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Renal fibrosis is a common pathological outcome of chronic kidney diseases (CKD) that is considered as a global public health issue with high morbidity and mortality. The dry corolla of
(L.) Medik. (AMC) has been used for chronic nephritis in clinic and showed a superior effect in alleviating proteinuria in CKD patients to losartan. However, the effective components and underlying mechanism of AMC in the treatment of renal fibrosis have not been systematically clarified.
Based on drug-likeness evaluation, oral bioavailability prediction and compound contents, a systematic network pharmacology analysis was conducted to predict the active ingredients. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway analysis and protein-protein interaction analysis were applied to predict the potential pathway and target of AMC against renal fibrosis. The formula of component contribution index (CI) based on the algorithm was used to screen the principal active compounds of AMC in the treatment of renal fibved comprehension of renal fibrosis pathogenesis.
Our results predicted active components and potential targets of AMC for the application to renal fibrosis from a holistic perspective, as well as provided valuable direction for further research of AMC and improved comprehension of renal fibrosis pathogenesis.Denosumab is a receptor activator of nuclear factor kappa-Β ligand inhibitor, which suppresses the bone resorption process to preserve bone mass. It is usually recommended to postmenopausal women and men with high fracture risk. With the recent publication of the results from FREEDOM study and its extension, the long-term effect of denosumab in preventing fragility fractures has been put forward. This review aims at summarising the evidence of denosumab in reducing fracture risk and its safety derived from clinical studies. Most of the evidence are derived from FREEDOM trials up to 10 years of exposure. Denosumab is reported to prevent vertebral and non-vertebral fractures. It is also proven effective in Japanese women, patients with chronic kidney diseases and breast cancer patients receiving antineoplastic therapy. Denosumab discontinuation leads to high remodeling, loss of bone mineral density and increased fracture risk. These negative effects might be preventable by bisphosphonate treatment. The safety profile of denosumab is consistent with increased years of exposure. In conclusion, denosumab is a safe and effective option for reducing fracture risk among patients with osteoporosis.Islet transplantation is regarded as the most promising treatment for type 1 diabetes (T1D). However, the function of grafted islet could be damaged on account of transplant rejection and/or hypoxia several years later after transplantation. We proposed a hypothetical functionalized hydrogel model, which encapsulates sufficient A20 high-expressing islets and supporting cells, and performs as a drug release system releasing immunosuppressants and growth factors, to improve the outcome of pancreatic islet transplantation. Once injected in vivo, the hydrogel can gel and offer a robust mechanical structure for the A20 high-expressing islets and supporting cells. The natural biomaterials (eg, heparin) added into the hydrogel provide adhesive sites for islets to promote islets' survival. Furthermore, the hydrogel encapsulates various supporting cells, which can facilitate the vascularization and/or prevent the immune system attacking the islet graft. Based on the previous studies that generally applied one or two combined strategies to protect the function of islet graft, we designed this hypothetical multifunctional encapsulation hydrogel model with various functions. We hypothesized that the islet graft could survive and maintain its function for a longer time in vivo compared with naked islets. This hypothetical model has a limitation in terms of clinical application. Future development work will focus on verifying the function and safety of this hypothetical islet transplantation hydrogel model in vitro and in vivo.
Lead (Pb) is an environmental toxic metal that threatens human health. Umbelliferone (UMB) is a coumarin with known medicinal and protective properties against cytotoxicity. This study explored the ameliorative effect of UMB against Pb-induced testicular toxicity in rats, focusing on steroidogenesis, oxidative stress and inflammation.
Rats received lead acetate (50 mg/kg) and UMB (25, 50 or 100 mg/kg) via oral gavage for 4 weeks.
Pb-intoxicated rats exhibited testicular tissue injury and decreased serum levels of LH, FSH and testosterone. The count, viability, motility and normal morphology of the sperms were decreased accompanied with downregulated steroidogenesis markers in Pb-induced group. UMB prevented testicular injury, increased serum levels of LH, FSH and testosterone, upregulated steroidogenesis markers and improved the semen quality. In addition, UMB attenuated oxidative stress and oxidative DNA damage, downregulated the expression of pro-inflammatory mediators and Bax, boosted antioxidant defenses and Bcl-2, and upregulated Nrf2/HO-1 signaling in Pb-intoxicated rats.
UMB prevents Pb-induced testicular injury by suppressing oxidative damage, inflammation and cell death, and boosting antioxidant defenses, Nrf2/HO-1 signaling and pituitary-gonadal axis. click here Thus, UMB may represent a protective and cost-effective agent against Pb testicular toxicity, pending further investigations to elucidate other underlying mechanisms.
UMB prevents Pb-induced testicular injury by suppressing oxidative damage, inflammation and cell death, and boosting antioxidant defenses, Nrf2/HO-1 signaling and pituitary-gonadal axis. Thus, UMB may represent a protective and cost-effective agent against Pb testicular toxicity, pending further investigations to elucidate other underlying mechanisms.The coronavirus disease 2019 (COVID-19) global pandemic continues and antiviral agents and vaccines are currently under investigation. Mesenchymal stem cell (MSC)-based therapy can be a suitable option for management of patients with COVID-19 at the urgent time of virus outbreak. Currently, MSCs are being explored against the novel infectious disease due to their therapeutic properties of anti-inflammation, immunomodulation and tissue repair and regeneration, albeit the precise mechanisms of MSC action toward COVID-19 remain unclear. To date, rigorous results from clinical trials using MSCs in human have been weakly positive. The pervasive uncertainty of using MSC therapeutic products as an effective combatant against COVID-19 requires rigorous resolution on several fronts, including MSC fate after infusion, safety issue, homing capability, and MSC resistance to the disease microenvironment. Focusing on these facets, a few important ones will be critically analyzed and addressed in this article for the development of safe and effective MSC-based therapies for COVID-19.
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