Protein interaction network of Arabidopsis thaliana female gametophyte development identifies novel proteins and relations

Although the female gametophyte in angiosperms consists of just seven cells, it has a complex biological network. In this study, female gametophyte microarray data from Arabidopsis thaliana were integrated into the Arabidopsis interactome database to generate a putative interaction map of the female gametophyte development including proteome map based on biological processes and molecular functions of proteins. Biological and functional groups as well as topological characteristics of the network were investigated by analyzing phytohormones, plant defense, cell death, transporters, regulatory factors, and hydrolases. This approach led to the prediction of critical members and bottlenecks of the network. Seventy-four and 24 upregulated genes as well as 171 and 3 downregulated genes were identified in subtracted networks based on biological processes and molecular function respectively, including novel genes such as the pathogenesis-related protein 4, ER type Ca2+ ATPase 3, dihydroflavonol reductase, and ATP disulfate isomerase. Biologically important relationships between genes, critical nodes, and new essential proteins such as AT1G26830, AT5G20850, CYP74A, AT1G42396, PR4 and MEA were found in the interactome’s network. The positions of novel genes, both upregulated and downregulated, and their relationships with biological pathways, in particular phytohormones, were highlighted in this study.Batool Hosseinpour, Vahid HajiHoseini, Rafieh Kashfi, Esmaeil Ebrahimie and Farhid Hemmatzade

The relationship between neuropsychological function and responsiveness to vitamin D supplementation using artificial neural networks

Background: Vitamin D has recently attracted interest for its pleiotropic effects. Vitamin D supplements are a potentially important public health intervention, but the response to supplementation varies between individuals. Aim: We aimed to assess the association between several neuropsychological parameters and the magnitude of response to vitamin D supplementation using an artificial neural network method. Methods: Neuropsychological function was assessed in 619 participants using standard questionnaires. The study participants received vitamin D capsules containing 50,000 IU vitamin D per week over 9 weeks. To assess the relationship between responsiveness to vitamin D supplements and the impact on these neuropsychological parameters, the best-performing artificial neural network algorithms were selected from a combination of different transfer functions in hidden and output layers and variable numbers of hidden layers (between two and 50). The performance of the artificial neural network algorithm was assessed by receiver operating characteristic analysis and variables of importance were identified. Results: The artificial neural network algorithm with sigmoid transfer function in both hidden and output layers could predict responsiveness to vitamin D supplementation effectively. The sensitivity and specificity were between 0.60 and 0.70 and 0.66 and 0.70, respectively. Cognitive abilities (42.5), basal vitamin D (21.3), body mass index (9.5), and daytime sleepiness (8) are the most widely used variables to predict changes in serum vitamin D levels. Conclusions: Cognitive abilities status and baseline 25-hydroxyvitamin D are important novel modifiers of the enhancement in circulating 25-hydroxyvitamin D after vitamin D supplementation. © The Author(s) 2020

Percutaneous transluminal mitral commissurotomy in pregnant women with severe mitral stenosis

Background: Mitral stenosis tends to worsen during pregnancy because of the increase in the cardiac output and the heart rate. In nonresponders to medical therapy, percutaneous transluminal mitral commissurotomy (PTMC) may be performed when there is a suitable valvular anatomy. In this study, we aimed to investigate the clinical and fetal outcomes of pregnant women with mitral stenosis who underwent PTMC. Methods: Thirty-one patients undergoing PTMC during pregnancy were enrolled in this study. The mitral valve area (MVA), the transmitral valve mean gradient (MVMG), and the severity of mitral regurgitation were assessed pre- and postprocedurally by transthoracic and transesophageal echocardiography. The radiation time was measured during the procedure. The patients were followed up during pregnancy, and the neonates were monitored for weight, height, the head circumference, the birth Apgar score, and the adverse effects of radiation for at least 12 months. Results: PTMC was successfully performed on 29 (93.5) patients. No maternal death or pulmonary edema was reported. The mean MVA significantly increased (from 0.73±0.17 cm2to 1.28±0.24 cm2; P<0.001), and the mean MVMG significantly decreased (from 19.62±5.91 mmHg to 8.90±4.73 mmHg; P<0.001) after the procedure. A significant decrease in the systolic pulmonary artery pressure was also detected. Mitral regurgitation did not increase in severity in 16 (51.6) patients. There was no significant relationship between the Apgar score, weight, height, and the head circumference at birth and at the radiation time. Conclusion: In our series, PTMC during pregnancy was a safe and effective procedure. Lowering the radiation time with low frame-count techniques confers a significant decrease in radiation-related complications. © 2019, Tehran Heart Center. All Rights Reserved

Structural Conformers of (1,3-Dithiol-2-ylidene)ethanethioamides: The Balance Between Thioamide Rotation and Preservation of Classical Sulfur-Sulfur Hypervalent Bonds

The reaction of N-(2-phthalimidoethyl)-N-alkylisopropylamines and S2Cl2 gave 4-N-(2-phthalimidoethyl)-N-alkylamino-5-chloro-1,2-dithiol-3-thiones that quantitatively cycloadded to dimethyl or diethyl acetylenedicarboxylate to give stable thioacid chlorides, which in turn reacted with one equivalent of aniline or a thiole to give thioanilides or a dithioester. Several compounds of this series showed atropisomers that were studied by a combination of dynamic NMR, simulation of the signals, conformational analysis by DFT methods, and single crystal X-ray diffraction, showing a good correlation between the theoretical calculations, the experimental values of energies, and the preferred conformations in the solid state. The steric hindering of the crowded substitution at the central amine group was found to be the reason for the presence of permanent atropisomers in this series of compounds and the cause of a unique disposition of the thioxo group at close-to-right angles with respect to the plane defined by the 1,3-dithiole ring in the dithiafulvene derivatives, thus breaking the sulfur–sulfur hypervalent bond that is always found in this kind of compounds.Ministerio de Economıá y Competitividad, Spain (Project CTQ2012- 31611), Junta de Castilla y León, Consejería de Educación y Cultura y Fondo Social Europeo (Project BU246A12-1), and the European Commission, Seventh Framework Programme (Project SNIFFER FP7-SEC-2012-312411

Erratum: COMPARE CPM-RMI trial: Intramyocardial transplantation of autologous bone marrow-derived CD133+ cells and MNCs during CABG in patients with recent MI: A phase II/III, multicenter, placebo-controlled, randomized, double-blind clinical trial. (Cell Journal (2018) 20:3 (449) DOI: 10.22074/cellj.2018.5197)

This article published in Cell J (Yakhteh), Vol 20, No 2, Jul-Sep 2018, on pages 267-277, four affiliations (1, 4, 5, and 10) were changed based on authors request. © 2018 Royan Institute (ACECR). All rights reserved

Induction of cell cycle changes and modulation of apoptogenic/anti-apoptotic and extracellular signaling regulatory protein expression by water extracts of I'm-Yunity™ (PSP)

BACKGROUND: I'm-Yunity™ (PSP) is a mushroom extract derived from deep-layer cultivated mycelia of the patented Cov-1 strain of Coriolus versicolor (CV), which contains as its main bioactive ingredient a family of polysaccharo-peptide with heterogeneous charge properties and molecular sizes. I'm-Yunity™ (PSP) is used as a dietary supplement by cancer patients and by individuals diagnosed with various chronic diseases. Laboratory studies have shown that I'm-Yunity™ (PSP) enhances immune functions and also modulates cellular responses to external challenges. Recently, I'm-Yunity™ (PSP) was also reported to exert potent anti-tumorigenic effects, evident by suppression of cell proliferation and induction of apoptosis in malignant cells. We investigate the mechanisms by which I'm-Yunity™ (PSP) elicits these effects. METHODS: Human leukemia HL-60 and U-937 cells were incubated with increasing doses of aqueous extracts of I'm-Yunity™ (PSP). Control and treated cells were harvested at various times and analyzed for changes in: (1) cell proliferation and viability, (2) cell cycle phase transition, (3) induction of apoptosis, (4) expression of cell cycle, apoptogenic/anti-apoptotic, and extracellular regulatory proteins. RESULTS: Aqueous extracts of I'm-Yunity™ (PSP) inhibited cell proliferation and induced apoptosis in HL-60 and U-937 cells, accompanied by a cell type-dependent disruption of the G(1)/S and G(2)/M phases of cell cycle progression. A more pronounced growth suppression was observed in treated HL-60 cells, which was correlated with time- and dose-dependent down regulation of the retinoblastoma protein Rb, diminution in the expression of anti-apoptotic proteins bcl-2 and survivin, increase in apoptogenic proteins bax and cytochrome c, and cleavage of poly(ADP-ribose) polymerase (PARP) from its native 112-kDa form to the 89-kDa truncated product. Moreover, I'm-Yunity™ (PSP)-treated HL-60 cells also showed a substantial decrease in p65 and to a lesser degree p50 forms of transcription factor NF-κB, which was accompanied by a reduction in the expression of cyclooxygenase 2 (COX2). I'm-Yunity™ (PSP) also elicited an increase in STAT1 (signal transducer and activator of transcription) and correspondingly, decrease in the expression of activated form of ERK (extracellular signal-regulated kinase). CONCLUSION: Aqueous extracts of I'm-Yunity™ (PSP) induces cell cycle arrest and alterations in the expression of apoptogenic/anti-apoptotic and extracellular signaling regulatory proteins in human leukemia cells, the net result being suppression of proliferation and increase in apoptosis. These findings may contribute to the reported clinical and overall health effects of I'm-Yunity™ (PSP)

COMPARE CPM-RMI Trial: Intramyocardial transplantation of autologous bone marrow-derived CD133+ Cells and MNCs during CABG in patients with recent MI: A Phase II/III, multicenter, placebo-controlled, randomized, double-blind clinical trial

Objective: The regenerative potential of bone marrow-derived mononuclear cells (MNCs) and CD133+ stem cells in the heart varies in terms of their pro-angiogenic effects. This phase II/III, multicenter and double-blind trial is designed to compare the functional effects of intramyocardial autologous transplantation of both cell types and placebo in patients with recent myocardial infarction (RMI) post-coronary artery bypass graft. Materials and Methods: This was a phase II/III, randomized, double-blind, placebo-controlled trial COMPARE CPM-RMI (CD133, Placebo, MNCs - recent myocardial infarction) conducted in accordance with the Declaration of Helsinki that assessed the safety and efficacy of CD133 and MNCs compared to placebo in patients with RMI. We randomly assigned 77 eligible RMI patients selected from 5 hospitals to receive CD133+ cells, MNC, or a placebo. Patients underwent gated single photon emission computed tomography assessments at 6 and 18 months post-intramyocardial transplantation. We tested the normally distributed efficacy outcomes with a mixed analysis of variance model that used the entire data set of baseline and between-group comparisons as well as within subject (time) and group�time interaction terms. Results: There were no related serious adverse events reported. The intramyocardial transplantation of both cell types increased left ventricular ejection fraction by 9 95% confidence intervals (CI): 2.14% to 15.78%, P=0.01 and improved decreased systolic wall thickening by -3.7 (95% CI: -7.07 to -0.42, P=0.03). The CD133 group showed significantly decreased non-viable segments by 75% (P=0.001) compared to the placebo and 60% (P=0.01) compared to the MNC group. We observed this improvement at both the 6- and 18-month time points. Conclusion: Intramyocardial injections of CD133+ cells or MNCs appeared to be safe and efficient with superiority of CD133+ cells for patients with RMI. Although the sample size precluded a definitive statement about clinical outcomes, these results have provided the basis for larger studies to confirm definitive evidence about the efficacy of these cell types (Registration Number: NCT01167751). © 2018 Royan Institute (ACECR). All Rights Reserved