mitra soleimani

Oligodendrocyte apoptosis is one of the principal mechanisms in progressive myelin destruction and the development of neurological disabilities. The oligodendrocyte cell death is usually caused by local inflammation and the toxic effects of some environmental factors. Valproic acid can increase cell survival and differentiation due to its diverse antioxidant, anti-apoptotic, anti-inflammatory, and neuroprotective effects. In the present study, the effects of this compound were investigated in preventing oligodendrocyte cell death in the mouse brain corpus callosum.

In this study, 40 mice were randomly divided into four groups: control, sham, cuprizone, and valproic acid/cuprizone. To kill oligodendrocyte cells, 0.2% caprizone compound was used. In addition, the combination of valproic acid was used intraperitoneally, daily with a dose of 300 mg/kg, and for three weeks. immunohistochemical and real-time methods were used to investigate the specific markers of oligodendrocyte cells.

The results showed that the percentage of cells expressing Oligodendrocyte transcription factor (Olig2) and Myelin oligodendrocyte glycoprotein (Mog) markers increased significantly in the group that received valproic acid compared to the groups that received cuprisone (P < 0.05). Also, an increase in the expression of oligodendrocytes-specific genes was reported in the Real Time-PCR method.

The results of this study showed that valproic acid can prevent oligodendrocyte cell death, therefore, the use of this compound can be a suitable solution to prevent the destruction of myelin in nerve tissue

Ovarian cancer is the deadliest gynecological cancer. Bromodomain and extra terminal domain (BET) proteins play major roles in the regulation of gene expression at the epigenetic level. Jun Qi (JQ1) is a potent inhibitor of BET proteins. Regarding the short half-life and poor pharmacokinetic profile, JQ1 was loaded into newly developed nano-carriers. Chitosan nanoparticles are one of the best and potential polymers in cancer treatment. The present study aimed to build chitosan-JQ1 nanoparticles (Ch-J-NPs), treat OVCAR-3 cells with Ch-J-NPs, and evaluate the effects of these nanoparticles on cell cycle and apoptosis-associated genes.

Experimental approach: 

Ch-J-NPs were synthesized and characterized. The size and morphology of Ch-J-NPs were defined by DLS and FE-SEM techniques. OVCAR-3 cells were cultured and treated with Ch-J-NPs. Then, IC50 was measured using MTT assay. The groups were defined and cells were treated with IC50 concentration of Ch-J-NPs, for 48 h. Finally, cells in different groups were assessed for the expression of genes of interest using quantitative RT-PCR.

IC50 values for Ch-J-NPs were 5.625 μg/mL. RT-PCR results demonstrated that the expression of genes associated with cell cycle activity (c-MYC, hTERT, CDK1, CDK4, and CDK6) was significantly decreased following treatment of cancer cells with Ch-J-NPs. Conversely, the expression of caspase-3, and caspase-9 significantly increased. BAX (pro-apoptotic) to BCL2 (anti-apoptotic) expression ratio, also increased significantly after treatment of cells with Ch-J-NPs.

Conclusion and implications:

 Ch-J-NPs showed significant anti-cell cyclic and apoptotic effects on OVCAR-3 cells.

Environmental toxic factors, with their destructive effects on nerve cells and myelin tissue, can induce nervous system dysfunction. The neuroprotective role of valproic acid as an inhibitor of Glycogen synthase kinase 3β (GSK3-β) has been proven in some neurodegenerative diseases. In the present study, the effects of this combination were investigated in preventing myelin tissue destruction and maintaining its density in the corpus callosum of mouse brain.

40 female C57BL/6 mice weighing 20-25 grams were divided into four groups including control, sham, cuprizone and, valproic acid/cuprizone groups. The valproic acid combination was used intraperitoneally, daily, and at a dose of 300 mg/kg. At the end of the research, to check myelin density, Teloidin blue staining, immunohistochemistry and, real-time methods were used.

The results showed that the density of myelin and the percentage of cells expressing the Myelin Basic Protein (MBP) marker increased significantly in the group that received valproic acid compared to the cuprizone group. In addition, the results of myelin-specific gene expression analysis showed that the use of valproic acid can increase the expression of this gene.

The results of the present study showed that valproic acid has the ability to prevent myelin tissue destruction and maintain its density, and therefore, the use of this combination can be a suitable combination to prevent and reduce the progression of diseases that destroy nerve tissue.

Many environmental factors are involved in the death of oligodendrocyte cells, myelin tissue destruction, and disturbance in the central nervous system function. The protective role of lithium chloride as a Glycogen synthase kinase 3β (GSK3-β) inhibitor has been proven in some neurological diseases. In the present study, the effects of this compound were investigated in the prevention of oligodendrocytes death in mouse brains.

In the present study, 40 female C57BL/6 mice weighing 20-25 grams were randomly divided into four groups: control, sham, cuprizone, and lithium chloride/cuprizone. Lithium chloride compound was used intra peritoneally daily. At the end of the study, in order to check the results, immunohistochemistry and Real-time PCR were used.

The results of immunohistochemistry staining showed that the percentage of cells that expressed Oligodendrocyte transcription factor (Olig2) and Myelin oligodendrocyte glycoprotein (Mog) markers increased significantly in the group that received lithium compared to the groups that received cuprizone (P < 0.05). In addition, Real-Time PCR results showed that the use of lithium can increase the expression of oligodendrocytes- specific genes.

The results of the present study showed that lithium chloride has the ability to prevent the oligodendrocytes death, and therefore, the use of this compound can be a suitable solution for preventing and reducing the progression of diseases that destroy central nervous tissue.

The disturbance of the myelination process and myelin tissue destruction leads to central nervous system dysfunction. The neuroprotective role of lithium chloride in the treatment of neurological diseases has been proven. In the present study, the effects of lithium chloride in preventing the destruction of myelin tissue induced by cuprizone in the corpus callosum of the mouse brain were investigated.

In this study, 40 female C57BL/6 mice weighing 20-25 grams were randomly divided into four groups including control, sham, cuprizone and lithium chloride/cuprizone groups. The compound of lithium chloride was used intra peritoneally at a dose of 50 mg/kg daily. At the end of the study, in order to check the average myelin density and myelin gene expression, toluidine blue staining, immunohistochemistry and Real Time-PCR were used.

The results of immunohistochemistry and toluidine blue staining showed that, the density of myelin and the percentage of cells which expressing the Myelin Basic Protein (MBP) marker increased significantly in the group which receiving lithium compared to the cuprizone group. In addition, Real Time-PCR results showed that the use of lithium can increase myelin gene expression.

The results of the present study showed that neuroprotective factors, such as lithium chloride, have the ability to prevent the destruction of myelin tissue, and therefore, the use of this combination can be a suitable manner to prevent and reduce the progression of neurodegenerative diseases.

Ovarian cancer is one of the most dangerous cancers among women. Pogostone has anticancer effects and is rich in polyphenol compounds. In the present study, we investigated the effects of pogostone on ovarian cancer cell lines (OVCAR-3).

Experimental approach: 

OVCAR-3 cells were treated with pogostone at IC50 (90 μg/mL) for 24 and 48 h. Cell viability and apoptotic rate in the cells were measured using MTT assay and flow cytometry. Real-time PCR was used to determine the expression of genes involved in the cell cycle and apoptosis. The expression of caspase-3 (CASP3) protein was evaluated by the CASP3 assay.

Treatment of OVCAR-3 cells with pogostone increased the expression levels of phosphatase and tensin homologue deleted on chromosome ten (PTEN) and Dapper antagonist of catenin-1 (DACT1) tumor suppressor genes, as well as the apoptotic genes CASPs3, 8, and 9. Moreover, the ratio of the expressed BCL2 associated X (BAX)/BCl2 genes, as pro- and anti-apoptotic genes, was increased. The expression levels of the genes related to the cell cycle progression including cyclin D1 (CCND1) and cyclindependent kinase 4 (CDK4) were inhibited. The data obtained from flow cytometry indicated that pogostone induced cell apoptosis in 24 and 48 pogostone groups. The CASP3 colorimetric assay revealed that pogostone increased the expression of CASP3 protein in the treated groups.

Conclusion and implication: 

Pogostone, by inducing the expression of PTEN and DACT1 tumor suppressor genes and regulation of downstream genes may decrease cell proliferation and increase the rate of apoptosis in OVCAR-3.

Growth factors and chemical stimulants have key role in cartilage tissue engineering, but these agents have unfavorable effects on cells. Avocado soybean unsaponifiables (ASU) has chondroprotective and anti‑inflammatory effects. In this study, fibrin2nanoparticles (FNP)/ASU, as a new delivery system, with stem cells applied for cartilage tissue engineering in poly (lactic‑co‑glycolic) acid (PLGA) scaffold.

FNP/ASU prepared by freeze milling and freeze drying. NFP/ASU was characterized by dynamic light scattering (DLS). PLGA‑NFP/ASU scaffold was fabricated and assessed by scanning electron microscope (SEM). Human adipose‑derived stem cells (hADSCs) were seeded on scaffold and induced for chondrogenesis. After 14 days, cell viability and gene/protein expression evaluated.

The results of DLS and SEM indicated that nanoparticles had high quality. The expression of type II collagen and SOX9 and aggrecan (ACAN) genes in differentiated cells in the presence of ASU was significantly increased compared with the control group (P and lt; 0.01), on the other hand, type I collagen expression was significantly decreased and western blot confirmed it.

This study indicated FNP/ASU loaded in PLGA scaffold has excellent effect on chondrogenic differentiation of hADSCs and tissue engineering.

Breast cancer is a highly heterogeneous disease and the most common malignancy in women. Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene that reduces in breast cancer. This gene is a phosphatase, and by its lipid phosphatase capacity separates a phosphate from PIP3, and produces PIP2. So, it tends to inhibition of phosphatidylinositol-3-kinase/AKT (PI3K/AKT) pathway and a break in its cellular cycle in phase G1, increase in apoptosis, and decrease in proliferation of cancer cells. The mammalian target of rapamycin (mTOR) gene is activated by phospho/AKT, and its expression increases in many cancers. The cyclin-dependent kinase 4 (CDK4) gene also acts as an oncogene and its expression increases in various types of human cancers, including breast cancer. Grape seed extract (GSE) is a reach source of natural antioxidants, and treatment with it can tend to inhibition of cell cycle and finally, inhibition of cancer progression. This study aimed to assess the expression of PTEN, CDK4, and mTOR genes and cell proliferation in breast cancer cell line (T47D) under GSE treatment.

T47D cells were purchased and cultured and treated with GSE of a concentration of 60 μg/ml. MTT and real time-polymerase chain reaction (PCR) methods were used to evaluate cell viability and gene expression. Colony survival assay method was used to assess colony formation.

The amount of cell life in the treatment group was significantly lower than the control group. Moreover, the results of real time PCR showed that the relative expression of PTEN gene was significantly higher than the control group, and also the expression of mTOR and CDK4 genes reduced.

The use of GSE can significantly increase the expression of PTEN tumor suppressor gene, and ultimately cause the death of T47D cancer cells.

The progressive destruction of nerve cells in nervous system will induce neurodegenerative diseases. Recently, cell‑based therapies have attracted the attention of researchers in the treatment of these abnormal conditions. Thus, the aim of this study was to provide a simple and efficient way to differentiate human dental pulp stem cells into neural cell‑like to achieve a homogeneous population of these cells for transplantation in neurodegenerative diseases.

In this basic research, human dental pulp stem cells were isolated and characterized by immunocytochemistry and flow cytometry techniques. In the following, the cells were cultured using hanging drop as three‑dimensional (3D) and tissue culture plate as 2D techniques. Subsequently, cultured cells were differentiated into neuron cell‑like in the presence of FGF and Sonic hedgehog (SHH) factors. Finally, the percentage of cells expressing Neu N and β tubulin III markers was determined using immunocytochemistry technique. Finally, all data were analyzed using the SPSS software.

Flow cytometry and immunocytochemistry results indicated that human dental pulp‑derived stem cells were CD90, CD106‑positive, but were negative for CD34, CD45 markers (P ≤ 0.001). In addition, the mean percentage of β tubulin positive cells in different groups did not differ significantly from each other (P ≥ 0.05). Nevertheless, the mean percentage of Neu N‑positive cells was significantly higher in differentiated cells with embryoid bodies’ source, especially in the presence of SHH than other groups (P ≤ 0.05).

It is concluded that due to the wide range of SHH functions and the facilitation of intercellular connections in the hanging droop method, it is recommended that the use of hanging drop method and SHH factor can be effective in increasing the efficiency of cell differentiation.

Ovarian cancer is the deadliest cancer in women. The main challenge in the inhibition of ovarian cancer cells is chemo-resistance. Seeking to overcome this issue, several strategies have been suggested, including the administration of natural products. Grape seed extract (GSE) is a good source of polyphenols and its anticancer effects have been reported by many studies. In this study we aimed to evaluate the effects of GSE on OVCAR-3, a chemo-resistant ovarian cancer line.

OVCAR-3 cells were treated with GSE (71 μg/mL) for 24 and 48 h. Cell viability and cell apoptosis were measured by MTT and flow cytometry. The real-time polymerase chain reaction was used to determine the expression of genes involved in the cell cycle (PTEN, DACT1, AKT, MTOR, GSK3B, C-MYC, CCND1, and CDK4) and apoptosis (BAX, BCl2, CASP3, 8 and 9). The expression of CASP3 protein was evaluated by the CASP3 assay.

The results showed that treatment of OVCAR-3 cells with GSE, increased the expression level of PTEN and DACT1 tumor suppressor genes, as well as apoptotic genes, CASP3, 8, and 9 (P < 0.001). Also, the induction of tumor suppressor genes expression was associated with an increase in the expression of BAX/BCL2 gene ratio as pro- and anti-apoptotic genes. The expression of the genes involved in the cell cycle, CCND1 and CDK4, was inhibited (P < 0.001). The results indicated that GSE induced cell apoptosis in a time-dependent manner (P < 0.001). Also, the GSE treatment resulted in the CASP3 protein expression (P < 0.001).

According to the results of this study, GSE may exert anti-tumorigenic effects on chemo-resistant OVCAR-3 ovarian cancer cells which might be mediated by the expression of tumor suppressor genes that interact with cell signaling pathways, cell cycle, and cell apoptosis. Hence, the consumption of GSE extract during chemotherapy may overcome part of chemo-resistance in ovarian cancer.

Astaxanthin (AST) is a carotenoid with anti-oxidative, anti-inflammatory, and anti-apoptotic properties. It has also been reported that AST exerts protective effects against neurodegenerative diseases and reduces oxidative stress-induced the central nervous system (CNS) injury. In this study, we aimed to evaluate the protective potential of AST in inhibiting demyelination and oligodendrocyte death in a rat model of multiple sclerosis (MS).

In this experimental study, forty Wistar rats were randomly assigned to four experimental groups: control group (with normal feeding), cuprizone (CPZ group) that daily received 0.6% CPZ for 4 weeks, sham group that daily received 0.6% CPZ plus dimethyl sulfoxid (DMSO) for 4 weeks, and AST group that daily received 0.6% CPZ and after 12 hours were treated with AST (3 mg/kg), for 4 weeks. Muscle strength was evaluated by the behavioral basket test at the end of every week for 4 weeks. Luxol Fast Blue (LFB) staining was utilized for the identification of myelination and demyelination. Myelin density was evaluated by the ImageJ software. The expression of A2B5 (oligodendrocyte precursor protein) and myelin oligodendrocyte protein (MOG) were assessed by immunohistochemistry (IHC) and the expression of myelin basic protein (MBP), MOG, and platelet-derived growth factor-alpha (PDGFR-α) genes was examined by the real-time polymerase chain reaction (RT-PCR) technique.

The administration of AST reduced the oligodendrocyte damage and myelin sheath disruption in a rat model of MS. The basket behavioral test showed the improvement of muscle strength in the AST group compared with CPZ and sham groups. Besides, the results of real-time PCR and IHC indicated the beneficial effects of AST in declining demyelination and oligodendrocyte death in a rat model of MS.

AST reduces damages to the myelin sheath and oligodendrocyte death in a rat model of MS.

Nanohydroxyapatite (nHAP) exhibit anti-proliferative effects on various cancer cells. However, to date, there are only a few studies on the radiosensitization effect of nHAP. The present study aimed to investigate the possible enhancement of the radiosensitization effect of nHAP on human breast adenocarcinoma cancer (MCF-7) and fibroblast. nHAP was extracted from fish scales using the thermal alkaline method and characterized at Babol University of Medical Sciences (Babol, Iran) in 2017. The anti-proliferative and the radiosensitization effects of nHAP were investigated by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide (MTT), clonogenic assay, and apoptosis assay. MCF-7 cells and fibroblasts were incubated with different concentrations of nHAP and at different periods. The MTT solution was added and the absorbance was measured at 570 nm. The MCF-7 cells were exposed to 0, 1.5, 3.5, and 5 Gy X-ray irradiation and incubated for 10-14 days. The data were compared using the one-way analysis of variance (ANOVA) followed by the post hoc tests (Tukey’s method). The results showed that nHAP significantly inhibited the growth of MCF-7 cells compared with controls (P<0.001), but the difference was not statistically significant for fibroblasts (P=0.686 at 400 µg/mL at 72 hours). After 48 hours, the proliferation of MCF-7 cells and fibroblasts was inhibited by about 81% and 34% at 400 µg/mL concentration, respectively. The radiosensitization enhancement factor for MCF-7 cells and fibroblasts at a dose of 3.5 Gy and 100 μg/mL concentration were 1.87 and 1.3, respectively. nHAP can be considered as a breast cancer radiosensitization agent with limited damage to the surrounding healthy tissue.

Nowadays, cartilage tissue engineering is the best candidate for regeneration of cartilage defects. This study evaluates the effect of fibrin/icariin (ICA) nanoparticles (F/I NPs) on chondrogenesis of stem cells.

F/I NPs were characterized by Dynamic Light Scattering DLS. Poly (lactic-co-glycolic) acid (PLGA)-F/I NP scaffold was fabricated and assessed by scanning electron microscope. Human adipose-derived stem cells (hADSCs) were seeded on scaffold and induced for chondrogenesis. After 14 days, cell viability and gene expression were analyzed by the 3-(4, 5- dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. MTT assay and real-time polymerase chain reaction (RT-PCR).

The size and surface charge of F/I NP were about 28–30 nm and − 17, respectively. The average of pore size of PLGA and PLGA–fibrin/ICA was 230 and 340 μm, respectively. Cell viability of differentiated cells in P/F group was higher than others significantly (P ≤ 0.05). Furthermore, quantitative RT-PCR analysis demonstrated that ICA upregulated cartilaginous-specific gene expression. Furthermore, the results of the expression of type I collagen revealed that ICA downregulated this gene significantly (P < 0.01).

The results indicated that F/I NP could be a potential factor for chondrogenesis of stem cells and downregulation of fibrocartilage marker.

 MBD1, the largest member of methyl binding domain family, has the most downregulated mRNA expression and upregulated methylation levels in advanced colorectal cancer (CRC). In this study, we evaluated the immune-histochemical expression of MBD1 in CRC and assessed its correlation with clinicopathological features to study its prognostic value in CRC.

A total of 60 samples of CRC, from patients who underwent surgical gastroenterology operations, were randomly selected. The samples included one tumor-rich section per case and one adjacent tumor-free section as a normal control for that case. Then, immunohistochemistry (ICH) was performed for MBD1 protein on all samples and the expression of MBD1 was analyzed in cancerous and normal samples. In the next step, the correlation between MBD1 and clinicopathological features including age, sex, location of the tumor, grade, and stage were evaluated.

 The expression of MBD1 protein had a significant downregulation in cancerous samples compared with normal control samples. This downregulation increased corresponding to both grade and stage of cancer. However, no correlation was seen between the expression of MBD1 and sex, age and location of the tumor.

 MBD1 protein may be considered as a protein marker in the detection of CRC and its progression.

Cartilage tissue is avascular and has no repairing capacity. For cartilage tissue engineering, stem cells and growth factors are used. In this study, the effect of pomegranate as inducer for chondrogenesis of adipose-derived stem cells (ADSCs) was evaluated.
Human adipose-derived stem cells in third passage seeded in fibrin were cultured in chondrogenic medium with pomegranate for 2 weeks. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay) and western blot technique were applied for evaluation of differentiated cells.
Findings: Adipose-derived stem cells differentiated into chondrocytes; and type II collagen production by differentiated cells was proved.
Pomegranate extract is an appropriate inducer for production of type II collagen in adipose-derived stem cells.

Stem cell-based therapy is a novel strategy for the treatment of neuro-degenerative diseases. The transplantation of fully differentiated cells instead of stem cells in order to decrease serious adverse complications of stem cell therapy is a new idea.
In this study, the effect of lithium chloride on dopaminergic differentiation of human immortalized RenVm cells was investigated in order to access a population of fully differentiated cells for transplantation in Parkinson disease.
The immortalized RenVm cells were induced to dopaminergic differentiation using a neurobasal medium supplemented with N2 and different concentrations (1, 3, 6 mM) of Lithium Chloride (LiCl) for 4, 8 and 12 days. The efficiency of dopaminergic differentiation was evaluated using immunocytochemistry and western blot techniques for tyrosine hydroxylase and β-catenin marker expression.
Our results indicated that LiCl can promote dopaminergic differentiation of RenVm cells in a dose-dependent manner.
It can be concluded that LiCl is able to facilitate dopaminergic differenti-ation of cultured cells by affecting Wnt-frizzled signaling pathway.