Molecular Biology Reports最新文献

Endometriosis is a chronic gynaecological disorder characterized by ectopic endometrial growth, inflammation, pain, and infertility. Current therapies, largely hormonal and surgical, have limited efficacy and compromise fertility, underscoring the need for alternative approaches that directly address the inflammatory drivers. Recent evidence suggests that gut microbiota dysbiosis and iron overload contribute to the pathophysiology of endometriosis, with excess iron potentially inducing ferroptosis, a regulated form of lipid peroxidation-driven cell death that amplifies inflammation. Concurrently, cytokine-mediated JAK/STAT signalling, particularly IL-6/STAT3, integrates signals from immune cells, ferroptotic processes, and microbial metabolites, positioning it as a central regulatory axis in endometriosis. This review synthesizes mechanistic data linking alterations in the gut microbiota, microbial metabolites, ferroptosis, and JAK/STAT signalling in the inflammatory microenvironment of endometriosis. While direct causal evidence remains limited, converging findings from preclinical and translational studies suggest that the microbiota-ferroptosis-JAK/STAT interaction network forms an interconnected system that contributes to sustained inflammation. Our discussion brings these mechanisms into a shared framework, suggesting that their combined influence may give clearer insight into endometriosis. We propose that exploring these molecular pathways may open new avenues for microbiota- and ferroptosis-informed strategies that target inflammation while preserving fertility.

Glioblastoma (GBM) is a highly aggressive and lethal form of brain cancer with limited treatment options, particularly for recurrent cases. Oncolytic virus (OV) therapy is a novel therapeutic strategy for recurrent GBM, leveraging its ability to selectively target and destroy malignant cells while sparing surrounding healthy tissue. Recent clinical trials have indicated that oncolytic virotherapy has an acceptable safety profile and the potential to enhance survival in recurrent GBM. For instance, CAN-3110, a Nestin-promoter-driven herpes simplex virus-1 (HSV-1), demonstrated a median overall survival of 14.9 months in patients with recurrent GBM, with HSV-1 seropositive patients achieving more prolonged survival (14.2 versus 7.8 months in seronegative patients). This review aims to synthesize the current evidence on clinical outcomes in patients with recurrent GBM receiving oncolytic virotherapy, with a specific focus on safety profiles, therapeutic efficacy, and survival outcomes.

Background: Alzheimer’s disease (AD) is the most common neurodegenerative dementia, with its primary symptoms appearing only after substantial neuronal death. Streptozotocin (STZ) is a neurotoxic compound that induces neurodegenerative effects similar to those seen in AD. AD is a complex and multifactorial disorder, and the exact etiology of neuronal loss remains elusive. In recent years, hyperactivation of mammalian ste-20-like kinase − 1/2 (MST1/2)-mediated Hippo signaling is critical for neuronal death in AD pathophysiology. Our previous research on a rat model of sporadic AD revealed that inhibiting Hippo signaling via the MST1/2 small-molecule antagonist Xmu-mp-1 is a promising therapeutic strategy for AD. Based on these findings, the present study aimed to investigate the therapeutic potential of Xmu-mp-1 in mitigating STZ-induced neurotoxicity using differentiated SH-SY5Y cells.

Methods and results: In this study, differentiated SH-SY5Y cells were pretreated with 1 µM Xmu-mp-1 for 2 h, prior to 2 mM STZ exposure for 24 h. We assessed the effects on cytotoxicity, oxidative stress, mitochondrial dysfunction, and apoptosis, followed by an investigation into the underlying mechanistic basis. Our findings revealed that Xmu-mp-1 pretreatment considerably attenuated toxicity and improved cell survival in STZ-exposed SH-SY5Y cells by attenuating STZ-induced intracellular oxidative stress, mitochondrial depolarization, neuronal apoptosis, and neurodegeneration. Xmu-mp-1 apparently involved modulation of Hippo signaling to mediate these neuroprotective effects.

Conclusions: Taken together, these findings suggest that MST1-mediated neuronal apoptosis may contribute to neuronal death in STZ-induced neurotoxicity, and inhibiting MST/Hippo signaling via Xmu-mp-1 could represent an effective approach to alleviate AD-associated neurotoxic events.

Lipid droplets (LDs) are ubiquitous subcellular organelles playing crucial roles in lipid and energy homeostasis. They are constantly generated in the intramembrane space of the endoplasmic reticulum (ER) through unique mechanisms. Upon maturation, they bud off from the ER outer membrane into the cytosol, travel through the cytosolic microtubular network, and make contacts to most of the other subcellular organelles to perform their cellular functions. On the one hand, these organelles can grow or fuse with other smaller ones and serve as storage for extra cellular lipid products. On the other hand, when metabolic needs arise such as in nutrient deprivation or during exercises, the esterified lipids inside the LDs undergo stepwise lipolysis, e.g. basal and stimulated lipolysis, under the regulation of a set of proteins and kinases that are specifically targeted to the monolayer phospholipid membrane of the LDs. The dynamic homeostasis of their biogenesis and lipolysis is also intimately related to other cellular signaling pathways in a paracrine or endocrine manner which actively participate in the regulation of cellular homeostasis and systemic health. This review will summarize the current understanding of the underlying mechanisms mediating the biogenesis and metabolic impact of LDs in normal and disease status with a focus on their roles in propelling and sustaining chronic inflammation.

Background: Autophagy is a conserved intracellular degradation and recycling process in eukaryotic cells. Autophagy dysfunction is linked to several diseases, including cancer. Depending on cancer type and context, autophagy may act as a tumor suppressor or promote tumor progression. Various cellular pathways regulate autophagy, among which the NFκB signaling pathway plays a dual role, either promoting or inhibiting autophagy. Since many cancer therapies affect both autophagy and NFκB, understanding their interaction can help develop more effective combination treatments. However, the specific mechanisms by which NFκB regulates autophagy in Non-Small Cell Lung Cancer (NSCLC) remain unclear. In this study, we aimed to elucidate this regulatory relationship and identify key genes involved.

Methods and results: We established NSCLC cell groups with NFκB overexpression or suppression, and with or without autophagy induction. Autophagy levels were assessed via western blot. RNA-seq analysis was performed to identify differentially expressed genes among these groups, and candidate regulators were selected based on expression patterns and in silico analysis. Selected genes were validated with qRT-PCR. Our results show that NFκB positively regulates autophagy-related processes in NSCLC cells, as reflected by altered LC3B-II levels. Genes with expression which decreased upon NFκB suppression but increased with NFκB overexpression under autophagy-induced conditions were identified as candidate regulators. Among these, the putative NFκB-NLRP3 regulatory relationship appears to play a particularly important role in the upregulation of autophagy.

Conclusions: This study provides an NSCLC-specific transcriptional framework linking NFκB activity to autophagy- and inflammation-associated gene networks. By integrating expression profiling and in silico analyses, we identify candidate NFκB-responsive genes, including NLRP3, that may contribute to autophagy-related cellular responses in NSCLC.