Pancreatic cancer (PC) is a highly deadly malignancy, due to late diagnosis and inadequate treatment. Therefore, potential diagnostic biomarkers and therapeutic targets are needed for PC patients. Today, long noncoding RNAs (lncRNAs) are used as new biomarkers in diagnosing and treating cancers. Hence, we studied the expression levels of inflammatory lncRNAs, NKILA, and PACER in the peripheral blood mononuclear cells of PC patients and healthy individuals. The expression level of lncRNA NKILA was significantly reduced in patients. However, no significant difference was observed in the expression level of lncRNA PACER in the cases compared to healthy subjects. In addition, significant pairwise correlations were indicated between expression levels of these lncRNAs in PC patients. Finally, the area under curve values for NKILA was 0.72. The current pilot results suggest that NKILA might serve as a diagnostic biomarker for discrimination between PC patients and controls. Altogether, the observed down-regulation of lncRNA NKLA in PC cases compared with the healthy controls ensures future functional studies to affirm the results of the present study in larger sample sizes to elaborate its putative role as PC biomarkers.

Understanding the new insight on conversion of organic waste into value-added products can improve the environmental activities driven by microorganisms and return the nutrients to environment and earth. Here, we comprehensively review the available knowledge on application of garbage enzyme (GE) for different environmental activities including waste activated sludge, composting process, landfill leachate treatment, soil remediation and wastewater treatment with special focus on their efficiency. To identify peer-reviewed studies published in English-language journals, a comprehensive search was performed across multiple electronic databases including Scopus, Web of Science, Pubmed, and Embase. The search was conducted systematically using relevant keywords. The eligible studies were analyzed to extract data and information pertaining to components of GE, fermentation process operational parameters, type of hydrolytic enzymes and improved environmental performance. The findings derived from this current review demonstrated that GE produced from the fruit and vegetable peels, molasses or brown sugar (carbon source), and water within fermentation process contain different hydrolytic enzymes in order to facilitate the organic waste degradation. Therefore, GE can be considered as a promising and efficient pathway in order to improve the environmental activities depended on microorganism including, composting, wastewater and leachate treatment and bioremediation process.

Background: A widespread crosstalk between inflammation and coagulation has been shown in numerous studies. This suggests that coagulation can trigger an inflammatory response which ultimately leads to coagulation activation. Previous research has shown that polyphenols can affect blood pressure and endothelial dysfunction, resulting in reduced risk of cardiovascular diseases. This study aimed to investigate whether Silymarin, a flavonolignans, could play a role in the interaction between inflammation and coagulation by influencing endothelial cells. Materials and Methods: In this experimental study, , human umbilical vein endothelial cells (HUVECs) were seeded with and without various concentrations of silymarin. In vivo, treatment with silymarin was also carried out. Coagulative and fibrinolytic factors, including Von Willebrand factor (VWF) and Factor VIII (FVIII), tissue plasminogen activator-1 (TPA-1), and inflammatory factors, including interleukin 8 (IL-8) and tumor necrosis alpha-factor (TNF-a), were evaluated by flow cytometry, Real-Time Polymerase Chain Reaction (qPCR), Enzyme-Linked Immunosorbent Assay (ELISA) and Immunocytochemistry (ICC). Results: Silymarin increased the gene expression, release, and storage of VWF while diminishing the gene expression, release, and storage of TPA-1 (P < 0.05). The activity of FVIII was dramatically increased, and IL-8 and TNF-a levels were augmented. The in vivo study also indicated an elevated plasma level of VWF and IL-8 by silymarin administration. Conclusion: The results showed that, although silymarin reduces inflammatory factors, it can affect coagulation factors by increasing the levels of VWF and FVIII activity and inhibiting TPA-1 production, thereby making thrombosis probable. Consequently, it is advisable to prescribe this medication with caution for individuals who are susceptible to thrombotic events.

Silymarin, a widely-used hepatoprotective agent, has shown antitumor properties in both in vitro and animal studies. Currently, there is limited knowledge regarding silymarin's antitelomerase effects on human colorectal cancer and hepatocyte carcinoma cells. In this study, we investigated the antiproliferative and antitelomerase effects of silymarin on four human colorectal cancer and HepG2 hepatocyte carcinoma cell lines. The cell viability and telomerase activity were assessed using MTT and the telomerase repeat amplification protocol assay, respectively. We also investigated the effects of silymarin on the expression of human telomerase reverse transcriptase and its promoter methylation in HepG2 cells by real-time RT-PCR and methylation-specific PCR, respectively. Silymarin treatment inhibited cell proliferation and telomerase activity in all cancer cells. After 24 h of treatment, silymarin exhibited IC 50 values ranging from 19 - 56.3 mu g/mL against these cancer cells. A 30-min treatment with silymarin at the IC 50 concentration effectively inhibited telomerase activity in cell-free extracts of both colorectal cancer and hepatocyte carcinoma cells. Treatment of HepG2 cells with 10 and 30 mu g/mL of silymarin for 48 h resulted in a decrease in human telomerase reverse transcriptase expression to 75 and 35% of the level observed in the untreated control (p < 0.01), respectively. Treatment with silymarin (10, 30, and 60 mu g/mL) for 48 h did not affect human telomerase reverse transcriptase promoter methylation in HepG2 cells. In conclusion, our findings suggest that silymarin inhibits cancer cell growth by directly inhibiting telomerase activity and downregulating its human telomerase reverse transcriptase catalytic subunit. However, silymarin did not affect human telomerase reverse transcriptase promoter methylation at the concentrations of 10 - 60 mu g/mL used in this study.

Background The oncogenic Wnt/β-catenin signaling plays a critical role in carcinogenesis, prognosis, and resistance to therapy. Pancreatic cancer (PC) has high mortality because of its poor prognosis. Several studies have suggested that lncRNAs are directly involved in the development and progression of PC as well as in Wnt/β-catenin signaling. In this study, we investigated and compared the expression of Wnt/β-catenin signaling-related ZFAS1 and HCG11 lncRNAs, and their targets, CTNNB1 and IGF2BP1 genes in the blood of patients with PC and healthy individuals. A total of 47 PC patients and 50 healthy individuals participated in this study. RNA was extracted from the peripheral blood samples of participants, and cDNA was synthesized. The expression level of the selected genes was quantified by real-time PCR. The expression of HCG11 lncRNA and CTNNB1 genes in patients with PC was significantly upregulated compared to healthy individuals, and the expression of the ZFAS1 lncRNA was significantly downregulated. According to the analysis of the ROC curve, the diagnostic powers of ZFAS1 and CTNNB1 in PC were 0.67 and 0.69, respectively. Altogether, the present study suggests a role for ZFAS1 and HCG11 lncRNAs and CTNNB1 and IGF2BP1 in the pathogenesis of pancreatic cancer. Moreover, the peripheral expression of these lncRNAs may be useful as potential biomarkers for PC.

BACKGROUND:Long non-coding RNAs (lncRNAs), including taurine upregulated gene 1 (TUG1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and maternally expressed 3 (MEG3) play a regulatory role in endoplasmic reticulum (ER) stress. The present study aimed to investigate the expression of these lncRNAs in patients with type 2 diabetes and their association with biochemical and ER stress parameters.MATERIALS AND METHODS:Participants included 57 patients with diabetes and 32 healthy individuals. Real-time PCR was performed to assess MALAT1, TUG1, MEG3, ATF4, and CHOP gene expression in peripheral blood mononuclear cells. Plasma GRP78, advanced glycation end products (AGEs), and insulin were measured using enzyme-linked immunosorbent assay (ELISA), and insulin resistance (IR) was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR).RESULTS:The expression of TUG1, MEG3, ATF4, and CHOP genes was significantly increased in the patients with diabetes compared to healthy individuals. MALAT1 gene expression was also higher in patients group; although it did not reach significant levels. TUG1 and MEG3 expression revealed significant positive correlations with the indices of glycemic control, including FBS, HbA1c, HOMA-IR, and AGEs, as well as markers of ER stress. MALAT1 expression was also positively correlated with ATF4 and AGEs.CONCLUSION:The expression levels of TUG1 and MEG3 lncRNAs were increased in patients with diabetes and were associated with glycemic control and components of ER stress. Thus, these lncRNAs might be considered appropriate markers to identify ER stress due to hyperglycemia.

Background and objectives: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder which presents with the accumulation of triglycerides in hepatocytes due to imbalances in the uptake, synthesis, export, and oxidation of fatty acids. Silymarin is a flavonolignan derived from milk thistle, a herbal medicine that has been used for centuries to treat liver disease. In this study, the effect of silymarin on genes involved in lipogenesis and endoplasmic reticulum (ER) stress was investigated in the cellular NAFLD model. Materials and methods: HepG2 cells were treated with 0.5 mM oleic acid (OA) in the presence or absence of silymarin for 24 h, and subsequently, lipid accumulation was assessed by staining the cells with Oil red O as well as the measurement of intracellular triglyceride (TG) content with an enzymatic method. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to measure the expression of sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FAS), Sirtuin 1 (SIRT1), TRB3, and ATF4. Results: Lipid accumulation was increased in OA-treated hepatocytes, an effect that was attenuated by silymarin. The expression of FAS, SREBP-1, TRB3, and ATF4 was significantly increased in OA-treated HepG2 cells, while the expression of SIRT1 was decreased. Treatment with silymarin could successfully diminish SREBP-1, FAS, TRB3, and ATF4 gene expression while augmenting the expression of SIRT1. Conclusions: Silymarin not only efficiently reduces lipogenesis but also decreases ER stress, which is a critical parameter in lipogenesis. Therefore, silymarin might be considered an effective supplementary option in the treatment of liver steatosis.

PURPOSE:Endoplasmic reticulum (ER) stress is implicated in the development of type 2 diabetes mellitus (T2DM) and insulin resistance. Tribbles homolog 3 (TRB3) is a pseudokinase upregulated by ER stress and hyperglycemia. Glucose-regulated protein 78 (GRP78) is an ER stress protein that is overexpressed under ER stress conditions. The current study aimed to investigate serum levels of TRB3 and GRP78, as an ER stress marker, in T2DM patients and their correlations with the metabolic profile.METHODS:Fifty-seven patients with type 2 diabetes and 23 healthy control subjects were evaluated for serum concentrations of TRB3, GRP78, and AGEs by enzyme-linked immunosorbent assay (ELISA). Fasting plasma glucose (FPG), HbA1c, lipid profile, TNF-α and insulin were also measured, and insulin resistance was calculated using a homeostasis model assessment of insulin resistance (HOMA-IR).RESULTS:Serum concentrations of TRB3, GRP78, AGEs, and TNF-α were significantly higher in T2DM patients compared to the healthy controls. Moreover, a statistically significant positive correlation was observed between plasma concentrations of TRB3 and FPG, HbA1c, HOMA-IR, and AGE. GRP78 levels were positively correlated with HbA1c and AGEs. There was also a positive correlation between GRP78 and TRB3. AGEs levels were positively correlated with the levels of FPG, HbA1c, HOMA-IR, and TNF-α.CONCLUSION:The current findings suggest that TRB3 and GRP78 may contribute to the pathogenesis of T2DM and might be considered as a therapeutic targets for the treatment of this disease.

BACKGROUND:Angiopoietin-like protein 2 (ANGPTL2) is one of the adipocyte-derived inflammatory factors which connects obesity to insulin resistance. ANGPTL3 has a direct role in regulation of lipid metabolism. The objective of this study was to evaluate ANGPTL2 and ANGPTL3 in childhood obesity and their relationship with metabolic syndrome.METHODS:70 children and adolescents, 35 obese and 35 normal-weight subjects, were enrolled in this research after complete clinical examination and anthropometric evaluations. Serum ANGPTL2 and ANGPTL3 and insulin were measured by enzyme-linked immunosorbent assay (ELISA). Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated and used to estimate insulin resistance (IR). Colorimetric methods were used for the assessment of fasting plasma glucose (FPG), LDL-C, HDL-C, total cholesterol (TC), and triglyceride (TG).RESULTS:The levels of ANGPTL2 and ANGPTL3 were significantly higher in obese subjects than those in controls, but they did not differ significantly in subjects with or without IR. ANGPTL3 was found to be significantly elevated in obese children with metabolic syndrome (MetS) in comparison with those without MetS. Both of the studied ANGPTLs were positively correlated with BMI, systolic blood pressure (SBP), diastolic blood pressure (DBP), TC, and LDL-C. The correlation between ANGPTL3 and either TC or LDL-C remained significant after adjusting for BMI.CONCLUSION:Serum ANGPTL2 and ANGPTL3 were elevated in obesity and associated with blood pressure and indices of metabolic syndrome, suggesting that they might be involved in the advancement of obesity-related hypertension and metabolic syndrome.

Organic products with the positive impacts that they have on health and the environment in the future will establish a new way of thinking about the relationship between food, health, and nature in human life. Therefore, it is important to examine the key factors that may affect the consumer’s mind to purchase organic food products. The present study aimed to investigate the factors affecting the actual behavior of organic product buyers. Data were collected by the field method, and a questionnaire was used as the data collection instrument. The statistical population of the study included the consumers of organic products in Guilan province, Iran. Due to the unlimited size of the research population, 384 people were sampled by the convenience random sampling method. Model evaluation and testing of hypotheses were performed by structural equation modeling in Smart PLS software. The research findings demonstrated that perceived price, health consciousness, availability, organic knowledge, and subjective norms were the key determinants of organic buying behavior and showed a significant positive impact on consumer attitudes. Consumer attitudes also influenced purchase intention and purchase intention on actual buying behavior. It was also found that consumers would be more willing to buy if they learned more about organic products and their environmental benefits. In addition, the results showed that preparing a brochure to introduce organic products and provide the results of studies on organic products to buyers and forming environmentally friendly groups and associations can change the attitude of buyers.

Providing organic food has many health and environmental benefits, nevertheless, the demand for inorganic food compared to organic is growing. The main objective of this study is to provide a behavioral model on buyers of organic products in terms of components, antecedents and consequences. This study has applied and mixed components. In the qualitative part, the Grounded theory is used and in the quantitative part, the technique of structural equations. Data were collected through semi-structured interviews and a completed questionnaire, where ten buyers were interviewed. Then, based on the systematic approach suggested by Strauss and Corbin on three main steps of open, axial and selective coding, the behavioral model of the buyers of organic products was presented in terms of components, antecedents and consequences. Finally, the validity of the developed theory was examined and hypotheses were developed. In the quantitative part, the results show that among the causal conditions, the price of organic products, trust, perceived health, advertising, supply of organic products and perceived value have a significant effect on buyers' behavior, while the characteristics of organic products and organic knowledge have no significant effect on buyer behavior. It was also found that buyers' behavior has a significant effect on increasing the share of the organic market and, consequently, on the environmental consequences, the growth of organic markets and the promotion of public health. Finally, it was conjectured via observation that social norms, systematic trust, individual norms, and environmental concerns would increase the share of the organic market further.

Background: Multiple Sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system, and genetic factors play an important role in its susceptibility. The expressions of many inflammatory genes implicated in MS are regulated by microRNA (miRNAs), whose function is to suppress the translation by pairing with miRNA Recognition Elements (MREs) present in the 3' untranslated region (3'UTR) of target mRNA. Recently, it has been shown that the Single Nucleotide Polymorphism (SNPs) present within the 3'UTR of mRNAs can affect the miRNA-mediated gene regulation and susceptibility to a variety of human diseases. Objective: The aim of this study was to analyze the SNPs within the 3'UTR of miRNA inflammatory target genes related to multiple sclerosis. Methods: By DisGeNET, dbGaP, Ovid, DAVID, Web of knowledge, and SNPs databases, 3'UTR genetic variants were identified in all inflammatory genes associated with MS. Also, miRNA's target prediction databases were used for predicting the miRNA binding sites. Results: We identified 125 SNPs with MAF>0.05 located in the binding site of the miRNA of 35 genes among 59 inflammatory genes related to MS. Bioinformatics analysis predicted 62 MRE-modulating SNPs and 59 MRE-creating SNPs in the 3'UTR of MSimplicated inflammatory genes. These candidate SNPs within miRNA binding sites of inflammatory genes can alter the miRNAs binding, and consequently lead to the mRNA gene regulation. Conclusion: Therefore, these miRNA and MRE-SNPs may play important roles in personalized medicine of MS, and hence, they would be valuable for further functional verification investigations.

Background: Accumulation of fatty acids in liver causes lipotoxicity which is followed by nonalcoholic fatty liver disease. The association between intakes of trans-fatty acids with metabolic diseases is still controversial. Accordingly, the objective of this study was to investigate the in vitro effects of trans-palmitoleic acid (tPA) and palmitic acid (PA) on lipid accumulation in hepatocytes, focusing on the gene expression of sirtuin 1 (SIRT1) as well as the transcriptional activity of peroxisome proliferator-activated receptor alpha (PPARα). Materials and Methods: In this experimental study, hepatocellular carcinoma (HepG2) cells were cultured and treated with various concentrations of tPA and PA (C16:0). The accumulation of triglyceride in the cells was measured by enzymatic method. Gene expression was evaluated by real-time polymerase chain reaction. The activity of PPARα was assessed by luciferase reporter assay after transfection of human embryonic kidney 293T cells by a vector containing the PPAR response element. Results: While concentration >1 mM for PA and cis-PA (cPA) reduced the viability of hepatocytes, tPA revealed an opposite effect and increased cell survival. Lipid accumulation in HepG2 cells after treatment with tPA was significantly lower than that in cells treated with PA. In addition, tPA at physiological concentration had no effect on the expression of SIRT1 while at high concentration significantly augmented its expression. There was a modest increase in PPARα activity at low concentration of tPA. Conclusion: tPA causes less lipid accumulation in hepatocytes with no detrimental effect on cell viability and might be beneficial for liver cells by the activation of SIRT1 and induction of PPARα activity.

: Increasing the prevalence of cardiovascular disease (CVD) has led to an investigation into components that might influence CVD. Accordingly, many recent studies have reported the benefits of resveratrol (RSV). Therefore, this study aimed to scrutinize the direct effect of RSV on human umbilical vein endothelial cells (HUVECs) by detecting coagulative, fibrinolytic, and inflammatory markers. HUVECs were cultured and treated with different concentrations of RSV. The effects of RSV were identified by representative markers of coagulation, fibrinolysis pathway, and inflammation, including von Willebrand factor (VWF), factor VIII, tissue plasminogen activator-1 (t-PA-1), and interleukin-8 (IL-8). The detection process was carried out using real-time PCR (qPCR), flow cytometry, ELISA, and immunocytochemistry (ICC) methods. The present findings demonstrated a significant decrease in VWF, t-PA-1, and IL-8 secretion levels. Furthermore, RSV diminished the activity of factor VIII and mRNA expression levels of VWF and t-PA-1. The ICC results also showed a decrease in the level of intracellular t-PA. Our data revealed the anti-inflammatory, anticoagulation, and antifibrinolytic effect of RSV in cell culture.

We have investigated the effect of photobiomodulation on the recovery of neurosensory function of the lip and chin after bilateral sagittal split osteotomy (BSSO). Laser irradiation was applied with a GaAs diode laser (continuous wave 980nm wavelength, power 100mW, and energy density 12J/cm2). It was maintained within a 0.5cm2 area in a total of 12 points for 60seconds at each visit on each point. Unilateral extraoral contact photobiomodulation treatment was applied the day before operation and then on days 1, 3, 7, 14, 21, and 28 postoperatively. One side of the mandible was the intervention side and the other the control side. On the control side, the laser probe was turned off and placed on the chosen area. Neurosensory evaluations were made before and immediately after operation, and 30 days and 60 days postoperatively. Twenty-five patients were screened, and 18 who met the inclusion criteria were included in the study; 14 were women and the mean (SD) age was 23 (5) years. Analysis of the visual analogue scales for general sensibility, pain discrimination, directional discrimination, and 2-point discrimination showed a significant difference between the intervention and control sides after 30 days (p=0.0011, 0.0034, 0.0023, and 0.0160, respectively). The difference was also significant after 60 days (p=0.0001, 0.0002, 0.0003, and 0.0010, respectively). The thermal discrimination rate was significantly higher in the laser group than the control group 30 days after surgery (p=0.002), but after 60 days the difference was not significant (p=1.000). We found no side effects from the laser radiation during the two-month follow up. The results suggest that photobiomodulation accelerated the patients’ improvement from neurosensory disturbance after BSSO.

Objective Nicotinamide phosphoribosyltransferase (NAMPT), which is responsible for biosynthesis of nicotinamide adenine dinucleotide (NAD), has a regulatory role in cellular metabolism and thus, might be implicated in non-alcoholic fatty liver disease (NAFLD). This study aimed to show how NAMPT down-regulation in liver cells influences lipid metabolism and sirtiun 1 (SIRT1), as the main NAD-dependent deacetylase enzyme. Materials And Methods In this experimental study, HepG2 cells were transfected with NAMPT siRNA and hepatic triglyceride (TG) content and SIRT1 deacetylase activity were measured by colorimetric and fluorometric methods, respectively. Gene expression of fatty acid synthase (FAS) and sterol regulatory element-binding protein-1c (SREBP- 1c) was evaluated by real-time polymerase chain reaction (PCR). Total protein level and the phosphorylated form of acetyl-CoA carboxylase (ACC) and AMP-activated protein kinase (AMPK) were also investigated by western blotting. Results Knockdown of NAMPT significantly promoted the accumulation of TG in HepG2 cells, accompanied by a remarkable decline in SIRT1 deacetylase activity. A significant rise in the gene expression of two key lipogenic factors, FAS and SREBP-1c was also observed. These effects were also accompanied by decreased phosphorylation of ACC and AMPK. On the other hand, treatment of transfected cells with either NAD, as the SIRT1 substrate or resveratrol, as the SIRT1 activator reversed the outcomes. Conclusion These results demonstrated a protective role for NAMPT against NAFLD and its involvement in the regulation of de novo lipogenesis through the SIRT1/AMPK pathway.

Background: Recently, adipocytokines have been shown to play a pivotal role in autoimmune and inflammatory related disease. The purpose of this study was to compare the levels of CTRP3, CTRP9, adiponectin and apelin- in Multiple Sclerosis (MS) patients with healthy subjects and their relationship with clinical parameters and the levels of pro-inflammatory mediators. Methods: Plasma levels of CTRP3, CTRP9, apelin, TNF-alpha, hs-CRP, and adiponectin were evaluated in 24 healthy women and 26 women with relapsing remitting MS using immunoassay methods. Results: The plasma apelin level of the MS patients was significantly lower than that of healthy controls. The concentration of TNF-alpha and adiponectin were significantly higher in MS patients compared to the healthy controls. Plasma CTRP3, CTRP9 and hs-CRP levels were not significantly different between the two groups. There was no correlation between these adipokines and inflammatory mediators. A statistically significant negative correlation was observed between plasma concentrations of apelin with expanded disability status scale (EDSS) scores and number of relapse. Conclusions: Our findings suggest that adipokines, particularly apelin and adiponectin, may contribute to the pathogenesis of MS and can be considered as a biomarker or as a therapeutic target for the treatment of this disease.