Pistacia and its Combination with Cisplatin: A Potential Anticancer Candidate by Modulating Apoptotic Genes.

INTRODUCTION: Many bioactive phytochemicals have essential significance for handling various diseases and developing new drugs. The aim was to investigate the anti-tumor activity and the underlying mechanisms of pistachio pericarp extract (PPE) and pistachio kernel extract (PKE) alone and combined with cisplatin (CP) in the treatment of prostate cancer. METHODS: The effects of the PPE, PKE, and CP alone and PPE and PKE in combination with CP (PPE+CP and PKE+CP) on the proliferation of PC-3 cells were determined using the MTT assay. The fold changes of BAX, BCL-2, P53, KLK2, TNF, TGF, and NANOG expression against ß-actin were determined by real-time technique. Data were analyzed by two-way ANOVA and repeated measure tests. RESULTS: These research results indicated that a greater anti-proliferative effect of the PPE and PKE was shown in combination with CP compared with treatments using the PPE and PKE or CP alone. The extracts and Cisplatin in vitro had good synergistic effects on the inhibition of the proliferation of PC-3 cells. The IC50 values of PKE+CP were 4.141, 2.140, and 0.884 ug/mL, and PPE+CP were 2.754, 2.061, and 0.753 ug/mL after 24h, 48 h, and 72h treatment, respectively. Also, this result presented that the mRNA expression of BAX and P53 increased, and BCL-2, KLK2, TNF, TGF, and NANOG decreased in PC-3 cells. CONCLUSIONS: The finding of this research showed for the first time the anti-carcinogenesis effects of separately and in the combination of PPE, PKE, and CP on the PC-3 prostate cancer cells via modulating some genes and that it may be nominated for the herbal anti-cancer medications.

The Serum Level of CXCL9, CXCL10, and CXCL11 and the Expression of CXCR3 of Peripheral Blood Mononuclear Cells in Brucellosis Patients.

Brucella spp. can replicate in human endothelial cells, inducing an inflammatory response with increased expression of chemokines. Although Brucella infects humans, its ability to induce the production of chemokines by lung cells is unknown. Therefore, the current investigation was designed to examine the association between brucellosis and CXCL9, 10, and 11 chemokines. The patient group included 71 patients suffering from Brucella infection and the control group consisted of 50 healthy ranchers from the same geographical area. Serum levels of CXCL9, CXCL10, and CXCL11 were analyzed by ELISA. The fold changes of CXCR3 expression against ß-actin were determined by real-time-PCR technique. Western blotting analysis was also applied for evaluating the expression of CXCR3 at protein level. The results of this study showed that the serum levels of CXCL9, CXCL10, and CXCL11 are significantly increased in acute brucellosis patients in comparison to control as indicated by ELISA test, mRNA levels of CXCR3 by Real-time PCR as well as protein levels of CXCR3 by Western blot analysis. According to findings, these chemokines have the potential to serve as markers for brucellosis patients. Taken together, cytokine/chemokine network was active in acute brucellosis patients, and it is suggested to evaluate other cytokines in future studies.

Prevalence of dyslipidemia and its association with opium consumption in the Rafsanjan cohort study.

The potential effects of opium consumption on lipid profile remain unquantified. We considered the association between opium use and dyslipidemia. In this cross-sectional study, we used data obtained from the Rafsanjan cohort study, as a part of the prospective epidemiological research studies in IrAN (PERSIAN) with detailed and validated data on opium consumption and selected other exposures. A total of 9932 adults were included in the study. Logistic regression models were used to assess the relationships of opium consumption with the prevalence of dyslipidemia and lipid disorders. In this population, 73.33% had dyslipidemia and the prevalence rates of high TC, high TG, high LDL and low HDL were 54.24%, 47.45%, 34.43% and 11.91% respectively. After adjustment for all confounders, opium users compared with non-users had lower odds ratios (OR) of high TC and high LDL [0.81 (95% confidence interval, CI 0.71-0.92) and 0.80 (95% CI 0.69-0.93) respectively] and greater OR of low HDL [1.30 (95% CI 1.04-1.62)]. Longer duration of opium consumption resulted in lower ORs of high TC, 0.68 (95% CI 0.55-0.84) and high LDL, 0.82 (95% CI 0.67-0.99), and shorter duration of opium consumption resulted in increased odds of low HDL, 1.30 (95% CI 1.02-1.66). High dose of opium consumption was associated with an OR of dyslipidemia of 0.80 (95% CI 0.65-0.97), high TC of 0.80 (95% CI 0.67-0.95), and high LDL of 0.78 (95% CI 0.64-0.96) and low dose of opium consumption, with an OR of low HDL of 1.30 (95% CI 1.02-1.65). In relation to route of consumption, opium smoking was a risk factor for low HDL with an adjusted odds ratio of 1.31 (1.04-1.63). Opium use was associated with selected changes on serum lipid levels, but opium users had higher frequency of cardiovascular disease history.

Serum liver enzymes and diabetes from the Rafsanjan cohort study.

BACKGROUND: We evaluated the relation between ALT, AST, GGT and ALP with diabetes in the Rafsanjan Cohort Study. MATERIALS AND METHODS: The present study is a cross-sectional research including 9991 adults participated via sampling. We used data obtained from the Rafsanjan Cohort Study (RCS), as a part of the prospective epidemiological research studies in IrAN (PERSIAN). Elevated serum levels of ALT, AST, GGT and ALP were defined according to the reference range of the laboratory in the cohort center. Serum liver enzymes levels within the normal range were categorized into quartiles, and their relationship with diabetes was evaluated by logistic regressions. FINDINGS: In present study, elevated serum levels of ALT, AST, GGT, and ALP were associated with increased odds of diabetes (adjusted ORs: 1.81, 95%CI 1.51-2.17; 1.75, 95%CI 1.32-2.32; 1.77, 95%CI 1.50-2.08; 1.60, 95%CI 1.35-1.90 respectively). Also, in subjects with normal levels of ALT, GGT and ALP, a dose-response increase was shown for diabetes. CONCLUSION: Elevated levels of ALT, AST, GGT and ALP are related to a higher odds of diabetes. Also, increased levels of ALT, GGT and ALP even within normal range were independently related with the increased odds of diabetes. These results indicated the potential of elevated liver enzymes as biomarkers for the possible presence of diabetes.

The therapeutic effect of PEGlated nanoliposome of pistachio unsaturated oils and its efficacy to attenuate inflammation in multiple sclerosis: A randomized, double-blind, placebo-controlled clinical trial phase I.

The aim of this study was to evaluate the therapeutic effect of PEGlated nanoliposome of pistachio unsaturated oils (PEGNLPUOs) and their efficacy to attenuate inflammation in multiple sclerosis (MS). This study was a randomized, double-blind, placebo-controlled clinical trial phase I. The level of docosahexaenoic and eicosapentaenoic acid was significantly increased and the level of matrix metallopeptidase-9 was significantly decreased in MS patients treated with PEGNLPUOs. The level of cytokine showed a Th2-biased response with attenuation of inflammation after treatment with PEGNLPUOs. The number of relapses, disability scores, and T2 lesions was significantly decreased after treatment with PEGNLPUOs.

Evaluation of the Effect of Orlistatorlistat on Expression of OCT4, Nanog, SOX2, and KLF4 Genes in Colorectal Cancer SW40 Cell Line.

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 ß-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 <0.05) and SOX2 (p <0.05) in the treated group in comparison to control (p <0.05). Also, the mRNA expression of KLF4 and Nanog was reduced significantly after treatment of SW40 cell lines was performed with 100 µM doses of Orlistat (p <0.05). CONCLUSION: It appears that after further studies in animal and human phases, orlistat can be used for the treatment of Colorectal Cancer.
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Diosgenin and 4-Hydroxyisoleucine from Fenugreek Are Regulators of Genes Involved in Lipid Metabolism in The Human Colorectal Cancer Cell Line SW480.

OBJECTIVE: Diosignin and 4-hydroxy-L-isulosine (4-OH-Ile) are the two active ingredients of Fenugreek (Trigonella foenumgraecum). Thus, in this study, we examined the effects of hydroalcoholic extract of fenugreek seeds (HEFS), diosgenin and 4-OH-Ile on the expression of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), peroxisome proliferator-activated receptor gamma (PPARγ) and low-density lipoprotein (LDL) receptor (LDLR) which are involved in lipid metabolism in SW480 cell line. MATERIALS AND METHODS: In this experimental study, SW480 cells were cultured in RPMI-1640 medium and treated with HEFS, diosignin, 4-OH-Ile or orlistat for 24 and 48 hours. Inhibitory concentration of 20% (IC20) was calculated using MTT method and cells were then pre-treated with the IC20 concentrations for 24 and 48 hours before RNA extraction and cDNA synthesis. Changes in the expression of ACC, FAS, PPARγ and LDLR genes were assayed by employing the real time-polymerase chain reaction (PCR) method. RESULTS: Our results showed a significant down-regulation in the expression of ACC (P<0.001 and P<0.001 after 24 and 48 hours, respectively) and FAS genes (P<0.001 and P<0.001 after 24 and 48 hours, respectively) in SW480 cells treated with HEFS, diosignin, 4-OH-Ile, or orlistat, but significant up-regulation in the expression of PPARγ (P<0.001 and P<0.001 after 24 and 48 hours, respectively) and LDLR (P=0.005 and P=0.001 after 24 and 48 hours, respectively). CONCLUSION: According to the results of the present study, HEFS, diosgenin and 4-OH-Ile up or down-regulate the expression of some predominant genes involved in lipid metabolism pathway, similar to that observed for orlistat. These types of regulatory effects are presumably proper for the treatment of obesity and overweight.

Attenuation of inflammatory response in the EAE model by PEGlated nanoliposome of pistachio oils.

The aim of this study was to investigate the effect of PEGlated nanoliposome of pistachio unsaturated oils (PEGNLPUOs) to attenuate the inflammatory response in the EAE model by modulating of NFKB and oxidative stress signaling pathway. Real-time PCR demonstrated that the administration of 10%v/v PEGNLPUOs significantly decreased the expression level of AKT1, MAPK, and NFKB genes from NFKB signaling pathway and MGST1, NOS2, and HO-1 genes from oxidative stress signaling pathway. This study showed that the administration of pistachio oil and PEGNLPUOs at a concentration of 10%v/v decreased the number and percentage of Th1(CD4+) and increased Th2(CD8+) cells.

Involvement of Eotaxins (CCL11, CCL24, CCL26) in Pathogenesis of Osteopenia and Osteoporosis.

BACKGROUND: The purpose of this study was to investigate the role of eotaxin family members including C-C motif chemokine 11 (CCL11), C-C motif chemokine 24 (CCL24), and C-C motif chemokine 26 (CCL26) as the subgroups of CC-chemokine in patients affected with osteoporosis and osteopenia. METHODS: Overall, 19 osteoporotic patients, 18 osteopenic individuals, and 20 healthy subjects were recruited in this study. The bone mineral density (BMD) was then measured at the lumbar spine (L1-L4) and the hip (femoral neck and total hip) using dual-energy X-ray absorptiometry for diagnosis of bone density and related disorders. Additionally, enzyme-linked immunosorbent assay (ELISA) technique was employed to measure the serum levels of CCL11, CCL24, and CCL26. RESULTS: The circulating levels of CCL11, CCL24, and CCL26 had been increased in both groups of patients with osteopenia and osteoporosis compared to those in healthy subjects (P<0.05); while no significant difference was observed between serum levels of these chemokines in such patients. CONCLUSION: Eotaxins can play a role in the pathogenesis of osteoporosis and osteopenia; however, further studies are needed to clarify various roles of eotaxins in the pathophysiology of osteoporosis and osteopenia.

Evaluating of Induction of Apoptosis by Cornus mass L. Extract in the Gastric Carcinoma Cell Line (AGS)

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 (0­10 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.

A New Indole Derivative Decreased SALL4 Gene Expression in Acute Promyelocytic Leukemia Cell Line (NB4)

Background: Acute myeloblastic leukemia (AML) is a clonal disorder due to bone marrow failure and uncontrolled proliferation of myeloid lineage. Acute promyelocytic leukemia (APL) is a subtype of AML. Heterocyclic compounds, such as indole, are considered as attractive candidates for cancer therapy, due to their abundance in nature and known biological activity. Sal-like protein (SALL4) is a zinc finger transcription factor involving in the multi-potency of stem cells, in the NB4 cell line. This study was aimed to evaluate the effects of basal indole and its new derivative, 2-(1-((2, 4-Aril)imino)-2,2,2-trifluoroethyl) phenyl-1H Indole-3- carbaldehyde (TFPHC), on the expression of SALL4. Methods: Cells were cultured and treated with different concentrations (75, 150, and 300 µg/mL) of the new indole derivative and DMSO, as a vehicle control, for 24 and 48 hours. Cell proliferation was evaluated by using Trypan blue exclusion and MTT assays. The percentage of apoptotic cells was determined by flowcytometry analysis using the Annexin V/PI apoptosis detection kit; mRNA expression of SALL4 was studied using absolute quantitative RT-PCR. Data were analyzed by student's t-test. P<0.05 were considered statistically significant. Results: Our findings demonstrated the effects of new indole derivatives on SALL4 mRNA expression. Expression of SALL4 mRNA was significantly decreased at 75, 150, and 300 µg/mL concentrations. Conclusion: SALL4 plays a role in the survival of APL cells. SALL4 expression could be suppressed by the novel indole derivative. Additionally, SALL4 gene suppression can serve as a target in APL therapy.

Significant Role(s) of CXCL12 and the SDF-1 3'A Genetic Variant in the Pathogenesis of Multiple Sclerosis.

Both cellular and molecular components of the immune system are among the substantial factors involved in the pathogenesis of multiple sclerosis (MS). Accumulating evidence confirms that chemokines, as the main members of the immune system, play key roles in the regulation of immune responses. Immune system genetic parameters are believed to influence the onset of immune system-related diseases. Regarding the significant role of the CXCR4/CXCL12 axis in cell differentiation and survival and homing of hematopoietic progenitors to the bone marrow and regulation of neuronal progenitor cell migration in the central nervous system (CNS), genetic factors can cause an increased expression of CXCL12 and induce a vigorous immune response against CNS antigens in MS patients. Previous studies have indicated that the expression of CXCL12 could be affected by its polymorphisms at position +801 at the region of the CXCL12 3'A genetic variation. Finally, CXCL12 seems to be involved in the cellular part of the events that take place in the CNS, and therefore it could be considered as a target in MS therapies. Thus, this review was aimed to describe the recent progress in understanding the role of CXCL12 in MS, with an emphasis on CXCL12 serum concentrations and its gene polymorphism at position +801.