江苏护理职业学院

Histone deacetylase 6 (HDAC6) is the sole member of the histone deacetylase (HDAC) family predominantly localized in the cytoplasm, characterized by dual catalytic domains and an ubiquitin-binding domain. In recent years, it has garnered substantial attention due to its critical role in tumor initiation and progression. This review delineates the unique structural features and core biological functions of HDAC6, while further exploring its expression patterns and prognostic significance in tumors. Additionally, it elaborates on the regulatory roles of HDAC6 in key biological behaviors of tumor cells, including promoting proliferation, suppressing apoptosis, enhancing migratory and invasive potentials, and inducing epithelial–mesenchymal transition (EMT). Concomitantly, the review analyzes the impacts of HDAC6 on the tumor immune microenvironment, its modulation of tumor metabolism, and its association with tumor drug resistance. To date, research on HDAC6 in tumors has firmly established its value as a potential therapeutic target, with specific inhibitors (e.g., ACY-1215 and Tubastatin A) demonstrating significant antitumor activity in preclinical studies and several clinical trials. Focused on the implications of HDAC6 in tumors, this review not only highlights its distinct functions compared to other HDAC family members but also integrates previously unreported mechanisms of action (e.g., HDAC6 cooperates with NEDD8/p62 to sustain proteostasis) and clinical translation perspectives. Collectively, it presents an innovative review that provides valuable references for subsequent basic research and clinical practice of HDAC6-targeted tumor therapy.

MZB1 is an endoplasmic reticulum (ER)-resident chaperone that facilitates immunoglobulin assembly and secretion, particularly polymeric IgM and dimeric IgA. Accumulating evidence links MZB1 to the regulation of intracellular Ca2⁺ signaling, integrin activation, and ER stress responses, which could influence innate-like B-cell functions and the maintenance of immune homeostasis. Aberrant expression of MZB1 has been implicated in the development of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), as well as in tumor progression, including hepatocellular carcinoma and multiple myeloma. In certain cancer, MZB1 expression is associated alterations in the tumor microenvironment that may be permissive for tumor progression. Conversely, its ability to enhance antibody responses suggests potential applications in immunotherapy. This review integrates current insights into MZB1 biology, summarizes its role in disease pathogenesis, and discusses future directions for therapeutic targeting.

Polycystic ovarian syndrome (PCOS) is a frequent metabolic disorder in premenopausal woman, featured with increased androgen, reduced ovulation and insulin resistance. An increasing number of reports have confirmed that microRNAs (miRNAs) play pivotal roles in PCOS. However, the diagnostic mechanisms of microRNA (miR)-206 in PCOS remain unclear. Liquiritin, extracted from Glycyrrhiza Radix, has multiple pharmacological activities in diseases, including PCOS. Our report was designed to explore whether liquiritin play a role in PCOS by regulating human ovarian granulosa cell-like KGN cells proliferation and apoptosis through miR-206/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, and to further elucidate the underlying molecular mechanisms. KGN cells were exposed to various concentration (0, 20, 40, 80 μM) of liquiritin for 48 h, cell proliferation and apoptosis were measured by 3-(45)-dimethylthiahiazo(-z-y1)-35-di-phenytetrazoliumromide (MTT) and flow cytometry analysis. Reverse transcription‑quantitative polymerase chain reaction was conducted to checked the levels of miR-206 in KGN cells. The protein expression levels of cleaved caspase3, caspase3, phosphorylated (p)-AKT and AKT were analyzed using Western blot assay. We found that liquiritin stimulation led to reduced viability and enhanced apoptotic KGN cells, which along with increased cleaved caspase3 and cleaved caspase3/caspase3 ratio. Moreover, liquiritin obviously reduced p-AKT expression and p-AKT/AKT ratio. MiR-206 was up-regulated in liquiritin-treated KGN cells, however, all these results were reversed by miR-206 inhibitor. In conclusion, our findings suggested that liquiritin exerted anti-proliferative and apoptosis-inducing roles in KGN cells via miR-206/PI3K/AKT pathway, suggesting that liquiritin may be an effective therapeutic target for PCOS treatment.

Ginkgolide B (GB) is a bioactive constituent found in Ginkgo biloba leaves that has been long recognized as a protective agent against many neurological disorders. Our study aimed to examine the effect of GB in an in vitro Parkinson’s disease (PD) model and to investigate its neuroprotective mechanism as a primary objective. SK-N-SH cells were challenged with 1-methyl-4-phenylpyridinium (MPP+) to act as a PD-like model of neuronal damage. CCK-8 method, flow cytometry assay, and fluorescent probe JC-1 respectively measured cell viability, apoptosis, and mitochondrial membrane potential (MMP). Oxidative stress parameters were examined with assay kits. Nicotinamide adenine dinucleotide phosphate level and adenosine triphosphate (ATP) synthesis were also appraised. RT-qPCR examined mitochondrial DNA (mtDNA) release. Western blotting analyzed the proteins implicated in apoptosis and the histone deacetylase 4 (HDAC4)/Jun N-terminal kinase (JNK) pathway. GB concentration-dependently alleviated MPP+-stimulated viability loss, apoptosis, oxidative stress, and mitochondrial dysfunction in SK-N-SH cells. GB docked with HDAC4 and downregulated the HDAC4/JNK pathway. HDAC4 overexpression further reduced the viability and aggravated apoptosis, oxidative stress, and mitochondrial dysfunction in GB-treated SK-N-SH cells challenged with MPP+. Altogether, GB might inactivate the HDAC4/JNK pathway to protect against MPP+-triggered neuronal damage in PD.

Triglyceride-glucose (TyG) index was regarded as a cost-efficient and reliable clinical surrogate marker for insulin resistance (IR), which was significantly correlated with cardiovascular disease (CVD). However, the TyG index and incident CVD in non-diabetic hypertension patients remains uncertain. The aim of study was to explore the impact of TyG index level and variability on risk of CVD among non-diabetic hypertension patients. A total of 9313 hypertensive patients without diabetes aged 30–70 years in Jiangsu Province who participated in the baseline survey from January 2010 to December 2010 and were followed up to May 2020 were included in this study. The TyG index was calculated as ln [fasting triglyceride (TG) (mg/dl) × fasting plasma glucose (FPG) (mg/dl)/2] and variation degree was calculated as the TyG index at first year follow-up (2011) minus that at baseline (2010). Cox proportional analysis regression and restricted cubic spline were used to investigate the association between TyG index level as well as variability and CVD risk. Of 9313 included participants, 5423(58.23