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Diabetic nephropathy (DN) is a kind of diabetic complication with capillary damage, and its pathogenesis remains obscure. Recently, microRNAs have been identified as diagnostic biomarkers in various diseases including DN. Toll-like receptor 4 (TLR4) contributes to inflammation, and it has been implicated in diabetes pathophysiology. This study was designed to investigate the role of miR-874 and TLR4 in a streptozotocin (STZ)-induced DN rat model and glucose-induced mouse podocyte model. In the current study, we reported that miR-874 was markedly downregulated in DN rats and glucose-induced mouse podocytes compared with the corresponding control groups with the activation of TLR4. In addition, we observed that overexpression of miR-874 was able to alleviate renal injury in DN rats. The cell counting kit (CCK-8) assay and 5-Ethynyl-2'-deoxyuridine (EdU) assay demonstrated that glucose simulation significantly inhibited podocyte proliferation and induced cell apoptosis, which can be reversed by miR-874 mimics significantly. Notably, miR-874 overexpression dramatically attenuated the inflammatory response, indicated by the decreased levels of interleukin-6, L-1β, and tumor necrosis factor α (TNF-α). Finally, the binding correlation between miR-874 and TLR4 was confirmed by carrying out dual-luciferase reporter assay in our study. It was found that overexpression of miR-874 depressed TLR4 levels in podocytes. These findings implied for the first time that the overexpression of miR-874 repressed glucose-triggered podocyte injury through targeting TLR4 and suggested that miR-874/TLR4 axis might represent a pathological mechanism of DN.

Coronavirus disease 2019 (COVID‐19) is a newly emerging infectious disease. Our understanding of the clinical characteristics of liver damage and the relationship with disease severity in COVID‐19 is still limited. To investigate the serum hepatic enzyme activities in different phenotypes of COVID‐19 patients, evaluate their relationship with the illness severity and analyze the correlation of glycyrrhizin treatment and abnormal liver enzyme activities, one hundred and forty‐seven patients with COVID‐19 were enrolled in a retrospective study that investigated hepatic dysfunction. Liver alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactic dehydrogenase (LDH), Y‐glutamyl transferase (GGT), superoxide dismutase (SOD), and alkaline phosphatase (ALP) were analyzed in these patients. Patients with diammonium glycyrrhizinate (DG) treatment were further investigated. Of the 147 patients, 56 (38.1%) had abnormal ALT activity and 80 (54.4%) had abnormal AST activity. The peak of abnormal hepatic enzyme activities occurred at 3 to 6 days after on admission. Serum AST and LDH levels were elevated, while the SOD level was decreased in severe and critical patients, compared with mild cases. DG treatment may alleviate the abnormal liver enzyme activities in non‐critical COVID‐19 patients. Abnormal liver functions may be observed in patients with COVID‐19, and were associated with SARS‐CoV‐2‐induced acute liver damage. Glycyrrhizin treatment may be an effective therapeutic approach for the outcome of abnormal hepatic enzyme activities in severe COVID‐19 cases. Serum hepatic enzyme tests may reflect the illness severity and should be monitored.

Evidence exists reporting that Saikosaponin-d can prevent experimental sepsis, and this study aims to illustrate the molecular events underlying its renoprotective effects on lipopolysaccharide (LPS)-induced renal inflammation simulating sepsis. Through network pharmacology analysis and bioinformatics analysis, we identified that saikosaponin-d may influence sepsis development by mediating TCF7. Dual luciferase reporter gene and ChIP assays were used to explore the interactions between TCF7, FOSL1 and MMP9. The experimental data suggested that Saikosaponin-d attenuated LPS-induced renal injury, as evidenced by reduced the production of proinflammatory cytokines as well as cell apoptosis in the renal tissues of LPS-induced mice. Mechanically, Saikosaponin-d inhibited FOSL1 by inhibiting TCF7, which reduced the expression of inflammatory factors in renal cells. TCF7 activated the FOSL1 expression and consequently promoted the expression of MMP9. Also, Saikosaponin-d reduced cell apoptosis and the expression of inflammatory factors by inhibiting the TCF7/FOSL1/MMP9 axis in vivo . In conclusion, Saikosaponin-d suppresses FOSL1 transcription by downregulating TCF7, thereby inhibiting MMP9 expression and ultimately reducing the renal inflammation and cell apoptosis induced by sepsis.

Acute renal failure is one of the most common complications observed in hospitals. Although extensive studies have been carried out to search for therapeutic treatments, no effective cure has been established. In recent years, stem cell therapy for tissue engineering and repair has become a key area of study. Bone marrow mesenchymal stem cells (MSCs) have been demonstrated to exhibit a reparative role in ischemia reperfusion-injured kidney tissue, and the stromal cell-derived factor-1 (SDF-1)/chemokine (C-X-C motif) receptor 4 (CXCR4) axis has been found to play an important role in the migration and homing of MSCs. In the present study, transforming growth factor-β1 (TGF-β1) in the homogenate of the acute ischemia reperfusion-injured renal tissue was found to markedly increase the CXCR4 surface expression of MSCs, which contributes to the migration of MSCs to SDF-1. Neutralization of TGF-β1 inhibited the migration in an antibody concentration-dependent manner, through downregulation of CXCR4 localized to the membrane. These observations suggest a potential mechanism for MSC migration to the kidney which may provide a possible therapeutic target for curing acute renal failure.

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Background With the widespread outbreak of novel coronavirus diseases 2019(COVID-19), more and more death cases were reported, however, limited data are available for the patients who died. We aimed to explore the clinical characteristics of deaths with COVID-19 pneumonia. Methods We abstracted and analyzed epidemiological, demographic, clinical, and laboratory data from 83 death cases with COVID-19 pneumonia in East Hospital of Wuhan University Renmin Hospital, between January 26, 2020, and February 28, 2020. Results Of the 83 deaths, none was the medical staff. The mean age was 71.8 years (SD 13.2; range, 34–97 years) and 53(63.9%) were male. The median from onset to admission was 10 days (IQR 7–14: range, 2–43 days), to death was 17 days (IQR 14–21: range, 6–54 days). Most deaths (66[80%]) had underlying comorbid diseases, the most of which was hypertension [47(57%)]. The main initial symptoms of these 83 deaths were shortness of breath(98.8%), fever(94%), and myalgia or fatigue(90.4%). Laboratory analyses showed the lymphocytopenia in 69(83%) deaths, hypoalbuminemia in 77(93%) deaths, the elevation of lactate dehydrogenase in 79(95%) deaths, procalcitonin in 69(83%) deaths and C-reactive protein in 79(95%) deaths. All 83 patients received antiviral treatment, 81(97.6%) deaths received antibiotic therapy, 54(65.1%) deaths received glucocorticoid therapy, and 20(24.1%) patients received invasive mechanical ventilation. Conclusion Most of the deaths with COVID-19 pneumonia were elderly patients with underlying comorbid diseases, especially those over 70 years of age. The time of death after the onset of the disease was mostly 15–21 days. More care should be given to the elderly in further prevention and control strategies of COVID-19.