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Background: This study aimed to investigate the combined effects of resveratrol (RES) and saroglitazar (SARO) on a high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in a rat model. Methods: In this animal study, rats were treated with RES, SARO, or a combination of both. Male rats were fed with an HFD to induce nonalcoholic steatohepatitis (NASH) and then divided into 4 groups: RES treatment, SARO treatment, combined RES and SARO treatment, and no treatment. Various parameters were measured, including body and liver weight, liver enzymes, gene expression of inflammatory markers and reactive oxygen species (ROS), protein expression levels of transforming growth factor-beta (TGF-β) and p-Smad3, and liver histology. Results: The combination of RES and SARO significantly reduced blood and hepatic lipids, attenuated weight gain, and decreased inflammatory cytokine production in a NAFLD study. The combination diminished hepatic lipid accumulation, oxidative stress, and TGF-β1 expression, suggesting antifibrotic effects. Histological evaluations showed antisteatotic and antifibrotic outcomes of the combined treatment. Improved glycemic index, blood lipids, and reduced NASH indicators (i.e., aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) were observed after 6 weeks. The treatment also decreased ROS and NOX family expression, lessening oxidative stress. The inhibition of the TGF-β-Smad3 pathway in HFD-induced rats resulted in reduced NASH(P< 0.05). Conclusions: The results indicated that the group receiving the combination of RES and SARO showed a more efficient reduction in fibrosis and steatosis in the NASH model induced by an HFD than the groups receiving RES or SARO alone. [ABSTRACT FROM AUTHOR]

Background: Since breast cancer is the most common type of cancer in women around theworld, finding newbiomarkers for early diagnosis of breast cancer is invaluable. Objectives: This research assessed them RNA expression of triggering receptors expressed onmyeloid cell 2 (TREM2) and tandem C2 domains nuclear protein (TC2N) genes among Iranian patients with breast cancer. Methods: We acquired 50 samples of cancerous breast tumors and corresponding adjacent non-cancerous tissues from Iranian women. The gene expression of TREM2 and TC2N wasmeasured by quantitative real-time polymerase chain reaction (q-RT-PCR). In addition, the association between TREM2 and TC2N levels with various clinicopathologic characteristics was also investigated. Results: The increased levels of TREM2 and TC2NmRNAs were shown in breast cancerous tissues in comparison with adjacent non-cancerous tissues (P < 0.05). Among the clinicopathological characteristics evaluated, tumor size, necrosis, and lymphatic tissue invasionwere significantly associatedwith high TREM2 expression. A significant relationship was also seen between increased TC2N expression and tumor grade. Sensitivity and specificity were shown at 84% and 94%, respectively, for TREM2 and 72% and 100% for TC2N. Conclusions: The data suggest that TREM2 expression, but not TC2N, could be a suitable biomarker for breast cancer diagnosis. [ABSTRACT FROM AUTHOR]

Objective: Breast cancer is the leading cause of death among women in many countries. Numerous factors serve as oncogenes or tumor suppressors in breast cancer. The large family of Tripartite-motif (TRIM) proteins with ~ 80 members has drawn attention for their role in cancer. TRIM3 and TRIM16 have shown suppressive activity in different cancers. This study aimed to evaluate the expression of TRIM3 and TRIM16 in cancerous and normal breast samples and to investigate their association with different clinical and pathological parameters. Results: qRT-PCR was utilized to determine the gene expression of TRIM3 and TRIM16. The expression of TRIM3 and TRIM16 genes in tumor samples were significantly reduced to 0.45 and 0.29 fold, respectively. TRIM3 and TRIM16 genes expression were both positively correlated with the invasion of breast cancer. TRIM3 gene expression was associated with tumors' histological grade. However, no significant association was found between the expression of the genes and tumor size, stage and necrosis. The expression of TRIM3 and TRIM16 are significantly reduced in breast cancer tissues. Besides, the expression of both TRIM3 and TRIM16 genes significantly plummet in lymphatic/vascular and perineural invasive samples. Hence, we suggest a potential tumor suppressor role for TRIM3 and TRIM16 in breast cancer. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis provides the oxygen and nutrients needed for metastasis and tumor growth, so by inhibiting angiogenesis, metastasis to other parts of the body can be prevented at the first steps of cancer. 5-Fluorouracil (5-FU) as a common chemotherapy drug and Quercetin as a natural compound both have anti-angiogenic properties. Objectives: In the current study improvement of the anti-angiogenic property of 5-FU by combination with quercetin was investigated. Methods: After treating the cells with alone or a combination of drugs the angiogenesis, vascular endothelial growth factor receptors (VEGFRs) gene expression, migration, and viability of the cells were evaluated using chicken chorioallantoic membrane (CAM) assay, real-time RT-PCR, wound healing and MTT assay, respectively. Results: Treatment with alone 5-FU and Que led to a significant reduction in angiogenesis, VEGFR2 and VEGFR1gene expression, migration, and Cell viability. The reductions were significant in the combination state compared to alone treatment. Conclusions: The results showed that the combination treatment with Que with 5-FU enhances the anti-angiogenic property of 5-FU, so it can be proposed as a potential anti-angiogenic and as a result anti-metastatic treatment for future animal studies. [ABSTRACT FROM AUTHOR]

Background: Cancer cell metastasis is facilitated by matrix-metalloproteinases through degradation of extracellular matrix (ECM) proteins and is a major cause of mortality. One of the most common remedies for cancer is chemotherapy, which has many side effects. Therefore, it seems necessary to find a way to reduce the side effects of these drugs while maintaining their anticancer effects. Quercetin (que) is a natural substance that has been reported to have anticancer activities. Objectives: This study aims at evaluating the effect of que in combination with doxorubicin (dox) on the migration of the MDA-MB-231 breast cancer cell line. Methods: The effects of que and dox on cell viability in 24h and 48 h was assessed by MTT assay. Also, the effects of the same drugs on the cancer cells migration were evaluated, using the wound healing assay. Lastly, the effects of que and dox were assessed on the expression of MMP-2 and MMP-9 genes. Results: The combination of 50 µMof que with 32 nM of dox was selected by CI comparison. The viability and migration of cancer cells and the gelatinases genes expression were decreased after treatment with individual drugs. The migration and the expression of MMP-2 and MMP-9 genes after treatment with the combination of que and dox was significantly reduced compared to the treatment with que and dox alone. Conclusions: Que inhibits the viability and migration of MDA-MB-231 cancer cells and synergistically enhances the effects of dox on the survival and migration of these cells. Hence, we propose this drug combination as a path for further research on breast cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Cyrtopodion scabrum is a kind of lizard, widely distributed in southwestern, central, and eastern Iran. In our previous studies, we showed the selective anticancer properties of Cyrtopodion scabrum extract (CSE) against certain gastrointestinal cancer cell lines with no significant harmful effects on the normal cells. Method: This in vitro study was conducted to investigate the mechanism of action of CSE in SW742 (colon cancer cell line) using western blotting, real-time polymerase chain reaction (PCR), and PI staining/flow cytometry analysis. Results: Western blot analysis showed that CSE upregulates P53 protein expression significantly in SW742 cancer cell line, while QRT-PCR results revealed that P53 mRNA did not increase accordingly. It is proposed that TP53 protein play its role as a tumor suppressor through the protein stability mechanism and not through the increase in the gene expression. Considering this fact, for TP53 stabilization, two of its target genes, p21 and mdm2, were regulated. We evaluated the mRNA expression of these two genes as well. The obtained data showed a significant increase in both genes by CSE (1000 μg/ml), suggesting that the induction of G2 cell cycle arrest, which we previously reported, may happen through P53 and P21over-expression. No significant decrease was observed in apoptosis when SW742 cells were co-treated with CSE and the inhibitor of P53 transcriptional activity, (PFT)-α, indicating that the induction of apoptosis with CSE did not occur through P53-dependent transcriptional activity. Conclusion: The obtained results herein revealed that the observed anticancer effect of CSE may occur through TP53 upregulation, yet with P53-independent transcriptional activity. [ABSTRACT FROM AUTHOR]

Background: Activated hepatic stellate cells (HSC) through the TGF-β signaling pathway are likely to exacerbate liver fibrosis, which is a later stage of NASH, a condition in which, in addition to HSC activation, the overexpression of extracellular matrix(ECM) proteins, specifically collagen-I a and a-SMA, is expected. MicroRNA-126a, a modulator of HSC activation, influences the phosphorylation of Smad2/3. Objectives: This study aimed to investigate the impact of exosomes on miRNAs implicated in the progression of liver fibrosis by focusing on the role of miR-126a in the HSC-T6 cell line. Methods: In the present study, we investigated the effects of exosomes derived from LPS-stimulated mesenchymal stem cells (MSCs) on the expression of miR-126a and the phosphorylation of Smad3c in the HSC-T6 cell line. First, HSC-T6 cells were cultured in DMEM supplemented with 10% FBS. Next, we isolated exosomes derived from MSCs using the ExoCib kit. Finally, we examined the gene expression levels of collagen-Ia, a-SMA, and miR-126a using real-time PCR. Results: The results showed that treatment with TGFβ1 increased the phosphorylation of p-Smad3c (P < 0.0001), as well as the expression of a-SMA and Collagen-Ia. Conversely, miR-126a expression was down-regulated after treatment with TGFβ1 (P < 0.01). However, exposure to LPS-treated MSC-derived exosomes resulted in a significant decrease in the levels of p-Smad3c phosphorylation (P < 0.001) and the gene expression of a-SMA and Collagen-Ia, accompanied by the up-regulation of miR-126a (P < 0.05). Conclusions: Based on our observations, MSCs-derived exosomes were able to reduce the expression of the genes associated with hepatic fibrosis, suchas collagen-Ia and a-SMA. Furthermore, exosomes inhibited Smad3c phosphorylation by increasing miR-126a expression, ultimately hindering the progression of liver fibrosis. Therefore, exosomes should be recognized as a valuable and beneficial therapeutic tool for liver fibrosis. [ABSTRACT FROM AUTHOR]

Background: Hepatocellularcarcinoma(HCC)isthe most common type of liver cancer worldwide. The current remedies for cancer, including chemotherapy and radiation therapy, might damage patients' organs, sometimes causing death. Etoposide (ETO), as a widely used chemo-drug, possesses the same problems. For years, combinational therapy has been considered a potential adjustor for common treatments, alleviating their side effects. Quercetin (Que), a phytochemical drug, has been used due to its potential against cancer. Objectives: This study explored whether synergy occurs between Que and ETO on the apoptosis of HepG2 HCC cells or not. Methods: The impacts of the drugs on cell growth were assessed through the MTT assay. The apoptotic death rates of treated cells were examined through Annexin/PI double staining and caspase-9 and caspase-3 activities. The relative expression of B-cell lymphoma 2 (Bcl-2) associated X-protein (Bax), and Bcl-2 genes and proteins were analyzed using quantitative reverse transcription polymerase chain reaction and western blot analysis. Additionally, the levels of p53 protein were determined. Results: Both Que and ETO reduced the cell viability and increased apoptotic rates, caspases activities, Baxgene and protein expression, and the p53 protein levels of HepG2 cells. The combination of Que and ETO showed apparent synergy in terms of cell growth and cell apoptosis. Que significantly enhanced the effects of ETO on caspase activities, Bax and Bcl-2 genes' expression, and p53 protein levels. Conclusions: The obtained results demonstrated that Que showed synergy when co-treated with ETO on HepG2 cells. Therefore, it is concluded that further studies on the aforementioned combination could lead to a potential anticancer compound against HCC. [ABSTRACT FROM AUTHOR]

Background: Iranian borage, Echium amoenum, is believed to improve reproduction according to folk medicine. Although E. amoenum distillate known as "Aragh Gav-zaban" is widely consumed as a safe and natural remedy, its possible effects on fertility have not yet been scientifically examined. The present study aimed to investigate the effects of borage distillate (BD) on reproductive parameters of male mice. Methods: In this experimental study, 30 adult male Mus musculus mice (30-35 g) were equally divided into three groups. The control group received distilled water (DW) for five weeks and the other two groups, BD1/2 and BD1/4, received borage distillate of 1/2 dilution (150±2.5 ml/kg/day) and 1/4 dilution (75±1.25 ml/kg/day), respectively, ad libitum for three weeks and DW for 2 weeks. On the day 35, mice were sacrificed, sperm analysis was performed, and sera were collected to evaluate gonadotropins, testosterone, and toxicity parameters. The left testis was excised for stereological study and the right testis was used to evaluate androgen receptor (AR) gene expression. Results: The administration of BD1/2 significantly increased serum FSH (P=0.004), LH (P=0.025), testosterone (P=0.014), the percentage of motile (P=0.011); slow progressive (P=0.001), coiled tail (P<0.001) sperms, and the number of Leydig cells (P=0.008) compared to the control group. Treatment with BD1/4 significantly increased sperm count (P=0.044) and motile sperms percentage (P=0.040) compared to the control group too. The administration of BD revealed no significant effects on toxicity parameters and AR gene expression. Conclusion: The findings of the present study showed that the consumption of borage distillate, as a safe herbal remedy, improves hormonal and sperm parameters in male mice. [ABSTRACT FROM AUTHOR]