Publications by authors named "Mohammad Soukhtanloo"

92 Publications

Protective effects of a standardized extract of on pancreas and liver in streptozotocin-induced diabetic rats.

Res Pharm Sci 2021 Feb 30;16(1):71-78. Epub 2020 Dec 30.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, I.R. Iran.

Background And Purpose: Previous studies have shown the antioxidant, anti-inflammatory, immunomodulatory, and hypolipidemic activities of . The aim of the present study was to evaluate the protective effects of hydroalcoholic extract of rhizomes on streptozotocin-induced diabetic rats.

Experimental Approach: Twenty-four male Wistar rats were randomly assigned into four groups including a normal control group, diabetic control group, diabetic groups treated for 4 weeks with 100 and 200 mg/kg/day of the extract (IGE).

Findings/results: Induction of diabetes significantly decreased the body weight gain and considerably increased the serum levels of glucose, triglyceride, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Diabetes also diminished the antioxidant capacity of the liver (decrease of thiol groups) and significantly degenerated pancreatic islands. The IGE at both doses of 100 and 200 mg/kg significantly reduced the levels of glucose, triglyceride, AST, ALT, and ALP. Moreover, IGE increased the total antioxidant capacity of the liver and ameliorated pancreatic island morphology. The extract had no significant effect on body weight and BUN level.

Conclusion And Implication: These findings suggest that rhizomes inhibits the progression of hyperglycemia and hypertriglyceridemia and has protective effects against diabetes-induced injury of the liver and pancreas. Therefore, this plant has the potential to be used as a natural product for controlling diabetes.
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http://dx.doi.org/10.4103/1735-5362.305190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074805PMC
February 2021

Cardioprotective effects of Fenugreek () seed extract in streptozotocin induced diabetic rats.

J Cardiovasc Thorac Res 2021 13;13(1):28-36. Epub 2021 Jan 13.

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

Inadequate control of diabetes mellitus (DM) leads to considerable cardiovascular implications like diabetic cardiomyopathy (DCM). Cardiomyocyte apoptosis is one of the main mechanisms of DCM pathogenesis associated with hyperglycemia, oxidative stress, inflammation, hyperlipidemia and several other factors. (Fenugreek) has been long used as a traditional medicine and has many therapeutic effects, including anti-diabetic, anti-hyperlipidemia, anti-inflammatory and anti-oxidant properties. The current study aimed to investigate cardioprotective effects of fenugreek seed on diabetic rats. Diabetes was induced in forty-two male rats by injection of streptozotocin (STZ) (60 mg/ kg). Diabetic animals were treated with three different doses of fenugreek seed extract (50, 100 and 200 mg/kg) or metformin (300 mg/kg) for six weeks by gavage. Nondiabetic rats served as controls. Glucose, cholesterol, and triglycerides levels were measured in the blood samples, and oxidative stress markers as well as gene expression of , and were assessed in the cardiac tissues of the experimental groups. Diabetic rats exhibited increased serum glucose, cholesterol and triglycerides levels, elevated markers of oxidative stress thiobarbituric acid-reacting substances (TBARS) levels , total thiol groups (SH), catalase (CAT) and superoxide dismutase (SOD) activity, and enhanced apoptosis cell death (ratio of Bax/Bcl2). Fenugreek seed extract considerably improved metabolism abnormalities, attenuated oxidative stress and diminished apoptosis index. Our study suggests that fenugreek seed may protect the cardiac structure in STZ-induced diabetic rats by attenuating oxidative stress and apoptosis.
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http://dx.doi.org/10.34172/jcvtr.2021.01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007891PMC
January 2021

A review on liposome-based therapeutic approaches against malignant melanoma.

Int J Pharm 2021 Apr 2;599:120413. Epub 2021 Mar 2.

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Melanoma is a highly aggressive form of skin cancer with a very poor prognosis and excessive resistance to current conventional treatments. Recently, the application of the liposomal delivery system in the management of skin melanoma has been widely investigated. Liposomal nanocarriers are biocompatible and less toxic to host cells, enabling the efficient and safe delivery of different therapeutic agents into the tumor site and further promoting their antitumor activities. Therefore, the liposomal delivery system effectively increases the success of current melanoma therapies and overcomes resistance. In this review, we present an overview of liposome-based targeted drug delivery methods and highlight recent advances towards the development of liposome-based carriers for therapeutic genes. We also discuss the new insights regarding the efficacy and clinical significance of combinatorial treatment of liposomal formulations with immunotherapy and conventional therapies in melanoma patients for a better understanding and successfully managing cancer.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120413DOI Listing
April 2021

Morus nigra L. extract prolongs survival of rats with hepatocellular carcinoma.

Phytother Res 2021 Jun 23;35(6):3365-3376. Epub 2021 Feb 23.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.

Morus nigra is a rich source of anthocyanins, phytochemicals that have anticancer effects. This study aimed to investigate the effects of M. nigra extract (MNE) on diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC). Male Sprague-Dawley rats were assigned into four groups (n = 10): control, DEN, and DEN +100 or 400 mg/kg of MNE. After 4 months, the DEN group showed a significant mortality rate, hepatic lipid peroxidation, dysplastic nodules in the cirrhotic liver, and an increase of blood bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Also, the body weight gain, blood albumin and glucose, liver antioxidant capacity (thiol groups), and some hematological parameters (RBC, hematocrit, hemoglobin, and platelet) were significantly decreased in the DEN group. MNE significantly increased survival, reduced the size of HCC nodules, improved liver oxidant/antioxidant status, and prevented the above-mentioned changes in the blood (except ALP, glucose, and platelet). Quantitative real-time PCR showed that MNE decreased the expression of Wnt4 and β-catenin, while had no significant effect on PI3K, Akt, and PTEN expression. The MNE did not exhibit antiproliferative activity against HepG2 liver cancer cells. In conclusion, MNE exhibits a hepatoprotective effect through inhibiting oxidative stress and Wnt4/β-catenin pathway and therefore prolongs the survival of rats with HCC.
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http://dx.doi.org/10.1002/ptr.7056DOI Listing
June 2021

The effects of nanomicelle of curcumin on the matrix metalloproteinase (MMP-2, 9) activity and expression in patients with coronary artery disease (CAD): A randomized controlled clinical trial.

ARYA Atheroscler 2020 May;16(3):136-145

Associate Professor, Pharmacological Research Center of Medicinal Plants AND Department of Clinical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Coronary artery disease (CAD) is the most common type of cardiovascular disease. Increasing the expression and activity of matrix metalloproteinases (MMPs) facilitates vascular remodeling and cardiovascular complications. Curcumin (the active ingredient of turmeric) is a potent natural anti-inflammatory agent, with cardiovascular protective effects. The present study was a clinical trial for investigating the effects of curcumin on activity and gene expression of MMP-2 and MMP-9 in patients with CAD.

Methods: In this study, 70 patients with CAD (with 40%-50% stenosis) were randomly divided into two groups of curcumin (80 mg nanomicelle per day) and placebo. The intervention lasted 3 months. The activity levels of MMP-2 and MMP-9 in serum samples of patients were measured using gelatin zymography assay before and after the intervention. MMP-2 and MMP-9 gene expression in peripheral blood mononuclear cells (PBMCs) was also analyzed using real-time polymerase chain reaction (PCR). Statistical significance was set at P < 0.0500.

Results: After 3 months of medication, the expression of MMP-9 produced by PBMCs significantly decreased in the curcumin group (0.811 ± 0.25) in comparison with the placebo group (2.23 ± 0.94) (P < 0.0001). Furthermore, the zymographic analysis showed that the administration of curcumin significantly inhibited the activity levels of MMP-2 (12469.7 ± 5308.64 pixels) and MMP-9 (14007.2 ± 5371.67 pixels) in comparison with that in patients receiving placebo (MMP-2: 17613.8 ± 5250.68 pixels; MMP-9: 20010.1 ± 3259.37 pixels) (P < 0.0500).

Conclusion: Our results show that curcumin can significantly reduce the expression and activity of MMP-2 and MMP-9. Because of the anti-inflammatory effects of curcumin, this compound can be considered as a new strategy for the prevention of cardiovascular events.
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http://dx.doi.org/10.22122/arya.v16i3.1938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778509PMC
May 2020

Effects of hydroalcoholic extract on the lipid and antioxidant profile in high fat diet-induced hepatic steatosis in rats.

Drug Chem Toxicol 2021 Jan 17;44(1):75-83. Epub 2018 Dec 17.

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

Oxidative stress is related to increased fat deposition in the liver, known as hepatic steatosis. The present study is an evaluation of the anti-oxidative and antihyperlipidemic effects of the hydroalcoholic extract of (HARE) in rats on a high-fat diet (HFD). Twenty male Wistar rats were divided into four groups: control, HFD, HFD + HARE 50 mg/kg/day, and HFD + HARE 250 mg/kg/day for 12 weeks. Animals were weighed weekly and treated with the HARE extract for 12 weeks by gavage. Subsequently, the histopathological changes, oxidative markers, and lipid profile were evaluated. Statistical analysis was performed using the one-way analysis of variance (ANOVA) for multiple comparisons. First, the active ingredients of the extract were determined by HPLC. Then, the levels in the serum lipid profile (TG, cholesterol, HDL, and LDL) in rats fed with the HFD + HARE were analyzed where a significant reduction was observed. The HFD proved to increase the activity of the liver enzymes, the serum lipid levels, and the malondialdehyde (MDA) level. The ferric-reducing antioxidant activity power (FRAP), catalase (CAT), and superoxide dismutase (SOD) catalytic activity were reduced in the liver homogenate of HFD rats compared to the controls. Additionally, the aforementioned liver enzymes activities were reduced in response to HARE. Evaluation of oxidative stress determined a reduction in the MDA level while a raised FRAP was confirmed. In accordance with the present results, histopathological observations have also demonstrated that HARE ameliorated grade-1 hepatic steatosis induced by HFD. Taken together, the findings of this study introduce HARE as a future potential therapeutic agent in treating hepatic steatosis and reducing oxidative damages of an HFD in the liver.
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http://dx.doi.org/10.1080/01480545.2018.1533024DOI Listing
January 2021

The Effect of Hydro-alcoholic Extract of Roots against Oxidative Stress in Endothelial Cells.

Int J Prev Med 2020 19;11:122. Epub 2020 Aug 19.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.

Introduction: Cardiovascular disorders (CVD) are a common cause of mortality worldwide. Oxidative stress is thought to be a major factor leading to CVD. Anti-oxidants such as medicinal plants may have a role in the mitigation of vascular problems through free radicals scavenging. In this study, we evaluated the protective effects of against hydrogen peroxide (HO)-induced toxicity in endothelial cells (BAE-1).

Methods: To evaluate the protective effect of against HO toxicity, four groups comprised of control group (the cells without any treatment), HO group (the cells incubated with HO200 μM)), and treatment groups (the cells treated with (12200 μg/ml) alone or 24h before exposure to HO). Quercetin (30.23 μg/ml) was used as a bioactive ingredient of the extract. Then the cell viability, reactive oxygen species, lipid peroxidation, and apoptosis were evaluated.

Results: HO exposure reduced cell viability to 13.6 ± 1.6%, enhanced ROS generation to 1445 ± 80.7%, lipid peroxidation (LPO, 290 ± 13% of control), and apoptotic cells ( < 0.001). In contrast, compared with HO group, and quercetin significantly restored the cell viability to 80.3 ± 1.6 and 87.2 ± 2.1%, ROS formation to 186 ± 10 and 129 ± 1%, as well as LPO to 130.7 ± 7.7 and 116 ± 2.5 of control, respectively ( < 0.001). Therefore, the extract reduced HO-induced toxicity in BAE-1 cells by scavenging of free radicals.

Conclusion: Our findings demonstrated that the extract might reduce toxicity of endothelial cells by attenuation of oxidative stress, which can be related to the presence of active ingredients including quercetin.
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http://dx.doi.org/10.4103/ijpvm.IJPVM_386_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554444PMC
August 2020

Evaluation Potential Antidiabetic Effects of in Streptozotocin-Induced Diabetic Rats.

J Pharmacopuncture 2020 Sep;23(3):158-164

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.

Objectives: The aim of the present work was to evaluate the possible beneficial effects of on blood glucose, lipids, and diabetes-related changes in the liver and kidney of streptozotocin-induced diabetic rats.

Methods: Male Wistar rats were randomly allocated into four groups (n = 6) normal control rats, diabetic control rats, diabetic rats treated for 4 weeks with root (400 mg/kg/day), and diabetic rats treated with aerial parts (400 mg/kg/day).

Results: Induction of diabetes significantly (p < 0.05) increased the levels of fasting blood glucose (FBG), triglyceride, total cholesterol, low-density lipoprotein (LDL), blood urea nitrogen (BUN), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Diabetes also increased (p < 0.05) oxidative stress in the kidney and liver (decrease of thiol and increase of superoxide dismutase). The root and aerial parts of significantly reduced the level of LDL (p < 0.05) and restored the content of thiol (p < 0.05) and superoxide dismutase (p < 0.01) in the kidney and liver. had no significant effect on the levels of FBG, BUN, AST, and ALT. The root of also reduced the serum level of total cholesterol (p < 0.05) and prevented the progression of hyperglycemia.

Conclusion: These findings suggest that may improve diabetic dyslipidemia by reducing serum LDL. Further studies are needed to confirm our findings.
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http://dx.doi.org/10.3831/KPI.2020.23.3.158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540228PMC
September 2020

The protective role of alpha-lipoic acid on the appearance of fibronectin and laminin in renal tubules following diazinon exposure: An experimental immunohistochemical study.

Toxicology 2020 11 8;444:152583. Epub 2020 Sep 8.

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.

Extracellular matrix (ECM) exerts a major role in maintaining the structure and developmental processes of tissues. To form the tubular basement membrane in the kidney, sulfate proteoglycans, collagen, laminin, fibronectin, and other glycoproteins congregate in the ECM. As an insecticide, diazinon (DZN) may alter the proportion of ECM by cholinesterase activity inhibition and oxidative stress. The naturally, alpha-lipoic acid (ALA) plays an effective and therapeutic role in the treatment of toxicities and diseases in the body. In the current study, an attempt was made to evaluate the impacts of alpha-lipoic acid on the distribution of fibronectin and laminin in the renal tubules of male Wistar rats following exposure to diazinon. In this study, the animal groups comprised 30 adult male Wistar rats (almost three months old) randomly distributed into the following groups; control, DZN (40 mg/kg), DZN + ALA (40 mg/kg+100 mg/kg), ALA (100 mg/kg), and sham. The rats were anesthetized after six weeks. Blood sampling was performed, and kidneys were removed for immunohistochemistry study. Diazinon reduced the distribution of fibronectin and laminin and significantly inhibited cholinesterase activity in the renal tubules. Furthermore, urea and creatinine levels were higher in diazinon than in other groups. ALA in the co-treatment group enhanced cholinesterase activity and distribution of both glycoproteins in the renal tubules. Urea and creatinine levels were meaningfully diminished in the DZN + ALA group. The nephrotoxic effect of diazinon in vivo was the reduced distribution of laminin and fibronectin, probably induced by cholinesterase activity inhibition. As an antioxidant with specific properties, ALA reduces the nephrotoxic effects of diazinon by multifarious mechanisms.
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http://dx.doi.org/10.1016/j.tox.2020.152583DOI Listing
November 2020

Angiotensin-Converting Enzyme Inhibitor Captopril: Does it Improve Renal Function in Lipopolysaccharide-induced Inflammation Model in Rats.

Saudi J Kidney Dis Transpl 2020 Jul-Aug;31(4):727-738

Neurogenic Inflammation Research Center; Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Renin-angiotensin system as an important regulator of renal function has also a major role in inflammation. In the present study, the effects of captopril on renal dysfunction, renal cytokine levels, and renal tissue oxidative damage were investigated in lipopolysaccharide (LPS)-induced inflammation model in rats. Treatment of five groups of the rats was carried out as follows: (1) saline as a control, (2) LPS 1 mg/kg, and (3-5) 10, 50, or 100 mg/kg captopril 30 min, respectively, before LPS. The treatments were given for 12 days. Finally, the animals were deeply anesthetized, the blood samples were obtained, and the renal tissues were removed and kept for biochemical measurements. Administration of LPS increased serum blood urea nitrogen and creatinine (P < 0.001). Pretreatment with all doses of captopril decreased these parameters (P < 0.001). LPS also increased interleukin-6 (IL-6), malondialdehyde, and nitric oxide metabolites in the renal tissues (P<0.05 - P < 0.001), which was prevented by captopril (P < 0.05 - P < 0.001). The total thiol concentration and superoxide dismutase and catalase activities in the kidney of the LPS group were lower than the control (P < 0.001), while they were enhanced when the animals were cotreated by captopril (P <0.01 - P < 0.001). The results of the present study showed that captopril improved renal function and attenuated tissue oxidative stress in LPS-induced inflammation model in rats.
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http://dx.doi.org/10.4103/1319-2442.292306DOI Listing
July 2021

Modulation of Calcium Signaling in Glioblastoma Multiforme: A Therapeutic Promise for Natural Products.

Mini Rev Med Chem 2020 ;20(18):1879-1899

Halal Research Center of IRI, FDA, Tehran, Iran.

Glioblastoma multiforme (GBM) continues as one of the most lethal cerebral cancers despite standard therapeutic modalities, such as maximum surgical resection and chemoradiation. The minimal effectiveness of existing therapies necessitates the development of additional drug candidates that could improve the prognosis of GBM patients. Accumulating evidence suggests that calcium (Ca) is involved in the processes of cell proliferation, metastasis, angiogenesis, migration, and invasiveness. Therefore, Ca could serve as a crucial regulator of tumorigenesis and a potential treatment target in GBM. In this context, specific natural products are known to modulate Ca signaling pathways implicated in tumor growth, apoptosis, angiogenesis, and development of GBM. Here, the focus is on the function of Ca as a therapeutic target in GBM and reviewing certain natural products that affect the signaling pathways of Ca.
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http://dx.doi.org/10.2174/1389557520666200807133659DOI Listing
May 2021

Deciphering the Role of Glutamate Signaling in Glioblastoma Multiforme: Current Therapeutic Modalities and Future Directions.

Curr Pharm Des 2020 ;26(37):4777-4788

Halal Research Center of IRI, FDA, Tehran, Iran

As the most popular intrinsic neoplasm throughout the brain, glioblastoma multiforme (GBM) is resistant to existing therapies. Due to its invasive nature, GBM shows a poor prognosis despite aggressive surgery and chemoradiation. Therefore, identifying and understanding the critical molecules of GBM can help develop new therapeutic strategies. Glutamatergic signaling dysfunction has been well documented in neurodegenerative diseases as well as in GBM. Inhibition of glutamate receptor activation or extracellular glutamate release by specific antagonists inhibits cell development, invasion, and migration and contributes to apoptosis and autophagy in GBM cells. This review outlines the current knowledge of glutamate signaling involvement and current therapeutic modalities for the treatment of GBM.
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http://dx.doi.org/10.2174/1381612826666200603132456DOI Listing
March 2021

Effects of Galbanic Acid on Proliferation, Migration, and Apoptosis of Glioblastoma Cells Through the PI3K/Akt/MTOR Signaling Pathway.

Curr Mol Pharmacol 2021 ;14(1):79-87

Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Glioblastoma is one of the most aggressive tumors of the central nervous system. Galbanic acid, a natural sesquiterpene coumarin, has shown favorable effects on cancerous cells in previous studies.

Objective: The aim of the present work was to evaluate the effects of galbanic acid on proliferation, migration, and apoptosis of the human malignant glioblastoma (U87) cells.

Methods: The anti-proliferative activity of the compound was determined by the MTT assay. Cell cycle alterations and apoptosis were analyzed via flow cytometry. Action on cell migration was evaluated by scratch assay and gelatin zymography. Quantitative Real-Time PCR was used to determine the expression of genes involved in cell migration (matrix metalloproteinases, MMPs) and survival (the pathways of PI3K/Akt/mTOR and WNT/β-catenin). Alteration in the level of protein Akt was determined by Western blotting.

Results: Galbanic acid significantly decreased cell proliferation, inhibited cell cycle, and stimulated apoptosis of the glioblastoma cells. Moreover, it could decrease the migration capability of glioblastoma cells, which was accompanied by inhibition in the activity and expression of MMP2 and MMP9. While galbanic acid reduced the gene expression of Akt, mTOR, and PI3K and increased the PTEN expression, it had no significant effect on WNT, β-catenin, and APC genes. In addition, the protein level of p-Akt decreased after treatment with galbanic acid. The effects of galbanic acid were observed at concentrations lower than those of temozolomide.

Conclusion: Galbanic acid decreased proliferation, cell cycle progression, and survival of glioblastoma cells through inhibiting the PI3K/Akt/mTOR pathway. This compound also reduced the migration capability of the cells by suppressing the activity and expression of MMPs.
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http://dx.doi.org/10.2174/1874467213666200512075507DOI Listing
January 2021

Production and Characterization of Monoclonal Antibody against Vit v1: A Grape Allergen Belonging to Lipid Transfer Protein Family.

Iran J Allergy Asthma Immunol 2020 Apr 16;19(2):139-148. Epub 2020 Apr 16.

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

Allergy to non-specific lipidtransfer protein (nsLTP), the major allergen of grape (Vit v1), is considered as one of the most common fruit allergies in Iran. Therefore, a specific monoclonal antibody (mAb) can be used for the characterization and assessment of. Accordingly, this study aimed to generate and characterize a mAb against Vit v1 with a diagnostic purpose. To this end, Vit v1 allergen (9 kDa) was extracted using a modified Bjorksten extraction method. Natural Vit v1-immunized mouse splenocytes were fused with SP2/0Ag-14 myeloma cells for generating hybridoma cells. Specific antibody-secreting Hybridoma cells were selected using ELISA. Finally, anti-Vit v1 mAb was characterized by western blotting, ELISA, and isotyping methods. In the current study, a 9 kDa (Vit v1) protein was attained fromcrude and fresh juice of grape extracts and the isotype of desired anti-Vit v1 mAb was determined as IgM with k light chain. In addition, The ELISA results demonstrated that anti-Vit v1 mAb was specified against natural Vit v1 in the grape cultivar and related LTP allergens, such as Pla or 3 (p<0.0001). In the present study, a specific mAb was produced for detecting the LTP allergen. This mAb with a confirmed specificity can be utilized for evaluating the LTP allergens and their allergenicity in different grape cultivars.
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http://dx.doi.org/10.18502/ijaai.v19i2.2776DOI Listing
April 2020

Anti-Hypolipidemic and Anti-Oxidative Effects of Hydroalcoholic Extract of on the Hepatosteatosis Induced with High-Fat Diet in Rats.

Malays J Med Sci 2020 Feb 27;27(1):57-69. Epub 2020 Feb 27.

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

Introduction: The aim of the current study is to evaluate the antihyperlipidemic and anti-oxidative effects of hydro-alcoholic extract of marjoram (HAEM) in rats fed with a high-fat diet (HFD).

Methods: In the experimental study, the rats were randomly divided into four groups of five rats in each and fed with high-fat diet for 12 weeks as follows: One group (normal diet group) was fed with a standard diet, one group was fed with HFD, and two groups were fed with HFD and orally fed with 150 and 450 mg/kg/day HAEM. The serum samples and liver tissues were used for measuring the biochemical and oxidative parameters and histopathological studies. HFD induced hepatosteatosis in rats as evidenced by the altered liver enzymes activity, serum lipid profile and oxidative status.

Results: Serum lipid profile (triglyceride, cholesterol and low-density lipoprotein) in rats fed with HFD + HAEM (150 and 450 mg/kg/day) was significantly decreased. Furthermore, the evaluation of oxidative stress showed a reduction of the malondialdehyde (MDA) level and an increase in ferric-reducing anti-oxidant power. Meanwhile, liver enzyme activities declined in response to HAEM.

Conclusion: Using the HAEM could be a future therapeutic agent in treating hepatosteatosis and reducing oxidative damages of HFD in the liver.
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http://dx.doi.org/10.21315/mjms2020.27.1.6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053549PMC
February 2020

Natural products as promising targets in glioblastoma multiforme: a focus on NF-κB signaling pathway.

Pharmacol Rep 2020 Apr 9;72(2):285-295. Epub 2020 Mar 9.

Department of Physiology and Pharmacology, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran.

Background: Glioblastoma multiforme (GBM), as the broadest cerebrum tumor, is resistant to current medical interventions, particularly chemo/radiation. Hence, it necessitates further therapeutic options that could enhance the efficacy of existing modalities.

Methods: A comprehensive and systematic review of literature on the NF-κB signaling pathway-contributed in the pathogenesis of GBM with a focus on natural products was carried out.

Results: Several examinations have shown that nuclear factor (NF)-κB is participated in apoptosis, cellular proliferation, angiogenesis, metastasis, invasion, and many other processes implicated in GBM pathobiology. Recent studies have provided that NF-κB regulation is the primary pharmacological target for GBM therapy. Specific natural products are involved in several signaling pathways implicated in tumor growth and apoptosis of GBM cells.

Conclusion: In the current review, we elaborate on the role of NF-κB as a promising target in GBM and discuss some natural products affecting the NF-κB signaling pathway.
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http://dx.doi.org/10.1007/s43440-020-00081-7DOI Listing
April 2020

Protective Role of Natural Products in Glioblastoma Multiforme: A Focus on Nitric Oxide Pathway.

Curr Med Chem 2021 ;28(2):377-400

Halal Research Center of IRI, FDA, Tehran, Iran.

In spite of therapeutic modalities such as surgical resection, chemotherapy, and radiotherapy, Glioblastoma Multiforme (GBM) remains an incurable fatal disease. This necessitates further therapeutic options that could enhance the efficacy of existing modalities. Nitric Oxide (NO), a short-lived small molecule, has been revealed to play a crucial role in the pathophysiology of GBM. Several studies have demonstrated that NO is involved in apoptosis, metastasis, cellular proliferation, angiogenesis, invasion, and many other processes implicated in GBM pathobiology. Herein, we elaborate on the role of NO as a therapeutic target in GBM and discuss some natural products affecting the NO signaling pathway.
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http://dx.doi.org/10.2174/0929867327666200130104757DOI Listing
February 2021

Effects of ethanolic extract of oleo-resin in a rat model of streptozotocin-induced diabetes.

Res Pharm Sci 2019 Apr 8;14(2):138-145. Epub 2019 Mar 8.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, I.R. Iran.

Previous studies have shown that some plants in the genus of (Apiaceae) have antidiabetic effects. The present work was aimed to evaluate effects of oleo-resin in a rat model of streptozotocin-induced diabetes. Male Wistar rats were randomized into five groups (n = 6): normal control, diabetic control, diabetic rats treated with insulin (3 IU/day), and diabetic rats treated with 100 or 400 mg/kg/day of an ethanolic extract of the oleo-resin. After 4 weeks, blood samples were collected for measuring fasting blood glucose (FBG), lipid profile, aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase, blood urea nitrogen, and creatinine. In addition, levels of lipid peroxidation, thiol groups, and superoxide dismutase (SOD) activity were evaluated in the liver and kidney. At the end of the fourth week, the level of FBG in rats treated with 100 mg/kg of the extract was lower than that in diabetic control rats (273 ± 39 mg/dL 471 ± 32 mg/dL). Administration of insulin and the extract had no significant effects on the serum lipids. Insulin and both doses of the extract significantly reduced the activity of ALT. In addition, the extract inhibited lipid peroxidation in the kidney and restored the elevated level of SOD in the liver and kidneys. oleo-resin has the potential to prevent or delay the complications of diabetes by inhibiting the progression of hyperglycemia and attenuating oxidative stress-induced damage in the liver and kidneys.
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http://dx.doi.org/10.4103/1735-5362.253361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791176PMC
April 2019

Auraptene-induced cytotoxicity mechanisms in human malignant glioblastoma (U87) cells: role of reactive oxygen species (ROS).

EXCLI J 2019 30;18:576-590. Epub 2019 Jul 30.

Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Glioblastoma multiforme (GBM), like the devastating type of astrocytic tumors, is one of the most challenging cancers to treat owing to its aggressive nature. Auraptene, as a prenyloxy coumarin from citrus species, represents antioxidant and antitumor activities; however, the underlying antitumor mechanisms of auraptene against GBM remain unclear. The present study aimed to evaluate the cytotoxic and apoptogenic effects of auraptene, as a promising natural product, and the possible signaling pathways affected in human malignant GBM (U87) cells. Reactive oxygen species (ROS) production significantly decreased in the first 2, and 6 hours after treatment with auraptene however, ROS levels increased in other incubation times (8 and 24 hours), dramatically. N-acetyl-cysteine (NAC) markedly attenuated auraptene-induced ROS production, and consequently reversed auraptene-induced cytotoxicity in 8 and 24 hours after treatment, as well. Induction of apoptosis occurred in the first 24- and 48-hours concentration-dependently. The qRT-PCR showed an up-regulation in p21, CXCL3, and a down-regulation in Cyclin D1 genes expression. Western blot analysis confirmed the up-regulation of the Bax/Bcl-2 ratio protein levels concentration-dependently. Hence, this study collectively revealed that the increase in ROS level is at least one of the mechanisms associated with auraptene-induced GBM cell toxicity as well as the induction of apoptosis through Bax/Bcl-2 modulation and genes expression involved that contribute to the cytotoxicity of auraptene in U87 cells. So, auraptene might be utilized as a potential novel anti-GBM agent after further studies.
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http://dx.doi.org/10.17179/excli2019-1136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785765PMC
July 2019

The effects of PPAR-γ agonist pioglitazone on hippocampal cytokines, brain-derived neurotrophic factor, memory impairment, and oxidative stress status in lipopolysaccharide-treated rats.

Iran J Basic Med Sci 2019 Aug;22(8):940-948

Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Objectives: The aim of current study was to evaluate improving effects of pioglitazone as an agonist of peroxisome proliferator-activated receptor gamma (PPARγ), on brain-derived neurotrophic factor (BDNF) and cytokines as well as tissue oxidative damage criteria in the hippocampus in a rat model of lipopolysaccharide (LPS) induced memory impairment.

Materials And Methods: The rats were classified and treated as follows (10 rats per group): (1) vehicle, (2) vehicle before LPS (1 mg/kg, 120 min before memory tests), (3-5) pioglitazone 10, 20 or 30 mg/kg 30 min before LPS. Finally, the hippocampal tissues were collected for biomedical analyses.

Results: In the Morris water maze test, the LPS group, had a longer latency to find the platform while they spent a shorter time in the target quadrant in the probe trial. In the passive avoidance test, the animals of the LPS group had shorter delay times to enter the dark compartment than those of the control group. Treatment with 20 and 30 mg of pioglitazone corrected these parameters. In the hippocampus of LPS group interleukin-6, tumor necrosis factor-α, nitric oxide metabolites, and malondialdehyde were higher while thiol, BDNF, and IL-10 concentrations and the activities of catalase (CAT) and superoxide dismutase (SOD) were lower than the control group. Treatment by both doses of 20 and 30 mg of pioglitazone corrected the biochemical parameters in the hippocampus.

Conclusion: The current findings revealed that pioglitazone protected the rats from learning and memory impairment induced by LPS. The effects were associated with improvement of cytokines, oxidative stress criteria, and BDNF.
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http://dx.doi.org/10.22038/ijbms.2019.36165.8616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760489PMC
August 2019

Cytotoxic Effects of Ferula Latisecta on Human Glioma U87 Cells.

Drug Res (Stuttg) 2019 Dec 9;69(12):665-670. Epub 2019 Sep 9.

Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Glioblastoma multiforme (GBM) is the fatal type of astrocytic tumors with a survival rate of 12 months. The present study, for the first time, evaluated the cytotoxic impacts of () hydroalcoholic extract on U87 GBM cell line. The MTT assay measured the cellular toxicity following 24- and 48 h treatment with various doses of (0-800 μg/mL). Apoptosis was evaluated by an Annexin V/propidium iodide (PI) staining 24 h after treatment by . Moreover, to determine the cellular metastasis of U87 cells, we used a gelatin zymography assay (matrix metalloproteinase [MMP]-2/-9 enzymatic activity). The outcomes showed that mitigated the viability of U87 cells in a concentration- and time-dependent manner with IC values of 145.3 and 192.3 μg/mL obtained for 24- and 48 h treatments, respectively. induced apoptosis in a concentration-dependent manner after 24 h. Also, MMP-9 activity was significantly decreased following 24 h after treatment concentration-dependently with no change in MMP-2 enzymatic activity. This study showed that induced cytotoxicity and apoptosis, and mitigated metastasis of U87 GBM cells. Hence, could be beneficial as a promising natural herb against GBM after further studies.
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http://dx.doi.org/10.1055/a-0986-6543DOI Listing
December 2019

Effects of monosodium glutamate on apoptosis of germ cells in testicular tissue of adult rat: An experimental study.

Int J Reprod Biomed 2019 Apr 28;17(4). Epub 2019 May 28.

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

Background: Monosodium glutamate (MSG) is used as a flavoring and food seasoning. Some studies have reported the oxidative effects of using this substance on various tissues.

Objective: This study has investigated the effects of MSG and the protective effect of vitamin C (vit C) on apoptosis of testicular germ cells and biochemical factors.

Materials And Methods: In this experimental study, 24 adult male Wistar rats were randomly divided into four groups: control (received distilled water), vit C group (150 mg/kg), experimental group 1 (MSG 3 gr/kg), experimental group 2 (MSG 3 gr/kg + vit C 150 mg/kg). The rats were gavaged for 30 days, and then were sacrificed, the right testis was isolated for biochemical examinations for the glutathione, malondialdehyde, and left testis used in histological experiments. Tunnel staining was used to determine the number of apoptotic cells.

Results: The results showed that apoptotic cells in the MSG group had a significant increase compared to the control group (P = 0.001), but the number of these cells in the MSG co-administered with vit C and vit C groups were significantly lower than the MSG group. Germinal epithelial thickness also decreased in MSG group compared to the control group.

Conclusion: MSG can lead to increase apoptotic changes in the germinal epithelial of the testicle, and vit C as an antioxidant can modify the pathological and biochemical changes induced by MSG.
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http://dx.doi.org/10.18502/ijrm.v17i4.4551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6686650PMC
April 2019

Role of AKT and mTOR signaling pathways in the induction of epithelial-mesenchymal transition (EMT) process.

Biochimie 2019 Oct 8;165:229-234. Epub 2019 Aug 8.

Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Epithelial-mesenchymal transition (EMT) is a critical process in the development of many tissues and organs in multicellular organisms that its important role in the pathogenesis of metastasis and tumor cell migration has been firmly established. Decreased adhesive capacity, cytoskeletal reorganization, and increased mobility are hallmarks of the EMT. Several molecular mechanisms promote EMT, Including regulation of the levels of specific cell-surface proteins, ECM-degrading enzymes, and altering the expression of certain transcription factors and microRNAs. EMT process is modulated through multiple signaling pathways including the AKT/mTOR pathway. AKT is a key component in numerous processes which was recently shown to regulate the EMT through suppression of the expression of E-cadherin via EMT transcription factors. On the other hand, mTOR complexes can also regulate the EMT through the regulation of cell's actin cytoskeleton by altering the PKC phosphorylation state and direct phosphorylation and activation of Akt. Here we review the effect of AKT and mTOR on EMT and consequently metastasis and cell motility.
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http://dx.doi.org/10.1016/j.biochi.2019.08.003DOI Listing
October 2019

and its main ingredient, carvacrol, affect on the renal function, histopathological, biochemical and antioxidant parameters in adriamycin-induced nephrotic rats.

Arch Physiol Biochem 2019 Aug 9:1-9. Epub 2019 Aug 9.

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

Oxidative stress has a major role in the nephrosis. In the present study, the effects of hydroalcoholic extract of (ZM) and carvacrol (CAR) were evaluated on the renal damage induced by adriamycin (ADR). The animals accidentally divided into four groups including: Control, ADR, ZM + ADR and CAR + ADR. The renal tissue, urine, and blood samples subjected to biochemical markers and histopathological evaluation. ADR significantly decreased glomerular filtration rate (GFR) while escalated urine protein excretion as well as protein clearance ( < .01 to  < .001). Also, ADR significantly reduced the antioxidants and boosted the malondialdehyde (MDA) compared to the control ( < .05 to  < .01). In groups treated by ZM and CAR, GFR, and antioxidants significantly increased, whereas urine protein excretion and MDA decreased ( < .05 to  < .001). ZM and CAR induced an improvement in ADR-induced renal damage by improving renal function as well as antioxidant activity.
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http://dx.doi.org/10.1080/13813455.2019.1650069DOI Listing
August 2019

Cytotoxic effects of auraptene against a human malignant glioblastoma cell line.

Avicenna J Phytomed 2019 Jul-Aug;9(4):334-346

Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Objective: Glioblastoma multiforme (GBM) is the deadliest type of primary brain tumors, and the survival of patients is estimated to be only about one year. This study, for the first time, investigated the cytotoxic effects of auraptene on U87 GBM cell line.

Materials And Methods: The cellular toxicity was measured by the MTT assay following 24 and 48-hr treatment with different concentrations of auraptene (0-400μg/ml). Apoptosis was evaluated by sub-G1 peak in cell cycle analysis of propidium-iodide- stained nuclei. Moreover, to determine the Ba, , , , , and genes expression, we used real-time polymerase chain reaction (RT-PCR).

Results: The results revealed that auraptene reduced the viability of U87 cells concentration- and time-dependently with IC values of 108.9 and 79.17μg/ml obtained for 24 and 48-hr treatments, respectively. Also, sub-G1 population was significantly increased following 24 (p<0.05 and p<0.001) and 48 (p<0.001) hours of treatment. The quantitative real-time RT-PCR showed an up-regulation in , , , and but a down-regulation in and genes expression.

Conclusion: This study showed that auraptene triggered apoptosis probably through Bax/Bcl-2 regulation, blocked cell cycle progression and inhibited proliferation in U87 GBM cells. Taken together, auraptene can be utilized as an effective natural medicine against GBM, after complementary studies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612248PMC
July 2019

Acute and sub-acute toxicity evaluation of the root extract of Janisch.

Drug Chem Toxicol 2020 Nov 2;43(6):609-615. Epub 2019 Jul 2.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.

Despite the widespread use of in herbal medicine, no study has yet examined its toxicity. The aim of this study is to evaluate the acute and sub-acute toxicity of hydroalcoholic extract of root. In acute toxicity experiment, female and male mice ( = 5/group/sex) were orally administrated with the extract at single doses of 300, 2000 and 3000 mg/kg and observed for 14 days. In the sub-acute study, the extract was orally administered daily at doses of 100 and 400 mg/kg to male rats ( = 8) for 4 weeks. During the acute toxicity test, there were no deaths or any signs of toxicity observed after administration of the extract at 300 mg/kg, which was the no-observed-adverse-effect level (NOAEL). The extract at a dose of 3000 mg/kg led to the death of one female and one male mouse (LD > 3000 mg/kg). In sub-acute toxicity experiment, the extract induced no mortality or significant changes in body weight, general behaviors, hematological parameters, serum biochemical factors (related to the kidney and liver function), and histopathology of the heart, liver, kidney, and brain up to the highest dose tested of 400 mg/kg (NOAEL). High-performance liquid chromatography-mass spectrometry revealed the presence of phenolic compounds, flavonoids, alkanes, and anthraquinones in the extract. In conclusion, short-term use of root does not appear to produce significant toxicity up to a dose of 400 mg/kg.
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http://dx.doi.org/10.1080/01480545.2018.1561713DOI Listing
November 2020

Effects of PPAR-γ agonist, pioglitazone on brain tissues oxidative damage and learning and memory impairment in juvenile hypothyroid rats.

Int J Neurosci 2019 Oct 3;129(10):1024-1038. Epub 2019 Jul 3.

Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences , Mashhad , Iran.

: The effect of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone on the brain tissues oxidative damage and learning and memory impairment in the juvenile hypothyroid rats was evaluated. : Rats were classified as: ( 1 ) Control; (2) Propylthiouracil (PTU); (3) PTU-Pio 10 and (4) PTU-Pio 20. PTU was given in drinking water (0.05%) during 6 weeks. Pioglitazone (10 or 20 mg/kg) was daily injected intraperitoneally. Passive avoidance (PA) and Morris water maze (MMW) were conducted. Later, the animals were sacrificed and the brain tissues were removed for biochemical measurements. : The results indicated that in the MWM escape latency as well as traveled path increased in the PTU group as compared to the control group. Also, the time spent in the target quadrant in the probe test of MWM and step-through latency in the PA test were decreased in the PTU group as compared to the control group. Pioglitazone reversed all the negative behavioral effects of hypothyroidism. Administration of PTU attenuated thiol and superoxide dismutase (SOD), and catalase (CAT) activities in the brain tissues, whereas increased malondialdehyde (MDA) and nitric oxide (NO) metabolites. PPARγ agonist improved thiol, SOD and CAT, while diminished MDA concentration. : Our finding in the present study indicated that PPARγ agonist pioglitazone prevented the brain tissues from oxidative damage and learning and memory impairments in juvenile hypothyroid rats.
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http://dx.doi.org/10.1080/00207454.2019.1632843DOI Listing
October 2019

Thymoquinone alleviates renal interstitial fibrosis and kidney dysfunction in rats with unilateral ureteral obstruction.

Phytother Res 2019 Aug 18;33(8):2023-2033. Epub 2019 Jun 18.

Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Unilateral ureteral obstruction (UUO) causes severe renal tubulointerstitial fibrosis. Because of many pharmacologic properties of thymoquinone (TQ), in this study, the effects of TQ against kidney fibrosis and dysfunction were investigated in rats with UUO. Forty male Wistar rats were divided into five groups: Sham operated, UUO, and the animals with UUO treated with losartan, captopril, or TQ. Collagen IV and transforming growth factor (TGF)-β1 expressions, interstitial fibrosis, histological changes, and kidney function were assessed. UUO markedly increased renal expression of TGF-β1 and collagen I and induced interstitial fibrosis (p < .001). Losartan, captopril, or TQ significantly downregulated the expression of these fibrotic markers and interstitial fibrosis (p < .01-p < .001). In UUO group, serum levels of urea and creatinine and protein excretion rate significantly increased, but glomerular filtration rate (GFR) and urine osmolarity showed a significant decrease (p < .001-p < .05). Administration of captopril and TQ caused no significant change in serum urea and protein excretion rate. Unlike losartan and captopril, TQ caused no significant alteration in GFR compared with Day 1. Losartan caused significant increases in serum urea and creatinine but significant decrease in urine osmolarity. TQ could be regarded as a potent therapeutic agent for treatment of UUO-induced kidney fibrosis and dysfunction.
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http://dx.doi.org/10.1002/ptr.6376DOI Listing
August 2019

Overexpression of Lactate Dehydrogenase in the Saliva and Tissues of Patients with Head and Neck Squamous Cell Carcinoma.

Rep Biochem Mol Biol 2019 Jan;7(2):142-149

Dental Research Center, Mashhad University of Medical Science, Mashhad, Iran.

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy that is associated with high morbidity and mortality. Salivary lactate dehydrogenase (LDH concentration), as an expression of cellular necrosis, may be a special marker of lesions that occur with changes in the integrity of the oral mucosa. This study was performed to determine the accuracy of salivary LDH as a clinical marker for HNSCC detection and to investigate the relationship between salivary LDH levels and tissue tumor detection.

Methods: The case group consisted of 44 HNSCC patients and the control group consisted of 44 healthy subjects. The stage and grade of HNSCC were determined, and the LDH levels in collected saliva samples were measured in all subjects. The expression of LDH in tumors and healthy tissue margins was evaluated via immunohistochemistry.

Results: The expression of LDH in the saliva of patients with HNSCC is significantly higher than that in the saliva of the healthy control group. The expression of salivary LDH in patients with oral squamous cell carcinoma (OSCC) is significantly higher than that in the other patients and healthy individuals in the control group. The levels of salivary LDH in patients with SCC of the tongue and lower oral cavity were significantly higher than those in other patients affected with SCC in other parts of the head and neck (P<0.01).

Conclusion: As this enzyme increases simultaneously in both tumoral tissues and saliva, it can serve as a useful diagnostic marker for the early diagnosis and prediction of HNSCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374058PMC
January 2019

PPAR-γ: Its ligand and its regulation by microRNAs.

J Cell Biochem 2019 Feb 15. Epub 2019 Feb 15.

Department of Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor superfamily. PPARs are categorized into three subtypes, PPARα, β/δ, and γ, encoded by different genes, expressed in diverse tissues and participate in various biological functions and can be activated by their metabolic derivatives in the body or dietary fatty acids. The PPAR-γ also takes parts in the regulation of energy balance, lipoprotein metabolism, insulin sensitivity, oxidative stress, and inflammatory signaling. It has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis, and cancers. Among various cellular and molecular targets that are able to regulate PPAR-γ and its underlying pathways, microRNAs (miRNAs) appeared as important regulators. Given that the deregulation of these molecules via targeting PPAR-γ could affect initiation and progression of various diseases, identification of miRNAs that affects PPAR-γ could contribute to the better understanding of roles of PPAR-γ in various biological and pathological conditions. Here, we have summarized the function and various ligands of PPAR-γ and have highlighted various miRNAs involved in the regulation of PPAR-γ.
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http://dx.doi.org/10.1002/jcb.28419DOI Listing
February 2019
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