It is confirmed that adipose-derived stem cells (ADSCs) transplantation effectively relieves kidney fibrosis and type 2 diabetes disease in mice. Currently, exosome from urine-derived stem cells (USCs) can protect type 1 diabetes-mediated kidney injury and attenuate podocyte damage in diabetic nephropathy (DN). Exosome derived from USCs has evolved into the strategy for DN treatment, but the role of ADSCs-derived exosome (ADSCs-Exo) in DN remains unclear. The present study is aimed to investigate the therapeutic action and molecular mechanism of ADSCs-derived exosome on DN. ADSCs and exosome were authenticated by immunofluorescence and flow cytometry. Morphology and the number of exosome were evaluated by electron microscope and Nanosight Tracking Analysis (NTA), respectively. Cell apoptosis was assessed using flow cytometry. Podocyte autophagy and signaling transduction were measured by immunofluorescence and immunoblotting. Dual Luciferase Reporter assay was employed to detect the regulatory relationship between miR-486 and Smad1. ADSCs-Exo attenuated spontaneous diabetes by reducing levels of urine protein, serum creatinine (Scr), blood urea nitrogen (BUN), and podocyte apoptosis in mice. In in vitro experiment, ADSCs-Exo also reversed high glucose-induced decrease of cell viability and the increase of cell apoptosis in MPC5 cells. In terms of mechanism, ADSCs-Exo could enhance autophagy flux and reduce podocyte injury by inhibiting the activation of mTOR signaling in MPC5 and spontaneous diabetic mice. Eventually, we found that miR-486 was the key factors in ADSCs and in the process of ADSCs-Exo-mediated improvement of DN symptom in vivo and in vitro. miR-486 reduced Smad1 expression by target regulating Smad1 whose reduction could inhibit mTOR activation, leading to the increase of autophagy and the reduction of podocyte apoptosis. In conclusion, we illustrated that ADSCs-Exo vividly ameliorated DN symptom by enhancing the expression of miR-486 which led to the inhibition of Smad1/mTOR signaling pathway in podocyte. Possibly, ADSCs-Exo was used as a main therapeutic strategy for DN in future.

Currently, renal cell carcinoma (RCC) is the most prevalent type of kidney cancer. Targeted therapy has replaced radiation therapy and chemotherapy as the main treatment option for RCC due to the lack of significant efficacy with these conventional therapeutic regimens. Sunitinib, a drug used to treat gastrointestinal tumors and renal cell carcinoma, inhibits the tyrosine kinase activity of a number of receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), c-Kit, rearranged during transfection (RET) and fms-related receptor tyrosine kinase 3 (Flt3). Although sunitinib has been shown to be efficacious in the treatment of patients with advanced RCC, a significant number of patients have primary resistance to sunitinib or acquired drug resistance within the 6-15 months of therapy. Thus, in order to develop more efficacious and long-lasting treatment strategies for patients with advanced RCC, it will be crucial to ascertain how to overcome sunitinib resistance that is produced by various drug resistance mechanisms. In this review, we discuss: 1) molecular mechanisms of sunitinib resistance; 2) strategies to overcome sunitinib resistance and 3) potential predictive biomarkers of sunitinib resistance.

To gain insight into willingness and its influencing factors to vaccinate against COVID-19 among health care workers (HCWs), and provide a scientific basis for more reasonable epidemic prevention and control strategies. A comprehensive literature search was conducted in four English databases (PubMed, EMBASE, Web of Science and the Cochrane Library) and four Chinese databases (Chinese National Knowledge Infrastructure (CNKI), the Chongqing VIP Chinese Science (VIP), Wanfang Database and China Biomedical Literature Database (CBM)) to collect the related studies. Quality evaluation was carried out for papers meeting the inclusion criteria using six items from the Downs and Black assessment checklist. The STATA statistical software version 15.1 was hired to perform meta-analysis. Nine records with a total of 24,952 subjects were included in this meta-analysis. The results of this meta-analysis revealed that the pooled effect value of COVID-19 vaccination willingness among HCWs using a random-effects model was 51% (95% confidence interval (CI) 0.41-0.62). Male, aged 30 years or older, having a history of prior influenza vaccination were facilitators for HCWs’ intention to vaccinate against COVID-19 (odds ratio (OR) 1.82, 95% CI 1.37-2.41, P=0.000, I2=59.4%; OR 1.32, 95% CI 1.16-1.51, P=0.000, I2=31.7%; OR 2.97, 95% CI 1.82-4.84, P=0.000, I2=88.1%). The impact of occupation on HCWs’ intention to get vaccinated could not yet be definitively confirmed (OR 0.85, 95% CI 0.69-1.06, P=0.160, I2=85.5%). COVID-19 vaccination acceptance of HCWs was at moderate level. Strengthening awareness of COVID-19 vaccine among HCWs, particularly female HCWs under 30 years who have no history of prior influenza vaccination, is crucial to eliminate concerns about vaccination and promote the application of COVID-19 vaccine in this population.

Aims: Diabetic nephropathy (DN) is characterized by microalbuminuria, mainly associated with pathological and morphological alterations of podocyte. New drug targeting podocyte injury is a promising approach for treating DN. The present study is aimed at developing new drug targeting podocyte injury for treating DN. Results: In this study, germacrone ameliorated kidney damage and inhibited podocyte apoptosis in a DN mouse model. Based on RNA-seq, mmu_mmu_circRNA_0000309, located in host gene vascular endothelial zinc finger 1 ( Vezf1 ), showed a sharp decline in DN mice and a remarkable recovery in germacrone-challenged DN mice. mmu_circRNA_0000309 silence or miR-188-3p mimics abrogated the antiapoptosis and anti-injury effects of germacrone through aggravating mitochondria damage, and elevating reactive oxygen species and ferroptosis-related protein levels. Mechanistically, mmu_circRNA_0000309 competitively sponged miR-188-3p, and subsequently promoted glutathione peroxidase 4 (GPX4) expression, thereby inactivating ferroptosis-dependent mitochondrial damage and podocyte apoptosis. In addition, GPX4 overexpression neutralized mmu_circRNA_0000309 silence-mediated mitochondria damage and ferroptosis in germacrone-exposed MPC5 cells. Innovation: We describe the novel effect and mechanism of germacrone on treating DN, which is linked to ferroptosis for the first time. Conclusion: mmu_circRNA_0000309 silence mediates drug resistance to germacrone in DN mice. mmu_circRNA_0000309 sponges miR-188-3p, and subsequently upregulates GPX4 expression, inactivating ferroptosis-dependent mitochondrial function and podocyte apoptosis. Possibly germacrone-based treatment for DN can be further motivated by regulating mmu_circRNA_0000309/miR-188-3p/GPX4 signaling axis. Antioxid. Redox Signal. 36, 740–759.

At the beginning of 2020, the outbreak of coronavirus disease 2019 (COVID-19) led to a worldwide pandemic and mass panic. The number of infected people has been increasing exponentially since, and the mortality rate has also been concomitantly increasing. At present, no study has summarized the mortality risk of COVID-19 in patients with chronic kidney disease (CKD). Therefore, the aim of the present study was to conduct a literature review and meta-analysis to understand the frequency of mortality among CKD patients infected with COVID-19. A comprehensive systematic search was conducted on the PubMed, Embase, and Cochrane databases to find articles published until May 15, 2020. Study quality was assessed using a modified version of the Newcastle–Ottawa Scale. After careful screening based on the inclusion and exclusion criteria, 3,867,367 patients from 12 studies were included. The mortality rate was significantly higher among CKD patients with COVID-19 infection than among CKD patients without COVID-19 infection, as indicated by a pooled OR of 5.81 (95% CI 3.78–8.94, P < 0.00001, I² = 30%). The patients were then stratified into ≥ 70 and < 70 years, and subgroup analysis revealed that among CKD patients with COVID-19 infection, the mortality rate was higher in the < 70 years group (OR 8.69, 95% CI 7.56–9.97, P < 0.0001) than in the ≥ 70 years group (OR 2.44, 95% CI 0.75–6.63, P = 0.15). Thus, COVID-19 patients with CKD have a high mortality risk and require a comprehensive multidisciplinary management strategy.

Context: Curcumin could ameliorate diabetic nephropathy (DN), but the mechanism remains unclear. Objective: The efficacy of curcumin on epithelial-to-mesenchymal transition (EMT) of podocyte and autophagy in vivo and in vitro was explored. Materials and methods: Thirty male Sprague–Dawley rats were divided into the normal, model and curcumin (300 mg/kg/d, i.g., for 8 weeks) groups. Rats received streptozotocin (50 mg/kg, i.p.) and high-fat-sugar diet to induce DN. Biochemical indicators and histomorphology of renal tissues were observed. In addition, cultured mouse podocytes (MPC5) was induced to EMT with serum from DN rats, and then exposed to curcumin (40 µM) with or without fumonisin B1, an Akt specific activator or 3BDO, the mTOR inducer. Western blot analysed the levels of EMT and autophagy associated proteins. Results: Administration of curcumin obviously reduced the levels of blood glucose, serum creatinine, urea nitrogen and urine albumen (by 28.4, 37.6, 33.5 and 22.4%, respectively), and attenuated renal histomorphological changes in DN rats. Podocytes were partially fused and autophagic vacuoles were increased in curcumin-treated rats. Furthermore, curcumin upregulated the expression of E-cadherin and LC3 proteins and downregulated the vimentin, TWIST1, p62, p-mTOR, p-Akt and P13K levels in DN rats and MPC5 cells. However, fumonisin B1 or 3BDO reversed the effects of curcumin on the expression of these proteins in cells. Discussion and conclusions: The protection against development of DN by curcumin treatment involved changes in inducing autophagy and alleviating podocyte EMT, through the PI3k/Akt/mTOR pathway, providing the scientific basis for further research and clinical applications of curcumin.