Mechanotransduction channels are widely expressed in both vertebrates and invertebrates, mediating various physiological processes such as touch, hearing and blood-pressure sensing. While previously known mechanotransduction channels in metazoans are primarily cation-selective, we identified Anoctamin-1 (ANOH-1), the C. elegans homolog of mammalian calcium-activated chloride channel ANO1/TMEM16A, as an essential component of a mechanosensory channel complex that contributes to the nose touch mechanosensation in C. elegans. Ectopic expression of either C. elegans or human Anoctamin-1 confers mechanosensitivity to touch-insensitive neurons, suggesting a cell-autonomous role of ANOH-1/ANO1 in mechanotransduction. Additionally, we demonstrated that the mechanosensory function of ANOH-1/ANO1 relies on CIB (calcium- and integrin- binding) proteins. Thus, our results reveal an evolutionarily conserved chloride channel involved in mechanosensory transduction in metazoans, highlighting the importance of anion channels in mechanosensory processes.

This study explores temporalis muscle thickness (TMT), a surrogate marker of nutritional and physiological reserves, as a potential prognostic indicator of outcomes in patients with severe traumatic brain injury (TBI) undergoing craniotomy. This retrospective study analyzed patients with severe TBI [Glasgow Coma Scale (GCS) 3–8] who underwent craniotomy between January 2020 and July 2024. TMT was measured on preoperative computed tomography scans using standardized protocols. Associations between TMT, clinical variables, and 6-month Glasgow Outcome Scale (GOS) scores were evaluated using Pearson correlation and multivariate regression. A total of 206 patients were included, with a median age of 47 years (interquartile range: 20–65). Higher TMT was significantly associated with favorable GOS scores (47.57% vs 2.43%, P < .001). Multivariate analysis identified TMT as an independent predictor of GOS (95% confidence interval: 0.21–0.53, P < .001), even after adjusting for age, sex, and GCS. Lower TMT was associated with an increased risk of postoperative hydrocephalus (95% confidence interval: 0.258–0.606, P = .001). Older age (51–65 years) independently predicted both poor prognosis ( P = .008) and hydrocephalus ( P = .014). Decompressive craniectomy was associated with improved outcomes ( P < .001). TMT is a robust, noninvasive prognostic marker that improves outcome prediction in severe TBI. Integrating TMT with GCS may optimize risk stratification and guide personalized rehabilitation strategies.

Glioma, an aggressively malignant brain tumor with a poor prognosis, comprises nearly 50% of all primary malignant brain tumors. Despite its significance in other cancers, the role of coiled-coil domain containing 86(CCDC86) in glioma remains largely unexplored. Our study revealed a significant up-regulation of CCDC86 expression in glioma tissues, correlating notably with patient age, tumor recurrence, and pathological grade. Moreover, elevated CCDC86 level was associated with a worsened prognosis among glioma patients. Functional assays demonstrated that CCDC86 knockdown attenuated glioma cell proliferation and migration while inducing apoptosis and cell cycle arrest in vitro and inhibited tumorigenesis in vivo. Furthermore, ATF3 emerged as a downstream target gene of CCDC86, as its knockdown could counteract the oncogenic effects induced by CCDC86 overexpression in glioma cells. Mechanistically, CCDC86 promoted the transcriptional regulation of ATF3 by BHLHE40 through interaction with it, stabilizing the expression of ATF3. Additionally, our investigation unveiled a potential mechanism whereby CCDC86 activated the ERK signaling pathway through ATF3, thus influencing glycolysis to drive tumor progression. In conclusion, our study highlights the pivotal role of CCDC86 in glioma progression, suggesting its potential as a therapeutic target for the development of novel glioma treatments.

Prostate cancer (PCa) remains among the most common genitourinary tumors in elderly men, as PCa diagnosis and treatment remain major challenges. Liquid biopsy is a minimally invasive method that causes minor harm to patients with cancer. Peripheral blood protein biomarkers provide real-time PCa information and are easily accessible. The present review summarizes recent progress in identifying candidate peripheral blood protein biomarkers of PCa, including pentraxin-3, soluble E-cadherin, serum T-cell immunoglobulin, serum B- and T-lymphocyte attenuator, myeloid differentiation factor-2, pleiotrophin, spondin 2, filamin A, soluble urokinase plasminogen activator receptor, laminin subunit β-1, Golgi membrane protein 1, vitamin D-binding protein, tumor necrosis factor receptor superfamily member 9, activated leukocyte cell adhesion molecule and trophoblastic cell-surface antigen. Notably, the present review summarizes and discusses the clinical value of these proteins in PCa prediction, diagnosis, prognosis and drug resistance monitoring. These emerging peripheral blood protein biomarkers are promising for improving PCa stratification and management.

Brain gliomas are among the most aggressive central nervous system tumors, with a 5-year survival rate of less than 10 %, underscoring the need for new therapeutic approaches. Ferroptosis, an iron-dependent form of regulated cell death involving GPX4, SLC7A11, and ACSL4, has been proposed as a potential target. In this study, we prepared resveratrol-loaded nanoparticles (1-Fru-2-ATPMS@RES) on a fructose-ATPMS scaffold and investigated their electrochemical and preliminary biological properties. Cyclic voltammetry in 5 mM [Fe(CN)6]3-/4- (0.1 M KCl) showed adsorption-controlled redox peaks at 0.42 V and 0.30 V, with linear current-scan rate relationships (Ipa = 2.25v + 0.005, R2 = 0.992; Ipc = -2.46v + 0.004, R2 = 0.994). Electrochemical impedance spectroscopy further indicated sensitive interaction with RES, as charge-transfer resistance (Rct) increased from 9.5 Ω to 2.8 kΩ, providing a linear ΔRct-log[RES] response over 0.1 nM-100 μM (R2 = 0.997), with a detection limit of 0.01 nM and a sensitivity of 1.15 kΩ/decade. In U251 cells, 1-Fru-2-ATPMS@RES treatment modulated the expression of ferroptosis-associated genes (GPX4, SLC7A11, and ACSL4), suggesting a potential role of ferroptosis in the observed anti-proliferative effects. While further in-depth mechanistic studies are required, these preliminary results support the potential of RES-NPs as a candidate platform for combined electrochemical sensing and potential ferroptosis-oriented therapeutic exploration.

Gliomas are aggressive brain tumors with high mortality and recurrence rates. Pleiotrophin (PTN), a cytokine that interacts with heparin, is upregulated in several cancers, including breast and lung cancer. PTN is implicated in cancer progression, recurrence, epithelial–mesenchymal transition (EMT), and metastasis. However, the role of PTN in glioma progression remains poorly understood. This study aimed to investigate the expression profile of PTN in glioma and its potential prognostic significance. The expression levels of PTN in glioma samples were analyzed using data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). Gene Ontology (GO) term analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to identify PTN-associated pathways. In vitro experiments were performed to assess the impact of PTN suppression on glioma cell growth, cell cycle progression, migration, and invasion. In addition, gene set enrichment analysis (GSEA) and Western blot were employed to investigate the link between PTN and NF-κB signaling pathways. PTN expression was significantly higher in glioma samples, and elevated PTN levels were associated with decreased overall survival. GO term and KEGG analysis showed that PTN is primarily linked to pathways related to cell mitosis, including the cell cycle and DNA replication. In vitro experiments demonstrated that the suppression of PTN inhibited glioma cell growth, arrested the cell cycle in the G0/G1 phase, and impaired the migratory and invasive capabilities of glioma cells. GSEA revealed a significant correlation between PTN and the NF-κB pathway. Further investigation showed that PTN suppression inhibited NF-κB activation and IκB phosphorylation, thereby preventing Slug-induced EMT in glioma cells. PTN plays a crucial role in glioma progression by regulating cell proliferation, migration, invasion, and EMT through the NF-κB pathway. PTN may serve as an important prognostic biomarker and therapeutic target in glioma treatment.

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Background While new genetic analysis methods are widely used in the clinic, few researchers have focused on trigeminal neuralgia (TN) with familial clustering (≥ 2 TN patients in one kindred family). Previous literature suggests that familial trigeminal neuralgia (FTN) may be associated with inherited genetic factors. To date, few next-generation sequencing studies have been reported for FTN. This study investigated the pathogenic mechanism of FTN by using whole-exome sequencing (WES) technology, which may enhance our understanding of human TN pathophysiology. Method We performed WES for 7 probands from families of FTN. Sanger sequencing was performed for two control groups (FTN family members group and nonfamilial TN subject group) to potentially identify new FTN-related gene mutations. In families where FTN probands carried potentially pathogenic gene mutations, the ribonucleic acid (RNA) of FTN probands and related family members, as well as nonfamilial TN patients were analysed by RNA sequencing (RNA-seq) to confirm differential gene expression. Results Seven probands were derived from 3 Chinese families. WES and Sanger sequencing identified MARS1 mutation c.2398C > A p.(Pro800Thr) in Family 1. MARS1 mutation was confirmed in 14/26 [53.8%] members of Family 1 in FTN family member group, while none of nonfamilial TN subjects had this MARS1 mutation. RNA-seq showed that 3 probands in Family 1 had higher expression of Fosl1 (Fos-like antigen 1) and NFE2 (Nuclear factor, erythroid 2) than 3 subjects in the nonfamilial TN subject group. Fosl1 and NFE2 are genes related to integrated stress response (ISR). Conclusion MARS1 mutations may cause chronic activation of ISR, contribute to ISR pathophysiological changes in FTN, and cause/accelerate peripheral nerve degeneration. The findings of this study can enrich our knowledge of the role of molecular genetics in TN in humans.

Ischemic stroke is a leading cause of disability and mortality worldwide. Thus, it is urgent to explore its pathophysiological mechanisms and find new therapeutic strategies for its successful treatment. The relationship between oxidative stress and ischemic stroke is increasingly appreciated and attracting considerable attention. ROS serves as a source of oxidative stress. It is a byproduct of mitochondrial metabolism but primarily a functional product of NADPH oxidases (NOX) family members. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is most closely related to the formation of ROS during ischemic stroke. Its expression is significantly upregulated after cerebral ischemia, making it a promising target for treating ischemic stroke. Several drugs targeting NOX4, such as SCM-198, Iso, G-Rb1, betulinic acid, and electroacupuncture, have shown efficacy as treatments of ischemic stroke. MTfp-NOX4 POC provides a novel insight for the treatment of stroke. Combinations of these therapies also provide new approaches for the therapy of ischemic stroke. In this review, we summarize the subcellular location, expression, and pathophysiological mechanisms of NOX4 in the occurrence and development of ischemic stroke. We also discuss the therapeutic strategies and related regulatory mechanisms for treating ischemic stroke. We further comment on the shortcomings of current NOX4-targeted therapy studies and the direction for improvement.

RNA modifications play a major role in tumorigenicity and progression, but the expression and function in glioblastoma (GBM) have not been well described. In this study, we developed a GBM score based on the differentially expressed genes (DEGs) between groups showing RNA modification patterns. We assessed the association between the GBM score and tumor microenvironment (TME) characteristics. Based on the gene expression of these regulators, we identified two clusters with distinct RNA modification patterns. Kaplan–Meier survival curves showed that patients in cluster 1 had worse survival than those in cluster 2. Kaplan–Meier and multivariate Cox regression analyses showed that GBM scores (based on DEGs between RNA modification patterns) are an independent predictive biomarker for patient prognosis. Besides, we found that samples with high scores were significantly associated with epithelial-to-mesenchymal transition and immune checkpoints, while samples with low scores were associated with cell cycle regulation. Importantly, GBM-score markedly positively correlated drug resistance, while negatively correlated with drug sensitive. The responders of anti-PD-1/PD-L1 immunotherapy tend to have a lower GBM score than non-responders. In conclusion, our comprehensive analysis of multiple RNA modifications in GBM revealed that RNA modification regulators were closely correlated with TME.

Metabolic signatures are frequently observed in cancer and are starting to be recognized as important regulators for tumor progression and therapy. Because metabolism genes are involved in tumor initiation and progression, little is known about the metabolic genomic profiles in low-grade glioma (LGG). Here, we applied bioinformatics analysis to determine the metabolic characteristics of patients with LGG from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). We also performed the ConsensusClusterPlus, the CIBERSORT algorithm, the Estimate software, the R package "GSVA," and TIDE to comprehensively describe and compare the characteristic difference between three metabolic subtypes. The R package WGCNA helped us to identify co-expression modules with associated metabolic subtypes. We found that LGG patients were classified into three subtypes based on 113 metabolic characteristics. MC1 patients had poor prognoses and MC3 patients obtained longer survival times. The different metabolic subtypes had different metabolic and immune characteristics, and may have different response patterns to immunotherapy. Based on the metabolic subtype, different patterns were exhibited that reflected the characteristics of each subtype. We also identified eight potential genetic markers associated with the characteristic index of metabolic subtypes. In conclusion, a comprehensive understanding of metabolism associated characteristics and classifications may improve clinical outcomes for LGG.

Background: Chemo-resistance is one of the key causal factors in cancer death and emerging evidences suggest that microRNAs (miRNAs) have critical roles in the regulation of chemo-sensitivity in cancers. Cervical cancer is one of the most common malignancies in women and insensitive to chemotherapy clinically. Methods: The differentially expressed miRNAs in cervical squamous cell carcinoma tissues were screened by using a microarray platform ( μ Paraflo Sanger miRBase release 13.0). The expression of miR-375 was determined by stem-loop RT–PCR using 23 clinical cervical cancer samples and 2 cervical cancer cell lines. We exogenously upregulated miR-375 expression in SiHa and Caski cells using a pre-miRNA lentiviral vector transfection and observed its impact on paclitaxel sensitivity using MTS. The cells that stably overexpressed miR-375 were subcutaneously injected into mice to determine tumour growth and chemo-sensitivity in vivo . Results: Twenty-one differentially expressed miRNAs were found by miRNA microarray between pro- and post-paclitaxel cervical cancer tissues. Of those, miR-375 showed consistent high expression levels across paclitaxel-treated cervical cells and tissues. Paclitaxel induced upregulated miR-375 expression in a clear dose-dependent manner. Forced overexpression of miR-375 in cervical cancer cells decreased paclitaxel sensitivity in vitro and in vivo . Conclusion: Collectively, our results suggest that miR-375 might be a therapeutic target in paclitaxel-resistant cervical cancer.