Elham Karimi-Sales

Human ovarian cancer is a highly aggressive malignancy in women, characterized by high mortality and poor prognosis. Dysregulation of microRNAs (miRNAs) plays a critical role in the pathogenesis of various cancers, including ovarian cancer. Among these, miR-34a functions as a tumor suppressor miRNA and represents a promising target for cancer therapy. Downregulation of miR-34a in ovarian cancer has been associated with disease initiation and progression. Sericin, a silk-derived glycoprotein, possesses diverse biological activities, including antioxidant, anti-inflammatory, and anticancer properties. The present study, for the first time, investigated the potential effects of sericin on miR-34a-mediated apoptotic pathways in the human ovarian cancer cell line OVCAR3. OVCAR3 cells were treated with sericin at concentrations of 2 mg/mL and 64 mg/mL for 48 h. The expression level of miR-34a was quantified using real-time quantitative PCR (qPCR), while the protein expression levels of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) and the pro-apoptotic protein Bcl-2–associated X protein (BAX) were evaluated by Western blot analysis. Sericin treatment at both 2 mg/mL and 64 mg/mL significantly upregulated miR-34a expression and increased BAX protein levels in OVCAR3 cells. Moreover, sericin at 64 mg/mL markedly decreased Bcl-2 protein expression. Given the central role of Bcl-2 in conferring resistance to anticancer therapies and the importance of apoptosis dysregulation in tumor progression and therapeutic resistance, these findings suggest sericin as a promising anticancer agent. In summary, the results indicate that sericin exerts its anticancer effect, at least in part, through activation of a miR-34a-dependent apoptotic pathway.

Background. Autophagy is responsible for maintaining cellular homeostasis by degrading and recycling macromolecules and unwanted intracellular components, such as damaged organelles. Trans-chalcone is a compound with anti-cancer and anti-inflammatory properties. However, its impact on autophagy in lung tissue has not been investigated yet. Therefore, this study evaluated the effects of trans-chalcone on autophagy-related Gene Expressions in the lung. Methods. Twelve male rats were randomly divided into control and chalcone groups. In the control group, rats were orally gavaged with Tween 80(10%), while in the chalcone group, rats were orally gavaged with trans-chalcone once a day for six weeks. Blood and lung samples were collected from overnight fasted rats. Serum insulin and glucose levels were used to estimate the fasting glucose-to-insulin ratio. Further, a real-time polymerase chain reaction was performed to assess the levels of p62, LC3, and Beclin-1 gene expression in the lungs of rats. Results. Trans-chalcone significantly increased the fasting glucose-to-insulin ratio (insulin sensitivity). In addition, this compound significantly increased Beclin-1 mRNA expression levels and decreased p62 expression levels in the lungs of rats. Nevertheless, the upregulatory effect of this compound on LC3 expression was not statistically significant. Conclusion. Based on the findings, trans-chalcone increases insulin sensitivity and has a regulatory effect on autophagy in the lungs of healthy rats. Changes in Beclin-1 and p62 mRNA levels reflect this issue. Practical Implications. The ability of trans-chalcone to up-regulate Beclin-1, a key marker of autophagy, and down-regulate p62 mRNA expression indicates its regulatory effect on autophagy. Further studies are required to validate the potential of this chalcone as a promising treatment for autophagy-related lung diseases.

Background. High-fat diet (HFD) intake is linked to ectopic fat deposition in the pancreas. It also causes pancreatic inflammatory lesions. trans-Chalcone is a simple chalcone with protective effects against HFD-induced metabolic disorders. This study, for the first time, explored the possible effects of this chalcone on high-fat emulsion-induced pancreatic abnormalities in rats. Methods. Twenty-one male rats were randomly assigned into three groups: control (received 10% tween 80); HFD (received high-fat emulsion + 10% tween 80); and HFD + chalcone (received high-fat emulsion + trans-chalcone). Real-time PCR was used to assess pancreatic mRNA expression levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor α (TNF-α) in the pancreas of all rats. Results. High-fat emulsion increased the mRNA expression levels of inflammatory biomarkers, including TNF-α and MCP-1 in the pancreas of rats, and treatment with trans-chalcone prevented these high-fat emulsion-induced changes. Conclusion. trans-Chalcone can protect the pancreas of male rats against HFD-induced abnormalities through its anti-inflammatory effects. Practical Implications. It seems that consumption of HFD up-regulates the production of inflammatory mediators in the pancreas. On the other hand, trans-chalcone can ameliorate HFD-related pancreatic inflammation.

Purpose: Non-alcoholic steatohepatitis (NASH) is an inflammatory disorder and an aggressive form of fatty liver disease. Certain microRNAs, including miR-122, 21, 34a, and 451, are involved in the transition from steatosis to NASH. This study examined how trans-chalcone (the core of chalcone derivatives) affects NAFLD progression by regulating miRNAs. Methods: Male rats were divided into three groups (n = 7/group) as follows: control, rats were gavaged with 10% tween 80 (for two weeks); NASH, rats were gavaged with a high-fat liquid diet (HFD; for six weeks) and 10% tween 80 (for two weeks); NASH + Chal, rats were gavaged with the HFD (for six weeks) and trans-chalcone (for two weeks). Hepatic expression levels of miR-122, 21, 34a, and 451 were determined. Results: trans-Chalcone reversed histological abnormalities, reduced liver injury markers, and attenuated insulin resistance in HFD-fed rats. In the liver, HFD-induced NASH increased the expression level of miR-34a and decreased expression levels of miR-122, 21, and 451. However, trans-chalcone inhibited HFD-induced changes in expression levels of these miRNAs. Conclusion: trans-Chalcone could inhibit the transition from steatosis to NASH through the modulation of miR-122, 21, 34a, and 451 expression levels in the liver.

High‐fat diet (HFD) intake is linked to chronic kidney disease. Farnesoid X receptor (FXR) controls the renal lipid metabolism and fibrosis. The purpose of the current study was to evaluate the possible impacts of trans‐chalcone on HFD‐induced changes in renal lipid metabolism and Smad‐3 expression through the regulation of FXR expression. To this aim, 28 rats were randomly divided into control, chalcone, HFD, and HFD + chalcone groups. At the end of treatments, renal FXR, sterol regulatory element‐binding protein (SREBP)‐1c, fatty acid synthase (FAS), Smad‐3, and neutrophil gelatinase‐associated lipocalin (NGAL) expression levels were assayed. Moreover, insulin sensitivity check index (QUICKI) was calculated. trans‐Chalcone significantly inhibited HFD‐induced reduction of insulin sensitivity. Moreover, HFD decreased the FXR expression, and trans‐chalcone reversed this change. trans‐Chalcone also inhibited HFD‐induced increases in expression levels of SREBP‐1c, FAS, Smad‐3, and NGAL. Therefore, trans‐chalcone, as a renoprotective agent, inhibits HFD‐induced disturbances in FXR/SREBP‐1c/FAS and FXR/Smad‐3 pathways. Practical applications Non‐alcoholic fatty liver disease and metabolic syndrome, two health concerns with increasing prevalence, are known as important risk factors for chronic kidney disease. The current study indicated the preventive effect of trans‐chalcone administration on HFD‐induced disturbances in renal FXR/SREBP‐1c/FAS and FXR/Smad‐3 pathways. According to these results, trans‐chalcone can be regarded as a renoprotective functional food component that can protect individuals with metabolic syndrome against chronic renal disease.

Objective: Hypoxia is the main stimulus for angiogenesis. Hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), and miR-210 are involved in the hypoxia-induced angiogenesis. This study examined the effects of hypoxia and/or ghrelin on miR-210, HIF-1α, and VEGF levels in the heart of rats. Methods: Wistar rats were randomly divided into 4 groups (n = 6): control; ghrelin, received daily intraperitoneal injections of ghrelin; hypoxia, was exposed to hypoxic condition; hypoxia + ghrelin, was exposed to hypoxic condition and received intraperitoneal injections of ghrelin, for 2 weeks. Myocardial angiogenesis, the expression level of miR-210, and protein levels of HIF-1α and VEGF were assayed in the heart samples. Results: Hypoxia increased myocardial angiogenesis and cardiac levels of miR-210, HIF-1α, and VEGF. However, ghrelin inhibited these hypoxia-induced changes. Interestingly, ghrelin had no significant effect on miR-210, HIF-1α, and VEGF levels in normoxic condition. Conclusion: Ghrelin may be useful as an anti-angiogenic factor.

High-fat diet (HFD) increases the risk of non-communicable inflammatory diseases including pulmonary disorders. Trans-chalcone is a chalcone with antioxidant and anti-inflammatory effects. This study aimed to explore the effect of this natural compound and molecular mechanism of its effect on HFD-induced pulmonary inflammation. Twenty-eight male Wistar rats were randomly divided into four main groups (n = 7 per each group): control, receiving 10% tween 80; Chal, receiving trans-chalcone, HFD, receiving a high-fat emulsion and 10% tween 80; HFD + Chal, receiving a high-fat emulsion and trans-chalcone. After 6 weeks, the lungs were dissected, and the expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and miR-146a were determined using real-time PCR. Moreover, histological analysis was done by hematoxylin and eosin staining. Significant elevations in TNF-α, IL-1β, IL-6, and miR-146a expression levels (P < 0.001) were observed within the lungs of HFD-fed rats compared with the control. However, oral administration of trans-chalcone reduced TNF-α, IL-1β, IL-6 (P < 0.001), and miR-146a (P < 0.05) expression levels and also improved HFD-induced histological abnormalities. These findings indicate that trans-chalcone ameliorates lung inflammatory response and structural alterations. It seems that this beneficial effect is associated with the down-regulation of pro-inflammatory cytokines and miR-146a.