Colorectal cancer (CRC) is currently ranked as the third most common type of cancer, contributing significantly to mortality and morbidity worldwide. Epigenetic and genetic changes occurred during CRC progression resulted in the cell proliferation, cancer progression, angiogenesis, and invasion. Angiogenesis is one of the crucial steps during cancer progression required for the delivery of essential nutrients to cancer cells and removes metabolic waste. During angiogenesis, different molecules are secreted from tumoral cells to trigger vascular formation including epidermal growth factor and the vascular endothelial growth factor (VEGF). The production and regulation of the secretion of these molecules are modulated by different subcellular pathways such as NF-κB. NF-κB is involved in regulation of different homeostatic pathways including apoptosis, cell proliferation, inflammation, differentiation, tumor migration, and angiogenesis. Investigation of different aspects of this pathway and its role in angiogenesis could provide a comprehensive overview about the underlying mechanisms and could be used for development of further therapeutic targets. In this review of literature, we comprehensively reviewed the current understanding and potential of NF-κB-related angiogenesis in CRC. Moreover, we explored the treatments that are based on the NF-κB pathway.

Colorectal cancer (CRC), the third most prevalent cancer worldwide, presents a significant burden in terms of both mortality and morbidity. The development of CRC is a complex process, driven by a combination of genetic mutations and epigenetic alterations that disrupt normal cellular functions. These changes influence a range of cancer-regulating mechanisms, including metabolism, cell proliferation, invasion, metastasis, and apoptosis. Apoptosis, a crucial process in maintaining cellular homeostasis, plays a paradoxical role in CRC progression. While it helps eliminate damaged cells, the evasion of apoptosis allows cancer cells to thrive, gain nutrients, and avoid metabolic waste accumulation, thereby facilitating tumor growth. Additionally, the process of neovascularization, the formation of new blood vessels, is critical for tumor sustenance and expansion. The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway is a key regulator involved in multiple physiological and pathological processes, including angiogenesis, tumor migration, cell proliferation, inflammation, apoptosis, and differentiation. Dysregulation of NF-κB activity is implicated in the progression of CRC. This review provides a comprehensive evaluation of the role of NF-κB signaling in CRC, particularly its involvement in apoptosis. Moreover, it explores the therapeutic potential of targeting the NF-κB pathway with natural and synthetic compounds, highlighting their ability to modulate CRC progression and improve patient outcomes. These insights underscore the potential of NF-κB inhibition as a novel therapeutic strategy in CRC management.

Background: Various surrogate markers of insulin resistance have been developed, capable of predicting coronary artery disease (CAD) without the need to detect serum insulin. For accurate prediction, they depend only on glucose and lipid profiles, as well as anthropometric features. However, there is still no agreement on the most suitable one for predicting CAD. Methods: We followed a cohort of 2,000 individuals, ranging in age from 20 to 74, for a duration of 9.9 years. We utilized multivariate Cox proportional hazard models to investigate the association between TyG-index, TyG-BMI, TyG-WC, TG/HDL, plus METS-IR and the occurrence of CAD. The receiver operating curve (ROC) was employed to compare the predictive efficacy of these indices and their corresponding cutoff values for predicting CAD. We also used three distinct embedded feature selection methods: LASSO, Random Forest feature selection, and the Boruta algorithm, to evaluate and compare surrogate markers of insulin resistance in predicting CAD. In addition, we utilized the ceteris paribus profile on the Random Forest model to illustrate how the model’s predictive performance is affected by variations in individual surrogate markers, while keeping all other factors consistent in a diagram. Results: The TyG-index was the only surrogate marker of insulin resistance that demonstrated an association with CAD in fully adjusted model (HR: 2.54, CI: 1.34–4.81). The association was more prominent in females. Moreover, it demonstrated the highest area under the ROC curve (0.67 [0.63–0.7]) in comparison to other surrogate indices for insulin resistance. All feature selection approaches concur that the TyG-index is the most reliable surrogate insulin resistance marker for predicting CAD. Based on the Ceteris paribus profile of Random Forest the predictive ability of the TyG-index increased steadily after 9 with a positive slope, without any decline or leveling off. Conclusion: Due to the simplicity of assessing the TyG-index with routine biochemical assays and given that the TyG-index was the most effective surrogate insulin resistance index for predicting CAD based on our results, it seems suitable for inclusion in future CAD prevention strategies.

Alcohol use disorder (AUD) is a major global health burden with high relapse rates and limited treatment uptake. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), developed for type 2 diabetes and obesity, may also reduce alcohol consumption by modulating central reward pathways. We performed a systematic review and meta-analysis following PRISMA guidelines (PROSPERO CRD420251009075). Randomized controlled trials (RCTs) and observational studies were included if they assessed the effect of GLP-1 RAs on alcohol-related outcomes in adults with hazardous drinking or AUD. The search covered all databases from inception to June 1, 2025. The primary outcome was change in Alcohol Use Disorders Identification Test (AUDIT) scores (range 0–40), a validated screening tool assessing hazardous use, dependence, and alcohol-related harm. Alcohol use was defined as self-reported consumption (drinks or units per week, grams per day), with thresholds for risky drinking determined by study-specific definitions (e.g., ≥14 drinks/week for men, ≥7 for women). Secondary outcomes included relapses, abstinence, alcohol-related diagnoses, intoxication or hospitalization, biomarkers (e.g., phosphatidylethanol [PEth], γ-GT), and neuroimaging measures of craving, reward, and cue-reactivity. Fourteen studies (four RCTs, ten observational; n = 5,262,268) were included. GLP-1 RAs studied were Semaglutide, liraglutide, dulaglutide, exenatide, and tripeptide. Pooled analysis demonstrated a significant reduction in AUDIT scores (mean difference −7.81 points; 95% CI −9.02 to −6.60; I² = 87.5%). RCTs also reported reduced drinking days, units per drinking day, and cravings particularly with Semaglutide. GLP-1 RA use was associated with reduced alcohol intake, relapse rates, and incidence of alcohol-related diagnoses, especially in individuals with type 2 diabetes or obesity prescribed Semaglutide or liraglutide. Population-based studies showed lower risks of incident and recurrent AUD, intoxication, and hospitalization. Biomarker analyses (PEth, γ-GT) demonstrated reductions with GLP-1 RA use, and neuroimaging studies reported attenuated alcohol cue reactivity and dopaminergic signaling. Weight loss and metabolic improvements reinforced abstinence and treatment adherence. GLP-1 RAs, particularly Semaglutide and liraglutide, reduce alcohol use as measured by AUDIT scores and show beneficial effects on consumption, relapse, and alcohol-related morbidity. Mechanistic evidence supports modulation of craving and reward pathways. These findings suggest that GLP-1 RAs are promising candidates for repurposing in AUD management, especially for patients with comorbid diabetes or obesity. Large, dedicated RCTs are needed to confirm efficacy and define optimal therapeutic strategies. No funding was received for this study.

In the fourth year of the COVID-19 occurrence, a new COVID-19 variant, JN.1, has emerged and spread globally and become the dominant strain in several regions. It has some specific mutations in its spike proteins, empowering it with higher transmissibility. Regarding the significance of the issue, understanding the clinical and immunological traits of JN.1 is critical for enhancing health strategies and vaccination efforts globally, with the ultimate goal of bolstering our collective response to the pandemic. In this study, we take a look at the latest findings of JN.1 characteristics and mutations as well as its consequences on bypassing immune system. We demonstrate the importance of continual surveillance and strategic adaptation within healthcare frameworks along with the significance of wastewater sampling for the rapid identification of emerging SARS-CoV-2 variants.