Role of arterial stiffness and endothelial dysfunction on lower limb performance in older adults with type 2 diabetes: A cross-sectional study

AimTo verify whether arterial stiffness and endothelial dysfunction influence lower limb muscle strength and gait speed in older adults with type 2 diabetes mellitus (T2DM).MethodsCross-sectional study including seventy-eight older adults with T2DM (aged 67 ± 6 years and 42 % male). Arterial stiffness was assessed using pulse wave velocity (PWV), while endothelial function was measured by flow-mediated dilation (FMD). Lower limb muscle strength and gait speed were assessed using the 30-second chair stand test (30s-CST) and 10-Meter Walk Test, respectively.ResultsBoth PWV (m/s) and FMD (%) were univariately associated with number of repetitions in 30s-CST and gait speed (P < 0.05). After control for age, sex and body mass index, PWV remained associated with repetitions in 30s-CST (95 % CI: ?0.494 to ?0.054; P = 0.015) and gait speed (95 % CI: ?0.039 to ?0.002; P = 0.031). After adjustments for control variables, T2DM duration and glycemic control, FMD was associated with repetitions in 30s-CST (95 % CI: 0.008 to 0.324; P = 0.039) and gait speed (95 % CI: 0.011 to 0.038; P = 0.001).ConclusionIn older adults with T2DM, both arterial stiffness and endothelial dysfunction are associated with decreased leg muscle strength and slower gait speed.     

Prevention of alloimmune rejection using XBP1-deleted bone marrow-derived dendritic cells in heart transplantation

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A case of sudden cardiac death due to mitochondrial disease

A 25-year-old, emaciated man without medical treatment was found to have died suddenly at home by his mother. At autopsy, there were no injuries to his body, but significant circulatory insufficiency was observed. Electron microscopy revealed abnormal mitochondria in cells of the cardiac conduction system. The conduction system was filled with mitochondrial size abnormalities and mitochondrial cristae abnormalities. No notable abnormal findings were observed in other organs. Genetic examination of the blood revealed the mitochondrial pathogenetic variant m.3243A>G. Epileptic seizures, diabetic ketoacidosis, and hyperosmolar hyperglycemic state were unlikely to be the cause of sudden death. The cause of death was diagnosed as arrhythmia possibly induced by the failure of the cardiac conduction system due to mitochondrial disease. This is a rare case of sudden death caused by an accumulation of abnormal mitochondria in the cardiac conduction system.     

CD19 + CD21lo/neg cells are increased in systemic sclerosis-associated interstitial lung disease

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21^lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21^lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21^lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21^lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.

     

Adjunctive therapies for in vitro carious lesions: Antimicrobial activity,activation of dentin metalloproteinases and effects on dental pulp cells

BackgroundAdjunctive therapies used before dental restorative procedures may encourage carious tissue removal. Beyond promising antimicrobial properties, treatments could positively modulate the dentin-pulp complex while not interfering with restoration survival. Herein, we evaluated a set of substances and their effects on carious lesions and the underlying dentin or pulp cells.MethodsArtificial caries lesions were developed in bovine teeth cavities immersed in Streptococcus mutans and Lactobacillus casei co-cultures. The cavities were treated according to the following groups: Phosphate Buffer Saline (PBS), Chlorhexidine (CHX), Papacárie® (Papain gel), Ozone (O₃), and antimicrobial Photodynamic Therapy (aPDT). After treatments, samples were cultivated to count isolated microbial colonies. The zymography assay evaluated the activity of dentin metalloproteinases (MMP-2 and MMP-9). Cell viability was indirectly assessed on human dental pulp cells after 24, 72, or 120 h, whereas the odontodifferentiation potential was evaluated after ten days of cell culture.ResultsCHX and aPDT led to around 1 log bacterial load reduction. PBS, CHX, and aPDT showed the eventual expression of MMP-2 and MMP-9. Cell viability was reduced (< 30%) after 120 h for all groups compared to the control. CHX, O3, and aPDT induced greater odontodifferentiation (≈ 20% higher) than PBS and papain gel.ConclusionAdjunctive therapies presented little or no biological significance in reducing bacterial load in artificial carious lesions. Although the activation of endogenous metalloproteinases may represent a possible concern for adhesive restorations, some of these treatments may have a positive role in dental pulp tissue repair.     

Integrative Expression,Survival Analysis and Cellular miR-2909 Molecular Interplay in MRN Complex Check Point Sensor Genes (MRN-CSG) Involved in Breast Cancer

BackgroundBreast cancer, an emerging global challenge, is evidenced by recent studies of miRNAs involvement in DNA repair gene variants (MRE11, RAD50, and NBN as checkpoint sensor genes (CSG) – MRN-CSG). The identification of various mutations in MRN-CSG and their interactions with miRNAs is still not understood. The emerging studies of miR-2909 involvement in other cancers led us to explore its role as molecular mechanistic marker in breast cancer.Materials and MethodsThe genomic and proteomic data of MRN-CSG of breast cancer patients (8426 samples) was evaluated to identify the mutation types linked with the patient's survival rate. Additionally, molecular, 3D-structural and functional analysis was performed to identify miR-2909 as regulator of MRN-CSG.ResultsThe genomic and proteomic data analysis shows genetic alterations with majority of missense mutations [RAD50 (0.7%), MRE11 (1.5%), and NBN (11%)], though with highest MRE11 mRNA expression in invasive ductal breast carcinoma as compared to other breast cancer types. The Kaplan–Meier survival curves suggest higher survival rate for unaltered groups as compared to the altered group. Network analysis and disease association of miR-2909 and MRN-CSG shows strong interactions with other partners. The molecular hybridization between miR-2909-RAD50 and miR-2909-MRE11 complexes showed thermodynamically stable structures. Further, argonaute protein, involved in RNA silencing, docking studies with miR-MRE11-mRNA and miR-RAD50-mRNA hybridized complexes showed strong binding affinity.ConclusionThe results suggest that miR-2909 forms strong thermodynamically stable molecular hybridized complexes with MRE11 and RAD50 mRNAs which further strongly interacts with argonaute protein to show potential molecular mechanistic role in breast cancer.