ali valiani

The most important strategy in tissue engineering is the relationship between the three components of biomaterials, living cells, and biologically active molecules suitable for tissue regeneration. To be clinically effective, these environments must replicate, as closely as possible, the main characteristics of the native Extracellular Matrix (ECM) on a cellular scale. Tissue engineering is generally employed to create hybrid scaffolding to support cartilage tissue regeneration using fabrication 3D printing techniques. The current study designed a three-dimensional scaffold using FDA-approved Polycaprolactone/Poly Lactic-co-Glycolic Acid (PCL/PLGA) polymers. Then, 40 and 45 (w/w) alginate nanoparticles were added to the bio-ink to improve the printability, mechanical properties, and biocompatibility of the scaffolds. Finally, 3D-printed scaffolds were evaluated using mechanical properties, surface hydrophilicity, water absorption, biodegradability, surface morphology, and cell viability. The results showed that increasing the percentage of alginate nanoparticles in the bio-ink would increase the percentage of porosity, surface hydrophilicity, mechanical properties, cell viability, and printability. In addition, water absorption and compression modules of PCL/PLGA 3D-printed scaffolds containing 45 % alginate were optimized, compared to those of other groups, hence used as bio-ink in 3D printing of scaffolds in tissue engineering defects.

Cartilage tissue engineering, by using stem cells, scaffolding and appropriate growth factors, seek to produce natural cartilage tissue to replace damaged tissue and solve the problems that exist in the treatment of cartilage damage. This study aims to compare chondrogenic differentiation of adipose-derived stem cells under the influence of the transforming growth factor beta 3 (TGF-β3), Kartogenin, and avocado/soybean unsaponifiables (ASU) on the fibrin scaffold in the laboratory and animal models.

In this experimental laboratory study, after extraction of stem cells from human adipose tissue, induction of chondrogenic differentiation was done for 14 days on the fibrin scaffold in laboratory. The cells differentiated in the fibrin scaffold were transplanted subcutaneously under the skin of male rats for two weeks. Then, comparison of histological and immunohistochemical studies was performed in both laboratory and animal models.

A significant increase in the density of Toluidine blue dye accumulation was observed in TGF-β3, Kartogenin and ASU groups in the animal model compared to the laboratory model. Immunohistochemical results for the collagen type X accumulation in the TGF-β3 group showed a significant increase in the animal model compared to the laboratory model. In the Kartogenin and ASU groups, the accumulation of collagen type Χ showed a significant decrease in the animal model compared to the laboratory model.

The implantation of differentiated cartilage cells in laboratory before subcutaneous transfer to the skin can help mature and complete the characteristics of the constructed cartilage.

Due to the lack of suitable therapeutic approaches to cartilage defect, the objective of this study was to determine the effect of Transforming growth factor-β3 (TGF-β3), avocado/soybean (ASU) and Kartogenin (KGN) on chondrogenic differentiation in human adipose-derived stem cells (hADSCs) on fibrin scaffold. hADSCs seeded in fibrin scaffold and cultured in chondrogenic media. These cells were divided into 4 groups (control, TGF-β3, ASU and KGN). Cell viability was estimated by MTT assay. Differentiated cells were evaluated by histological and immunohistochemical (IHC) techniques. Expression genes [sex determining region Y-box 9 (SOX9), Aggrecan (AGG), type II collagen (Coll II) and type X collagen (Coll X)] were assessed by real-time PCR. For a study on an animal model, differentiated cells in fibrin scaffolds were subcutaneously transplanted in rats. Histological and immunohistochemistry were done in the animal model. The results of the real-time PCR indicated that SOX9, AGG and Col II genes expression in TGF-β3, KGN and ASU groups were significantly higher (p < 0.01) compared to the control group, Col X gene expression only in the TGF-β3 group was significantly higher (p < 0.01) compared to the control group. The glycosaminoglycan (GAG) deposition was higher in TGF-β3, KGN and ASU groups compared to the control group. The immunohistological analysis showed the distribution of collagen type X in the extracellular matrix in the fibrin scaffold TGF-β3 group was significantly higher in control, KGN and ASU groups, and (p < 0.001). ASU, particularly KGN, was suitable for successful chondrogenic differentiation of hADSCs and a suppressor of the consequent hypertrophy.

Corporation of Hyaluronic acid (HA) with PLGA is an effective way to potentially enhance chondrogenesis. The aim of this study was to use HA macroporous biodegradable poly(lactic acid-co-glycolic acid) [PLGA] scaffold to enhance the attachment, proliferation and differentiation of chondrocytes for cartilage tissue engineering and articular cartilage regeneration of human adipose derived stem cells (hADSCs) in the presence of avocado/soybean unsaponifible (ASU).

The PLGA and PLGA/HA scaffolds were prepared and hADSCs were cultured separately on the scaffolds and 14 days after differentiation, chondrogenic genes in each scaffold evaluated using real time PCR and cell viability examined by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.

The viability and proliferation of cells in-group of PLGA significantly decreased in comparison with the control (P=0.002) and PLGA/HA (P=0.013) groups.The expression of (SOX9), Aggrecan (AGG), and Collagen type II (Col II) genes was significantly higher in the PLGA and PLGA/HA groups compared to the control group (P≥0.05).The gene expression of SOX9 (P=0.003) and AGG (P=0.009) was significantly higher in the PLGA/HA groups compared to the PLGA group. The results of real time PCR showed that collagen type X (Col X) gene expression in the PLGA group, was significantly higher than the control and PLGA/HA groups (P=0.000).

The corporation of HA with PLGA is an effective way to potentially enhance chondrogenesis and articular cartilage regeneration of hADSCs in the presence of avocado/soybean unsaponifiables (ASU).

Improper prognosis in brain cancers requires new treatments. Using family of purinergic receptors with confirmed apoptotic effect can be beneficial. As the role of type A1 receptor in multiform glioblastoma in relation to the P53 gene and apoptotic pathways is nor reported, we studied the role of agonist (N6-cyclopentyladenosine or CPA) and antagonist (8-cyclopentyl-1,3-dipropylxanthine or DPCPX) of this receptor on cell apoptosis and also expression of P53 genes and caspases 7, 8, and 9.

In this study, MTT assay was used to investigate the rate of cellular proliferation, and flowcytometry method with annexin and Pi was also used to investigate early and late cell apoptosis. To evaluate the internal and external apoptotic pathways expression of P53 genes and caspases 7, 8, and 9, real-time reverse transcription polymerase chain reaction (real-time RT PCR) was used.

The treatment of U87Mg cells with DPCPX increased the expression of P53 gene. Expression of caspase 7 as an executive caspase and caspase 9 as a caspase of the mitochondrial pathway of apoptosis increased, but no expression change was observed in the caspase 8 gene.

The results of MTT and flowcytometry showed that DPCPX, in addition to suppressing cell proliferation, stimulated apoptosis in U87Mg cells. Inhibition of adenosine A1 receptors by stimulating the expression of genes involved in apoptotic pathways, especially mitochondrial pathway genes, suppressed cell proliferation and induced apoptosis in U87Mg cells.

Avocado/soybean unsaponifible (ASU) possesses properties including chondroprotective, anticatabolic, and anabolic. The goal behind this research was to detect the effect of ASU and TGF-β3 on the chondrogenesis of human adipose-derived stem cells (hADSCs) on poly (lactic-co-glycolic) acid (PLGA)/ hyaluronic acid (PLGA/HA) hybrid scaffold. First hADSCs were seeded in PLGA/Hyaluronic acid scaffold and cultured in chondrogenic media. These cells were assigned into 4 groups: control, TGFβ-3, ASU, and TGFβ-3+ASU. The viability was assessed separately by MTT. Real-time PCR was used to quantify the expression of chondrogenic specific genes [Sox9, collagen type II (ColII), Aggrecan (AGG)] and collagen type X (ColX). Moreover, Western blotting was employed to evaluate protein expression levels of collagens type II and X. These findings indicated a significant increase in the proliferation and survival of hADSCs differentiated cells by ASU compared with the control group (P=0.008). Real-time PCR results revealed significant differences in the expression of AGG, SOX9, ColII, and ColX genes in the control group when compared with other groups (ASU, TGF-β3, and TGF-β3+ASU). ColII protein production significantly dropped in the TGF-β3 group in comparison with the TGF-β3+ASU group (0.000). The ColII (P=0.002) and ColX (P=0.002) protein production proved significantly higher in the TGF-β3+ASU group compared with the ASU group. Using the synergist form TGFβ-3, ASU induces chondrogenesis in hADSCs in PLGA/HA composite scaffold. This can be deduced with reduction of special markers of hyaline cartilage in comparison with ASU and decreased hypertrophic marker compared with TGF-β3.

Adenosine receptor family, especially A1 type is-overexpressed in breast-derived tumor cells and the P53 gene is mutant in some of these cells while the casps gene is of wild type as well. The aim of this study was to evaluate the effect of the A1 receptor function on cell programmed death or proliferation, as well as the relationship between this receptor stimulation/inhibition and caspase 3 (casp3) expression in T47D cell line that has a mutant and non-functional P53 gene.

The expression of casps3 was measured by real-time polymerase chain reaction and then flow cytometery and MTT assay were used to assess the apoptotic and proliferation cell rate after the treatment of T47D cells with specific agonist N6-cyclopentyladenosine (CPA) and antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) of this receptor 24, 48, and 72 hours after treatment.

Our results indicated that DPCPX significantly induces apoptosis in T47D cells and the rate of survival cell after the reduction of this treatment, especially 72 hours after treatment. Finally, the expression of casp3 was up-regulated by DPCPX treatment, especially in 72 hours while CPA treatment had opposite results (P > 0.05).

In general, DPCPX could up-regulate casp3 gene expression and subsequently increase the apoptosis rate in T47D cells with casp3 expression without the P53 gene interference. Therefore, adenosine A1 receptor antagonists may be introduced as anti-cancer agents.

Tissue engineering is a relatively novel field that has been intensely developing during recent years and has shown to be excessively promising when used for cartilage regeneration. Scaffolds represent important components for tissue engineering.

The Poly Lactic-Co-Glycolic Acid (PLGA) impregnated with fibrin and hyaluronic acid (HA) produce hybrid scaffolds. human adipose-derived stem cells (hADSCs) were seeded in scaffolds and cultured in chondrogenic media. The viability of cells in different groups was assessed by MTT. The expression of chondrogenic related genes [Sox9, type II collagen (Col II), Aggrecan(AGG)] and type X collagen (Col X) was quantified by real-time polymerase chain reaction.

The results of the real-time PCR showed SOX9, AGG and Col X gene expression in the control groups being significantly lower than the other groups (p≤0.05). It also demonstrated Col II gene expression in the control group being significantly lower than the PLGA/Fibrin and PLGA/Fibrin/HA groups (p≤0.05). The Col X gene expression of cells in PLGA/HA and PLGA/Fibrin/HA groups significantly decreased in comparison with the PLGA/Fibrin group (p≤0.05).

These conclusions indicate that administration of PLGA/ Fibrin and PLGA/HA scaffolds, particularly PLGA/Fibrin/ HA, motivates chondrogenesis in hADSCs. This can be diminished by decreasing hypertrophic markers and increasing characteristic markers of hyaline cartilage.

Recently, cartilage tissue engineering is the best candidate for regeneration of cartilage defects. We evaluated the potential of fibrin and PLGA/fibrin scaffolds in providing a suitable environment for growth and chondrogenic differentiation of human adipose derived stem cells (hADSCs) in the presence of icariin. The Three-dimensional (3-D) PLGA scaffold was prepared using the solvent casting/salt leaching technique and the hybrid scaffold was fabricated by fibrin. hADSCs were isolated from human adipose tissue. 3-D PLGA/fibrin scaffolds were seeded with cultured hADSCs and analyzed 14 days later, Monolayer culture was used for the control group. The viabilities of cells in different groups were assessed by MTT. The expression of chondrogenic related genes, hypertrophic marker and Fibrotic marker were quantified by RT-PCR. MTT results show that viability in the control group was significantly higher than those in the Fibrin and PLGA/Fibrin groups. Also viability in the PLGA/Fibrin group affected by icariin was higher than that in Fibrin group. The results of the real-time PCR showed that SOX9, Agg, Coll 2, and Coll 1 gene expression in the fibrin and PLGA/fibrin groups were significantly higher than those in the control group. Coll 10 gene expression in the fibrin group was higher in comparison to the control group but not significantly. type SOX9, Coll 2 and Coll 1 gene expression in the fibrin group was significantly lower compared to the PLGA/fibrin group. The study reveals that the corporation of PLGA with fibrin is an effective way to potentially enhance articular cartilage regeneration of hADSCs in the presence of icariin.

The use of stem cells, growth factors, and scaffolds to repair damaged tissues is a new idea in tissue engineering. The aim of the present study is the investigation of Avocado/soybean (A/S) effects on chondrogenic differentiation of human adipose‑derived stem cells (hADSCs) in micromass culture to access cartilage tissue with high quality.

In this an experimental study After hADSCs characterization, chondrogenic differentiation was induced using transforming growth factor beta 1 (TGF‑β1) (10 ng/ml) and different concentrations (5, 10, and 20 μg/ml) of A/S in micromass culture. The efficiency of A/S on specific gene expression (types I, II, and X collagens, SOX9, and aggrecan) was evaluated using quantitative polymerase chain reaction. In addition, histological study was done using hematoxylin and eosin and toluidine blue staining all data were analyzed using one‑way analysis of variance (ANOVA) and P ≤ 0.05 was considered to be statistically significant.

The results of this study indicated that A/S can promote chondrogenic differentiation in a dose‑dependent manner. In particular, 5 ng/ml A/S showed the highest expression of type II collagen, SOX9, and aggrecan which are effective and important markers in chondrogenic differentiation. In addition, the expression of types I and X collagens which are hypertrophic and fibrous factors in chondrogenesis is lower in present of 5 ng/ml A/S compared with TGF‑β1 group (P ≤ 0.05). Moreover, the sulfated glycosaminoglycans in the extracellular matrix and the presence of chondrocytes within lacuna were more prominent in 5 ng/ml A/S group than other groups.

It can be concluded that A/S similar to TGF‑β1 is able to facilitate the chondrogenic differentiation of hADSCs and do not have adverse effects of TGF‑β1. Thus, TGF‑β1 can be replaced by A/S in the field of tissue engineering.

Avocado and soya unsaponifiables (ASU) have been reported to be useful for the treatment of cartilage diseases. The aim of this study was to detect whether avocado/soybean can have any effect on the chondrogenesis of human adipose-derived stem cells on polylactic-co-glycolic acid/fibrin hybrid scaffold or not. The poly-lactic-co-glycolic acid (PLGA)/fibrin scaffolds were seeded with cultured human adipose tissue-derived stem cells (hADSCs), which were then divided into three groups: control, TGF-β3, and ASU and the results were analyzed 14 days later. The viability of the cells in different groups were assessed by MTT. The expression of chondrogenic-related genes Sox9, type II collagen, Aggrecan, type X collagen, and type I collagen were quantified by real time polymerase chain reaction (PCR). Protein expression levels of collagen type II and X were evaluated by Western blotting. Enhanced cellular viability was observed in the ASU group compared to the transforming growth factor beta-3 (TGF-β3) group. Analysis of aggrecan (Agg), type II collagen (Coll2) and SOX9 revealed that ASU and TGF-β3 induce hADSCs on PLGA/fibrin scaffold to differentiate into chondrocytes in-vitro. Moreover, a significant decrease was observed in the expression of type X (Coll10) and I collagen (Coll1) genes in the ASU group compared to the TGF-β3 group. Protein levels of type II collagen (Coll2) significantly increased in TGF-β3 and ASU groups in comparison with those of the control group. However, protein levels of Type X collagen (Coll10) significantly declined in the ASU group when compared with the TGF-β3 group. The results of the present study indicated that hADSCs containing the ASU in PLGA/fibrin hybrid scaffold are an effective way to potentially enhance Cartilage-specific genes with less hypertrophy and Fibrosis in-vitro.

Electrospun nanofibers have shown significant potential as an origin for forming cartilage tissue engineering scaffolds. Acellular extracellular matrices have been incorporated into nanofiber scaffolds to more closely replicate the extracellular niche. The aim of this study was to investigate the electrospinning of poly(ε-caprolactone)/extracellular matrix (PCL/ECM) and its mechanical and biological behavior for tissue engineering. PCL and PCL/ECM scaffolds were prepared via electrospinning of the 10% (w/v) solution contain PCL and PCL/ECM by dichloromethane (DCM) and dimethylsulfoxide (DMSO) solutions. The MTT technique was used to study the survival and proliferation of human adipose-derived stem cells in scaffold. The morphology, stability, and scaffold surface properties were studied using scanning electron microscopy, tensile strength test, water absorption, and contact angle measurement. The PCL/ECM electrospinning scaffold showed significant increase in hydrophobicity, water absorption, and tensile strength compared to PCL electrospinning scaffold. The porosity and diameter of the fibers in the scaffold had a relative reduction. Moreover, the viability and proliferation of cells on the seventh day showed a significant increase. The results of this study showed that adding extracellular matrix to PCL scaffold improves the properties of the scaffold for tissue engineering.

Nowadays, cartilage tissue engineering is the best candidate for regeneration of cartilage defects. This study evaluates the function of herbal extracts icariin (ICA), the major pharmacological constituent of herba Epimedium, compared with transforming growth factor β3 (TGFβ3) to prove its potential effect for cartilage tissue engineering.

ICA, TGFβ3, and TGFβ3 + ICA were added fibrin‑cell constructions derived from adipose tissue stem cells. After 14 days, cell viability analyzed by 3‑(4,5‑dimethyl‑2‑thiazolyl)‑2,5‑diphenyl‑2H‑ tetrazolium bromide assay and the expression of cartilage genes was evaluated with real‑time polymerase chain reaction (RT‑PCR).

The results showed ICA, TGFβ3, and TGFβ3 + ICA increased the rate of proliferation and viability of cells; but there were no significant differences between them (P > 0.05). Furthermore, quantitative RT‑PCR analysis demonstrated that cooperation of ICA with TGFβ3 showed a better effect in expression of cartilaginous specific genes and increased Sox9, type II collagen, and aggrecan expression significantly. Furthermore, the results of the expression of type I and X collagens revealed that TGFβ3 increased the expression of them (P < 0.01); However, treatment with ICA + TGFβ3 down regulated the expression of these genes significantly.

The results indicated ICA could be a potential factor for chondrogenesis and in cooperation with TGFβ3 could reduce its hypertrophic effects and it is a promising factor for cartilage tissue engineering.

One of the main causes of mortality is hepatocellular carcinoma (HCC) which accounts for the third leading cause of deaths and one in forty deaths worldwide. The flavonoids, natural antioxidant compounds, account for a major group of polyphenolic compounds. One of the major isoflavones in soybean is genistein (GE) which can inhibit proliferation and induce apoptosis. Isoflavones, major type of phenolic materials, derived from dietary plants and medicinal herbs play a signifcant role in cancer prevention and treatment. Correlation between dietary habits and cancer risk including breast, prostate, and colon cancer has been reported. Various bioactivities of these compounds such as anticarcinogenic and antioxidant are responsible for their chemopreventive activities by which induce migration, proliferation, cell cycle arrest, and apoptosis. GE, one of the major isoflavones, is considered as a potent chemopreventive agent against cancer. The aim of this study was to investigate the inhibitory and apoptotic effects of GE on HCC Hepa1‑6 cell line.
Cell viability assay and cell cycle analysis with flow cytometry were used to evaluate proliferative and apoptotic effect GE.
GE inhibited the growth of Hepa1‑6 cells and induced apoptosis with a concentration and time‑dependent fashion. During GE treatment for 24, the half maximal inhibitory concentration (IC50) was 20 μM, and the maximum inhibition of cell growth was 52% (P Our fnding clearly indicated that GE can signifcantly inhibit proliferation of hepatocellular carcinoma Hepa 1‑6 cell line and induce apoptosis in this cell line.

The aim of this study was to compare the chondrogenic induction potential of Piascledine and TGF-β1 on adipose-derived stem cells (ADSCs) in fibrin and fibrin-alginate scaffolds.
Human subcutaneous adipose tissues were harvested from three patients who were scheduled to undergo liposuction. Isolated ADSCs were proliferated in a culture medium. Then, the cells were seeded in fibrin or fibrin-alginate scaffolds and cultured for 14 days in a chondrogenic medium containing Piascledine, TGF-β1, or both. The rate of cell proliferation and survival was evaluated by using MTT [3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide] assay and the rate of the expression of type II collagen, aggrecan, and type X collagen genes was evaluated by real-time polymerase chain reaction (real-time PCR) method.
The MTT results showed that Piascledine is able to enhance the proliferation and survival of ADSCs in fibrin scaffolds in comparison to other groups (P Piascledine can enhance the proliferation and differentiation of ADSCs in fibrin scaffolds.

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.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. This cancer may be due to a multistep process with an accumulation of epigenetic alterations in tumor suppressor genes (TSGs), leading to hypermethylation of the genes. Hypermethylation of TSGs is associated with silencing and inactivation of them. It is well‑known that DNA hypomethylation is the initial epigenetic abnormality recognized in human tumors. Estrogen receptor alpha (ERα) is one of the TSGs which modulates gene transcription and its hypermethylation is because of overactivity of DNA methyltransferases. Fortunately, epigenetic changes especially hypermethylation can be reversed by pharmacological compounds such as genistein (GE) and 17‑beta estradiol (E2) which involve in preventing the development of certain cancers by maintaining a protective DNA methylation. The aim of the present study was to analyze the effects of GE on ERα and DNMT1 genes expression and also apoptotic and antiproliferative effects of GE and E2 on HCC.

Cells were treated with various concentrations of GE and E2 and the 3‑(4,5‑dimethyl‑2‑thiazolyl)‑2,5‑diphenyl‑2H‑tetrazolium bromide assay was used. Furthermore, cells were treated with single dose of GE and E2 (25 μM) and flow cytometry assay was performed. The expression level of the genes was determined by quantitative real‑time reverse transcription polymerase chain reaction.

GE increased ERα and decreased DNMT1 genes expression, GE and E2 inhibited cell viability and induced apoptosis significantly.

GE can epigenetically increase ERα expression by inhibition of DNMT1 expression which in turn increases apoptotic effect of E2. Furthermore, a combination of GE and E2 can induce apoptosis more significantly.

Nowadays, the biodegradable polymer nano-composites have particular importance in tissue engineering because of mechanical properties and good biocompatibility. The aim of this study was to design and evaluate nano-composite fibrin/polyvinyl alcohol (PVA) scaffold using electrospinning method and cell viability on it.
Nano-composite scaffold fibrin/PVA were prepared by electrospinning method while 28.5% of the polymer was formed of fibrin. The porosity of the scaffolds was calculated via scanning electron microscopy by using “Matlab” software and porosity morphology, their distribution and size of the nanofibers. Water absorption test and contact angle measurement were performed. Also, human adipose-derived stem cells were used for cell viability evaluation on scaffolds.
Findings: The mean diameter of electrospun fibrin/PVA scaffold was measured 500 nm. The average pore size and porosity of the prepared sample was 1.7 micrometers and 83.81%, respectively. The average contact angle was 31.71 degrees and 24-hour average water absorption was measured 68.5%. Evaluation test of the cell viability has a significant difference compared to control groups.
The results of this study show that electrospun scaffolds fibrin/PVA can be used in cartilage and nerve tissue engineering.

Adenosine receptor family especially A1 type is expressed in breast cancer cells in which P53 and caspase genes are wild-type. The aim of this study was to investigate the correlation between A1 receptor and either cell apoptosis or proliferation and also to recognize the relationship between this receptor and P53 and the expression of caspases 3, 8 and 9 in MCF-7 cell line. MCF-7 cells were treated intermittently with A1 receptor agonist N6-Cyclopentyladenosine (CPA) and A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) in different times to measure the expression of p53, caspase 3, 8 and 9 besides apoptosis and survival rate. Our findings indicated that DPCPX significantly induced apoptosis in MCF-7 cells while the cell viability was reduced specially 72 h after the treatment and the expression of p53 gene and caspase expressions was dramatically up-regulated. On the other hand, CPA increased the cell viability and reduced apoptosis in MCF-7 cells. Our results indicated a significant down-regulation in the MCF-7 mRNA expression of p53 and caspases 3, 8 and 9. Furthermore, DPCPX induced p53 and caspase 3, 8 and 9 expressions that consequently promotes the cell apoptosis in MCF‑7 cells. Therefore, DPCPX can be considered as an anti-cancer drug.

Cartilage injuries are the leading cause of disability in the elderly in developed countries. In addition, articular cartilage has a limited ability to repair. Current treatment methods for cartilage tissue injuries lead to fibrous tissue formation. Cell therapy is a treatment in which stem cells using tissue engineering can be differentiated into chondrocytes by using growth factors and scaffolds. Since growth factors such as transforming growth factor beta1 (TGF-β) leads to hypertrophy of cartilage chondrocytes tissue and many scaffolds are weak in terms of mechanics and stability, it is essential to achieve the appropriate scaffolds and inducing factors. Studies have shown that fibrin alginate scaffold is appropriate in terms of mechanical and stability and piascledine increases the cartilage-specific genes expression. Therefore, in this study the chondrogenic effect of TGF-β1 and piascledine on adipose derived stem cells in fibrin alginate scaffold was compared and evaluated.
Fat samples were obtained from three persons. Adipose derived stem cells (ADSCs) was extracted from adipose tissue and proliferated. Then the cells were transferred to the fibrin alginate scaffold and the cells were cultured for 21 days under the influence of the induction medium. The rate of proliferation and survival of cells was evaluated by [3 (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide] MTT method and the rate of gene expression of Aggrecan and Collagen II and X was evaluated with Real-time polymerase chain reaction (Real-Time PCR) method.
Findings: The results showed that proliferation rate and survival of cells in a fibrin alginate scaffold in the group containing Piascledine increased compared to the other groups, but this increase is not significant (P> 0.050). Also, Piascledine increased collagen II gene expression (P Piascledine was found as a proper effective inducer in chondrogenic differentiation of human adipose derived stem cells cultured in fibrin alginate scaffold.

The basal nuclei are a group of subcortical structures that act as a cohesive functional unit. These nuclei are situated at the base of the forebrain and are strongly connected with the cerebral cortex and thalamus. The basal ganglia are associated with a variety of functions, including voluntary motor control, learning, eye movements, cognitive and emotional functions. The basal nuclei include the motor, cognitive, eye movement, and limbic system circuits. The motor circuit contains a cortico-basal cortical pathway. Stuttering is a disorder in speech production with blocks, repetition, prolongation, or cessation of sound. The main cause of stuttering is unknown. Some speech disorders, such as stuttering, may be the result of disturbances in the circuits between the basal nuclei and the language motor area of the cerebral cortex. Due to their association with the cerebral cortex, especially Broca's area and speech motor cortex, the basal ganglia can influence the motor features of speech. In this review article, the possible relation between stuttering and basal nuclei was discussed.

Cartilage tissue damage is one of the problems in the clinic and the current treatment methods would not be lead to full repair of damage; therefore, tissue engineering in this field is considered. In tissue engineering, biomaterials such as growth factors and appropriate cells are used. Since the growth factors such as transforming growth factor beta (TGF-β) leads to hypertrophy of cartilage, it is essential to achieve the appropriate inducer factors. Studies have shown that piasclidine had a positive effect on cultured chondrocytes. In this study, the effect of the piasclidine on chondrogenesis of human adipose-derived stem cells was examined. Fat samples were obtained from three liposuction surgeries. Stem cells were extracted from adipose tissue and proliferated via the third passage. Then, the cells were transferred to the fibrin scaffold and cultured for 21 days under the influence of the chondrogenic imedium in three groups. The rate of cell proliferation was evaluated using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] method and the rate of gene expression of aggrecan and types II and X collagen was evaluated via real-time polymerase chain reaction (PCR) method. The rate of proliferation and survival of cells in a fibrin scaffold was not different significantly between the groups (P > 0.05); but the gene expression of type II collagen and aggrecan was significantly more expression of type X collagen was significantly less in piasclidine group compared to the of TGF-β group (P < 0.01). Piasclidine is an effective factor in induction of chondrogenesis of stem cells and also has a significant effect on reduction of the cell hypertrophy.

Natural compounds including flavonoids like genistein (GE) are able to inhibit cell proliferation and induce apoptosis. GE is the main representative of these groups. GE inhibits carcinogenic tumors such as colon, stomach, lung, and pancreas tumors. The aim of the present study was to analyze the apoptotic effect of GE in the hepatocellular carcinoma (HCC) PLC/PRF5 cell line. Cells were treated with various doses of GE (1, 5, 10, 25, 50, 75, and 100 μM/L) at different times (24, 48, and 72 h) and the MTT assay was commonly used. Furthermore, cells were treated with single dose of GE (25 μM) at different times and flow cytometry was performed. GE inhibited the growth of liver cancer cells significantly with a time‑ and dose‑dependent manner. The percentage of living cells in GE treatment groups with a concentration of 25 μM at different times were 53, 48 and 47%, respectively (P < 0.001). Result of flow cytometry demonstrated that GE at a 25 μM concentration induces apoptosis significantly in a time‑dependent manner. The percentage of apoptotic cells at different times were 44, 56, and 60%, respectively (P < 0.001). GE can significantly inhibit the growth of HCC cells and plays a significant role in apoptosis of this cell line.

Osteoarthritis is one of the most common diseases in middle‑aged populations in the World and could become the fourth principal cause of disability by the year 2020. One of the critical properties for cartilage tissue engineering (TE) is the ability of scaffolds to closely mimic the extracellular matrix and bond to the host tissue. Therefore, TE has been presented as a technique to introduce the best combination of cells and biomaterial scaffold and to stimulate growth factors to produce a cartilage tissue resembling natural articular cartilage. The aim of study is to improve differentiation of adipose derived stem cells (ADSCs) into chondrocytes in order to provide a safe and modern treatment for patients suffering from cartilage damages. After functionalization, dispersions and sterilizing carbon nano‑tubes (CNTs), a new type of nanocomposite gel was prepared from water‑soluble CNTs and alginate. ADSCs seeded in 1.5% alginate scaffold and cultured in chondrogenic media with and without transforming growth factor‑β1 (TGF‑β1) for 7 and 14 days. The genes expression of sex determining region Y‑box 9 (SOX9), types II and X collagens was assessed by real‑time polymerase chain reaction and the amount of aggrecan (AGC) and type I collagen was measured by ELISA. Our findings showed that the expression of essential cartilage markers, SOX9, type II collagen and AGC, in differentiated ADSCs at the concentration of 1 μg/ml CNTs in the presence of TGF‑β1 were significantly increased in comparison with the control group (P < 0.001). Meanwhile, type X collagen expression and also type I collagen production were significantly decreased (P < 0.001). The results showed that utilized three‑dimensional scaffold had a brilliant effect in promoting gene expression of chondrogenesis.

Nowadays, adipose-derived stem cells (ADSCs) are widely used for cartilage tissue engineering. However, most studies are in the field of scaffolds, growth factors and mechanical stimulation methods. But, few studies have been conducted regarding changes in surface markers during chondrogenesis. Accordingly, this study aimed to assess the changes in surface markers CD14 and CD44 during chondrogenesis.

Human subcutaneous adipose tissue were isolated and cultured from 3 persons influenced by collagenase enzyme and stem cells. The cells of second passage were used for flow cytometry analysis of CD14 and CD44 surface markers. Second passage cells were cultured in alginate scaffolds under the influence of chondrogenic medium. Differentiated cells at the days 7 and 14 were used to evaluate CD14 and CD44 surface markers.

The mean expression of CD44 in ADSCs was 96.8% but CD14 did not expressed in 98.6% of the cells. In stem cells, the mean expression of CD44 differentiated in alginate scaffolds on the day 7 was 96.3%; but on the day 14, it fell to 52.8%. The mean expression of CD14 at the days 7 and 14 was 99.7% and 99.9%, respectively.

Our investigation revealed that the stem cells and differentiated cells at the day 7 express CD44 at high level, but at day 14, the expression of CD44 in differentiated cells is reduced. CD14 is not expressed on stem cells but in differentiated cells is expressed in high level. Due to these changes in surface markers during chondrogenesis, using them can be offered to determine chondrogenesis and to compare differentiated and normal chondrocytes.