Apigenin ameliorates genitourinary dysfunction in a type 1 diabetic rat model via Drp1 modulation.

The present study aimed to explore the potential ameliorative effect of apigenin (APG) against diabetes-associated genitourinary complications in rats. A diabetic rat model was induced by the intraperitoneal injection of streptozotocin (STZ). All experimental animals were treated with vehicle or vehicle plus APG at a dose of 0.78 mg/kg/day for 10 days, either once diabetes was confirmed or at the end of the 3rd week after confirmation of diabetes. Rats were sacrificed at the end of the fifth week. In addition to the histological assessment, an analysis of kidney function tests and serum testosterone was performed to assess diabetic genitourinary complications. Gene expression of the mitochondrial fission protein, dynamin related protein 1 (Drp1), was measured in renal and testicular tissues using qRT PCR. APG can increase body weight, reduce blood glucose levels, and improve renal and testicular functions in diabetic rats. APG decreased Drp1 overexpression in diabetic animals' kidneys and testes. In summary, our current work discloses that APG attenuates diabetic genitourinary lesions in rats via suppressing Drp1 overexpression.

Prediction of acute kidney injury using a combined model of inflammatory vascular endothelium biomarkers and ultrasound indices.

BACKGROUND: Acute kidney injury (AKI) is a common complication of sepsis, with the burden of long hospital admission. Early prediction of AKI is the most effective strategy for intervention and improvement of the outcomes. OBJECTIVE: In our study, we aimed to investigate the predictive performance of the combined model using ultrasound indices (grayscale and Doppler indieces), endothelium injury (E-selectin, VCAM-1, ICAM1, Angiopoietin 2, syndecan-1, and eNOS) as well as inflammatory biomarkers (TNF-a, and IL-1ß) to identify AKI. METHODS: Sixty albino rats were divided into control and lipopolysaccharide (LPS) groups. Renal ultrasound, biochemical and immunohistological variables were recorded 6 hrs, 24 hrs, and 48 hrs after AKI. RESULTS: Endothelium injury and inflammatory markers were found to be significantly increased early after AKI, and correlated significantly with kidney size reduction and renal resistance indices elevation. CONCLUSIONS: Using area under the curve (AUC), the combined model was analyzed based on ultrasound and biochemical variables and provided the highest predictive value for renal injury.

CRISPR/Cas9 mediated knock-out of VPREB1 gene induces a cytotoxic effect in myeloma cells.

BACKGROUND: Multiple Myeloma (MM) is a heterogeneous, hematological neoplasm that accounts 2% of all cancers. Although, autologous stem cell transplantation and chemotherapy are currently the most effective therapy, it carries a notable hazards, in addition for being non curative. Recently, the Clustered Regular Interspaced Short Palindromic Repeats (CRISPR-cas9) has been successfully tried at the experimental level, for the treatment of several hematological malignancies. OBJECTIVES: We aimed to investigate the in-vitro effect of CRISPR-cas9-mediated knock-out of V-set pre B-cell surrogate light chain 1"VPREB1" gene on the malignant proliferation of primary cultured myeloma cells. METHODS: Bioinformatics' analysis was performed to explore the gene expression profile of MM, and the VPREB1 gene was selected as a target gene for this study. We knocked-out the VPREB1 gene in primary cultured myeloma cells using CRISPR-cas9, the VPREB1 gene editing efficacy was verified by determining VPREB1 gene expression at both the mRNA and protein levels by qPCR and immunofluorescence, respectively. Furthermore, the cytotoxic effect on primary myeloma cells proliferation was evaluated using cytotoxicity assay. RESULTS: There was a statistically significant reduction of both VPREB1 mRNA and protein expression levels (p<0.01). knock-out of VPREB1 gene in myeloma cell line resulted in a statistically significant reduction of myeloma cell proliferation. CONCLUSION: CRISPR-cas9-mediated knock-out of VPREB1 gene is effective for inhibiting the proliferation of primary myeloma cells. This would provide a basis for a promising therapeutic strategy for patients with multiple myeloma.

Novel pyrimidine-bichalcophene derivatives as corrosion inhibitors for copper in 1 M nitric acid solution.

This study targets the investigation of three pyrimidine-bichalcophene derivatives (MA-1230, MA-1231, MA-1232) for the prevention of corrosion on copper in 1 M HNO3 via weight loss (WL), potentiodynamic polarization (PDP), and electrochemical impedance spectroscopy (EIS) techniques. The surface morphology was also analyzed by different methods. It was found that the inhibition efficiency (% η) increased by increasing the doses of pyrimidine derivatives and the temperature of the medium. Weight loss data revealed the better adsorption of MA-1232 on the Cu surface at increased inhibitor dose, reaching a maximum efficiency of 99.14% at a dose of 21 µM at 45 °C. The best description of the adsorption of the investigated derivatives on the copper surface was given by the Langmuir isotherm. Some important thermodynamic parameters for the studied inhibitors were computed and are discussed herein. The polarization studies showed that the pyrimidine-bichalcophenes act as mixed inhibitors. Computational chemical approaches were used with informative yields, including quantum-chemical and molecular dynamics simulation techniques, which agree with the experimental results. The results obtained from all tested methods are strongly accepted.