We intended to investigate the presence and medical application of serum hypoxia-inducible factor-1 alpha (HIF-1α) along with the already known systemic inflammatory markers and the new one’s inflammatory indices, the proportion of mean corpuscular volume and lymphocytes (MCVL) and the cumulative inflammatory index (IIC), for patients with ulcerative colitis (UC). We sought to establish correlations that may be present between the serum levels of HIF-1α and these inflammatory indices, as well as their relationship with disease activity and the extent of UC, which can provide us with a more precise understanding of the evolution, prognosis, and future well-being of patients. Serum samples were collected from 46 patients diagnosed with UC and 23 controls. For our assessment of the serum levels of HIF-1α, we used the Enzyme-Linked Immunosorbent Assay (ELISA) technique. Thus, for HIF-1α we detected significantly higher values in more severe and more extensive UC. When it came to MCVL and IIC, we observed statistically significant differences between the three groups being compared (Severe, Moderate, and Mild). Our study highlighted that HIF-1α correlated much better with a disease activity score, MCVL, and IIC. With MCVL and IIC, a strong and very strong correlation had formed between them and well-known inflammation indices. By examining the ROC curves of the analyzed parameters, we recognized that TWI (accuracy of 83.70%) provides the best discrimination of patients with early forms of UC, followed by HIF-1α (73.90% accuracy), MCVL (70.90% accuracy), and PLR (70.40%). In our study, we observed that HIF-1α, MCVL, and PLR had the same sensitivity (73.33%) but HIF-1α had a much better specificity (60.87% vs. 58.70%, and 54.35%). Also, in addition to the PLR, HIF-1α and MCVL can be used as independent predictor factors in the discrimination of patients with early forms of UC.

Metabolic syndrome (MetS) and its associated cardiometabolic phenotypes significantly contribute to the global burden of cardiovascular disease (CVD), especially in individuals with type 2 diabetes mellitus (T2DM) and prediabetes. This study aimed to explore the association between cardiometabolic phenotypes—specifically, metabolically unhealthy normal weight (MUHNW) and metabolically unhealthy obese (MUHO)—and various cardiovascular risk indices including the triglyceride-glucose (TyG) index and its derivatives, the atherogenic index of plasma (AIP), the cardiometabolic index (CMI), and the cardiac risk ratio (CRR). A total of 300 participants were evaluated (100 with prediabetes and 200 with T2DM). Anthropometric, biochemical, and lifestyle parameters were assessed and stratified across phenotypes. The results demonstrated that cardiovascular risk indices were significantly elevated in the MUHO compared to MUHNW phenotypes, with T2DM patients consistently exhibiting higher risk profiles than their prediabetic counterparts. TyG-derived indices showed strong correlations with BMI, waist–hip ratio (WHR), waist–height ratio (WHtR), and body fat percentage (%BF). The findings suggest that cardiometabolic phenotypes are more strongly associated with elevated cardiometabolic risk indices than body weight alone. These indices may enhance early risk stratification and intervention efforts. The study investigates the association of cardiometabolic phenotypes with surrogate cardiovascular risk indices, not direct CVD outcomes, However, the cross-sectional design and population homogeneity limit the generalizability of the results and preclude causal inference.

Neuroendocrine tumors are uncommon in the gastrointestinal system but can develop in the majority of the body’s epithelial organs. Our goal was to examine the presence and clinical application of serum dopamine (DA), serotonin (ST), norepinephrine (NE), and epinephrine (EPI), in addition to determining the significance of the Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), and systemic inflammatory response (SIR) markers as a prognostic factor for patients with colorectal neuroendocrine tumors (CR-NETs), in various tumor–node–metastasis (TNM) stages. We also wanted to identify the possible connection between them. This study included 25 consecutive patients who were diagnosed with CR-NETs and a control group consisting of 60 patients with newly diagnosed colorectal cancer (CRC). We used the Enzyme-Linked Immunosorbent Assay (ELISA) technique. This study revealed that CR-NET patients showed significantly higher serum levels of DA compared to CRC patients. We showed that serum DA was present in the early stages of CR-NETs, with increasing levels as we advanced through the TNM stages. Moreover, we found a close relationship between the levels of DA and the inflammation and nutritional status of the CR-NET patients in this study. CR-NET patients from the PNI < 47.00 subgroup had a higher level of DA than those from the PNI ≥ 47.00 subgroup. Pearson’s correlation analysis revealed correlations between DA, PNI, and the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR). Both hematological indices were negatively correlated with albumin (ALB). Our investigation’s findings relating to the PNI, GPS, SIR, and DA indicate that these tools can be markers of nutritional and systemic inflammatory status, are simple to use, and are repeatable. Further research on this topic could provide valuable insights into which biomarkers to incorporate into clinical practice for the management of CR-NET patients.

Adiponectin and omentin are adipose tissue-derived adipokines implicated in insulin sensitivity and cardiometabolic regulation. Their behavior across different stages of dysglycemia, as well as in relation to visceral adiposity and cardiometabolic phenotypes, remains incompletely understood. In this cross-sectional study, circulating adiponectin and omentin levels were evaluated in individuals with prediabetes (PreDM, n = 100) and newly diagnosed type 2 diabetes mellitus (T2DM, n = 128). Associations with insulin resistance-related indices, including the triglyceride–glucose (TyG) index and TyG-derived composites, the visceral adiposity index (VAI), cardiometabolic phenotypes, and cardiovascular risk categories, were assessed using correlation and multivariable regression analyses. Discriminatory performance for metabolically unhealthy obesity was evaluated using receiver operating characteristic (ROC) curve analysis. Both adiponectin and omentin levels were lower in T2DM compared with PreDM (22.05 vs. 30.30 and 25.72 vs. 38.84, p < 0.0001 for both). In PreDMs, omentin showed a significant inverse correlation with the TyG index (weak correlation, ρ = −0.197, p = 0.050), whereas adiponectin demonstrated only weak trends. In multivariable models, VAI and male sex were independent predictors of circulating omentin levels, whereas fasting insulin was not. In contrast, adiponectin did not retain independent associations with metabolic or visceral adiposity indices. In T2DM, adipokine–metabolic associations were largely absent. Neither adipokine differed substantially across cardiometabolic phenotypes or cardiovascular risk categories. ROC analyses revealed modest overall discriminatory performance for metabolically obese phenotypes, with poor discrimination after stratification by glycemic status (area under the ROC curve (AUC) of 0.704 for adiponectin and 0.710 for omentin, and AUC of 0.431 for adiponectin and 0.461 for omentin, respectively). Circulating adipokines appear to exhibit stage-dependent relationships with metabolic dysfunction, being more informative in PreDM than in established T2DM. Omentin may reflect visceral adiposity-related metabolic alterations in early dysglycemia, whereas adiponectin shows limited independent associations. Overall, these findings suggest that adipokines have limited diagnostic or cardiovascular risk-stratification utility when considered in isolation and may be better interpreted within multimarker cardiometabolic assessment frameworks.

Background/Objectives: Microsatellite-stable colorectal cancer (MSS CRC) accounts for the vast majority of CRC cases and remains largely resistant to immune checkpoint inhibitors. Emerging evidence suggests that the gut microbiome is an important regulator of antitumor immunity and may contribute to immunotherapy resistance through multiple mechanisms involving the tumor microenvironment. This review aims to summarize current knowledge of the microbiome–immunity–therapy axis in MSS CRC and to explore microbiome-based strategies to enhance immunotherapy responsiveness. Methods: A narrative review of the recent literature was conducted, focusing on studies published within the last five years that investigated gut microbiota composition, microbial metabolites, tumor immune regulation, immunotherapy response, and microbiome-targeted therapeutic interventions in CRC. Evidence from mechanistic studies, translational research, clinical investigations, and multi-omics analyses was integrated. Results: Current evidence indicates that gut dysbiosis contributes to immune resistance in MSS CRC through immune exclusion, myeloid-driven immuno-suppression, T-cell dysfunction, chronic inflammation, and altered microbial metabolite signaling. Specific microorganisms, including Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, pks-positive Escherichia coli, and other CRC-associated pathobionts, have been implicated in tumor progression and modulation of antitumor immunity. Microbial metabolites such as short-chain fatty acids, tryptophan-derived compounds, bile acids, succinate, and inosine represent key functional mediators linking microbial communities to host immune responses. Emerging microbiome-targeted interventions, including fecal microbiota transplantation, next-generation probiotics, postbiotics, selective microbial depletion, and engineered bacterial therapeutics, show potential to restore antitumor immunity and improve immunotherapy efficacy. In parallel, advances in metagenomics, metabolomics, spatial transcriptomics, and artificial intelligence are facilitating the development of precision immuno-microbiome oncology approaches. Conclusions: The gut microbiome functions as a critical regulator of immune resistance in MSS CRC through coordinated effects on microbial composition, metabolite production, and tumor immune remodeling. Microbiome-targeted interventions, combined with multi-omics-based patient stratification, may provide new opportunities to overcome immunotherapy resistance and expand the clinical benefits of immune checkpoint blockade in this traditionally refractory disease.