Evidence suggests that the degree of insulin resistance in pregnancy (IRiP) seems to affect pregnancy outcomes regardless of the presence of gestational diabetes. A physiological moderate increase in IRiP is a protective factor for fetal development, but excessive enhancement can lead to maternal metabolic disorders and placental dysfunction, increasing the risk of gestational diabetes and adverse pregnancy outcomes, as well as having adverse effects on the long-term health of the offspring. This review briefly explores the key factors influencing IRiP, including pregnancy-specific and non-pregnancy-specific factors. It also discusses the assessment methods for insulin resistance that can be implemented during pregnancy and the increased probabilities of adverse effects on both the mother and the offspring, such as preeclampsia or eclampsia, neonatal hypoglycemia, and the risk of obesity and metabolic diseases in the offspring in the future. Finally, the intervention strategies were briefly described, such as in terms of diet, exercise, and medication, etc. This provides a basis and insights for the management and research of IRiP.
Background: Human cytomegalovirus (CMV) infection is frequently detected in patients with ulcerative colitis (UC), particularly in severe or refractory disease. Its impact on disease activity, long-term course, and clinical outcomes remains controversial. Methods: In this retrospective single-center cohort study conducted at the University Hospital M & uuml;nster (Germany), adult UC patients undergoing colonoscopy between May 2002 and May 2024 were included. CMV status was determined by tissue-based PCR from colonic biopsies at baseline colonoscopy (BL). Patients with at least one follow-up colonoscopy (FU) were analyzed. Clinical and endoscopic disease activity (total Mayo score [tMayo], endoscopic Mayo score [eMayo]), remission rates, treatment exposure, and outcomes were compared between patients with CMV-positive and CMV-negative biopsies at BL and FU. Results: A total of 181 UC patients were included (63 CMV-positive, 118 CMV-negative biopsies). At BL, CMV-positive patients had significantly higher endoscopic disease activity (eMayo, p = .03) and numerically higher clinical activity. At FU (median interval 34 vs. 45 months), both groups showed improvement; however, CMV-positive patients continued to exhibit significantly higher disease activity (tMayo p = .001; eMayo p < .001). Rates of clinical/endoscopic remission were significantly lower in CMV-positive patients at both BL and FU. No significant association was observed between CMV status of biopsies and colectomy rates (p = .21). Antiviral therapy was administered in 60% of CMV-positive patients and was associated with higher baseline disease activity but not with differences at FU. Conclusions: Molecular detection of CMV in the intestinal mucosa is associated with increased mucosal inflammation and a less favorable long-term disease course in UC, but has no effect on hard outcome parameters such as colectomy. Antiviral therapy has no effect on clinical outcome parameters. These findings indicate that further studies are needed to clarify the pathophysiological influences of CMV infection on disease course in ulcerative colitis and its impact on the efficacy of advanced therapies.
Background: Gastroesophageal reflux disease (GERD) is a common gastrointestinal condition associated with significantly impaired quality of life. While tea consumption has been associated with various health benefits, its relationship with GERD remains controversial. The aim of this study was to evaluate the relationship between the prevalence of GERD and tea consumption, including the type, drinking frequency and daily intake of tea, in a large Taiwanese cohort. Methods: The type of tea was categorized as fully fermented, semi-fermented, and non-fermented; frequency and daily intake were recorded. Standardized self-reported questionnaires were used to record GERD status. Multivariable logistic regression was used to examine the association between tea consumption and GERD. Results: Of the 27,119 participants, 4706 (17.4%) had GERD and 22,413 did not. A significant association was found between habitual tea consumption and a low prevalence of GERD (odds ratio [OR], 0.843; 95% confidence interval [CI], 0.779-0.911; p < 0.001) compared to non-drinkers. However, this association was only identified for semi-and non-fermented teas (OR, 0.832; 95% CI, 0.765-0.905; p < 0.001), but not fully fermented tea. Daily consumption of 1-2 cups (350-700 mL) (OR, 0.881 and 0.765, respectively) was significantly associated with a low prevalence of GERD, however drinking more than 3 cups per day was not significantly associated with GERD prevalence. Furthermore, drinking tea every day (OR, 0.847) was significantly associated with a low prevalence of GERD, while only drinking tea weekly or monthly was not. Conclusion: The consumption of semi-fermented and non-fermented tea was associated with a low prevalence of GERD, but the association depended on the frequency and quantity of consumption. Further studies are needed to investigate the biological mechanisms of different types of tea and establish interventional strategies for those at high risk of GERD.
Background: Mitochondrial dysfunction is a hallmark of acute and chronic kidney diseases. This study investigates the expression landscape and potential association of FNDC5 with renal injury. Methods: We integrated human scRNA-seq, mouse spatial transcriptomics (ischemia-reperfusion injury model), in vitro high-glucose (HG) models in proximal tubule cells and podocytes, and a constitutive Fndc5 knockout mouse model. Candidate transcription factor occupancy at the FNDC5 promoter was examined by ChIP-qPCR, and associations were assessed in a non-insulin-dependent diabetes mellitus mouse model. Results: scRNA-seq localized FNDC5 to specific tubules, showing downregulation in diabetic nephropathy. Spatial transcriptomics confirmed a distinct loss of cortical Fndc5 following ischemia-reperfusion injury. In vitro, HG treatment suppressed FNDC5, reduced cell viability, and triggered mitochondrial fragmentation, evidenced by increased DRP1 phosphorylation and downregulated MFN1/OPA1. ZEB1 and CREB1 were identified as candidate transcription factors showing occupancy at the FNDC5 promoter. Genetic deletion of Fndc5 reproduced this fission-permissive shift and reduced PGC1 alpha expression under basal, non-diabetic conditions, providing loss-of-function evidence that Fndc5 deficiency is sufficient to reproduce this phenotype, independent of any additional metabolic stressor. In vivo, diabetic mice exhibited diminished FNDC5 levels, which correlated with an oxidative stress-associated marker (4-HNE) and reduced expression of the biogenesis-associated marker PGC1 alpha. Conclusion: FNDC5 downregulation is a conserved feature of renal injury associated with mitochondrial fission, and genetic loss-of-function data indicates that Fndc5 deficiency is sufficient to reproduce selected features of this fission-permissive mitochondrial phenotype; whether FNDC5 acts through a defined downstream pathway remains to be established.
In this study, we designed a novel 'metformin-coated nanoselenium nanocomposite' (Met+SeNP) to leverage the synergistic potential of both agents delivered via a single nanoplatform, aiming to restore metabolic and hormonal homeostasis in a letrozole-induced PCOS rat model. Met+SeNP was synthesized via a redox reaction of sodium selenite and ascorbic acid in the presence of metformin, creating a stable metformin-functionalized selenium nanocomposite. The particles were characterized using UV-Vis spectroscopy, SEM, and EDX. Female Sprague-Dawley rats were divided into five groups: Healthy, PCOS (letrozole-induced), Metformin (300 mg/kg), SeNP (0.4 mg/kg), and Met+SeNP (nanocomposite dose, SeNP 0.4 mg/kg + Metformin 300 mg/kg). The nanocomposite treatment most effectively minimized weight gain (39.36% vs. PCOS controls), normalized HOMA-IR, and restored circulating LH, estrogen, and testosterone levels. Histopathological evaluation demonstrated a marked reduction in cystic follicles and recovery of corpus luteum formation following Met+SeNP therapy. suppression of INR, IRS-1, and IRS-2 expression in both liver and skeletal muscle tissues. In addition, the nanocomposite significantly improved serum ALT, AST, and ALP levels while maintaining normal urea and creatinine concentrations, supporting hepatic protection and systemic safety. The metforminfunctionalized SeNP nanocomposite represents a promising potent therapeutic strategy for PCOSassociated metabolic dysfunction, outperforming monotherapies in restoring insulin signaling, endocrine balance, and tissue integrity.
