When treatment with BIT225 started at 24 h post-infection, body weight loss and mortality was also prevented (100% survival, n=5). In the group of mice where treatment started at 48 h after infection, body weight loss and mortality were prevented in 4 of 5 mice. Treatment efficacy was associated with significant reduction in lung viral load (3.5 log10), virus titer (4000 pfu/ml) and lung and serum cytokine levels. Conclusion(s): BIT225 is an inhibitor of SARS-CoV-2 E-protein viroporin activity. In the K18 model BIT225 protected mice from weight loss and death, inhibited virus replication and reduced inflammation. These effects were noted when treatment with BIT225 was initiated before or 24-48 hours after infection and validate viroporin E as a viable antiviral target and support the clinical study of BIT225 in treatment of SARS-CoV-2.
ABSTRACT
Background: HIV is a risk factor for severe acute COVID-19, but it is unknown whether HIV is a risk factor for long COVID. Method(s): We conducted a prospective observational cohort study of US adults with HIV (PWH) and HIV-seronegative adults with first SARS-CoV-2 infection within 4 weeks together with people who never had COVID-19. At enrollment, participants recalled the presence and severity of 49 long COVID-associated symptoms in the month prior to COVID-19. The same symptom survey was administered at 1, 2, 4, and 6 months post-COVID or post-enrollment for never- COVID participants. Post-COVID participants donated blood 1 and 4 months post-COVID, and never-COVID participants donated blood 0-1 times. Antibody titers to 18 coronavirus antigens and levels of 30 cytokines and hormones were quantified (Meso Scale Discovery). The Mann Whitney U test was used to compare continuous variables between groups, and Pearson's chi-squared test for categorical variables. Spearman correlation analyses were used to build networks of associations between cytokines and symptoms. Result(s): 341 participants enrolled between June 2021 and September 2022. Of these, 73 were PWH post-COVID, 121 were HIV-seronegative post-COVID, 78 were PWH never-COVID, and 69 were HIV-seronegative never-COVID. Over 85% of participants were vaccinated prior to COVID-19. Most participants with HIV were male sex at birth (83% post-COVID, 59% never-COVID), on ART ( >95%), with median CD4 counts >500. Over 60% of participants reported 1+ new or worsened symptoms 2-6 months post-COVID, with higher percentages in PWH at 2 months post-COVID (p< 0.05). PWH were more likely to report body ache, pain, confusion, memory problems, and thirst and had higher levels of creatine phosphokinase post-COVID than HIV-seronegative people. SARS-CoV-2 and non-SARS human coronavirus antibody titers did not differ between PWH and HIV-seronegative post-COVID participants. Cytokine associations with each other (network density) were significantly enriched at 1 month post-COVID in both PWH and HIV-seronegative people, with significantly less enrichment at 4 months post-COVID and in never- COVID participants. Levels of four analytes (cortisol, C5a, TGF-beta1, and TIM-3) associated with specific symptoms of long COVID. Conclusion(s): PWH may experience more symptoms post-COVID with a slightly different symptom profile than people without HIV. Inflammatory networks were active in PWH and people without HIV at 1 month post-COVID.
ABSTRACT
Atrial fibrillation (AF) is the most frequent form of cardiac arrhythmia in COVID-19 infected patients. The occurrence of AF paroxysms is often associated with the acute period of infection in time. At the same time, the pathophysiological mechanisms of the occurrence of AF associated with COVID-19 remain insufficiently studied. The review considers the available literature data on the influence of factors such as reduced availability of angiotensin-converting enzyme 2 receptors, interaction of the virus with the cluster of differentiation 147 and sialic acid, increased inflammatory signaling, "cytokine storm", direct viral damage to the endothelium, electrolyte and acid-alkaline balance in the acute phase of severe illness and increased sympathetic activity.Copyright © Autors 2023.
ABSTRACT
Background: Infections with SARS-CoV- 2 cause the coronavirus disease 2019 (COVID-19) pandemic. Alterations in immune cells of COVID-19 patients may predict the subsequent severity of disease. The changes in composition of immune cells in COVID-19 patients include lymphopenia, lower neutrophil to lymphocyte-ratios and an eosinopenia in about 50 to 80% of hospitalized patients. Eosinophils and neutrophils can interact with T cells via immune checkpoints receptors such as programmed death (PD)-1 on T cells and its counterpart PD-ligand 1 (PD-L1) on eosinophils or neutrophils. There are only limited studies on PD-1 and PD-L1 expressions in viral infections, we aimed to elucidate the interplay of T cells and other peripheral cells by analysing the immune checkpoints PD-1 and PD-L1 in expression during COVID-19. Method(s): Using flow cytometry, we have now analysed the immune checkpoint receptor expressions on whole blood cells from a total of 38 COVID-19 patients. The patient cohort comprises all ages and both sexes with the disease severity ranging from mild, moderate to severe, with ~10% mortality. We have further been investigating 21 biomarkers (G-CSF, GM-CSF, IFN-gamma, TGF-beta1, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-17A, IL-18, IL-23, IL-33, IP-10, MCP-1, MIP-1beta, TNF-alpha, and YKL-40) in plasma on a cohort of 76 COVID-19 patients using the MesoScale Multiplex Assay platform, with 48 healthy controls. Result(s): PD-L1 expression on eosinophils was significantly lower in COVID-19 patients in initial stages of infection, relative to healthy controls. There was an inverse relationship between disease progression and the expression of PD-1 on CD8+ T cells. These data suggests that analysis of PD-L1- PD1 cell networks in immune cells of EDTA blood of COVID-19 patients can predict disease outcomes. While most detectable biomarkers are strongly increased in COVID samples overall compared to healthy controls, the more severe the disease the higher the blood biomarker concentration. Conclusion(s): Taken together, the analysis of PD-L1- PD1 cell networks in immune cells together with plasma biomarkers of COVID-19 patients can predict disease outcomes.
ABSTRACT
Introduction: Generating adequate cellular and humoral responses are essential principle of vaccination. Immune system of renal transplant recipient remained compromised and speculated to less likely to develop antibody after vaccination. SARS-CoV-2 neutralizing antibody after anti-SARS-CoV-2 vaccination is required for the protection from subsequent viral infection. During COVID-19 disease, anti-SARS-CoV-2 specific antibody formation was correlated with the inflammatory cytokines level. Although, there is limited informations about serum cytokines and antibody formation after COVAXINTM, COVISHIELDTM vaccination in RTRs. Therefore, in the current study, we have evaluated the inflammatory cytokines response and anti-SARS-CoV-2 specific antibody formation in renal transplant recipient. Method(s): In this study, we have recruited 171 live-related renal transplant recipients vaccinated with two doses of either COVAXINTM (whole inactivated virus-based vaccine) or COVISHIELDTM (Simian adenovirus containing full-length spike protein-based vaccine). A 5 ml blood sample was collected after two weeks of 2nd dose of vaccination. The serum was separated and stored at -200C till the analysis. Anti-SARS-CoV-2 spike protein-specific IgG antibody titer was determined by chemiluminescent microparticle immunoassay methods and Cytokines IL-10, TGF-beta, IFN-gamma, IL-6 were measured by the ELISA techniques. Result(s): The overall anti-SARS-CoV-2 spike protein specific seroconversion after vaccination was observed in 149/171(87.13%) of RTRs with median IgG titer in seroconversion group 1191.90 (IQR, 398.70-2652.45) au/ml. The median and interquartile serum cytokines IL-10 level in seroconversion (n=149) vs non-seroconversion (n=22) group was 88.89 (IQR, 55.5-125.92) vs 92.59 (IQR, 48.14-148.14) pg/ml. The median TGF-beta level in seroconversion vs non-seroconversion group was 692.10 (IQR, 446.05-927.63) vs 1001.31 (IQR, 813.15-1125.65) pg/ml. The median IL-6 level in seroconversion vs non-seroconversion group was 46.66 (33.3-66.66) vs 28.33 (16.66-34.16) pg/ml. The median IFN-gamma level in seroconversion vs non-seroconversion group was 98.0 (IQR, 57.40-111.60) vs 50.0 (IQR, 30.55-52.55) pg/ml. The cytokines IL-6 and IFN-gamma level was positively correlated with anti-SARS-CoV-2 specific protein antibody titer (r=0.192;p=0.012), IFN-gamma (r=0.188;p=0.014). TGF-beta and IL-10 were negatively correlated with anti-SARS-CoV-2 specific protein antibody titer. For IL-10 (r=-0.065;p=0.39), for TGF-beta (r=-0.246;p=0.002). Further IFN-gamma was negatively correlated with TGF-beta (r=-0.268;p<0.001). Conclusion(s): Higher pro-inflammatory cytokines (IL-6, IFN-gamma) levels were associated with anti-SARS-CoV-2 spike protein-specific seroconversion, whereas higher anti-inflammatory cytokines IL-10 and TGF-beta were negatively associated with seroconversion after vaccination in renal transplant recipients. No conflict of interestCopyright © 2023
ABSTRACT
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.
ABSTRACT
Patients with severe COVID-19-associated pneumonia are at risk to develop pulmonary fibrosis. To study the underlying mechanisms, we aim to develop advanced cell culture models that reliably reflect COVID-19-related profibrotic microenvironment. To identify key cellular players, we performed pilot immunohistochemistry analysis on lung tissue from COVID-19 patients with fibrosis collected during autopsy. Results revealed diffuse alveolar damage with macrophage infiltration, and myofibroblast accumulation with enriched collagen deposition surrounding the damaged alveoli. To mimic SARS-CoV-2 infection in alveoli, we infected human primary type II alveolar epithelial cells (AEC2) and found enhanced signaling of profibrotic cytokine transforming growth factor beta (TGFbeta) in some donors. To recreate the early fibrotic niche, an alveolar-macrophage-fibroblast (AMF) tri-culture model was established. After infecting AEC2 with SARS-CoV-2 in this AMF model, gene expression analysis provided evidence for fibroblast-to-myofibroblast transition. Furthermore, we found that overexpression of SARS-CoV-2 papain-like protease (PLpro) can promote TGFbeta signaling in HEK293T and A549 cells. After infecting AEC2 with SARS-CoV-2 PLpro lentivirus in the AMF model, we found signs of epithelial-to-mesenchymal transition and fibroblast-to myofibroblast transition. In future studies, we will use a detailed analysis of COVID-19-associated lung fibrosis with other types of lung fibrosis, to further refine COVID-19-related fibrosis models, including lung-on-chip models.
ABSTRACT
Introduction: Renal fibrosis is a main outcome of acute kidney injury in COVID-19 survivors, which is emerging as a global public health concern. Lung damage in the COVID-19 patients leads to acute and chronic hypoxia, which results in inflammation, epithelial-mesenchymal transformation, and fibrosis in kidney. Quercetin is an abundant flavonoid in plant materials. Previous studies indicate that quercetin alleviates the decline of renal function, suppress epithelial to mesenchymal transformation in renal tubules, and reduce fibrosis. The study aimed to explore potential targets of quercetin on treating renal fibrosis in patients with COVID-19-induced hoxpia. Method(s): Gene/protein targets related to COVID-19, renal fibrosis, or quercetin were searched from ten databases, and Cytoscape 3.8.2 was then used to construct the protein-protein interaction network and to identify the core targets. The Metascape platform was used for bioconcentration analysis, while AutoDock Vina was used as the primary molecular docking tool. In vitro, the combination model of hypoxia- and transforming growth factor-beta (TGF-beta)- treated human proximal tubule epithelial cells (HK2 cells) was applied to determine the reno-protective effect of quercetin. Result(s): The network analysis showed that quercetin targeted on TGF-beta pathway in treating COVID-19 induced renal fibrosis. In the intersection PPI network, 115 targets were obtained, and gene enrichment analysis was conducted on 109 key nodes. Molecular docking analysis revealed that quercetin could spontaneously bind to eight targets on the TGF-beta pathway, and the binding energy of TGF-beta1 was 29.82 kJ/mol. The in vitro experiment further showed that quercetin significantly suppressed fibrosis in TGF-beta and hypoxia treated HK2 cells in a dose dependent manner by inhibiting TGF-beta/Smad3 pathway. Conclusion(s): Quercetin could attenuate renal fibrosis in patients with COVID-19 by suppressing TGF-beta/Smad3 pathway. No conflict of interestCopyright © 2023
ABSTRACT
Increasing number of severe COVID 19 patients develop pulmonary Fibrosis, but the management of this complication is still unclear due to a lack of clinical trials. Aim of this study was to characterize mesenchymal cells (MC) isolated from 10 broncho-alveolar lavage (BAL, at 2 months after discharge) from patients with COVID19 fibrosis (COVID19-f) and to compare them with those isolated from 8 patients with collagen tissue diseaseassociated interstitial fibrosis(CTD-ILD). BAL fluid (BALf) levels of TGFbeta, VEGF, TIMP2, RANTES, IL6, IL8, and PAI1 were assessed by ELISA. Primary MC foci were cultured and expanded in D-MEM +10% FBS, characterized by flow cytometry and osteogenic and adipogenic differentiation. Collagen 1 production (+/-TGF-beta) was tested by WB and mRNA expression. BALf cytokine and GF levels were comparable in the two groups. Efficiency of MC isolation from BAL was 100% in COVID-f compared to 65% in CTD-ILD. MC antigen surface expression of CD105, CD73, CD90 (>90%, respectively), CD45, CD34, CD19 and HLA-DR (<5%, respectively) was comparable. None of MC samples differentiated in adipocytes, while COVID19-f were positive for calcium deposition. COVID19-f MC showed at WB, higher Collagen 1 production with respect to CTD-ILD with TGF-beta stimulation. Our preliminary data suggest MC from COVID19-f share several features with CTD-ILD but might have a higher response to fibrogenic and differentiation signals.
ABSTRACT
Introduction: Retroperitoneal fibrosis (RPF) is a rare disease which can be primary (idiopathic) or secondary to drugs, tumors or infections. We are reporting the first case of RPF causing renal atrophy, renal artery stenosis and renovascular hypertension associated with SARS-CoV2. Method(s): A 37-year-old female nurse presented to her PCP with a new-onset of hypertension. She had recovered from severe SARS-CoV2 infection merely two months ago. Physical examination was remarkable for BP 170/110 mmHg, HR 88 beats/min, BMI of 31 alongside trace pitting edema. Initial lab data showed her creatinine to be 1.1mg/dl and ultrasound of her kidneys showed an atrophied right kidney with a size of 7.8 cm while the left kidney was 11.6 cm. An ultrasound KUB of that same time showed that the size of the right kidney was 10.4 cm and left 11.5 with normal renal parenchyma. She was started on amlodipine 10 mg and valsartan 160 mg per day. Two weeks later she was referred to a nephrologist when her creatinine was increased to 3.1 mg/dl. Renovascular hypertension secondary to right renal artery stenosis or thrombus was suspected. Autoimmune & hypercoagulable work up was negative. CT angiogram showed an ill-defined, poorly enhancing retroperitoneal soft tissue thickening draping the mid abdominal aorta, the origin of SMA, and bilateral renal arteries which terminated above the aortoiliac bifurcation. This, RPF, involved segment of 8.6 cm of the mid and lower abdominal aorta, causing moderate narrowing of proximal SMA, short segment narrowing of proximal left main and accessory renal artery, and diffuse long segmental narrowing of the right main renal artery. RPF encasement of right renal artery lead to poor right renal nephrogram and atrophic kidney. (Figure no A: Abdominal contrast-enhanced computed tomographic (CT) scan showing the encasement of the both renal arteries by the retroperitoneal fibrosis (RPF).Figure no B : Renal angiogram showing the renal artery stenosis on right side) Acute kidney injury (AKI) was initially thought to be due to angiotensin receptor blockade in the setting of bilateral renal artery stenosis. Valsartan was swapped for metoprolol and the serum creatinine levels decreased to 1.5 mg/dl in two weeks. Prednisone was started for RPF at a dose of 60 mg per day with a slow taper over 4 months. Over the next 8 weeks, creatinine became normal and blood pressure was controlled with amlodipine 2.5 mg/day. Subsequently at 4 months her creatinine was 1.0 mg/dl and she was off all anti-hypertensive drugs. A repeat CTA after 6 months showed that there was significant reduction in RPF. Atrophic right kidney was noted without any significant interval change. RPF, renal artery stenosis, renovascular hypertension and right renal atrophy was strongly suspected to be associated with SARS-Cov2 since none of these were identified prior to her suffering from SARS-CoV2. Result(s): [Formula presented] [Formula presented] Conclusion(s): To our knowledge, this is the first case of RPF associated with SARS-CoV-2 causing renovascular hypertension and renal atrophy. Local and systemic production of IL-6, TGF- beta and Th2 cytokines has been demonstrated in idiopathic RPF and pulmonary fibrosis due to SARS-CoV2. The presumptive pathogenesis could involve SARS-Cov2 induced release of IL-6 and other cytokines which can activate B cells and fibroblasts. No conflict of interestCopyright © 2023
ABSTRACT
Patients (around 40-50%) who were infected by SARS-CoV-2 develop a condition called as long-COVID-19 that lasted longer than the infection. One of the complications of post-COVID-19 (PC) is pulmonary fibrosis. T he purpose of this study was to identify blood biomarkers to predict PC patients undergoing pulmonary fibrosis. We analysed blood samples of healthy, anti-SARS-CoV-2 vaccinated subjects and PC patients, who were stratified according to the severity of the disease and chest computed tomography (CT) scan data that revealed fibrotic or non-fibrotic areas. PC patients had higher levels of the inflammatory C reactive protein (CRP), complement complex C5b-9, LDH, but not IL-6, independently of the severity of the disease and lung fibrotic areas. Interestingly, PC patients who presented signs of lung fibrosis were characterized by higher plasma levels of IL-1alpha, CXCL-10, TGF-beta, but not of IFN-beta, compared to healthy and vaccinated (VAX) subjects. In particular, 19 out of 23 (82.6%) severe PC and 8 out of 29 (27.6%) moderate PC patients presented signs of lung fibrosis, associated to lower levels of IFN-beta but higher IL-1alpha and TGF-beta. Instead, t he levels of IFN-beta were associated to the capability of the patient to respond to the infection without signs of lung fibrosis, implying a beneficial role of this cytokine. In conclusion, we found that higher plasma levels of IL-1alpha and TGF-beta, but not of IFN-beta, could predict an increased relative risk (RR=2.8) of lung fibrosislike changes in PC patients.
ABSTRACT
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has taken over the world, and more than 38 lakh deaths had been reported till now due to this infectious disease. It has been declared a global pandemic by the world health organization. SARS-CoV-2 causes coronavirus disease of 2019 (COVID-19), and the major problem called "Cytokine storm" is reported, which may lead to death among the COVID-19 patients. This study aimed to review the Cytokine storm and its mechanism along with few immunomodulatory therapies for SARSCoV-2 infection suppression effectively. Method(s): The recently published works of literature were selected and reviewed based on the subject of this study. The databases, including Pubmed, ScienceDirect, Scopus, and Google Scholar, were searched extensively. Result(s): The review of the literature showed that an uncontrolled immune response causes excess inflammation. Evidence from recent trials has demonstrated that cytokine storms can be an important factor in the COVID-19 severity, leading to multiple organ failure and death. Conclusion(s): This study reviewed immunomodulatory therapies and strategies for SARS-CoV-2 infected patients to suppress the immune response. Ultimately, the cytokine storm can prove to be a boon and reduce the significant death tolls to SARS-CoV-2 infection.Copyright © 2022 Bentham Science Publishers.
ABSTRACT
The proceedings contain 429 papers. The topics discussed include: a short peptide encoded by long non-coding RNA small nucleolar RNA host gene 6 promotes cell migration and epithelial-mesenchymal transition by activating transforming growth factor-beta/SMAD signaling pathway in human endometrial cells;a short peptide encoded by long non-coding rna small nucleolar rna host gene 6 promotes cell migration and epithelial-mesenchymal transition by activating transforming growth factor-beta/smad signaling pathway in human endometrial cells;compatible cut-off values for luteinizing hormone and the luteinizing hormone/follicle-stimulating hormone ratio in diagnostic criteria of the Japan society of obstetrics and gynecology for polycystic ovary syndrome;intracytoplasmic sperm injection cycle success in patients under 35 years old with diminished ovarian reserve plus severe male factor;assisted reproductive technology and neonatal intensive care unit: a retrospective observational study from a single center;the value of clinical symptoms, the neutrophil-to-lymphocyte ratio, and ultrasonographic features in predicting adnexal torsion: a case-control study;construction of a diagnostic classifier for cervical intraepithelial neoplasia and cervical cancer based on xgboost feature selection and random forest model;and impact of the COVID-19 pandemic on surgery for benign diseases in gynecology: a nationwide survey by the japan society of obstetrics and gynecology.
ABSTRACT
Introduction: Findings on cells and cytokines analyses in BAL are poorly described during and after resolution of non-severe COVID-19 pneumonia, that are the objectives of this study Methods: This study included 54 pts in whom a BAL was performed (04/2020-02/2021) for the diagnosis or follow-up of suspected COVID-19 pneumonia. Cytological and cytokine analyses (IL-1b, IL-6, IL-8, IL-10, TNFa, IFNg, HGF, TGFb) were performed in BAL blinded to the classification of pts into 3 groups: non-COVID (n=20);COVID (n=13) and post-COVID pneumonia (n=24) Results: Total cell counts were not different between groups. % macrophages were similar between non-COVID and COVID groups, while % neutrophils (PN) were higher - although NS in non-COVID and % lymphocytes (Ly) higher in COVID pneumonia (p<0.024). Plasmocytes were observed in 4/13 COVID and in 1/20 of non-COVID BAL (p=0.042). Compared with COVID pneumonia, post-COVID BAL showed lower % PN, but a persistent Ly alveolitis. Alveolar Ly, in COVID/post-COVID groups were mainly of a CD3/CD4-T cell subset. TGFb was not measurable in the 3 groups. IL-10, IFNg and HGF BAL levels were higher in COVID vs non-COVID pneumonia group (p=0.0128, p=0.005, p=0.007). IL-6, IL-8, IL-10, TNFa, IFNg and HGF levels were lower in post-COVID compared to COVID BAL (all p< 0.005). In COVID pts, IL-1b and IL-6 inversely correlated with %Ly in BAL (r=-0.8, p=0.005;r=-0.7, p=0.02, respectively Conclusion(s): Lymphocytic alveolitis associated with plasmacytosis is found in non-severe COVID-19 pneumonia. This alveolitis is associated with the presence of IL-6, IL-8, IL-10, TNFa, IFN g and HGF. BAL alveolitis and cytokine levels normalize in post-COVID-19 pneumonia.
ABSTRACT
Transforming growth factor beta (TGF-ß) is a ubiquitously distributed cytokine known to contribute to the pathogenesis of numerous pathological processes. The aim of this study was to measure serum concentrations of TGF-ß1 in severely ill COVID-19 patients and to analyze its relationship with selected hematological and biochemical parameters and with the disease outcome. The study population included 53 COVID-19 patients with severe clinical expression of the disease and 15 control subjects. TGF-ß1 was determined in serum samples and supernatants from PHA-stimulated whole blood cultures using ELISA assay. Biochemical and hematological parameters were analyzed using standard accepted methods. Our results showed that serum levels of TGF-ß1 in COVID-19 patients and controls correlate with the platelet counts. Also, positive correlations of TGF-ß1 with white blood cell and lymphocyte counts, platelet-to-lymphocyte (PLR) ratio, and fibrinogen level were shown, while negative correlations of this cytokine with platelet distribution width (PDW), D-dimer and activated partial thromboplastin time (a-PTT) values in COVID-19 patients were observed. The lower serum values of TGF-ß1 were associated with the unfavorable outcome of COVID-19. In conclusion, TGF-ß1 levels were strongly associated with platelet counts and unfavorable disease outcome of severely ill COVID-19 patients.
ABSTRACT
Introduction: A worldwide pandemic infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a deadly disease called COVID-19. Interaction of the virus and the Angiotensin converting-enzyme 2 (ACE2) receptor leads to an inflammatory-induced tissue damage. Thymus vulgaris L. (TvL) is a plant with a long history in traditional medicine that has antimicrobial, antiseptic, and antiviral properties. Thymol and Carvacrol are two important biological components in Thyme that have anti-inflammatory, antioxidant, and immunomodulatory properties. This study is a molecular review on the potential effects of TvL and its active compounds on SARS-COV2 infection. Method: This is a narrative review in which using PubMed, Scopus, ISI, Cochrane, ScienceDirect, Google scholar, and Arxiv preprint databases, the molecular mechanisms of therapeutic and protective effects of TvL and its active compounds have been discussed regarding the molecular pathogenesis in COVID-19. Results: Thyme could suppress TNF-alpha, IL-6, and other inflammatory cytokines. It also enhances the anti-inflammatory cytokines like TGF-beta and IL-10. Thyme extract acts also as an inhibitor of cytokines IL-1-beta and IL-8, at both mRNA and protein levels. Thymol may also control the progression of neuro-inflammation toward neurological disease by reducing some factors. Thyme and its active ingredients, especially Thymol and Carvacrol, have also positive effects on the renin-angiotensin system (RAS) and intestinal microbiota. Conclusions: Accordingly, TvL and its bioactive components may prevent COVID-19 complications and has a potential protective role against the deleterious consequences of the disease.