In vitro and in vivo effects of Galectin-3 inhibitor TD139 on inflammation and ERK/JNK/p38 pathway in gestational diabetes mellitus.

This study aims to investigate the effects of the Galectin-3 (Gal-3) inhibitor TD139 on inflammation and the extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/p38 pathway in gestational diabetes mellitus (GDM). Human placental tissues were treated with TD139 and TNF-α, assessing Gal-3, ERK/JNK/p38 activation, and inflammatory cytokines. GDM was induced in mice via subcutaneous injections of streptozotocin (STZ). After confirming GDM, mice were treated with 15 mg/kg TD139 on GD 10.5 12.5, 14.5, 16.5, and 18.5. Serum inflammatory cytokines were measured on GD 20.5, and post-delivery placental tissues were analyzed. Data were analyzed using one-way or two-way repeated measures ANOVA with post hoc tests. TD139 suppressed TNF-α-induced increases in Gal-3, IL-1ß, IL-6, MCP-1, and ERK/JNK/p38 activation in placental tissues. In STZ-induced GDM mice, TD139 reduced glucose levels, weight loss, and food and water intake. TD139 significantly lowered TNF-α, IL-1ß, IL-6, and MCP-1 in serum and placental tissues and inhibited the ERK/JNK/p38 pathway. TD139 improved pup numbers in GDM mice compared to untreated ones. TD139 reduces inflammation and inhibits the ERK/JNK/p38 pathway in TNF-α stimulated placental tissues and STZ-induced GDM mice, suggesting its therapeutic potential for managing GDM-related placental inflammation and improving pregnancy outcomes. The study used TNF-α to mimic GDM in placental tissues and an STZ-induced GDM mouse model, which may not fully represent human GDM complexity. Future research should explore alternative models, and broader signaling pathways, and thoroughly evaluate TD139's safety in pregnancy.

Effects of insulin aspart and metformin on gestational diabetes mellitus and inflammatory markers.

BACKGROUND: Gestational diabetes mellitus (GDM) refers to hyperglycemia caused by insulin resistance or insufficient insulin secretion during pregnancy. Patients with GDM have a high risk of pregnancy complications, which can adversely affect both maternal and fetal health. Therefore, early diagnosis, treatment and monitoring of GDM are essential. In recent years, a new treatment scheme represented by insulin aspart combined with metformin has received increasing attention. AIM: To explore the effects of insulin aspart combined with metformin on patients with GDM and inflammatory markers. METHODS: From April 2020 to September 2022, 124 patients with GDM in Sanya Women and Children's Hospital Managed by Shanghai Children's Medical Center were collected and analyzed retrospectively. The control group (CG) comprised 62 patients treated with insulin aspart alone, and 62 patients treated with insulin aspart and metformin formed the observation group (OG). Before and after treatment, improvement of blood-glucose-related indexes [fasting blood glucose (FBG), 2-h postprandial glucose (2h PG) and hemoglobin A1c (HbA1c)], serum related factor [serum homocysteine (Hcy)], serum inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-6 and C-reactive protein (CRP)] were compared between the two groups. The clinical efficacy, adverse pregnancy outcomes and incidence of pregnancy complications were compared between the two groups. RESULTS: After treatment, the levels of FBG, 2h PG, HbA1c, Hcy, TNF-α, IL-6 and CRP in both groups were significantly decreased (P < 0.05), and the levels of FBG, 2h PG, HbA1c, Hcy, TNF-α, IL-6 and CRP in the OG were lower than in the CG (P < 0.05). The total clinical effectiveness in the OG was higher than that in the CG (P < 0.05). The total incidence of adverse pregnancy outcomes and complications in the OG was significantly lower than in the CG (P < 0.05). CONCLUSION: Insulin aspart combined with metformin are effective for treatment of GDM, which can reduce blood-glucose-related indexes, Hcy and serum inflammatory cytokines, and risk of adverse pregnancy outcomes and complications.

YcgC represents a new protein deacetylase family in prokaryotes.

Reversible lysine acetylation is one of the most important protein posttranslational modifications that plays essential roles in both prokaryotes and eukaryotes. However, only a few lysine deacetylases (KDACs) have been identified in prokaryotes, perhaps in part due to their limited sequence homology. Herein, we developed a 'clip-chip' strategy to enable unbiased, activity-based discovery of novel KDACs in the Escherichia coli proteome. In-depth biochemical characterization confirmed that YcgC is a serine hydrolase involving Ser200 as the catalytic nucleophile for lysine deacetylation and does not use NAD(+) or Zn(2+) like other established KDACs. Further, in vivo characterization demonstrated that YcgC regulates transcription by catalyzing deacetylation of Lys52 and Lys62 of a transcriptional repressor RutR. Importantly, YcgC targets a distinct set of substrates from the only known E. coli KDAC CobB. Analysis of YcgC's bacterial homologs confirmed that they also exhibit KDAC activity. YcgC thus represents a novel family of prokaryotic KDACs.