ABSTRACT
Purpose: Diabetes mellitus is a serious health problem worldwide, and diabetic nephropathy is the complication. The diabetic nephropathy considerably enhances the oxidative stress, glycation, lipid parameters and inflammatory reaction. Ellipticine has potent free radical scavenging and anti-inflammatory effect. Methods: In the current study, our objectives were to thoroughly examine the renal protective effects of ellipticine in a rat model of streptozotocin (STZ)-induced diabetic nephropathy (DN) and to elucidate the underlying mechanisms involved. For the induction of diabetic nephropathy, streptozotocin (50 mg/kg) was used, and rats were separated into groups and given varying doses of ellipticine (2.5, 5 and 7.5 mg/kg). The body weight, and renal weight were estimated. The inflammatory cytokines, renal biomarkers, inflammatory antioxidant, and urine parameters were estimated. Results: Result showed that ellipticine considerably enhanced the body weight and reduced the renal tissue weight. Ellipticine treatment significantly (P < 0.001) repressed the level of blood urea nitrogen, serum creatinine, uric acid, blood glucose and altered the lipid parameters. Ellipticine significantly (P < 0.001) repressed the level of malonaldehyde and boosted the glutathione, catalase, superoxide dismutase, and glutathione peroxidase. Ellipticine treatment significantly (P < 0.001) reduced the inflammatory cytokines and inflammatory mediators. Conclusions: Ellipticine could be a renal protective drug via attenuating the inflammatory reaction, fibrosis and oxidative stress in streptozotocin induced rats.
Subject(s)
Animals , Rats , Streptozocin , Oxidative Stress , Diabetic Nephropathies , Ellipticines , Inflammation , AntioxidantsABSTRACT
Objective::To analyze the potential targets and mechanism of Ginseng Radix et Rhizoma-Astragali Radix treatment in lung cancer based on network pharmacology. Method::The Ginseng Radix et Rhizoma, Astragali Radix ingredients and target genes were screened by the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP). Lung cancer-related target genes were obtained from the human gene database (GeneCards). Cytoscape was used for constructing a " drug-ingredient-target-disease" network. Protein-to-protein interaction (PPI) data was downloaded from STRING and then PPI core genes was constructed by CentiScape. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of key target genes was performed using R software. Result::A total of 17 Ginseng Radix et Rhizoma and 16 Astragali Radix ingredients were screened. 50 target genes of Astragali Radix and 95 target genes of Ginseng Radix et Rhizoma in the treatment of lung cancer were obtained. A " drug-ingredient-target-disease" network was constructed. 38 PPI core genes were screened using CentiScape. GO function enrichment showed that biological functions of Ginseng Radix et Rhizoma-Astragali Radix were concentrated in nuclear receptor function, transcription-related function, ubiquitination and apoptosis. KEGG pathway enrichment showed that Ginseng Radix et Rhizoma-Astragali Radix treatment in lung cancer were mainly involved in phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), apoptosis, tumor necrosis factor (TNF) and other pathways. Conclusion::By constructing a " drug-ingredient-target-disease" network, the mechanism of Ginseng Radix et Rhizoma-Astragali Radix treatment in lung cancer was discussed from the perspective of multi-component, multi-target and multi-pathway, which provides reference for further research.
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@# Objective：To analyze the expression and clinic significance of activity-dependent neuroprotective protein (ADNP) in bladder urothelial carcinoma. Methods: A total of 28 pairs of bladder cancer tissues and corresponding adjacent normal tissuesthat surgically resected at the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University from June 1, 2019 to July 15, 2019 were collected for this study. The mRNAexpression ofADNP in 20 pairs of tissue samples was detected by qPCR, and the protein expressionin the other 8 pairs was detected by WB. Mean while, the clinicopathological data of patients with bladder urothelial carcinoma treated in our hospital from January 1, 2005 to December 31, 2007 were retrospectively analyzed; and the expression of ADNP in the corresponding paraffin tumor sections were determined with immunohistochemical staining, and normal bladder tissue sections from patients who underwent surgery for other bladder diseases during the same period were collected for comparison. Chi-square test was used to analyze the correlation between ADNP expression and different clinicopathological features, Kaplan-Meier method was used for survival analysis, and Cox risk regression model was used forunivariate and multivariate analysis of prognosticfactors. Results: ThetranscriptionalandtranslationallevelsofADNPincancertissues were higher than those in adjacent normal tissues (all P<0.05), and the expression level ofADNP was correlated with the histological grade, clinical stages and survival status of patients with bladder cancer (P<0.05). Of all the 221 patients included in the study, 32 patients lost to follow-up,and patients with high ADNP expression had
ABSTRACT
To discover novel fluoroquinolone lead compounds as possible anti-infective or/and antitumor chemotherapies, combination principle of pharmacophore-based drug design, a series of novel tricyclic fluoroquinolone title compounds, [1,2,4]triazino[3,4-h][1,8]naphthyridine-8-one-7-carboxylic acid derivatives ( 5a-5p), were designed and synthesized with a fused [1,2,4]-triazine ring unit. Their structures were characterized by spectral data and elemental analysis and the in vitro antibacterial and anti-cell proliferation activities were also evaluated. The results showed that the titled compounds exhibited more significant inhibitory activities against drug-resistant bacteria (Methicillin-resistant Staphylococcus aureus and multi drug-resistant Escherichia coli strains) and three tested cancer cell lines (human hepatoma SMMC-7721, murine leukemia L1210 and human murine leukemia HL60 cells). Interestingly, SAR showed that compounds with electron-donating groups attached to benzene ring had stronger antibacterial activity than antitumor activity, but electron-withdrawing compounds displayed more potential antitumor activity than antibacterial activity, especially antitumor activity of nitro compounds was comparable to comparison doxorubicin. Thus, novel triazine-fused tricyclic fluoroquinolones as potent anti-infective or/and antitumor lead compounds are valuable to pay attention and for further development.