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

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

The Regenerative Effect of Intra-Articular Injection of Autologous Fat Micro-Graft in Treatment of Chronic Knee Osteoarthritis

Osteoarthritis (OA) is one of the most prevalent conditions resulting to disability particularly in elderly population About 13% of women and 10% of men aged 60 years and older have symptomatic knee OA. The proportions of people affected with symptomatic knee OA is likely to increase due to the aging of the population and the rate of obesity or overweight in the general population. There are multiple factors associated with this progressive disease such as obesity, female gender, and repetitive trauma. Pain is the most common symptom in knee OA, a leading cause of chronic disability, clinical diagnosis will be supported by certain radiological findings. There are numerous conservative therapies that help to relive symptoms depend on severity of Osteoarthritis, and knee replacement remains standard of care in advance disease. Fat Micrografting is evolving technique with promising result in selected patients with regenerative and reparative effect of adipocyte-derived stem cell toward damaged cartilage and bone, which supported by clinical evidence

Gene Regulation of The Human Pregnane-X Receptor Gene.

The Pregnane X Receptor (PXR) is regarded as a central factor in the body's response to alterations in chemical levels: It is activated by a variety of chemically unrelated endogenous and exogenous compounds and regulates genes involved in the uptake, metabolism, and excretion of these chemicals. The aim of this study was to delineate the molecular mechanisms underlying regulation of the PXR gene. Initial in silico analysis of 2200 bp of DNA 5' to the PXR putative transcription start site suggests a complex promoter with binding sites for a large number of both liver-enriched and ligand-activated transcription factors. This region of the PXR proximal promoter was cloned from genomic DNA and a reporter gene assay deletion series constructed. Over-expression of liver-enriched and ligand-activated transcription factors in Huh7 hepatoma cells was used to examine the role of these factors in regulating the PXR reporter gene. The liver-enriched transcription factors HNF3α/β and HNF4α showed positive regulation of fragments containing putative interaction sites for these factors. Amongst the ligand-activated transcription factors examined, GRα, ER and PPARα produced a net positive effect on PXR reporter gene expression, whereas PXR and CAR produced a net inhibitory effect, suggesting feedback regulation of PXR expression by PXR and CAR proteins, potentially to prevent disruption of cellular homeostasis. The effect of PPARα action of PXR gene expression was examined in more detail, and I have demonstrated for the first time that PPARα regulates gene expression of the PXR by binding directly to its promoter. This is of particular interest as PPARα ligands are not classical PXR ligands, suggesting a complex relationship with implications for drug-drug interactions. In addition, PPARα-mediated activation of PXR gene expression is probably a cross species event, in contrast to the rodent-specific carcinogenesis elicited by PPARα ligands, raising the important question of the implications of this activation in man

Gene regulation of the human pregnane-X receptor gene

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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

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