Asmaa Mohammed ShamsEldeen

BACKGROUND Myocardial infarction (MI) is a significant global cause of chronic heart failure. In post-ischemic cardiac hypertrophy, multiple molecular targets and signals within the cardiac tissue are evident. Mesenchymal stem cell-derived exosomes (MSC-EXO) and exercise (EXE) showed promise in enhancing post-ischemic cardiac repair. AIM To investigate how the exosomes released by stem cells and/or EXE can promote cardiac repair and improve isoproterenol (ISO)-induced post-ischemic hypertrophy. METHODS The enrolled animals were divided into 8 control rats and 32 experimental rats. Induction of MI was performed using ISO. Then, the experimental rats were divided into 4 groups: Rats subjected to 4 weeks of swimming EXE, rats treated with exosomes, and the combined treatment. Additionally, functional and interactional exploration of targeted proteins was conducted using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and STRING database, along with histological examination. RESULTS Both MSC-EXO or EXE significantly improved ISO induced elevation of cardiac enzymes, oxidative stress, and inflammatory markers, as well as the degenerative changes of the cardiac muscles, fibrosis, and apoptosis. Meanwhile, the combined treatment of EXE and MSC-EXO resulted in a significant improvement in cardiac function and structure as compared to all groups that synchronized with dual inhibition of extracellular signal-regulated kinase and protein kinase B/mammalian target of rapamycin (P < 0.01) signaling and modulation of matrix metalloproteinase 9 and sarcoplasmic endoplasmic reticulum calcium ATPase type 2a, with significant improved angiogenesis. CONCLUSION Functional and structural cardiac improvements are accompanied by reduced inflammation, oxidative stress, and apoptosis. Both MSC-EXO and EXE exert cardio-protection by upregulating sarcoplasmic endoplasmic reticulum calcium ATPase, the critical pump for normal calcium handling.

Mesenchymal stem cells (MSCs) derived from bone marrow or adipose tissue have promising potential in regenerative medicine. The regenerative capacity of MSCs depends on their successful migration and engraftment at the injured site. Several preclinical and clinical studies have reported that MSCs effectively treat cardiac dysfunction. However, significant obstacles to MSC homing include peripheral sequestration and low survival rates. MSC-secreted extracellular vesicles exhibit effects similar to those of MSCs, contributing to cellular proliferation, differentiation, and various paracrine functions. This review explores the molecular pathways and mechanisms by which MSCs and extracellular vesicles modulate cardiac injuries. Additionally, we discuss the challenges associated with MSC homing and various strategies to enhance the process.

Consumption of a high-fat diet (HFD) contributes to numerous chronic illnesses, including neurological disorders and gastrointestinal dysfunction. The study design included four groups, each consisting of six rats: the control group was fed regular chow, while groups 2 (HFD 2W), 3 (HFD 4W), and 4 (HFD 8W) were given a 60% HFD for 2, 4, and 8 weeks, respectively. A significant change in the latency to the platform in the water maze, a decrease in the percentage of successful cycles in the Y-maze, and a reduction in the percentage of time spent with the novel object were observed between the baseline and endpoint results in the HFD 4W and HFD 8W groups; notably, this was not the case in the control and HFD 2W groups. Consistent with the increased duration of HFD intake, marked damage to the cortical pyramidal cells as well as the mucosa of the ileum and colon was recorded. The optical density of amyloid deposition was significantly increased in the myenteric plexus before the cerebral cortex. In conclusion, increasing the duration of 60% HFD consumption was associated with significant deterioration of spatial and working memory, an increase in lipid profile, and amyloid deposition in the enteric nervous system, which began even before the observable involvement of the cerebral cortex. Graphical Abstract

Background: Disturbed intestinal integrity and increased permeability are linked to dysbiosis. This disruption involves GIT-related and unrelated diseases, such as neurological diseases. Intake of a high-fat diet (HFD) leads to an imbalance of gut microbiota and regression of bacteria producing “short-chain fatty acids (SCFAs)”. These SCFAs can modulate brain functions. Therefore, we investigated the therapeutic effect of Clostridium Butyricum (CB) bacteria extracted from human faeces on intestinal and neurological impairments induced by HFD and explored their modulation of tight junction protein expression. Materials and methods: Twenty-four adult male rats were classified into the control group, which received regular rat chow; the HFD group, which received HFD for 16 weeks; and the HFD-Microbiota group, which received HFD as in group II for 16 weeks, but from week 9 received CB (dose of 2 ml (2.3 × 10¹¹ cfu/ml) daily till scarification. Results: The microbiota improved working memory, episodic-like memory, and emotional memory. Also, there was a substantial decline in the animals’ body weights, serum lipopolysaccharides, interleukin-1β, tumour necrosis factor-α, insulin, glucose, and HOMA index compared to the HFD group. A remarkable increase in brain and colonic claudin-5 and occluding expression of its gene in the microbiota-treated group in comparison with the HFD group was reported. SCFAs, intestinal, brain claudin-5, and occludin genes were positively correlated. Also, a positive correlation was found between the F/B ratio and both brain beta-amyloid and Tau proteins. Conclusion: Repeated intake of CB hindered systemic /neuroinflammation, enhanced the tight junction proteins’ expression in the gut/brain barrier, and improved cognitive functions.

Lead is a common heavy metal used in a variety of products. We investigated the effect of lead-oxide nanoparticles (PbO-NPs) on the histological structure of the rat olfactory bulb (OB) and the potential therapeutic effect of stem cell–derived exosomes (EXOs). Forty male rats were included: 8 for EXO isolation and 32 were distributed into 4 groups: control, PbO-NPs group [intranasal (IN) 50 µL PbO-NPs/rat for 3 weeks], recovery group (PbO-NPs for 3 weeks and left for another 4 weeks), and PbO-NP-EXO (PbO-NPs for 3 weeks then IN EXO for another 3 weeks). After 7 weeks, olfactory behavioral tests were done before scarification. OBs were stained with hematoxylin and eosin, toluidine blue, and immunohistochemistry for synaptophysin (SYP), and ionized calcium-binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP). The results were confirmed by histomorphometry and statistical analysis. PbO-NPs and recovery groups showed a significant olfactory dysfunction, significant decrease in the thickness of OB layers and diameter of glomeruli, Nissl's granules of mitral cells and SYP immunostaining, and a significant increase in Iba-1 and GFAP expression compared with control rats. In PbO-NP-EXO, notable regaining of OB structure and function was obvious with reversal of most of the behavioral and morphometric findings compared with the untreated groups. IN EXO administration improved the structure and function of PbO-NP-induced OB neurotoxicity.

Autism spectrum disorder (ASD) is a collective neurodevelopmental disorder affecting young children and accounting for 1% of the world’s population. The cerebellum is the major part of the human brain affected by ASD and is associated with a substantial reduction in the number of Purkinje cells. An association between ASD and the expression of the nitrosative stress biomarker inducible nitric oxide synthase (iNOS), as well as glycogen deposition in damaged Purkinje cells, has not been previously reported in the medical literature. To explore this correlation, young rats were injected with propionic acid (PPA) (500 mg/kg) for 5 days (model group), while the protection groups were treated with either erythropoietin (EPO, 5,000 U/kg) or 2 mg/kg zinc sulfate immediately after the PPA injections. ASD-like features were developed in the model group, as evidenced by cerebellum damage (degeneration of Purkinje cells) and cerebellar dysfunction (behavioral impairment). This study documented the exclusive expression of iNOS in the degenerated Purkinje cells, along with glycogen deposition in these cells. Additionally, PPA significantly (p < 0.001) modulated cerebellar tissue levels of mammalian target of rapamycin (mTOR), gamma-aminobutyric acid (GABA), GABAA receptor, serotonin, the marker of neuronal loss (calbindin D28K), and social interaction deficit. Some of these parameters were differentially protected by EPO and zinc sulfate, with the former providing greater protection than zinc sulfate. Furthermore, a significant correlation between the iNOS score and these parameters associated with ASD was observed. These findings demonstrate the colocalization of iNOS and glycogen in the damaged Purkinje cells induced by ASD, along with the modulation of ASD parameters, which were protected by EPO and zinc sulfate treatments. Thus, these potential novel biomarkers may offer possible therapeutic targets for the treatment of ASD.

Polycystic ovarian syndrome (PCOS) is a complex endocrine-metabolic disorder, and multiple factors contribute to its pathophysiology. The current study assessed a PCOS-like animal model induced by consuming a high-fat sugar (HFHS) diet and compared the treatment outcome of mitochondrial-targeted antioxidants versus heat therapy. Sixty rats were divided into the following study groups: three control groups (negative and positive for the treatments used), HFHS, hot tub therapy (HTT) treatment, and MitoQ10 treatment (500 mu mol/L MitoQ10 in clean drinking water daily, from week fourteen till week twenty-two of the study). At week fourteen, PCOS was confirmed by vaginal smear examination; measurements of blood testosterone (T), anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), glucose, and insulin; and determination of the homeostatic model assessment of IR (HOMA-IR). At week 22, blood samples were collected for measurement of the serum LH, FSH, AMH, T, insulin, glucose, lipid profile, kisspeptin, ADAM metallopeptidase with thrombospondin type 1 motif 19 (ADAMTS19), S100 calcium-binding protein B (S100B), fibulin 1 (FBLN1), immunoglobulin free light chains (FLCs), kappa and lambda. Ovaries were examined for morphological changes; for the levels of glutathione (GSH), catalase, SOD, malondialdehyde (MDA), and nitric oxide (NO); and the expression of FK506 binding protein 52 (FKBP52) and the androgen receptor (AR). The consumption of HFHS diet-induced PCOS-like features, which have been ameliorated by both HTT and mitoQ10 as potential therapies, with MitoQ10 showing a superior effect over HTT.

I would like to thank the editor for the kind invitation to review Novel Method to Assess Group Dynamics in Rats Reveals Deficits in Behavioral Contagion in KM Rats [https://doi.org/10.32388/jqa2k6] Some questions need to be answered: 1- What is th...