PPBP as a marker of diabetic nephropathy podocyte injury via Bioinformatics Analysis.

Diabetic nephropathy (DN) is a type of kidney injuries associated with diabetes mellitus and the prevalence of DN has increased dramatically. However, DN still pose problems in therapy, and prognosis. Identifying new DN biomarkers would be helpful in reducing morbidity and mortality from DN and developing novel preventive approaches. In the study, from GSE36336 dataset with DN glomeruli samples, we screened for 238 differentially expressed genes. Enrichment analysis were performed to find out biological function and diseases of DEGs. Next, depended on protein-protein interaction network, We identified top 10 hub genes (Serpine1, Cxcl10, Cfd, Ppbp, Retn, Socs2, Ccr5, Mmp8, Pf4, Cxcl9) may played potential roles in DN. Meanwhile, transcriptome sequencing on podocyte were performed to reconfirm the reliability of Ppbp. To verify the efficiency of the selected genes as biomarkers, several experiments like qRT-PCR, renal histologic analysis and immunofluorescence were conducted to validate. Our results showed that PPBP have the potential to become a novel biomarker for DN podocyte injury.

Immune-related SERPINA3 as a biomarker involved in diabetic nephropathy renal tubular injury.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease and has become a serious medical issue globally. Although it is known to be associated with glomerular injury, tubular injury has been found to participate in DN in recent years. However, mechanisms of diabetic renal tubular injury remain unclear. Here, we investigated the differentially expressed genes in the renal tubules of patients with DN by analyzing three RNA-seq datasets downloaded from the Gene Expression Omnibus database. Gene set enrichment analysis and weighted gene co-expression network analysis showed that DN is highly correlated with the immune system. The immune-related gene SERPINA3 was screened out with lasso regression and Kaplan-Meier survival analyses. Considering that SERPINA3 is an inhibitor of mast cell chymase, we examined the expression level of SERPINA3 and chymase in human renal tubular biopsies and found that SERPINA3 was upregulated in DN tubules, which is consistent with the results of the differential expression analysis. Besides, the infiltration and degranulation rates of mast cells are augmented in DN. By summarizing the biological function of SERPINA3, chymase, and mast cells in DN based on our results and those of previous studies, we speculated that SERPINA3 is a protective immune-related molecule that prevents renal tubular injury by inhibiting the proliferation and activation of mast cells and downregulating the activity of chymase.

Synthesis and bioevaluation of diaryl urea derivatives as potential antitumor agents for the treatment of human colorectal cancer.

The development of inhibitors targeting the PI3K-Akt-mTOR signaling pathway has been greatly hindered by the on-target AEs, such as hyperglycemia and hepatotoxicities. In this study, a series of diaryl urea derivatives has been designed and synthesized based on clinical candidate gedatolisib (6aa), and most of the newly synthesized derivatives showed kinase inhibitory and antiproliferative activities within nanomolar and submicromolar level, respectively. The terminal l-prolineamide substituted derivative 6 ab showed 8.6-fold more potent PI3Kα inhibitory activity (0.7 nM) and 4.6-fold more potent antiproliferative effect against HCT116 cell lines (0.11 µM) compared with control 6aa. The potential antitumor mechanism and efficacy of 6 ab in HCT116 xenograft models have also been evaluated, and found 6 ab showed comparable in vivo antitumor activity with 6aa. The safety investigations revealed that compound 6 ab exhibited more safer profiles in the selectivity of liver cells (selectivity index: >6.6 vs 1.85) and blood glucose regulation than 6aa. In addition, the in vitro stability assays also indicated our developed compound 6 ab possessed good metabolic stabilities.

A comparison of dioctahedral smectite and iodine glycerin cream with topical mouth rinse in treatment of chemotherapy induced oral mucositis: a pilot study.

PURPOSE OF THE RESEARCH: To compare the efficacy of dioctahedral smectite and iodine glycerin (DSIG) cream with topical mouth rinse (composed of saline, gentamicin and Vitamin B12) in treatment of chemotherapy induced oral mucositis (OM). METHODS AND SAMPLE: A total of 130 intensive chemotherapy or stem cells transplantation induced OM patients were recruited. Among these patients, 67 patients received topical mouth rinse and 63 patients received DSIG cream treatment. The OM would be treated on the OM appearance and sustained for 5 days. OM severity was measured daily using The American Oncology Nursing Society recommended Oral Assessment Guideline (OAG) score system. KEY RESULTS: Compared with topical mouth rinse treatment, a significant lower OAG score was observed in DSIG cream treated patients. Specifically, the OAG scores were respectively 12.1 ± 1.1, 12.0 ± 1.2, 11.3 ± 1.3 and 10.4 ± 1.3 from day 2 to day 5 in topical mouth rinse treatment subgroup. Correspondingly, the OAG scores were respectively 10.2 ± 1.0, 9.3 ± 0.9, 8.5 ± 0.6 and 8.0 ± 0.2 for DSIG cream treatment subset (all P < 0.05). Importantly, compared with topical mouth rinse treatment, the DSIG cream significantly shortened OM repair time (4.68 ± 0.98 vs. 8.76 ± 1.80 days, P < 0.001). After 5 days treatment, 54 patients (85.7%) obtained complete regression with an OAG score ≤8, and 7 patients (11.1%) had partial regression with an OAG score of 9-10 in DSIG cream treatment subgroup. However, only 2 patients (3.0%) obtained completed regression and 32 patients (47.8%) had partial regression in topical mouth rinse treatment cohort. Moreover, no serious side-effect was observed in both cohorts. CONCLUSIONS: Compared with topical mouth rinse, DSIG cream significantly lowered the OAG score and shortened OM duration.