Mesenchymal stem cell-conditioned medium accelerates regeneration of human renal proximal tubule epithelial cells after gentamicin toxicity

Bone marrow-derived mesenchymal stem cells (MSCs) have the capacity to regenerate renal tubule epithelia and repair renal function without fusing with resident tubular cells. The goal of the present project was to investigate the role of MSCs secreted cytokines on tubule cell viability and regeneration after a toxic insult, using a conditionally immortalized human proximal tubule epithelial cell (ciPTEC) line. Gentamicin was used to induce nephrotoxicity, and cell viability and migration were studied in absence and presence of human MSC-conditioned medium (hMSC-CM) i.e. medium containing soluble factors produced and secreted by MSCs. Exposure of ciPTEC to 0–3000 μg/ml gentamicin for 24 h caused a significant dose-dependent increase in cell death. We further demonstrated that the nephrotoxic effect of 2000 μg/ml gentamicin was recovered partially by exposing cells to hMSC-CM. Moreover, exposure of ciPTEC to gentamicin (1500–3000 μg/ml) for 7 days completely attenuated the migratory capacity of the cells. In addition, following scrape-wounding, cell migration of both untreated and gentamicin-exposed cells was increased in the presence of hMSC-CM, as compared to exposures to normal medium, indicating improved cell recovery. Our data suggest that cytokines secreted by MSCs stimulate renal tubule cell regeneration after nephrotoxicity.     

Assessment of Image Quality for Selective Intracoronary Contrast-Injected CT Angiography in a Hybrid Angio-CT System: A Feasibility Study in Swine

PurposeTo compare image quality in selective intracoronary contrast-injected computed tomography angiography (Selective-CTA) with that in conventional intravenous contrast-injected CTA (IV-CTA).Materials and MethodsSix pigs (35 to 40 kg) underwent both IV-CTA using an intravenous injection (60 mL) and Selective-CTA using an intracoronary injection (20 mL) through a guide-wire during/after percutaneous coronary intervention. Images of the common coronary artery were acquired. Scans were performed using a combined machine comprising an invasive coronary angiography suite and a 320-channel multi-slice CT scanner. Quantitative image quality parameters of CT attenuation, image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), mean lumen diameter (MLD), and mean lumen area (MLA) were measured and compared. Qualitative analysis was performed using intraclass correlation coefficient (ICC), which was calculated for analysis of interobserver agreement.ResultsQuantitative image quality, determined by assessing the uniformity of CT attenuation (399.06 vs. 330.21, p<0.001), image noise (24.93 vs. 18.43, p<0.001), SNR (16.43 vs. 18.52, p=0.005), and CNR (11.56 vs. 13.46, p=0.002), differed significantly between IV-CTA and Selective-CTA. MLD and MLA showed no significant difference overall (2.38 vs. 2.44, p=0.068, 4.72 vs. 4.95, p=0.078). The density of contrast agent was significantly lower for selective-CTA (13.13 mg/mL) than for IV-CTA (400 mg/mL). Agreement between observers was acceptable (ICC=0.79±0.08).ConclusionOur feasibility study in swine showed that compared to IV-CTA, Selective-CTA provides better image quality and requires less iodine contrast medium.     

Saturation recovery-prepared magnetic resonance angiography for assessment of left atrial and esophageal anatomy

Objectives:Magnetic resonance angiography (MRA) has been established as an important imaging method in cardiac ablation procedures. In pulmonary vein (PV) isolation procedures, MRA has the potential to minimize the risk of severe complications, such as atrio-esophageal fistula, by providing detailed information on esophageal position relatively to cardiac structures. However, traditional non-gated, first-pass (FP) MRA approaches have several limitations, such as long breath-holds, non-uniform signal intensity throughout the left atrium (LA), and poor esophageal visualization. The aim of this observational study was to validate a respiratory-navigated, ECG-gated (EC), saturation recovery-prepared MRA technique for simultaneous imaging of LA, LA appendage, PVs, esophagus, and adjacent anatomical structures.Methods:Before PVI, 106 consecutive patients with a history of AF underwent either conventional FP-MRA (n = 53 patients) or our new EC-MRA (n = 53 patients). Five quality scores (QS) of LA and esophagus visibility were assessed by two experienced readers. The non-parametric Mann–Whitney U-test was used to compare QS between FP-MRA and EC-MRA groups, and linear regression was applied to assess clinical contributors to image quality.Results:EC-MRA demonstrated significantly better image quality than FP-MRA in every quality category. Esophageal visibility using the new MRA technique was markedly better than with the conventional FP-MRA technique (median 3.5 [IQR 1] vs median 1.0, p < 0.001). In contrast to FP-MRA, overall image quality of EC-MRA was not influenced by heart rate.Conclusion:Our ECG-gated, respiratory-navigated, saturation recovery-prepared MRA technique provides significantly better image quality and esophageal visibility than the established non-gated, breath-holding FP-MRA. Image quality of EC-MRA technique has the additional advantage of being unaffected by heart rate.Advances in knowledge:Detailed information of cardiac anatomy has the potential to minimize the risk of severe complications and improve success rates in invasive electrophysiological studies. Our novel ECG-gated, respiratory-navigated, saturation recovery-prepared MRA technique provides significantly better image quality of LA and esophageal structures than the traditional first-pass algorithm. This new MRA technique is robust to arrhythmia (tachycardic, irregular heart rates) frequently observed in AF patients.     

Dynamics of host immune responses to SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the most recent global health threat, is spreading throughout the world with worrisome speed, and the current wave of coronavirus disease 2019 (COVID-19) seems to have no mercy. While this mysterious virus challenges our ability to control viral infections, our opportunities to control the COVID-19 pandemic are gradually fading. Currently, pandemic management relies on preventive interventions. Although prevention is a good strategy to mitigate SARS-CoV-2 transmission, it still cannot be considered an absolute solution to eliminate this pandemic. Currently, developing a potent immunity against this viral infection seems to be the most promising strategy to drive down this ongoing global tragedy. However, with the emergence of new challenges in the context of immune responses to COVID-19, the road to control this devastating pandemic seems bumpier; thus, it is pivotal to characterize the dynamics of host immune responses to COVID-19, in order to develop efficient prophylactic and therapeutic tools. This begs the question of whether the effector mechanisms of the immune system are indeed potent or a possible contributing factor to developing more severe and lethal forms of COVID-19. In this review, the possible role of the immunopathologic phenomena including antibody-dependent enhancement, cytokine storm, and original antigenic sin in severity and mortality of COVID-19 will be discussed.     

Efficacy and Safety of Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation Undergoing Elective Surgical Procedures: A Meta-analysis

Objective: The study objective was to determine if peri-operative bridging anticoagulation in patients with atrial fibrillation is beneficial or harmful.Design: Systematic review and meta-analysis.Setting: Inpatient or in-hospital setting.Participants: Adults with atrial fibrillation having a CHADS2 score >1 undergoing elective surgical procedure on anticoagulation.Methods: A systemic search of multiple databases (Cochrane, Medline, PubMed) was performed regarding studies conducted on efficacy and safety of perioperative bridging anticoagulation in patients with atrial fibrillation. Studies identified were reviewed by two authors individually before inclusion. The results were then pooled using Review Manager to determine the combined effect. Stroke/systemic embolism was considered as the primary efficacy outcome. Major bleeding was the primary safety outcome.Results: The systematic search revealed 108 potential articles. The full texts of 28 articles were retrieved for assessment of eligibility. After full text review, 25 articles were excluded. Three articles met inclusion criteria. No significant difference in stroke/systemic embolism with bridging anticoagulation was noted (risk ratio, 1.25-95% confidence interval [CI], 0.55–2.85). Bridging was associated with significantly higher risk of major bleeding (risk ratio, 3.29-95% CI, 2.25–4.81).Conclusion: An individualized approach is required when initiating peri-operative bridging anticoagulation. There is certainly a higher risk of bleeding with bridging anticoagulation and no difference in stroke/systemic embolism. However, the results cannot be extrapolated to patients who have valvular atrial fibrillation or CHADS2 score of 5 or greater.     

Selective photocatalytic oxidation of aromatic alcohols to aldehydes with air by magnetic WO3ZnO/Fe3O4. In situ photochemical synthesis of 2-substituted benzimidazoles

Recently, visible light-driven organic photochemical synthesis has been a pioneering field of interest from academic and industrial associations due to its unique features of green and sustainable chemistry. Herein, WO₃ZnO/Fe₃O₄ was synthesized, characterized, and used as an efficient magnetic photocatalyst in the preparation of a range of 2-substituted benzimidazoles via the condensation of benzyl alcohol and o-phenylenediamine in ethanol at room temperature for the first time. The key feature of this work is focused on the in situ photocatalytic oxidation of benzyl alcohols to benzaldehydes under atmospheric air and in the absence of any further oxidant. This new heterogeneous nanophotocatalyst was characterized via XRD, FT-IR, VSM and SEM. Short reaction time, cost-effectiveness, broad substrate scope, easy work-up by an external magnet, and excellent product yield are the major advantages of the present methodology. A number of effective experimental parameters were also fully investigated to clear broadness and generality of the protocol.

WO₃ZnO/Fe₃O₄ is used as a magnetic photocatalyst in the preparation of 2-substituted benzimidazoles in EtOH at RT. The key feature is the in situ photocatalytic oxidation of benzyl alcohols to benzaldehydes under atmospheric air in the absence of further oxidant.