The Protective Effect of 11-Keto-β-Boswellic Acid against Diabetic Cardiomyopathy in Rats Entails Activation of AMPK

This study examined the protective effect of 11-keto-β-boswellic acid (AKBA) against streptozotocin (STZ)-induced diabetic cardiomyopathy (DC) in rats and examined the possible mechanisms of action. Male rats were divided into 5 groups (n = 8/each): (1) control, AKBA (10 mg/kg, orally), STZ (65 mg/kg, i.p.), STZ + AKBA (10 mg/kg, orally), and STZ + AKBA + compound C (CC/an AMPK inhibitor, 0.2 mg/kg, i.p.). AKBA improved the structure and the systolic and diastolic functions of the left ventricles (LVs) of STZ rats. It also attenuated the increase in plasma glucose, plasma insulin, and serum and hepatic levels of triglycerides (TGs), cholesterol (CHOL), and free fatty acids (FFAs) in these diabetic rats. AKBA stimulated the ventricular activities of phosphofructokinase (PFK), pyruvate dehydrogenase (PDH), and acetyl CoA carboxylase (ACC); increased levels of malonyl CoA; and reduced levels of carnitine palmitoyltransferase I (CPT1), indicating improvement in glucose and FA oxidation. It also reduced levels of malondialdehyde (MDA); increased mitochondria efficiency and ATP production; stimulated mRNA, total, and nuclear levels of Nrf2; increased levels of glutathione (GSH), heme oxygenase (HO-1), superoxide dismutase (SOD), and catalase (CAT); but reduced the expression and nuclear translocation of NF-κB and levels of tumor-necrosis factor-α (TNF-α) and interleukin-6 (IL-6). These effects were concomitant with increased activities of AMPK in the LVs of the control and STZ-diabetic rats. Treatment with CC abolished all these protective effects of AKBA. In conclusion, AKBA protects against DC in rats, mainly by activating the AMPK-dependent control of insulin release, cardiac metabolism, and antioxidant and anti-inflammatory effects

Esculeoside A alleviates reproductive toxicity in streptozotocin-diabetic rats’ s model by activating Nrf2 signaling

This examination studied if Esculeoside A (ESA) alleviates reproductive toxicity in a type 1 diabetes mellitus (T1DM) rat model and if activating Nrf2 underlies this protection. T1DM was established by a single injection of STZ. Aged-matched adult control and STZ-DM rats were administered either the vehicle (5% carboxymethyl cellulose) or ESA (100 mg/kg). An additional group [STZ-DM + ESA (100 mg) + brusatol (2 m/kg] was added. All treatments were conducted for 16 weeks. ESA failed to attenuate weight loss, hyperglycemia, and hypoinsulinemia but significantly attenuated the associated dyslipidemia in STZ-DM rats. In parallel, ESA also enhanced total sperm count, motility, survival, reduced head and tail sperm abnormalities, increased circulatory concentrations of follicular stimulating hormone (FSH), testosterone, and Luteinizing hormone (LH), and stimulated the testicular expression of several steroidogenic enzymes (StAR, CYP11A1, CYP17A1, 3β-HSD1) in STZ-DM rats. These observations were associated with a higher testicular increase in the transcription, protein levels, and nuclear activities of Nrf2 that coincided with a reduction in the total levels of MDA and keap1 and a significant increase in the total levels of some antioxidants such as HO-1, SOD, and GSH. In concomitance, ESA reduced the testicular mRNA and nuclear concentrations of NF-κB and depressed the levels of TNF-α and IL-6. Brusatol prevented all these protective effects of ESA. In conclusion, activation of Nrf2 triggers the protective potential of ESA against reproductive toxicity in STZ-DM rats

Computational intelligence modeling using Artificial Intelligence and optimization of processing of small-molecule API solubility in supercritical solvent

Preparation of small-molecule API (Active Pharmaceutical Ingredient) at submicron size would be of great benefit for pharmaceutical engineering, as the drug particles at submicron size possess higher solubility in water. Indeed, the drug bioavailability can be enhanced when the nanomedicine is prepared. In this study, the solubility of the drug desoxycorticosterone acetate (DA) is being examined to assess its viability of nanonization using supercritical operation. Two inputs are temperature and pressure which were considered for machine learning modeling in this study. The drug's solubility is the only output to be estimated by the optimized models. This dataset has 45 rows of data that were gathered at 5 different pressure and temperature levels. Support vector machine (SVM) is used as the core of the models built in this research. Epsilon-SVR and nu-SVR are models based on this concept, which together with two different polynomial and RBF kernels form the four models built in this research for estimation of DA drug solubility. The models are also optimized with the help of a new TLCO method. All four final models have an R2 score higher than 0.9, and among them, the Epsilon-SVR model with RBF kernel has the best performance with 0.967

Assessing Acetabular Index Angle in Infants: A Deep Learning-Based Novel Approach

Developmental dysplasia of the hip (DDH) is a disorder characterized by abnormal hip development that frequently manifests in infancy and early childhood. Preventing DDH from occurring relies on a timely and accurate diagnosis, which requires careful assessment by medical specialists during early X-ray scans. However, this process can be challenging for medical personnel to achieve without proper training. To address this challenge, we propose a computational framework to detect DDH in pelvic X-ray imaging of infants that utilizes a pipelined deep learning-based technique consisting of two stages: instance segmentation and keypoint detection models to measure acetabular index angle and assess DDH affliction in the presented case. The main aim of this process is to provide an objective and unified approach to DDH diagnosis. The model achieved an average pixel error of 2.862 ± 2.392 and an error range of 2.402 ± 1.963° for the acetabular angle measurement relative to the ground truth annotation. Ultimately, the deep-learning model will be integrated into the fully developed mobile application to make it easily accessible for medical specialists to test and evaluate. This will reduce the burden on medical specialists while providing an accurate and explainable DDH diagnosis for infants, thereby increasing their chances of successful treatment and recovery