ARG1 and CXCL2 are potential biomarkers target for psoriasis patients.

BACKGROUND: Psoriasis is a common chronic skin inflammatory disease. Understanding the pathogenesis of psoriasis and identifying novel therapeutic targets are under investigation. METHODS: Gene expression profiles were obtained from GSE13355, GSE30999 and GSE54456 datasets to identify differentially expressed genes (DEGs) between psoriasis and normal controls. Enrichment analysis was used to identify the biological functions and pathways of common genes from three groups of DEGs. Protein-protein interaction (PPI) network was then constructed to identify key genes according to degree of connectivity. Expression of genes was detected by the method of qRT-PCR and immunohistochemistry. The infiltration of immune cells of psoriasis were quantified and detected by flow cytometry. RESULTS: A total of 146 common genes were identified between psoriasis and normal controls. They were significantly enriched in IL-17, chemokine, and NOD-like receptor (NLR) signaling pathway. Ten key genes were selected with bigger degree of connectivity through PPI network, and ARG1 and CXCL2 had better predictive ability based on ROC curves. Increased expression of ARG1 and CXCL2 in psoriasis patients were verified by qRT-PCR and immunohistochemistry method. In addition, a lot of immune cells were upregulated in psoriasis compared to healthy controls through ssGSEA and flow cytometry. CONCLUSION: ARG1 and CXCL2 may serve as biomarkers and potential therapy for psoriasis. This may be related to the immune response and NLR pathway.

MiR-21 alleviates renal tubular epithelial cells injury induced by ischemia by targeting TLR4.

Renal ischemia is the initial stage of kidney damage, leading to mitochondrial metabolism disorders and cell necrosis. In this study, we aimed to investigate the biological functions and potential mechanisms of miR-21 in protecting renal tubular epithelial cells from oxidative stress and apoptosis following oxygen glucose deprivation (OGD). Following an OGD injury, miR-21 levels increased in HK-2 renal tubular epithelial cells. Overexpression of miR-21 decreased the protein expressions of cleaved caspase-3, BAX, P53, cell apoptosis and increased Bcl-2 expression in HK-2 cells with OGD injury. In vivo studies found that miR-21 agomir reduced renal tissue apoptosis, while miR-21 antagomir increased it. In addition, overexpression of miR-21 reduced levels of reactive oxygen species (ROS), malondialdehyde (MDA) and lactate dehydrogenase (LDH) in HK-2 cells with OGD injury. However, miR-21 inhibition exhibited the opposite effect. A dual-luciferase reporter assay demonstrated that miR-21 directly regulates Toll-like receptor 4 (TLR4) by targeting the 3'-UTR of TLR4 mRNA. Overexpression of miR-21 led to decreased TLR4 protein expression, and TLR4 knockdown was shown to greatly increase AKT activity in HK-2 cells by in vitro kinase assay. Additionally, TLR4 knockdown promoted AKT phosphorylation and hypoxia-inducible factor-1α (HIF-1α) expression, while TLR4 overexpression inhibited these processes. Furthermore, AKT activation abolished the effect of TLR4 on HIF-1α, while AKT inhibition decreased the expression of TLR4 on HIF-1α in TLR4 knockdown HK-2 cells. Further study revealed that HIF-1α inhibition abolished the protective effect of miR-21 overexpression on ROS, LDH levels and cell apoptosis in HK-2 cells after OGD injury, which is indicated by increased levels of ROS and LDH, as well as increased cell apoptosis after HIF-1α inhibition in miR-21-treated HK-2 cells. In conclusion, miR-21 defends OGD-induced HK-2 cell injury via the TLR4/AKT/HIF-1α axis.

Efficacy and safety of mizoribine combined with losartan in the treatment of IgA nephropathy: a multicenter, randomized, controlled study.

INTRODUCTION: Few have tried to prove the effectiveness of mizoribine combined with losartan for adult IgA nephropathy patients in a randomized controlled trial. METHODS: A multicenter, randomized, controlled, 12-month study was performed to evaluated the efficacy and safety of mizoribine combined with losartan for adult IgA nephropathy. Ninety-nine patients with primary IgA nephropathy from 8 clinical institutions were randomly assigned to the losartan group (n = 30), the mizoribine group (n = 35) or the combination (losartan+mizoribine) group (n = 34). The primary outcome was 24-hour urinary protein excretion (24 hours-UP). RESULTS: There were no significant differences in baseline data among the 3 groups. In all 3 groups, 24 hours-UP after 3, 6, 9 and 12 months of treatment were significantly lower than the baseline level. The reduction in 24 hours-UP in the losartan group was observed early and reached maximum after 6 months of treatment. Twenty-four hours-UP in the mizoribine group and combination group continuously decreased during the study. Comparisons among the 3 groups showed that the losartan group was superior to the mizoribine group after 3 months of treatment, but that after 12 months of treatment, both the combination group and the mizoribine group were superior to the losartan group in the reduction of 24 hours-UP. There were no significant differences among the 3 groups in serum creatinine. No serious adverse events occurred in any of the 3 groups. CONCLUSIONS: The treatment of adult IgA nephropathy with mizoribine alone, losartan alone or a combination of the 2 reduced 24 hours-UP. Mizoribine and losartan, when used in combination, complement each other's activities.