Mobilizing Endogenous Progenitor Cells Using pSDF1α-Activated Scaffolds Accelerates Angiogenesis and Bone Repair in Critical-Sized Bone Defects.

Mobilizing endogenous progenitor cells to repair damaged tissue in situ has the potential to revolutionize the field of regenerative medicine, while the early establishment of a vascular network will ensure survival of newly generated tissue. In this study, a gene-activated scaffold containing a stromal derived factor 1α plasmid (pSDF1α), a pro-angiogenic gene that is also thought to be involved in the recruitment of mesenchymal stromal cells (MSCs) to sites of injury is described. It is shown that over-expression of SDF1α protein enhanced MSC recruitment and induced vessel-like structure formation by endothelial cells in vitro.

Dual Glyoxalase-1 and β-Klotho Gene-Activated Scaffold Reduces Methylglyoxal and Reprograms Diabetic Adipose-Derived Stem Cells: Prospects in Improved Wound Healing.

Tissue engineering approaches aim to provide biocompatible scaffold supports that allow healing to progress often in healthy tissue. In diabetic foot ulcers (DFUs), hyperglycemia impedes ulcer regeneration, due to complications involving accumulations of cellular methylglyoxal (MG), a key component of oxidated stress and premature cellular aging which further limits repair. In this study, we aim to reduce MG using a collagen-chondroitin sulfate gene-activated scaffold (GAS) containing the glyoxalase-1 gene (GLO-1) to scavenge MG and anti-fibrotic β-klotho to restore stem cell activity in diabetic adipose-derived stem cells (dADSCs).

Dual delivery gene-activated scaffold directs fibroblast activity and keratinocyte epithelization.

Fibroblasts are the most abundant cell type in dermal skin and keratinocytes are the most abundant cell type in the epidermis; both play a crucial role in wound remodeling and maturation. We aim to assess the functionality of a novel dual gene activated scaffold (GAS) on human adult dermal fibroblasts (hDFs) and see how the secretome produced could affect human dermal microvascular endothelial cells (HDMVECs) and human epidermal keratinocyte (hEKs) growth and epithelization. Our GAS is a collagen chondroitin sulfate scaffold loaded with pro-angiogenic stromal derived factor (SDF-1α) and/or an anti-aging β-Klotho plasmids.

Longitudinal Analysis of Respiratory Function of Different Types of Limb Girdle Muscular Dystrophies Reveals Independent Trajectories.

Background And Objectives: The prevalence and progression of respiratory muscle dysfunction in patients with limb girdle muscular dystrophies (LGMDs) has been only partially described to date. Most reports include cross-sectional data on a limited number of patients making it difficult to gain a wider perspective on respiratory involvement throughout the course of the disease and to compare the most prevalent LGMD subtypes.

Methods: We reviewed the results of spirometry studies collected longitudinally in our cohort of patients in routine clinical visits from 2002 to 2020 along with additional clinical and genetic data.

High-Depth PRNP Sequencing in Brains With Sporadic Creutzfeldt-Jakob Disease.

Background And Objectives: Sporadic Creutzfeldt-Jakob disease (sCJD) has established genetic risk factors, but, in contrast to genetic and acquired CJD, the initial trigger for misfolded prion aggregation and spread is not known. In this study, we tested the hypotheses that pathologic somatic variants in the prion gene are increased in sCJD, potentially leading to the seeding of misfolded prion protein.

Methods: High-depth amplicon-based short read sequencing of the coding region was performed on postmortem brain tissue from patients with a clinical and neuropathologic diagnosis of sCJD (n = 142), Alzheimer disease (AD) (n = 51) and controls with no clinical or neuropathologic diagnosis of a neurodegenerative disease (n = 71).

Anti-Aging β-Klotho Gene-Activated Scaffold Promotes Rejuvenative Wound Healing Response in Human Adipose-Derived Stem Cells.

Wound healing requires a tight orchestration of complex cellular events. Disruption in the cell-signaling events can severely impair healing. The application of biomaterial scaffolds has shown healing potential; however, the potential is insufficient for optimal wound maturation.

SDF-1α gene-activated collagen scaffold enhances provasculogenic response in a coculture of human endothelial cells with human adipose-derived stromal cells.

Novel biomaterials can be used to provide a better environment for cross talk between vessel forming endothelial cells and wound healing instructor stem cells for tissue regeneration. This study seeks to investigate if a collagen scaffold containing a proangiogenic gene encoding for the chemokine stromal-derived factor-1 alpha (SDF-1α GAS) could be used to enhance functional responses in a coculture of human umbilical vein endothelial cells (HUVECs) and human adipose-derived stem/stromal cells (ADSCs). Functional responses were determined by (1) monitoring the amount of junctional adhesion molecule VE-cadherin released during 14 days culture, (2) expression of provasculogenic genes on the 14th day, and (3) the bioactivity of secreted factors on neurogenic human Schwann cells.

SDF-1α Gene-Activated Collagen Scaffold Restores Pro-Angiogenic Wound Healing Features in Human Diabetic Adipose-Derived Stem Cells.

Non-healing diabetic foot ulcers (DFUs) can lead to leg amputation in diabetic patients. Autologous stem cell therapy holds some potential to solve this problem; however, diabetic stem cells are relatively dysfunctional and restrictive in their wound healing abilities. This study sought to explore if a novel collagen-chondroitin sulfate (coll-CS) scaffold, functionalized with polyplex nanoparticles carrying the gene encoding for stromal-derived factor-1 alpha (SDF-1α gene-activated scaffold), can enhance the regenerative functionality of human diabetic adipose-derived stem cells (ADSCs).

SDF-1α gene-activated collagen scaffold drives functional differentiation of human Schwann cells for wound healing applications.

Enhancing angiogenesis is the prime target of current biomaterial-based wound healing strategies. However, these approaches largely overlook the angiogenic role of the cells of the nervous system. Therefore, we explored the role of a collagen-chondroitin sulfate scaffold functionalized with a proangiogenic gene stromal-derived factor-1α (SDF-1α)-an SDF-1α gene-activated scaffold on the functional regulation of human Schwann cells (SCs).

Disappearing "Myxoma": Left Atrial Thrombus Masquerading as a Myxoma.

Intracardiac masses can be challenging to differentiate by echocardiography. We present a case of several intracardiac masses with echocardiographic features of both thrombi and myxoma in a patient with heart failure symptoms. The masses were confirmed to be thrombi after complete resolution on repeat echocardiography following anticoagulation.

Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity.

The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once.

Characterization of BRCA1 and BRCA2 genetic variants in a cohort of Bahraini breast cancer patients using next-generation sequencing.

Background: Breast cancer is the most common malignancy in women worldwide. About 5%-10% are due to hereditary predisposition. The contribution of BRCA1/2 mutations to familial breast cancer in Bahrain has not been explored.

A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity.

The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls.

Germline selection shapes human mitochondrial DNA diversity.

Approximately 2.4% of the human mitochondrial DNA (mtDNA) genome exhibits common homoplasmic genetic variation. We analyzed 12,975 whole-genome sequences to show that 45.

High prevalence of focal and multi-focal somatic genetic variants in the human brain.

Somatic mutations during stem cell division are responsible for several cancers. In principle, a similar process could occur during the intense cell proliferation accompanying human brain development, leading to the accumulation of regionally distributed foci of mutations. Using dual platform >5000-fold depth sequencing of 102 genes in 173 adult human brain samples, we detect and validate somatic mutations in 27 of 54 brains.

Frequency and signature of somatic variants in 1461 human brain exomes.

Purpose: To systematically study somatic variants arising during development in the human brain across a spectrum of neurodegenerative disorders.

Methods: In this study we developed a pipeline to identify somatic variants from exome sequencing data in 1461 diseased and control human brains. Eighty-eight percent of the DNA samples were extracted from the cerebellum.

Somatic variants in autosomal dominant genes are a rare cause of sporadic Alzheimer's disease.

Introduction: A minority of patients with sporadic early-onset Alzheimer's disease (AD) exhibit de novo germ line mutations in the autosomal dominant genes such as APP, PSEN1, or PSEN2. We hypothesized that negatively screened patients may harbor somatic variants in these genes.

Methods: We applied an ultrasensitive approach based on single-molecule molecular inversion probes followed by deep next generation sequencing of 11 genes to 100 brain and 355 blood samples from 445 sporadic patients with AD (>80% exhibited an early onset, <66 years).

Effect of Gum Arabic (Acacia Senegal) supplementation on visceral adiposity index (VAI) and blood pressure in patients with type 2 diabetes mellitus as indicators of cardiovascular disease (CVD): a randomized and placebo-controlled clinical trial.

Background: There is a strong association between cardiometabolic risk and adipose tissue dysfunction with great consequences on type 2 diabetic patients. Visceral Adiposity Index (VAI) is an indirect clinical marker of adipose tissue dysfunction. Gum Arabic (GA) is a safe dietary fiber, an exudate of Acacia Senegal.

Pro-angiogenic impact of SDF-1α gene-activated collagen-based scaffolds in stem cell driven angiogenesis.

Ensuring an adequate angiogenic response during wound healing is a prevailing clinical challenge in biomaterials science. To address this, we aimed to develop a pro-angiogenic gene-activated scaffold (GAS) that could activate MSCs to produce paracrine factors and influence angiogenesis and wound repair. A non-viral polyethyleneimine (PEI) nanoparticles carrying a gene encoding for stromal derived factor-1 alpha (SDF-1α) was combined with a collagen-chondroitin sulfate scaffold to produce the GAS.

Oligogenic genetic variation of neurodegenerative disease genes in 980 postmortem human brains.

Background: Several studies suggest that multiple rare genetic variants in genes causing monogenic forms of neurodegenerative disorders interact synergistically to increase disease risk or reduce the age of onset, but these studies have not been validated in large sporadic case series.

Methods: We analysed 980 neuropathologically characterised human brains with Alzheimer's disease (AD), Parkinson's disease-dementia with Lewy bodies (PD-DLB), frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) and age-matched controls. Genetic variants were assessed using the American College of Medical Genetics criteria for pathogenicity.

Innovations in gene and growth factor delivery systems for diabetic wound healing.

The rise in lower extremity amputations due to nonhealing of foot ulcers in diabetic patients calls for rapid improvement in effective treatment regimens. Administration of growth factors (GFs) are thought to offer an off-the-shelf treatment; however, the dose- and time-dependent efficacy of the GFs together with the hostile environment of diabetic wound beds impose a major hindrance in the selection of an ideal route for GF delivery. As an alternative, the delivery of therapeutic genes using viral and nonviral vectors, capable of transiently expressing the genes until the recovery of the wounded tissue offers promise.