TAZ reverses the inhibitory effects of LPS on the osteogenic differentiation of human periodontal ligament stem cells through the NF-κB signaling pathway.

BACKGROUND: Human periodontal ligament stem cells (hPDLSCs) are important candidate seed cells for periodontal tissue engineering, but the presence of lipopolysaccharide(LPS) in periodontal tissues inhibits the self-renewal and osteogenic differentiation of hPDLSCs. Our previous studies demonstrated that TAZ is a positive regulator of osteogenic differentiation of hPDLSCs, but whether TAZ can protect hPDLSCs from LPS is still unknown. The present study aimed to explore the regulatory effect of TAZ on the osteogenic differentiation of hPDLSCs in an LPS-induced inflammatory model, and to preliminarily reveal the molecular mechanisms related to the NF-κB signaling pathway. METHODS: LPS was added to the culture medium of hPDLSCs. The influence of LPS on hPDLSC proliferation was analyzed by CCK-8 assays. The effects of LPS on hPDLSC osteogenic differentiation were detected by Alizarin Red staining, ALP staining, Western Blot and qRT-PCR analysis of osteogenesis-related genes. The effects of LPS on the osteogenic differentiation of hPDLSCs with TAZ overexpressed or knocked down via lentivirus were analyzed. NF-κB signaling in hPDLSCs was analyzed by Western Blot and immunofluorescence. RESULTS: LPS inhibited the osteogenic differentiation of hPDLSCs, inhibited TAZ expression, and activated the NF-κB signaling pathway. Overexpressing TAZ in hPDLSCs partly reversed the negative effects of LPS on osteogenic differentiation and inhibited the activation of the NF-κB pathway by LPS. TAZ knockdown enhanced the inhibitory effects of LPS on osteogenesis. CONCLUSION: Overexpressing TAZ could partly reverse the inhibitory effects of LPS on the osteogenic differentiation of hPDLSCs, possibly through inhibiting the NF-κB signaling pathway. TAZ is a potential target for improving hPDLSC-based periodontal tissue regeneration in inflammatory environments.

Cuproptosis-related genes score and its hub gene GCSH: A novel predictor for cholangiocarcinomas prognosis based on RNA seq and experimental analyses.

Background: Recent researches have demonstrated that cuproptosis, a copper-dependent cell death mechanism, is related to tumorigenesis, progression, clinical prognosis, tumor microenvironment, and drug sensitivity. Nevertheless, the function and impact of cuproptosis in cholangiocarcinoma (CCA), remain elusive. Methods: Utilizing data obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA-CHOL) datasets, we conducted subgroup typing of CCA according to cuproptosis-related genes (CRGs) and explored functional differences and prognostic value between groups. A CRG score was established considering clinical prognosis and gene expression. Furthermore, differences in the immune microenvironment, response to immunotherapy, metabolic patterns, and cancer progression characteristics between high- and low-risk groups were examined on the basis of these scores. In vitro experiments validated the function of the key gene glycine cleavage system protein H (GCSH) in cellular and tissues, respectively. Results: Prognostic models established on the basis of subgroup genetic differences achieved satisfactory results in validation. Metabolic-related gene expression levels and tumor microenvironment distribution were significantly different between the high and low CRG groups. GCSH was revealed as the singular prognostic CRG in CCA (HR =6.04; 95% CI: 1.15-31.80). Moreover, inhibition of the cupcoptosis key gene GCSH attenuated the malignant ability of CCA cell lines in vitro, including cell proliferation, migration and invasion, and this function of GCSH may be achieved via JAK-STAT signaling in CCA. Conclusion: The CRG scoring system accurately predicts prognosis and opens up new possibilities for cuproptosis-related therapy for CCA. The cuproptosis key gene GCSH has been preliminarily confirmed as a reliable therapeutic target or prognostic marker for CCA patients.

Management of a uterine serosal heterotopic pregnancy after in vitro fertilization in a woman with bilateral salpingectomy: A case report and literature review.

RATIONALE: Heterotopic pregnancy (HP) is defined as the simultaneous presence of intrauterine pregnancy and ectopic pregnancy (EP). HP after bilateral salpingectomy is extremely rare and may lead to serious complications if it is misdiagnosed and untreated timely. Here, we presented the first reported case of uterine serosal HP in a woman after assisted reproductive technology with bilateral salpingectomy because of bilateral tubal ectopic pregnancy. PATIENT CONCERNS: A 27-years-old pregnant woman after in vitro fertilization with bilateral salpingectomy complained of a sudden onset of unprovoked abdominal pain, which was persistent and dull. She denied vaginal bleeding. DIAGNOSES: Serum beta-human chorionic gonadotropin levels are difficult to predict HP. Transvaginal ultrasonography demonstrated 1 gestational sac in the uterine cavity and 1 thick-walled cystic mass over the upper of the uterus, with a large amount of fluid in the Pouch of Douglas. Emergency laparotomy revealed a uterine serosal pregnancy combined with intrauterine pregnancy. INTERVENTIONS: This patient was successfully managed via emergency laparotomy to remove residual tissue and repair the rupture of the uterine serosal pregnancy. OUTCOMES: At postoperative 4 days, repeat transvaginal ultrosonography presented 1 intrauterine gestational sac with a visible fetal bud and cardiac tube pulsation. Now the patient recover well and is in an ongoing pregnancy. LESSONS: It is noteworthy that HP/ectopic pregnancy is still not prevented after bilateral salpingectomy. In cases of multiple embryo transfer, even if intrauterine pregnancy has been established, it is important to rule out HP/ectopic pregnancy in time. Early diagnosis and early management can significantly improve clinical outcomes.