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The epigenetic abnormality is generally accepted as the key to cancer initiation. Epigenetics that ensure the somatic inheritance of differentiated state is defined as a crucial factor influencing malignant phenotype without altering genotype. Histone modification is one such alteration playing an essential role in tumor formation, progression, and resistance to treatment. Notably, changes in histone acetylation have been strongly linked to gene expression, cell cycle, and carcinogenesis. The balance of two types of enzyme, histone acetyltransferases (HATs) and histone deacetylases (HDACs), determines the stage of histone acetylation and then the architecture of chromatin. Changes in chromatin structure result in transcriptional dysregulation of genes that are involved in cell-cycle progression, differentiation, apoptosis, and so on. Recently, HDAC inhibitors (HDACis) are identified as novel agents to keep this balance, leading to numerous researches on it for more effective strategies against cancers, including glioblastoma (GBM). This review elaborated influences on gene expression and tumorigenesis by acetylation and the antitumor mechanism of HDACis. Besdes, we outlined the preclinical and clinical advancement of HDACis in GBM as monotherapies and combination therapies.

Pulmonary tuberculosis (PTB) is an infectious disease of major public health problem, China is one of the PTB high burden counties in the word. Hubei is one of the provinces having the highest notification rate of tuberculosis in China. This study analyzed the temporal and spatial distribution characteristics of PTB in Hubei province for targeted intervention on TB epidemics. The data on PTB cases were extracted from the National Tuberculosis Information Management System correspond to population in 103 counties of Hubei Province from 2011 to 2021. The effect of PTB control was measured by variation trend of bacteriologically confirmed PTB notification rate and total PTB notification rate. Time series, spatial autonomic correlation and spatial-temporal scanning methods were used to identify the temporal trends and spatial patterns at county level of Hubei. A total of 436,955 cases were included in this study. The total PTB notification rate decreased significantly from 81.66 per 100,000 population in 2011 to 52.25 per 100,000 population in 2021. The peak of PTB notification occurred in late spring and early summer annually. This disease was spatially clustering with Global Moran's I values ranged from 0.34 to 0.63 (P< 0.01). Local spatial autocorrelation analysis indicated that the hot spots are mainly distributed in the southwest and southeast of Hubei Province. Using the SaTScan 10.0.2 software, results from the staged spatial-temporal analysis identified sixteen clusters. This study identified seasonal patterns and spatial-temporal clusters of PTB cases in Hubei province. High-risk areas in southwestern Hubei still exist, and need to focus on and take targeted control and prevention measures.

Background Treatment of gliomas, the most prevalent primary malignant neoplasm of the central nervous system, is challenging. Arachidonate 5-lipoxygenase activating protein (ALOX5AP) is crucial for converting arachidonic acid into leukotrienes and is associated with poor prognosis in multiple cancers. Nevertheless, its relationship with the prognosis and the immune microenvironment of gliomas remains incompletely understood. Methods The differential expression of ALOX5AP was evaluated based on public Databases. Kaplan–Meier, multivariate Cox proportional hazards regression analysis, time-dependent receiver operating characteristic, and nomogram were used to estimate the prognostic value of ALOX5AP. The relationship between ALOX5AP and immune infiltration was calculated using ESTIMATE and CIBERSORT algorithms. Relationships between ALOX5AP and human leukocyte antigen molecules, immune checkpoints, tumor mutation burden, TIDE score, and immunophenoscore were calculated to evaluate glioma immunotherapy response. Single gene GSEA and co-expression network-based GO and KEGG enrichment analysis were performed to explore the potential function of ALOX5AP. ALOX5AP expression was verified using multiplex immunofluorescence staining and its prognostic effects were confirmed using a glioma tissue microarray. Result ALOX5AP was highly expressed in gliomas, and the expression level was related to World Health Organization (WHO) grade, age, sex, IDH mutation status, 1p19q co-deletion status, MGMTp methylation status, and poor prognosis. Single-cell RNA sequencing showed that ALOX5AP was expressed in macrophages, monocytes, and T cells but not in tumor cells. ALOX5AP expression positively correlated with M2 macrophage infiltration and poor immunotherapy response. Immunofluorescence staining demonstrated that ALOX5AP was upregulated in WHO higher-grade gliomas, localizing to M2 macrophages. Glioma tissue microarray confirmed the adverse effect of ALOX5AP in the prognosis of glioma. Conclusion ALOX5AP is highly expressed in M2 macrophages and may act as a potential biomarker for predicting prognosis and immunotherapy response in patients with glioma.

Objective To explore the epidemiological characteristics of patients with lymphoepithelial carcinoma (LEC) of the head and neck and the prognostic factors. Methods We conducted a retrospective cohort study of cases of head and neck LEC retrieved from the Surveillance, Epidemiology and End Results database. Kaplan–Meier survival analysis and the log-rank test were employed to assess overall survival (OS) and cancer-specific survival (CSS). Univariate and multivariate analyses were used to construct Cox regression models. We established nomograms to predict OS and CSS among patients with nasopharyngeal LEC, who were divided into high- and low-risk groups based on the OS nomograms to compare the effects of treatment using the restricted mean survival time (RMST). Results The 5-year OS and CSS rates of the cohort were 70.8% and 74.8%, respectively. Advanced age, unmarried status, black race, distant metastasis, and the absence of surgical treatment were significantly associated with decreased survival rates. RMST did not differ between the combined treatment (radiotherapy and chemotherapy) and radiotherapy monotherapy groups, but chemotherapy alone displayed poor efficacy. Conclusions Head and neck LEC is associated with a favorable prognosis. Radiotherapy plays a significant role in managing patients with nasopharyngeal LEC, which is influenced by multiple prognostic factors.

The intestinal epithelium undergoes rapid turnover driven by Lgr5 + intestinal stem cells at the crypt base, and can recover upon damage. Histone crotonylation plays a critical role in chromatin regulation and gene expression. However, the role of histone crotonylation, specifically H3K14 crotonylation (H3K14cr) in the intestine remains poorly understood. Here we demonstrate that both crotonate and H3K14cr levels are increased in the regenerating crypts. Treatment with sodium crotonate significantly alleviates dextran sulfate sodium induced colitis, an effect largely dependent on HBO1-mediated H3K14cr. Notably, HBO1 deficiency severely dampens regeneration, correlating with reduced H3K14ac and H3K14cr levels, decreased chromatin accessibility at transcriptional start sites, and impaired expression of stem and fetal genes. Single-cell RNA sequencing analysis reveals that HBO1 is expressed in stem cells and regenerative cells during recovery after irradiation, further supporting the critical role of HBO1 in intestinal regeneration. Together, our findings uncover a mechanism by which crotonate, HBO1, and H3K14cr contribute to epithelial regeneration and suggest that crotonate may represent a promising therapeutic agent for the treatment of gastrointestinal diseases. Here the authors show that crotonate and H3K14cr levels are increased in regenerating crypts. Treatment with sodium crotonate (NaCr) significantly alleviates dextran sulfate sodium induced colitis, an effect largely dependent on HBO1-mediated H3K14cr.

Abstract Introduction: Restoration of podocyte autophagy is considered as a feasible strategy for the treatment of diabetic kidney disease (DKD). This study aimed at investigating the protective effect and potential mechanism of vitamin D on podocyte injury of DKD. Methods: Type 2 diabetic db/db mice received intraperitoneal injections of vitamin D analog paricalcitol 400 ng/kg per day for 16 weeks. Immortalized mouse podocytes were cultured in high glucose (HG) medium with active vitamin D3 calcitriol or autophagy inhibitor 3-methyladenine. Renal function and urine albumin creatinine ratio were assessed at week 24. HE, PAS staining, and electron microscopy were used to evaluate renal histopathology and morphological changes. Immunohistochemistry, immunofluorescence, and Western blot were used to evaluate protein expression of nephrin and podocin in kidney tissue and podocytes. The expression of autophagy-related proteins (LC3, Beclin-1, Vps34) and apoptosis-related proteins (cleaved caspase-3, Bax) was determined by Western blotting. Podocyte apoptosis was further evaluated by using flow cytometer. Results: Albuminuria in a db/db mouse model was markedly attenuated after treatment with paricalcitol. This was accompanied by alleviation of mesangial matrix expansion and podocyte injury. Besides, the impaired autophagy in podocytes under diabetic conditions was also markedly enhanced after paricalcitol or calcitriol treatment, accompanied by restored decreased podocyte slit diaphragm proteins podocin and nephrin. Furthermore, the protective effect of calcitriol against HG-induced podocyte apoptosis could be abated by autophagy inhibitor 3-methyladenine. Conclusion: Vitamin D ameliorates podocyte injury of DKD by enhancing podocyte autophagy activity, which may become a potential candidate autophagy activator for the therapeutic interventions for DKD.

Glioblastoma is highly aggressive and resistant to treatment, making it crucial to understand the regulatory mechanisms underlying its invasion. LIN7A, a polar protein, has been implicated in tumor cell migration and invasion, but its role in glioblastoma remains unclear. This study aimed to manipulate LIN7A gene expression in U87 cells, analyze its impact on invasion, and explore the potential mechanisms through which LIN7A regulates glioblastoma cell invasion. Lentiviral vectors were used to silence the LIN7A gene in U87 cells, selecting the most effective vector. LIN7A gene transcription, protein expression and localization were analyzed using RT-qPCR, Western blotting, and immunofluorescence. U87 cell invasion was assessed via real-time cell analysis and spheroid invasion assay, while MMP-2 and MMP-9 protease activities were measured using zymography. β-catenin protein levels and localization were evaluated through Western blotting and immunofluorescence. Expression of target genes in the β-catenin pathway was also measured. An orthotopic xenograft glioblastoma model in nude mice was established by intracranial implantation of U87 cells, with tumor growth monitored using immunofluorescence analysis of brain slices. The clinical significance of LIN7A expression was confirmed by comparing its levels in core and peripheral invading areas of glioblastoma and analyzing RNASeq data and clinical information from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) GBM cohort. Transfection of U87 cells with a lentiviral vector led to decreased LIN7A levels and altered distribution patterns. Silencing the LIN7A gene increased U87 cell proliferation and invasiveness, reduced clonal formation ability, and enhanced MMP-2 and MMP-9 protease activity. It also resulted in a slight increase in cytoplasmic β-catenin content, although not statistically significant, but a significant increase in nuclear β-catenin accumulation and transcriptional activity of target genes in the pathway. Animal studies showed that LIN7A gene silencing caused U87 cells to transition from clumpy to invasive growth mode. LIN7A expression was significantly lower in the peripheral invading area compared to the core area in clinical samples of glioblastoma. Data mining of the CPTAC-GBM cohort revealed a strong association between LIN7A gene expression and survival time. Silencing LIN7A may promote U87 tumor cell invasion by disrupting intercellular junctions, altering cell polarity, and activating the β-catenin pathway. Further research is warranted to elucidate the role of LIN7A in glioblastoma cell invasion.

The intestinal epithelium undergoes fast turnover, and the villus length in the small intestine gradually decreases from the duodenum to the ileum. However, the underlying mechanisms remain poorly understood. In this study, we investigate the regulatory mechanism underlying the regional disparity of villus length. A progressive strengthening of BMP signaling from the duodenum to the jejunum and ileum establishes a signaling gradient, resulting in differences in the rates of cell proliferation and apoptosis. We show that BMP signaling regulates the survival of the small intestine epithelial cells by inhibiting integrin expression and thereby inducing cell apoptosis. Combined with mathematical modeling, our data reveal that BMP signaling provides positional cues and antagonizes Wnt signaling to control villus growth, while Wnt signaling promotes BMP signaling to counteract excessive proliferation, thus maintaining villus length. Our findings provide insights into the signaling dynamics governing epithelial turnover and villus length in the small intestine. BMP signaling forms an intestinal gradient regulating villus length by balancing cell proliferation with apoptosis to optimize nutrient absorption efficiency across regions.

Background: Increased fatty acid metabolism (FAM) is an important marker of tumor metabolism. However, the characterization and function of FAM-related genes in glioblastoma (GBM) have not been fully explored. Method: In the TCGA-GBM cohort, FAM-related genes were divided into three clusters (C1, C2, and C3), and the DEGs between the clusters and those in the normal group and GBM cohort were considered key genes. On the basis of 10 kinds of machine learning methods, we used 101 combinations of algorithms to construct prognostic models and obtain the best model. In addition, we also validated the model in the GSE43378, GSE83300, CGGA, and REMBRANDT datasets. We also conducted a multifaceted analysis of F13A1, which plays an important role in the best model. Results: C2, with the worst prognosis, may be associated with an immunosuppressive phenotype, which may be related to positive regulation of cell adhesion and lymphocyte-mediated immunity. Using multiple machine learning methods, we identified RSF as the best prognostic model. In the RSF model, F13A1 accounts for the most important contribution. F13A1 can support GBM malignant tumor cells by promoting fatty acid metabolism in GBM macrophages, leading to a poor prognosis for patients. This metabolic reprogramming not only enhances the survival and proliferation of macrophages, but also may promote the growth, invasion, and metastasis of GBM cells by secreting growth factors and cytokines. F13A1 is significantly correlated with immune-related molecules, including IL2RA, which may activate immunity, and IL10, which suggests immune suppression. F13A1 also interferes with immune cell recognition and killing of GBM cells by affecting MHC molecules. Conclusions: The prognostic model developed here helps us to further enhance our understanding of FAM in GBM and provides a compelling avenue for the clinical prediction of patient prognosis and treatment. We also identified F13A1 as a possibly novel tumor marker for GBM which can support GBM malignant tumor cells by promoting fatty acid metabolism in GBM macrophages.

Heterogeneous ribonucleoproteins (hnRNPs) are involved in a variety of key cellular functions and are most likely involved in different steps of pre-mRNA processing. Over the past decades, the central roles of hnRNPs have been detected, which show that they are involved in RNA splicing, telomere biogenesis, DNA repair, cell signaling, and in transcription and translation. Mounting evidence suggests that they are involved in the regulation of mRNA stability and translation in many cancer types. The hnRNPs have a variety of potential roles in inhibition of apoptosis, angiogenesis, cell invasion, and epithelial-mesenchymal transition (EMT). It is thus suggested that hnRNP might be a novel and promising therapeutic target and a marker for treatment response and prognostic evaluation. The aims of this review are to survey the existing evidence and discuss the diverse functions of hnRNPs in cancer metastasis.