Pregnancy is associated with profound metabolic, hormonal, and immunological adaptations accompanied by dynamic alterations in maternal gut microbiota composition and function. Emerging evidence suggests that maternal diet is a major regulator of these microbiota-related changes and may influence maternal-fetal health through microbial metabolites and host signaling pathways. Fermented foods and functional dietary components, including prebiotics, probiotics, synbiotics, and polyphenols, have gained increasing attention because of their potential to modulate gut microbial diversity, intestinal barrier integrity, inflammatory responses, and metabolic homeostasis. Mechanistically, these effects are mediated through pathways involving short-chain fatty acids, G protein-coupled receptors, nuclear factor kappa B signaling, histone deacetylase inhibition, and immune cell regulation. Altered microbiota-associated signaling has been linked to gestational metabolic disorders such as obesity, gestational diabetes mellitus, and preeclampsia, as well as fetal immune and metabolic programming. Particular emphasis is placed on the maternal-infant microbiome axis, highlighting how maternal nutrition and microbiota-mediated signaling may influence microbial transmission, fetal programming, and early-life microbiome development. This review summarizes current evidence regarding pregnancy-associated gut microbiota alterations and discusses the molecular mechanisms through which fermented foods and functional nutrition may influence maternal and fetal health outcomes.

Uncoupling protein 1 (UCP1) is a mitochondrial inner-membrane carrier classically recognized as the molecular effector of non-shivering thermogenesis in brown adipose tissue. By dissipating the proton-motive force generated by oxidative phosphorylation, UCP1 converts stored chemical energy into heat and enables adaptive thermogenesis during cold exposure. The rediscovery of metabolically active brown adipose tissue (BAT) and inducible beige adipocytes in adult humans has renewed interest in UCP1-positive thermogenic adipose tissue as a regulator of systemic metabolism and a potential target for therapeutic modulation in obesity and cardiometabolic disease. Beyond thermogenesis, accumulating evidence indicates that UCP1-positive brown/beige adipocytes and thermogenic adipose tissue are involved in lipid and glucose metabolism, mitochondrial redox homeostasis, inflammatory remodeling, organ protection, and tumor-associated metabolic adaptation, mainly through adipocyte-autonomous mechanisms and adipose-organ communication. However, UCP1 biology is complex: BAT activity measured by imaging does not directly quantify UCP1 proton conductance, non-adipose UCP1 expression is often low and technically challenging to validate, local cell-autonomous UCP1 function in non-adipose tissues remains controversial, and UCP1-independent thermogenic pathways may compensate in selected contexts. In this review, we summarize the molecular and structural basis of UCP1 function, its regulation at transcriptional and post-transcriptional levels, and its biological roles in cellular and systemic homeostasis, with explicit distinction between direct adipocyte-autonomous UCP1 functions, indirect systemic effects mediated by thermogenic adipose tissue, and preliminary or incompletely validated evidence of local UCP1 activity in non-adipose cells. We further discuss the association of UCP1-positive thermogenic adipose tissue with obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease, kidney injury, liver disease, neurological disorders, and cancer. Finally, we evaluate UCP1-related thermogenic adipose tissue activity as a biomarker and therapeutic target, highlighting current limitations, safety concerns, and future directions for precision metabolic medicine.

Diabetes mellitus (DM) is increasing rapidly worldwide, and diabetic cardiomyopathy (DCM) has become a leading cause of death in diabetic patients. Therefore, effective strategies for the prevention and treatment of DCM are urgently needed. Ferroptosis, a form of regulated cell death, has been implicated in the pathogenesis of DCM. This study integrated network pharmacology, data mining, molecular docking, molecular dynamics simulations, and in vitro experiments to investigate whether baicalein inhibits high glucose and sodium palmitate (HG + PA)-induced ferroptosis in cardiomyocytes and to elucidate the underlying mechanisms. Baicalein significantly improved the viability of H9c2 and AC16 cells, reduced cell death, and decreased LDH release under HG + PA conditions. Network pharmacology predicted that the protective effects of baicalein against HG + PA-induced cardiomyocyte injury were associated with ferroptosis regulation. Transcriptomic data mining further identified ferroptosis-related pathway enrichment in complementary in vitro and diabetic rat cardiac datasets. Molecular docking predicted favorable binding poses of baicalein with Nrf2, SLC7A11, and GPX4, while molecular dynamics simulations suggested general stability of the modeled complexes. In vitro experiments further confirmed ferroptosis involvement, as the ferroptosis inhibitor Ferrostatin-1 (Fer-1) reversed the HG + PA-induced decline in cell viability. Conversely, the ferroptosis inducer Erastin diminished cell survival and antagonized the protection conferred by baicalein, indicating that baicalein acts by inhibiting ferroptosis. Baicalein reduced lipid peroxidation, MDA and Fe²⁺ levels, and the mRNA expression of ACSL4 and PTGS2, while restoring the GSH/GSSG ratio and the protein expression of Nrf2, SLC7A11, and GPX4. These protective effects were partially reversed by the Nrf2 inhibitor ML385. In conclusion, baicalein protects cardiomyocytes from HG + PA-induced injury by activating the Nrf2/SLC7A11/GPX4 signaling pathway and inhibiting ferroptosis.

Type 2 diabetes mellitus is characterized by chronic low-grade inflammation, immune dysregulation, and metabolic impairment. This study investigated cytokine profiles associated with physical exercise and insulin therapy in patients with Type 2 diabetes mellitus.

Blood samples were collected from 51 volunteers to evaluate metabolic parameters and cytokine concentrations. According to glycemic status and insulin use, participants were classified into non-diabetic, non-insulin-dependent Type 2 Diabetes Mellitus, and insulin-dependent Type 2 Diabetes Mellitus groups.

Physically active individuals with non-insulin-dependent Type 2 Diabetes Mellitus exhibited increased IL-4, IL-6, and IL-10 levels, suggesting enhanced immunoregulatory and anti-inflammatory responses. Physically active patients with insulin-dependent Type 2 Diabetes Mellitus showed elevated IL-17 concentrations. In contrast, sedentary individuals with insulin-dependent Type 2 Diabetes Mellitus exhibited higher TNF-α levels, indicating a more pronounced proinflammatory profile. IFN-γ concentrations were significantly higher in patients with insulin-dependent Type 2 Diabetes Mellitus, regardless of exercise status. Correlation analyses demonstrated distinct cytokinemetabolic interaction patterns according to metabolic condition and physical exercise.

Cytokines can serve as molecular markers of immunometabolic responses associated with physical exercise and insulin therapy in Type 2 Diabetes Mellitus, reflecting alterations in systemic inflammatory regulation and immune-metabolic crosstalk related to glycemic adaptation.

Dendrobium officinale polysaccharide (DOP) shows efficacy against type 2 diabetes (T2D), but its mechanisms remain unclear. The present investigation aimed to identify potential biomarkers associated with DOP-mediated therapeutic interventions in T2D. Datasets related to T2D were excavated from the Gene Expression Omnibus (GEO) database. Candidate genes were acquired from the intersection of genes obtained from weighted gene co-expression network analysis (WGCNA) and differential analysis. Subsequently, Mendelian randomization (MR) identified causal biomarkers, validated by Receiver Operating Characteristic (ROC) curves and expression profiling. Then, a nomogram, immune infiltration, single-cell analysis, and molecular docking were performed. Among the 12 candidate genes, 7 with available eQTL instruments were included in MR analysis, while 5 lacking genome-wide significant IVs (p < 5 × 10^-8) were excluded. Three genes demonstrated significant MR associations with T2D, and biomarkers GLI1 and LGALS9 showed strong diagnostic performance and were upregulated in T2D. The nomogram had good predictive value. Seventeen immune cells differed significantly between T2D and controls, with GLI1 and LGALS9 positively correlating with most and primarily expressed in stellate cells. Finally, D-Galacturonic acid, D-Mannose, and L-rhamnose monohydrate were compounds showing predicted binding potential with candidate biomarkers GLI1 and LGALS9 emerged as promising potential molecular candidates associated with DOP-mediated T2D regulation, offering novel mechanistic perspectives on DOP's anti-diabetic properties.

Obesity is a major global health problem and is closely associated with a broad range of metabolic disorders, including metabolic syndrome (MetS), dyslipidemia, hypertension, atherosclerosis, type 2 diabetes mellitus, and cardiovascular disease. The gut microbiota plays a central role in maintaining intestinal epithelial integrity, regulating glucose and lipid metabolism, and modulating immune function. Through the gut-brain axis, it also contributes to appetite regulation and energy homeostasis by influencing the release of anorexigenic hormones. Dysbiosis, including alterations in the relative abundance of major bacterial phyla such as Firmicutes and Bacteroidetes, has been associated with increased intestinal permeability, metabolic endotoxemia, and chronic low-grade inflammation, all of which may contribute to the development of obesity and insulin resistance. Diets rich in plant-derived fiber can beneficially shape gut microbiota composition. Bacterial fermentation of dietary fiber produces short-chain fatty acids (SCFAs), including butyrate, acetate, and propionate, which contribute to intestinal barrier integrity, inflammatory regulation, immune regulation, and metabolic homeostasis. Overall, the interaction between gut microbiota, diet, and host metabolic pathways represents a promising field for therapeutic and nutritional interventions aimed at preventing and managing MetS and metabolic diseases.

Pregnancy is a physiological state of transient, reversible insulin resistance accompanied by major adaptations in glucose and lipid metabolism. Although placental hormones are key drivers of gestational insulin resistance, the mechanisms underlying the rapid restoration of insulin sensitivity after delivery remain incompletely understood. This review proposes a conceptual framework in which fibroblast growth factor 21 (FGF21) and sex hormone-binding globulin (SHBG) are considered as complementary hepatic signals potentially involved in maternal metabolic adaptation. During late pregnancy, FGF21 may function as a metabolic stress-response factor associated with fatty acid oxidation, lipid handling, and mitochondrial adaptation through AMPK-PPARα-related pathways. Reduced SHBG, in contrast, may reflect hepatic insulin resistance and altered hepatic metabolic regulation. After delivery, changes in FGF21 and SHBG levels may be associated with recovery of hepatic metabolic homeostasis and insulin sensitivity, while persistent adaptive FGF21 signaling facilitate metabolic reprogramming may contribute to ongoing metabolic adaptation. Postpartum metabolic recovery may therefore represent an active and dynamic process rather than a purely passive consequence of placental hormone withdrawal. Disruption of FGF21- and SHBG-mediated pathways may contribute to persistent insulin resistance and increased cardiometabolic risk after gestational diabetes. Understanding hepatokine-mediated regulation of maternal metabolic flexibility may provide further insight into postpartum metabolic recovery and may support future development of risk stratification strategies, biomarker-based approaches, and preventive interventions aimed at reducing the risk of type 2 diabetes after pregnancy.

Background/Objectives: Preoperative risk stratification of indeterminate thyroid nodules, particularly category IV nodules diagnosed as follicular neoplasm, remains challenging. Molecular testing may support clinical decision-making, but its cost and limited availability restrict routine use. This study evaluated whether the digitally quantified Ki-67 labeling index, alone and combined with the Korean Thyroid Imaging Reporting and Data System (K-TIRADS), could predict malignancy in thyroid core needle biopsy (CNB) specimens. Methods: We retrospectively analyzed 130 thyroid nodules sampled by ultrasound-guided CNB. The Ki-67 labeling index was digitally quantified in immunohistochemically stained CNB sections, and ultrasound features were classified according to K-TIRADS. Receiver operating characteristic curve analysis was performed in the overall cohort. Logistic regression analyses were restricted to 57 category IV nodules. Results: In the overall cohort, the Ki-67 labeling index showed excellent diagnostic performance for predicting malignancy, with an area under the curve of 0.924. The optimal cutoff was 1.73%, with 88.7% sensitivity and 83.1% specificity. In category IV nodules, K-TIRADS category and Ki-67 labeling index were independently associated with malignancy. The odds ratios were 6.02 (95% CI, 1.53-23.74) for each one-category increase in K-TIRADS and 4.44 (95% CI, 1.69-11.70) for each percentage-point increase in Ki-67. In the Ki-67-only model, a Ki-67 index of 5% corresponded to a predicted malignancy probability of 98.1%. Conclusions: Digital Ki-67 quantification, integrated with K-TIRADS, may serve as a practical adjunct for malignancy risk stratification in thyroid CNB specimens, particularly for category IV nodules. Further external validation is warranted.

Background/Objectives: Salivary gland tumors account for 2.0-6.5% of all head and neck neoplasms, approximately 70% of which are located in the parotid gland. Preoperative determination of tumor histology is a crucial step in the diagnostic and therapeutic pathway because it guides the choice of surgical technique, affecting the achievement of adequate resection margins and preservation of the facial nerve. Fine-needle aspiration (FNA) cytology is the most commonly used cytologic method. However the complex and heterogenous histologic architecture of salivary gland tumors is associated with a significant proportion of false results. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a valuable complementary diagnostic tool that enables noninvasive analysis based on perfusion assessment and tissue characterization. The aim of this study is to evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the diagnosis of salivary gland tumors and to compare its diagnostic performance with fine-needle aspiration (FNA). Methods: We present a study of 25 patients who underwent DCE-MRI, FNA and postoperative histopathologic examination. Results: Among the 25 patients included, DCE-MRI results were concordant with the postoperative histopathologic diagnosis in 76% of cases, whereas only 36% of positive FNA results correlated with the histopathologic diagnosis. Conclusions: DCE-MRI demonstrates greater correlation with postoperative histopathologic diagnosis compared with FNA. Advantages of DCE-MRI include its noninvasive nature and the ability to image the entire region of interest. Key benefits of FNA are its wide availability and low cost. Selecting the most appropriate preoperative diagnostic modality can positively influence subsequent diagnostic and therapeutic management.

A tadpole-shaped appendix has been described as a characteristic morphology of appendiceal mucinous lesions, but its clinical and ultrasonographic significance has not been fully clarified. We report a case of low-grade appendiceal mucinous neoplasm (LAMN) in which a tadpole-shaped appendiceal lesion acted as the leading point of extensive intestinal intussusception. A woman in her 60s presented with abdominal pain and difficulty with defecation. Abdominal ultrasonography demonstrated extensive intestinal intussusception extending to the transverse colon. At the leading point, the long-axis view showed a tadpole-shaped configuration composed of a spherical cystic dilated portion and a contiguous tubular structure. Dynamic observation suggested that these findings represented a single continuous appendiceal structure rather than separate cystic lesions. The short-axis view of the same structure showed a multilayered concentric ring appearance. Surgical and histopathologic examination established the diagnosis of appendiceal intussusception associated with LAMN, with secondary intestinal intussusception. Although prior or serial imaging was not available to directly demonstrate temporal progression from appendiceal to intestinal intussusception, previous reports have described appendiceal mucinous lesions with tadpole-shaped or cup-and-ball morphology as the leading point of intussusception. Therefore, when this morphology is identified on ultrasonography, careful assessment for appendiceal or intestinal intussusception is warranted. Recognition of this morphology and its continuity on ultrasonography may serve as a practical diagnostic clue and contribute to preoperative diagnosis and appropriate surgical management.