Regulatory effects of trimetazidine in cardiac ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury is a tissue damage during reperfusion after an ischemic condition. I/R injury is induced by pathological cases including stroke, myocardial infarction, circulatory arrest, sickle cell disease, acute kidney injury, trauma, and sleep apnea. It can lead to increased morbidity and mortality in the context of these processes. Mitochondrial dysfunction is one of the hallmarks of I/R insult, which is induced via reactive oxygen species (ROS) production, apoptosis, and autophagy. MicroRNAs (miRNAs, miRs) are non-coding RNAs that play a main regulatory role in gene expression. Recently, there are evidence, which miRNAs are the major modulators of cardiovascular diseases, especially myocardial I/R injury. Cardiovascular miRNAs, specifically miR-21, and probably miR-24 and miR-126 have protective effects on myocardial I/R injury. Trimetazidine (TMZ) is a new class of metabolic agents with an anti-ischemic activity. It has beneficial effects on chronic stable angina by suppressing mitochondrial permeability transition pore (mPTP) opening. The present review study addressed the different mechanistic effects of TMZ on cardiac I/R injury. Online databases including Scopus, PubMed, Web of Science, and Cochrane library were assessed for published studies between 1986 and 2021. TMZ, an antioxidant and metabolic agent, prevents the cardiac reperfusion injury by regulating AMP-activated protein kinase (AMPK), cystathionine-γ-lyase enzyme (CSE)/hydrogen sulfide (H2S), and miR-21. Therefore, TMZ protects the heart against I/R injury by inducing key regulators such as AMPK, CSE/H2S, and miR-21.

Upregulation of Neurotrophic Factors and Myelin Basic Protein in Schwann-like Cells by T3 Hormone Following Transdifferentiation of Human Adipose-derived Stem Cells.

Peripheral nerve regeneration is a complicated phenomenon. Thyroid hormones are known as critical regulators in the nervous system development. The Schwann cells have the regenerative potency in the peripheral nervous system. In this study, the human adipose-derived stem cells were assessed in vitro, for transdifferentiation potency into Shwann-like cells (SLCs) as a candidate source for clinical cell therapy, under the treatment of triiodothyronine (T3) hormone, and compared with the untreated cells. The cell viability rate, myelination and neurotrophic factors expression of SLCs were evaluated two weeks post- induction by MTT assay, immunocytochemistry and real-time RT-PCR techniques, respectively. The obtained results revealed a significant decrease in SLCs viability, compared to the adipose-derived stem cells (P < 0.001). Immunocytochemistry technique was applied to detect SLCs markers, such as S100ß, GFAP and myelin basic proteins (MBP) in the presence and absence of T3 treatment. The results indicated that administering T3 can significantly increase the differentiation and myelination potency of SLCs (P < 0.01). The findings of real-time RT-PCR technique indicated that the expression of Schwann cells markers, MBP, brain-derived neurotrophic factor and glial cell-derived neurotrophic factor were upregulated significantly with T3 hormone administration in comparison with the untreated cells (P < 0.05). The SLCs were able to express the neurotrophic factors and myelination related genes in the presence of T3 hormone. Furthermore, T3 administration improved myelination potency of adipose-derived stem cells, in vitro. Further in vivo experiments are necessary to confirm the advantages of using a combination of autologous SLCs and T3 hormone for peripheral nerve injury recovery.

pH-responsive glucosamine anchored polydopamine coated mesoporous silica nanoparticles for delivery of Anderson-type polyoxomolybdate in breast cancer.

AIM: This study aimed to develop novel pH-sensitive Glucosamine (Glu) targeted Polydopamine (PDA) coated mesoporous silica (SBA-15) nanoparticles (NPs) for selective delivery of anticancer Anderson-type manganese polyoxomolybdate (POMo) to breast cancer. METHODS: The POMo@SBA-PDA-Glu NPs were prepared via direct hydrothermal synthesis of SBA, POMo loading, in situ PDA post functionalization, and Glu anchoring; the chemical structures were fully studied by different characterisation methods. The anticancer activity was studied by MTT method and Annexin V-FITC apoptosis detection kit. RESULTS: The optimised NPs had a hydrodynamic size (HS) of 195 nm, a zeta potential (ZP) of -18.9 mV, a loading content percent (LC%) of 45%, and a pH-responsive release profile. The targeted NPs showed increased anticancer activity against breast cancer cell lines compared to the free POMo with the highest cellular uptake and apoptosis level in the MDA-MB-231 cells. CONCLUSIONS: POMo@SBA-PDA-Glu NPs could be a promising anticancer candidate for further studies.

Biotin-Targeted Nanomicellar Formulation of an Anderson-Type Polyoxomolybdate: Synthesis and In Vitro Cytotoxicity Evaluations.

This study is aimed at developing a micellar carrier for an Anderson-type manganese polyoxomolybdate (TRIS-MnPOMo) to improve the potency and reduce the general toxicity. The biotin-targeted stearic acid-polyethylene glycol (SPB) polymeric conjugate was selected for the first time as a micelle-forming basis for the delivery of TRIS-MnPOMo to breast cancer cells. The cytotoxicity of TRIS-MnPOMo and its nanomicellar form (TRIS-MnPOMo@SPB) was evaluated against MCF-7, MDA-MB-231 (breast cancer cell lines), and HUVEC (normal cell line) in vitro using the MTT assay. The quantity of cellular uptake and apoptosis level were studied properly using standard methods. The hydrodynamic size, zeta potential, and polydispersity index of the prepared micelles were 140 nm, -15.6 mV, and 0.16, respectively. The critical micelle concentration was about 30 µg/mL, which supports the colloidal stability of the micellar dispersion. The entrapment efficiency was interestingly high (about 82%), and a pH-responsive release of TRIS-MnPOMo was successfully achieved. The micellar form showed better cytotoxicity than the free TRIS-MnPOMo on cancer cells without any significant heme and normal cell toxicity. Biotin-targeted nanomicelles internalized into the MDA-MB-231 cells interestingly better than nontargeted micelles and TRIS-MnPOMo, most probably via the endocytosis pathway. Furthermore, at the same concentration, micelles remarkably increased the level of induced apoptosis in MDA-MB-231 cells. In conclusion, TRIS-MnPOMo@SPB could profoundly improve potency, safety, and cellular uptake; these results are promising for further evaluations in vivo.

Cartilage tissue formation from human adipose-derived stem cells via herbal component (Avocado/soybean unsaponifiables) in scaffold-free culture system.

BACKGROUND: 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. MATERIALS AND METHODS: In this an experimental study After hADSCs characterization, chondrogenic differentiation was induced using transforming growth factor beta 1 (TGF-ß1) (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. RESULTS: 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-ß1 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. CONCLUSION: It can be concluded that A/S similar to TGF-ß1 is able to facilitate the chondrogenic differentiation of hADSCs and do not have adverse effects of TGF-ß1. Thus, TGF-ß1 can be replaced by A/S in the field of tissue engineering.

Differential effect of polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles on BT-474 human breast cancer cell viability.

Polyvinylpyrrolidone superparamagnetic iron oxide nanoparticles (PVP-SPIONs) have unique properties. Due to these characteristics, PVP-SPIONs have been used in several medical applications such as magnetic resonance imaging (MRI) contrast agent or drug delivery system. However, a more comprehensive understanding of the environmental safety of PVP-SPIONs is vital for consumption of these nanomaterials. In this study, we describe the effects of PVP-SPIONs on cell viability of the BT-474 human breast cancer cells. Cell viability of the BT-474 cells treated with PVP-SPIONs (10-800 µg/ml) was assessed by MTT assay. MRC-5 cell line was used as a control. Quantitative real-time PCR was performed to investigate the mRNA expression levels of apoptotic (caspase 3) and anti-apoptotic (BCL2) genes Confluent BT-474 monolayers exposed to PVP-SPIONs showed biphasic effects on cell proliferation. PVP-SPIONs at 10-100 µg /ml promote proliferation of BT-474 cells but not the MRC-5 cells. At higher dosage, PVP-SPIONs have toxicity on BT-474 cells. The results of real-time PCR was in line with MTT assay. The increase of cell proliferation at low PVP-SPIONs concentrations is different from what would be expected for these nanoparticles. Our results suggest that more attentions are needed to ensure the safer use of SPION in nanomedicine.

Exposure to Global System for Mobile Communication 900 MHz Cellular Phone Radiofrequency Alters Growth, Proliferation and Morphology of Michigan Cancer Foundation-7 Cells and Mesenchymal Stem Cells.

BACKGROUND: Today, using cellular phone and its harmful effects in human life is growing. The aim of this study is to investigate the effect of the global system for mobile communication (GSM) 900 MHz cellular phone radiofrequency waves on growth, morphology, and proliferation rate of mesenchymal stem cells and Michigan Cancer Foundation (MCF-7) cells within the specific distance and intensity. METHODS: MCF-7 and human adipose-derived stem cells (HADSCs) were exposed to GSM cellular phones 900 MHz frequency with intensity of 354.6 µW/cm2 during different exposure times 6, 21, 51, and 101 min/day with an interval of 10 min for each subsequent radiation exposure for 3 and 5 days at 10 and 20 cm distances from antenna. 3-(4,5-dimethythiazol- 2-yl)-2,5-diphenyl tetrazolium bromide assay and trypan blue test were used to determine the growth of cells and cell viability, respectively. Statistical analyses were carried out using three-way ANOVA. Differences were significant when P < 0.05. RESULTS: The proliferation rates of both MCF-7 and HADSCs cells in all exposure groups were significantly lower than controls (P < 0.05). There was a significant effect on the percentage of cell survival with increase the period of time from 3 to 5 days for MCF-7 (P < 0.01) and HADSCs (P = 0.02), respectively. Variations in distance had no significant effect on the percentage of cell survival (P = 0.35) on MCF-7 (P = 0.02) and HADSCs (P = 0.09) cells, respectively. CONCLUSIONS: The results showed that radiation of GSM 900 MHz cellular phone may be reduced cell viability and proliferation rates of both cells. It is recommended to reduce exposure time, increase distance from antenna, and reserve the use of cell phones for shorter conversations to prevent its biological and harmful effects. Further studies with other intensities and frequencies on different cells are recommended.

Comparison of the efficacy of piascledine and transforming growth factor ß1 on chondrogenic differentiation of human adipose-derived stem cells in fibrin and fibrin-alginate scaffolds.

OBJECTIVES: The aim of this study was to compare the chondrogenic induction potential of Piascledine and TGF-ß1 on adipose-derived stem cells (ADSCs) in fibrin and fibrin-alginate scaffolds. MATERIALS AND METHODS: 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-ß1, 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. RESULTS: 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<0.05). Real-time PCR evaluation revealed that the expression of type II collagen was higher in TGF- ß1groups, but the expression of aggrecan was higher in TGF-ß1 alone or along with Piascledine in fibrin-alginate scaffolds. Furthermore, the expression of type X collagen was lower in Piascledine alone or along with TGF-ß1 in fibrin scaffold. CONCLUSION: Piascledine can enhance the proliferation and differentiation of ADSCs in fibrin scaffolds.