Serum leptin (LEP) is elevated in polycystic ovary syndrome (PCOS) patients, especially in obese PCOS patients, which may link to the etiology and development of PCOS. Obesity adversely affects female fertility, and most PCOS patients are obese. Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, regulates adipokine production, causes weight loss, and regulates ovarian physiology to improve or manage reproductive status, thus ameliorating obesity and PCOS. This study investigated the impact of liraglutide on LEP promoter methylation levels in ovarian granulosa cells of obese PCOS patients to seek possible potential targets for the clinical treatment. This prospective observational study enrolled 348 PCOS patients with strong fertility desire in our hospital during March 2020-January 2022 who were planned to undergo in vitro fertilization and embryo transfer. Based on the inclusion and exclusion criteria, 207 eligible patients (72 non-obese and 135 obese PCOS patients, 23-37 year-old) were enrolled. Obese PCOS patients [body mass index (BMI) ≥ 25 kg/m²] received liraglutide treatment. Obese PCOS patients exhibited elevated BMI, fasting insulin, fasting blood glucose, HOMA-IR, triglyceride, estradiol, and testosterone levels and reduced high-density lipoprotein cholesterol, luteinizing hormone (LH), LH/follicle-stimulating hormone ratio, and LEP promoter methylation. Liraglutide increases LEP promoter methylation, decreases LEP levels, and affects sex hormone secretion, providing a reference for the investigation of the mechanism of liraglutide in obese PCOS patients. Additionally, weight and fat loss, decreased serum and follicular fluid LEP levels, and increased LEP promoter methylation levels in ovarian granulosa cells may be crucial strategies for treating obese PCOS patients.

The current study focused on the molecular mechanisms behind high glucose (HG)-induced ferroptosis in HK-2 cells. HG-induced epithelial-to-mesenchymal transition (EMT) HK-2 cell model displayed elevated Vimentin, α-SMA, Fe²⁺ and MDA expression, suppressed cell viability and proliferation capabilities, decreased E-cadherin, GPX4 and GSH levels, and increased cell death. Additionally, knockdown of Vimentin or α-SMA caused the opposite outcomes. Restaint of ferroptosis partially reversed the promotion role of knockdown of Vimentin or α-SMA in HK-2 cell proliferation. Further inhibition of the Hippo/YAP pathway could partly regulate the effects of Vimentin or α-SMA on HG-induced ferroptosis and proliferation in HK-2 cells. Conclusively, HG could increase the expression levels of Vimentin and α-SMA in HK-2 cells, and induce EMT, thereby inhibiting the activation of the Hippo/YAP signaling axis and cell proliferation, and promoting cell ferroptosis of HK-2 cells.

Long non-coding RNAs are major regulators in the pathophysiology of osteoarthritis (OA), which involves the dysfunction of cartilage and synovium. The aim of this study was, therefore, to discover the role of RASSF8-AS1 in cartilage degradation and M1 macrophage polarization during OA. Healthy and OA cartilage and synovium were collected. After measuring RASSF8-AS1 levels in tissues and lipopolysaccharide (LPS)- or IL-1β-induced cells, the role of RASSF8-AS1 in the expression of cartilage degradation markers and M1 macrophage molecules was assessed in vitro. The apoptotic rate of IL-1β-stimulated chondrocytes, with or without RASSF8-AS1 overexpression, was quantified using flow cytometry. RASSF8-AS1 was significantly upregulated not only in cartilage and synovium from OA patients, but also in IL-1β- or LPS-induced cells, compared to normal controls. A decrease in RASSF8-AS1 level increased the expression of chondrogenic markers, but reduced the expression of genes encoding matrix-degrading proteases, thereby reducing cell apoptosis. Downregulation of RASSF8-AS1 reduced the M1 macrophage markers in RAW264.7 cells and bone marrow-derived macrophages. RASSF8-AS1 may be a ceRNA for miR-27a-3p. These findings support the role of RASSF8-AS1 as a promoting factor of cartilage degradation and M1 macrophage polarization in OA.

This study was to examine the association between the long noncoding RNA (lncRNA) HOTAIR polymorphism (rs4759314, rs4759314) and the risk of recurrent spontaneous abortion (RSA) in Chinese Han women. 378 women with RSA and 361 pregnant women with normal pregnancies were selected as study subjects. The expression level of lncRNA HOTAIR was detected by fluorescence quantitative PCR. PCR restriction fragment length polymorphism (PCR-RFLP) method was used to detect genotyping. Logistic regression analysis was used to assess the independent factors of HOTAIR rs4759314 affecting recurrent miscarriage. The lncRNA HOTAIR gene expression level was significantly reduced in RSA patients. Rs1899663 polymorphism and rs4759314 GG genotype do not significantly increase the risk of developing RSA (P > 0.050). Rs4759314 AG genotype and rs4759314G allele significantly increased the risk of developing RSA (P < 0.050). Logistic analysis showed a significant correlation between rs4759314 and the occurrence of RSA (OR = 0.367, 95% CI = 0.232-0.580, P < 0.050). The lncRNA HOTAIR rs4759314 locus may serve as a biomarker for RSA susceptibility in the Chinese Han population.

Featured with frequent recurrence and distant metastasis, the mortality of breast cancer (BC) increased year by year in recent decades. MINDY lysine 48 deubiquitinase 1 (MINDY1) played an oncogenic role in several tumors. The role of MINDY1 deserved further study in BC. A wide ranges of assays including qRT-PCR, Western blotting, CCK-8 flow cytometry analysis, co-immunoprecipitation assay, Pearson’s coefficient tests, and tumor xenograft assay were designed and carried out to determine the role of MINDY1 in BC. Both MINDY1 and programmed death-ligand 1 (PD-L1) is upregulated in BC tissues and cells. In addition, knockdown of MINDY1 attenuated cell viability and promoted the activation of T cells. Mechanistically, MINDY1 stabilized PD-L1 protein by interacting with PD-L1 in BC cells, and MINDY1 is positively associated with PD-L1 in BC tissues. Moreover, rescue assay revealed that the effect of MINDY1 silencing on cell viability and T cell activation was reversed by PD-L1 overexpression. The in vivo study also demonstrated that the effect of MINDY1 knockdown on tumor growth induced by was counteracted by PD-L1 overexpression.In conclusion, we identified PD-L1 as a novel target of MINDY1 and established a significant association between MINDY1 and the cancer immune response. Importantly, our findings reveal that MINDY1 promoted BC progression via PD-L1-mediated immune evasion.

Claudin-18.2 is considered a promising target in cancer treatment. However, studies on the role of Claudin-18.2 in pancreatic cancer are scarce, and a systematic exploration of its mechanisms of action in disease progression is missing. This research sought to reveal the detailed mechanisms by Claudin-18.2 impacts pancreatic cancer development and metastasis. Claudin-18.2 expression levels in pancreatic cancer were investigated through The Cancer Genome Atlas (TCGA) database, with subsequent validation by immunohistochemistry and quantitative reverse transcription polymerase chain reaction analysis. The potential regulatory transcription factors (TFs) for Claudin-18 were forecasted by the KnockTF database. Pearson’s correlation was applied to ascertain the correlation between Claudin-18 and ZIC2, and the Molotool was utilized to analyze their potential binding sites. The TCGA database facilitated our analysis of ZIC2 expression levels within pancreatic cancer. Activation of the ERK signaling pathway was validated by western blot (WB). The colony formation assay evaluated cell proliferation, while the cell scratch and Transwell assays were used to determine cell migration and invasion abilities. WB was used to detect the expression of E-cadherin, N-cadherin and Vimentin associated with epithelial-mesenchymal transition. The ZIC2-Claudin-18.2 regulatory axis, via ERK1/2 signaling pathway activation, enhanced the malignant behaviors of pancreatic cancer. Claudin-18.2, when highly expressed in pancreatic cancer, facilitated tumor malignancy, primarily through activating the ERK1/2 signaling pathway. Additionally, ZIC2 was identified as an upstream regulatory molecule for Claudin-18.2. Our findings reveal that ZIC2, a TF, can upregulate Claudin-18.2, and initiate the ERK1/2 signaling pathway, eventually facilitating the malignant progression of pancreatic cancer.

Epidural labor analgesia is a widely employed method of analgesia in current clinical practice. This study aimed to investigate the relationship between NTRK1 gene polymorphism and epidural labor analgesia, offering a novel perspective for labor analgesia related research. Epidural labor analgesia was administered with hydromorphone in 208 eligible pregnant women. Genomic DNA was extracted from EDTA anticoagulant blood samples. The NTRK1 single nucleotide polymorphisms (SNPs) rs1800880 (T > C) and rs6334 (G > A) were genotyped utilizing PCR-RFLP. Parameters such as the 24 h visual analogue score (VAS), modified Bromage score, 48 h patient controlled intravenous analgesia (PCIA) compression counts, dosage of anesthetic, adverse reactions were meticulously recorded. The immune functions were assessed by flow cytometry, and oxidative stress levels were measured by radioimmunoassay. The findings indicated that NTRK1 rs1800880 T > C and rs6334 G > A were similar, 24 h VAS score and anesthetic dosage were decreased. rs1800880 C allele was no significant difference in adverse reactions, but the level of oxidative stress was significantly reduced. The nausea and emesis response of rs6334 mutant AA was significantly reduced. Both rs1800880 TC + CC vs. TT and rs6334 GA + AA vs. GG showed significant effects on 24 h VAS score. Mutations in rs1800880 and rs6334 reduce postoperative pain, adverse reactions, and oxidative stress responses. The NTRK1 SNP may play an important role in labor analgesia and may be an effective predictor of individual pain perception, thereby providing patients with a more personalized approach to labor analgesia.

Insufficient sleep is common among adolescents in the Republic of Korea because of competitive academic environments. Many students compensate for lack of sleep through weekend catch-up sleep (CUS), however the degree of effectiveness is unclear. This study aimed to determine the association between weekend CUS and perceived stress in a large, school-based Korean adolescent sample. Data from the Korean Youth Risk Behavior Web-based Survey 2020 (KYRBWS) was used. The participants included 46,187 middle and high school students in the Republic of Korea who participated in self-administered questionnaire surveys. Weekend CUS was divided into four categories: 0 h, 0-1 h, 1-2 h, and ≥ 2 h. Odds ratios (ORs) with 95% confidence intervals (CIs) were derived using logistic regression analyses. We found that the risk of perceived stress decreased significantly in weekend CUS groups (0 < CUS < 1 [OR]: 0.879, [95% CI: 0.808-0.957]; 1 ≤ CUS < 2 [OR]: 0.852, [95% CI: 0.785-0.924]; 2 ≥ CUS [OR]: 0.836, [95% CI: 0.775-0.902]) compared to the non-CUS group after adjusting for several confounding variables. Furthermore, the higher CUS group tended to have a lower risk of perceived stress. However, in the Grade 12 participants, in both the unadjusted and adjusted models, the weekend CUS groups did not show a significant association with the risk of perceived stress. Our study showed that weekend CUS is associated with a low risk of perceived stress among Korean adolescents.

We herein report a case of abscess formation from the subcutaneous area of the face to the submucosa of the nasal cavity. To our knowledge, this case was unprecedented, but we were able to cure the patient by applying endoscopic sinus surgery techniques. A 13-year-old boy visited a local clinic because of right facial swelling. Contrast-enhanced computed tomography (CT) showed abscess formation from the subcutaneous region of the face to the submucosa of the nasal cavity, and endoscopic surgery was performed. In surgery, endoscopic modified medial maxillectomy (EMMM) and a direct approach to the anterior and lateral parts of the maxillary sinus with an endoscope (DALMA) were applied to perform radical drainage. The patient was discharged from the hospital on postoperative day 7 after completion of antimicrobial therapy because of good progress. Two months postoperatively, healing of the incision and maintenance of openness of the maxillary sinus were confirmed, and the follow-up was terminated. Endoscopic surgery is the first-choice treatment because of its superior therapeutic efficacy and functional preservation.

The importance of the microenvironment in cancer progression is widely recognized, and interactions between cancer cells and stromal cells play an important role in the progression of the disease. A major component of stromal cells are fibroblasts, known as cancer-associated fibroblasts (CAFs). CAFs are thought to enhance the malignant properties of cancer cells through various secreted proteins. It is also known that CAFs function as a leading cell in cancer invasion, and their migratory ability is involved in local cancer invasion. The aim of this study was to elucidate the function of CAF in gallbladder cancer, which is one of the gastrointestinal malignancies with the worst prognosis.

CAFs were primarily cultured from surgical specimens of gallbladder cancer patients. We investigated the migration ability of established CAFs and the effects of conditioned medium obtained from CAFs on the growth and invasion ability of gallbladder cancer cell lines. Functional analysis showed that the migration ability of certain CAFs was enhanced compared to control, and that conditioned medium enhanced the migration and invasion of gallbladder cancer cell lines. Gene expression analysis of CAFs revealed that tenascin-C (TNC) and podoplanin (PDPN) were highly expressed in CAFs with the enhancing functions. Immunohistochemical staining of TNC and PDPN on surgical specimens was performed to investigate the relationship with the prognosis. Disease-free survival and overall survival were found to be reduced in patients with high expression of those genes. The results of this study indicate that CAFs expressing TNC and PDPN promote cancer progression in gallbladder cancer.

The number of temporary custody cases due to child maltreatment and other reasons at child guidance centers in Japan is increasing, prompting imperative scrutiny of re-entry risk assessment. We aimed to derive and internally validate a risk prediction model for re-entry into temporary custody. The risk prediction model was developed from an analysis of data from 725 children recruited in this retrospective single-center longitudinal cohort study conducted in Japan. The anticipated outcome was re-entry into temporary custody. Predictor variables were selected from 15 prospective variables concerning information on children and their familial contexts. A risk prediction model was developed using stepwise logistic regression. The final risk model was validated via C-statistic using cross-validation and bootstrap resampling methods. Calibration was assessed using the Hosmer-Lemeshow test. Of 725 children under temporary custody, 178 (24.6%) experienced re-entry into temporary custody. The predictors in the conclusive risk model were a history of temporary custody (p < 0.001), age at first birth of < 25 years (p < 0.002), single mother or stepfamily (p < 0.001), reasons for temporary custody including child abuse (p = 0.076) and child sex (p = 0.152), and child disability certificate (p = 0.252). Calibration scrutiny via the Hosmer-Lemeshow test revealed no discernible irregularities (p = 0.320). The naïve C-statistic of the model was 0.70, whereas the optimism-corrected C-statistics was 0.67-0.69. The presented risk prediction model showed acceptable calibration and discriminatory capability. The model can optimize limited human resources by providing valid risk estimates of the likelihood of re-entry to temporary custody within one year.