INTRODUCTION:Ulcerative colitis (UC) is a refractory disease with complex pathogenesis, and its pathogenesis is not clear. The present study aimed to investigate the potential target and related mechanism of Compound Sophora Decoction (CSD) in treating UC. METHODS:A network pharmacology approach predicted the components and targets of CSD to treat UC, and cell and animal experiments confirmed the findings of the approach and a new target for CSD treatment of UC. RESULTS:A total of 155 potential targets were identified for CSD treatment of UC, with some related to macrophage polarization, such as nitric oxide synthase (NOS2), also known as inducible nitric oxide synthase (iNOS). GO and KEGG enrichment analysis indicated that oxidative stress response and multiple inflammatory signaling pathways such as TNF-α may play a significant role. In vitro experiments revealed that Interferon-stimulated DNA (ISD) interference can cause polarization imbalances in Raw 264.7 and bone marrow-derived macrophages (BMDMs). Flow cytometry demonstrated that polarization of macrophages in the intestine, spleen, and lymph nodes in vivo was also unbalanced after dextran sulfate sodium (DSS) modeling with pathological intestinal injury. Both in vitro and in vivo studies indicated that after inducing inflammation, the levels of macrophage polarization-related markers (iNOS and Arg1) and inflammation-related factors (CCL17, IL10, TNF-α, and CXCL10) changed, accompanied by increased expression of cGAS. However, CSD treatment based on inflammation can inhibit the expression of cGAS protein and mRNA, lower the level of inflammatory factors, promote the expression of anti-inflammatory factors, and regulate macrophage polarization. CONCLUSION:We concluded that CSD alleviated DSS-induced UC by inhibiting cGAS, thus regulating macrophage polarization.

Macrophage polarization is closely associated with the pathogenesis of ulcerative colitis (UC). Quercetin, a flavonoid, has shown promise as a treatment for inflammatory diseases, but its specific mechanism of action remains unclear. This study investigates whether quercetin can regulate intestinal macrophage polarization and promote intestinal tissue repair via the cGAS-STING pathway for the treatment of UC. In vivo, mice with 3% DSS-induced UC were intraperitoneally injected with quercetin and RU.521 for 7 days, following which their general conditions and corresponding therapeutic effects were assessed. The impact of interferon-stimulated DNA (ISD) and quercetin on macrophage polarization and the cGAS-STING pathway was investigated using RAW264.7 cells and bone marrow-derived macrophages (BMDMs) in vitro. The results demonstrated that ISD induced M1 macrophage polarization and activated the cGAS-STING pathway in vitro, while quercetin reversed ISD’s inflammatory effects. In vivo, quercetin suppressed the cGAS-STING pathway in the intestinal macrophages of DSS-induced UC mice, which reduced M1 macrophage polarization, increased M2 polarization, and facilitated intestinal barrier repair in UC. Taken together, these findings provide new insights into the mechanisms via which quercetin could be used to treat UC.

Myocardial infarction (MI) is one of the diseases with high fatality rate. Berberine (BBR) is a monomer compound with various biological functions. And some studies have confirmed that BBR plays an important role in alleviating cardiomyocyte injury after MI. However, the specific mechanism is unclear. In this study, we induced a model of MI by ligation of the left anterior descending coronary artery and we surprisingly found that BBR significantly improved ventricular remodeling, with a minor inflammatory and oxidative stress injury, and stronger angiogenesis. Moreover, BBR inhibited the secretion of Wnt5a/β-catenin pathway in macrophages after MI, thus promoting the differentiation of macrophages into M2 type. In summary, BBR effectively improved cardiac function of mice after MI, and the potential protective mechanism was associated with the regulation of inflammatory responses and the inhibition of macrophage Wnt5a/β-catenin pathway in the infarcted heart tissues. Importantly, these findings supported BBR as an effective cardioprotective drug after MI.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis. Previous studies have indicated that celastrol (CSR) has strong anti-inflammatory and immune-inhibitory effects. Here, we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model, and addressed the mechanism by which CSR exerts the protective effects. We characterized the therapeutic effects and the potential mechanism of CSR on treating UC using histological staining, intestinal permeability assay, cytokine assay, flow cytometry, fecal microbiota transplantation (FMT), 16S rRNA sequencing, untargeted metabolomics, and cell differentiation. CSR administration significantly ameliorated the dextran sodium sulfate (DSS)-induced colitis in mice, which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index (DAI) score and intestinal permeability. Meanwhile, CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels, and improved the balances of Treg/Th1 and Treg/Th17 to maintain the colonic immune homeostasis. Notably, all the therapeutic effects were exerted in a gut microbiota-dependent manner. Furthermore, CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites, which is probably associated with the gut microbiota-mediated protective effects. In conclusion, this study provides the strong evidence that CSR may be a promising therapeutic drug for UC.

Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colon, and it has become one of the world-recognized medical problems as it is recurrent and refractory. Berberine (BBR) is an effective drug for UC treatment. However, the underlying mechanism and targets remain obscure. In this study, we systematically investigated the therapeutic effect and its mechanism of BBR in ameliorating DSS-induced mouse colitis. Expectedly, the colon inflammation was significantly relieved by BBR, and microbiota depletion by antibiotic cocktail significantly reversed the therapeutic effect. Further studies showed that BBR can regulate the abundance and component of bacteria, reestablish the broken chemical and epithelial barriers. Meanwhile, BBR administration dramatically decreased ILC1 and Th17 cells, and increased Tregs as well as ILC3 in colonic tissue of DSS-induced mice, and it was able to regulate the expression of various immune factors at the mRNA level. Moreover, a proteomic study revealed that Wnt/β-catenin pathway was remarkably enhanced in colonic tissue of BBR-treated mice, and the therapeutic effect of BBR was disappeared after the intervention of Wnt pathway inhibitor FH535. These results substantially revealed that BBR restores DSS-induced colon inflammation in a microbiota-dependent manner, and BBR performs its protective roles in colon by maintaining the structure and function of the intestinal mucosal barrier, regulating the intestinal mucosal immune homeostasis and it works through the Wnt/β-catenin pathway. Importantly, these findings also provided the proof that BBR serves as a potential gut microbiota modulator and mucosal barrier protector for UC prevention and therapy.

BACKGROUND:Since December 2019, novel coronavirus (SARS-CoV-2)-induced pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China. COVID-19 patients demonstrated significantly different outcomes in clinic. We aimed to figure out whether obesity is a risk factor influencing the progression and prognosis of COVID-19.METHODS:95 patients with COVID-19 were divided into obesity group and non-obesity group according to their body mass index (BMI). The demographic data, clinical characteristics, laboratory examination, and chest computed tomography (CT) were collected, analyzed and compared between two groups.RESULTS:Our data showed that COVID-19 patients with obesity had more underlying diseases and higher mortality rate compared to those without obesity. Furthermore, patients with obesity also demonstrated more severe pathological change in lung and higher blood lymphocytes, triglycerides, IL-6, CRP, cystatin C, alanine aminotransferase (ALT), erythrocyte sedimentation rate (ESR), which may greatly influence disease progression and poor prognosis of COVID-19.CONCLUSIONS:It suggest that obesity contributes to clinical manifestations and may influence the progression and prognosis of COVID-19 and it is considered as a potential risk factor of the prognosis of COVID-19. Special medical care and appropriate intervention should be performed in obesity patients with COVID-19 during hospitalization and later clinical follow-up, especially for those with additional other comorbidities.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) induced Coronavirus Disease 2019 (COVID-19) has posed a global threat to public health. The immune system is crucial in defending and eliminating the virus and infected cells. However, immune dysregulation may result in the rapid progression of COVID-19. Here, we evaluated the subsets, phenotypic and functional characteristics of natural killer (NK) and T cells in patients with COVID-19 and their associations with disease severity. Methods: Demographic and clinical data of COVID-19 patients enrolled in Wuhan Union Hospital from February 25 to February 27, 2020, were collected and analyzed. The phenotypic and functional characteristics of NK cells and T cells subsets in circulating blood and serum levels of cytokines were analyzed via flow cytometry. Then the LASSO logistic regression model was employed to predict risk factors for the severity of COVID-19. Results: The counts and percentages of NK cells, CD4+ T cells, CD8+ T cells and NKT cells were significantly reduced in patients with severe symptoms. The cytotoxic CD3-CD56dimCD16+ cell population significantly decreased, while the CD3-CD56dimCD16- part significantly increased in severe COVID-19 patients. More importantly, elevated expression of regulatory molecules, such as CD244 and programmed death-1 (PD-1), on NK cells and T cells, as well as decreased serum cytotoxic effector molecules including perforin and granzyme A, were detected in patients with COVID-19. The serum IL-6, IL-10 and TNF-α were significantly increased in severe patients. Moreover, the CD3-CD56dimCD16- cells were screened out as an influential factor in severe cases by LASSO logistic regression. Conclusions: The functional exhaustion and other subset alteration of NK and T cells may contribute to the progression and improve the prognosis of COVID-19. Surveillance of lymphocyte subsets may in the future enable early screening for signs of critical illness and understanding the pathogenesis of this disease.

Objective: Sero-surveillance was conducted in the patients with or without COVID-19. Methods: Sera were collected from 3062 patients of Wuhan, and the levels of SARS-CoV-2 antibody IgM and IgG were measured by the immuno-colloidal gold method. Nucleic acid (NA) of SARS-CoV-2 was measured by reverse transcription-polymerase chain reaction (RT-PCR). Results: The study consisted of 1652 men and 1410 women. The mean seroprevalence for IgM and IgG in all participants was 2•81% and 7•51%, respectively. The positive rate of IgG was significantly higher in women than in men (P<0•05). As for subgroups, seroprevalence for IgM and IgG was significantly different among the age group, the highest positive rate of IgM was observed in 41-60 years of age (3•49%), while the highest seroprevalence for IgG observed in persons >60 years of age (8•61%). The positive rates of IgM and IgG in the convalescent patients were 31•82% and 77•27%, respectively, which was significantly higher compared with individuals with suspected syndromes or individuals without any clinical signs (P<0•01). Seroprevalence for IgG in medical staff was markedly higher than those in residents. Notably, the positive rate was higher in the individuals from the fever clinic where specifically for the screen the suspected patients. The seroprevalence in patients with various comorbidity was no significant difference (P>0•05). Conclusion: The low positive rate of the SARS-CoV-2 IgM and NA test in residents of Wuhan indicated that SARS-CoV-2 outbreak is subsiding, and the possibility of reintroduction of the virus from an unidentified natural reservoir is low. Seroprevalence for IgG various among the patients with different comorbidity, which provide the information for humoral immunity and vaccine in the future.Funding Statement: This study was funded by the National Key Research and Development Program of China (grant number 2018YFE0204500), National Natural Science Foundation of China (Grant No. 81702273), Science and technology key project of Guangdong Province: Study on the source and epidemiology of COVID-19 (No .2020B111107001) ,and Scientific research project of COVID-19 epidemic prevention and control in Guangdong universities (No.2020KZDZX1087).Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: The study received ethics approval from the Ethics Committee of Zhongnan Hospital, Wuhan University

An outbreak of pneumonia caused by a novel coronavirus (COVID-19) began in Wuhan, China in December 2019 and quickly spread throughout the country and world. An efficient and convenient method based on clinical characteristics was needed to evaluate the potential deterioration in patients. We aimed to develop a simple and practical risk scoring system to predict the severity of COVID-19 patients on admission. We retrospectively investigated the clinical information of confirmed COVID-19 patients from 10 February 2020 to 29 February 2020 in Wuhan Union Hospital. Predictors of severity were identified by univariate and multivariate logistic regression analysis. A total of 147 patients with confirmed SARS-CoV-2 infection were grouped into non-severe (94 patients) and severe (53 patients) groups. We found that an increased level of white blood cells (WBC), neutrophils, D-dimer, fibrinogen (FIB), IL-6, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), α-hydroxybutyrate dehydrogenase (HBDH), serum amyloid A (SAA) and a decreased level of lymphocytes were important risk factors associated with severity. Furthermore, three variables were used to formulate a clinical risk scoring system named COVID-19 index = 3 × D-dimer (µg/L) + 2 × lgESR (mm/hr) - 4 × lymphocyte (×109 /L) + 8. The area under the receiver operating characteristic (ROC) curve was 0.843 (95% CI, 0.771-0.914). We propose an effective scoring system to predict the severity of COVID-19 patients. This simple prediction model may provide healthcare workers with a practical method and could positively impact decision-making with regard to deteriorating patients.

Background In December 2019, a novel coronavirus (SARS-CoV-2) caused infectious disease, termed COVID-19, outbroke in Wuhan, China. COVID-19 patients manifested as lung injury with complications in other organs, such as liver, heart, gastrointestinal tract, especially for severe cases. However, whether COVID-19 causes significant acute kidney injury (AKI) remained controversial. Methods We retrospectively analyzed the clinical characteristics, urine and blood routine tests and other laboratory parameters of hospitalized COVID-19 patients in Wuhan Union Hospital. Findings 178 patients, admitted to Wuhan Union hospital from February 02 to February 29, 2020, were included in this study. No patient (0 [0%]) presented increased serum creatinine (Scr), and 5 (2.8%) patients showed increased blood urea nitrogen (BUN), indicating few cases with “kidney dysfunction”. However,for patients (83) with no history of kidney disease who received routine urine test upon hospitalization, 45 (54.2%) patients displayed abnormality in urinalysis, such as proteinuria, hematuria and leukocyturia, while none of the patients was recorded to have acute kidney injury (AKI) throughout the study. Meanwhile, the patients with abnormal urinalysis usually had worse disease progression reflecting by laboratory parameters presentations, including markers of liver injury, inflammation, and coagulation. Conclusion Many patients manifested by abnormal urinalysis on admission, including proteinuria or hematuria. Our results revealed that urinalysis is better in unveiling potential kidney impairment of COVID-19 patients than blood chemistry test and urinalysis could be used to reflect and predict the disease severity. We therefore recommend pay more attention in urinalysis and kidney impairment in COVID-19 patients.