1.
Understanding Sorafenib-Induced Cardiovascular Toxicity: Mechanisms and Treatment Implications.
Li, J, Zhang, L, Ge, T, Liu, J, Wang, C, Yu, Q
Drug design, development and therapy. 2024;:829-843
Abstract
Tyrosine kinase inhibitors (TKIs) have been recognized as crucial agents for treating various tumors, and one of their key targets is the intracellular site of the vascular endothelial growth factor receptor (VEGFR). While TKIs have demonstrated their effectiveness in solid tumor patients and increased life expectancy, they can also lead to adverse cardiovascular effects including hypertension, thromboembolism, cardiac ischemia, and left ventricular dysfunction. Among the TKIs, sorafenib was the first approved agent and it exerts anti-tumor effects on hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC) by inhibiting angiogenesis and tumor cell proliferation through targeting VEGFR and RAF. Unfortunately, the adverse cardiovascular effects caused by sorafenib not only affect solid tumor patients but also limit its application in curing other diseases. This review explores the mechanisms underlying sorafenib-induced cardiovascular adverse effects, including endothelial dysfunction, mitochondrial dysfunction, endoplasmic reticulum stress, dysregulated autophagy, and ferroptosis. It also discusses potential treatment strategies, such as antioxidants and renin-angiotensin system inhibitors, and highlights the association between sorafenib-induced hypertension and treatment efficacy in cancer patients. Furthermore, emerging research suggests a link between sorafenib-induced glycolysis, drug resistance, and cardiovascular toxicity, necessitating further investigation. Overall, understanding these mechanisms is crucial for optimizing sorafenib therapy and minimizing cardiovascular risks in cancer patients.
2.
MicroRNA-specific therapeutic targets and biomarkers of apoptosis following myocardial ischemia-reperfusion injury.
Ge, T, Ning, B, Wu, Y, Chen, X, Qi, H, Wang, H, Zhao, M
Molecular and cellular biochemistry. 2023
Abstract
MicroRNAs are single-stranded non-coding RNAs that participate in post-transcriptional regulation of gene expression, it is involved in the regulation of apoptosis after myocardial ischemia-reperfusion injury. For example, the alteration of mitochondrial structure is facilitated by MicroRNA-1 through the regulation of apoptosis-related proteins, such as Bax and Bcl-2, thereby mitigating cardiomyocyte apoptosis. MicroRNA-21 not only modulates the expression of NF-κB to suppress inflammatory signals but also activates the PI3K/AKT pathway to mitigate ischemia-reperfusion injury. Overexpression of MicroRNA-133 attenuates reactive oxygen species (ROS) production and suppressed the oxidative stress response, thereby mitigating cellular apoptosis. MicroRNA-139 modulates the extrinsic death signal of Fas, while MicroRNA-145 regulates endoplasmic reticulum calcium overload, both of which exert regulatory effects on cardiomyocyte apoptosis. Therefore, the article categorizes the molecular mechanisms based on the three classical pathways and multiple signaling pathways of apoptosis. It summarizes the targets and pathways of MicroRNA therapy for ischemia-reperfusion injury and analyzes future research directions.
3.
Amino acid metabolism reprogramming: shedding new light on T cell anti-tumor immunity.
Zheng, Y, Yao, Y, Ge, T, Ge, S, Jia, R, Song, X, Zhuang, A
Journal of experimental & clinical cancer research : CR. 2023;(1):291
Abstract
Metabolic reprogramming of amino acids has been increasingly recognized to initiate and fuel tumorigenesis and survival. Therefore, there is emerging interest in the application of amino acid metabolic strategies in antitumor therapy. Tremendous efforts have been made to develop amino acid metabolic node interventions such as amino acid antagonists and targeting amino acid transporters, key enzymes of amino acid metabolism, and common downstream pathways of amino acid metabolism. In addition to playing an essential role in sustaining tumor growth, new technologies and studies has revealed amino acid metabolic reprograming to have wide implications in the regulation of antitumor immune responses. Specifically, extensive crosstalk between amino acid metabolism and T cell immunity has been reported. Tumor cells can inhibit T cell immunity by depleting amino acids in the microenvironment through nutrient competition, and toxic metabolites of amino acids can also inhibit T cell function. In addition, amino acids can interfere with T cells by regulating glucose and lipid metabolism. This crucial crosstalk inspires the exploitation of novel strategies of immunotherapy enhancement and combination, owing to the unprecedented benefits of immunotherapy and the limited population it can benefit. Herein, we review recent findings related to the crosstalk between amino acid metabolism and T cell immunity. We also describe possible approaches to intervene in amino acid metabolic pathways by targeting various signaling nodes. Novel efforts to combine with and unleash potential immunotherapy are also discussed. Hopefully, some strategies that take the lead in the pipeline may soon be used for the common good.
4.
Probiotics for prevention and treatment of respiratory tract infections in children: A systematic review and meta-analysis of randomized controlled trials.
Wang, Y, Li, X, Ge, T, Xiao, Y, Liao, Y, Cui, Y, Zhang, Y, Ho, W, Yu, G, Zhang, T
Medicine. 2016;95(31):e4509
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Respiratory tract infections (RTIs) are a leading cause of morbidity and mortality among children worldwide. Probiotics are thought to be able to balance the gut microbiota and interact with the immune system, which may promote resistance against pathogens. There are conflicting results from studies investigating the effect of probiotics on RTI infection. The aim of this systematic review and meta-analysis was to provide the latest and convincing evidence of the effect of probiotic consumption on RTIs in children. 32 studies were included in the qualitative analysis, and 23 in the quantitative meta-analysis. All trials were randomised, double-blinded, and placebo-controlled. Probiotic supplementation had a significant effect on the reduction of number of subjects having at least 1 respiratory symptom episode, on the number of days the children were ill and the number of days absent from day care/school. There was no significant statistical difference of illness episode duration. There was statistical heterogeneity among the trials, and subgroup analysis did not highlight the source of this. It was noted, however, that the probiotic strain, the duration of regimens, administration forms, doses, and follow-up times differed across the included studies, as did the age of children. The authors conclude that probiotic consumption may decrease the incidence and illness duration of RTIs, and that further research is needed to establish optimal probiotic strains, dosing, administration form, time of intervention, and long-time follow-up.
Abstract
BACKGROUND Respiratory tract infections (RTIs) represent one of the main health problems in children. Probiotics are viable bacteria that colonize the intestine and affect the host intestinal microbial balance. Accumulating evidence suggests that probiotic consumption may decrease the incidence of or modify RTIs. The authors systematically reviewed data from randomized controlled trials (RCTs) to investigate the effect of probiotic consumption on RTIs in children. METHODS MEDLINE/PubMed, Embase, Cochrane Library, and Web of Science were systematically searched for RCTs regarding the effect of probiotics on RTIs in children. The outcomes included number of children experienced with at least 1 RTI episode, duration of illness episodes, days of illness per subject, and school/day care absenteeism due to infection. A random-effects model was used to calculate pooled relative risks, or mean difference (MD) with the corresponding 95% confidence interval (CI). RESULTS A total of 23 trials involving 6269 children were eligible for inclusion in the systematic review. None of the trials showed a high risk of bias. The quality of the evidence of outcomes was moderate. The age range of subjects was from newborn to 18 years. The results of meta-analysis showed that probiotic consumption significantly decreased the number of subjects having at least 1 RTI episode (17 RCTs, 4513 children, relative risk 0.89, 95% CI 0.82-0.96, P = 0.004). Children supplemented with probiotics had fewer numbers of days of RTIs per person compared with children who had taken a placebo (6 RCTs, 2067 children, MD -0.16, 95% CI -0.29 to 0.02, P = 0.03), and had fewer numbers of days absent from day care/school (8 RCTs, 1499 children, MD -0.94, 95% CI -1.72 to -0.15, P = 0.02). However, there was no statistically significant difference of illness episode duration between probiotic intervention group and placebo group (9 RCTs, 2817 children, MD -0.60, 95% CI -1.49 to 0.30, P = 0.19). CONCLUSION Based on the available data and taking into account the safety profile of RCTs, probiotic consumption appears to be a feasible way to decrease the incidence of RTIs in children.