Heilongjiang University of Chinese Medicine

Viscum coloratum (Kom.) Nakai has been widely used in traditional Chinese medicine and clinical treatment mainly for rheumatoid arthritis (RA). Our latest study demonstrated that it could alleviate clinical symptoms of RA and decrease osteoclastogenesis-related gene expression in the CIA mouse model. However, whether Viscum coloratum (Kom.) Nakai could inhibit osteoclastogenesis and its underlying mechanisms need to be further elucidated. In this study, we demonstrated that extract of Viscum coloratum (Kom.) Nakai (EVC) exhibited extraordinary activity against RANKL-induced osteoclast differentiation identified by inhibiting the formation of TRAP-positive multinucleated osteoclasts, TRAP activity, and decreasing osteoclast-specific genes NFATc1 expression. The network pharmacology-based method integrating Protein-Protein interaction analysis revealed that Viscum coloratum (Kom.) Nakai could inhibit osteoclastogenesis by regulating PI3K-AKT signaling pathways. Then, the predicted signaling pathway of EVC on osteoclast differentiation was determined by Western blot. Using TRAP activity and nitric oxide assays, Viscumneoside III, which was identified as the main ingredient from Viscum coloratum (Kom.) Nakai in our previous study, was confirmed as the primary effective ingredient. These findings reveal that EVC executed the traditional effects on strengthening muscles and bones for the treatment of RA by inhibiting osteoclastogenesis via the regulated PI3K/AKT/mTOR signaling pathway, and Viscumneoside III was its effective ingredient.

Type 2 diabetes mellitus (T2DM) is a major risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), and their convergence presents a significant therapeutic challenge. Palmatine, an isoquinoline alkaloid with lipid-regulating and anti-inflammatory properties, is a promising candidate; however, its multi-target mechanisms remain undefined. To address this, we employed a sequential, multi-omics bioinformatics workflow to generate a testable mechanistic hypothesis, followed by rigorous experimental validation. First, integrative analyses-including target prediction, differential gene expression, pathway enrichment, and machine learning-converged to identify five core targets: ADRB2, BCL3, EGR1, FOS, and MAP3K8. Molecular docking predicted strong binding, and single-cell sequencing contextualized their expression within specific hepatic cell types. To experimentally test this predictive framework, we evaluated palmatine in a rat model of T2DM-associated MASLD. Palmatine treatment significantly improved liver function(reduced ALT, AST), attenuated inflammation (lowered TNF-α, IL-6) and oxidative stress (increased SOD, GSH; decreased MDA), ameliorated glycolipid metabolism (reduced TC, TG, LDL-C, and GLU), and reduced hepatic steatosis and fibrosis. Mechanistically, confirming the bioinformatic prediction, palmatine downregulated the expression of the five key targets and concurrently suppressed the activation of critical apoptotic executers (Caspase-3, Caspase-8, GSDME). These findings demonstrate that palmatine alleviates MASLD by modulating a novel target network to inhibit hepatocyte apoptosis, providing a robust, hypothesis-driven preclinical foundation for its therapeutic development.

The albumin–bilirubin (ALBI) score is a novel marker linked to an adverse prognosis in many diseases. Nevertheless, its predictive value for the risk of mortality in COPD has been rarely explored. Therefore, this study delves into the association of ALBI score with the risk of mortality in patients with COPD. Data from Multiparameter Intelligent Monitoring in Intensive Care IV (MIMIC-IV) 3.0 were reviewed. The associations of ALBI scores with patients' short and long-term all-cause mortality were investigated using Kaplan–Meier curves, COX regression models, and receiver operating characteristic (ROC) curves, and the potential nonlinear relation was explored by restricted cubic spline (RCS) curves. The predictive value of ALBI scores for the risk of mortality was evaluated by ROC curves. In addition, subgroup analyses and propensity score matching were conducted. Among 3325 included patients, Kaplan–Meier curves demonstrated significant survival disparities across ALBI groups at 30, 90, 180, and 365 days (log-rank P < 0.0001). Multivariable COX regression identified ALBI as an independent predictor of 30-day mortality (HR = 1.76, 95% CI 1.35–2.29, *P* < 0.001) and long-term mortality. RCS revealed a nonlinear association (*P*nonlinear < 0.05). ROC analysis confirmed ALBI's predictive capacity for 30 day mortality (AUC = 0.711, 95% CI 0.6743–0.7478). Subgroup analyses showed consistent associations without interaction effects (*P*interaction > 0.05). Propensity score-matched cohorts validated ALBI's positive correlation with mortality across all timepoints. The ALBI score has a significant association with an elevation of mortality risk in critically ill patients with COPD, which can act as a predictor for the COPD prognosis.

Alzheimer's disease (AD) is pathologically characterized by the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles composed of hyperphosphorylated tau protein. In recent years, two cellular processes have emerged as pivotal drivers of neurodegeneration in AD: mitophagy, the selective autophagic clearance of damaged mitochondria, and ferroptosis, an iron-dependent form of regulated cell death. This review outlines the molecular mechanisms of mitophagy and ferroptosis, with a focus on their interplay in AD. We propose that impaired mitophagy disrupts intracellular redox and iron homeostasis, thereby increasing neuronal susceptibility to ferroptosis. Conversely, ferroptosis-executing events, such as lethal lipid peroxidation, can further exacerbate mitochondrial dysfunction. This establishes a self-amplifying vicious cycle that accelerates disease progression. Furthermore, we summarize potential therapeutic strategies targeting this interactive network (e.g., Urolithin A, ferroptosis inhibitors) and highlight promising directions for future research. In contrast to previous reviews that have focused on each process in isolation, this work synthesizes evidence for a self-amplifying feedback loop between impaired mitophagy and exacerbated ferroptosis in AD. We posit that targeting this self-amplifying loop between mitophagy and ferroptosis may offer a novel and effective therapeutic paradigm for halting Alzheimer's disease progression.