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Background: Changes in gene expression related to obesity are linked to microRNAs, such as miR‐141, which play a crucial role in metabolic homeostasis. Sirtuin 1 (SIRT1), an enzyme that plays a crucial role in regulating various cellular functions and metabolism, is implicated in obesity and the ensuing non‐alcoholic fatty liver disease (NAFLD). The aim of this research was to evaluate the levels of miR‐141 and its relationship with SIRT1 and NAFLD. Methods: A group of 100 adults (50 with obesity and 50 with normal‐weight) were selected and underwent complete clinical evaluation and anthropometric measurements. Biochemical parameters were assessed in blood serum, and the levels of miR‐141 in plasma were measured by real‐time PCR. The expression of the SIRT1 gene was also evaluated in the peripheral blood mononuclear cells using Real‐time PCR. The ELISA technique was used to determine insulin levels. Liver steatosis was assessed by ultrasound. Results: The results showed that levels of miR‐141 were significantly increased in participants with obesity compared with the control group. Conversely, the expression of the SIRT1 gene in individuals with obesity was lower than that in control participants. A strong negative correlation was observed between miR‐141 and SIRT1 and a strong positive association was observed between miR‐141 and metabolic parameters. Furthermore, participants with fatty liver had significantly elevated levels of miR‐141 gene expression and lower expression of SIRT1 gene, compared to those without fatty liver. Conclusion: elevated levels of miR‐141 in individuals with obesity might be a contributing factor in the repression of SIRT1 in obesity and its consequences, including NAFLD. Therefore, miR‐141 might serve as a suitable diagnostic and therapeutic target in obesity and NAFLD. [ABSTRACT FROM AUTHOR]

Introduction: Imidazo[1,2- a ]pyridine derivatives with diverse pharmacological properties and curcumin, as a potential natural anti-inflammatory compound, are promising compounds for cancer treatment. This study aimed to synthesize a novel imidazo[1,2- a ]pyridine derivative, (MIA), and evaluate its anti-inflammatory activity and effects on nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) pathways, and their target genes, alone and in combination with curcumin, in MDA-MB-231 and SKOV3 cell lines. Methods: We evaluated the interaction between imidazo[1,2- a ]pyridine ligand, curcumin, and NF-κB p50 protein, using molecular docking studies. MTT assay was used to investigate the impacts of compounds on cell viability. To evaluate the NF-κB DNA binding activity and the level of inflammatory cytokines in response to the compounds, ELISA-based methods were performed. In addition, quantitative polymerase chain reaction (qPCR) and western blotting were carried out to analyze the expression of genes and investigate NF-κB and STAT3 signaling pathways. Results: Molecular docking studies showed that MIA docked into the NF-κB p50 subunit, and curcumin augmented its binding. The MTT assay results indicated that MIA and its combination with curcumin reduced cell viability. According to the results of the ELISA-based methods, MIA lowered the levels of inflammatory cytokines and suppressed NF-κB activity. In addition, real-time PCR and Griess test results showed that the expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) genes, and nitrite production were reduced by MIA. Furthermore, the western blotting analysis demonstrated that MIA increased the expression of inhibitory κB (IκBα) and B-cell lymphoma 2 (Bcl-2)-associated X proteins (BAX), and suppressed the STAT3 phosphorylation, and Bcl-2 expression. Our findings revealed that curcumin had a potentiating role and enhanced all the anti-inflammatory effects of MIA. Conclusion: This study indicated that the anti-inflammatory activity of MIA is exerted by suppressing the NF-κB and STAT3 signaling pathways in MDA-MB-231 and SKOV3 cancer cell lines. [ABSTRACT FROM AUTHOR]

Introduction: Adipose triglyceride lipase (ATGL) is a crucial enzyme responsible for the release of fatty acids from various tissues. The expression of ATGL is regulated by insulin and this enzyme is linked to Insulin resistance (IR). On the other hand, ATGL‐mediated lipolysis is connected to macrophage function and thus, ATGL is involved in inflammation and the pathogenesis of lipid‐related disorders. This study aimed to investigate the correlation between ATGL, obesity, Metabolic Syndrome (MetS), and inflammation. Methods: A total of 100 participants, including 50 individuals with obesity and 50 healthy participants, were recruited for this study and underwent comprehensive clinical evaluations. Blood samples were collected to measure plasma lipid profiles, glycemic indices, and liver function tests. Additionally, peripheral blood mononuclear cells (PBMCs) were isolated and used for the assessment of the gene expression of ATGL, using real‐time PCR. Furthermore, PBMCs were cultured and exposed to lipopolysaccharides (LPS) with simultaneous ATGL inhibition, and the gene expression of inflammatory cytokines, along with the secretion of prostaglandin E2 (PGE2), were measured. Results: The gene expression of ATGL was significantly elevated in PBMCs obtained from participants with obesity and was particularly higher in those diagnosed with MetS. It exhibited a correlation with insulin levels and Homeostatic Model Assessment for IR (HOMA‐IR), and it was associated with lipid accumulation in the liver. Stimulation with LPS increased ATGL expression in PBMCs, while inhibition of ATGL attenuated the inflammatory responses induced by LPS. Conclusions: Obesity and MetS were associated with dysregulation of ATGL. ATGL might play a role in the upregulation of inflammatory cytokines and act as a significant contributor to the development of metabolic abnormalities related to obesity. [ABSTRACT FROM AUTHOR]

One of the most common cancers and a main cause of death worldwide among women is breast cancer (BC). Combination therapy is being widely investigated to reduce the dose of chemotherapy drugs, prevent the development of drug resistance, and improve treatment outcomes. Here we tested PEI-PBA-SAP-F15 (PPSF) polymeric nanoparticles to efficiently deliver a microRNA antagonist (anti-miR19a-3p) to BC cell lines. We evaluated the combination of anti-miR19a-3p plus doxorubicin (DOX) in both 2D and 3D cell cultures. We cultured 3D tumor spheroids in an innovative microfluidic device that was fabricated using a 3D printing system. The PPSF polyplexes had the correct size and zeta potential to efficiently transfer anti-miR19a-3p into MCF7 cells. The expression level of phosphatase and tensin homolog (PTEN), the attainment gene of microRNA-19a-3p was increased. PTEN up-regulation inhibited cell migration and caused cell cycle arrest. Apoptosis was also significantly induced with the combination treatment. Confocal microscopy studies revealed that the population of dead cells was in an important degree higher in MCF7 spheroids transfected with anti-miR19a-3p-PPSF plus DOX. [ABSTRACT FROM AUTHOR]