Mahmoud Hashemitabar | Ahvaz Jundishapur University of Medical Sciences (original) (raw)

Papers by Mahmoud Hashemitabar

Research paper thumbnail of Dexamethasone effects on Bax expression in the mouse testicular germ cells

Folia Histochemica Et Cytobiologica, 2009

Materials and methods Animals. NMRI male mice weighing 25-30 g were kept in individual stainless ... more Materials and methods Animals. NMRI male mice weighing 25-30 g were kept in individual stainless steel cages under standardized conditions

Research paper thumbnail of Progesterone and Cilostazol Protect mice pancreatic islets from oxidative stress induced by hydrogen peroxide

Iranian Journal of Pharmaceutical Research, 2014

Reactive oxygen species and oxidative stress impair β-cell function and reduce insulin secretion.... more Reactive oxygen species and oxidative stress impair β-cell function and reduce insulin secretion. It has been shown that progesterone and cilostazol possess antioxidant properties. The present study was aimed to investigate in-vitro pretreatment effect of progesterone and cilostazol on insulin secretion as well as their protective effects against hydrogen peroxideinduced oxidative stress in pancreatic isolated islets from mouse.

Research paper thumbnail of Application of Alginate capsules as a three dimensional scaffold for differentiation of Wharton's Jelly Mesenchymal stem Cells to definitive endoderm

Arak Medical University Journal, Jul 15, 2014

Background: Wharton's Jelly Mesenchymal Stem Cells (WJMSc) are potential renewable source of cell... more Background: Wharton's Jelly Mesenchymal Stem Cells (WJMSc) are potential renewable source of cells in replacement therapies of many diseases. Different biomaterials have been used as a scaffold to mimic the stem cell niche, which is important for promoting cellular interactions, cell proliferation and differentiation. Encapsulation involves entrapment of living cells within the semipermeable membrane for the exchange of nutrients, oxygen and stimuli, whereas antibodies and host immune cells are kept out. In this study, a new approach for culturing and differentiating Wharton's Jelly Mesenchymal Stem Cells to definitive endoderm in a three dimensional environment using alginate capsules is presented.

Research paper thumbnail of In Vitro Activity of Camellia Sinensis Extracts Against L.MAJOR and L.INFANTUM Promastigotes Using the Colorometric MTT Assay

Urmia Medical Journal, Dec 15, 2014

Plant extracts and plant-derived compounds are unlimited sources of chemical diversity for identi... more Plant extracts and plant-derived compounds are unlimited sources of chemical diversity for identification of new medicinal agents that are commonly used to treat infectious diseases. The purpose of this study was to evaluate the in vitro antileishmanial activity of camellia sinensis extracts against L. infantum and L. major promastigotes by using colorimetric MTT assay as compared to the pentavalent antimonial compound (meglumine antimonite).

Research paper thumbnail of Combination effects of prednisolone and interleukin-4 protect bovine nasal cartilage explants from interleukin-1α induced degradation

Iranian Biomedical Journal, Oct 1, 2011

Background: Current treatments for joint diseases are moderately successful, but unfortunately ar... more Background: Current treatments for joint diseases are moderately successful, but unfortunately are associated with significant side effects. This study was undertaken to investigate the combination effects of IL-4 and prednisolone on tissue characteristics and production of matrix metalloproteinase-1(MMP-1) in IL-lα-treated bovine nasal cartilage (BNC) explants. Methods: BNC explants were cultured in DMEM with IL-lα (10 ng/ml), IL-4 (50 ng/ml) and prednisolone (1 or 1,000 nM) at the same time for 28 days. At days 3, 7, 14, 21and 28, the media were collected and replaced with fresh media, and the removed media were stored at -20°C. The alterations of tissue characteristics were assessed by using histology techniques. Western-blot method was used to determine the effects of IL-4 and prednisolone combination on MMP-1 production. The cell viability was evaluated by using lactate dehydrogenase assay test. Results: In the presence of IL-lα alone, most chondrocytes were transformed into fibroblast-like morphology with pyknotic nuclei at day 28. In addition, a clear band of MMP-1 and extracellular matrix (ECM) degradation were observed. In combination of IL-4 and prednisolone, chondrocytes preserved their ordinary normal features. MMP-1 band formation was completely inhibited and ECM absolutely showed normal characteristics. IL-4 and prednisolone did not show cytotoxicity effects on BNC explant culture. Conclusion: This combination can strongly preserve cartilage from degradation features and the data possibly suggest that the combination of IL-4 and prednisolone could be a candidate for alternative therapy in joint diseases. Iran. Biomed. J. 15 (4): 143-150, 2011

Research paper thumbnail of Protective Effects of Interleukin-4 on Tissue Destruction and Morphological Changes of Bovine Nasal Chondrocytes in vitro

Iranian Biomedical Journal, Oct 1, 2013

Previous studies have shown that some cytokines have protective effects on cartilage in joint dis... more Previous studies have shown that some cytokines have protective effects on cartilage in joint diseases. In the current study, effects of IL-4 against morphological changes and tissue degradation induced by IL-1α on bovine nasal cartilage (BNC) explants were investigated. Methods: Fresh BNC samples were prepared from a slaughterhouse under sterile conditions. BNC explants culture was treated with both IL-lα (10 ng/ml) and IL-4 (50 ng/ml) at the same time for 28 days. The morphological characteristics of explants were assessed by using histology techniques and invert microscopy. Matrix metalloproteinase-1 (MMP-1) production was assessed within different days by using Western blotting. Results: IL-lα induced prominent cartilage morphology degradation. The pro and active form of MMP-1 band substantially increased at day 21 of culture. In the presence of both IL-lα and IL-4, chondrocytes preserved their ordinary normal phenotype with intact extracellular matrix. In addition, a significant reduction in pro-MMP-1and inhibition of active MMP-1 was seen. Conclusion: In conclusion, IL-4 could be regarded as a potential candidate in cartilage protecting against the degradation changes of IL-lα. It seems that the preservation effect of IL-4 is associated with significant reduction of MMP-1. Iran. Biomed.

Research paper thumbnail of Morphological Changes of Bovine Nasal ChondrocytesInduced by Interleukin-1α

Cell Journal, 2013

Objective:A study of the histological events under interleukin-1α (IL-lα) induction of bovine nas... more Objective:A study of the histological events under interleukin-1α (IL-lα) induction of bovine nasal cartilage (BNC) could result in useful data to better understand the mechanisms involved in tissue breakdown in joint diseases. The aim of this study was to investigate the effects of IL-lα on chondrocyte phenotype and extracellular matrix (ECM) changes in BNC explants.Materials and Methods:In this experimental study, samples were divided into two groups. Group I (control group) BNC explants were cultured only in Dulbecco’s modified Eagle’s medium (DMEM). In group II, BNC explants were treated with IL-lα (10 ng/ ml) for 28 days. Then, samples were harvested on culture days 3, 7, 14, 21 and 28 and chondrocyte morphology and ECM alterations were assessed by invert microscopy and histology by hematoxylin and eosin (H&E) and Alcian blue. Cell viability was evaluated by the lactate dehydrogenase (LDH) assay test. Data were analyzed by the t test and p<0.05 was considered significant.Results:IL-lα induced significant morphological changes in cartilage. In the presence of IL-lα, most chondrocytes transformed into a fibroblast-like morphology with a granular black point appearance. An increase in the cell: matrix ratio was observed and there were decreased numbers of chondrocytes.IL-lα induced breakdown of ECM. We observed partial degradation of ECM between days 7-14 and complete degradation occurred between days 21-28 of culture. The LDH levels increased.Conclusion:IL-1α induced morphological changes in chondrocytes and increased destruction of cartilage ECM. There was a parallel correlation between proteoglycan degradation and changes in chondrocyte morpholgy.

Research paper thumbnail of Isolation and Characterization of Human Umbilical Cord Mesenchymal Stem Cells and Their Differentiation into Pdx-1<sup>+</sup> Cells

Journal of Biomedical Science and Engineering, 2015

Research paper thumbnail of Glucose plus metformin compared with glucose alone on β‑cell function in mouse pancreatic islets

Biomedical Reports, 2015

Metformin is currently the first drug of choice for treatment of type II diabetes. The primary fu... more Metformin is currently the first drug of choice for treatment of type II diabetes. The primary function of metformin is to decrease hepatic glucose production mainly by inhibiting gluconeogenesis. The aim of the present study was to investigate the effects of glucose alone (control groups) and glucose and metformin (treatment groups) on pancreatic islets functions. Pancreatic islets were isolated by collagenase digestion and incubated for 24 or 48 h in RPMI-

Research paper thumbnail of Effect of bone morphogenetic (BMP-2) on the aged human articular chondrocytes

Toxicology Letters, 2010

Current in vitro cytotoxicity models are limited by their incomplete modeling of other cell types... more Current in vitro cytotoxicity models are limited by their incomplete modeling of other cell types and of cell functions and interactions within a tissue, organ, systems and whole body. The MCB system was designed to minimize these discrepancies by connecting different cell types together through the flow of a common medium. The objective of this study was to demonstrate that the MCB system is a more effective toxicological screen than existing assays, particularly for difficult compounds, since it is more predictive of the in vivo behavior of drug candidates than simple cellular assays.

Research paper thumbnail of Progesterone and cilostazol protect mice pancreatic islets from oxidative stress induced by hydrogen peroxide

Iranian journal of pharmaceutical research : IJPR, 2014

Reactive oxygen species and oxidative stress impair β-cell function and reduce insulin secretion.... more Reactive oxygen species and oxidative stress impair β-cell function and reduce insulin secretion. It has been shown that progesterone and cilostazol possess antioxidant properties. The present study was aimed to investigate in-vitro pretreatment effect of progesterone and cilostazol on insulin secretion as well as their protective effects against hydrogen peroxide-induced oxidative stress in pancreatic isolated islets from mouse. Pancreatic islets were isolated from 84 male NMRI mice (25-30 g) by collagenase digestion method and pretreated for 48 h with cilostazol (10 μM), progesterone (0.5 μM) and glibenclamide (10 μM) in culture medium. Then islets were exposed to hydrogen peroxide (H2O2. 500 μM) for 2 h. Next, culture mediums containing glucose concentration of 2.8 mM or 16.7 mM were added to them and incubated in this status for 1 h. At the end, the rate of insulin output from islets, lipid peroxidation and antioxidant enzymes activities in islet tissues were assayed. Exposure o...

Research paper thumbnail of Protective effects of interleukin-4 on tissue destruction and morphological changes of bovine nasal chondrocytes in vitro

Iranian biomedical journal, 2013

Previous studies have shown that some cytokines have protective effects on cartilage in joint dis... more Previous studies have shown that some cytokines have protective effects on cartilage in joint diseases. In the current study, effects of IL-4 against morphological changes and tissue degradation induced by IL-1α on bovine nasal cartilage (BNC) explants were investigated. Fresh BNC samples were prepared from a slaughterhouse under sterile conditions. BNC explants culture was treated with both IL-lα (10 ng/ml) and IL-4 (50 ng/ml) at the same time for 28 days. The morphological characteristics of explants were assessed by using histology techniques and invert microscopy. Matrix metalloproteinase-1 (MMP-1) production was assessed within different days by using Western blotting. IL-lα induced prominent cartilage morphology degradation. The pro and active form of MMP-1 band substantially increased at day 21 of culture. In the presence of both IL-lα and IL-4, chondrocytes preserved their ordinary normal phenotype with intact extracellular matrix. In addition, a significant reduction in pro...

Research paper thumbnail of Morphological changes of bovine nasal chondrocytes induced by interleukin-1α

Cell journal, 2013

A study of the histological events under interleukin-1α (IL-lα) induction of bovine nasal cartila... more A study of the histological events under interleukin-1α (IL-lα) induction of bovine nasal cartilage (BNC) could result in useful data to better understand the mechanisms involved in tissue breakdown in joint diseases. The aim of this study was to investigate the effects of IL-lα on chondrocyte phenotype and extracellular matrix (ECM) changes in BNC explants. In this experimental study, samples were divided into two groups. Group I (control group) BNC explants were cultured only in Dulbecco's modified Eagle's medium (DMEM). In group II, BNC explants were treated with IL-lα (10 ng/ ml) for 28 days. Then, samples were harvested on culture days 3, 7, 14, 21 and 28 and chondrocyte morphology and ECM alterations were assessed by invert microscopy and histology by hematoxylin and eosin (H&E) and Alcian blue. Cell viability was evaluated by the lactate dehydrogenase (LDH) assay test. Data were analyzed by the t test and p<0.05 was considered significant. IL-lα induced significant...

Research paper thumbnail of Combination effects of prednisolone and interleukin-4 protect bovine nasal cartilage explants from interleukin-1α induced degradation

Iranian biomedical journal, 2011

Current treatments for joint diseases are moderately successful, but unfortunately are associated... more Current treatments for joint diseases are moderately successful, but unfortunately are associated with significant side effects. This study was undertaken to investigate the combination effects of IL-4 and prednisolone on tissue characteristics and production of matrix metalloproteinase-1(MMP-1) in IL-lα-treated bovine nasal cartilage (BNC) explants. BNC explants were cultured in DMEM with IL-lα (10 ng/ml), IL-4 (50 ng/ml) and prednisolone (1 or 1,000 nM) at the same time for 28 days. At days 3, 7, 14, 21 and 28, the media were collected and replaced with fresh media, and the removed media were stored at -20°C. The alterations of tissue characteristics were assessed by using histology techniques. Western-blot method was used to determine the effects of IL-4 and prednisolone combination on MMP-1 production. The cell viability was evaluated by using lactate dehydrogenase assay test. In the presence of IL-lα alone, most chondrocytes were transformed into fibroblast-like morphology with...

Research paper thumbnail of Comparsion of the enzymatic and explant methods for the culture of keratinocytes isolated from human foreskin

Biomedical Reports, 2015

Currently, culture and growth keratinocytes are important stages in achieving a reliable and repr... more Currently, culture and growth keratinocytes are important stages in achieving a reliable and reproducible skin tissue. In the present study, two different methods, enzymatic and explant methods, for keratinocytes isolation from human foreskin were compared. Foreskins were cut into 2-3 mm pieces and placed in trypsin at 4°C overnight for separation of the epidermis from the dermis. Subsequently, these samples were divided into two groups: i) Keratinocytes separated from the epidermis by trypsin and ii) by the explant method. These keratinocytes were divided into two groups: i) With no feeder layer and ii) onto a type I collagen scaffold. The cells were evaluated using immunocytochemistry and 4&amp;amp;amp;amp;amp;amp;#39;,6-diamidine-2&amp;amp;amp;amp;amp;amp;#39;-phenylindole dihydrochloride (DAPI) staining. In the enzymatic treatment, after 7-10 days no attached cells were found in the cell culture dishes. In the explant method, keratinocytes were separated after ~24 h, attached rapidly and formed big colonies into a collagen scaffold. In the absence of a feeder layer, small colonies were developed with rapid loss of proliferation within 2-3 days. Keratinocytes showed positive immunoreactivity for the pan-cytokeratin marker and keratinocytes&amp;amp;amp;amp;amp;amp;#39; nuclei were clearly observed. This method could be applied and developed as a component of skin substitutes to treat burns and wounds and also in laboratory testing.

Research paper thumbnail of Interleukin-4 and Prednisolone affect the matrix metalloproteinase-13 releasing from degenerative bovine nasal cartilage in vitro

Research paper thumbnail of Gamma-Tocopherol Enhances Apoptotic Effects of Lovastatin in Human Colorectal Carcinoma Cell Line (HT29)

Nutrition and Cancer, 2014

Recently, we found that lovastatin, a HMG-CoA reductase inhibitor, and gamma-tocopherol, one of t... more Recently, we found that lovastatin, a HMG-CoA reductase inhibitor, and gamma-tocopherol, one of the significant types of vitamin E in diet, additively induced apoptosis in a colorectal carcinoma cell line. In this study we mechanistically monitored the loss of mitochondrial membrane potential, amount of cytosolic cytochrome c and caspase 3 activity after treatment by lovastatin and gamma-tocopherol. HT29 cells were treated with different doses of lovastatin and gamma-tocopherol for 48 and 72 h. Lovastatin and gamma-tocopherol in combination induced the release of cytochrome c, caspase 3 activation, and loss of mitochondrial membrane potential more significantly compared to their controls. Our data showed that lovastatin plus gamma tocopherol potently induced mitochondrial membrane potential collapse, cytochrome c release along with caspase 3 activation that reveals the importance of targeting programmed cell death signaling at different points of its signaling pathway for cancer therapy.

Research paper thumbnail of Ginsenoside Rb1 stimulates adiponectin signaling in C2C12 muscle cells through up-regulation of AdipoR1 and AdipoR2 proteins

Pharmaceutical Biology, 2015

Rb1 ginsenoside, the key element of ginseng root, is widely used as an herbal therapeutic drug in... more Rb1 ginsenoside, the key element of ginseng root, is widely used as an herbal therapeutic drug in diabetic patients. Various hypoglycemic mechanisms have been described for Rb1; however, to date, there has been no report on the effect of Rb1 on adiponectin signaling. The current study was performed to establish the effects of ginsenoside Rb1 on the gene expression of AdipoR1 and AdipoR2 and their correlation to GLUT4 translocation in C2C12 myocytes. C2C12 myotubes were incubated with various concentrations of Rb1 (0.001-100 µM) for different incubation times (1-12 h). Real time PCR and western blot analyses were performed to investigate the expression changes of adiponectin receptors (AdRs) and GLUT4 translocation, respectively. Gene silencing of AdipoR1 using specific siRNA was used to determine whether inhibition of AdipoR1 would reduce Rb1-induced GLUT-4 translocation in C2C12 cells. Rb1 significantly stimulated basal AdRs expression levels in a time and dose-dependent manner; the maximal effect was attained at a concentration of 100 µM and a time of 3 h (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). In muscle cells, Rb1 increased GLUT4 translocations to the cell surface, which was correlated with increasing the adiponectin receptors gene expression. Rb1-induced GLUT4 translocation was inhibited by the silencing of AdipoR1 mRNA. These results suggest that ginsenoside Rb1 promote translocations of GLUT4 by activating the adiponectin signaling pathway. The results can be helpful in understanding the novel antidiabetic mechanism of Rb1 ginsenoside and gain further support for its use as an antidiabetic drug.

Research paper thumbnail of Impact of Cell Density on Differentiation Efficiency of Rat Adipose-derived Stem Cells into Schwann-like Cells

International journal of stem cells, Jan 30, 2016

Schwann-like (SC-like) cells induced from adipose-derived stem cells (ASCs) may be one of the ide... more Schwann-like (SC-like) cells induced from adipose-derived stem cells (ASCs) may be one of the ideal alternative cell sources for obtaining Schwann cells (SCs). They can be used for treating peripheral nerve injuries. Co-culture with SCs or exposure to glial growth factors are commonly used for differentiation of ASCs to SC-like cells. However, the effect of initial cell density as an inductive factor on the differentiation potential of ASCs into the SC-like cells has not been yet investigated. ASCs were harvested from rat and characterized. The cells were seeded into the culture flasks at three different initial cell densities i.e. 2×10³, 4×10³ and 8×10³ cells/cm² an overnight and differentiated toward SC-like cells using glial growth factors. After two weeks, the differentiation rate of ASCs to SC-like cells at different densities was assessed by immunofluorescence, fluorescence-activated cell sorting analysis and real time RT-PCR. Expression of the typical SCs markers, S-100 prote...

Research paper thumbnail of Skin-derived precursors possess the ability of differentiation into the epidermal progeny and accelerate burn wound healing

Cell biology international, 2017

Skin-derived precursors (SKPs) are remnants of the embryonic neural crest stem cells that reside ... more Skin-derived precursors (SKPs) are remnants of the embryonic neural crest stem cells that reside in the dermis until adulthood. Although they possess a wide range of differentiation potentials, their differentiation into keratinocyte-like cells and their roles in skin wound healing are obscure. The present study aimed to investigate the differentiation of SKPs into keratinocyte-like cells and evaluate their role in healing of third degree burn wounds. To this aim, SKPs were differentiated into keratinocyte-like cells on tissue culture plate and collagen-chitosan scaffold prepared by freeze-drying. Their differentiation capability was detected by real-time RT-PCR and immunofluorescence. Thereafter, they were cultured on scaffold and implanted in a rat model of burn wound. Histopathological and immunohistochemical analyses were employed to examine the reconstituted skin. The research findings revealed that SKPs were able to differentiate along the epidermal lineage and this ability ca...

Research paper thumbnail of Dexamethasone effects on Bax expression in the mouse testicular germ cells

Folia Histochemica Et Cytobiologica, 2009

Materials and methods Animals. NMRI male mice weighing 25-30 g were kept in individual stainless ... more Materials and methods Animals. NMRI male mice weighing 25-30 g were kept in individual stainless steel cages under standardized conditions

Research paper thumbnail of Progesterone and Cilostazol Protect mice pancreatic islets from oxidative stress induced by hydrogen peroxide

Iranian Journal of Pharmaceutical Research, 2014

Reactive oxygen species and oxidative stress impair β-cell function and reduce insulin secretion.... more Reactive oxygen species and oxidative stress impair β-cell function and reduce insulin secretion. It has been shown that progesterone and cilostazol possess antioxidant properties. The present study was aimed to investigate in-vitro pretreatment effect of progesterone and cilostazol on insulin secretion as well as their protective effects against hydrogen peroxideinduced oxidative stress in pancreatic isolated islets from mouse.

Research paper thumbnail of Application of Alginate capsules as a three dimensional scaffold for differentiation of Wharton's Jelly Mesenchymal stem Cells to definitive endoderm

Arak Medical University Journal, Jul 15, 2014

Background: Wharton's Jelly Mesenchymal Stem Cells (WJMSc) are potential renewable source of cell... more Background: Wharton's Jelly Mesenchymal Stem Cells (WJMSc) are potential renewable source of cells in replacement therapies of many diseases. Different biomaterials have been used as a scaffold to mimic the stem cell niche, which is important for promoting cellular interactions, cell proliferation and differentiation. Encapsulation involves entrapment of living cells within the semipermeable membrane for the exchange of nutrients, oxygen and stimuli, whereas antibodies and host immune cells are kept out. In this study, a new approach for culturing and differentiating Wharton's Jelly Mesenchymal Stem Cells to definitive endoderm in a three dimensional environment using alginate capsules is presented.

Research paper thumbnail of In Vitro Activity of Camellia Sinensis Extracts Against L.MAJOR and L.INFANTUM Promastigotes Using the Colorometric MTT Assay

Urmia Medical Journal, Dec 15, 2014

Plant extracts and plant-derived compounds are unlimited sources of chemical diversity for identi... more Plant extracts and plant-derived compounds are unlimited sources of chemical diversity for identification of new medicinal agents that are commonly used to treat infectious diseases. The purpose of this study was to evaluate the in vitro antileishmanial activity of camellia sinensis extracts against L. infantum and L. major promastigotes by using colorimetric MTT assay as compared to the pentavalent antimonial compound (meglumine antimonite).

Research paper thumbnail of Combination effects of prednisolone and interleukin-4 protect bovine nasal cartilage explants from interleukin-1α induced degradation

Iranian Biomedical Journal, Oct 1, 2011

Background: Current treatments for joint diseases are moderately successful, but unfortunately ar... more Background: Current treatments for joint diseases are moderately successful, but unfortunately are associated with significant side effects. This study was undertaken to investigate the combination effects of IL-4 and prednisolone on tissue characteristics and production of matrix metalloproteinase-1(MMP-1) in IL-lα-treated bovine nasal cartilage (BNC) explants. Methods: BNC explants were cultured in DMEM with IL-lα (10 ng/ml), IL-4 (50 ng/ml) and prednisolone (1 or 1,000 nM) at the same time for 28 days. At days 3, 7, 14, 21and 28, the media were collected and replaced with fresh media, and the removed media were stored at -20°C. The alterations of tissue characteristics were assessed by using histology techniques. Western-blot method was used to determine the effects of IL-4 and prednisolone combination on MMP-1 production. The cell viability was evaluated by using lactate dehydrogenase assay test. Results: In the presence of IL-lα alone, most chondrocytes were transformed into fibroblast-like morphology with pyknotic nuclei at day 28. In addition, a clear band of MMP-1 and extracellular matrix (ECM) degradation were observed. In combination of IL-4 and prednisolone, chondrocytes preserved their ordinary normal features. MMP-1 band formation was completely inhibited and ECM absolutely showed normal characteristics. IL-4 and prednisolone did not show cytotoxicity effects on BNC explant culture. Conclusion: This combination can strongly preserve cartilage from degradation features and the data possibly suggest that the combination of IL-4 and prednisolone could be a candidate for alternative therapy in joint diseases. Iran. Biomed. J. 15 (4): 143-150, 2011

Research paper thumbnail of Protective Effects of Interleukin-4 on Tissue Destruction and Morphological Changes of Bovine Nasal Chondrocytes in vitro

Iranian Biomedical Journal, Oct 1, 2013

Previous studies have shown that some cytokines have protective effects on cartilage in joint dis... more Previous studies have shown that some cytokines have protective effects on cartilage in joint diseases. In the current study, effects of IL-4 against morphological changes and tissue degradation induced by IL-1α on bovine nasal cartilage (BNC) explants were investigated. Methods: Fresh BNC samples were prepared from a slaughterhouse under sterile conditions. BNC explants culture was treated with both IL-lα (10 ng/ml) and IL-4 (50 ng/ml) at the same time for 28 days. The morphological characteristics of explants were assessed by using histology techniques and invert microscopy. Matrix metalloproteinase-1 (MMP-1) production was assessed within different days by using Western blotting. Results: IL-lα induced prominent cartilage morphology degradation. The pro and active form of MMP-1 band substantially increased at day 21 of culture. In the presence of both IL-lα and IL-4, chondrocytes preserved their ordinary normal phenotype with intact extracellular matrix. In addition, a significant reduction in pro-MMP-1and inhibition of active MMP-1 was seen. Conclusion: In conclusion, IL-4 could be regarded as a potential candidate in cartilage protecting against the degradation changes of IL-lα. It seems that the preservation effect of IL-4 is associated with significant reduction of MMP-1. Iran. Biomed.

Research paper thumbnail of Morphological Changes of Bovine Nasal ChondrocytesInduced by Interleukin-1α

Cell Journal, 2013

Objective:A study of the histological events under interleukin-1α (IL-lα) induction of bovine nas... more Objective:A study of the histological events under interleukin-1α (IL-lα) induction of bovine nasal cartilage (BNC) could result in useful data to better understand the mechanisms involved in tissue breakdown in joint diseases. The aim of this study was to investigate the effects of IL-lα on chondrocyte phenotype and extracellular matrix (ECM) changes in BNC explants.Materials and Methods:In this experimental study, samples were divided into two groups. Group I (control group) BNC explants were cultured only in Dulbecco’s modified Eagle’s medium (DMEM). In group II, BNC explants were treated with IL-lα (10 ng/ ml) for 28 days. Then, samples were harvested on culture days 3, 7, 14, 21 and 28 and chondrocyte morphology and ECM alterations were assessed by invert microscopy and histology by hematoxylin and eosin (H&E) and Alcian blue. Cell viability was evaluated by the lactate dehydrogenase (LDH) assay test. Data were analyzed by the t test and p<0.05 was considered significant.Results:IL-lα induced significant morphological changes in cartilage. In the presence of IL-lα, most chondrocytes transformed into a fibroblast-like morphology with a granular black point appearance. An increase in the cell: matrix ratio was observed and there were decreased numbers of chondrocytes.IL-lα induced breakdown of ECM. We observed partial degradation of ECM between days 7-14 and complete degradation occurred between days 21-28 of culture. The LDH levels increased.Conclusion:IL-1α induced morphological changes in chondrocytes and increased destruction of cartilage ECM. There was a parallel correlation between proteoglycan degradation and changes in chondrocyte morpholgy.

Research paper thumbnail of Isolation and Characterization of Human Umbilical Cord Mesenchymal Stem Cells and Their Differentiation into Pdx-1<sup>+</sup> Cells

Journal of Biomedical Science and Engineering, 2015

Research paper thumbnail of Glucose plus metformin compared with glucose alone on β‑cell function in mouse pancreatic islets

Biomedical Reports, 2015

Metformin is currently the first drug of choice for treatment of type II diabetes. The primary fu... more Metformin is currently the first drug of choice for treatment of type II diabetes. The primary function of metformin is to decrease hepatic glucose production mainly by inhibiting gluconeogenesis. The aim of the present study was to investigate the effects of glucose alone (control groups) and glucose and metformin (treatment groups) on pancreatic islets functions. Pancreatic islets were isolated by collagenase digestion and incubated for 24 or 48 h in RPMI-

Research paper thumbnail of Effect of bone morphogenetic (BMP-2) on the aged human articular chondrocytes

Toxicology Letters, 2010

Current in vitro cytotoxicity models are limited by their incomplete modeling of other cell types... more Current in vitro cytotoxicity models are limited by their incomplete modeling of other cell types and of cell functions and interactions within a tissue, organ, systems and whole body. The MCB system was designed to minimize these discrepancies by connecting different cell types together through the flow of a common medium. The objective of this study was to demonstrate that the MCB system is a more effective toxicological screen than existing assays, particularly for difficult compounds, since it is more predictive of the in vivo behavior of drug candidates than simple cellular assays.

Research paper thumbnail of Progesterone and cilostazol protect mice pancreatic islets from oxidative stress induced by hydrogen peroxide

Iranian journal of pharmaceutical research : IJPR, 2014

Reactive oxygen species and oxidative stress impair β-cell function and reduce insulin secretion.... more Reactive oxygen species and oxidative stress impair β-cell function and reduce insulin secretion. It has been shown that progesterone and cilostazol possess antioxidant properties. The present study was aimed to investigate in-vitro pretreatment effect of progesterone and cilostazol on insulin secretion as well as their protective effects against hydrogen peroxide-induced oxidative stress in pancreatic isolated islets from mouse. Pancreatic islets were isolated from 84 male NMRI mice (25-30 g) by collagenase digestion method and pretreated for 48 h with cilostazol (10 μM), progesterone (0.5 μM) and glibenclamide (10 μM) in culture medium. Then islets were exposed to hydrogen peroxide (H2O2. 500 μM) for 2 h. Next, culture mediums containing glucose concentration of 2.8 mM or 16.7 mM were added to them and incubated in this status for 1 h. At the end, the rate of insulin output from islets, lipid peroxidation and antioxidant enzymes activities in islet tissues were assayed. Exposure o...

Research paper thumbnail of Protective effects of interleukin-4 on tissue destruction and morphological changes of bovine nasal chondrocytes in vitro

Iranian biomedical journal, 2013

Previous studies have shown that some cytokines have protective effects on cartilage in joint dis... more Previous studies have shown that some cytokines have protective effects on cartilage in joint diseases. In the current study, effects of IL-4 against morphological changes and tissue degradation induced by IL-1α on bovine nasal cartilage (BNC) explants were investigated. Fresh BNC samples were prepared from a slaughterhouse under sterile conditions. BNC explants culture was treated with both IL-lα (10 ng/ml) and IL-4 (50 ng/ml) at the same time for 28 days. The morphological characteristics of explants were assessed by using histology techniques and invert microscopy. Matrix metalloproteinase-1 (MMP-1) production was assessed within different days by using Western blotting. IL-lα induced prominent cartilage morphology degradation. The pro and active form of MMP-1 band substantially increased at day 21 of culture. In the presence of both IL-lα and IL-4, chondrocytes preserved their ordinary normal phenotype with intact extracellular matrix. In addition, a significant reduction in pro...

Research paper thumbnail of Morphological changes of bovine nasal chondrocytes induced by interleukin-1α

Cell journal, 2013

A study of the histological events under interleukin-1α (IL-lα) induction of bovine nasal cartila... more A study of the histological events under interleukin-1α (IL-lα) induction of bovine nasal cartilage (BNC) could result in useful data to better understand the mechanisms involved in tissue breakdown in joint diseases. The aim of this study was to investigate the effects of IL-lα on chondrocyte phenotype and extracellular matrix (ECM) changes in BNC explants. In this experimental study, samples were divided into two groups. Group I (control group) BNC explants were cultured only in Dulbecco's modified Eagle's medium (DMEM). In group II, BNC explants were treated with IL-lα (10 ng/ ml) for 28 days. Then, samples were harvested on culture days 3, 7, 14, 21 and 28 and chondrocyte morphology and ECM alterations were assessed by invert microscopy and histology by hematoxylin and eosin (H&E) and Alcian blue. Cell viability was evaluated by the lactate dehydrogenase (LDH) assay test. Data were analyzed by the t test and p<0.05 was considered significant. IL-lα induced significant...

Research paper thumbnail of Combination effects of prednisolone and interleukin-4 protect bovine nasal cartilage explants from interleukin-1α induced degradation

Iranian biomedical journal, 2011

Current treatments for joint diseases are moderately successful, but unfortunately are associated... more Current treatments for joint diseases are moderately successful, but unfortunately are associated with significant side effects. This study was undertaken to investigate the combination effects of IL-4 and prednisolone on tissue characteristics and production of matrix metalloproteinase-1(MMP-1) in IL-lα-treated bovine nasal cartilage (BNC) explants. BNC explants were cultured in DMEM with IL-lα (10 ng/ml), IL-4 (50 ng/ml) and prednisolone (1 or 1,000 nM) at the same time for 28 days. At days 3, 7, 14, 21 and 28, the media were collected and replaced with fresh media, and the removed media were stored at -20°C. The alterations of tissue characteristics were assessed by using histology techniques. Western-blot method was used to determine the effects of IL-4 and prednisolone combination on MMP-1 production. The cell viability was evaluated by using lactate dehydrogenase assay test. In the presence of IL-lα alone, most chondrocytes were transformed into fibroblast-like morphology with...

Research paper thumbnail of Comparsion of the enzymatic and explant methods for the culture of keratinocytes isolated from human foreskin

Biomedical Reports, 2015

Currently, culture and growth keratinocytes are important stages in achieving a reliable and repr... more Currently, culture and growth keratinocytes are important stages in achieving a reliable and reproducible skin tissue. In the present study, two different methods, enzymatic and explant methods, for keratinocytes isolation from human foreskin were compared. Foreskins were cut into 2-3 mm pieces and placed in trypsin at 4°C overnight for separation of the epidermis from the dermis. Subsequently, these samples were divided into two groups: i) Keratinocytes separated from the epidermis by trypsin and ii) by the explant method. These keratinocytes were divided into two groups: i) With no feeder layer and ii) onto a type I collagen scaffold. The cells were evaluated using immunocytochemistry and 4&amp;amp;amp;amp;amp;amp;#39;,6-diamidine-2&amp;amp;amp;amp;amp;amp;#39;-phenylindole dihydrochloride (DAPI) staining. In the enzymatic treatment, after 7-10 days no attached cells were found in the cell culture dishes. In the explant method, keratinocytes were separated after ~24 h, attached rapidly and formed big colonies into a collagen scaffold. In the absence of a feeder layer, small colonies were developed with rapid loss of proliferation within 2-3 days. Keratinocytes showed positive immunoreactivity for the pan-cytokeratin marker and keratinocytes&amp;amp;amp;amp;amp;amp;#39; nuclei were clearly observed. This method could be applied and developed as a component of skin substitutes to treat burns and wounds and also in laboratory testing.

Research paper thumbnail of Interleukin-4 and Prednisolone affect the matrix metalloproteinase-13 releasing from degenerative bovine nasal cartilage in vitro

Research paper thumbnail of Gamma-Tocopherol Enhances Apoptotic Effects of Lovastatin in Human Colorectal Carcinoma Cell Line (HT29)

Nutrition and Cancer, 2014

Recently, we found that lovastatin, a HMG-CoA reductase inhibitor, and gamma-tocopherol, one of t... more Recently, we found that lovastatin, a HMG-CoA reductase inhibitor, and gamma-tocopherol, one of the significant types of vitamin E in diet, additively induced apoptosis in a colorectal carcinoma cell line. In this study we mechanistically monitored the loss of mitochondrial membrane potential, amount of cytosolic cytochrome c and caspase 3 activity after treatment by lovastatin and gamma-tocopherol. HT29 cells were treated with different doses of lovastatin and gamma-tocopherol for 48 and 72 h. Lovastatin and gamma-tocopherol in combination induced the release of cytochrome c, caspase 3 activation, and loss of mitochondrial membrane potential more significantly compared to their controls. Our data showed that lovastatin plus gamma tocopherol potently induced mitochondrial membrane potential collapse, cytochrome c release along with caspase 3 activation that reveals the importance of targeting programmed cell death signaling at different points of its signaling pathway for cancer therapy.

Research paper thumbnail of Ginsenoside Rb1 stimulates adiponectin signaling in C2C12 muscle cells through up-regulation of AdipoR1 and AdipoR2 proteins

Pharmaceutical Biology, 2015

Rb1 ginsenoside, the key element of ginseng root, is widely used as an herbal therapeutic drug in... more Rb1 ginsenoside, the key element of ginseng root, is widely used as an herbal therapeutic drug in diabetic patients. Various hypoglycemic mechanisms have been described for Rb1; however, to date, there has been no report on the effect of Rb1 on adiponectin signaling. The current study was performed to establish the effects of ginsenoside Rb1 on the gene expression of AdipoR1 and AdipoR2 and their correlation to GLUT4 translocation in C2C12 myocytes. C2C12 myotubes were incubated with various concentrations of Rb1 (0.001-100 µM) for different incubation times (1-12 h). Real time PCR and western blot analyses were performed to investigate the expression changes of adiponectin receptors (AdRs) and GLUT4 translocation, respectively. Gene silencing of AdipoR1 using specific siRNA was used to determine whether inhibition of AdipoR1 would reduce Rb1-induced GLUT-4 translocation in C2C12 cells. Rb1 significantly stimulated basal AdRs expression levels in a time and dose-dependent manner; the maximal effect was attained at a concentration of 100 µM and a time of 3 h (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). In muscle cells, Rb1 increased GLUT4 translocations to the cell surface, which was correlated with increasing the adiponectin receptors gene expression. Rb1-induced GLUT4 translocation was inhibited by the silencing of AdipoR1 mRNA. These results suggest that ginsenoside Rb1 promote translocations of GLUT4 by activating the adiponectin signaling pathway. The results can be helpful in understanding the novel antidiabetic mechanism of Rb1 ginsenoside and gain further support for its use as an antidiabetic drug.

Research paper thumbnail of Impact of Cell Density on Differentiation Efficiency of Rat Adipose-derived Stem Cells into Schwann-like Cells

International journal of stem cells, Jan 30, 2016

Schwann-like (SC-like) cells induced from adipose-derived stem cells (ASCs) may be one of the ide... more Schwann-like (SC-like) cells induced from adipose-derived stem cells (ASCs) may be one of the ideal alternative cell sources for obtaining Schwann cells (SCs). They can be used for treating peripheral nerve injuries. Co-culture with SCs or exposure to glial growth factors are commonly used for differentiation of ASCs to SC-like cells. However, the effect of initial cell density as an inductive factor on the differentiation potential of ASCs into the SC-like cells has not been yet investigated. ASCs were harvested from rat and characterized. The cells were seeded into the culture flasks at three different initial cell densities i.e. 2×10³, 4×10³ and 8×10³ cells/cm² an overnight and differentiated toward SC-like cells using glial growth factors. After two weeks, the differentiation rate of ASCs to SC-like cells at different densities was assessed by immunofluorescence, fluorescence-activated cell sorting analysis and real time RT-PCR. Expression of the typical SCs markers, S-100 prote...

Research paper thumbnail of Skin-derived precursors possess the ability of differentiation into the epidermal progeny and accelerate burn wound healing

Cell biology international, 2017

Skin-derived precursors (SKPs) are remnants of the embryonic neural crest stem cells that reside ... more Skin-derived precursors (SKPs) are remnants of the embryonic neural crest stem cells that reside in the dermis until adulthood. Although they possess a wide range of differentiation potentials, their differentiation into keratinocyte-like cells and their roles in skin wound healing are obscure. The present study aimed to investigate the differentiation of SKPs into keratinocyte-like cells and evaluate their role in healing of third degree burn wounds. To this aim, SKPs were differentiated into keratinocyte-like cells on tissue culture plate and collagen-chitosan scaffold prepared by freeze-drying. Their differentiation capability was detected by real-time RT-PCR and immunofluorescence. Thereafter, they were cultured on scaffold and implanted in a rat model of burn wound. Histopathological and immunohistochemical analyses were employed to examine the reconstituted skin. The research findings revealed that SKPs were able to differentiate along the epidermal lineage and this ability ca...