Protective potential of mesenchymal stem cells against COVID-19 during pregnancy.

SARS-CoV-2 causes COVID-19. COVID-19 has led to severe clinical illnesses and an unprecedented death toll. The virus induces immune inflammatory responses specifically cytokine storm in lungs. Several published reports indicated that pregnant females are less likely to develop severe symptoms compared with non-pregnant. Putative protective role of maternal blood circulating fetal mesenchymal stem cells (MSCs) has emerged and have been put forward as an explanation to alleviated symptoms. MSCs with immune-modulatory, anti-inflammatory and anti-viral roles, hold great potential for the treatment of COVID-19. MSCs could be an alternative to treat infections resulting from the SARS-CoV-2 and potential future outbreaks. This review focuses on the MSCs putative protective roles against COVID-19 in pregnant females.

The COVID-19 outbreak is still posing a global health concern. Despite the herd immunity provided by vaccination programs, no efficient treatments are yet available especially against the severe forms of the disease. According to published reports, pregnant females are less likely to develop the severe form of the disease due to the protective effect of specialized cells named mesenchymal stem cells (MSCs). These cells are present in the placenta and amniotic fluid. They can migrate from these tissues to the mother's blood stream and are believed to confer protection to the pregnant females against severe form of COVID-19. Further investigations are on the way to uncover the potential role of MSC as an alternative therapy for COVID-19 and other diseases.

The virus SARS-CoV-2 results in COVID-19 infection. Several reports indicated that pregnant females are less likely to develop severe symptoms. Circulating fetal Mesenchymal stem cells in pregnant females might protect them.

The Prevalence and Predictors of Atherosclerotic Coronary Artery Disease in Rheumatic and Non-rheumatic Valvular Heart Disease Patients.

OBJECTIVES: The paradox of concurrent coronary artery disease (CAD) among patients with rheumatic and non-rheumatic valvular heart disease (RVHD; non-RVHD) is unclear. We aimed to evaluate the impact of the RVHD and non-RVHD on the prevalence of CAD and various risk factors, assess the number of diseased coronaries, clinical profile and the possible predictors of CAD in these patients, which may clarify the paradox and provide an insight for the prevention of CAD. METHODS: The records of 106 valvular heart disease patients who had undergone valve replacement surgery at the King Faisal Cardiac Centre from January 2014 to October 2019 were evaluated. The clinical data and established risk factors were compared and logistic regression analyses were performed to identify plausible predictors of CAD. RESULTS: Transthoracic echocardiographic diagnosis of 106 patients confirmed, 43 had RVHD (56.4 ± 8 years), of whom six (13.9%) had CAD with the highest mitral valve regurgitation (p < 0.01), and 63 had non-RVHD (60.0 ± 12 years). Of these, 31 patients showed the highest CAD (49.2%). Single- and triple-vessel disease was most common in RVHD and non-RVHD patients with concurrent CAD (33.3%; 41.9%, respectively), while non-RVHD patients also had quadruple vessel disease. The mean age of the RVHD and non-RVHD patients with coexisting CAD was significantly higher (66.7 ± 5; 66.7 ± 8 years) than those without CAD (46.1 ± 12.0; 54.7 ± 20, respectively). RVHD patients showed a significantly lower prevalence of diabetes, dyslipidaemia, hypertension, inflammatory cells, hepatorenal function markers, ejection fraction, and regional wall motion abnormality compared to RVHD patients with coexisting CAD (p < 0.01). Bivariate analysis indicated white blood cells, monocytes, neutrophils, gamma-glutamyl-transferase (GGT), bilirubin and blood urea nitrogen (BUN) to be significantly lower in RVHD patients. Predictors of high risk of CAD were BUN and hyperlipidaemia for RVHD and BUN, creatinine and GGT for non-RVHD patients. CONCLUSIONS: The prevalence of CAD in Saudi RVHD patients was significantly lower than in the Western countries, whereas non-RVHD was higher. The low prevalence may partly be attributed to age, reduced mitral regurgitation, and low frequency of risk and inflammatory factors.

Transcriptomics Demonstrates Significant Biological Effect of Growing Stem Cells on RGD-Cotton Scaffold.

Stem cell therapy provides a viable alternative treatment for degenerated or damaged tissue. Stem cells have been used either alone or in conjunction with an artificial scaffold. The latter provides a structural advantage by enabling the cells to thrive in three-dimensional (3D) settings, closely resembling the natural in vivo environments. Previously, we disclosed the development of a 3D scaffold made from cotton, which was conjugated with arginyl-glycyl-aspartic acid (RGD), to facilitate the growth and proliferation of mesenchymal stem cells (MSCs). This scaffold allowed the MSCs to adhere and proliferate without compromising their viability or their stem cell markers. A comprehensive analysis investigation of the molecular changes occurring in MSCs adhering to the cotton fibers will contribute to the advancement of therapy. The objective of this study is to analyze the molecular processes occurring in the growth of MSCs on a cotton-RGD conjugated-based scaffold by examining their gene expression profiles. To achieve this, we conducted an experiment where MSCs were seeded with and without the scaffold for a duration of 48 h. Subsequently, cells were collected for RNA extraction, cDNA synthesis, and whole-transcriptomic analysis performed on both populations. Our analysis revealed several upregulated and downregulated differently expressed genes in the MSCs adhering to the scaffold compared with the control cells. Through gene ontology analysis, we were able to identify enriched biological processes, molecular functions, pathways, and protein-protein interactions in these differentially expressed genes. Our data suggest that the scaffold may have the potential to enhance osteogenesis in the MSCs. Furthermore, our results indicate that the scaffold does not induce oxidative stress, inflammation, or aging in the MSCs. These findings provide valuable insights for the application of MSCs in tissue engineering and regenerative medicine.

Generation of iPSC lines (KAIMRCi003A, KAIMRCi003B) from a Saudi patient with Dravet syndrome carrying homozygous mutation in the CPLX1 gene and heterozygous mutation in SCN9A.

The most prevalent form of epileptic encephalopathy is Dravet syndrome (DRVT), which is triggered by the pathogenic variant SCN1A in 80% of cases. iPSCs with different SCN1A mutations have been constructed by several groups to model DRVT syndrome. However, no studies involving DRVT-iPSCs with rare genetic variants have been conducted. Here, we established two DRVT-iPSC lines harboring a homozygous mutation in the CPLX1 gene and heterozygous mutation in SCN9A gene. Therefore, the derivation of these iPSC lines provides a unique cellular platform to dissect the molecular mechanisms underlying the cellular dysfunctions consequent to CPLX1 and SCN9A mutations.

Identification of SPP1 as a Prognostic Biomarker and Immune Cells Modulator in Urothelial Bladder Cancer: A Bioinformatics Analysis.

Secreted phosphoprotein-1 (SPP1) expression is differentially altered in many malignancies and could serve as a potential prognostic biomarker. Recent findings indicated that SPP1 possesses a broader role in bladder cancer (BC) pathogenesis than previously envisioned; however, the underlying mechanisms governing its expression, cellular localization, prognostic value and immune-related role in bladder cancer remain poorly understood. The expression and the prognosis value of SPP1 were assessed using immunohistochemistry (IHC) staining on a tissue microarray. SPP1 expression was correlated with the clinicopathological parameters, and survival analysis was calculated using a Kaplan-Meier plotter. Bioinformatics analysis of TCGA data was queried using UALCAN, CIBERSORT and TIMER datasets to decipher the biological processes enrichment pattern, protein-protein interactions and characterize tumor-infiltrating immune cells, respectively. IHC revealed that SPP1 expression is significantly associated with tumor type, stage, grade and smoking status. The Kaplan-Meier survival curve showed that low SPP1 expression is an unfavorable prognostic indicator in bladder cancer patients (p = 0.02, log-rank). The significant increased expression of the SPP1 level is associated with evident hypomethylation of the gene promoter in cancer compared to normal tissues in the TCGA-bladder dataset. Missense mutation is the most frequent genetic alteration of the SPP1 gene. Protein-protein interactions demonstrated that SPP1 shares the same network with many important genes and is involved in many signaling pathways and biological processes. TIMER reported a significant correlation between SPP1 expression and multiple immune cells infiltration. Furthermore, the expression of SPP1 was found to be positively correlated with a number of immune checkpoint genes such as PD-1 and CTLA4. The current investigation indicates that the SPP1 protein could serve as a prognostic biomarker and merit further investigation to validate its clinical usefulness in patients with bladder cancer.

An Update on Alopecia and its Association With Thyroid Autoimmune Diseases.

Alopecia is comorbid with several illnesses, including various autoimmune conditions such as thyroid disease. Leukocyte-mediated inflammation of hair follicles in alopecia was first described over a century ago. However, the high prevalence of the role of thyroid autoimmune disease in the pathogenesis of alopecia has only recently come to light, together with a strong association between the two. Therefore, this review focuses on articles published between 2011 and 2022 on alopecia's association with thyroid autoimmune disease, and the mechanism behind it. In addition, it highlights the link between alopecia and thyroid cancer, as patients with alopecia have increased risk of thyroid cancer. In conclusion, this comprehensive, focused, scoping review will serve as a reference highlighting recent information on alopecia, exploring its association with thyroid autoimmune diseases.

Dietary trends and obesity in Saudi Arabia.

Introduction: Dietary habits in Saudi Arabia have been shifting toward the Western diet, which is high in fat, salt, and sugar, leading to a high obesity rate. Different dietary strategies such as the Ketogenic Diet (KD), Intermittent Fasting (IF), Gluten Free Diet (GFD), and Calorie Restriction Diet (CRD) have shown an influential role in weight loss. This study aimed to compare trending diets and correlate different types of diet with obesity and lifestyle among adults in Saudi Arabia. Methods: A cross-sectional study was performed on Saudis and non-Saudis over 18 years old. We used convenience sampling, an online questionnaire distributed via social media channels, including WhatsApp, LinkedIn, and Twitter. SPSS 28 software was applied for data analysis. The chi-square test was used to determine associations between different variables. Statistical significance was considered at a value of p less than 0.05. Results: Most participants were females residing in the Eastern and Central regions of Saudi Arabia. Although most do not follow any dietary plan, they exhibited acceptable exercise and lifestyle. The minority of the study population followed different types of diet plans, such as KD, IF, and GFD. The purpose of most of the participants who have used these strategies was for weight loss but failed to sustain the dietary plan for more than 1 month. Conclusion: Obesity remains a challenging issue in Saudi Arabia. Adherence to dietary regimes could help in controlling obesity. Increasing the awareness of the benefits of each dietary plan for health, choosing the appropriate one, and sustaining a balanced nutrition pattern.

Stem cell growth and proliferation on RGD bio-conjugated cotton fibers.

BACKGROUND: Merging stem cells with biomimetic materials represent an attractive approach to tissue engineering. The development of an alternative scaffold with the ability to mimic the extracellular matrix, and the 3D gradient preventing any alteration in cell metabolism or in their gene expression patterns, would have many medical applications. OBJECTIVE: In this study, we introduced the use of RGD (Arg-Gly-Asp) bio-conjugated cotton to promote the growth and proliferation of mesenchymal stem cells (MSCs). METHODS: We measured the expression of stem cell markers and adhesion markers with Q-PCR and analyzed the transcriptomic. The results obtained showed that the MSCs, when cultured with bio-conjugated cotton fibers, form aggregates around the fibers while proliferating. The seeded MSCs with cotton fibers proliferated in a similar fashion to the cells seeded on the monolayer (population doubling level 1.88 and 2.19 respectively). RESULTS: The whole genome sequencing of cells adhering to these cotton fibers and cells adhering to the cell culture dish showed differently expressed genes and pathways in both populations. However, the expression of the stem cell markers (Oct4, cKit, CD105) and cell adhesion markers (CD29, HSPG2 and CD138), when examined with quantitative RT-PCR, was maintained in both cell populations. CONCLUSION: These results clearly show the ability of the cotton fibers to promote MSCs growth and proliferation in a 3D structure mimicking the in vivo environment without losing their stem cell phenotype.

The Impact of Natural Antioxidants on the Regenerative Potential of Vascular Cells.

With advances in technology, the impact of natural antioxidants on vascular cell regeneration is attracting enormous attention as many current studies are now exploring the clinical potential of antioxidants in regenerative medicine. Natural antioxidants are an important step for improving future treatment and prevention of various diseases such as cardiovascular, cancer, neurodegenerative, and diabetes. The use of natural antioxidants which have effects on several types of stem cells with the potential to differentiate into functional endothelium and smooth muscle cells (known as vascular progenitors) for vascular regeneration might override pharmaceutical and surgical treatments. The natural antioxidant systems comprise of several components present in fruits, vegetables, legumes, medicinal plants, and other animal-derived products that interact with reactive free radicals such as oxygen and nitrogen species to neutralize their oxidative damaging effects on vascular cells. Neutralization by antioxidants involves the breaking down of the oxidative cascade chain reactions in the cell membranes in order to fine-tune the free radical levels. The effect of natural antioxidants on vascular regeneration includes restoration or establishment of new vascular structures and functions. In this review, we highlight the significant effects of natural antioxidants on modulating vascular cells to regenerate vessels, as well as possible mechanisms of action and the potential therapeutic benefits on health. The role of antioxidants in regenerating vessels may be critical for the future of regenerative medicine in terms of the maintenance of the normal functioning of vessels and the prevention of multiple vascular diseases.

New generation of electrochemical immunoassay based on polymeric nanoparticles for early detection of breast cancer.

Screening and early diagnosis are the key factors for the reduction of mortality rate and treatment cost of cancer. Therefore, sensitive and selective methods that can reveal the low abundance of cancer biomarkers in a biological sample are always desired. Here, we report the development of a novel electrochemical biosensor for early detection of breast cancer by using bioconjugated self-assembled pH-responsive polymeric micelles. The micelles were loaded with ferrocene molecules as "tracers" to specifically target cell surface-associated epithelial mucin (MUC1), a biomarker for breast and other solid carcinoma. The synthesis of target-specific, ferrocene-loaded polymeric micelles was confirmed, and the resulting sensor was capable of detecting the presence of MUC1 in a sample containing about 10 cells/mL. Such a high sensitivity was achieved by maximizing the loading capacity of ferrocene inside the polymeric micelles. Every single event of binding between the antibody and antigen was represented by the signal of hundreds of thousands of ferrocene molecules that were released from the polymeric micelles. This resulted in a significant increase in the intensity of the ferrocene signal detected by cyclic voltammetry.

Differential development of neuronal physiological responsiveness in two human neural stem cell lines.

BACKGROUND: Neural stem cells (NSCs) are powerful research tools for the design and discovery of new approaches to neurodegenerative disease. Overexpression of the myc family transcription factors in human primary cells from developing cortex and mesencephalon has produced two stable multipotential NSC lines (ReNcell VM and CX) that can be continuously expanded in monolayer culture. RESULTS: In the undifferentiated state, both ReNcell VM and CX are nestin positive and have resting membrane potentials of around -60 mV but do not display any voltage-activated conductances. As initially hypothesized, using standard methods (stdD) for differentiation, both cell lines can form neurons, astrocytes and oligodendrocytes according to immunohistological characteristics. However it became clear that this was not true for electrophysiological features which designate neurons, such as the firing of action potentials. We have thus developed a new differentiation protocol, designated 'pre-aggregation differentiation' (preD) which appears to favor development of electrophysiologically functional neurons and to lead to an increase in dopaminergic neurons in the ReNcell VM line. In contrast, the protocol used had little effect on the differentiation of ReNcell CX in which dopaminergic differentiation was not observed. Moreover, after a week of differentiation with the preD protocol, 100% of ReNcell VM featured TTX-sensitive Na+-channels and fired action potentials, compared to 25% after stdD. Currents via other voltage-gated channels did not appear to depend on the differentiation protocol. ReNcell CX did not display the same electrophysiological properties as the VM line, generating voltage-dependant K+ currents but no Na+ currents or action potentials under either stdD or preD differentiation. CONCLUSION: These data demonstrate that overexpression of myc in NSCs can be used to generate electrophysiologically active neurons in culture. Development of a functional neuronal phenotype may be dependent on parameters of isolation and differentiation of the cell lines, indicating that not all human NSCs are functionally equivalent.

Transcriptional regulation of the human pregnane-X receptor.

This review addresses the general structure and function of nuclear receptors and places specific emphasis on their role in xenosensing, resulting in the activation of a battery of genes mediating drug metabolism, conjugation, and transport. The pregnane-X receptor is a nuclear receptor that functions to control a battery of genes predominantly involved in drug metabolism and we place emphasis on how this important cellular mediator is transcriptionally activated. We have identified both positive and negative regulatory elements in the PXR promoter, the balance of which dictates the steady state expression of the PXR gene.

Transcriptional regulation of the PXR gene: identification and characterization of a functional peroxisome proliferator-activated receptor alpha binding site within the proximal promoter of PXR.

The pregnane X receptor (PXR, NR1I2) is widely regarded as a central factor in the body's response to changes in the fluxome, the overall metabolite profile in the body. PXR expression is regulated by a number of chemicals at the transcriptional level; the majority of these chemicals are ligands for PXR and substrates for PXR target genes. However, transcriptional activators of PXR, such as clofibrate, do not seem to be PXR ligands or substrates for its target genes. Understanding the molecular mechanisms underlying both these expected and, more importantly, unexpected transcriptional activations is central to fully understanding the roles of PXR in the human body. We have carried out an in silico analysis of the human PXR proximal promoter, identifying putative protein/DNA interaction sites within the 2 kilobases (kb) 5' to the putative transcription start site. These sites included several for liver-enriched transcription factors, such as the hepatic nuclear factors and CAAT-enhancer binding protein alpha, and chicken ovalbumin upstream promoter transcription factor, commensurate with the high expression of PXR in liver. Furthermore, we identified putative binding sites for a number of ligand-activated transcription factors, suggesting that these factors may regulate PXR gene expression. Further analysis of this regulatory region has shown that transcriptional activation of PXR by peroxisome proliferator-activated receptor alpha (PPARalpha) is via a binding site located approximately 1.3 kb upstream of the putative transcription start site, with ablation of this site preventing PPARalpha-mediated activation of PXR gene expression. We present a model of how regulation of PXR gene expression by ligand-activated transcription factors may play a central role in the body's response to xenobiotic exposure.