Lemei Zhu

Background: Obesity-associated cognitive vulnerability involves peripheral metabolic organs, the circulation, and the neurovascular unit/blood–brain barrier (NVU/BBB). Whether adipose and hepatic dysfunction contribute through compartment-specific redox remodelling remains unclear. Methods: We searched PubMed/MEDLINE, Web of Science Core Collection, and Scopus for human, rodent, and cellular studies published from 1 January 2017 to 13 September 2026. Ninety-seven publications met the inclusion criteria. No meta-analysis or formal risk-of-bias assessment was undertaken. Results: Human studies associated adipose or hepatic dysfunction and circulating redox markers with brain and cognitive outcomes but rarely established tissue origin, temporal ordering, or mediation. Animal and cellular studies supported adipose mitochondrial and NOX-derived ROS, MASLD/MASH-related hepatic redox dysfunction, liver-derived signals, NVU/BBB impairment, and brain mitochondrial, inflammatory, synaptic, and cognitive changes. Conclusions: The adipose–liver–brain network is biologically plausible but remains unproven as a causal model. Future longitudinal and intervention studies should establish compartment specificity, temporal ordering, mediator reproducibility, reversibility, and domain-specific cognitive effects.

Alveolar bone resorption, which accompanies periodontitis, post-extraction mechanical unloading, and aging-related inflammation, is governed by interacting epigenetic and post-transcriptional mechanisms. Evidence from DNA methylation, histone modification, non-coding RNA (ncRNA), RNA-binding protein, and N6-methyladenosine (m6A) studies indicates that these layers jointly regulate the balance between bone formation and resorption, although their causal hierarchy and tissue specificity remain incompletely defined. This review integrates that evidence into a graded framework that separates mechanisms demonstrated functionally in alveolar bone or periodontal models from those supported only by correlational data or extrapolated from long-bone, calvarial, and osteoporosis models, and assigns each mechanism to the cell types in which it has been demonstrated. Because the effects of individual regulators (for example, DNMTs, HDACs, and m6A writers) depend on cell type, differentiation stage, dose, and timing, conflicting reports are examined explicitly. We further dissect the bidirectional crosstalk between epigenetic modifiers and ncRNAs, distinguishing experimentally verified links from hypothetical ones, and critically assess emerging therapeutic strategies—small-molecule epigenetic inhibitors, oligonucleotide therapeutics, and biomaterial-assisted delivery—together with their safety and delivery barriers. By formalizing an evidence-graded conceptual framework, this review provides a basis for mechanism-based strategies against alveolar bone resorption.

Drug resistance in acute promyelocytic leukemia (APL) remains clinically challenging despite the success of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) therapy. Existing explanations, including promyelocytic leukemia protein–retinoic acid receptor alpha (PML–RARα) mutations and alterations in individual death pathways, do not fully account for the heterogeneity of resistant phenotypes. This review proposes regulated cell death network (RCDN) remodeling as a testable framework for APL resistance. RCDN remodeling is defined as coordinated changes in network coupling, stress routing, and cellular death thresholds. We hypothesize that resistance emerges from coordinated adaptation across redox, survival signaling, and mitochondrial gating, rather than from defects in any single pathway. This predicts coupled shifts across multiple death modules and non-additive responses to combinatorial perturbations, distinguishing network-level remodeling from pathway-specific resistance. We further define experimental criteria for distinguishing network-level remodeling from pathway-specific resistance and discuss Tanshinone IIA (Tan IIA) as a preclinical multi-node perturbation probe.

Mitochondria, the cell’s powerhouses, generate ATP to sustain essential biological functions. Dysfunctional mitochondria can lead to cell death and subsequent tissue damage. Mitochondrial impairment is a key driver of cellular dysfunction in cardiomyocytes, endothelial cells, and macrophages, contributing to cardiovascular diseases such as atherosclerosis, myocardial ischemia–reperfusion injury, and cardiac hypertrophy. The signal transducer and activator of transcription (STAT) family regulates immune responses, apoptosis, and cell proliferation. Despite evidence suggesting that STATs influence mitochondrial pathways in various cardiovascular conditions, their roles are often contradictory and context-dependent. This review examines the structural and functional dynamics of STATs, their upstream and downstream signaling networks, and therapeutic strategies targeting STAT3 (the most extensively studied isoform), with a particular focus on natural compounds and pharmacological inhibitors. By synthesizing current findings, this review offers valuable insights into STATs as potential therapeutic targets for mitochondrial dysfunction in cardiovascular diseases, while also highlighting directions for future research.