Background/Objectives: Obesity-associated hyperleptinemia has been linked to breast cancer (BC) progression via mechanisms that remain incompletely understood. This study explores the role of leptin and its receptor (LEPR) in facilitating BC cell proliferation, migration, epithelial–mesenchymal transition (EMT), and STAT3 signaling pathway activation. Methods: We analyzed gene expression and survival data from TCGA BRCA dataset. MCF-7 and MDA-MB-231 BC cells were exposed to leptin at 10 ng/mL (lean-associated levels) and 100 ng/mL (elevated levels linked to obesity). MTT assays, colony formation tests, wound-healing and tumor spheroid dissemination experiments evaluated cell proliferation and migration. Immunofluorescence and Western blot analysis assessed changes in EMT markers and cytoskeletal alterations, while Western blotting and qPCR assessed STAT3 and NCOA1 expression and activation levels. Results: Elevated LEPR expression was linked with unfavorable prognosis in BC patients. Higher doses of leptin (100 ng/mL) significantly enhanced cellular proliferation rates and migratory capabilities, in both cell lines, and promoted EMT characteristics marked by downregulated E-cadherin and cytoskeleton structural changes. Whereas heightened JAK2/STAT3 signaling correlated with elevated leptin dosages, STAT3 inhibition using AG490 reversed leptin-induced migration while reinstating E-cadherin levels to baseline. Furthermore, leptin upregulated NCOA1, an essential STAT3 coactivator, facilitating increased expression of Cyclin D1 and VEGF target genes. Clinical positive relationships were seen between LEP/LEPR expressions and NCOA1 levels and between NCOA1 and various gene signatures related to STAT3/P-STAT3 within BC specimens. Conclusions: Obesity-associated hyperleptinemia enhances aggressiveness in BC through a mechanism involving LEPR-mediated activation pathways encompassing NCOA1/STAT3, which drive proliferation, migration, and EMT. This assigns a potential therapeutic utility for obesity-related advancements found within BC pathology.

Marine-derived natural products are increasingly recognized for their therapeutic potential in cancer and other chronic diseases. Despite significant advances, current cancer treatments remain challenged by toxicity, drug resistance, and limited survival benefits. Natural compounds offer promising alternatives due to their multi-target mechanisms and favorable safety profiles. Among them, Spirulina, a filamentous cyanobacterium, stands out for its rich composition and diverse biological activities. Its anticancer effects involve apoptosis induction via intrinsic and extrinsic pathways, cell cycle arrest at G1/S or G2/M phases, inhibition of angiogenesis through the VEGF/VEGFR2 axis, and suppression of epithelial–mesenchymal transition. These activities are mainly attributed to C-phycocyanin, allophycocyanin, phenolic compounds, and immunomodulatory polysaccharides. Spirulina also exhibits potent immunomodulatory effects by enhancing natural killer cell activity, promoting M1 macrophage polarization, and regulating Th1 and Th17 cytokine responses, highlighting its potential as both an immunotherapeutic and chemoprotective agent. Moreover, preclinical findings suggest it may reduce chemotherapy-associated side effects. However, translation into clinical therapy remains limited by low bioavailability, lack of standardized extracts, and scarce clinical evidence. This review summarizes current mechanistic and immunological insights and highlights the need for optimized formulations, defined dosing strategies, and well-designed clinical trials to validate Spirulina’s potential in cancer treatment.

This study investigates the impact of immunological and clinical factors on COVID-19 outcomes among unvaccinated individuals. A cohort of 42 unvaccinated patients admitted to an intensive care unit was analyzed, focusing on age, comorbidities, inflammatory cytokines (IL-6, TNF-α), and anti-SARS-CoV-2 spike protein antibody levels (IgG) to assess their influence on hospital stay duration, recovery time, complications, and mortality rates. The findings revealed that advanced age, cardiovascular disease, and elevated pro-inflammatory cytokines significantly heightened the risks of severe complications and mortality. Conversely, low IgG levels correlated with prolonged hospital stays and slower recovery. Multivariate analysis identified high IL-6 and TNF-α levels as strong predictors of adverse outcomes. This research emphasizes the need for the early monitoring of cytokines and targeted management strategies to mitigate the impact of COVID-19, especially among high-risk unvaccinated populations.

Obesity-driven hyperleptinemia is a key driver of breast cancer (BC) aggressiveness; nevertheless, strategies to counteract leptin-mediated tumor progression remain limited. Curcumin, a natural polyphenol with established anti-obesity, anti-inflammatory, and anticancer properties, has emerged as a promising metabolic and tumor-modulating biomolecule, although its effects on leptin-induced oncogenic signaling remain unclear. This study evaluated Curcumin as an adjuvant nutraceutical against leptin-induced oncogenesis in MCF-7 and MDA-MB-231 cells. Cells were exposed to obesity-mimicking leptin levels alone or with non-toxic Curcumin doses. MTT, clonogenic, wound-healing, and 3D spheroid dissemination assays were used to assess phenotypic changes, while network pharmacology and molecular docking explored underlying mechanisms. Curcumin significantly inhibited leptin-induced proliferation (8–17%), colony formation (60–90%), migration (20–45%), and 3D spheroid dissemination (20%) in both BC cell lines. Network pharmacology identified shared hub proteins, including AKT1, RHOA, MAP2K1, and MAPK14, linking Curcumin targets with leptin-driven BC signatures, and molecular docking supported direct interactions of Curcumin with these proteins. These findings suggest that Curcumin counteracts hyperleptinemia-induced tumor progression by targeting the PI3K/AKT, MAPK/ERK, and RHOA/ROCK pathways. This integrated in vitro and in silico study supports Curcumin as a promising adjuvant nutraceutical for obesity-associated BC, although experimental pathway validation is still required.

Background/Objectives: Chronic inflammation in the tumor microenvironment (TME) promotes immune evasion and metastasis in breast cancer, where the IL-23/IL-17 axis is a key mediator. We investigated the expression of IL-23 in breast cancer and identified a small natural molecule therapeutically targeting this axis. Methods: IL-23 expression and its clinicopathological significance were assessed in a Moroccan breast cancer cohort and the METABRIC dataset. A High-throughput virtual screening of Allium sativum L. compounds was conducted to target the IL-23/IL-17 axis. In vitro, the selected candidate, IL-23RI, was evaluated for its effects on IL-17A and IFNγ production in human PBMCs using flow cytometry, as well as on the migration of MCF-7 and MDA-MB-231 breast cancer cells using wound-healing assays. Results: IL-23 was found to be overexpressed in aggressive breast cancer subtypes and correlated with unfavorable clinicopathological features and a poor prognosis. Elevated IL-23 expression was associated with an immunosuppressive TME, characterized by increased inhibitory immune checkpoints and immunosuppressive chemokines. In silico, IL-23RI demonstrates a high binding affinity for the IL-23 receptor, with a docking score of −7.482 kcal/mol and a binding free energy of −48.80 kcal/mol, stabilized by five hydrogen bonds. In vitro, IL-23RI selectively suppressed IL-17A production by CD4⁺ T cells without affecting IFNγ secretion by both CD4⁺ and CD8⁺ T cells. Furthermore, IL-23RI significantly inhibited the migration of MCF-7 and MDA-MB-231 breast cancer cells. Conclusions: These findings establish the IL-23/IL-17 axis as a critical therapeutic target and present IL-23RI as a promising dual-function agent for breast cancer treatment, concurrently modulating immunity and inhibiting tumor cell migration.