Journal of Biomedical Research最新文献

Chronic hypoxia is a key factor in the pathogenesis of cardiovascular diseases, including ischemia, heart failure, and hypertension. Under hypoxia, oxygen deficiency disrupts oxidative phosphorylation in mitochondria, impairing ATP production and generating reactive oxygen species (ROS). These reactive species induce mitochondrial dysfunction, leading to oxidative stress, calcium imbalance, and activation of apoptosis pathways. The mitochondrial ATP-sensitive potassium channel (mitoK _ATP) and mitochondrial permeability transition pore (mPTP) channels are particularly affected, contributing to membrane potential loss, cytochrome c release, and cell death. This review delves into the molecular mechanisms underlying hypoxia-induced cardiovascular diseases, with a focus on mitochondrial impairment, ion channel dysfunction, and ROS overproduction. Additionally, we examine hypoxia-inducible factor 1-alpha (HIF-1α) as a biomarker of cellular adaptation and discuss therapeutic strategies targeting mitochondrial function and oxidative stress. Antioxidants and compounds modulating key ion channels, such as mitoK _ATP and mPTP, are highlighted as promising interventions for mitigating hypoxia-induced damage. Furthermore, we emphasize the potential of integrating in vitro, in vivo, and in silico studies to develop novel therapies aimed at preserving mitochondrial integrity and preventing cardiovascular diseases.

Emerging evidence highlights the role of thyroid hormones in cancer, although findings are controversial. Research on thyroid-related traits in lung carcinogenesis is limited. Using UK Biobank data, we performed bidirectional Mendelian randomization (MR) to assess causal associations between lung cancer risk and thyroid dysfunction (hypothyroidism and hyperthyroidism) or functional traits (free thyroxine [FT4] and normal-range thyroid-stimulating hormone [TSH]). Furthermore, in the smoking-behavior-stratified MR analysis, we evaluated the mediating effect of thyroid-related phenotypes on the association between smoking behaviors and lung cancer. We demonstrated significant associations between lung cancer risk and hypothyroidism (hazard ratio [HR] = 1.14, 95% confidence interval [CI] = 1.03-1.26, P = 0.009) and hyperthyroidism (HR = 1.55, 95% CI = 1.29-1.87, P = 1.90 × 10 ^-6) in the UKB. Moreover, the MR analysis indicated a causal effect of thyroid dysfunction on lung cancer risk (OR _{inverse variance weighted [IVW]} = 1.09, 95% CI = 1.05-1.13, P = 3.12 × 10 ^-6 for hypothyroidism; OR _IVW = 1.08, 95% CI = 1.04-1.12, P = 8.14 × 10 ^-5 for hyperthyroidism). We found that FT4 levels were protective against lung cancer risk (OR _IVW = 0.93, 95% CI = 0.87-0.99, P = 0.030). Additionally, the stratified MR analysis demonstrated distinct causal effects of thyroid dysfunction on lung cancer risk among smokers. Hyperthyroidism mediated the effect of smoking behaviors, especially the age of smoking initiation (17.66% mediated), on lung cancer risk. Thus, thyroid dysfunction phenotypes play causal roles in lung cancer development exclusively among smokers and act as mediators in the causal pathway from smoking to lung cancer.

Intermediate filaments (IFs) in human cells are the products of six distinct gene families, all sharing homology in a core rod domain. These IFs assemble into non-polar polymers, providing cytoplasmic and nuclear mechanical support. Recent research has revealed the active and dynamic properties of IFs and their binding partners. This regulation extends beyond cell mechanics to include migration, mechanotransduction, and tumor growth. Therefore, this comprehensive review aims to catalog all human IF genes and IF-associated proteins (IFAPs), detailing their names, sizes, functions, associated human diseases, relevant literature, and links to resources like UniProt and the Protein Atlas database. These links provide access to additional information such as protein structure, subcellular localization, disease-causing mutations, and pathology. Using this catalog, we will provide an overview of the current understanding of the biological functions of IFs and IFAPs. This overview is crucial for identifying gaps in their characterization and understanding IF-mediated mechanotransduction. Additionally, we will consider potential future research directions.

The current study aimed to evaluate the efficacy and safety of Compound Danshen Dripping Pills (CDDP) in improving cardiac function in patients with acute anterior ST-segment elevation myocardial infarction (AAMI). Between February 2021 and February 2023, 247 eligible patients with AAMI after primary percutaneous coronary intervention were enrolled and randomly assigned (1∶1) to receive CDDP ( n = 126) or placebo ( n = 121), with a follow-up of 48 weeks. Compared with the placebo group, the CDDP group demonstrated a significant increase in left ventricular ejection fraction values after 24 weeks of treatment (least squares mean: 3.31; 95% confidence interval [CI]: 1.72-4.90; P < 0.001) and at the 48-week follow-up (least squares mean: 4.35; 95% CI: 2.76-5.94; P < 0.001). Significant reductions in N-terminal pro-B-type natriuretic peptide levels were observed in both groups at the 24- and 48-week visits with no significant difference between the two groups ( P > 0.1 for all). The incidence of major adverse cardiovascular and cerebrovascular events was 6.35% in the CDDP group and 5.79% in the placebo group ( P = 0.822). Notably, no serious adverse events were attributed to CDDP. These findings suggest that CDDP may be well tolerated and could improve left ventricular ejection fraction in patients with AAMI at 24 and 48 weeks.