Genetic and inflammatory factors underlying gestational diabetes mellitus: a review.

Gestational diabetes mellitus (GDM) poses a significant global health concern, impacting both maternal and fetal well-being. Early detection and treatment are imperative to mitigate adverse outcomes during pregnancy. This review delves into the pivotal role of insulin function and the influence of genetic variants, including SLC30A8, CDKAL1, TCF7L2, IRS1, and GCK, in GDM development. These genetic variations affect beta-cell function and insulin activity in crucial tissues, such as muscle, disrupting glucose regulation during pregnancy. We propose a hypothesis that this variation may disrupt zinc transport, consequently impairing insulin production and secretion, thereby contributing to GDM onset. Furthermore, we discussed the involvement of inflammatory pathways, such as TNF-alpha and IL-6, in predisposing individuals to GDM. Genetic modulation of these pathways may exacerbate glucose metabolism dysregulation observed in GDM patients. We also discussed how GDM affects cardiovascular disease (CVD) through a direct correlation between pregnancy and cardiometabolic function, increasing atherosclerosis, decreased vascular function, dyslipidemia, and hypertension in women with GDM history. However, further research is imperative to unravel the intricate interplay between inflammatory pathways, genetics, and GDM. This understanding is pivotal for devising targeted gene therapies and pharmacological interventions to rectify genetic variations in SLC30A8, CDKAL1, TCF7L2, IRS1, GCK, and other pertinent genes. Ultimately, this review offers insights into the pathophysiological mechanisms of GDM, providing a foundation for developing strategies to mitigate its impact.

Association between GLO1 variants and gestational diabetes mellitus susceptibility in a Chinese population: a preliminary study.

Background: Glyoxalase 1 (GLO1) plays a crucial role in defending against glycation. Single nucleotide polymorphism (SNP) variants in the GLO1 gene may affect gene expression and alter enzyme activity. However, there have been limited studies evaluating the association between GLO1 and diabetes, especially gestational diabetes mellitus (GDM). Therefore, this study is the first to explore the association of GLO1 SNPs and GDM risk. Methods: The study included a total of 500 GDM patients and 502 control subjects. The SNPscan™ genotyping assay was used to genotype rs1781735, rs4746 and rs1130534. To assess the disparities in genotype, allele, and haplotype distributions and their correlation with GDM risk, the independent sample t-test, logistic regression, and chi-square test were employed during the data processing phase. Furthermore, one-way ANOVA was conducted to determine the differences in genotype and blood glucose and methylglyoxal(MG) levels. Results: Significant differences were observed in prepregnancy body mass index (pre-BMI), age, systolic blood pressure (SBP), diastolic blood pressure (DBP), and parity between GDM and healthy subjects (P < 0.05). After adjusting for these factors, GLO1 rs1130534 TA remained associated with an increased risk of GDM (TA vs. TT + AA: OR = 1.320; 95% CI: 1.008-1.728; P = 0.044), especially in the pre-BMI ≥ 24 subgroup (TA vs. TT + AA: OR = 2.424; 95% CI: 1.048-5.607; P = 0.039), with fasting glucose levels being significantly elevated in the TA genotype compared to the TT genotype (P < 0.05). Conversely, the GLO1 rs4746 TG was associated with a decreased risk of GDM (TG vs. TT: OR = 0.740; 95% CI: 0.548-0.999; P = 0.049; TG vs. TT + GG: OR = 0.740; 95% CI: 0.548-0.998; P = 0.048). Additionally, the haplotype T-G-T of rs1781735, rs4746 and rs1130534 was associated with a decreased risk of GDM among individuals with a pre-BMI ≥ 24 (OR = 0.423; 95% CI: 0.188-0.955; P = 0.038). Furthermore, the rs1781735 GG genotype was found to be more closely related to maternal MG accumulation and neonatal weight gain (P < 0.05). Conclusion: Our findings suggested that GLO1 rs1130534 was associated with an increased susceptibility to GDM and higher blood glucose levels, but GLO1 rs4746 was associated with a decreased risk of GDM. The rs1781735 has been associated with the accumulation of maternal MG and subsequent weight gain in neonates.

Positive Correlation Between LTA Expression and Overall Immune Activity Suggests an Increased Probability of Survival in Uterine Corpus Endometrial Carcinoma.

Mounting evidence indicates that immune status plays a crucial role in tumor progress and metastasis, while there are no effective and easily assayed biomarkers to reflect it in uterine corpus endometrial carcinoma (UCEC) patients. Here, we attempted to identify the potential biomarkers that were differentially expressed between normal and tumor tissues and involved in prognosis and immune microenvironment of UCEC patients. RNA-seq data with relevant clinical information were obtained from The Cancer Genome Atlas (TCGA). ssGSEA algorithm was applied to calculate the enrichment scores of every tumor infiltration lymphocyte (TIL) set in each sample, and patients were then divided into three clusters using multiple R packages. Cox analysis, ESTIMATE, and CIBERSORT were utilized to determine the differentially expressed immune-related genes (DEIGs) with overall survival, and to explore their roles in prognosis, immune microenvironment, and immunotherapeutic response. The TIMER and TISIDB databases were utilized to predict the effectiveness of immunotherapy in UCEC patients. LTA was finally identified to be significantly upregulated in tumor tissues and closely associated with prognosis and immunological status, which was then verified in GSE17025. In multivariate analysis, the hazard ratio of LTA was 0.42 with 95% CI (0.22-0.80) (p = 0.008). Patients with high LTA expression had better survival and apparently immune-activated phenotypes, such as more tumor mutation burden (TMB), stronger immune cell infiltrations, higher expression of immunosuppressive points, and higher immunophenoscore, meaning they had an immunotherapeutic advantage over those with low LTA expression. TIMER and TISIDB indicated that LTA was highly expressed in UCEC, and its expression was negatively correlated with stages and positively related to prognosis. Additionally, we found that LTA ectopic expression weakened the proliferation ability of RL95-2 cells. All these findings indicated that LTA could act as a novel and easily assayed biomarker to predict immunological status and clinical outcomes and even as an antioncogene to explore UCEC in depth.

Synthesis and gas sensing properties of α-Fe(2)O(3)@ZnO core-shell nanospindles.

α-Fe(2)O(3)@ZnO core-shell nanospindles were synthesized via a two-step hydrothermal approach, and characterized by means of SEM/TEM/XRD/XPS. The ZnO shell coated on the nanospindles has a thickness of 10-15 nm. Considering that both α-Fe(2)O(3) and ZnO are good sensing materials, we have investigated the gas sensing performances of the core-shell nanocomposite using ethanol as the main probe gas. It is interesting to find that the gas sensor properties of the core-shell nanospindles are significantly enhanced compared with pristine α-Fe(2)O(3). The enhanced sensor properties are attributed to the unique core-shell nanostructure. The detailed sensing mechanism is discussed with respect to the energy band structure and the electron depletion theory. The core-shell nanostructure reported in this work provides a new path to fabricate highly sensitive materials for gas sensing applications.