Introducing Circulating Vasculature-Related Transcripts as Biomarkers in Coronary Artery Disease.

BACKGROUND: Atherosclerotic plaque is considered the hallmark of atherosclerotic lesions in coronary atherosclerosis (CAS), the primary pathogenesis in coronary artery disease (CAD), which develops and progresses through a complex interplay between immune cells, vascular cells, and endothelial shear stresses. Early diagnosis of CAS is critical for avoiding plaque rupture and sudden death. Therefore, identifying new CAD biomarkers linked to vessel wall functions, such as RNA molecules with their distinct signature, is a promising development for these patients. With this rationale, the present study investigated the expression level of the vascular-related RNA transcripts (lncRNA ANRIL, miRNA-126-5p, CDK4, CDK6, TGF-ß, E-cadherin, and TNF-α) implicated in the cellular vascular function, proliferation, and inflammatory processes. METHODS: A case-control study design with a total of 180 subjects classified participants into two groups; CAD and control groups. The relative expression levels of the seven transcripts under study-selected using online bioinformatics tools and current literature-were assessed in the plasma of all study participants using RT-qPCR. Their predictive significance testing, scoring of disease prioritization, enrichment analysis, and the miRNA-mRNA regulatory network was investigated. RESULTS: The relative expression levels of all seven of the circulating vascular-related transcripts under study were statistically significant between CAD patients and controls. Receiver operating characteristic (ROC) analysis results indicated the statistical significance of all the transcripts under study with CDK4 showing the highest area under the curve (AUC) equivalent to 0.91, followed by E-cadherin (0.90), miRNA-126-5p (0.83), ANRIL (0.82), TNF-α (0.63), TGF-ß (0.62), and CDK6 (0.59), in descending order. A strong association was detected between most of the transcripts studied in CAD patients with a significant Spearman's correlation coefficient with a two-tailed significance of p < 0.001. Network analysis revealed a strong relationship between the five circulating vasculature transcripts studied and their target miRNAs and miR-126-5p, but not for ANRIL. CONCLUSION: The seven circulating vascular-related RNA transcripts under study could serve as potential CAD biomarkers, reflecting the cellular vascular function, proliferation, and inflammatory processes in CAD patients. Therefore, blood transcriptome analysis opens new frontiers for the non-invasive diagnosis of CAD.

Identification of a circulating microRNAs biomarker panel for non-invasive diagnosis of coronary artery disease: case-control study.

BACKGROUND: Circulating microRNAs (miRNAs) are considered a hot spot of research that can be employed for monitoring and/or diagnostic purposes in coronary artery disease (CAD). Since different disease features might be reflected on altered profiles or plasma miRNAs concentrations, a combination of miRNAs can provide more reliable non-invasive biomarkers for CAD. SUBJECTS AND METHODS: We investigated a panel of 14-miRNAs selected using bioinformatics databases and current literature searching for miRNAs involved in CAD using quantitative real-time PCR technique in 73 CAD patients compared to 73 controls followed by function and pathway enrichment analysis for the 14-miRNAs. RESULTS: Our results revealed three out of the 14 circulating miRNAs understudy; miRNAs miR133a, miR155 and miR208a were downregulated. While 11 miRNAs were up-regulated in a descending order from highest fold change to lowest: miR-182, miR-145, miR-21, miR-126, miR-200b, miR-146A, miR-205, miR-135b, miR-196b, miR-140b and, miR-223. The ROC curve analysis indicated that miR-145, miR-182, miR-133a and, miR-205 were excellent biomarkers with the highest AUCs as biomarkers in CAD. All miRNAs under study except miR-208 revealed a statistically significant relation with dyslipidemia. MiR-126 and miR-155 showed significance with BMI grade, while only miR-133a showed significance with the obese patients in general. MiR-135b and miR-140b showed a significant correlation with the Wall Motion Severity Index. Pathway enrichment analysis for the miRNAS understudy revealed pathways relevant to the fatty acid biosynthesis, ECM-receptor interaction, proteoglycans in cancer, and adherens junction. CONCLUSION: The results of this study identified a differentially expressed circulating miRNAs signature that can discriminate CAD patients from normal subjects. These results provide new insights into the significant role of miRNAs expression associated with CAD pathogenesis.

Roles of clock genes in the pathogenesis of Parkinson's disease.

Parkinson's disease (PD) is a common motor disorder that has become increasingly prevalent in the ageing population. Recent works have suggested that circadian rhythms disruption is a common event in PD patients. Clock genes regulate the circadian rhythm of biological processes in eukaryotic organisms, but their roles in PD remain unclear. Despite this, several lines of evidence point to the possibility that clock genes may have a significant impact on the development and progression of the disease. This review aims to consolidate recent understanding of the roles of clock genes in PD. We first summarized the findings of clock gene expression and epigenetic analyses in PD patients and animal models. We also discussed the potential contributory role of clock gene variants in the development of PD and/or its symptoms. We further reviewed the mechanisms by which clock genes affect mitochondrial dynamics as well as the rhythmic synthesis and secretion of endocrine hormones, the impairment of which may contribute to the development of PD. Finally, we discussed the limitations of the currently available studies, and suggested future potential studies to deepen our understanding of the roles of clock genes in PD pathogenesis.

Cellular Therapy via Spermatogonial Stem Cells for Treating Impaired Spermatogenesis, Non-Obstructive Azoospermia.

Male infertility is a major health problem affecting about 8-12% of couples worldwide. Spermatogenesis starts in the early fetus and completes after puberty, passing through different stages. Male infertility can result from primary or congenital, acquired, or idiopathic causes. The absence of sperm in semen, or azoospermia, results from non-obstructive causes (pretesticular and testicular), and post-testicular obstructive causes. Several medications such as antihypertensive drugs, antidepressants, chemotherapy, and radiotherapy could lead to impaired spermatogenesis and lead to a non-obstructive azoospermia. Spermatogonial stem cells (SSCs) are the basis for spermatogenesis and fertility in men. SSCs are characterized by their capacity to maintain the self-renewal process and differentiation into spermatozoa throughout the male reproductive life and transmit genetic information to the next generation. SSCs originate from gonocytes in the postnatal testis, which originate from long-lived primordial germ cells during embryonic development. The treatment of infertility in males has a poor prognosis. However, SSCs are viewed as a promising alternative for the regeneration of the impaired or damaged spermatogenesis. SSC transplantation is a promising technique for male infertility treatment and restoration of spermatogenesis in the case of degenerative diseases such as cancer, radiotherapy, and chemotherapy. The process involves isolation of SSCs and cryopreservation from a testicular biopsy before starting cancer treatment, followed by intra-testicular stem cell transplantation. In general, treatment for male infertility, even with SSC transplantation, still has several obstacles. The efficiency of cryopreservation, exclusion of malignant cells contamination in cancer patients, and socio-cultural attitudes remain major challenges to the wider application of SSCs as alternatives. Furthermore, there are limitations in experience and knowledge regarding cryopreservation of SSCs. However, the level of infrastructure or availability of regulatory approval to process and preserve testicular tissue makes them tangible and accurate therapy options for male infertility caused by non-obstructive azoospermia, though in their infancy, at least to date.

Mesenchymal stem cell-based therapy and exosomes in COVID-19: current trends and prospects.

Novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2. The virus causes an exaggerated immune response, resulting in a cytokine storm and acute respiratory distress syndrome, the leading cause of COVID-19-related mortality and morbidity. So far, no therapies have succeeded in circumventing the exacerbated immune response or cytokine storm associated with COVID-19. Mesenchymal stem cells (MSCs), through their immunomodulatory and regenerative activities, mostly mediated by their paracrine effect and extracellular vesicle production, have therapeutic potential in many autoimmune, inflammatory, and degenerative diseases. In this paper, we review clinical studies on the use of MSCs for COVID-19 treatment, including the salutary effects of MSCs on the pathophysiology of COVID-19 and the immunomodulation of the cytokine storm. Ongoing clinical trial designs, cell sources, dose and administration, and populations are summarized, and the paracrine mode of benefit is discussed. We also offer suggestions for optimizing MSC-based therapies, including genetic engineering, strategies for cell surface modification, nanotechnology applications, and combination therapies.

Heterologous expression of lytic polysaccharide monooxygenases (LPMOs).

Lytic polysaccharide monooxygenases (LPMOs) are relatively new enzymes that have been discovered 10 years ago. LPMOs comprise a diverse group of enzymes which play a pivotal role in the depolymerization of sugar-based biopolymers including cellulose, hemicellulose, chitin, and starch. Their mechanism of action relies on the correct coordination of a copper ion in the active site, which is partly composed of the N-terminal histidine. Therefore, correct secretion and folding of these copper-enzymes is fundamental for obtaining a catalytic activity. LPMOs occur in all kingdoms of life; they have been found in viruses, bacteria and eukaryotes, including fungi, plants and animals. In many cases, using homologous expression of these proteins is not feasible and an alternative organism, which can be cultured and is able to heterologously express the protein of interest, is required for studying enzyme properties. Therefore, we made an extensive compilation of expression techniques used for LPMOs the expression and characterization of which have been reported to date. In the current review, we provide a summary of the different techniques, including expression hosts and vectors, secretion methods, and culturing conditions, that have been used for the overexpression and production of this important class of enzymes at laboratory scale. Herein, we compare these techniques and assess their advantages and disadvantages.

Mesenchymal stem cells as a treatment for multiple sclerosis: a focus on experimental animal studies.

Multiple sclerosis (MS) is a progressive and debilitating neurological condition in which the immune system abnormally attacks the myelin sheath insulating the nerves. Mesenchymal stem cells (MSCs) are found in most adult tissues and play a significant systemic role in self-repair. MSCs have promising therapeutic effects in many diseases, such as autoimmune diseases, including MS. MSCs have been tested in MS animal models, such as experimental autoimmune encephalomyelitis. Other studies have combined other agents with MSCs, genetically modified MSCs, or used culture medium from MSCs. In this review, we will summarize these studies and compare the main factors in each study, such as the source of MSCs, the type of animal model, the route of injection, the number of injected cells, and the mechanism of action.