Metabolic dysfunction-associated fatty liver disease (MAFLD) has been related to a series of harmful health consequences. The triglyceride-glucose index (TyG index) appears to be associated with MAFLD. However, no consistent conclusions about the TyG index and incident MAFLD have been reached. PubMed, MEDLINE, Web of Science, EMBASE and the Cochrane Library were searched. Sensitivities, specificities and the area under the receiver operating characteristic (AUC) with a random-effects model were used to assess the diagnostic performance of the TyG index in NAFLD/MAFLD participants. Potential threshold effects and publication bias were evaluated by Spearman’s correlation and Deeks’ asymmetry test, respectively. A total of 20 studies with 165725 MAFLD participants were included. The summary receiver operator characteristic (SROC) curve showed that the sensitivity, specificity and AUC were 0.73 (0.69–0.76), 0.67 (0.65, 0.70) and 0.75 (0.71–0.79), respectively. Threshold effects (r = 0.490, p < 0.05) were confirmed to exist. Subgroup analyses and meta-regression showed that some factors including country, number of samples, age and disease situation were the sources of heterogeneity (p < 0.05). Our meta-analysis suggests that the TyG index can diagnose and predict MAFLD patients with good accuracy. The number of studies remains limited, and prospective studies are needed.
Oxidative cell death is caused by an overproduction of reactive oxygen species and an imbalance in the antioxidant defense system, leading to neuronal dysfunction and death. The harm of oxidative stress in the central nervous system (CNS) is extensive and complex, involving a variety of molecular and cellular level changes that may lead to a variety of acute and chronic brain pathologies, such as stroke, traumatic brain injury, or neurodegenerative diseases and psychological disorders. This review provides an in-depth look at the mechanisms of oxidative cell death in the central nervous system diseases. In addition, the review evaluated existing treatment strategies, including antioxidant therapy, gene therapy, and pharmacological interventions targeting specific signaling pathways, all aimed at alleviating oxidative stress and protecting nerve cells. We also discuss current advances and challenges in clinical trials, and suggest new directions for future research, including biomarker discovery, identification of potential drug targets, and exploration of new therapeutic techniques, with a view to providing more effective strategies for the treatment of CNS diseases.
Osteosarcoma (OS) is a serious primary bone malignant tumor that can easily affect children and adolescents. Chemotherapy is one of the important and feasible clinical treatment strategies for the treatment of OS at present, which is severely limited due to insufficient retention time, poor penetration ability, and serious side effects of current anti-tumor drug preparations. In this work, a novel injectable thermo-sensitive hydrogel (mPEG45–PLV19) loaded with methotrexate and alendronate, and the sustained release at the tumor site synergistically inhibited the progression of OS. The mPEG45–PLV19 shows excellent physical and chemical properties. Compared with other treatment groups, the in vivo treatment of gel+ methotrexate + alendronate effectively inhibited the growth of tumor. More importantly, it significantly reduced bone destruction and lung metastasis caused by OS. Therefore, this injectable thermo-sensitive hydrogel drug delivery system has broad prospects for OS chemotherapy.
The instability of PEGylated polylactide micelles is a challenge for drug delivery. Stereocomplex interaction between racemic polylactide chains with different configurations provides an effective strategy to enhance the stability of micelles as the nanocarriers of drugs. In this work, a stereocomplex micelle (SCM) self-assembled from the amphiphilic triblock copolymers comprising poly(ethylene glycol) (PEG), and dextrorotatory and levorotatory polylactides (PDLA and PLLA) was applied for efficient drug delivery. The spherical SCM showed the smallest scale and the lowest critical micelle concentration (CMC) than the micelles with single components attributed to the stereocomplex interaction between PDLA and PLLA. 10-Hydroxycamptothecin (HCPT) as a model antitumor drug was loaded into micelles. Compared with the loading micelles from individual PDLA and PLLA, the HCPT-loaded SCM exhibited the highest drug loading efficiency (DLE) and the slowest drug release in phosphate-buffered saline (PBS) at pH 7.4, indicating its enhanced stability in circulation. More fascinatingly, the laden SCM was demonstrated to have the highest cellular uptake of HCPT and suppress malignant cells most effectively in comparison to the HCPT-loaded micelles from single copolymer. In summary, the stereocomplex-enhanced PLA–PEG–PLA micelle may be promising for optimized drug delivery in the clinic.