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Hyperglycemia during the first trimester leads to an increased risk of innate malformations as well as death at times close to delivery dates. The methylated genes include those from paternal H19 and PEG3 and those from maternal MEST and MEG3 that are necessary for the growth and regulation of the human fetus and its placenta. The aim of this study was to evaluate and compare the expression of these genes in the cord blood of healthy infants born to mothers with gestational diabetes mellitus (GDM) and healthy mothers.This case-control study was conducted on the cord blood of 40 infants born to mothers with GDM and 35 infants born to healthy mothers. Mothers were identified by measuring oral glucose tolerance in the 24th–26th week of pregnancy. Cord blood was obtained post-delivery, and cord blood mononuclear cells were immediately extracted, using Ficoll solution. Then, RNA extraction and cDNA synthesis were performed, and gene expression of MEG3, PEG3, H19, and MEST was assessed through quantitative real-time PCR.Findings show that the expression levels of MEG3, PEG3, H19, and MEST genes were significantly decreased in mononuclear cord blood cells of infants born to mothers with GDM when compared to those of the healthy control group.These findings reveal that the reduction of imprinted genes in mothers with GDM is most likely due to changes in their methylation by an epigenetic process. Considering the importance of GDM due to its high prevalence and its side effects both for mother and fetus, recognizing their exact mechanisms is of high importance. This has to be studied more widely.

Aims: The aim of the present study was to assess and compare the effect of different methods of cooking on B-group vitamins (B1, B2, and B6), As, Cd, Ni, Pb, and some essential elements (Cu, Co, and Mn) in the main local varieties of Iranian rice. Background: Different cooking procedures have been shown to have contradictory benefits in terms of nutritional value by affecting the bioavailability of vitamins and microminerals. Objective: The aim of the present study was to assess and compare the effect of different methods of cooking on B-group vitamins (B1, B2 and B6), As, Cd, Ni, Pb, and some essential elements (Cu, Co, and Mn) in the main local varieties of Iranian rice. Method: The effectiveness of different cooking procedures, including direct cooking (Dampokht) and cooking by washing the rice with water and draining off the water (Abkesh), on B1, B2, and B6 vitamins contents and Cd, As, Pb, Ni, Cu, Co, Mn elements in the different local varieties of Iranian rice was evaluated. For the Dampokht method, the non-rinsed cooked samples were directly used for evaluation, but for the Abkesh method, the cooked rice samples were first rinsed and then evaluated. Results: Generally, our results showed decreased levels of vitamins and trace elements in cooking with the Abkesh method in comparison to that of Dampokht. Interestingly, the amount of B1 vitamin increased after the Dampokht method. Conclusion: The results indicate that the rice cooking procedure is very important in the maintenance of B vitamins and trace elements in the foodstuff, and the Abkesh method leads to the loss of a great deal of water-soluble vitamins and essential elements. However, it is good for decreasing poisonous heavy metals and should be recommended for populations that consume rice as the main staple food and who live in the areas with a high level of toxic heavy metals in drinking water.

Background and objectives: Quercetin is a naturally occurring phenolic compound abundantly present in plants as a secondary metabolite. The purpose of this study was to investigate the effect of quercetin on improving RINm5F β-insulinemia cell viability, glucose-stimulated insulin secretion (GSIS), and cell insulin content in the presence or absence of streptozotocin (STZ). Methods: This experimental study was conducted on RINm5F β-insulinemia cell line. The cell viability was evaluated by MTT assay. The necrosis was confirmed by flowcytometry and insulin ELISA kit was used to measure the GSIS level and cell insulin content. It should be noted that for testing of cells by 50μM of quercetin, simultaneous treatment and pre-treatment of quercetin were performed in the presence of STZ (20mM). Results: The quercetin was able to improve the viability of RINm5F cells in the presence of STZ and to increase the GSIS level and cell insulin content under STZ and glucotoxic conditions Conclusion: The quercetin seems to have beneficial effects on β-cells, especially the synthesis and secretion of insulin. In addition to the therapeutic effect, given the low toxicity of this flavonoid and the results of this study, the quercetin as a preventive agent may play an important role in maintaining the health of β-cells in people at risk of diabetes.

Background: Morphine independent reduces the expression level of Brain-derived Neurotrophic Factor (BDNF) and Cyclic-AMP Response Element Binding protein (CREB). BDNF and CREB play a vital role in protecting and regulating the proper functioning of neurons. There has not been any study on the effect of methadone maintenance treatment and its comparison with morphine. Therefore, this study was conducted to examine the effect of methadone maintenance on the expression of BDNF and CREB genes in brain VTA of male morphine treated rats Methods: I Morphine independent reduces the expression level of Brain-derived Neurotrophic Factor (BDNF) and Cyclic-AMP Response Element Binding protein (CREB). BDNF and CREB play a vital role in protecting and regulating the proper functioning of neurons. There has not been any study on the effect of methadone maintenance treatment and its comparison with morphine. Therefore, this study was conducted to examine the effect of methadone maintenance on the expression of BDNF and CREB genes in brain VTA of male morphine treated rats Results: According to the findings of this study, similar to morphine treated group, methadone maintenance in morphine treated animals led to significant reduction in the expression of BDNF and CREB genes at VTA as well as BDNF serum level compared with control group. Conclusion: It was concluded that methadone, like morphine, causes significant reduction in the expression of BDNF and CREB genes in brain VTA area of rat as well as BDNF serum level compared with control group.

Objective: The present study aims to examine the effects of nisin on the survival and apoptosis of the hepatoma cell line HepG2 and to investigate possible apoptosis pathways activated by nisin. Materials and methods: For this purpose, viability and apoptosis of the cells were accomplished by the nisin treatment using the MTT assay and Annexin-V-fluorescein/propidium iodide (PI) double staining, respectively. Additionally, the human apoptosis PCR array was performed to determine pathways or genes activated by nisin during possible apoptosis. Results: The results of the present study showed that nisin was able to decrease cell viability (IC50 ~ 40 µg/ml) in a dose-dependent manner and could induce apoptosis in HepG2 cells. PCR data indicated a considerable increase in the expression of genes, such as caspase and BCL2 families, involved in the induction of apoptosis. Conclusions: The data from this study showed that overexpression of genes involved in the intrinsic pathway of apoptosis, especially caspase-9 and BID, increased apoptosis in HepG2 cells treated by nisin, compared to the control group.

Background and Objective: Orlistat drug is one of the most criticalanti-obesity drugs that widely used around the world. The aim of this study was evaluation the effect of orlistat on the expression of OCT4, Nanog, SOX2, and KLF4 genes in the colorectal cancer SW40 cell line. Materials and Methods: SW40 cell line was cultured in DMEM medium contained orlistat for 24h, and cell viability was assessed by MTT assay. The fold changes of expression of OCT4, NANOG, KLF4, and SOX2 at mRNA level against β-actin were determined by real-timePCR. Two-sample t-test and one-way ANOVA were used to compare the mean of expression of different genes in different groups and different concentrations; a significant level of 0.05 was considered in all tests. Results: Our results showed a significant difference in cell viability, when different doses of Orlistat were used for 24 hour. concentrations of 25 and 100 μM reduce significantly the expression of OCT4 (p

Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disease in which the immune system abnormally reacts against cells and tissues leading to inflammation. Epigenetic alterations, including DNA methylation and histone modification, have critical effects on autoimmune disease and SLE pathogenesis via dysregulation of critical genes. Aims: The purpose of this study was to evaluate the epigenetic-related gene expression of DNA methyltransferase (DNMT) and Histone Deacetylase 1 (HDAC1) in Iranian patients with SLE. Methods: This matched case-control study included 16 people with SLE and 16 healthy people who were referred to the Rafsanjan rheumatology clinic, in the southeast of Iran. The expression of DNMT and HDAC1 genes was measured through a Real-time PCR assay of blood samples. Results: DNMT gene expression did not differ significantly between SLE and healthy groups (P=0.21). In contrast, HDAC1 gene expression was enhanced in the SLE group, but this enhancement failed to reach statistical significance (P=0.94). Conclusion: The results of this study suggest that overexpression of HDAC1 could serve as a diagnostic for SLE disease. Additional studies with larger sample sizes are required to confirm our findings. Evaluation of other genes are related to SLE disease is essential and may help to form an accurate diagnosis of the disease.

Background : Metabolic syndrome (MetS) is a complex clinical disorder that can lead to an increase in oxidative stress. Patients with this syndrome are at risk of diabetes and cardiovascular disease. The Trigonella foenum-graecum L. (fenugreek) plant has many therapeutic effects, including anti-diabetic and antioxidant. The present study aimed to investigate the effects of the hydro-alcoholic extract of fenugreek seeds (HEFS) on dyslipidemia and oxidative stress due to high-fructose diet-induced MetS. Methods : In this experimental study, to induce MetS, animals received water containing 20% fructose for 8 weeks. After induction of MetS, 48 male Wistar rats (200-250 g) were randomized into six groups. HEFS was administered to animals at doses of 100 and 200 mg/kg orally for 4 weeks. Animal blood samples were collected to measure biochemical and antioxidant parameters of fasting plasma glucose (FPG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), malondialdehyde (MDA), glutathione peroxidase (GPX), catalase (CAT), and total antioxidant capacity (TAC). Results : The findings showed that the serum levels of FPG, TC, LDL-C, TG, and MDA were significantly reduced in HEFS-exposed groups compared with the control group (P

Introduction: Recently it has been shown that Astragalus fasciculifolius may be an effective remedy in the treatment of diabetes and wound healing. Current study was designed to examine the effects of topical administration of A. fasciculifolius (common name: sarcocolla) cream on treatment of wounds in streptozotocin-induced diabetic rats. Methods: A circle deep wound having 15-mm diameter was created on the back of 32 streptozotocin-induced diabetic rats. Thirty-two wounds were evaluated in four groups of animals (n = 8). The animals in first and second groups were treated using distilled water and petrolatum for 20 days, respectively. The third and fourth groups were treated using sarcocolla cream 5% and 10% for 20 days, respectively. The evaluation was performed in all groups on days 1, 3, 5, 7, 10, 14, 17 and 20. Results: The sarcocolla cream 5% and sarcocolla cream 10% exerted significant healing effects on diabetic rat wounds (PConclusion: Sarcocolla (topical) therapy is possibly a useful approach for wound healing in diabetic rats. More investigations are needed to elucidate the possible protective mechanisms and safety.

Objectives Alpha-1-antitrypsin (AAT) has different phenotypes. Evidence suggests that the abundance of each of these phenotypes may be associated with a disease. The purpose of this study was to evaluate the frequency of AAT phenotypes in patients with liver cirrhosis as well as in healthy individuals. Methods In this study, 42 patients with liver cirrhosis were selected. The results of the previous research done by the researcher on healthy individuals were used to construct the control group. After obtaining informed consent, 5 mL of fasting venous blood sample was taken, and phenotypes were analyzed by isoelectric focusing. Data were analyzed using Chi-square and Fisher’s exact tests at a significant level of 0.05. Results The results of this study indicated that all 42 healthy subjects had an MM allele (100%). However, among 42 patients, 35 (83.3%) had an MM allele, 5 (11.9%) had an MS allele, and 2 (4.8%) had MZ allele. The difference between the two groups was significant (p=0.02). There was no difference between men and women in the allele type (p=0.557). Conclusions This study revealed that MS and MZ alleles were observed only in patients with liver cirrhosis, and none of these alleles were found in healthy subjects. Therefore, MS and MZ alleles can be further investigated as risk factors for liver cirrhosis.

Recent advances have put fundamental focus on the application of copper (II) (Cu [II]) complexes as agents for fighting against cancer. To determine whether [Cu(L)(2imi)] complex as a novel Cu complex can induce apoptosis in HepG2 as cancerous cells and L929 as normal cells via extrinsic or intrinsic apoptotic pathways, both cell lines were treated for 24 and 48 hours at IC50 concentrations of [Cu(L)(2imi)] complex. Then, the expression of some apoptosis-related genes including p53, caspase-8, bcl-2, and bax were assayed by real-time polymerase chain reaction. The [Cu(L)(2imi)] complex seems to inhibit the expression of bcl-2 in complex-treated HepG2 cancerous cells following the 24- and 48-hour treatment. The complex upregulated the p53, bax, and caspase-8 genes, therefore treatment of HepG2 cancerous cells with [Cu(L)(2imi)] complex induces programmed cell death via the upregulation of relative bax/bcl-2 ratio. Finally, this copper complex triggered apoptosis in HepG2 cells via both intrinsic and extrinsic pathway, whereas treatment of normal L929 cells with this complex induce apoptosis only via intrinsic pathway with the upregulation of relative bax/bcl-2 ratio and does not affect the expression level of caspase-8 gene and does not trigger the extrinsic pathway. Finally, these results obtained from present study confirm the role of a novel Cu complex on the induction of apoptosis process in HepG2 and L929 cells by overexpression of bax, inhibition of bcl-2 and increase of the relative bax/bcl-2 ratio. These results support that the [Cu(L)(2imi)] complex is able to induce apoptosis in cancerous cells, therefore, it has a potential for development as a novel anticancer drug.

Aim and objectives: Natural products and derivatives of medicinal vegetation can play an important role to the cure tumor. The Present study was focused to determine the effect of Cornus mass L. extract on the induction of apoptosis in AGS gastric carcinoma cell line in compared to L929 cells. Methods: In this experimental study, AGS and L929 cells were cultured and treated with different concentrations (0–10 mg/ml) of Cornus mass L. extract for 48 and 72 hours. Cell proliferation was assessed by MTT assay. The optical density of the colored solution was quantified at 570 nm wavelengths by an ELISA Reader. Making use of the apoptosis detection kit of Annexin V-FITC, PI and double staining with Annexin V-FITC were carried out for flow cytometry investigations. Data were analyzed by ANOVA. Variations with a P-value less than 0.05 were considered significant. Results: shows a noticeable deviation among various concentrations of extract when cells were treated for 48, 72 h declined cell viability in AGS cell line in comparison L929 cell lines in a dose and time-dependent manner (P < 0.05). This extract also displayed approximately several-fold increased anti-cancer potency in AGS compared to L929 cells. The IC50 value in AGS cells (evaluated after 48,72h) of the extract against AGS cells was 5/44, 2/44 mg/ml (p≤0.05). The analysis results of flow cytometry indicated that apoptosis was induced by the extract in AGS cells treated, compared with L929 cells. Conclusion: Each of our results implicates the reality that Cornus mass L. extract acts as a novel, potent inhibitor of cancer proliferation in in vitro. This may result in developing a promising therapeutic agent for the treatment of indole-sensitive cancers.

The low solubility of the plant-extracted agent like D-limonene in cancer therapy is a critical problem. In this study, we prepared D-limonene-loaded niosomes (D-limonene/Nio) for cancer therapy through in vitro cytotoxicity assay of HepG2, MCF-7, and A549 cell lines. The niosomal formulation was prepared by film hydration technique with Span® 40: Tween® 40: cholesterol (35:35:30 molar ratio) and characterized for vesicle distribution size, morphology, entrapment efficiency (EE%), and in vitro release behaviour. The obtained niosomes showed a nanometric size and spherical morphology with EE% about 87 ± 1.8%. Remarkably prolonged release of D-limonene from niosomes compared to free D-limonene observed. The loaded formulation showed significantly enhanced cytotoxic activity with all three cancer cell lines (HepG2, Macf-7 and A549) at the concentration of 20 μM. These results indicated that niosome loaded with phytochemicals can be a promising nano-carrier for cancer therapy applications

Background: Previous studies have shown that several microRNAs (miRNAs) are dysregulated in the whole blood as well as diverse cells and tissues from rheumatoid arthritis (RA) patients. The aim of the current study was to determine if the expression of miR-146a, miR-103a, and miR-155 in whole blood of RA patients could confer potential markers in evaluating of activity-severity of the disease in RA patients with established disease. Methods: Whole blood samples were obtained from 30 RA patients and 30 healthy subjects. The RNA content of blood samples was isolated, cDNA was synthesized, and transcript levels of miR-146a, miR-103a, and miR-155 were determined using Real-time PCR. The clinicopathological characteristics of the patients were also evaluated. Results: It was detected that expression level of miR-146a (fold change=1.85, P=0.004), miR-103a (fold change=2.44, P=0.0018), and miR-155 (fold change=1.94, P=0.0025) were significantly upregulated in the whole blood samples of RA patients in comparison to that of healthy subjects. Expression level of miRNAs was correlated with clinicopathological characteristics of the patients, including Disease Activity Score 28 (DAS28), Simple Disease Activity Index (SDAI), 28Tender Joint Count (TJC-28), 28Swollen Joint Count (SJC-28), C-reactive protein (CRP), Rheumatoid factor (RF), and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Conclusions: Upregulated levels of miR-146a, miR-103a, and miR-155 in the whole blood samples of RA patients could confer a potential marker of activity-severity of the disease in RA patients with established disease.

Background and Aims: Previous studies have shown that adipose-derived mesenchymal stem/ stromal cells are one of the sources of mesenchymal stem cells (MSCs) with the capacity to differentiate into various mesodermal cell lineages. MSCs with cytokines secretion capability, which contributes to repair damaged tissues have gained wide credence for future cell-based therapeutic applications. In this study, the effect of the different dosages of vitamin E and Selenium was assessed on the stemness of the human adipose tissue-derived MSCs (AD-MSCs). Materials and Methods: Following 24 hours of cell treatments with different dosages of vitamin E and Selenium, MTT assay was used to assess the effect of them on cell proliferation. Moreover, the stemness of the AD-MSCs was assessed using osteogenic and adipogenic induction medium supplemented with the different dosages of the vitamin E and Selenium. Finally, Alizarin red and Oil-red O staining were performed to detect matrix mineralization and lipid droplet accumulation, respectively. Results: MTT data revealed that the optimal concentration for vitamin E and Selenium were 125 µM and 121 µM for the viability of the AD-MSCs. Moreover, the effect of vitamin E and Selenium were assessed by osteogenic and adipogenic differentiation by optimal dosages obtained by MTT assay, respectively. Maximum mineralization and lipid droplet aggregation of the differentiated cells were detected at IC50 in comparison with the control group. Conclusions: These results suggest that different dosages of vitamin E and Selenium could have various impacts on the proliferation and differentiation induction of human AD-MSCs.

OBJECTIVE: Diabetes mellitus (DM) is typically a disorder of carbohydrate, fat, and protein metabolism. It develops due to a lack of or loss associated with insulin and/or resistance to insulin. Regarding complications of chemical substance use, drugs with few complications and high-reliability tannins are needed. This study aimed to determine the effect and mechanism of action of Citrullus colocynthis extract on the formation of glycated hemoglobin (HbA1c). MATERIALS AND METHODS: A solution containing hemoglobin and glucose was incubated for 1, 2, 3, 4, 30, and 60 days by adding Citrullus colocynthis extract or glutathione. Quantitative measurement of HbA1c was performed using ion-exchange chromatography. Data were analyzed using ANOVA and two-way repeated measures test. A p

Natural convection in porous media (NCPM) is governed by highly nonlinear dynamics due to the dependence of fluid density and viscosity to temperature. Given the high computational cost associated with numerical modeling of NCPM, data-driven metamodels are commonly used to reduce the computational time in applications that require repetitive model runs. However, to various degrees, all metamodels previously used in this context struggle at scaling to high dimensional input and output problems. This work aims at investigating the performance of encoder-decoder convolutional neural networks (ED-CNNs), as a specialized deep learning architecture, in assisting the procedure of numerical modeling of NCPM. Our interest is directed to image-to-image regression tasks in which both the inputs and outputs of the model are high-dimensional, often high resolution, spatial distributions of the features. Large datasets of images (for e.g. heat map) can be generated by numerical modeling of NCPM, and also through high-resolution imaging and non-destructive scanning techniques. Hence, we apply ED-CNNs to develop a methodology for image-to-image regression. The goals are twofold: (1) to assess the robustness of ED-CNNs in metamodeling and uncertainty propagation analysis, and (2) to evaluate the performance of ED-CNNs as optimizer in input parameter estimation. To do so, we apply the ED-CNNs to the common benchmark of natural convection in a porous cavity. Numerical experiments highlight the robustness and efficiency of the ED-CNNs in handling heterogeneous domains.

Hepatocellular carcinoma (HCC) is a prevalent human malignancy which its drug resistance is increasing world-wide. This project was designed to assess the anti-cancer effects of 4-bromo-2-(((5-chloro-2-hydroxyphenyl) imino) methyl) phenol ([IV(L)] complex) on the HepG2 cell line and also L929 cells, as normal cells. HepG2 and L929 cells were cultured in RPMI culture medium and the survival rates of the cells were determined after 24 and 48 h using MTT assay to find IC50 concentration of vanadium m, [IV(L)] complex. The early apoptosis and necrosis/late apoptosis were determined by means of annexin V/PI apoptosis detection kit. The results revealed that vanadium m, [IV(L)] complex induce early apoptosis higher in HepG2 cell line than L929 cells. The rates of necrosis/late apoptosis were also induced in HepG2 cells more than L929 cells. Based on the results, vanadium m, [IV(L)] complex might be considered as a safe new drug for treatment of HCC with low side effects on control liver cells.

A variety of biological activities, such as anti-microbial and anti-tumor properties was reported for 1,10-phenanthroline and its copper complexes. In this study, the anti-proliferative activity of a novel [Cu(L)(phen)] complex was investigated on MCF-7 breast cancer cells using MTT assay. Since chemotherapy is lake of ability to distinguish between normal cells from cancerous cells, therefore we also investigated the effect of [Cu(L)(phen)] complex on normal L929 cells. The results showed that following 24 and 48 h exposure of cells with [Cu(L)(phen)] complex, the IC50 values for MCF-7 were significantly lower than that recorded for L929 and normal cells were less sensitive than cancerous cells to the complex. Additionally, the [Cu(L)(phen)] complex displayed a time- and concentration-dependent cytotoxic response, with MCF-7 and L929 cells. Also flow cytometry findings suggest that [Cu(L)(phen)] complex is capable of decreasing cancer cell viability through apoptosis and did not efficiently activate the necrosis process.

The potential exists to improve treatment through characterization of tumor stem cells and identification of therapeutic targets Using OCT-4 and NANOG genes. Here we have synthesized and investigated the potential of; New Indole-3-carbaldehyde derivative (NI-3-CD) in inhibiting the expression of self-renewal regulatory factors and cancer stem cell gene in a leukemia cell line NB4.The NB4 cells were cultured in RPMI1640 medium contained NI-3-CD and I3F (15.12-1000μg/mL) for 24, 48 and 72h. Inhibition of cell proliferation was assessed by trypan blue staining technique and MTT assay. The percentage of apoptotic cells was determined by flow cytometry analysis using Annexin V/PI apoptosis detection kit. The fold changes of NANOG/OCT4 expression against β-actin were determined by real-time-PCR technique. Western blotting analysis was also applied for evaluating the expression of NANOG/OCT4 at protein level. Data were analyzed by student t and repeated measure tests. Differences were considered significant if (P0.01).There was a significant difference in cell viability, when various concentrations of NI-3- were used for 24, 48 and 72h in comparison to I3C regarding the cellular viability. Furthermore, the NI-3-CD, had markedly elevated anticancer activity than I3C (IC50 values for novel I3C in 24, 48 and 72h were 225.77, 123.13 and 63.72M respectively while for I3C were 728.05, 407.82 and 277.92M respectively). Flow cytometry results exhibited an obviously significant augmentation in apoptotic NB4 cells. Real Time- PCR analysis indicated that the expression of NANOG/OCT4 was down regulated in compare to untreated control cells and I3C treated cells (P0.05). In concert with RT-PCR, western blot analysis showed that the OCT4 expression in NI-3-CD treated cells was also significantly decreased in compare to both untreated control cells and I3C treated cellular populations.Our results imply that NI-3-CD treatment decreases the sphere-forming ability of NB4 cells. In summary, this study provides valuable information on the presence of stem-cell genes expression in NB4 cells.

In the current study, the effects of troxerutin (TRX) on muscle fatigue and gene expression of Bcl-2 and Bax in the hepatic tissue of rats was investigated. Forty male Wistar rats were randomly divided into 4 groups and designated as control and TRX treatment at 75 (TRX75), 150 (TRX150), and 300 mg/kg per day (TRX300). The treated groups and control group received TRX and water orally for 7 days. After an exhaustive swimming test on the 7th day, all animals were euthanized immediately and several biochemical parameters related to fatigue and gene expression of Bcl-2 and Bax in the hepatic tissue were measured. Our results showed that the exhaustion swimming time in the TRX300 groups significantly increased 1.2-fold compared with the control group (P < 0.001). TRX300 significantly reduced ALT (P < 0.05) activity and increased liver SOD activity compared with the control group (P < 0.01). Additionally, TRX significantly reduced the liver mRNA expressions of Bax (P < 0.001) and increased the Bcl-2/Bax ratio (P < 0.001) compared with the control group. Based on our data, TRX possesses anti-apoptotic and hepatoprotective action following exhaustive swimming exercise.

Graphical abstract, Background Non-alcoholic fatty liver disease (NAFLD) is one of the hepatic disorders which is characterized by increasing fat deposits in the liver. This disorder may lead to elevation the activity of liver enzymes and is associated with obesity, dyslipidemia, hypertension, and type II diabetes. The aim of present study was to investigate the effect of Berberis integerrima extract on NAFLD patients compare to placebo. Methods The present clinical trial was performed on 42 NAFLD patients who were randomly divided into two groups. The case group received a capsule (750 mg) containing hydro-alcoholic extract of Berberis integerrima extract every 12 h for 2 months, while the control (placebo) group received a capsule containing cellulose. Baseline characteristics, biochemical factors, antioxidant parameter, functional liver and renal test were evaluated before and after the treatment. Results Comparison rate of different parameters in case group before and after treatment demonstrated that BMI, cholesterol, triglyceride, LDL-C, fasting blood glucose, liver enzymes and renal parameters such as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were significantly decreased while HDL-C, glutathione peroxidase enzyme, and total antioxidant capacity were significantly elevated. The comparison of the mean parameters difference in two groups indicated that cholesterol, triglyceride, LDL-C, fasting blood glucose, liver enzymes and renal factors were significantly decreased, however HDL-C, glutathione peroxidase enzyme, and total antioxidant capacity were significantly increased in case group compared to control group. Conclusion The study findings revealed that the Berberis integerrima extract could reduce biochemical factors of blood, except HDL-C and increases total antioxidant capacity and glutathione peroxidase enzyme. Therefore, hydro-alcoholic extract of Berberis integerrima may be used as a great supplementary medicine in treating NAFLD.

BACKGROUND Previous studies on the efficacy of platinum-based drugs and selective inhibitors of proteasome have revealed promising outcomes. This study is aimed to evaluate the effects of the combination of cisplatin and carfilzomib on the cell death induction and drug efflux transporters expression in cisplatin-sensitive (A2780s) and cisplatin-resistant (A2780cp) ovarian cancer cells lines. METHODS MTT cytotoxic assay was conducted to determine the cytotoxicity. Drug interactions were analyzed based on Chou-Talalay's principles and real-time PCR analysis was performed to determine possible alterations in mRNA levels of MRP1 and BCRP. RESULTS A2780s cells were more susceptible to both cisplatin and carfilzomib while analyses of drug interactions between the two agents showed synergistic effects in all affected fractions of drug-treated A2780s and A2780cp cells (CI

BACKGROUND: The use of phytochemicals to prevent or suppress tumours is known as chemoprevention. Numerous plant-derived agents have been reported to have anticancer potentials. As one such anticancer phytochemical, diosgenin has several applications which are nevertheless limited due to its low solubility in water. METHODS: We loaded diosgenin into niosome to increase its solubility and hence efficiency. Diosgenin-niosome (diosgenin loaded into niosome) was prepared by thin-film hydration method and characterised by optical microscopy, dynamic light scattering (DLS), scanning electron microscopy (SEM), and UV-visible spectrophotometry. Also, loading efficiency, in vitro drug release, and cytotoxicity assay were performed on HepG2 cell line. RESULTS AND DISCUSSION: Diosgenin-niosome has a nanometric size with a normal size distribution and spherical morphology. The loading efficiency of diosgenin was about 89% with a sustainable and controllable release rate. Finally, the viability of free diosgenin was 61.25%, and after loading into niosomes, it was improved to 28.32%. CONCLUSION: The results demonstrated that niosomes increase the solubility of naturally derived hydrophobic chemicals and thus enhance their anticancer effect. [Figure: see text]

Objective Liver cancer is common worldwide and its occurrence is increasing globally; the most prevalent type is hepatocellular carcinoma. Cressa cretica is a halophyte plant that contains flavonoids, which are antibacterial, antioxidant agents. We investigated the effects of C. cretica extract on apoptosis and expression of Bcl2, Bax and P53 genes in the hepatoma cell line, HepG2. Methods HepG2 cells were cultured in RPMI 1640 medium, then incubated in various concentrations of hydroalcoholic extract of C. cretica. Cell proliferation was investigated using MTT assay and apoptosis was measured using flow cytometry. The expression of apoptosis- related genes were determined by real-time PCR. Results Proliferation of HepG2 cells treated with different concentrations of C. cretica were diminished significantly in a dose-dependent pattern. The concentration of C. cretica required for 50% cell viability was 2300 μg/ml. Expression of P53 increased significantly in the treatment groups compared to control group. Bcl2 gene expression was decreased significantly compared to the control group, while the Bax gene was overexpressed in the extract treated groups. Conclusion C. cretica is able to effect on the expression of apoptosis-related genes; therefore, it could play a role in treatment of cancer.

Objective Dyslipidemia is a disorder in lipoprotein metabolism. This disorder could lead to atherosclerosis and it promotes the coronary artery disease and stroke. Turmeric and its active compound, curcumin, modulate the lipid metabolism and also have been used to treat the fatty liver. The present study evaluated the effect of Curcuma longa extract and curcumin on gene expression profiles of lipid metabolism pathway in human HepG2. Methods HepG2 cell line was cultured in RpMI-1640 media. The cells in each well were incubated in various concentration of curcumin and hydro-alcoholic extract of Turmeric (15, 30, 60, 125, 250, 1000, 2000 μg/ml). The cell viability was investigated by MTT assay and the expression of lipid metabolism genes was determined using real-time PCR in IC20 concentration. Results The proliferation of HepG2 cells significantly reduced in curcumin-treated and hydro-alcoholic extract of Turmeric-treated groups with increasing the concentrations. The expression of lipogenesis-related genes such as PGC1A, CPT1A and ACOX1 significantly increase in both treatment groups as compared with the control group. Curcumin and hydro-alcoholic extract of Turmeric significantly diminished the expression of lipid synthesis genes such as SCD1, SREBF2, and DGAT1. Conclusion According to our study, Turmeric and curcumin reduce the viability of HepG2 cells in a concentration-dependent manner; in addition, these ingredients decrease the lipogenesis genes while they increase the lipid synthesis genes. This report suggests that Turmeric could remove the lipid and fatty acids. This herbal substance could be a helpful treatment for obesity and fatty liver.

Objectives: In the present study, we aimed to identify the anti-proliferative potential of [Cu(L)(2imi)] complex [L = 2-(((5-chloro-2-oxyphenyl)imino)methyl)phenolato) and 2imi = 2-methyl imidazole] against HepG2 cells as an in vitro model of human hepatocellular carcinoma and normal mouse fibroblast L929 cells. Methods: The cytotoxic and apoptotic effects of [Cu(L)(2imi)] complex on HepG2 cells and normal fibroblasts (L929) were examined by MTT assay and flow cytometry, respectively. Results: Cytotoxicity induced by [Cu(L)(2imi)] complex was time dependent. Also, there was a positive correlation between cytotoxicity and an increase in Cu complex concentration. For HepG2 cells, the cell viability percentage was 50% at 58 μg/mL after 24 h treatment, whereas in the same concentration and conditions, the viability percentage was surprisingly higher (about 100%) for L929 cells. Also, after 48 h treatment, the viability percentage of HepG2 cells at 55 μg/mL concentration was 50% in contrast with 89.3% for L929 cells in the same conditions. Flow cytometry findings suggest that [Cu(L)(2imi)] complex is capable of decreasing cancer cell viability through apoptosis and did not efficiently activate the necrosis process. Conclusions: Finally, we found that [Cu(L)(2imi)] complex possess the potential for development as an anti-cancer drug for human hepatocellular carcinoma.

Aim of study Diabetes mellitus is related to the development of neuronal tissue injury in different peripheral and central nervous system regions. A common complication of diabetes is painful diabetic peripheral neuropathy (PDN). We have studied the neuroprotective and anti-nociceptive properties of neuropeptide orexin-A in an animal experimental model of diabetic neuropathy. Methods All experiments were carried out on male Wistar rats (220-250 g). Diabetes was induced by a single intraperitoneal injection of 55 mg/kg (i.p.) streptozotocin (STZ). Orexin-A was chronically administrated into the implanted intrathecal catheter (0.6, 2.5 and 5 nM/L, daily, 4 weeks). The tail-flick and rotarod treadmill tests were used to evaluate the nociceptive threshold and motor coordination of these diabetic rats, respectively. Cleaved caspase-3, Bax, Bcl2 and the Bax/Bcl-2 ratio, as the biochemical indicators of apoptosis, were investigated in the dorsal half of the lumbar spinal cord tissue by western blotting method. Results Treatment of the diabetic rats with orexin-A (5 nM/L) significantly attenuated the hyperalgesia and motor deficit in diabetic animals. Furthermore, orexin-A (5 nM/L) administration suppressed pro-apoptotic cleaved caspase-3 and Bax proteins. Also, orexin-A (5 nM/L) reduced the expression of Bax/Bcl-2 ratio in spinal cord dorsal half of rats with PDN. Conclusions Altogether our data suggest that the orexin-A has anti-hyperalgesic and neuroprotective effects in rats with PDN. Cellular mechanisms underlying the observed effects may, at least partially, be related to reducing the neuronal apoptosis.

Recently the role of indole and pyran rings in carcinogenesis has been well studied. Here we studied the effects and the possible mechanisms of the action of basal indole (I3A) and its novel indole derivative (C19H15F3N2O) on inhibition of proliferation cells in acute promyelocytic leukemia NB4 cell line by examining the expression of cell cycle genes. We treated NB4 cells with concentration of C19H15F3N2O for 24-72 h. The MTT and PI/Annexin V examinations were employed for assessment of the proliferation and apoptosis of NB4 cells. Both of Cyclin D and P21 were detected by the Real-time PCR. The western blotting analysis was also performed to show the protein levels for P21. A difference was regarded significant if p-value was less than 0.05. MTT assay showed that 15.12-1000 µg/mL C19H15F3N2O caused a time and concentration-dependent inhibition of NB4 cell proliferation. Exposure to higher concentrations of C19H15F3N2O resulted in significantly increased apoptosis rate in NB4 cells. RT PCR showed that C19H15F3N2O has up-regulated the expression of P21 and down-regulated the expression of Cyclin D. Western blotting experiments also demonstrated that the P21 expression in C19H15F3N2O treated cells has significantly increased, where compared with either untreated control cells or I3A treated cells. This newly (C19H15F3N2O) was able to inhibit NB4 cells proliferation and causes apoptosis of these cells more than I3A, and these effects are probably facilitated via cell cycle arrest. C19H15F3N2O might probably be introduced as a promising organic therapeutic reagent against APL.

This study investigated the potential of Persian shallot extract as an anticancer agent in HepG2 tumor cell line, an in vitro human hepatoma cancer model system. The inhibitory effect of Persian shallot on the growth of HepG2 cells was measured by MTT assay. To explore the underlying mechanism of cell growth inhibition of Persian shallot, the activity of Persian shallot in inducing apoptosis was investigated through the detection of annexin V signal by flow cytometry and expression of some apoptosis related genes such p21, p53, puma, caspase-8 family-Bcl-2 proteins like bid, bim, bcl-2 and bax were measured by real-time PCR in HepG2 cells. Persian shallot extract inhibited the growth of HepG2 cells in a dose-dependent manner. The IC50 value (inhibiting cell growth by 50%) was 149 μg/ml. The results of real-time PCR revealed a significant up-regulation of bid, bim, caspase-8, puma, p53, p21 and bax genes and a significant downregulation of bcl-2 gene in HepG2 cells treated with Persian shallot extract significantly. Therefore, this is the first report on an increased expression of bid, bim, caspase-8, puma, p53, p21 and bax genes and down regulation of bcl-2 gene indicating that the Persian shallot extract possibly induced the process of cell death through the intrinsic and extrinsic apoptosis pathways and triggers the programmed cell death in HepG2 tumor cell lines by modulating the expression of pro-/anti-apoptotic genes. Furthermore, we showed that Persian shallot extract increased annexin V signal and expression, resulting in apoptotic cell death of HepG2 cells after 24 h treatment. Therefore, according to the results of this study, the Persian shallot extract could be considered as a potential candidate for production of drug for the prevention or treatment of human hepatoma.