Therapeutic potential of vitamin D3 in mitigating high glucose­induced renal damage: Mechanistic insights into oxidative stress inhibition and TXNIP/NLRP3 signaling pathway blockade.

In the development of diabetic nephropathy, pathological damage such as interstitial fibrosis and cell apoptosis often occur in renal tubules. In the present study, diabetic and control group mice were randomly treated with vitamin D3 or vehicle for 6 months. In addition, human renal tubular epithelial (HK-2) cells were cultured in high-glucose medium and treated with vitamin D3 or the oxidative inhibitor NAC. Immunohistochemistry, western blotting, quantitative PCR), and ELISA showed that vitamin D3 decreased the expression of α-smooth muscle actin and E-cadherin in renal tubular epithelial cells, improving interstitial fibrosis. It also downregulated the ratio of Bax/Bcl2 protein, alleviating apoptosis in renal tubular epithelial cells. Furthermore, vitamin D3 significantly inhibited oxidative stress response in renal tubular epithelial cells and blocked the (Thioredoxin Interacting Protein) TXNIP/NLRP3 inflammatory pathway. Therefore, vitamin D3 can protect renal tubular epithelial cells from fibrosis and apoptosis by inhibiting oxidative stress response and blocking the TXNIP/NLRP3 inflammatory pathway in diabetic nephropathy.

Preparation of ultrasound contrast agents: The exploration of the structure-echogenicity relationship of contrast agents based on neural network model.

There is a need to standardize the process of micro/nanobubble preparation to bring it closer to clinical translation. We explored a neural network-based model to predict the structure-echogenicity relationship for the preparation and fabrication of ultrasound-enhanced contrast agents. Seven formulations were screened, and 109 measurements were obtained. An artificial neural network-multilayer perceptron (ANN-MLP) model was used. The original data were divided into the training and testing groups, which included 73 and 36 groups of data, respectively. The hidden layer was selected from three hidden layers and included bias. The classification graph showed that the predicted values of the training and testing groups were 76.7% and 66.7%, respectively. According to the receiver operating characteristic curve, the accuracy of different imaging effects could achieve a prediction rate of 88.1-96.5%. The percentage graph showed that the data were gradually converging. The predictive analysis curves of different ultrasound effects gradually approached stable value of Gain. Normalized importance predicted contributions for the Pk1, poly-dispersity index (PDI), and intensity account were 100%, 98.5%, and 89.7%, respectively. The application of the ANN-MLP model is feasible and effective for the exploration of the synthesis process of ultrasound contrast agents. 1,2-Distearoyl-sn-glycero-3 phosphoethanolamine-N (methoxy[polyethylene glycol]-2000) (DSPE PEG-2000) correlated highly with the success rate of contrast agent synthesis.