Mina Hemmati

Oxidative stress promotes the initiation and progression of diabetic complications. Fibrinogen is a thrombotic factor proposed as a biomarker for prognostic assessment, as a marker for tracking vascular complications, and as a therapeutic target in diabetes. Aminoguanidine, an inhibitor of advanced glycation end products and inducible nitric oxide synthase, has been shown to reduce oxidative stress and related vascular injury. However, the underlying processes still need to be entirely elucidated. This study investigated the effects of aminoguanidine on oxidative stress biomarkers and fibrinogen gene expression in diabetic rats. Twenty-four male rats, matched for body weight and age, were randomly assigned to five groups: (intended n = 6 per group). Due to mortality during the study, the final group sizes were: healthy controls (n = 5), untreated diabetic controls (n = 4), and diabetic rats treated with aminoguanidine at 50, 100, or 200 mg/kg (n = 6, 4, and 5, respectively). Diabetes mellitus was induced by intraperitoneal injection of streptozotocin (50 mg/kg) in rats fasted for 12 h. One week later, diabetic rats received aminoguanidine for 28 days. The liver was selected for analysis due to its key role in oxidative stress and metabolism. Malondialdehyde (MDA) and ferric-reducing ability of plasma (FRAP) were measured in liver tissue as markers of oxidative stress, and fibrinogen gene expression was assessed by real-time polymerase chain reaction. Aminoguanidine at 50 mg/kg significantly reduced fibrinogen gene expression (p = 0.047). Hepatic MDA levels decreased at all doses (50, 100, and 200 mg/kg, p < 0.05), while FRAP levels increased significantly at 50 and 100 mg/kg (p < 0.05). Aminoguanidine may attenuate oxidative stress and fibrinogen gene expression in the livers of diabetic rats.

Adjuvant chemotherapy with TMZ (Temozolomide) does not improve the survival of patients suffering from GBM (Glioblastoma). Given the importance of autophagy and UPR (Unfolding Protein Response) in chemotherapy resistance, as well as the role of Beclin-1, LC3IIβ, and P62 in the regulation of autophagy, we evaluated the effect of TMZ along with CPUK02 on U87 cells as a model of Glioblastoma cancer in this study. To achieve this goal, we treated the U87 cells with different doses of TMZ (50, 100, 200, 400, and 800 μM) and CPUK02 (1, 0.5, 0.25, 0.125, 0.06, 0.03, 0.01, and 0.007 μM); then, cell viability was assessed by MTT assay. The gene expression of Beclin1, P62, LC3IIβ, and XBP-1s was analyzed using quantitative real-time polymerase chain reaction. The comparison of the control group with the groups treated with the TMZ drug showed that, in 48 and 72 hours, doses of TMZ more than IC₅₀ (100 μM) (ppBeclin-1, LC3IIβ, and P62 and activated the IRE-1 arm of UPR by increasing the expression of XBP-1s. TMZ and CPUK02 treatment inhibits the autophagic flux (p62, LC3IIβ). Increased XBP-1s expression might contribute to the enhanced TMZ sensitivity. This combination therapy is promising for TMZ-resistant cancers, but it needs further investigation.

EXCLI Journal - Experimental and Clinical Sciences, International Online Journal for Advances in Sciences

Cuproptosis is a new mode of cell death that is closely related to mitochondrial stress. The purpose of this study is to investigate the amount of copper, copper-associated genes DLAT and FDX1 oxidative stress (OS) status in obesity. Since there is a close relationship between OS and cuproptosis, evaluating the effect of various strategies to reduce OS, including quercetin (QUER) and caloric restriction (CR), is another goal of this study. In this study, 30 male BALB-C mice aged 8 weeks and weighing 25 g, including the groups receiving normal diet (ND), ND with QUER (15 mg/kg, IP) and CR, a high-fat diet (HFD) with the QUER, CR or a combination of both were used. The activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX), and glutathione reductase (GR), amount of copper in the liver and kidney tissues, and expression of DLAT and FDX1 genes were measured in all studied groups. The amount of copper in the liver and kidney tissue as well as the expression of FDX1 and DLAT in the HFD group increased significantly compared with the ND group. QUER, CR or their combination could significantly reduce the amount of copper as well as the expression of FDX1 and DLAT in liver and kidney tissues. QUER and CR, also significantly increased the activity of GR, SOD and GPX in serum, liver, and kidney tissues. Based on the results, QUER, CR and especially the simultaneous use of both, was able to reduce the amount of copper and its related cuproptosis. These effects may reduce cuproptosis-associated cell death. Therefore, the use of antioxidants and CR may be a promising solution to protect the human body against the effects of cuproptosis in conditions like obesity.

Breast cancer (BC) is a significant contributor to cancer-related deaths in women, and it has complex connections with obesity and aging. This review explores the interaction between obesity and aging in relation to the development and progression of BC, focusing on the controlling role of microRNAs (miRNAs). Obesity, characterized by excess adipose tissue, contributes to a proinflammatory environment and metabolic dysregulation, which are important in tumor development. Aging, associated with cellular senescence and systemic changes, further exacerbates these conditions. miRNAs, small noncoding RNAs that regulate gene expression, play key roles in these processes, impacting pathways involved in cell proliferation, apoptosis, and cancer metastasis, either as tumor suppressors or oncogenes. Importantly, specific miRNAs are implicated in mediating the impact of obesity and aging on BC. Exploring the regulatory networks controlled by miRNAs provides valuable information on new targets for therapy and predictive markers, demonstrating the potential for using miRNA-based interventions to treat BC in obese and elderly individuals. This review emphasizes the importance of integrated research strategies to understand the complex connections between obesity, aging, and miRNA regulation in BC.

Background: Aging is caused by the progressive accumulation of various changes in the body, which is associated with an increase in free radicals and oxidative stress (OS). The aim of this study was to investigate the potential of caloric restriction (CR) and quercetin (QUER) in alleviating OS in aging and the involvement of the NAD (P) H quinone oxidoreductase 1 (NQO1)/SIRT1 signaling pathway in these effects. Methods: Two age groups of male Wistar rats (eight and 20 weeks of age) were included in the study and subdivided into normal diet (ND), ND with QUER (15 mg Kg^-1, IP), ND with CR, and ND with QUER and CR groups. The activities of catalase (CAT), paraoxonase (PON1), liver enzymes and lipid profiles, and the expression of SIRT1 and NQO1 genes were analyzed using the desired methods. Results: We showed higher liver enzymes (aspartate aminotransferase [AST], alanine transaminase [ALT], and alkaline phosphatase [ALP]), increased atherogenic lipids, and reduced PON1 activity in 20-week-old rats compared with eight-week-old rats, and the administration of QUER and CR restored these values to the normal range. The expression of NQO1 and SIRT1 is also affected by CR and QUER. CR alone and in combination with QUER significantly raised the expression of the NQO1 and SIRT1 genes. This effect was notable in SIRT1. Conclusions: QUER and CR together improved the detrimental effects of aging by modulating antioxidant signaling pathways, suggesting this combination is a complementary therapeutic regime for aging and age-related diseases.

The structural and functional disorders of the testis and ovary are one of the main complications of hyperglycemia. Betaine is a trimethyl glycine with antioxidant, antidiabetic, and anti‐inflammatory potential. The aim of this study is to investigate the potential of betaine on the expression of aging and oxidative stress markers in ovarian and testicular cells under hyperglycemic conditions. Testicular and ovarian cells were subjected to four different conditions, including normal glucose and hyperglycemia, with or without betaine (5 mM). The cells with hyperglycemia saw an increase in malondialdehyde (MDA), methylglyoxal (MGO), expression of a receptor for AGE, and aging‐related genes (β‐GAL), and a decrease in the activity of antioxidant enzymes including catalase, glutathione peroxidase, and superoxide dismutase. The treatment with betaine, in contrast, decreased the amount of MGO and MDA, and also downregulated aging‐related signaling. Although hyperglycemia induces senescence in testicular and ovarian cells, the use of betaine may have a protective effect against the cell senescence, which may be useful in the management of infertility.

Ackground and Objective: Bisphenol A [BPA; 2,2-bis-(4 hydroxyphenyl) propane] is an environmental estrogenic and endocrine-disrupting compound that exerts its destructive effects through increasing oxidative stress, but the mechanisms underlying this effect have not yet been fully explained. This study evaluates BPA toxicity in muscle cells and the therapeutic potential of adiponectin ...

Cutaneous leishmaniasis is a major health problem in several parts of the world. However, existing drugs have various therapeutic effects on different Leishmania species and also cause many side effects. This study focuses on the use of the aqueous extract of quercetin in producing silver nanoparticles for the experimental treatment of cutaneous leishmaniasis in laboratory mice. Silver nanoparticles (AgNPs) were synthesized using quercetin and characterized by UV-Vis spectroscopy, DLS, FTIR, and FESEM. We investigated the antileishmanial activity of green synthesized AgNPs in vitro and in vivo. Synthesized AgNPs from quercetin macromolecules showed promising antileishmanial activity at an IC50 of 125 μg/ml against promastigotes in vitro. In the in vivo study, L. major-infected BALB/c mice were treated topically with luteolin/quercetin-capped silver nanoparticle (AgNPQct) ointment for 21 consecutive days. As a result, this ointment reduced the inflammatory response compared to the untreated group ( < 0.05). The size of lesions in the luteolin/AgNPQct group showed a slight increase compared to other groups ( < 0.01). Biogenic silver nanoparticles along with the luteolin macromolecule can be an effective and reliable candidate for the design of antileishmanial drugs in the future.