Bioinformatics led discovery of biomarkers related to immune infiltration in diabetes nephropathy.

BACKGROUND: The leading cause of end-stage renal disease is diabetic nephropathy (DN). A key factor in DN is immune cell infiltration (ICI). It has been shown that immune-related genes play a significant role in inflammation and immune cell recruitment. However, neither the underlying mechanisms nor immune-related biomarkers have been identified in DNs. Using bioinformatics, this study investigated biomarkers associated with immunity in DN. METHODS: Using bioinformatic methods, this study aimed to identify biomarkers and immune infiltration associated with DN. Gene expression profiles (GSE30528, GSE47183, and GSE104948) were selected from the Gene Expression Omnibus database. First, we identified 23 differentially expressed immune-related genes and 7 signature genes, LYZ, CCL5, ALB, IGF1, CXCL2, NR4A2, and RBP4. Subsequently, protein-protein interaction networks were created, and functional enrichment analysis and genome enrichment analysis were performed using the gene ontology and Kyoto Encyclopedia of Genes and Genome databases. In the R software, the ConsensusClusterPlus package identified 2 different immune modes (cluster A and cluster B) following the consistent clustering method. The infiltration of immune cells between the 2 clusters was analyzed by applying the CIBERSORT method. And preliminarily verified the characteristic genes through in vitro experiments. RESULTS: In this study, the samples of diabetes nephropathy were classified based on immune related genes, and the Hub genes LYZ, CCL5, ALB, IGF1, CXCL2, NR4A2 and RBP4 related to immune infiltration of diabetes nephropathy were obtained through the analysis of gene expression differences between different subtypes. CONCLUSIONS: This study was based on bioinformatics technology to analyze the biomarkers of immune related genes in diabetes nephropathy. To analyze the pathogenesis of diabetes nephropathy at the RNA level, and ultimately provide guidance for disease diagnosis, treatment, and prognosis.

Improvement of resistance to rice blast and bacterial leaf streak by CRISPR/Cas9-mediated mutagenesis of Pi21 and OsSULTR3;6 in rice (Oryza sativa L.).

Rice (Oryza sativa L.) is a staple food in many countries around the world, particularly in China. The production of rice is seriously affected by the bacterial leaf streak and rice blast, which can reduce rice yield or even cause it to fail to be harvested. In this study, susceptible material 58B was edited by CRISPR/Cas9, targeting a target of the Pi21 gene and a target of the effector-binding element (EBE) of the OsSULTR3;6 gene, and the mutants 58b were obtained by Agrobacterium-mediated method. The editing efficiency of the two targets in the T0 generation was higher than 90.09%, the homozygous mutants were successfully selected in the T0 generation, and the homozygous mutation rate of each target was higher than 26.67%. The expression of the edited pi21 and EBE of Ossultr3;6 was significantly reduced, and the expression of defense responsive genes was significantly upregulated after infected with rice blast. The lesion areas of rice blast and bacterial leaf streak were significantly reduced in 58b, and the resistance of both was effectively improved. Furthermore, the gene editing events did not affect the agronomic traits of rice. In this study, the resistance of 58b to rice blast and bacterial leaf streak was improved simultaneously. This study provides a reference for using Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 (CRISPR/Cas9) to accelerate the improvement of rice varieties and the development of new materials for rice breeding.

Inhibitory action of chamaejasmin A against human HEP-2 epithelial cells: effect on tubulin protein.

In this work, the anticancer activity of chamaejasmin A was studied by evaluating its in vitro cytotoxicity against several cell lines (CAL-27, UMSCC-1, UMSCCG19, HEP-2 and Vero cells) using the 3-(4,5)-dimethylthiazoly1)-3,5-diphenytetrazolium bromide assay. Results indicated chamaejasmin A shows more notable anticancer activity against HEP-2 cells, with IC(50) values of 3.48 µM. Furthermore, western blot analysis showed that chamaejasmin A is able to increase the expression of ß-tubulin (TB), but not α-TB. In vivo, chamaejasmin A intake through gavage resulted in ß-TB depolymerization inhibition in HEP-2 tumors. In silico simulations indicated that chamaejasmin A specifically interacts with the binding site which is located at the top of ß-TB, thanks to the presence of strong hydrophobic effects between the core templates and the hydrophobic surface of the TB protein active site, associated with two strong H-bonds. The binding energy (E (inter)) was calculated to be -129.40 kcal mol(-1). Results above suggest that chamaejasmin A possesses anti-cancer properties relating to ß-TB depolymerization inhibition.

Ezetimibe analogs with a reorganized azetidinone ring: Design, synthesis, and evaluation of cholesterol absorption inhibitions.

The underlying principle of drug design in this paper is that the maximum retention of the functional groups that exist in the marketed drug would provide a higher probability for comparable safety while the conformational changes in the newly created analogs should not constitute a significant structural variation to adversely affect biological activity. Four individual isomers of backbone re-organized ezetimibe analogs were designed and synthesized. Their effects on the cholesterol levels in rat serum were evaluated by a high-cholesterol and high-fat diet feeding experiment. All the new analogs showed significant effect in lowering the levels of total cholesterol in serum.

[The antitumor activity of Diosgenin in vivo and in vitro].

OBJECTIVE: To investigate the antitumor activity of Diosgenin in vivo and in vitro. METHOD: S-180, HepA, U14 and EAC transplant mice were given Diosgenin ig or i.p. everyday for 10 days, from the next day when they were inoculated in axilla. Tumor growth inhibit rates were calculated. Four kinds of cells, MCF, L929, A375-S2 and HeLa, were incubated respectively with Diosgenin in vitro. Tumor growth inhibit rates were also calculated. RESULT: In vivo, both ig and i.p., Diosgenin inhibited S-180, HepA, U 14 mice transplant tumor, the inhibit rates being 30%-50%, but it did not inhibit the EAC mice transplant tumor. In vitro, Diosgenin inhibited L929, HeLa, MCF cell growth, and IC50 were 1.2, 18.2, 19.8 micrograms.mL-1 respectively, but it did not significantly affect A375-S2 cells. CONCLUSION: Diosgenin has an obvious antitumor activity on S-180, HepA, U14 transplant mice in vivo and L929, HeLa, MCF cells in vitro.