Lishang Liao

Alzheimer’s disease (AD) is a neurodegenerative disorder primarily affecting the geriatric population, characterized by progressive cognitive impairment and behavioral abnormalities. Due to the absence of effective disease-modifying therapies, AD imposes a substantial burden on patients and their families. The etiology and pathogenesis of AD have not been fully elucidated; multiple pathological alterations have been implicated, including the deposition of β-amyloid (Aβ) plaques, abnormal tau phosphorylation, and neuroinflammatory responses. These pathological changes contribute to neuronal damage, synaptic dysfunction, and neuronal death, ultimately leading to brain atrophy. Recent studies have identified PANoptosis as a critical regulatory mechanism of programmed cell death that influences the pathological progression of AD through multiple pathways, including modulation of Aβ plaque deposition and regulating neuroinflammatory responses. However, the precise mechanisms of these effects remain unclear. This review aims to comprehensively analyze recent research findings, focusing on the regulatory role of PANoptosis in AD, exploring the specific manifestations of the intricate network of cell death regulation in AD pathogenesis. By providing a systematic overview of emerging findings, this review offers new insights into the pathogenesis of AD and highlights potential directions for the development of targeted therapeutic strategies.

Alcoholic brain damage (ABD) stems from chronic excessive alcohol consumption, causing neuroinflammation, oxidative stress, mitochondrial dysfunction, and neuronal apoptosis, all of which severely impair cognition and quality of life. However, traditional treatments have shown limited efficacy. Quercetin (QE), a natural flavonoid with antioxidant, anti-inflammatory, and neuroprotective properties, may therefore offer a promising approach for ABD. Accordingly, this study examines QE’s potential mechanisms, with an emphasis on its modulation of the JNK/P38 MAPK pathway. In vitro, QE’s effects on BV2 and HT22 cell viability were assessed via the CCK8 assay. Additionally, oxidative stress markers, including reactive oxygen species (ROS) and glutathione, were measured. Transmission electron microscopy was employed to observe cellular changes, while flow cytometry was used to evaluate apoptosis. Furthermore, western blotting was conducted to analyze the expression of BAX, Bcl-2, Caspase-3, IL-1, IL-6, TNF-α, P-P38, P-JNK, P38, and JNK. In vivo, SD rats were divided into a control group, an ethanol group, and three QE groups (25, 50, 100 mg/kg body weight), which were treated concurrently with ethanol for 12 weeks. Behavioral tests, histological staining, oxidative stress markers, and protein expression were examined. QE increased superoxide dismutase (SOD) activity, lowered ROS and malondialdehyde (MDA) levels, and reduced mitochondrial damage in vitro. It also significantly inhibited ethanol-induced apoptosis, inflammation, and JNK/P38 MAPK activation. Furthermore, QE improved spatial cognition, reduced anxiety, and ameliorated oxidative and inflammatory damage. Overall, QE alleviated alcohol-induced neuronal injury by suppressing oxidative stress, apoptosis, and inflammation via the JNK/P38 MAPK pathway, highlighting its therapeutic potential for ABD.

Subarachnoid hemorrhage (SAH) is a fatal pathological condition in the central nervous system (CNS), characterized by severe clinical consequences. Its treatment remains a significant challenge, especially due to the incomplete understanding of its molecular mechanisms. In this study, we integrated comprehensive bioinformatics analyses with experimental validation to explore the potential pathogenic mechanisms and immune cell infiltration characteristics of SAH, aiming to identify novel diagnostic biomarkers and therapeutic targets. We selected relevant gene expression data from the gene expression omnibus (GEO) database and obtained a gene set associated with SAH from the GeneCards database. Through bioinformatics analysis, we constructed a protein-protein interaction (PPI) network and performed functional enrichment analysis using gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases. The analysis revealed 11 key genes and indicated 3 main signaling pathways. Additionally, Drug target prediction and molecular docking analyses revealed that Isorhynchophylline (IRN) exhibits a strong binding affinity to these hub proteins. Importantly, Western blot (WB) experiments confirmed that IRN significantly downregulates the expression of CCL20, IL6, TLR4, and MMP9 in LPS-induced microglial cells, validating its anti-inflammatory effects. In conclusion, our findings not only elucidate the molecular mechanisms underlying SAH but also provide robust bioinformatics and experimental evidence supporting IRN as a promising therapeutic candidate, offering novel insights for future intervention strategies in SAH.

DNA Damage-Induced Apoptosis Suppressor Triggers Progression and Stemness of Glioma by Enhancing Lymphoid Enhancer-Binding Factor 1 Expression

Polycystic ovary syndrome (PCOS), a prevalent reproductive endocrine disorder, frequently coincides with insulin resistance, lipid dysregulation, and cellular apoptosis. In this study, we aimed to evaluate the therapeutic potential of Dried Zingiber officinale (DZO), renowned for its antibacterial, antiviral, anti‐inflammatory, and antioxidant properties, in the context of PCOS. To this end, we induced a PCOS mouse model through the administration of dehydroepiandrosterone (DHEA) and a high‐fat diet (HFD), followed by DZO treatment to assess its effects on ovarian pathology, insulin resistance, and hormonal imbalances. The anti‐apoptotic effect of DZO on PCOS ovarian granulosa cells was confirmed through network pharmacological analysis, TUNEL staining, FITC‐PI staining, and protein blotting. Notably, DZO treatment significantly alleviated ovarian pathological changes in PCOS mice and normalized hormone levels, including testosterone, estradiol, and progesterone/follicle‐stimulating hormone ratios. Furthermore, our findings confirmed the anti‐apoptotic effect of DZO on PCOS ovarian granulosa cells. Mechanistically, DZO primarily exerted its therapeutic effects in PCOS by inhibiting apoptosis induced by the accumulation of reactive oxygen species (ROS). In conclusion, our study demonstrates the promising therapeutic role of DZO in the management of obese PCOS patients, particularly in reversing ROS‐mediated apoptosis in ovarian granulosa cells.

Glioblastoma multiforme (GBM) is the most malignant primary tumour in the central nervous system, but the molecular mechanisms underlying its pathogenesis remain unclear. In this study, data set GSE50161 was used to construct a co‐expression network for weighted gene co‐expression network analysis. Two modules (dubbed brown and turquoise) were found to have the strongest correlation with GBM. Functional enrichment analysis indicated that the brown module was involved in the cell cycle, DNA replication, and pyrimidine metabolism. The turquoise module was primarily related to circadian rhythm entrainment, glutamatergic synapses, and axonal guidance. Hub genes were screened by survival analysis using The Cancer Genome Atlas and Human Protein Atlas databases and further tested using the GSE4290 and Gene Expression Profiling Interactive Analysis databases. The eight hub genes (NUSAP1, SHCBP1, KNL1, SULT4A1, SLC12A5, NUF2, NAPB, and GARNL3) were verified at both the transcriptional and translational levels, and these gene expression levels were significant based on the World Health Organization classification system. These hub genes may be potential biomarkers and therapeutic targets for the accurate diagnosis and management of GBM.