Effects of extraosseous talotarsal stabilization on the biomechanics of flexible flatfoot subtalar joints in children: a finite element study

Background: Objective of the study was to generate an experimental foundation for the clinical application of extraosseous talotarsal stabilization (EOTTS) in treatment of flexible flatfeet in children by investigating the biomechanical characteristics of flexible flatfoot and the effects of EOTTS on hindfoot biomechanics.Methods: Three-dimensional finite element models of the foot and ankle complex were generated from computer tomography images of a volunteer’s left foot in three states: normal, flexible flatfoot, and post-EOTTS. After validation by X-ray, simulated loads were applied to the three models in a neutral position with both feet standing.Results: In the flexible flatfoot model, the contact stress on the subtalar joint increased and contact areas decreased, resulting in abnormal stress distribution compared to the normal model. However, following treatment of the foot with EOTTS, these parameters returned to close to normal. Subtalar joint instability leads to a flexible flat foot. Based on this study, it is proposed that EOTTS can restore the normal function of the subtalar joint in and is an effective treatment for flexible flatfoot in children. We and many clinical data studies provide evidence for sinus tarsi implants in pediatric patients. It is showed that the formation of flexible flatfoot is induced by subtalar joint instability.Conclusions: Because of the EOTTS provides the best biomechanical solution to subtalar joint instability, the EOTTS became an effective form for subtalar joint instability treatment

Emodin Protects against Diabetic Cardiomyopathy by Regulating the AKT/GSK-3β Signaling Pathway in the Rat Model

Diabetes mellitus (DM) has been recognized as a major health problem. Emodin (Emo) has been reported to exhibit protective effects against diabetic nephropathy. However, little has been known about the effect of Emo on diabetic cardiomyopathy (DCM). A type 2 DM model was induced in rats by low dose streptozotocin (STZ) combined with high energy intake. We found that Emo-treated groups displayed significantly higher body weight (BW) and lower heart weight (HW)/BW. Furthermore, Emo could significantly decrease blood glucose, total cholesterol (TG) levels, and triglyceride (TC) levels in diabetic rats. Moreover, the Emo-treated group showed a marked increase in heart rate (HR) and showed lower left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular posterior wall thickness (LWPWT), and interventricular septal diastolic wall thickness (IVSD). Emo induced a significant increase in phosphorylation of Akt and GSK-3β in myocardium. These results suggest that Emo may have great therapeutic potential in the treatment of DCM by Akt/GSK-3β signaling pathway

Analysis of genetic biomarkers, polymorphisms in ADME-related genes and their impact on pharmacotherapy for prostate cancer

Abstract Prostate cancer (PCa) is a non-cutaneous malignancy in males with wide variation in incidence rates across the globe. It is the second most reported cause of cancer death. Its etiology may have been linked to genetic polymorphisms, which are not only dominating cause of malignancy casualties but also exerts significant effects on pharmacotherapy outcomes. Although many therapeutic options are available, but suitable candidates identified by useful biomarkers can exhibit maximum therapeutic efficacy. The single-nucleotide polymorphisms (SNPs) reported in androgen receptor signaling genes influence the effectiveness of androgen receptor pathway inhibitors and androgen deprivation therapy. Furthermore, SNPs located in genes involved in transport, drug metabolism, and efflux pumps also influence the efficacy of pharmacotherapy. Hence, SNPs biomarkers provide the basis for individualized pharmacotherapy. The pharmacotherapeutic options for PCa include hormonal therapy, chemotherapy (Docetaxel, Mitoxantrone, Cabazitaxel, and Estramustine, etc.), and radiotherapy. Here, we overview the impact of SNPs reported in various genes on the pharmacotherapy for PCa and evaluate current genetic biomarkers with an emphasis on early diagnosis and individualized treatment strategy in PCa

An erythrocyte-delivered photoactivatable oxaliplatin nanoprodrug for enhanced antitumor efficacy and immune response

10.1039/d1sc02941jCHEMICAL SCIENCE124314353-1436

Organocatalytic Discrimination of Non-Directing Aryl and Heteroaryl Groups: Enantioselective Synthesis of Bioactive Indole-Containing Triarylmethanes

Despite the enormous developments of asymmetric catalysis, the basis for asymmetric induction is largely limited to spatial interaction between substrate and catalyst. Consequently, asymmetric discrimination between two sterically similar groups remains a challenge. This is particularly formidable for enantiodifferentiation between aryl and heteroaryl groups without a directing group or electronic manipulation. Here we address this challenge by a robust organocatalytic system leading to excellent enantioselection between aryl and heteroaryl groups. With the versatile 2-indole imine methide as platform, an excellent combination of a superb chiral phosphoric acid and the optimal hydride source provided efficient access to a range of highly enantioenriched indole-containing triarylmethanes. Control experiments and kinetic studies provided important insights into the mechanism. DFT calculations also indicated that, while hydrogen bonding is important for activation, the key interaction for discrimination of the two aryl groups is mainly π-π stacking. Preliminary biological studies also demonstrated the great potential of these triarylmethanes for anticancer and antiviral drug development