Publications by authors named "Jamshid Karimi"

52 Publications

Urinary epidermal growth factor is a novel biomarker for early diagnosis of antibody mediated kidney allograft rejection: A urinary proteomics analysis.

J Proteomics 2021 May 27;240:104208. Epub 2021 Mar 27.

Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. Electronic address:

Although antibody mediated rejection (AMR) accounts for 20-30% of all acute renal allograft rejections, introducing biomarkers for a timely detection of allograft rejection has been remained challenging. This study investigated novel diagnostic biomarkers of AMR by examining of urine proteome in renal transplant patients. Thirty-six patients with kidney transplantation including 22 AMR patients and 14 patients with stable renal function (control group) were enrolled in this study. Urinary samples were collected and Label free quantification (LFQ) proteomics technique was applied on urine samples and data was subjected to Random Forest (RF) algorithm to predict main candidate proteins contributing in AMR. Finally, applicability of candidate diagnostic biomarkers was evaluated in new sets of AMR subjects, stable patients and healthy volunteers. A total of 1020 proteins were detected in urine proteome. RF algorithm predicted 20 differentially expressed proteins with the highest sensitivity and specificity and combination of EGF, COL6A, and NID-1 was identified as possible panel for early diagnosis of AMR. Applicability of EGF as diagnostic biomarker was validated in urine samples of independent set of AMR subjects. This is the first urinary proteomics study in AMR patients demonstrating that urinary EGF might be used as early diagnostic biomarker for AMR. SIGNIFICANCE: Renal antibody mediated rejection (AMR) accounts for 20-30% of all acute rejections of allografted kidneys. Although several possible biomarkers have been proposed to predict AMR, ineffectiveness of current urinary biomarkers in early diagnosing of AMR patients and in distinguishing AMR subjects from patients with stable kidney function casts doubts on their applicability in clinic. Here for the first time and based on the analysis of urinary proteome we showed that uEGF and uEGF/Cr might be candidate biomarkers to predict AMR with high diagnostic power.
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http://dx.doi.org/10.1016/j.jprot.2021.104208DOI Listing
May 2021

Imbalance in thioredoxin system activates NLRP3 inflammasome pathway in epicardial adipose tissue of patients with coronary artery disease.

Mol Biol Rep 2021 Feb 10;48(2):1181-1191. Epub 2021 Feb 10.

Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Shahid Fahmideh Street, Hamadan, Iran.

Atherosclerosis is the leading cause of death worldwide and has in part an inflammatory basis. Since epicardial adipose tissue (EAT) is in close contact with coronary arteries we hypothesized that an imbalance in thioredoxin-1 (TRX-1) and thioredoxin interacting protein (TXNIP) in EAT, activates NLRP3 inflammasome and promotes production of IL-1β, leading to the development of atherosclerosis. Thirty-eight patients with coronary artery disease (CAD) and thirty patients with no clinical signs of atherosclerosis who underwent open-heart surgery for valve replacement were classified as CAD and control groups, respectively. Biopsy samples from EAT were collected and expression of TXNIP, TRX-1, NLRP3 and IL-1β genes were assessed using qRT-PCR. Tissue protein levels of TXNIP and TRX-1 were determined by Western blotting while ELISA was applied to measure IL-1β. Haematoxylin and eosin staining was used for histological examination. mRNA and protein levels of TXNIP in EAT were significantly higher in patients with CAD compared with control group, whereas CAD patients showed lower TRX-1 gene and protein expression. In addition, in CAD patients the NLRP3 gene expression was almost doubled and IL-1β significantly increased at the both mRNA and protein levels. Enhancment in NLRP3 gene expression and TXNIP protein levels were accompanied with the increase in IL-1β protein level whereas TRX-1 protein content showed a negative correlation with IL-1β level. Concurrent increase in TXNIP, NLRP3, and IL-1β suggests possible involvement of thioredoxin system in the activation of NLRP3 inflammasome, production of IL-1β, and the presence of inflammation in CAD patients.
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http://dx.doi.org/10.1007/s11033-021-06208-0DOI Listing
February 2021

Downregulation of Sirt1 is correlated to upregulation of p53 and increased apoptosis in epicardial adipose tissue of patients with coronary artery disease.

EXCLI J 2020 2;19:1387-1398. Epub 2020 Oct 2.

Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

The higher expression level of p53 in epithelial adipose tissue (EAT) has previously been reported in atherosclerosis. Since we hypothesized that the expression of p53 is modulated by Sirt1, the aim of this study was to determine the expression levels of Sirt1 and p53 and to investigate their correlation to apoptosis in EAT of patients with coronary artery disease (CAD). Thirty-five patients with more than 50 % stenosis in at least one of the main coronary arteries were considered as CAD group while 29 patients with no clinical signs of atherosclerosis who underwent open-heart surgery for valve replacement were classified as control group. EAT biopsy samples were collected from all participants during surgery. Sirt1, p53, Bax, and Bcl-2 gene expression levels were determined in EAT by qRT-PCR and Western blotting was carried out to assess Sirt1 and p53 protein levels. Hematoxylin and eosin staining was used for histopathological analysis. mRNA and protein levels of Sirt1 in EAT were significantly lower in patients with CAD compared with control group, whereas CAD patients showed greater p53 gene and protein expressions. In addition, inverse correlations were observed between Sirt1 and p53 at both mRNA and protein levels. The Bax and ratio of Bax/Bcl-2 gene expressions were higher in CAD group, but no difference was observed in Bcl-2 expression. Histopathological analysis showed apoptotic bodies and infiltrated immune cells in EAT of CAD group. Our results suggest that the Sirt1-p53 axis may involve in atherosclerosis by promotion of apoptosis.
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http://dx.doi.org/10.17179/excli2020-2423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689241PMC
October 2020

Effects of post-training administration of LY341495, as an mGluR2/3 antagonist on spatial memory deficit in rats fed with high-fat diet.

IBRO Rep 2020 Dec 25;9:241-246. Epub 2020 Sep 25.

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

High-fat diets (HFDs) adversely influence glutamate metabolism and neurotransmission. The precise role of the group II metabotropic glutamate receptors (mGluR2/3) antagonist on spatial memory deficit following consumption of HFD has not yet been clarified. Therefore, in this study, we examined the effects of post-training administration of mGluR2/3 antagonism; LY341495 on spatial memory in rats fed with HFD (for 10 weeks) by using Morris Water Maze (MWM) task. The training session for testing memory acquisition in MWM consisted of 4 trials per day for 4 consecutive days. Twenty-four hours after the last training session the spatial probe test (retention) was given. Intraperitoneal injection (i.p) injection of LY341495 was done 30 min before probe test. Our results showed that 10 weeks consumption of HFD had no significant effect on escape latency and swimming distance in memory acquisition. Our finding showed that consumption of a HFD leads to reference memory impairment in the probe test. HFD animals spent less time in the target zone in compare with control animals. Also, LY341495 improved HFD-induced reference memory (retention) impairment. HFD animals treated with LY341495 spent more time in the target zone in compare with HFD animals. Escape latencies to find the visible platform during visual task were same in all experimental groups, indicating no visual impairment in the animals. We propose that a HFD may act through mGluR2/3 within the brain to reduce synaptic plasticity, which impairs memory retrieval, and post-training administration of LY341495 can reduce HFD-induced reference memory impairment.
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http://dx.doi.org/10.1016/j.ibror.2020.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527618PMC
December 2020

Dill tablet and Ocimum basilicum aqueous extract: Promising therapeutic agents for improving cognitive deficit in hypercholesterolemic rats.

J Food Biochem 2020 12 4;44(12):e13485. Epub 2020 Oct 4.

Faculty of Medicine, Department of Clinical Biochemistry, Hamadan University of Medical Sciences, Hamadan, Iran.

High-cholesterol diet (HCD) is correlated with Alzheimer's disease (AD) and impairment of memory. This study investigated beneficial therapeutic effects of Dill tablet and Ocimum basilicum (Basil) aqueous extract on hypercholesterolemia-induced cognitive deficits and oxidative stress in hippocampus tissues of rats. Hippocampal Aβ(1-42) level was measured. The gene expression levels of superoxide dismutase and inducible-nitric oxide synthase were determined in hippocampus. Cognitive functions were examined and oxidative status was evaluated in serum and hippocampus. Phytochemical properties and in vitro antioxidant activity of Basil extract were assessed. HCD significantly increased serum cholesterol, induced deposition of Aβ plaque, altered hippocampus morphology, and impaired memory function, whereas receiving Basil extract or Dill tablet increased antioxidant potency in serum and hippocampus and normalized HCD-induced deleterious effects. Basil extract and Dill tablet may exhibit their beneficial effects in AD by lowering serum cholesterol and evoking antioxidant system in the brain. PRACTICAL APPLICATIONS: Dill tablet and Basil aqueous extract lowered serum cholesterol in hypercholesterolemic animal models, therefore, they can be used as hypocholesterolemic agents. These edible herbs significantly retarded deposition of Aβ plaque and normalized hippocampal morphology, thus, they favorably protected hippocampus tissue from deleterious effects-induced by hypercholesterolemia. Dill tablet and Basil aqueous extract also corrected oxide-redox balance and normalized HCD-induced oxidative stress to some extent and significantly improved impairments in learning and memory suggesting that these medicinal plants can be considered as surrogate therapeutic agents for the synthetic medicines in the treatment of AD and in postponement of its complications.
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http://dx.doi.org/10.1111/jfbc.13485DOI Listing
December 2020

Carvacrol Downregulates Lysyl Oxidase Expression and Ameliorates Oxidative Stress in the Liver of Rats with Carbon Tetrachloride-Induced Liver Fibrosis.

Indian J Clin Biochem 2020 Oct 30;35(4):458-464. Epub 2019 Aug 30.

Department of Pathobiology, Veterinary Medicine Faculty, Razi University, Kermanshah, Iran.

In the current study, we aimed to investigate the effect of carvacrol on the suppression of liver fibrosis progression through targeting lysyl oxidase (LOX) expression. The rats received carbon tetrachloride (CCl) intraperitoneally and carvacrol orally for 10 weeks. Liver damage was evaluated by measuring the serum level of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase and hepatic oxidative stress parameters including total antioxidant capacity, total thiol group and total oxidant status spectrophotometry and malondialdehyde fluorometrically. Extracellular deposition of collagen was detected using Masson's trichrome standing. Furthermore the gene expression of lysyl oxidase homolog 2 (Loxl2) was analyzed using quantitative reverse transcription-polymerase chain reaction. And then the protein level of LOX was detected in liver tissue by western blot method. Carvacrol administration normalized serum biochemical parameters and improved oxidative stress status in liver homogenate of CCl treated rats. Collagen fiber bundles in interlobular spaces were decreased remarkably by carvacrol treatment. Also, carvacrol downregulated hepatic gene expression of Loxl2 and protein level of LOX. Our data clearly revealed that carvacrol suppresses progression of liver fibrosis development via attenuating of liver damage and oxidative stress status as well as via downregulation of hepatic gene expression of Loxl2 and protein level of LOX.
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http://dx.doi.org/10.1007/s12291-019-00845-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502637PMC
October 2020

Tissue stiffness contributes to YAP activation in bladder cancer patients undergoing transurethral resection.

Ann N Y Acad Sci 2020 08 19;1473(1):48-61. Epub 2020 May 19.

Urology & Nephrology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

Changes in the cellular microenvironment play a critical role in the development of bladder cancer (BC). Yes-associated protein (YAP), a central mediator of the Hippo pathway, functions as a nuclear sensor of mechanotransduction that can be induced by stiffness of the extracellular matrix (ECM), including stiffness resulting from surgical manipulations. We aimed to clarify the possible association between surgically-related ECM stiffness and YAP activation in BC patients. We compared 30 bladder cancer tissues with grade II (n = 15 recurrent and n = 15 newly diagnosed) with 30 adjacent healthy tissues. Atomic force microscopy showed that patients with recurrent BC had stiffer ECM than newly diagnosed patients (P < 0.05). Gene expression profiles showed that β1 integrin (ITGB1), focal adhesion kinase (FAK), CDC42, and YAP were upregulated in cancerous tissues (P < 0.05); additionally, β1 integrin activation was confirmed using a specific antibody. Nuclear localization of YAP was higher in recurrent cancerous tissues compared with newly diagnosed and it was positively associated with higher stiffness (P < 0.05). Our results suggest that postsurgery-induced ECM stiffness can influence integrin-FAK-YAP activity and thereby YAP trafficking to the nucleus where it contributes to BC progression and relapse.
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http://dx.doi.org/10.1111/nyas.14358DOI Listing
August 2020

Overexpression of ROMO1 and OMA1 are Potentially Biomarkers and Predict Unfavorable Prognosis in Gastric Cancer.

J Gastrointest Cancer 2020 Sep;51(3):939-946

Department of Internal Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Purpose: One of the worst types of cancers is gastric cancer and no specific tumor marker is found in relation to it. Reactive oxygen species modulator 1 (ROMO1) and the overlapping with the M-AAA protease 1 homolog (OMA1) proteins are the most important mitochondrial membrane proteins, which are involved in modulating reactive oxygen species (ROS) production and the regulation of mitochondrial structure dynamics. If these proteins do not function properly, oxidative stress increases in the cell, and this can initiate the cancer or worsen the condition.

Methods: In this study, ROMO1 and OMA1 gene expressions in 40 fresh frozen gastric cancer tissue and healthy adjacent tissues were evaluated by real-time PCR, and some of the important parameters related to oxidative stress such as TAC, TOS, MDA, and TTG in the serum of cancer patients compared to healthy people were measured by spectrophotometric and fluorometric techniques.

Results: We observed that ROMO1 and OMA1 gene expressions in gastric cancer tissues increased compared to that in healthy adjacent tissues. In addition, oxidative stress parameters including TOS, OSI, and MDA in the serum of cancer patients have increased significantly and the parameters including TAC and TTG have decreased.

Conclusion: The results in our study represented that ROMO1 and OMA1 gene expressions in gastric cancer tissue have increased compared to that in healthy adjacent tissues, and oxidative stress levels have also increased significantly in relation to these proteins; therefore, these two proteins may be considered as an important cause of gastric cancer, and even introduced as tumor markers.
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http://dx.doi.org/10.1007/s12029-019-00330-wDOI Listing
September 2020

Co-administration of resveratrol and beta-aminopropionitrile attenuates liver fibrosis development via targeting lysyl oxidase in CCl-induced liver fibrosis in rats.

Immunopharmacol Immunotoxicol 2019 Dec 14;41(6):644-651. Epub 2019 Nov 14.

Department of Clinical Biochemistry, Hamadan University of Medical Sciences, Hamadan, Iran.

In the current study, we aimed to investigate the effect of administration of resveratrol (RES) and beta-aminopropionitrile (BAPN) separately and together on the liver fibrosis progression via regulation of the gene expression and protein level of lysyl oxidase (LOX). The six-week old Wistar rats received carbon tetrachloride (CCl) intraperitoneally and RES and BAPN were administrated orally for eight weeks. The hepatoprotective effects of RES, BAPN, and combination treatment were evaluated. Then the hepatic protein and gene expression levels of LOX were measured. Both RES and BAPN showed the antifibrotic effect through the reduction of collagen fiber bundles, hepatic hydroxyproline content, and protein level of LOX. The antifibrotic effect increased when RES and BAPN up-taken together. The co-administration of RES and BAPN can be considered as a promising therapeutic approach via targeting LOX.
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http://dx.doi.org/10.1080/08923973.2019.1688829DOI Listing
December 2019

Correlation between miR-103 and miR-133a Expression and the Circulating ANGPTL8 in Type 2 Diabetic Patients and Healthy Control Subjects.

Clin Lab 2019 Nov;65(11)

Background: Angiopoietin-like protein 8 (ANGPTL8) is a circulatory hormone that plays an important role in the proliferation of the pancreatic beta cells and lipid metabolism. MicroRNAs (miRs) are small non-coding RNAs that play an important role in the pathogenesis of diabetes mellitus. Therefore, we investigated the correlation of miR-103 and miR-133a expression with the ANGPTL8 and other type 2 diabetes mellitus (T2DM)-related factors.

Methods: Seventy subjects (controls: n = 35 and type 2 diabetic patients: n = 35) participated in this study. The ANGPTL8 concentration and miR-103/133a expression were measured using ELISA and real-time PCR, respectively.

Results: The circulatory ANGPTL8 concentration and miR-103/133a expression was significantly higher in T2D patients than in healthy controls (p < 0.05). There was a positive and significant correlation between miR-103/133a with triglycerides (TG), total cholesterol, fasting blood sugar (FBS), and glycated hemoglobin (p < 0.05) in the T2D group. The results also showed a negative and significant correlation between miR-103/133a expression with ANGPTL8 levels in the T2D group (p < 0.05).

Conclusions: Our results suggest that miR-103/133a expression is correlated with the ANGPTL8 and T2D-related factors.
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http://dx.doi.org/10.7754/Clin.Lab.2019.190436DOI Listing
November 2019

Liver stiffness correlates with serum osteopontin and TAZ expression in human liver cirrhosis.

Ann N Y Acad Sci 2020 04 7;1465(1):117-131. Epub 2019 Nov 7.

Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

The pivotal role of the extracellular matrix (ECM) as both a cause and consequence of liver fibrosis is striking. However, mechanotransducer molecules and profibrogenic factors induced by liver stiffness are still unclear. The current study aimed to investigate liver stiffness and its correlation with the expression of the transcriptional coactivator with PDZ-binding motif (TAZ) and serum osteopontin (OPN) in human cirrhosis. In this case-control study, liver tissue stiffness was determined using atomic force microscopy in cirrhotic livers (n = 38) of different etiologies and in controls (n = 10). Immunohistochemical and qRT-PCR analyses were performed to analyze TAZ expression. Besides, western blotting and ELISA were performed to assess liver Indian hedgehog and serum OPN levels, respectively. Liver stiffness, TAZ expression, and hepatic gene expression and serum protein levels of OPN were significantly increased in patients with cirrhosis compared with the control groups (all P < 0.001), specifically in autoimmune- and alcohol-related cirrhosis. In cirrhotic patients, liver stiffness was significantly associated with the expression of nuclear TAZ and OPN. The correlation between matrix stiffness as a mechanical property, TAZ as a potential mechanotransducer, and OPN as a matricellular factor suggests possible effects of mechanical features of the ECM on the expression of the aforementioned profibrogenic markers, which is predominant in autoimmune- and alcohol-related cirrhosis.
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http://dx.doi.org/10.1111/nyas.14259DOI Listing
April 2020

Changes in the distribution of etiologies of cirrhosis among patients referred for liver transplantation over 11 years in Iran.

Eur J Gastroenterol Hepatol 2020 07;32(7):844-850

Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan.

Background And Aim: Cirrhosis is a major public health problem worldwide. The prevalence of cirrhosis is various in different geographical regions. The aim of the present study was to determine the distribution of the etiologies of cirrhosis and their proportional changes through recent 11 years in Iran.

Methods: In this retrospective, observational study, the data of cirrhotic patients who have been listed for liver transplantation in the Namazi Transplant Center (Shiraz, Iran) between January 2006 and December 2016 were analyzed. Demographic and clinical data of the patients including model for end-stage liver disease score, year of registration, and the etiologic diagnosis for each patient were retrieved.

Results: The ratio of males to females was the highest (2.6:1) in patients with age over 50 years. Of 4891 patients, hepatitis B virus cirrhosis had the highest frequency (23.53%) and alcoholic cirrhosis had the lowest frequency (1.70%). The percentages of waiting list patients with hepatitis B virus (34.48%-17.48%) (P < 0.001), autoimmune hepatitis (12.64%-8.50%) (P = 0.037), and alcoholic cirrhosis (2.30%-1.10%) were decreased (P = 0.008) and the percentages of waiting list patients with cholestatic (12.64%-25.20%) and nonalcoholic steatohepatitis cirrhosis (0.77%-8.82%) were increased over 11 years (both P < 0.001). Hepatitis B virus and autoimmune hepatitis cirrhosis were the most prevalent in male and female patients, respectively.

Conclusion: The results of the present study showed an increase in the frequency of cholestasis and nonalcoholic steatohepatitis cirrhosis and therefore it should be considered in the health policy implementation.
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http://dx.doi.org/10.1097/MEG.0000000000001590DOI Listing
July 2020

Overexpression of PURPL and downregulation of NONHSAT062994 as potential biomarkers in gastric cancer.

Life Sci 2019 Nov 10;237:116904. Epub 2019 Oct 10.

Iran National Tumor Bank, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran.

Aims: Long non-coding RNAs (LncRNAs) play central roles in the formation and development of gastric cancer (GC). The aim of this study was to evaluate the expression of PURPL and NONHSAT062994 and the relationship between their expressions with clinical characteristics in GC.

Main Methods: PURPL and NONHSAT062994 LncRNAs and p53 gene expression levels were analyzed both in 50 pairs of cancerous and adjacent noncancerous tissue samples in GC patients using qRT-PCR and in four sets of data obtained from Gene Expression Omnibus (GEO) database. Chi-square (χ2) test was used to determine the relationship between PURPL, NONHSAT062994 RNA levels and the clinicopathological characteristics of GC. Receiver operating characteristic (ROC) curves were drawn to represent sensitivity and specificity of PURPL and NONHSAT062994 expression as markers of GC.

Key Findings: Expression of PURPL was significantly upregulated in 50 GC samples as well as in GC tissues from GSE13911 and GSE27342 datasets. Our results demonstrated that PURPL RNA level in GC was significantly related to tumor size and histopathological grade. p53 expression at both protein and mRNA levels were significantly decreased in GC tissues compared to adjacent control samples. NONHSAT062994 expression was downregulated in 50-pair GC and GC tissues from GSE13915 dataset. However, NONHSAT062994 showed no consistently differential expression in GSE2637dataset. NONHSAT062994 was significantly associated with histological grade and tumor size.

Significance: Overall, these results suggest that PURPL and NONHSAT062994 may play critical roles in the progression of GC and therefore might be considered as candidate tumor markers for therapeutic goals.
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http://dx.doi.org/10.1016/j.lfs.2019.116904DOI Listing
November 2019

Reactive Oxygen Species Modulator 1 (ROMO1), a New Potential Target for Cancer Diagnosis and Treatment.

Chonnam Med J 2019 Sep 24;55(3):136-143. Epub 2019 Sep 24.

Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Today, the incidence of cancer in the world is rising, and it is expected that in the next several decades, the number of people suffering from cancer or (the cancer rate) will double. Cancer is defined as the excessive and uncontrolled growth of cells; of course (in simple terms), cancer is considered to be a set of other diseases that ultimately causes normal cells to be transformed into neoplastic cells. One of the most important causes of the onset and exacerbation of cancer is excessive oxidative stress. One of the most important proteins in the inner membrane of mitochondria is Reactive Oxygen Species (ROS) Modulator 1 (ROMO1) that interferes with the production of ROS, and with increasing the rate of this protein, oxidative stress will increase, which ultimately leads to some diseases, especially cancer. In this overview, we use some global databases to provide information about ROMO1 cellular signaling pathways, their related proteins and molecules, and some of the diseases associated with the mitochondrial protein, especially cancer.
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http://dx.doi.org/10.4068/cmj.2019.55.3.136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769249PMC
September 2019

Cerium Oxide Nanoparticle Effects on Paraoxonase-1 Activity and Oxidative Toxic Stress Induced by Malathion: A Potential Antioxidant Compound, Yes or No?

Indian J Clin Biochem 2019 Jul 6;34(3):336-341. Epub 2018 Jun 6.

4Department of Toxicology and Pharmacology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, 6517838678 Iran.

Cerium oxide nanoparticles (CeNPs) are one of the most widely used and important nanoparticles in addition to possessing strong antioxidative properties and inhibiting free radicals. Paraoxonase-1 (PON1) is one of the enzymes that protect the body against damage caused by oxidative stress. The purpose of this study was to investigate the effect of CeNPs on the activity of PON1 as well as biomarkers of oxidative stress in the toxicity of malathion. 48 Albino Wistar male rats with weight range of 180-250 g were randomly divided into 8 groups, Group 1: healthy control, injection of normal saline, Group 2: administration by the malathion 100 mg/kg/day, Group 3: treated with CeNPs 15 mg/kg/day, Group 4: treated with CeNPs 30 mg/kg/day, Group 5: combination of malathion with dose of 100 mg/kg/day and CeNPs 15 mg/kg, Group 6: combination of malathion with dose of 100 mg/kg/day and CeNPs 30 mg/kg for 14 days and 24 h after termination of treatment period, serum and liver tissue samples were collected from all rats. Biochemical test of PON1 activity, oxidative stress biomarkers including total antioxidant capacity (TAC), lipid peroxidation (LPO), total thiol groups (TTG), were carried out. Malathion reduced plasma TTG levels, TAC and increased LPO in malathion group. However, CeNPs increased TTG, TAC and reduced PON1 activity. Results showed that CeNPs alone had antioxidant properties while with malathion it shows different properties.
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http://dx.doi.org/10.1007/s12291-018-0760-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660592PMC
July 2019

Silymarin Attenuates ELMO-1 and KIM-1 Expression and Oxidative Stress in the Kidney of Rats with Type 2 Diabetes.

Indian J Clin Biochem 2019 Apr 6;34(2):172-179. Epub 2018 Feb 6.

1Department of Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Chronic diabetes mellitus is accompanied with overexpression of ELMO1 and KIM1 and enhanced oxidative stress. This study was aimed to evaluate the effects of administration of silymarin on oxidative stress markers and ELMO1 and KIM1 expression in the kidney tissue of type 2 diabetic rats. In this experimental study, 36 male Wistar rats were divided into 6 groups: Control, silymarin-treated control (60 and 120 mg/kg/day), diabetic, and silymarin-treated diabetic groups (60 and 120 mg/kg/day). Tissue levels of oxidative stress and biochemical parameters were measured by spectrophotometric methods. Lipid peroxidation levels in the kidney tissue were measured by fluorometric method. Insulin was determined using immunoassay. Gene expression analysis was determined by qPCR technique. The level of expression of ELMO1 and KIM1 in the diabetic groups treated with silymarin was significantly reduced ( < 0.001). Total antioxidant levels and thiol groups contents increased ( < 0.001) dramatically in treated groups. A significant decrease in tissue levels of malondialdehyde and total oxidant were observed in the silymarin treated diabetic rats ( < 0.001). The results showed that the urinary amount of protein in the treatment groups was significantly lower than of diabetic control ( < 0.001). These results indicate that silymarin has a blood glucose lowering effect and, due to its antioxidant properties, increases the antioxidant parameters and reduces the oxidant markers. The administration of silymarin has beneficial effects on kidney of diabetic rats with reduction of ELMO1 and KIM1expression.
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http://dx.doi.org/10.1007/s12291-018-0735-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486928PMC
April 2019

Intricate role of yes-associated protein1 in human liver cirrhosis: TGF-β1 still is a giant player.

IUBMB Life 2019 10 14;71(10):1453-1464. Epub 2019 May 14.

Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Numerous investigations have been performed on the role of the transforming growth factor-β1 (TGF-β1) pathway in the development of chronic liver diseases (CLDs); however, they failed to explain the underlying mechanism of its pathogenesis, suggesting that other alternative pathways might have been overlooked. The involvement of yes-associated protein1 (YAP1) has been attributed to liver fibrosis; yet, the precise function of this protein has not been fully understood. Therefore, this study aimed to investigate the activity of the YAP1 pathway in human liver cirrhosis (regardless of its causality) and its correlation with the TGF-β1 and sonic hedgehog (SHH) pathways. In this case-control study, the immunohistochemical and quantitative real-time polymerase chain reaction analyses were carried out to determine the activation of the YAP1 pathway in patients with liver cirrhosis (n = 38) and control 1 individuals (n = 10). The western blot analysis and ELISA method were also performed to assess the SHH and TGF-β1 pathways. Although significantly increased expression of cytoplasmic YAP1 was found in patients with liver cirrhosis (P < 0.045), the rate of the nuclear YAP1 expression was similar to that of the control 1 subjects. Moreover, the hepatic expression of amphiregulin (AREG), known as the YAP1 target, along with proteins involved in the TGF-β1 pathway was significantly elevated in all cirrhotic patients, compared with the control subjects. Our results showed that the increased activity of the TGF-β1 pathway is strongly associated with the expression of AREG, denoting a direct and positive relationship between the TGF-β1 and YAP1 pathways. It seems that, unlike the TGF-β1 and SHH pathways, the YAP1 pathway does not play a significant role in the development of liver cirrhosis.
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http://dx.doi.org/10.1002/iub.2052DOI Listing
October 2019

Downregulation of hedgehog ligands in human simple steatosis may protect against nonalcoholic steatohepatitis: Is TAZ a crucial regulator?

IUBMB Life 2019 09 14;71(9):1382-1390. Epub 2019 May 14.

Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

The conversion of simple steatosis into nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease (NAFLD) has attracted many attentions in recent years. The role of the hedgehog (HH) pathway in the regulation of lipogenesis has been addressed in the literature. This study aimed to investigate the levels of the sonic hedgehog (SHH) and Indian hedgehog (IHH) ligands and the correlation of these ligands with levels of proteins involved in the transforming growth factor-β1 (TGF-β1) pathway, as well as the evaluation of the transcriptional coactivator with PDZ binding motif (TAZ) expression in human simple steatosis, NASH cirrhosis, and controls. Patients were divided into two groups: the first group consisted of patients diagnosed with simple steatosis (n = 16) and the second group included those diagnosed with NASH cirrhosis (n = 15). As a control group, 18 histologically normal liver tissues were collected in this study. The expression of the TGF-β1pathway components and SHH and IHH ligands were analyzed by means of the quantitative real-time polymerase chain reaction and western blot analyses. A significant decrease was found in the hepatic expression of the SHH, IHH, and TGF-β1 pathways along with the expression of TAZ in tissue specimens with simple steatosis in comparison with patients affected by NASH cirrhosis and controls. Also, the levels of SHH and IHH proteins were significantly correlated with the expression of proteins involved in the TGF-β1 pathway. Moreover, the expression of the HH pathway ligands was positively associated with the expression of TAZ, supporting the notion that TAZ may play a role in the activation of the HH pathway thereby regulating the expression of its ligands. It seems that in patients with NAFLD, the downregulation of the HH pathway ligands may stem from steatosis; however, at the same time, it may prevent the conversion of simple steatosis into NASH in patients with liver diseases. © 2019 IUBMB Life, 71(9):1382-1390, 2019.
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http://dx.doi.org/10.1002/iub.2068DOI Listing
September 2019

Hepatoprotective Effects of Silymarin on Liver Injury via Irisin Upregulation and Oxidative Stress Reduction in Rats with Type 2 Diabetes.

Iran J Med Sci 2019 Mar;44(2):108-117

Department of Pathobiology, Veterinary Medicine Faculty, Razi University, Kermanshah, Iran.

Background: Diabetes is one of the most prevalent metabolic diseases. Irisin (FNDC5 protein) is involved in the new strategy of combating type 2 diabetes. In the liver, the antidiabetic mechanism of silymarin at the molecular level is unknown. This study investigated the effects of silymarin on irisin and the related gene expression and oxidative stress status in the liver of type 2 diabetic rats.

Methods: Thirty-six rats were divided into 6 groups (n=6 each) by simple randomization: control, control+silymarin (60 mg/kg daily in normal saline orally for 60 days), control+silymarin (120 mg/kg daily in normal saline orally for 60 days), diabetic, diabetic+silymarin (60 mg/kg daily for 60 days), and diabetic+silymarin (120 mg/kg daily for 60 days). Biochemical parameters were measured by spectrophotometric and immunoassay methods, and quantitative polymerase chain reaction was used to evaluate gene expression. The data were analyzed by one-way ANOVA, followed by the Tukey test, using SPSS software, version 16.0. The results were considered statistically significant at a P value less than 0.05.

Results: In the diabetic rats treated with silymarin (60 and 120 mg/kg), by comparison with the diabetic group, body weight (P=0.04 and P=0.02), insulin (P<0.001), expression of PGC-1α (P=0.04 and P=0.02), expression of FNDC5 (P=0.03 and P=0.01), and concentration of irisin in the liver (P=0.02 and P=0.01) and serum (P<0.001) were significantly increased, whereas the levels of glucose (P<0.001), HOMA-IR (P=0.03 and P=0.01), and liver injury markers (P<0.001) were significantly reduced. Oxidative stress status and histopathological changes were improved in the treated groups.

Conclusion: These results suggest that silymarin because of its ability to upregulate irisin and antioxidant effects can be considered an antidiabetic agent.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423431PMC
March 2019

Carvacrol ameliorates the progression of liver fibrosis through targeting of Hippo and TGF-β signaling pathways in carbon tetrachloride (CCl)-induced liver fibrosis in rats.

Immunopharmacol Immunotoxicol 2019 Feb 1;41(1):163-171. Epub 2019 Feb 1.

c Department of Pathobiology , Veterinary Medicine Faculty Razi University , Kermanshah , Iran.

Little is known about the exact underlying molecular mechanisms of the hepatoprotective effect of carvacrol against liver fibrosis. In the current study, we aimed to investigate the effect of carvacrol on the suppression of liver fibrosis progression via regulation of yes-associated protein (YAP) and transcriptional coactivators with a PDZ-binding motif (TAZ) and transforming growth factor beta (TGF-β) pathway. To fulfill our target, rats received carbon tetrachloride (CCl) and carvacrol intraperitoneally, and orally, respectively for 10 weeks. Body weight, liver weight, serum biochemical parameters, hepatic hydroxyproline content, and histological changes were determined. Furthermore, gene expression of collagen and key elements of Hippo and TGF-β pathways were analyzed and then the protein levels of YAP, TAZ, and TGF-β were detected in liver tissue. Carvacrol administration normalized liver and body weight, serum biochemical parameters and hepatic hydroxyproline in CCl treated rats. Also, carvacrol downregulated TAZ and TGF-β signaling pathway at transcriptional levels. Furthermore, carvacrol decreased hepatic protein levels of TGF-β, TAZ, and YAP. Low expression of TAZ and YAP were accompanied with inhibition of TGF-β signaling pathway. Our data clearly revealed that carvacrol suppresses the progression of liver fibrosis via targeting of TAZ, YAP, and TGF-β signaling pathway.
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http://dx.doi.org/10.1080/08923973.2019.1566926DOI Listing
February 2019

Effects of insulin-loaded chitosan-alginate nanoparticles on RAGE expression and oxidative stress status in the kidney tissue of rats with type 1 diabetes.

Iran J Basic Med Sci 2018 Oct;21(10):1035-1042

Department of Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Objectives: Chronic hyperglycemia leads to activation of the advanced glycation end products (AGE)-receptor (RAGE) for AGE axis and oxidative stress, which promote diabetic renal damage. This study examines the effect of insulin-loaded trimethyl chitosan nanoparticles on the kidney tissue of diabetic rats.

Materials And Methods: Twenty-five male Wistar rats were randomly divided into 5 groups: normal control (C), diabetic group without treatment (DM), diabetic group treated with chitosan-based nanoparticle (DM+NP, 1 ml by gavage), diabetic group treated with 8 IU/kg insulin-loaded trimethyl chitosan nanoparticles (DM+N.in, 1 ml by gavage), and diabetic group treated with 8 IU/kg trade insulin (DM+SC.in, 0.2 ml by subcutaneous injection). The animals were treated from weeks 8 to 10. At the end of the study, serum urea, creatinine, and uric acid were measured. Also, the level of AGE and RAGE mRNA expression, and oxidative stress markers were studied in the kidney tissue.

Results: Insulin-loaded nanoparticles similar to trade insulin could significantly reduce urea, creatinine, and uric acid parameters, while the elevated total antioxidant capacity (TAC), thiol groups, and catalase activity also reduced total oxidant status (TOS) and malondialdehyde (MDA) levels (<0.05). However, the reduction in AGE and RAGE mRNA expression is not statistically significant in both treatments. Of course, the influence of insulin-loaded trimethyl chitosan nanoparticles on the amelioration of all these parameters is higher compared to that of the injected form. No markedly significant differences were observed between these two kinds of treatments.

Conclusion: This data reveals that insulin-loaded trimethyl chitosan nanoparticle is a better therapeutic approach than injected insulin.
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http://dx.doi.org/10.22038/IJBMS.2018.28463.6899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281063PMC
October 2018

Protective effects of combined Losartan and Nilotinib on carbon tetrachloride (CCl)-induced liver fibrosis in rats.

Drug Chem Toxicol 2020 Sep 12;43(5):468-478. Epub 2018 Sep 12.

Faculty of Medicine, Department of Pharmacology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Tyrosine kinase inhibitors (TKIs) have been developed as therapeutic compounds for inhibiting the progression of liver fibrosis. In the present study, the simultaneous treatment of Nilotinib (TKIs) and Losartan was studied. Forty rats were divided into eight groups of fibrosis induced by carbon tetrachloride (CCl) and therapeutics (Nilotinib, Losartan, and combination therapy). In the end, serum parameters of the liver and gene expression analysis of transforming growth factor-β, its receptors (TβRII), platelet-derived growth factor, its receptors (PDGFR), matrix metalloproteinases (MMP-2 and MMP-9), tumor necrosis factor-α, cytochrome P450 2E1, and collagen1 type 1 were performed. The oxidant/antioxidant factors were also analyzed. Histopathology analysis along with α-SMA immunohistochemistry and hydroxyproline evaluation was also conducted for a more in-depth study. The overall results indicated a better therapeutic effect of co-treatment of Nilotinib-Losartan in comparison with the treatment of each of them alone. Interestingly, some gene and protein factors and fibrotic indices were reduced even to the normal levels of the control group. The results of this study suggest that co-administration of these two combinations, strengthens their anti-fibrotic properties and, due to the routine use of these compounds against AML and blood pressure, these compounds can be used with caution against human liver fibrosis.
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http://dx.doi.org/10.1080/01480545.2018.1504960DOI Listing
September 2020

Association between rs2278426 (C/T) and rs892066 (C/G) variants of ANGPTL8 (betatrophin) and susceptibility to type2 diabetes mellitus.

J Clin Lab Anal 2019 Jan 7;33(1):e22649. Epub 2018 Sep 7.

Department of Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Background: Angiopoietin-like protein 8 (ANGPTL8) is a hormone that mainly secreted from the liver and adipose tissue and plays an important role in the proliferation of pancreatic beta cells and lipid metabolism. Therefore, we studied the association of ANGPTL8 rs2278426 (C/T) and rs892066 (C/G) polymorphisms with the risk of type 2 diabetes mellitus (T2DM) and their association with biochemical parameters.

Methods: Two hundred and eighty-eight subjects (controls; n = 138 and type 2 diabetic patients; n = 150) were enrolled in this study. Direct haplotyping was performed using amplification-refractory mutation system (ARMS)-RFLP-PCR.

Results: The CT genotype frequency of rs2278426 (C/T) variant was significantly higher in T2DM patients compared to the controls group (P = 0.02), and there was a significant association between this genotype and increased risk of T2DM (OR: 2.41, CI: 1.26-4.59, P = 0.007). In addition, there was a significant relationship between CT genotype of this variant and high-density lipoprotein cholesterol (HDL-C), fasting blood sugar (FBS), insulin, insulin resistance and glycated hemoglobin (P < 0.05). Furthermore, bioinformatics analysis revealed that arginine (Arg) to tryptophan (Trp) substitution at rs2278426 position causes structural instability of ANGPTL8 protein. Genotype and allele distribution of rs892066 (C/G) was not statistically significant in T2DM patients compared to the control group. The distribution of haplotypes had no significant difference between controls and T2DM patients (P = 0.24).

Conclusion: Our results suggest that the rs2278426 (C/T) variant is associated with increased risk of T2DM and may cause dyslipidemia due to its effect on decreasing HDL-C levels.
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http://dx.doi.org/10.1002/jcla.22649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430336PMC
January 2019

Anticancer activity, calf thymus DNA and human serum albumin binding properties of Farnesiferol C from .

J Biomol Struct Dyn 2019 Jul 22;37(11):2789-2800. Epub 2018 Oct 22.

a Research Center for Molecular Medicine , Hamadan University of Medical Sciences , Hamadan , Iran.

In this study, Farnesiferol C was introduced as an anti-colon cancer agent. Its cytotoxicity was investigated on two cancer cell lines, HCT116 and CT26, and mesenchymal stem cells (MSCs) as normal cells employing MTT assay. Moreover, Farnesiferol C interactions with ct-DNA and HSA were investigated by various techniques. The IC values of Farnesiferol C on HCT116 and CT26 cells were 42 and 46 μM, respectively, while its IC value on MSCs cells was 92 μM, indicating that Farnesiferol C was more efficacious against cancer cell lines than normal cells. DNA competitive binding studies, viscosity and zeta potential measurements confirmed that Farnesiferol C bound to DNA through intercalation binding. HSA binding investigations revealed that there were two different binding sites for Far C on HSA with higher binding affinity in site 2 compared to site 1. Furthermore, Farnesiferol C could bind to HSA and quench its intrinsic fluorescence in a static quenching mechanism, with a distance of 2.54 nm. Competitive binding in the presence of warfarin and ibuprofen was carried out and the resulting quenching constant was strongly changed in the presence of warfarin. Consequently, Farnesiferol C most probably will be located within sub-domain IIA. In this study, molecular modeling buttressed and confirmed our laboratory results. Conclusively, we proposed that DNA is an appropriate target for Farnesiferol C. Therefore, Farnesiferol C and its semisynthetic analogues can be one of the priority innovations in research on anticancer drugs.
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http://dx.doi.org/10.1080/07391102.2018.1497543DOI Listing
July 2019

In vitro cytotoxicity and DNA/HSA interaction study of triamterene using molecular modelling and multi-spectroscopic methods.

J Biomol Struct Dyn 2019 Jun 13;37(9):2242-2253. Epub 2018 Nov 13.

a Faculty of Chemistry , Bu-Ali Sina University , Hamedan , Iran.

The anticancer activity of triamterene on HCT116 and CT26 colon cancer cells lines was investigated. Furthermore, the mechanism of interaction between triamterene and calf thymus DNA (ct-DNA) and also human serum albumin (HSA) was conducted using spectroscopic and molecular docking techniques. In vitro cytotoxicity of triamterene against HCT116 and CT26 cells showed promising anticancer effects with IC50 values of 31.30 and 24.45 μM, respectively. Competitive studies of the triamterene with NR (neutral red) and MB (methylene blue) as intercalator probes showed that triamterene can be replaced by these probes. The viscosity data also confirmed that triamterene binds to calf-thymus DNA through intercalation binding mode. Binding properties of triamterene with HSA in the presence of warfarin and ibuprofen showed that triamterene competes with warfarin for the site I of human serum albumin (HSA). In addition, the binding modes of triamterene with DNA and HSA were verified by molecular docking technique. Abbreviations ct-DNA calf thymus DNA CV cyclic voltammetry DNA deoxyribonucleic acid DPV differential pulse voltammetry FBS fetal bovine serum HSA human serum albumin NR neutral red MB methylene blue MTT 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazoliumbromide Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2018.1489305DOI Listing
June 2019

MiR-185 enhances radiosensitivity of colorectal cancer cells by targeting IGF1R and IGF2.

Biomed Pharmacother 2018 Oct 11;106:763-769. Epub 2018 Jul 11.

Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. Electronic address:

Objective: Radioresistance is a significant obstacle for effective treatment of colorectal cancer (CRC). Recent studies have indicated that miR-185 inhibits proliferation, survival, and invasion of CRC; however, the role of this miRNA in radioresistance of CRC has not been identified yet. The aim of this study is to investigate the role of miR-185 in radiosensitivity of CRC.

Methods: After transfecting the cells with mimic miR-185, expressions of IGF1R and IGF2 were evaluated by real-time PCR and western blot. The radiation response of transfected cells was also examined by colony forming assay. Sub-G1 fraction analysis through flow cytometry and caspase 3 activity was used to evaluate apoptosis.

Results: The results of real-time PCR and western blot indicated that IGF1R and IGF2 are downregulated in the transfected cells. Colony forming assay revealed that transfected cells were more radiosensitive than other cells. On the other hand,following irradiation the rate of apoptosis was significantly higher in the transfected cells than in the other cells.

Conclusion: In summary, our study is the first to show that upregulation of miR-185 enhances the sensitivity of CRC cells to ionizing radiation. miR-185 may act as a novel biomarker of radioresistance and may clinically enhance the radiation response of CRC.
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http://dx.doi.org/10.1016/j.biopha.2018.07.002DOI Listing
October 2018

Calcium: A novel and efficient inducer of differentiation of adipose-derived stem cells into neuron-like cells.

J Cell Physiol 2018 11 5;233(11):8940-8951. Epub 2018 Jun 5.

Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

This study comparatively investigated the effectiveness of calcium and other well-known inducers such as isobutylmethylxanthine (IBMX) and insulin in differentiating human adipose-derived stem cells (ADSCs) into neuronal-like cells. ADSCs were immunophenotyped and differentiated into neuron-like cells with different combinations of calcium, IBMX, and insulin. Calcium mobilization across the membrane was determined. Differentiated cells were characterized by cell cycle profiling, staining of Nissl bodies, detecting the gene expression level of markers such as neuronal nuclear antigen (NeuN), microtubule associated protein 2 (MAP2), neuron-specific enolase (NSE), doublecortin, synapsin I, glial fibrillary acidic protein (GFAP), and myelin basic protein (MBP) by quantitative real-time polymerase chain reaction (quantitative real-time polymerase chain reaction (qRT-PCR) and protein level by the immunofluorescence technique. Treatment with Ca + IBMX + Ins induced neuronal appearance and projection of neurite-like processes in the cells, accompanied with inhibition of proliferation and halt in the cell cycle. A significantly higher expression of MBP, GFAP, NeuN, NSE, synapsin 1, doublecortin, and MAP2 was detected in differentiated cells, confirming the advantages of Ca + IBMX + Ins to the other combinations of inducers. Here, we showed an efficient protocol for neuronal differentiation of ADSCs, and calcium fostered differentiation by augmenting the number of neuron-like cells and instantaneous increase in the expression of neuronal markers.
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http://dx.doi.org/10.1002/jcp.26826DOI Listing
November 2018

Association between seminal plasma neopterin and oxidative stress in male infertility: A case-control study.

Int J Reprod Biomed 2018 Feb;16(2):93-100

Endometer and Endometriosis Centre, Fatemieh Hospital, Hamadan University of Medical Sciences, Hamadan, Iran.

Background: Neopterin is a significant and sensitive marker in estimating the activity of cellular immune system. Oxidative stress plays a role in the etiology of male infertility. Increased reactive oxygen species is accompanied with increase in neopterin level. Hence neopterin may be involved in male infertility.

Objective: The objective of this case-control study was to determine neopterin level in idiopathic infertile and normospermic men; furthermore, to identify its relationship with oxidative stress markers including total oxidant, malondialdehyde, sperm DNA fragmentation, and total antioxidant capacity of seminal plasma.

Materials And Methods: Forty seven infertile and forty three normospermic males were selected according to WHO criteria. Their semen and blood samples were taken; subsequently, the levels of neopterin, total oxidant, total antioxidant, malondialdehyde, and sperm DNA fragmentation were measured.

Results: The levels of neopterin, total oxidant, and malondialdehyde in seminal plasma of infertile males were significantly higher than those of normospermic group (p=0.038, 0.018, and 0.028, respectively). Furthermore, sperm DNA fragmentation in infertile men was higher than that of control group (p<0.001). Moreover, total antioxidant capacity of seminal plasma in infertile males was significantly lower than that of normospermic subjects (p=0.002). No significant difference was observed in serum neopterin, total oxidant, and malondialdehyde between the infertile and normospermic groups.

Conclusion: The significant inverse correlation between seminal plasma neopterin and total antioxidant in the infertile males supports a possible role of neopterin in male infertility. Neopterin can be suggested as a marker in monitoring and diagnosis of idiopathic male infertility.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899823PMC
February 2018

Silymarin ameliorates expression of urotensin II (U-II) and its receptor (UTR) and attenuates toxic oxidative stress in the heart of rats with type 2 diabetes.

Biomed Pharmacother 2018 May 27;101:244-250. Epub 2018 Feb 27.

Department of Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular disease (CVD). Urotensin II ((U-II)) and its receptor (UTR) are involved in the progression of CVD through enhancement in the production of reactive oxygen species (ROS). Since silymarin (SMN) is a natural agent with anti-diabetic effects, this study aimed to investigate the antioxidant potency of SMN on the expression of (U-II)/UTR system and oxidative stress status in the heart of type 2 diabetic rats. Thirty-six male Wistar rats were randomly divided into six groups (n = 6). Control and diabetic groups treated with or without SMN (60 and 120 mg/kg/day) for 2 months. Fasting blood sugar (FBS), insulin, lipid profile, creatine kinase-MB ((CK-MB)), lactate dehydrogenase (LDH) and markers of oxidative stress were measured by spectrophotometric methods while (U-II) and UTR gene expression was determined by qPCR method. SMN significantly reduced the FBS level, increased the concentration of insulin and improved HOMA-IR. SMN prevented diabetes-induced weight loss, and attenuated the increased levels of total oxidative status (TOS), malondialdehyde (MDA), and nitric oxide (NO). Diabetes-induced reduction of total thiol molecules content (TTM) was normalized to the normal level in SMN treated rats. SMN significantly modulated serum lipid profile, reduced the expression of (U-II) and UTR in the heart, and improved histopathological changes in the heart tissues. Therefore, the current study indicated that SMN ameliorated unpleasant diabetic characteristics via down-regulation of (U-II) and UTR gene expression and modulation of oxidative stress in the heart tissue of type 2 diabetic rats.
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http://dx.doi.org/10.1016/j.biopha.2018.02.075DOI Listing
May 2018

Silymarin prevents lipid accumulation in the liver of rats with type 2 diabetes via sirtuin1 and SREBP-1c.

J Basic Clin Physiol Pharmacol 2018 Jun;29(3):301-308

Department of Pathobiology, Veterinary Medicine Faculty, Razi University, P.O. Box 67156-85414, Kermanshah, Iran.

Background: In this study, we have investigated whether silymarin intake influences lipid and glycogen content in conjunction with sirtuin1 (SIRT1) and sterol regulatory element-binding protein 1c (SREBP-1c) expressions in liver of type 2 diabetic rat.

Methods: Thirty-six male Wistar rats were randomly divided into six groups: control groups (C) and diabetic groups (D); the control groups received 60 or 120 mg/kg silymarin (C+S60 or C+S120), and the diabetic groups received 60 or 120 mg/kg silymarin (D+S60 or D+S120) daily for 8 weeks. Serum biochemical parameters, as well as glycogen, lipid and oxidative stress biomarkers, in the liver tissue were measured by spectrophotometric methods. Additionally, SIRT1 and SREBP-1c messenger RNA (mRNA) expressions were evaluated by quantitative polymerase chain reaction.

Results: Diabetes caused a significantly increased fasting blood sugar, homeostasis model assessment for insulin resistance, liver total cholesterol and triglyceride (TG) content, which were attenuated after the administration of silymarin. Dietary silymarin caused the improvement of lipid content in the liver of diabetic rats. Moreover, silymarin administration promoted SIRT1, suppressed SREBP-1c mRNA expression, reduced liver nitric oxide and protein carbonyl content, and increased liver glycogen, catalase and glutathione peroxidase activity. Furthermore, histopathological changes were improved in the treated groups.

Conclusions: Silymarin administration considerably restored hepatic changes induced by streptozotocin and nicotinamide. The upregulation of SIRT1 mRNA expression by silymarin may be associated with decreased lipid, increased glycogen content and downregulation of the SREBP-1c gene in the liver.
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http://dx.doi.org/10.1515/jbcpp-2017-0122DOI Listing
June 2018