Ferrelllindgaard6181
Both, alfacalcidol and calcifediol were more cytotoxic than cholecalciferol on the tested cell lines as they are partially active metabolites. Breast cancer (MCF-7) was the most sensitive to all metabolites at all-time intervals with the best IC
values of 4.35μM±1.06 after 72h continuous exposure of alfacalcidol.
Vitamin D metabolites are a potential option for cancer treatment along with or an alternative to chemo-therapeutics although extensive preclinical studies are required to prove this effect.
Vitamin D metabolites are a potential option for cancer treatment along with or an alternative to chemo-therapeutics although extensive preclinical studies are required to prove this effect.Staphylococcus aureus is a major human pathogen, which encounters reactive oxygen, nitrogen, chlorine, electrophile and sulfur species (ROS, RNS, RCS, RES and RSS) by the host immune system, during cellular metabolism or antibiotics treatments. To defend against redox active species and antibiotics, S. aureus is equipped with redox sensing regulators that often use thiol switches to control the expression of specific detoxification pathways. In addition, the maintenance of the redox balance is crucial for survival of S. aureus under redox stress during infections, which is accomplished by the low molecular weight (LMW) thiol bacillithiol (BSH) and the associated bacilliredoxin (Brx)/BSH/bacillithiol disulfide reductase (YpdA)/NADPH pathway. Here, we present an overview of thiol-based redox sensors, its associated enzymatic detoxification systems and BSH-related regulatory mechanisms in S. aureus, which are important for the defense under redox stress conditions. SNDX-5613 Application of the novel Brx-roGFP2 biosensor provides new insights on the impact of these systems on the BSH redox potential. These thiol switches of S. aureus function in protection against redox active desinfectants and antimicrobials, including HOCl, the AGXX® antimicrobial surface coating, allicin from garlic and the naphthoquinone lapachol. Thus, thiol switches could be novel drug targets for the development of alternative redox-based therapies to combat multi-drug resistant S. aureus isolates.The mechanical properties of red blood cells (RBCs) are fundamental for their physiological role as gas transporters. RBC flexibility and elasticity allow them to survive the hemodynamic changes in the different regions of the vascular tree, to dynamically contribute to the flow thereby decreasing vascular resistance, and to deform during the passage through narrower vessels. RBC mechanoproperties are conferred mainly by the structural characteristics of their cytoskeleton, which consists predominantly of a spectrin scaffold connected to the membrane via nodes of actin, ankyrin and adducin. Changes in redox state and treatment with thiol-targeting molecules decrease the deformability of RBCs and affect the structure and stability of the spectrin cytoskeleton, indicating that the spectrin cytoskeleton may contain redox switches. In this perspective review, we revise current knowledge about the structural and functional characterization of spectrin cysteine redox switches and discuss the current lines of research aiming to understand the role of redox regulation on RBC mechanical properties. These studies may provide novel functional targets to modulate RBC function, blood viscosity and flow, and tissue perfusion in disease conditions.Cys-based redox regulation was long regarded a major adjustment mechanism of photosynthesis and metabolism in plants, but in the recent years, its scope has broadened to most fundamental processes of plant life. Drivers of the recent surge in new insights into plant redox regulation have been the availability of the genome-scale information combined with technological advances such as quantitative redox proteomics and in vivo biosensing. Several unexpected findings have started to shift paradigms of redox regulation. Here, we elaborate on a selection of recent advancements, and pinpoint emerging areas and questions of redox biology in plants. We highlight the significance of (1) proactive H2O2 generation, (2) the chloroplast as a unique redox site, (3) specificity in thioredoxin complexity, (4) how to oxidize redox switches, (5) governance principles of the redox network, (6) glutathione peroxidase-like proteins, (7) ferroptosis, (8) oxidative protein folding in the ER for phytohormonal regulation, (9) the apoplast as an unchartered redox frontier, (10) redox regulation of respiration, (11) redox transitions in seed germination and (12) the mitochondria as potential new players in reductive stress safeguarding. Our emerging understanding in plants may serve as a blueprint to scrutinize principles of reactive oxygen and Cys-based redox regulation across organisms.
Studies that investigate the accuracy and precision of M-protein quantification are scarce. These studies are prone to give a biased view, since they are exclusively performed by institutions with international top-expertise on M-protein diagnostics. To obtain a realistic impression of the accuracy and precision of M-protein quantification, we studied results of 73 laboratories participating in the Dutch External Quality Assessment (EQA) program for M-protein diagnostics.
To measure accuracy, healthy serum was spiked with respectively 1 and 5g/L human IgG-kappa monoclonal antibody daratumumab. To measure precision, five sera were selected to be repeatedly send to all blinded EQA-participants.
The reported concentrations for the EQA-sample spiked with 5g/L daratumumab ranged from 2.6 to 8.0g/L (mean 4.9g/L, between-laboratory CV=23%). 98% of the participants detected and correctly characterized the 1g/L daratumumab band. Both the accuracy (mean 1.7g/L) and precision (between-laboratory CV=46%) of this 1gwith both accuracy and precision. These data indicate that M-protein quantification to monitor patients is appropriate, when subsequent testing is performed within the same laboratory.
Epilepsy is one of the most common neurological disorders, diagnosis of which is challenging as many unrelated conditions may mimic seizure. Epilepsy impairs the quality of life of patients due to associated physical and psychological trauma. Epileptic patients are also at increased risk of premature death due to autonomic disturbance and fatal accidents. The aim of the present research work was to study ischemia modified albumin (IMA) as an early biomarker of epilepsy in the adolescent population.
Twenty-five diagnosed cases of epilepsy and 25 healthy volunteers as control of adolescent group were recruited as study subjects. The study subjects were age and sex matched. Clinical evaluation, routine biochemical parameters and IMA estimation were carried out. Serum IMA was measured by spectrophotometric method.
The mean serum IMA levels were significantly raised in epileptic patients (0.69
0.1 absorbance units [ABSU]) as compared to the healthy control group (0.52
0.24 ABSU) (p=0.004). ROC curve of IMA predicted that at cut off of 0.
