The effect of resistin on the redox state of breast cancer cells.

PURPOSE: Resistin is an inflammatory cytokine secreted mostly by adipocytes and immune cells that plays a role in the development of insulin resistance, diabetes, and cancer. We hypothesized that resistin's inflammatory activity influences the free radical and oxidative stress pathways. METHODS: We used human breast carcinogenic (MCF-7 and MDA-MB-231) and non-carcinogenic (MCF-10A) cells in this investigation and correlated the absorbed resistin concentration with the change in oxidative stress (TBARS, carbonated proteins) and antioxidant activity (Antioxidant Capacity, SuperOxideDismutase, CATalase, Glutathione Peroxidase). RESULTS: Resistin was substantially more effective as a prooxidant at lower (12.5 ng/ml) concentrations, than at higher concentrations (25.0 ng/ml). Vitamin C did not appear to be an effective oxidative stress protector at antioxidant concentrations of 5.10-4 M. Leptin, at 100 ng/ml, did not result in conclusive oxidative stress or antioxidant defence stimulation, as expected. CONCLUSION: Taken together, the findings support resistin's role as a non-oxidative stress marker and a metabolic signaling molecule.

The Microbiome in the Obesity-Breast Cancer Axis: Diagnostic and Therapeutic Potential.

A growing body of evidence has demonstrated a relationship between the microbiome, adiposity, and cancer development. The microbiome is emerging as an important factor in metabolic disease and cancer pathogenesis. This review aimed to highlight the role of the microbiome in obesity and its association with cancer, with a particular focus on breast cancer. This review discusses how microbiota dysbiosis may contribute to obesity and obesity-related diseases, which are linked to breast cancer. It also explores the potential of the gut microbiome to influence systemic immunity, leading to carcinogenesis via the modulation of immune function. This review underscores the potential use of the microbiome profile as a diagnostic tool and treatment target, with strategies including probiotics, fecal microbiota transplantation, and dietary interventions. However, this emphasizes the need for more research to fully understand the complex relationship between the microbiome, metabolic disorders, and breast cancer. Future studies should focus on elucidating the mechanisms underlying the impact of the microbiome on breast cancer and exploring the potential of the microbiota profile as a biomarker and treatment target.

Efficacy of the monocarbonyl curcumin analog C66 in the reduction of diabetes-associated cardiovascular and kidney complications.

Curcumin is a polyphenolic compound derived from turmeric that has potential beneficial properties for cardiovascular and renal diseases and is relatively safe and inexpensive. However, the application of curcumin is rather problematic due to its chemical instability and low bioavailability. The experimental results showed improved chemical stability and potent pharmacokinetics of one of its analogs - (2E,6E)-2,6-bis[(2-trifluoromethyl)benzylidene]cyclohexanone (C66). There are several advantages of C66, like its synthetic accessibility, structural simplicity, improved chemical stability (in vitro and in vivo), presence of two reactive electrophilic centers, and good electron-accepting capacity. Considering these characteristics, we reviewed the literature on the application of C66 in resolving diabetes-associated cardiovascular and renal complications in animal models. We also summarized the mechanisms by which C66 is preventing the release of pro-oxidative and pro-inflammatory molecules in the priming and in activation stage of cardiomyopathy, renal fibrosis, and diabetic nephropathy. The cardiovascular protective effect of C66 against diabetes-induced oxidative damage is Nrf2 mediated but mainly dependent on JNK2. In general, C66 causes inhibition of JNK2, which reduces cardiac inflammation, fibrosis, oxidative stress, and apoptosis in the settings of diabetic cardiomyopathy. C66 exerts a powerful antifibrotic effect by reducing inflammation-related factors (MCP-1, NF-κB, TNF-α, IL-1ß, COX-2, and CAV-1) and inducing the expression of anti-inflammatory factors (HO-1 and NEDD4), as well as targeting TGF-ß/SMADs, MAPK/ERK, and PPAR-γ pathways in animal models of diabetic nephropathy. Based on the available evidence, C66 is becoming a promising drug candidate for improving cardiovascular and renal health.