The Kaohsiung journal of medical sciences最新文献

Blunt chest trauma (BCT) is common and frequently associated with adverse complications. Beyond merely impeding regular respiration, adverse events (AEs) such as hemothorax or pneumothorax can hinder the patient's recovery. Herein, we aim to validate potential predictive factors for AEs among adults with BCT who were admitted concurrently through the dataset focusing on the limited information available upon their arrival at the emergency department (ED). Seventeen variables-including patients' demographics, comorbidities, and vital signs/hemogram data upon arrival at the ED-were investigated. A penalized logistic regression model was applied to the derivation cohort and validated in a subgroup using the same dataset (80%:20%). In addition, we employed the least absolute shrinkage and selection operator (LASSO) logistic regression to develop a nomogram, which enhances the accuracy of estimating individual probabilities for AEs after admission for BCT. Our retrospective review encompassed 3,668 adult patients between 2017 and 2021, and the incidence of AEs was 15.6% (572 out of 3,668). Penalized logistic regression was conducted both without and with the hemogram data (Model 1 and Model 2), yielding relatively satisfactory results (R ²: 0.271 vs. 0.291; area under the curve: 0.784 vs. 0.797, respectively). Despite the model's relatively high predictive value in the derivation cohort, the validation data still maintained an acceptable accuracy of 0.7456 and 0.7049, respectively. Employing our penalized logistic regression analysis, the recently formulated nomogram exhibited proficiency in predicting AEs following BCT. This effectiveness was achieved by integrating vital signs, hemogram data, and comorbidities recorded upon their arrival at the ED.

Endometrial cancer (EC) is one of the most prevalent gynecologic malignancies, with increasing incidence worldwide. Recent studies have highlighted the critical roles of long noncoding RNAs (lncRNAs) in regulating tumor progression. This study investigated the oncogenic function of lncRNA LINC00958 in EC and its underlying mechanism involving the miR-129-2-3p/NOTCH3 signaling axis. Experimental results showed that LINC00958 was significantly upregulated in EC cell lines. Overexpression of LINC00958 enhanced cell proliferation, migration, and invasion, while inhibiting apoptosis, as evidenced by increased Bcl-2 and decreased cleaved caspase-3 and Bax expression. Conversely, silencing LINC00958 suppressed these malignant behaviors. Mechanistically, LINC00958 acted as a competing endogenous RNA (ceRNA), directly binding to miR-129-2-3p and thereby relieving its suppression on NOTCH3. Dual-luciferase reporter assays confirmed the direct interaction between LINC00958 and miR-129-2-3p, as well as between miR-129-2-3p and NOTCH3. Immunofluorescence analysis further demonstrated enhanced nuclear translocation of NOTCH3 following LINC00958 overexpression. Functional rescue experiments showed that miR-129-2-3p overexpression or NOTCH3 knockdown effectively counteracted the tumor-promoting effects of LINC00958. In vivo xenograft experiments using Ishikawa cells supported the in vitro findings, confirming that LINC00958 promotes tumor growth by modulating the miR-129-2-3p/NOTCH3 axis. Overall, this study identifies LINC00958 as a novel oncogenic lncRNA in EC, which facilitates tumor progression by sponging miR-129-2-3p and enhancing NOTCH3 signaling. These findings provide new insights into the molecular mechanisms of EC and suggest that targeting the LINC00958/miR-129-2-3p/NOTCH3 axis may represent a promising therapeutic strategy.

This study investigates the impact of cardiometabolic risk factors (CMRF) on the prevalence and incidence of hypertension (HTN) and diabetes mellitus (DM) in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) and nonsteatotic liver disease (non-SLD), using both cross-sectional and longitudinal data. A total of 32,569 Taiwanese adults without viral hepatitis or significant alcohol consumption who underwent health checkups from 1999 to 2013 were analyzed cross-sectionally. Among them, 27,109 individuals free of HTN and DM at baseline and within 1 year of enrollment were followed longitudinally. Participants were classified into four groups based on hepatic steatosis assessed by ultrasound and presence of CMRF: healthy control (non-SLD/CMRF-), simple SLD (SLD/CMRF-), non-SLD/CMRF+, and MASLD. MASLD patients exhibited markedly higher annual incidence rates of HTN and DM (19.7 and 6.3 per 1000 person-years) compared to non-SLD individuals (HTN: 9.0; DM: 0.6 per 1000 person-years). The risk of incident HTN and DM increased progressively with the number of CMRF, with adjusted hazard ratios (aHR) ranging from 2.02 to 15.53 for HTN and from 2.92 to 82.38 for DM. Regression of cardiometabolic dysfunction decreased the risk of HTN and/or DM, and vice versa. The presence of CMRF significantly increased the likelihood of developing HTN and DM in both SLD and non-SLD groups, with aHRs up to 7.48 for HTN and 15.38 for DM. In conclusion, MASLD is strongly associated with increased prevalence and incidence of HTN and DM, and the burden and trajectory of CMRF critically modulate these risks.

Natural killer (NK) cells present in the tumor microenvironment serve as a critical line of defense against various malignancies, including cervical cancer. While MYB is known to drive malignancy progression, its influence on NK cell activity remains poorly understood. This study aimed to elucidate the role of MYB in regulating NK cell cytotoxicity and its underlying mechanism in cervical cancer cells. MYB expression in cervical cancer tissues and cells was analyzed using bioinformatics and qRT-PCR. Cell viability was assessed via CCK-8 assay, while NK cell-mediated killing of cervical cancer cells was evaluated through cytotoxicity assays. The expression levels of cytotoxic factors (IFN-γ and TNF-α) were measured by ELISA, whereas perforin and granzyme B were detected via immunofluorescence. Apoptosis was analyzed using flow cytometry. To investigate the impact of MYB on the hedgehog signaling pathway, the expression levels of related factors (PTCH1, Gli1, and Gli2) were assessed using qRT-PCR and Western blot. Bioinformatics and qRT-PCR analyses revealed MYB overexpression in cervical cancer. Signaling pathway prediction indicated MYB enrichment in cytotoxic signaling pathways. Functional experiments demonstrated that MYB overexpression activated the hedgehog signaling pathway, thereby suppressing NK cell cytotoxicity in cervical cancer. Rescue experiments using the hedgehog signaling inhibitor GANT58 attenuated the suppressive effect of MYB overexpression on NK cytotoxicity. In summary, MYB inhibited NK cell cytotoxicity by activating the hedgehog signaling pathway in cervical cancer, suggesting its potential as a novel diagnostic marker and immunotherapeutic target.

Our previous study revealed the role of glycerol phosphate O-acyltransferase (GNPAT) in regulating chronic obstructive pulmonary disease (COPD). However, its further mechanisms remained unclear. In this study, COPD models were established by exposing mice to cigarette smoke particulates. H&E staining and immunohistochemistry assays were performed on COPD tissue. A549 cells were stimulated with 5% cigarette smoke extract (CSE) and transfected with GNPAT, ubiquitin-specific protease 30 (USP30), and dynamin-related protein 1 (DRP1) plasmids. Cell viability, cell apoptosis, lactate dehydrogenase (LDH) release, ATP production, and reactive oxygen species (ROS) levels were determined using commercial kits. Quantitative real-time PCR and western blotting were used to evaluate mRNA and protein expression. Mitochondrial morphology was examined by transmission electron microscopy. A co-immunoprecipitation assay determined the binding relationships among GNPAT, USP30, and DRP1. Our results showed that GNPAT and DRP1 were highly expressed in the COPD model mice. CSE promoted mitochondrial fission, mitochondrial dysfunction, and cell apoptosis, which were further enhanced by treatment with a mitochondrial fission inducer (TA9). GNPAT promoted mitochondrial fission, mitochondrial dysfunction, and cell apoptosis by enhancing DPR1 protein stability, which depended on USP30. DRP1 enhanced mitochondrial fission, mitochondrial dysfunction, and cell apoptosis, which were both reversed by GNPAT/USP30 inhibition. Collectively, our present study found that GNPAT recruited USP30 and stabilized DRP1, thereby mediating mitochondrial fission and mitochondrial dysfunction that contributed to cell apoptosis in COPD. This study suggests a promising therapeutic biomarker for COPD.

Periodontal ligament stem cells (PDLSCs) are derived from periodontal tissue and can differentiate into osteoblasts, which are ideal materials for alveolar bone repair and periodontal tissue regeneration. In this study, we aimed to explore the effects of Y-box binding protein 1 (YB-1) on the osteogenic differentiation and proliferation of PDLSCs and its underlying mechanism. hPDLSC proliferation was detected by CCK-8 and EdU assays. The osteogenic differentiation of hPDLSCs was clarified using alkaline phosphatase (ALP) activity detection and Alizarin red S (ARS) staining. The expression levels of osteogenic differentiation-related factors, Akt/GSK3β/β-catenin pathway-related factors, YB-1, and fibroblast growth factor 2 (FGF2) were evaluated using qPCR and Western blotting. The interplay between YB-1 and FGF2 was clarified using ChIP and dual-luciferase reporter gene assays. YB-1 expression was markedly decreased in periodontitis clinical tissues but increased in hPDLSCs during osteogenic differentiation. Moreover, silencing YB-1 suppressed the osteogenic differentiation and proliferation of hPDLSCs. In addition, YB-1 promotes hPDLSC proliferation and osteogenic differentiation in a manner dependent on the activation of the Akt/GSK3β/β-catenin signaling pathway, which is mediated by FGF2 transcriptional activation. Furthermore, the inhibitory effects of YB-1 knockdown on the osteogenic differentiation and proliferation of hPDLSCs were antagonized by human recombinant FGF2. Taken together, our findings revealed that YB-1 facilitates hPDLSC proliferation and osteogenic differentiation through increasing the level of FGF2 via transcriptional regulation, thereby activating the Akt/GSK3β/β-catenin pathway.

Traumatic brain injury (TBI) causes a high level of blood glutamate, which triggers host defense by activating oxidative stress and inflammation response. However, the concrete mechanism underlying its exacerbating effects on acute lung injury (ALI) severity remains unknown. In the present study, we aim to demonstrate the special role of N-methyl-D-aspartate receptor (NMDAR) in regulating glutamate-related inflammation signaling to facilitate the sustaining injury. After the interventions, blood glutamate concentration was measured using HPLC-MS/MS. The level of pro-inflammation cytokines, wet/dry weight ratio, protein concentration, and lung injury score were measured to examine the severity of lung damage. The oxidative status was evaluated by measuring the levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) activity, and intracellular Ca²⁺ concentration. Endothelial cell dysfunction was assessed through dye extravasation assay and quantification of p-NFAT, p-p65, ICAM-1, and VCAM-1 expression levels. Results showed that glutamate activated the NMDAR pathway, inducing endothelial barrier dysfunction via ROS/MDA elevation and SOD suppression. This cascade promoted the concentration of Ca²⁺, activating both nuclear factor of activated T cells (NFAT) and nuclear factor kappa-B (NF-κB) pathway. Glutamate administration exacerbated NMDAR activation, leading to persistent lung injury following TBI. Memantine-mediated NMDAR blockade effectively attenuated this injury. Our findings indicate that blood glutamate elevation may trigger TBI-associated acute lung injury (TBI-ALI) through endothelial NMDAR/ROS/Ca²⁺ signaling.