Cellular Imaging and Uptake Studies of PEG-coated SPION in Human Derived Endometrium Mesenchymal Stem Cell

Introduction: As human endometrium Mesenchymal stem cells (hEMSCs) therapy has been used to treat different diseases, its tracing is essential. Low image sensitivity is one of the most critical problems. So, in this study, transplanted hEMSCs were labeled with the PEG-coated SPION nanoparticles for the first time to improve low image sensitivity at Magnetic resonance imaging (MRI) for more efficient in vivo tracking of cells. To achieve the goals, we evaluated the effects of various concentrations of PEG-coated SPION (20nm) incubated with hEMSCs on cytotoxicity and cell survival. Materials and Methods: PEG-coated SPION was synthesized and its uptake into the cytoplasm of hEMSCs was confirmed by Prussian Blue staining 48 and 72h after incubation at 0, 100, 200, and 300 μg/ml concentrations. Several assessments were done to track the cell differentiation. Then gene expression was assessed by RT-PCR. Results: The data of Atomic Absorption Spectroscopy (AAS) confirmed that PEG-coated SPION absorption by hEMSCs was as increased as the dose (P<0.05). In general, higher concentrations of PEG-coated SPION improved MRI image contrast and enhanced cell fate tracking. Our results suggested that 100 μg/ml PEG-coated SPION was ideal because the cytotoxicity was not statically significant compared to the control group (p<0.05). At 200 and 300 μg/ml concentrations, PEG-coated SPION caused increased oxidative stress and initiated apoptosis and autophagy in hEMSCs. The mechanism of its action was found by evaluation of several key genes; the mRNA levels of apoptosis and autophagy markers, including Bax, Caspase3, BECLIN, LC3, and TP53 raised significantly (P<0.05), while BCL2 decreased at 300 μg/ml concentration (P<0.05). Conclusions: Higher concentrations of PEG-coated SPION can increase ROS production in a dose and time-dependent manner

Intra-Myocardial Injection of Human Amniotic Membrane-Derived Stem Cells Influened Inflammatory Cytokines in HF Model of Rat

Heart failure (HF) is considered one of the most common heart disorders. Recent studies suggest that injections of amniotic membrane stem cells (AMSC) can improve heart function. Therefore, the current study investigated the effect of intra-myocardial injection of human amniotic membrane-derived stem cells (hAMCs) on inflammatory-related cytokines like IL-10 and IL-17 in the HF model of rats. Twenty-eight male Wistar rats were categorized into four groups: control, HF, culture medium injection group, and hAMCs injection group. After 60 days, blood samples were taken from the animals, and the expression levels of interleukins 10 and 17 were measured by the ELISA technique. The results showed that injection of hAMCs into male rats with HF caused down-regulation of IL-17 inflammatory cytokine and over-expression of IL-10 anti-inflammatory cytokine. Based on the results of this study and previous ones, we concluded that hAMCs could be considered one of the candidates in future studies on reducing inflammation in HF treatment by adjusting some inflammatory cytokines

4-methylumbilliferon (4-MU) as a Potential Treatment Against Cerebral ischemia and Reperfusion Injury in Rats; An Experimental Study

Introduction: Ischemic stroke (IS) is one of the three main fatal disorders and is a major health challenge. 4-methylumbelliferone (4-MU) is one of the coumarin derivatives (7–hydroxy‐4–methylcoumarin) with antioxidant and anti-inflammatory impact. This study was conducted to elucidate the neuroprotective effects and anti-inflammatory impact of 4-MU in a rodent model of IS. Methods: The IS model was induced by middle cerebral artery occlusion (MCAO) for 1 hour and reperfusion was established for 24 hours. 44 Male Wistar rats were assigned into four groups: (1) Sham, (2) MCAO (3) MCAO + Vehicle, and (4) MCAO + 4-MU (25 mg/kg). Evaluation of neurological deficit was performed using Garcia's score. 2,3,5-triphenoyl-2H-tetrazolium chloride (TTC) staining was employed to measure infarct size.  Nissl staining was applied to determine neuronal loss. Moreover, western blotting was utilized to detect the expression of the proteins relevant to the TLR4/NF-κB/NLRP3 axis (p–NF–κB p65, TLR4, NLRP3, IL-1β, IL-10, IL-18, ASC, and Caspase-1). Results: It was observed that MCAO caused neurological deficit (P<0.0001), infarct (P<0.0001), and neuronal loss (P<0.002); up-regulated NLRP3 (P<0.0001), TLR4 (P<0.0001), p–NF–κB p65 (P<0.0005), IL-1β (P<0.0014), IL-18 (P<0.0001), ASC (P<0.0027), and Caspase-1 (P<0.0052); and reduced IL-10 concentrations (P<0.0024). Administration of 4-MU (25 mg/kg) quickly after reperfusion reduced neurological deficit (P<0.0001), infarct size (P<0.0001), neuronal loss (P<0.0058), and down-regulated NLRP3 (P<0.0257), TLR4 (P<0.0001), p–NF–κB p65 (P<0.0075), IL-1β (P<0.0106), IL-18 (P<0.0005), ASC (P<0.0072), and Caspase-1 (P<0.0315), and increased IL-10 concentrations (P<0.0215). Conclusion: These results indicate that 4-MU can attenuate injury after MCAO by suppressing the TLR4/NF-κB/NLRP3 axis. Our findings show that 4-MU can be considered a novel therapeutic compound to cure IS

The Combined Effect of D-peptide B and Bifidobacterium bifidum Lysate on the Expression of MAP1LC3A and CASP3 Genes in Human Colorectal Adenocarcinoma Cells

In the realm of cancer research, novel approaches complementing conventional treatments are gaining prominence to improve patient outcomes. Antimicrobial peptides (AMPs), and bacteria, as emerging strategies, hold promise for cancer therapy. Recent studies suggested that the administration of peptides and bacteria may eliminate colorectal cancer (CRC) cells by triggering apoptosis, and autophagy processes, underscoring the potential of these compounds in CRC treatment. Using the human CRC cell line HT-29, we evaluated the combined effects of D-peptide B and Bifidobacterium bifidum lysate on the expression of the microtubule associated protein 1 light chain 3 alpha (MAP1LC3A), referred to as LC3A hereafter, and caspase 3 (CASP3) genes. D-peptide B and B. bifidum lysate were applied to control human embryonic kidney epithelial cell line HEK293 and HT-29 at their respective half-maximal inhibitory concentration (IC50) values. We performed total RNA extraction, complementary DNA (cDNA) synthesis, and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) with gel electrophoresis to examine changes in the gene expression. Tukey's test and GraphPad Prism One-Way ANOVA were used for the statistical study. The combined treatment of D-peptide B and B. bifidum lysate with HT-29 cells resulted in a considerable decrease in the vitality of cancer cells. Furthermore, when HT-29 cells were compared to control cells, the expression of LC3A and CASP3 genes increased. The results point to the possibility of combining D-peptide B with B. bifidum lysate as a supplementary therapy for CRC. Furthermore, these findings may help improve our knowledge of the molecular processes driving apoptosis and autophagy, as well as their potential therapeutic implications in CRC

Systemic delivery of menstrual blood stem cells is more effective in preventing remote organ injuries following myocardial infarction in comparison with bone marrow stem cells in rat

Objective(s): Remote organ injury is a phenomenon that could happen following myocardial infarction (MI). We evaluated the potency of menstrual blood stromal (stem) cells (MenSCs) and bone marrow stem cells (BMSCs) to alleviate remote organ injuries following MI in rats.Materials and Methods: 2 × 106 MenSCs or BMSCs were administrated seven days after MI induction via the tail vein. Four weeks after cell therapy, activities of aspartate aminotransferase (AST), urea, creatinine, and Blood Urea Nitrogen (BUN) were evaluated. The level of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were determined by ELISA assay. The expression of Nuclear Factor-κB (NF-κB) was evaluated by immunohistochemical staining. Apoptosis activity and tissue damage were also determined by TUNEL and H&E staining, respectively.Results: MenSCs and BMSCs administration caused a significant reduction in AST, urea, and BUN levels compared with the MI group. In addition, systemic injection of MenSCs significantly decreased the IL-1β level compared with BMSCs and MI groups (P0.05).Conclusion: MenSCs are probably more protective than BMSCs on remote organ injuries following MI via decreasing cell death and immunoregulatory properties

Circulating visfatin concentrations in patients with chronic obstructive pulmonary disease: systematic review and meta-analysis

ObjectiveThe current study was designed with the aim of conducting a systematic review and meta-analysis to determine the circulating levels of visfatin in patients with chronic obstructive pulmonary disease (COPD) compared to healthy individuals.MethodsUntil March 2024, we searched the Web of Science, PubMed/Medline, and Scopus databases. The analysis included case–control studies assessing the association between circulating visfatin and COPD. The random effects model was utilized to analyse the results with the help of Standard Mean of Differences (SMD) and 95% confidence interval (CI). The heterogeneity of the data was assessed using Cochrane Q and I2 values.ResultsSeven studies were eligible to be included in the meta-analysis, with the COPD and healthy (control) groups having 265 and 244 subjects, respectively. The pooled results showed that although the circulating concentration of visfatin was lower in patients with COPD, no significant difference was observed (SMD: −0.48 mg/L; 95% CI: −1.67 to 0.70; p = 0.43). Subgroup analysis revealed that visfatin levels were significantly reduced in FEV1 less than 50% (p &lt; 0.001) and in GOLD grade I-II (p &lt; 0.05). Visfatin was shown to be significantly associated with IL-6 (p &lt; 0.001) and TNF-α (p &lt; 0.01) in the correlation meta-analysis. Meta-regression analysis revealed a significant correlation between the pooled SMD visfatin and pooled SMD age (p &lt; 0.01), BMI (p &lt; 0.001), FEV1 (p &lt; 0.001), and IL-6 (p &lt; 0.001).ConclusionThe findings showed an insignificant decline in visfatin level among COPD patients, but additional research is necessary due to the heterogeneity in study results.Systematic review registrationPROSPERO (CRD42023450851), https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023450851