Molecular and Cellular Biochemistry最新文献

Heart failure (HF) represents the terminal stage of multiple cardiovascular disorders and is characterized by substantial morbidity, disability, and mortality. Although standard pharmacotherapies offer partial symptomatic relief, their capacity to halt or reverse disease progression remains limited. In recent years, autophagy-an essential intracellular degradation and recycling process that safeguards cardiomyocyte homeostasis-has emerged as a critical determinant in the onset and progression of HF. In this review, we systematically examined approximately 170 research articles related to "natural compounds-autophagy-HF" published up to 2025, and synthesized major advances reported over the past five years. Based on chemical structure and natural source, representative bioactive compounds were categorized into five major classes: flavonoids, polyphenols, alkaloids, terpenoids, and marine-derived molecules. We then integrated evidence on the principal autophagy-regulatory signaling cascades influenced by these compounds, including the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) axis, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), sirtuin 1 (SIRT1)/forkhead box O (FOXO), BCL2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3)/NIP3-like protein X (NIX), and Beclin-1 pathways. Moreover, this review summarizes how these natural compounds modulate autophagy to attenuate key pathological processes associated with HF, including cardiac hypertrophy, adverse ventricular remodeling, mitochondrial dysfunction, and cardiomyocyte apoptosis. By comparing convergent mechanisms and compound-specific differences in autophagy-mediated cardioprotection, we highlight emerging mechanistic patterns and therapeutic implications. Collectively, through structured classification of compounds, integration of autophagy signaling pathways, and assessment of translational potential, this review provides a systematic framework to guide the rational application and further development of natural products for the prevention and treatment of HF.

T-cell acute lymphocytic leukemia (T-ALL) is a malignant transformation of immature precursor T-cells that is highly aggressive. The disruption of SETD2 is thought to be a unique epigenetic mechanism for leukemia. This study aimed to investigate the role and possible mechanism of SETD2 in T-ALL. The expression of SETD2 in T-ALL tissues and cells was detected by RT-PCR, and siRNA (si-NC/si-SETD2) and overexpressed plasmids (ov-NC/ov-SETD2) were used to transfected T-ALL cell lines JURKAT and MOLT-4, and cell proliferation, migration/invasion and cell cycle were detected by CCK8, Transwell, flow cytometry, respectively. WB was used to detect the changes in the JAK/STAT pathway. The JAK/STAT inhibitor AG490 was further used to demonstrate the role of JAK/STAT in SETD2 regulation of T-ALL. Then, the effects of SETD2 on T-ALL tissue infiltration were verified in vivo. Results showed that SETD2 was significantly lowly expressed in T-ALL, and si-SETD2 promoted the proliferation, migration, invasion, cell cycle, and activation of the JAK/STAT pathway of T-ALL cells, while overexpression of SETD2 showed the opposite inhibitory effect. The use of AG490 inhibited the promoting effect of si-SETD2 on T-ALL, suggesting that JAK/STAT was involved in the regulation of SETD2 on T-ALL. In vivo experiments further confirmed that silencing SETD2 decreased the body weight of mice and increased the infiltration of JURKAT cells in the liver, kidney, spleen, lung, and brain, while overexpression of SETD2 showed inhibitory effects. In conclusion, SETD2 played an important role in T-ALL by inhibiting the JAK/STAT pathway to inhibit T-ALL proliferation, invasion, and transfection.

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.