Kaohsiung Journal of Medical Sciences最新文献

Endometriosis (EMS) is a prevalent gynecological condition lacking reliable diagnostic biomarkers. This prospective study aimed to analyze the potential of serum heat shock transcription factor 1 (HSF1) as a diagnostic marker for EMS. Clinical features of 92 EMS patients and 52 controls were recorded, revealing significant differences in dysmenorrhea, dyspareunia, pelvic pain, nulliparity, and CA125 levels. Serum HSF1 was upregulated in EMS patients, with higher levels in American Society for Reproductive Medicine (ASRM) III/IV than ASRM I/II. Receiver operating characteristic curve analysis demonstrated good diagnostic function for serum HSF1 (AUC: 0.857, sensitivity: 91.30%, specificity: 63.46%). Serum HSF1, dysmenorrhea, dyspareunia, and nulliparity were independent risk factors for EMS, while dysmenorrhea and serum HSF1 were independent risk factors for EMS severity. Additionally, the GSE25628 dataset was downloaded from the GEO database for differential analysis of gene expression. The HSF1 downstream target genes PTGES3, HSP90AA1, and HSPB1 showed significant differential expression in EMS, suggesting their involvement in the regulatory mechanism of HSF1 in EMS.

Epidemiological data show people with diabetes mellitus (DM) have three-fold increase in risk of periodontitis. A vitamin D insufficiency can affect the progression of DM and periodontitis. This study evaluated the effects of different-dose vitamin D supplementation to nonsurgical periodontal therapy for vitamin-D-insufficient diabetic patients coexisting with periodontitis and changes of gingival bone morphogenetic protein-2 (BMP-2) levels. The study included 30 vitamin-D-insufficient patients receiving nonsurgical treatment followed by administration of 25,000 international units (IU) vitamin D3 per week (the low-VD group) and 30 patients receiving 50,000 UI vitamin D per week (the high-VD group). The decreases of probing pocket depth, clinical attachment loss, bleeding index, and periodontal plaque index values of patients after the six-month supplementation of 50,000 UI vitamin D3 per week to nonsurgical treatment were more significant than those after the six-month supplementation of 25,000 UI vitamin D3 per week to nonsurgical treatment. It was found that 50,000 IU per week vitamin D supplementation for 6 months could lead to a better glycemic control for vitamin-D-insufficient diabetic patients coexisting with periodontitis after nonsurgical periodontal therapy. Increased levels of serum 25(OH) vitamin D3 and gingival BMP-2 were found in both low- and high-dose VD groups, and the high-dose VD group exhibited higher levels than the low-dose VD group. Vitamin D supplementation in large doses for 6 months tended to improve the treatment of periodontitis and increase gingival BMP-2 levels in diabetic patients coexisting with periodontitis who were vitamin D deficient.

The epithelial-mesenchymal transition (EMT) is closely associated with Crohn's disease (CD) related intestinal fibrosis, a condition whose prevalence is increasing annually among children. Recently, the CD marker gene microarray screening revealed an upregulation of circ_0001666 in the colon tissues of CD patients, but its underlying mechanisms remain unclear. In this study, we explored the molecular mechanism of circ_0001666 in regulating EMT-mediated fibrosis in CD in vitro. The levels of circ_0001666 and EMT-associated proteins were assessed in CD clinical samples, and a CD cell model was established using TGF-β1 to induce human intestinal epithelial cells (HIECs). Additionally, the expression levels of genes and proteins related to EMT and fibrosis were analyzed by quantitative real-time PCR and western blot, cell migration, and invasion were assessed via wound healing assay and transwell, respectively, and RNA pull-down and RNA immunoprecipitation assays were performed to verify the relationship between SRSF1 and BMP7 or circ_0001666. Circ_0001666 was overexpressed in the intestinal mucosal tissues of CD patients and was positively correlated with EMT. Silencing circ_0001666 inhibited the migration, invasion, EMT, and fibrosis of HIECs induced by TGF-β1. Mechanistically, circ_0001666 regulated BMP7 expression by interacting with SRSF1. Furthermore, the effects of inhibiting circ_0001666 on HIECs could be partially reversed by overexpressing SRSF1 or silencing BMP7. Collectively, circ_0001666 regulates TGF-β1-induced HIEC migration, invasion, EMT, and fibrosis. Circ_0001666 also promoted EMT-mediated fibrosis by interacting with SRSF1 to accelerate BMP7 mRNA decay. These findings provide new insights into the pathogenesis of CD and suggest that circ_0001666 might be a potential therapeutic target for CD.

Heart failure (HF) is a disease with high mortality and morbidity rate. Autophagy is critically implicated in HF progression. The current research was designed to investigate the function of Dioscin on oxidative stress, autophagy, and apoptosis in HF. In this study, doxorubicin (Dox) was employed to induce HF model and HL-1 cell damage model. Echocardiography implied that Dioscin could dramatically relieve heart function in vivo. Western blotting determined that Dioscin treatment reversed the promotive effect of autophagy caused by Dox through modulating levels of key autophagy-associated molecules, including Atg5 and Beclin1. Dioscin also impaired apoptosis by regulating apoptosis-related protein, including Bcl-2 and cleaved caspase-3 following Dox treatment in vivo and in vitro. Furthermore, the impacts of Dioscin were mediated by upregulation of PDK1-mediated Akt/mTOR signaling. The mTOR inhibitor (rapamycin) could counteract the therapeutic impact of Dioscin in vitro. Taken together, Dioscin could relieve cardiac function through blocking apoptosis and autophagy by activating the PDK1-elicited Akt/mTOR pathway.

The blood-retinal barrier (BRB), homeostasis, neuronal integrity, and metabolic processes are all directly influenced by Müller cells, the most important retinal glial cells. We isolated primary Müller cells from Sprague-Dawley (SD) neonatal rats and treated them with glucose at varying doses. CCK-8 was used to quantify cellular viability, and a TUNEL assay was performed to detect cell apoptosis. ELISA, immunofluorescence, and western blotting were used to assess cAMP/PKA/CREB signaling, Kir4.1, AQP4, GFAP, and VEGF levels, respectively. H&E staining was used to examine histopathological alterations in diabetic retinopathy (DR)-affected retinal tissue in rats. As glucose concentration increases, gliosis of Müller cells became apparent, as evidenced by a decline in cell activity, an increase in apoptosis, downregulation of Kir4.1 level, and overexpression of GFAP, AQP4, and VEGF. Treatments with low, intermediate, and high glucose levels led to aberrant activation of cAMP/PKA/CREB signaling. Interestingly, blocking cAMP and PKA reduced high glucose-induced Müller cell damage and gliosis by a significant amount. Further in vivo results suggested that cAMP or PKA inhibition significantly improved edema, bleeding, and retinal disorders. Our findings showed that high glucose exacerbated Müller cell damage and gliosis via a mechanism involving cAMP/PKA/CREB signaling.

Cancer stem cells (CSCs), a rare subset of tumor cells, have been recognized as promotive role on tumor initiation and propagation. Among, aerobic glycolysis, widely clarified in multiple tumor cells, is the key for maintaining cancer stemness. Regrettably, it is largely unknown about the connection of cellular metabolic reprogramming and stemness in gastric carcinoma (GC). Two GC parental cells lines PAMC-82 and SNU-16 and their spheroids were obtained to determine the expression status of POU1F1 using quantitative real-time PCR (qRT-PCR) and western blotting analysis, respectively. Gain or loss-of-function assay was employed to assess its biological effects. Sphere formation and transwell assays were performed to evaluate the stem cell-like traits, including self-renewal capacity, migration and invasion. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were conducted for determining the binding relationship of POU1F1 on ENO1 promoter region. Herein, aberrantly upregulated POU1F1 was observed in spheroids, compared with the parental PAMC-82 and SNU-16 cells, which promoted stem cell-like traits, as representing increasing sphere formation, enhanced cell migration and invasion. Additionally, POU1F1 expression was positively with glycolytic signaling, as displaying increasing glucose consumption, lactic acid production, and extracellular acid ratio (ECAR). Furthermore, POU1F1 was identified to be a transcriptional activator of ENO1, of which overexpression remarkably abolished POU1F1 knockdown-mediated blocking effects. Taken together, we draw a conclusion that POU1F1 facilitated the stem cell-like properties of GC cells through transcriptionally augmenting ENO1 to enhance glycolysis.

Endobronchial ultrasound bronchoscopy (EBUS) and needle confocal laser endomicroscopy (nCLE) are techniques for screening benign and malignant lesions of the hilar and mediastinal lymph node (HMLN). This study investigated the diagnostic potential of EBUS, nCLE, and combined EBUS and nCLE in HMLN lesions. We recruited 107 patients with HMLN lesions who were examined by EBUS and nCLE. A pathological examination was performed, and the diagnostic potential of EBUS, nCLE, and combined EBUS-nCLE approach was analyzed according to the results. Among the 107 cases of HMLN lesions, 43 cases were benign and 64 cases were malignant on pathological examination, 41 cases were benign and 66 cases were malignant on EBUS examination; 42 cases were benign and 65 cases were malignant on nCLE examination; 43 cases were benign and 64 cases were malignant on combined EBUS-nCLE examination. The combination approach had 93.8% sensitivity, 90.7% specificity, and 0.922 area under the curve, which was higher than those of EBUS (84.4%, 72.1%, and 0.782, respectively) and nCLE diagnosis (90.6%, 83.7%, and 0.872, respectively). The combination approach had a higher positive predictive value (0.908), negative predictive value (0.881), and positive likelihood ratio (10.09) than that of EBUS (0.813, 0.721, and 3.03, respectively) and nCLE (0.892, 0.857, and 5.56, respectively), whereas, the negative likelihood ratio was lower than that for EBUS (0.22) and nCLE (0.11). No serious complications occurred in patients with HMLN lesions. To summarize, the diagnostic efficacy of nCLE was better than EBUS. The EBUS-nCLE combination is a suitable approach for diagnosing HMLN lesions.

Colorectal cancer (CRC) is a prevalent malignant tumor of the digestive tract. Circular RNAs may play important roles in the progression of CRC. In this study, we investigated the roles and mechanisms of action of circ-MALAT1 in CRC. Gene expression and protein abundance were determined using qRT-PCR and western blot, respectively. Cell proliferation and migration were assessed by MTT, clone formation, and wound-healing assays. The interactions among the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (circ-MALAT1), miR-506-3p, and lysine acetyltransferase 6B (KAT6B) were predicted using the StarBase software and confirmed by the luciferase activity assay. Circ-MALAT1 and KAT6B were upregulated, while miR-506-3p was downregulated in CRC cells. We validated that knocking down of circ-MALAT1 suppressed proliferation, migration, and epithelial-mesenchymal transition (EMT) of CRC cells, and these effects were abolished by miR-506-3p downregulation or KAT6B sufficiency. Our study suggests that circ-MALAT1 could sponge miR-506-3p to regulate the expression of KAT6B. Moreover, KAT6B sufficiency could neutralize miR-506-3p-dependent growth arrest, migration, and EMT. Circ-MALAT1 promotes cell proliferation, migration, and EMT of CRC cells via the miR-506-3p/KAT6B axis, thereby acting as a novel potential therapeutic target for the treatment of colorectal cancer.

The incidence of early-onset colorectal cancer (CRC), which affects people under 50, is increasing for unknown reasons. Additionally, no underlying genetic cause is found in 20%-30% of patients suspected of having familial CRC syndrome. Whole exome sequencing (WES) has generated evidence for new genes associated with CRC susceptibility, but many patients remain undiagnosed. This study applied WES in five early-onset CRC patients from three unrelated families to identify novel genetic variants that could be linked to rapid disease development. Furthermore, the candidate variants were validated using Sanger sequencing. Two heterozygote variations, c.1077-2A>G and c.199G>A, were found in the MSH2 and the MLH1 genes, respectively. Sanger sequencing analysis confirmed that these (likely) pathogenic mutations segregated in all the affected families' members. In addition, we identified a rare heterozygote variant (c.175C>T) with suspected pathogenic potential in the MAP3K1 gene; formally the variant is of uncertain significance (VUS). Our findings support the hypothesis that CRC onset may be oligogenic and molecularly heterogeneous. Larger and more robust studies are needed to understand the genetic basis of early-onset CRC development, combined with novel functional analyses and omics approaches.

Sepsis-associated acute lung injury (ALI) is a life-threatening condition in intensive care units with high mortality. LncRNAs have been confirmed to participate in the underlying pathogenesis of septic ALI. This study investigated the biological functions of lncRNA CDKN2B-AS1 in septic ALI and its potential mechanism.BEAS-2B cells were challenged with lipopolysaccharide (LPS) and mice were subjected to caecal ligation and puncture (CLP) to induce septic ALI in vitro and in vivo. The expression levels of CDKN2B-AS1, LIN28B, HIF-1α, and pyroptosis-related molecules were assessed by qRT-PCR or Western blotting. The production of IL-1β and IL-18 was detected by ELISA. BEAS-2B cell pyroptosis was examined by flow cytometry. The interaction between LIN28B and CDKN2B-AS1/HIF-1α was validated by RIP and RNA pull-down assays. Colocalization of CDKN2B-AS1 and LIN28B was observed by FISH. ALI was determined by HE staining, the lung wet-to-dry (W/D) weight ratio, inflammatory cell numbers, and total protein concentration in bronchoalveolar lavage fluid (BALF). Caspase-1 expression in the lung tissues was examined by immunohistochemical staining.CDKN2B-AS1 was upregulated in BEAS-2B cells after LPS stimulation. CDKN2B-AS1 knockdown inhibited pyroptosis in LPS-exposed BEAS-2B cells in vitro and the lung tissues of septic mice in vivo. Mechanistically, CDKN2B-AS1 interacted with LIN28B to enhance HIF-1α stability. Rescue experiments showed that HIF-1α overexpression counteracted the inhibitory effect of sh-CDKN2B-AS1 on LPS-induced pyroptosis. CDKN2B-AS1 bound to LIN28B to trigger NLRP3-mediated pyroptosis by stabilizing HIF-1α, which promoted sepsis-induced ALI. CDKN2B-AS1 might be a novel therapeutic target for this disease.