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Transforming growth factor β1 (TGF-β1) plays a central role in chronic kidney diseases. TGF-β1 induction causes podocyte injury, which results in proteinuria and renal failure. However, the effect of the prostaglandin E2 /E-prostanoid receptor (EP2) on TGF-β1-induced podocyte injury remains unknown. Previous studies have shown that phosphoinositide 3-OH kinase (PI3K)/Akt is widespread in cells, and is vital for the regulation of cell proliferation, differentiation, apoptosis and metabolism. In this study, we cultured immortalized mouse podocytes in vitro in different groups: control group; TGF-β1 (5ng/ml) group; EP2 agonist Butaprost treatment (10−7, 10−6, or 10-5mol/L) +TGF-β1 group; EP2 antagonist AH6809 treatment (10−7, 10−6, or 10-5mol / L) + TGF-β1 group. We found that compared with the control group, proliferation of podocytes in the TGF-β1 group significantly decreased and apoptosis increased. Expression of cAMP decreased, whereas PGE2 increased. Meanwhile, expressions of nephrin, podocin and CD2AP mRNA and protein were dramatically downregulated, activated caspase-3 was increased, and activated PI3K/Akt activity were depressed. Butaprost intervention promoted podocyte proliferation with reduced apoptosis. Conversely, AH6809 intervention led to opposite results (P<0.05). Our findings suggested that EP2 agonist protects podocytes by increasing expression of cAMP, which creates feedback of inhibiting PGE2 expression. This causes the interaction of nephrin, podocin and CD2AP resulting the inhibition of apoptosis induced by activation of the PI3K / Akt signaling pathway.

BackgroundSARS-CoV-2 is highly contagious and poses a great threat to epidemic control and prevention. The possibility of fecal-oral transmission has attracted increasing concern. However, viral shedding in feces has not been completely investigated.MethodsThis study retrospectively reviewed 97 confirmed coronavirus disease 2019 (COVID-19) patients hospitalized at the First Affiliated Hospital, School of Medicine, Zhejiang University, from January 19 to February 17, 2020. SARS-CoV-2 RNA in samples of sputum, nasopharyngeal or throat swabs, bronchoalveolar lavage and feces was detected by real-time reverse transcription polymerase chain reaction (RT–PCR). Clinical characteristics and parameters were compared between groups to determine whether fecal RNA was positive.ResultsThirty-four (35.1%) of the patients showed detectable SARS-CoV-2 RNA in feces, and 63 (64.9%) had negative detection results. The median time of viral shedding in feces was approximately 25 days, with the maximum time reaching 33 days. Prolonged fecal-shedding patients showed longer hospital stays. Those patients for whom fecal viral positivity persisted longer than 3 weeks also had lower plasma B-cell counts than those patients in the non-prolonged group [70.5 (47.3-121.5) per μL vs. 186.5 (129.3-376.0) per μL, P = 0.023]. Correlation analysis found that the duration of fecal shedding was positively related to the duration of respiratory viral shedding (R = 0.70, P &lt; 0.001) and negatively related to peripheral B-cell counts (R = -0.44, P &lt; 0.05).ConclusionsCOVID-19 patients who shed SARS-CoV-2 RNA in feces presented similar clinical characteristics and outcomes as those who did not shed SARS-CoV-2 RNA in feces. The prolonged presence of SARS-CoV-2 nucleic acids in feces was highly correlated with the prolonged shedding of SARS-CoV-2 RNA in the respiratory tract and with lower plasma B-cell counts.

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This research investigated the relationship between the concentration of Lactobacillus salivarius Li01 and its impact on mice that had a thioacetamide-induced acute liver injury and hyperammonemia. These findings could provide new insights into the effective, proper, and safe use of probiotics.

Background Dietary fiber is effective for colorectal cancer (CRC) treatment. Interleukin-6 (IL-6) and its adaptors are potential targets for CRC therapy. Butyrate, a metabolite of dietary fiber, is a new, highly safe type of targeted drug. Methods In this study, Cell Counting Kit-8 cell viability and wound healing assays, western blot analysis, immunofluorescence staining, and xenograft tumor mouse models were used to evaluate the anticancer effect of butyrate and its possible mechanism in vivo and in vitro. Results Dietary fiber and sodium butyrate (NaB) decreased CRC burden by decreasing IL-6 receptor gp130 and blocking IL-6/JAK2/STAT3 axis activation in vitro and in vivo. Furthermore, NaB reduced the gp130 protein level by regulating its degradation rate via targeting TRAF5. Conclusions The fiber metabolite butyrate inhibits CRC development by reducing gp130 via TRAF5.

Background Perianal cancer is a relatively rare disease, but it is prevalent in men who have sex with men and in patients who are positive for human immunodeficiency virus (HIV). Here, we report a case of a massive anal squamous cell carcinoma that measured 19 cm in length and 10 cm in diameter in a male patient living with HIV. Case presentation A 28-year-old man with a 5-year history of peri-anal condyloma acuminatum developed a rapidly enlarging mass in the anal region since the past few months. He had both HIV and syphilis infection, but never sought further treatment. Pathological analysis and immunohistochemistry confirmed squamous cell carcinoma with high-risk HPV infection. After multi-disciplinary treatment, albumin-paclitaxel combined with anti-programmed cell death protein 1 therapy and simultaneous antiretroviral therapy was initiated. The mass began to shrink after chemotherapy, but this did not prevent tumor progression. He eventually died from tumor-cachexia. Conclusion Early screening and treatment of perianal disease can help prevent progression to invasive anal carcinoma in high-risk groups such as men who have sex with men and immunosuppressed patients.

Background Perianal cancer is a relatively rare disease, but it is prevalent in men who have sex with men and in patients who are positive for human immunodeficiency virus (HIV). Here, we report a case of a massive anal squamous cell carcinoma that measured 19 cm in length and 10 cm in diameter in a male patient living with HIV. Case presentation A 28-year-old man with a 5-year history of peri-anal condyloma acuminatum developed a rapidly enlarging mass in the anal region since the past few months. He had both HIV and syphilis infection, but never sought further treatment. Pathological analysis and immunohistochemistry confirmed squamous cell carcinoma with high-risk HPV infection. After multi-disciplinary treatment, albumin-paclitaxel combined with anti-programmed cell death protein 1 therapy and simultaneous antiretroviral therapy was initiated. The mass began to shrink after chemotherapy, but this did not prevent tumor progression. He eventually died from tumor-cachexia. Conclusion Early screening and treatment of perianal disease can help prevent progression to invasive anal carcinoma in high-risk groups such as men who have sex with men and immunosuppressed patients.