Electrochemical monitoring of malondialdehyde biomarker in biological samples via electropolymerized amino acid/chitosan nanocomposite

This study reports on the electropolymerization of a low toxic and biocompatible nanopolymer with entitle poly arginine‐graphene quantum dots‐chitosan (PARG‐GQDs‐CS) as a novel strategy for surface modification of glassy carbon surface and preparation of a new interface for measurement of malondialdehyde (MDA) in exhaled breath condensate. Electrochemical deposition, as a well‐controlled synthesis procedure, has been used for subsequently layer‐by‐layer preparation of GQDs‐CS nanostructures on a PARG prepolymerized on the surface of glassy carbon electrode using cyclic voltammetry techniques in the regime of ?1.5 to 2 V. The modified electrode appeared as an effective electroactivity for detection of MDA by using cyclic voltammetry, linear sweep voltammetry, and differential pulse voltammetry. The prepared modified electrode demonstrated a noticeably good activity for electrooxidation of MDA than PARG. Enhancement of peak currents is ascribed to the fast heterogeneous electron transfer kinetics that arise from the synergistic coupling between the excellent properties of PARG and semiconducting polymer, GQDs as high density of edge plane sites and subtle electronic characteristics and unique properties of CS such as excellent film‐forming ability, high permeability, good adhesion, nontoxicity, cheapness, and a susceptibility to chemical modification. The prepared sensor showed 1 oxidation processes for MDA at potentials about 1 V with a low limit of quantification 5.94 nM. Finally, application of new sensor for determination of MDA in exhaled breath condensate was suited. In general, the simultaneous attachment of GQDs and CS to structure of poly amino acids provides new opportunities within the personal healthcare.     

Cytotoxic Activity of Herbal Medicines as Assessed in Vitro: A Review

Since time immemorial, human beings have sought natural medications for treatment of various diseases. Weighty evidence demonstrates the use of chemical methodologies for sensitive evaluation of cytotoxic potentials of herbal agents. However, due to the ubiquitous use of cytotoxicity methods, there is a need for providing updated guidance for the design and development of in vitro assessment. The aim of this review is to provide practical guidance on common cell-based assays for suitable assessment of cytotoxicity potential of herbal medicines and discussing their advantages and disadvantages Relevant articles in authentic databases, including PubMed, Web of Science, Science Direct, Scopus, Google Scholar and SID, from 1950 to 2022 were collected according to selection criteria of in vitro cytotoxicity assays and protocols. In addition, the link between cytotoxicity assay selection and different factors such as the drug solvent, concentration and exposure duration were discussed.     

Modulation of autophagy as the target of mesenchymal stem cells-derived conditioned medium in rat model of myocardial ischemia/reperfusion injury

Molecular Biology Reports - Human amniotic membrane mesenchymal stem cells-derived conditioned medium (hAM-MSCs-CM) has positive effects against myocardial ischemia/reperfusion (MI/R) injury....     

Assessment of genetic diversity among and within Carthamus species using sequence-related amplified polymorphism (SRAP) markers

Due to precise evaluation of genetic diversity of Carthamus species, sixty-two genotypes consisting fifty-two from five wild (C. oxyacanthus M. Bieb, C. lanatus L., C. dentatus Vahl, C. boissieri Halácsy, C. glaucus M.B.) and ten from cultivated species (C. tinctorius L.) were selected for evaluation of the genetic diversity in Carthamus species. A total of 238 (81.2 %) polymorphic bands were detected by 12 SRAP primer combinations with an average of 22 bands per combination. Me4-Em1 and Me5-Em2 primer combinations were known as the most informative SRAP markers based on the PIC values (0.34) where they distinguished all studied Carthamus species. Cluster analysis classified all accessions into five main groups among which clusters containing cultivated individuals were distinctly separated from those containing wilds. The most and the least genetic variation based on analysis of molecular variance, were detected within (76.90 %) and among (22.84 %) groups, respectively. The obtained results suggested that C. dentatus, C. glaucus and C. boissieri species may be classified in one section including C. dentatus in one and C. glaucus and C. boissieri in another subsection. The results also revealed high genetic similarity between C. oxyacanthus and C. tinctorius despite their different morphological characteristics.     

TGF-β1 induces EMT reprogramming of porcine bladder urothelial cells into collagen producing fibroblasts-like cells in a Smad2/Smad3-dependent manner

Activation of fibroblasts and their differentiation into myofibroblasts, excessive collagen production and fibrosis occurs in a number of bladder diseases. Similarly, conversion of epithelial cells into mesenchymal cells (EMT) has been shown to increase fibroblasts like cells. TGF-β1 can induce the EMT and the role of TGF-β1-induced EMT during bladder injury leading to fibrosis and possible organ failure is gaining increasing interest. Here we show that EMT and fibrosis in porcine bladder urothelial (UC) cells are Smad dependent. Fresh normal porcine bladder urothelial cells were grown in culture with or without TGF-β1 and EMT markers were assessed. TGF-β1 treatment induced changes in cellular morphology as depicted by a significant decrease in the expression of E-cadherin and corresponding increase in N-cadherin and α-SMA. We knocked down Smad2 and Smad3 by Smad specific siRNA. Downregulation of E-cadherin expression by TGF-β1 was Smad3-dependent, whereas N-cadherin and α-SMA were dependent on both Smad2 and Smad3. Connective tissue growth factor (CTGF/CCN2), matrix metalloproteinase-2 and -9 (MMP-2, MMP-9) has been shown to play important roles in the pathogenesis of fibrosis. Induction of these genes by TGF-β1 was found to be time dependent. Upregulation of CTGF/CCN2 by TGF-β1 was Smad3 dependent; whereas MMP-2 was Smad2 dependent. Smad2 and Smad3 both participated in MMP-9 expression. TGF-β1 reprogrammed mesenchymal fibroblast like cells robustly expressed collagen I and III and these was inhibited by SB-431542, a TGF-β receptor inhibitor. Our results indicate that EMT of porcine bladder UC cells is TGF-β1 dependent and is mediated through Smad2 and Smad3. TGF-β1 may be an important factor in the development of bladder fibrosis via an EMT mechanism. This identifies a potential amenable therapeutic target.     

Determination of pholcodine in syrups and human plasma using the chemiluminescence system of tris(1,10 phenanthroline)ruthenium(II) and acidic Ce(IV)

Pholcodine is an opiate derivative drug which is widely used in pediatric medicine. In this study, a chemiluminescence (CL) method is described that determines pholcodine in human plasma and syrup samples. This method is based on the fact that pholcodine can greatly enhance the weak CL emission of reaction between tris(1,10 phenanthroline)ruthenium(II), Ru(phen)₃²⁺, and acidic Ce(IV). The CL mechanism is described in detail using UV–vis light, fluorescence and CL spectra. Effects of chemical variables were investigated and under optimum conditions, CL intensity was proportional to the pholcodine concentration over the range 4.0 × 10^?8 to 8.0 × 10^?6 mol  L^?1. The limit of detection (LOD) (S/N = 3) was 2.5 × 10^?8 mol  L^?1. Percent of relative standard deviations (%RSD) for 3.0 × 10^?7 and 3.0 × 10^?6 mol  L^?1 of pholcodine was 2.9 and 4.0%, respectively. Effects of common ingredients were investigated and the method was applied successfully to the determination of pholcodine in syrup samples and human plasma.     

Lifelong reduction of LDL-cholesterol related to a common variant in the LDL-receptor gene decreases the risk of coronary artery disease--a Mendelian Randomisation study

Background

Rare mutations of the low-density lipoprotein receptor gene (LDLR) cause familial hypercholesterolemia, which increases the risk for coronary artery disease (CAD). Less is known about the implications of common genetic variation in the LDLR gene regarding the variability of cholesterol levels and risk of CAD.

Methods

Imputed genotype data at the LDLR locus on 1 644 individuals of a population-based sample were explored for association with LDL-C level. Replication of association with LDL-C level was sought for the most significant single nucleotide polymorphism (SNP) within the LDLR gene in three European samples comprising 6 642 adults and 533 children. Association of this SNP with CAD was examined in six case-control studies involving more than 15 000 individuals.

Findings

Each copy of the minor T allele of SNP rs2228671 within LDLR (frequency 11%) was related to a decrease of LDL-C levels by 0.19 mmol/L (95% confidence interval (CI) [0.13–0.24] mmol/L, p = 1.5×10⁻¹⁰). This association with LDL-C was uniformly found in children, men, and women of all samples studied. In parallel, the T allele of rs2228671 was associated with a significantly lower risk of CAD (Odds Ratio per copy of the T allele: 0.82, 95% CI [0.76–0.89], p = 2.1×10⁻⁷). Adjustment for LDL-C levels by logistic regression or Mendelian Randomisation models abolished the significant association between rs2228671 with CAD completely, indicating a functional link between the genetic variant at the LDLR gene locus, change in LDL-C and risk of CAD.

Conclusion

A common variant at the LDLR gene locus affects LDL-C levels and, thereby, the risk for CAD.