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.

Introduction: The aim of this review was to review and summarize the current evidence regarding the expression and role of leptin and its receptor (LEPR) in colorectal cancer (CRC). This includes discussing their involvement in carcinogenesis, progression, and prognosis, as well as assessing their potential as biomarkers and therapeutic targets. Content: We conducted a scoping literature review using several databases. We included studies in English or French that analyzed the expression of leptin and LEPR in the serum or tissue of CRC patients. Additionally, the GEPIA2 platform was employed to investigate the association between leptin and LEPR expression levels and overall survival, as well as their expression across pathological stages and microsatellite subtypes in CRC. Summary: A total of 76 eligible studies published between 1994 and 2024 were included. Analyses through immunohistochemical methods, transcriptomics, and serum measurements indicated elevated expression of leptin and LEPR in CRC. However, findings regarding their prognostic value varied: some studies reported a link between high leptin and LEPR levels and poor prognosis, while others found no correlation or even suggested favorable outcomes. This variability in results can be attributed to differences in methodology, patient diversity, and genetic polymorphisms. Outlook: The leptin-LEPR system seems to play a significant role in the development and progression of CRC, but its exact prognostic impact remains uncertain due to inconsistent findings. Further standardized and large-scale studies are necessary to clarify its clinical relevance. The leptin-LEPR axis shows promise as a biomarker and potential therapeutic target, particularly in the context of obesity-related CRC.

Objectives: Cisplatin (CDDP) therapy for glioblastoma (GBM) is linked with several limitations, which include poor penetration of the blood-brain barrier (BBB), systemic toxicity, and the development of drug resistance mechanisms implicating oxidative stress dysregulation and compromised apoptotic pathways. This study evaluates C-Phycocyanin (C-PC) as a potential adjuvant to enhance CDDP efficacy by modulating redox balance and apoptosis. Methods: GBM cells (U87 and U87-EGFRvIII) were treated with CDDP, C-PC, or their combination. Cell viability was assessed by MTT assay; apoptosis was evaluated by DAPI staining and Western blot analysis of cleaved Caspase-3 and poly (ADP-ribose) polymerase (PARP). Both intracellular and extracellular reactive oxygen species (ROS) were measured using 2′,7′-dichlorodihydrofluorescein diacetate (DCF-DA) fluorescence and lucigenin chemiluminescence, respectively. Catalase activity was quantified via hydrogen peroxide (H2O2) decomposition assay, and manganese superoxide dismutase (MnSOD) expression by Western blot. Results: C-PC selectively decreased U87 GBM cell viability while sparing normal cells. C-PC enhanced CDDP cytotoxicity, reducing viability to 26.5% vs. 53.2% for CDDP alone. This effect correlated with increased apoptosis, evidenced by DNA fragmentation and higher cleaved caspase-3 and PARP levels. Combined treatment lowered ROS below survival thresholds while upregulating MnSOD and catalase activity. In U87-EGFRvIII cells, CDDP reduced viability modestly (85.2%), C-PC alone decreased viability significantly (51.5%) and induced cell death, but the combination did not further increase apoptosis. Here, C-PC’s pro-apoptotic effects, alone or with CDDP, were also associated with reduced oxidative stress in cells. Conclusion: We demonstrate that C-PC enhances CDDP cytotoxicity in sensitive U87 cells by promoting apoptosis and modulating ROS, suggesting potential for improved therapeutic efficacy with reduced systemic toxicity. Compared to the combination, C-PC monotherapy achieves superior cytotoxicity in CDDP-resistant U87-EGFRvIII cells, underscoring its potential as a standalone therapeutic approach for chemotherapy-resistant glioblastoma subtypes.

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.