Emerging roles of PDGF-D signaling pathway in tumor development and progression

Platelet-derived growth factor-D (PDGF-D) can regulate many cellular processes, including cell proliferation, apoptosis, transformation, migration, invasion, angiogenesis and metastasis. Therefore PDGF-D signaling has been considered to be important in human malignancies, and thus PDGF-D signaling may represent a novel therapeutic target, and as such suggests that the development of agents that will target PDGF-D signaling is likely to have a significant therapeutic impact on human cancers. This mini-review describes the mechanisms of signal transduction associated with PDGF-D signaling to support the role of PDGF-D in the carcinogenesis. Moreover, we summarize data on several PDGF-D inhibitors especially naturally occurring “chemopreventive agent” such an indole compound, which we believe could serve as a novel agent for the prevention of tumor progression and/or treatment of human malignancies by targeted inactivation of PDGF-D signaling.     

Site-directed chemically-modified magnetic enzymes: fabrication,improvements, biotechnological applications and future prospects

Numerous enzymes of biotechnological importance have been immobilized on magnetic nanoparticles (MNP) via random multipoint attachment, resulting in a heterogeneous protein population with potential reduction in activity due to restriction of substrate access to the active site. Several chemistries are now available, where the modifier can be linked to a single specific amino acid in a protein molecule away from the active-site, thus enabling free access of the substrate. However, rarely these site-selective approaches have been applied to immobilize enzymes on nanoparticles. In this review, for the first time, we illustrate how to adapt site-directed chemical modification (SDCM) methods for immobilizing enzymes on iron-based MNP. These strategies are mainly chemical but may additionally require genetic and enzymatic methods. We critically examine each method and evaluate their scope for simple, quick, efficient, mild and economical immobilization of enzymes on MNP. The improvements in the catalytic properties of few available examples of immobilized enzymes are also discussed. We conclude the review with the applications and future prospects of site-selectively modified magnetic enzymes and potential benefits of this technology in improving enzymes, including cold-adapted homologues, modular enzymes, and CO₂-sequestering, as well as non-iron based nanomaterials.     

Cryptochrome Mediates Light-Dependent Magnetosensitivity of Drosophila's Circadian Clock

Since 1960, magnetic fields have been discussed as Zeitgebers for circadian clocks, but the mechanism by which clocks perceive and process magnetic information has remained unknown. Recently, the radical-pair model involving light-activated photoreceptors as magnetic field sensors has gained considerable support, and the blue-light photoreceptor cryptochrome (CRY) has been proposed as a suitable molecule to mediate such magnetosensitivity. Since CRY is expressed in the circadian clock neurons and acts as a critical photoreceptor of Drosophila's clock, we aimed to test the role of CRY in magnetosensitivity of the circadian clock. In response to light, CRY causes slowing of the clock, ultimately leading to arrhythmic behavior. We expected that in the presence of applied magnetic fields, the impact of CRY on clock rhythmicity should be altered. Furthermore, according to the radical-pair hypothesis this response should be dependent on wavelength and on the field strength applied. We tested the effect of applied static magnetic fields on the circadian clock and found that flies exposed to these fields indeed showed enhanced slowing of clock rhythms. This effect was maximal at 300 μT, and reduced at both higher and lower field strengths. Clock response to magnetic fields was present in blue light, but absent under red-light illumination, which does not activate CRY. Furthermore, cry^b and cry^OUT mutants did not show any response, and flies overexpressing CRY in the clock neurons exhibited an enhanced response to the field. We conclude that Drosophila's circadian clock is sensitive to magnetic fields and that this sensitivity depends on light activation of CRY and on the applied field strength, consistent with the radical pair mechanism. CRY is widespread throughout biological systems and has been suggested as receptor for magnetic compass orientation in migratory birds. The present data establish the circadian clock of Drosophila as a model system for CRY-dependent magnetic sensitivity. Furthermore, given that CRY occurs in multiple tissues of Drosophila, including those potentially implicated in fly orientation, future studies may yield insights that could be applicable to the magnetic compass of migratory birds and even to potential magnetic field effects in humans.     

Reproducibility of swallow-induced cortical BOLD positive and negative fMRI activity

Functional MRI (fMRI) studies have demonstrated that a number of brain regions (cingulate, insula, prefrontal, and sensory/motor cortices) display blood oxygen level-dependent (BOLD) positive activity during swallow. Negative BOLD activations and reproducibility of these activations have not been systematically studied. The aim of our study was to investigate the reproducibility of swallow-related cortical positive and negative BOLD activity across different fMRI sessions. We studied 16 healthy volunteers utilizing an fMRI event-related analysis. Individual analysis using a general linear model was used to remove undesirable signal changes correlated with motion, white matter, and cerebrospinal fluid. The group analysis used a mixed-effects multilevel model to identify active cortical regions. The volume and magnitude of a BOLD signal within each cluster was compared between the two study sessions. All subjects showed significant clustered BOLD activity within the known areas of cortical swallowing network across both sessions. The cross-correlation coefficient of percent fMRI signal change and the number of activated voxels across both positive and negative BOLD networks were similar between the two studies (r ≥ 0.87, P < 0.0001). Swallow-associated negative BOLD activity was comparable to the well-defined "default-mode" network, and positive BOLD activity had noticeable overlap with the previously described "task-positive" network. Swallow activates two parallel cortical networks. These include a positive and a negative BOLD network, respectively, correlated and anticorrelated with swallow stimulus. Group cortical activity maps, as well as extent and amplitude of activity induced by volitional swallowing in the cortical swallowing network, are reproducible between study sessions.     

Biochemical and hematological findings and risk factors associated with kidney impairment in patients with COVID-19

BackgroundCOVID-19 is a new pandemic that has infected millions of people worldwide and caused a high morbidity and mortality rate. COVID-19 may have a harmful effect on organs, especially the kidneys. Aims: The main aim of our research is to study the association between the severity of COVID-19 disease and biochemical parameters related to kidney function and to investigate certain risk factors of COVID-19-associated kidney disease.MethodsA total of 174 individuals, 121 COVID-19 positive and 53 COVID-19 negative, were enrolled in this study. The relation between COVID-19 infection, severity, kidney function test, and hematological indicators were examined.ResultsThe most prominent symptoms among COVID-19 were fever (95% ) and fatigue (92%). Regarding biochemical parameters, median creatinine, MPV, and CRP were significantly higher in COVID-19 patients, whereas median eGFR, Na+, WBC, MCH, MCHC, and eosinophil percentages were significantly lower in this group. Severely infected patients were observed to have higher urea, creatinine, neutrophils, and NLR. However, median sodium, eGFR, hemoglobin, hematocrit, RBC, lymphocytes, and platelet count were significantly lower in the severe group. Urine examination of the severe group showed a significantly lower specific gravity, while urine pH, protein, and glucose were significantly higher.ConclusionsOur analysis indicates that COVID-19 infection affects kidney function, mainly creatinine level, urea, eGFR, Na+ and urine protein. Additionally, comorbidities such as older age (>65), hypertension, taking medications, and CRP (>33.55 mg/L) are considered risk factors that are more likely to contribute to kidney impairment in COVID-19 positive patients.     

Removal of heavy metals from industrial wastewater using microbial fuel cell

Removal efficiency of gold from a solution of pure tetrachloroaurate ions was investigated using microbial fuel cell (MFC) technology. The effects of type of catholyte solution and initial gold concentration on the removal efficiency were considered. Due to its presence at high levels in the gold wastewater, the effect of copper ions on the removal efficiency of the gold ions was also studied. The effects of pH and initial biomass concentration on the gold removal efficiency was also determined. The results showed that after 5 h contact time, 95% of gold removal efficiency from a wastewater containing 250 ppm of initial gold ions at ambient temperature using 80 g/L yeast concentration was achieved. After 48 h of the cell''s operation under the same condition, 98.86% of AuCl₄ ^– ions were successfully removed from the solution. At initial gold concentration in the waste solution of 250 ppm, pH 2, and initial yeast concentration of 80 g/L, 100% removal efficiency of the gold was achieved. On the other hand, the most suitable condition for copper removal was found at a pH of 5.2, where 53% removal efficiency from the waste solution was accomplished.