Molecular and Cellular Biochemistry最新文献

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in the molecular pathophysiology of the cardiorenal axis by facilitating the degradation of LDL receptors, which results in increased LDL cholesterol levels, inflammation, and fibrosis. PCSK9 is involved in activating various pathways, including NF-κB and the NLRP3 inflammasome, while simultaneously inhibiting PPAR and SIRT3. This dysregulation contributes to oxidative stress, apoptosis, and renal lipotoxicity through the impairment of megalin function. The resultant molecular processes lead to the secretion of proinflammatory cytokines such as IL-1β, IL-6, TNF-α, and NF-κB, which exacerbate fibrosis and tissue injury. The heightened activity of PCSK9 is associated with the accumulation of LDL in the kidneys, causing nephrotoxicity and dysfunction within the cardiorenal system. Notably, the inhibition or deficiency of PCSK9 has been shown to confer protective effects, mitigating inflammation, oxidative stress, and apoptosis in the cardiorenal axis. Consequently, targeting PCSK9 and its related pathways may pave the way for innovative therapeutic approaches aimed at reducing inflammation, oxidative stress, and apoptosis, thereby enhancing the clinical outcomes for individuals with cardiorenal dysfunction.

Background: Mild cognitive impairment (MCI) is a common non-motor manifestation of Parkinson's disease (PD) and often precedes dementia. However, evidence on its demographic and clinical risk factors remains inconsistent. This study aimed to synthesize available data through a meta-analysis to identify determinants of MCI in PD.

Methodology: This systematic review and meta-analysis followed PRISMA guidelines. Electronic databases were searched using MeSH terms and validated keywords. Studies were selected through a multi-step screening process by independent reviewers. Data extraction and quality assessment were performed using the Newcastle-Ottawa Scale. Meta-analyses were conducted using Comprehensive Meta-Analysis (v2). Random- or fixed-effects models were applied based on heterogeneity (I² threshold = 50%). Beggs and Mazumdar test assessed publication bias, with significance set at (P < 0.1).

Results: This meta-analysis included 33 studies, Significant risk factors for MCI in individuals with PD included older age (effect size = 0.4, 95% CI: 0.315-0.498, P ≤ 0.001), older age at disease onset (effect size = 0.18, 95% CI: 0.05-0.327, P ≤ 0.001), and longer disease duration (effect size = 0.14, 95% CI: 0.08-0.2, P ≤ 0.001). Higher educational attainment showed a protective effect (effect size = -0.438, 95% CI: -0.555 to -0.321, P ≤ 0.001). No significant association was found between gender and MCI (OR = 0.899, 95% CI: 0.749-1.079, P = 0.253). Disease severity, based on UPDRS and Hoehn and Yahr scales, was significantly associated with increased MCI risk.

Conclusion: Advanced age, later disease onset, longer disease duration, and greater severity are key risk factors for MCI in PD. These findings highlight the need for early detection and proactive management to guide clinical decisions.

Long non-coding RNAs (lncRNAs) are involved in tumorigenesis. The telomerase RNA component (TERC) is a lncRNA that functions as an essential template for the addition of the telomere repeats; its dysfunctions has been associated with various human diseases. However, how dysregulation of TERC expression and activity affects lung adenocarcinoma (LUAD) progression remains elusive. RNA sequencing (RNA-seq) analysis was used to compare the expression levels of TERC in cancerous and adjacent normal lung tissues. Functional assays of TERC in LUAD cell lines were performed by siRNA-mediated knockdown. Cell proliferation was assessed using the water-soluble tetrazolium salt-1 (WST-1) assay, while colony formation capability was evaluated through colony formation assays. Cell migration and invasion were analyzed using Transwell assays. Reactive oxygen species (ROS) levels were determined by flow cytometry and examined by fluorescence microscopy. The morphology of mitochondria was observed using transmission electron microscopy. Protein expression was analyzed by western blot. The formation of autophagosomes was monitored by fluorescence microscopy following the expression of fluorescently tagged LC3. Xenograft experiments were conducted to test the inhibition of TERC knockdown in LUAD proliferation in vivo. RNA-seq analysis showed that the expression of TERC was upregulated in lung cancer tissues. Silencing TERC suppressed the proliferation, migration, and invasion of lung cancer cells in vitro. Additionally, it inhibited the growth of pulmonary xenografts in mice in vivo. Mechanistic analyses indicated that silencing of TERC increased the expression of autophagy-related proteins LC3B, Beclin-1, and AMP-activated protein kinase (AMPK), while the expression of p62 protein and ferroptosis-regulated proteins GPX4 and SLC7A11 were diminished. Importantly, inhibition of AMPK function counterbalanced the effects of TERC knockdown on autophagy and ferroptosis in LUAD cells. These findings reveal that suppression of TERC in lung cancer promotes autophagy and ferroptosis via regulation of AMPK. They help to understand the mechanism underlying TERC activity in tumorigenesis. It will be of interest to determine the clinical significance of TERC dysregulation in lung cancer.

The purinergic ligand-gated ion channel 7 receptor (P2X7R) is a non-selective ion channel activated by extracellular adenosine triphosphate. It promotes intracellular signal transduction by inducing Na⁺ and Ca²⁺ influx and K⁺ efflux. Moreover, this receptor is involved in the regulation of the inflammatory response, oxidative stress, cell death, and immune response. P2X7R is associated with the onset and progression of various chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, pulmonary arterial hypertension, and pulmonary tuberculosis. In this review, we comprehensively summarize the structure and functions of P2X7R as well as its roles and potential molecular mechanisms in chronic respiratory diseases. Additionally, we explored the application of P2X7R antagonists in clinical practice. In summary, targeting P2X7R may be a new strategy for treating chronic respiratory diseases, but we should still pay attention to its dual roles, especially in lung cancer.