Therapeutic effect of mesenchymal stem cell therapy in the LVEF, LVEDV, and LVESV after myocardial infarction.

OBJECTIVES: The present study was aimed to investigate the therapeutic effect of mesenchymal Stem Cell Therapy in the left ventricular ejection fraction (LVEF), left ventricular enddiastolic volume (LVEDV), and  left ventricular endsystolic volume (LVESV) after myocardial infarction (MI). BACKGROUND: Previous investigations propose that stem cell therapy may help treat myocardial infarction (MI). However, there are controversial data from different studies. METHODS: We studied the relevant scientific literature available up to 2020. Comprehensive Meta-Analysis Software (CMAS) Version 2.0 were used for statistical analyses. Fixed or random-effect model was used to identify the weighted mean difference (WMD) with 95% confidence intervals (CI). The statistically significant level used for interpreting publication bias was less than 0.05. RESULTS: We identified 30 studies that met the inclusion criteria. In the overall pooled estimate, cell therapy had an effect on the LVEF change from baseline to follow-up (WMD: 2.98 mL, 95% CI: 1.66 to 4.29). The pooled WMD was found to be -4.16 (95% CI: -7.91 to -0.40) and -5.62 (95% CI: -9.20 to -2.00), for LVEDV, and LVESV, respectively. Thus, reduction in LVEDV and LVESV were significant in the treatment group participants. CONCLUSIONS: The present systematic review indicated that cell therapy in patients, who have MI could be effective and applicable clinically (Tab. 3, Fig. 7, Ref. 48). Text in PDF www.elis.sk Keywords: myocardial infarction, stem cell, systematic review, randomized clinical trials.

Neural stem cells neuroprotection by simvastatin via autophagy induction and apoptosis inhibition.

OBJECTIVE: This study was conducted to investigate the effects of Simvastatin (SIM), a member of statin family, on the cellular antioxidant system, autophagy and apoptosis in NSCs exposed to hydrogen peroxide. BACKGROUND: Reduction in cellular oxidative stress increases the survival of neural stem cells (NSCs) after transplantation into the damaged area of the affected central nervous system. MATERIAL AND METHODS: NSCs derived from bone marrow stromal cells (BMSCs) were exposed to H2O2 (100 µM) for 48 hours after pretreatment with SIM (2 µM). Next, the expressions of the master antioxidant transcription factor, Nrf2/nuclear factor erythroid 2 (NFE2)-related factor 2, autophagy-related proteins (microtubule-associated proteins 1A/1B light chain 3B known as LC3I and LC3II and also p62/Sequestosome), and apoptosis (Bcl-2/ B-cell lymphoma 2 and Bax/BCL2 associated X protein) were analyzed. RESULTS: SIM caused Nrf2 over-activation (more localizations in the cellular nucleus), reduction in reactive oxygen species (ROS), induction of autophagy (decrease in p62 expression and increase in LC3II/LC3I ratio) and inhibition of apoptosis (decrease in Bax protein and increase in Bcl-2) in NSCs exposed to H2O2-induced oxidative stress, thereby prolonging the cell viability within 48 hours at low concentration (2 µM). CONCLUSION: SIM protects NSCs against H2O2-induced apoptosis in a pleiotropic signaling manner (Fig. 7, Ref. 35).

Nod-like receptor protein 3 and nod-like receptor protein 1 inflammasome activation in the hippocampal region of postmortem methamphetamine chronic user.

OBJECTIVE AND BACKGROUND: Methamphetamine (Meth) is one of the most important central nervous system (CNS) stimulant abuse drugs that cause long-term or permanent damage to different regions of the brain, particularly hippocampus, by neuronal apoptosis and inflammation. In this study, we evaluated Nod-like Receptor Protein 3(NLRP3) and Nod-like Receptor Protein1 (NLRP1) Inflammasome Activation in the Hippocampal Region of postmortem Meth Chronic User. METHODS: Molecular and histological analyses were conducted on the brain of 14 non-addicted and 11 Meth users separately. The expression level of NLRP1, NLRP3 was measured using western blotting and immunohistochemistry (IHC) techniques. Histopathological assessment was performed with stereological Cell Counting of hippocampal cells stained with hematoxylin and eosin (H et E). Moreover, Tunel staining was carried out in order to detect any kind of DNA damage. RESULTS: Based on our findings using western blotting and immunohistochemistry assay, overexpression of NLRP1 and NLRP3 proteins in the hippocampal region of Meth addicts was observed. The stereological analysis in the hippocampus of the human brain revealed increased neurodegeneration. Furthermore, the increased rate of apoptosis and cell death were significant and confirmed by Tunel assay in the hippocampus of Meth groups. CONCLUSION: Chronic Meth abuse could result in increases of NLRP1 and NLRP3 and induction of inflammation and apoptosis in the hippocampus in Meth groups (Tab. 1, Fig. 9, Ref. 40).

Deferoxamine promotes mesenchymal stem cell homing in noise-induced injured cochlea through PI3K/AKT pathway.

OBJECTIVE: Over 5% of the world's population suffers from disabling hearing loss. Stem cell homing in target tissue is an important aspect of cell-based therapy, which its augmentation increases cell therapy efficiency. Deferoxamine (DFO) can induce the Akt activation, and phosphorylation status of AKT (p-AKT) upregulates CXC chemokine receptor-4 (CXCR4) expression. We examined whether DFO can enhance mesenchymal stem cells (MSCs) homing in noise-induced damaged cochlea by PI3K/AKT dependent mechanism. MATERIALS AND METHODS: Mesenchymal stem cells were treated with DFO. AKT, p-AKT protein and hypoxia inducible factor 1- α (HIF-1α) and CXCR4 gene and protein expression was evaluated by RT- PCR and Western blot analysis. For in vivo assay, rats were assigned to control, sham, noise exposure groups without any treatment or receiving normal, DFO-treated and DFO +LY294002 (The PI3K inhibitor)-treated MSCs. Following chronic exposure to 115 dB white noise, MSCs were injected into the rat cochlea through the round window. Number of Hoechst- labelled cells was determined in the endolymph after 24 hours. RESULTS: Deferoxamine increased P-AKT, HIF-1α and CXCR4 expression in MSCs compared to non-treated cells. DFO pre-conditioning significantly increased the homing ability of MSCs into injured ear compared to normal MSCs. These effects of DFO were blocked by LY294002. CONCLUSIONS: Pre-conditioning of MSCs by DFO before transplantation can improve stem cell homing in the damaged cochlea through PI3K/AKT pathway activation.

Evaluation of the effect of BMSCs condition media and methylprednisolone in TGF-ß expression and functional recovery after an acute spinal cord injury.

The purpose of this experimental study is evaluation of the effect of BMSCs Condition Media and Methylprednisolone in TGF-ß expression and functional recovery after acute spinal cord injury in adult wistar rat. MATERIAL AND METHODS: After an acute spinal cord injury, MP and BMSC-CM were injected intraperitoneally and the recovery rate was evaluated by BBB and narrow beam test. Real time PCR, H[et]E staining, cavity formation and stereology was done after 12 weeks post injury. RESULT: There were significant differences in functional recovery between MP+CM group, relative to other groups. TGF-ß1 expression decreased in MP+CM group compared to the control group. Cavity size in experimental groups decreased compared to the control group. The mean volume of spinal cord demonstrated a significant increase in the MP+CM group in comparison to the other experimental groups. CONCLUSION: Simultaneous use of MP and BMSC-CM will improve recovery from the spinal cord injury, reduce inflammation and improve functional recovery (Tab. 1, Fig. 8, Ref. 26).

Impact of melatonin supplementation in the rat spermatogenesis subjected to forced swimming exercise.

Oxygen consumption increases many times during exercise, which can increase reactive oxygen species. It negatively affects fertility in male athletes. Melatonin is exerting a regulatory role at different levels of the hypothalamic-pituitary-gonadal axis. However, there is no evidence that the protective effects of melatonin persist after long duration exercise on the spermatogenesis. Therefore, this study was conducted to examine the impacts of melatonin on the testis following the administration of swimming exercise. Rats were separated into five different groups, including Control, sham M: received the solvent of melatonin, M: received melatonin, S: the exercise protocol, MS: received melatonin and the exercise protocol. After 8 weeks, animals were scarified and antioxidant enzymes levels of testes, spermatogenic cells apoptosis and sperm quality were measured. Swimming decreased all parameters of spermatozoa. Nevertheless, melatonin could significantly improve the progressive motility of spermatozoa in MS rats. Swimming caused an increased apoptosis of S group and decreased all antioxidant enzymes. Melatonin could drastically reduce apoptosis and increased these enzymes. Therefore, melatonin seems to induce the production of antioxidant enzymes of testicular tissues and diminish the extent of apoptotic changes caused by forced exercise on the testis, which can, in turn, ameliorate the sperm parameters.