Bioprinting of freestanding vascular grafts and the regulatory considerations for additively manufactured vascular prostheses.
Abstract Vasculature is the network of blood vessels of an organ or body part that allow for the exchange of nutrients and waste to and from every cell, thus establishing a circulatory equilibrium. Vascular health is at risk from a variety of conditions that includes disease and trauma. In some cases, medical therapy can alleviate the impacts of the condition. Intervention is needed in other instances to restore the health of abnormal vasculature. The main approaches to treat vascular conditions are endovascular procedures and open vascular reconstruction that often requires a graft to accomplish. However, current...
Source: Translational Research : the journal of laboratory and clinical medicine - June 3, 2019 Category: Laboratory Medicine Authors: Abdollahi S, Boktor J, Hibino N Tags: Transl Res Source Type: research

Noninvasive glucose detection in exhaled breath condensate.
Abstract Two-thirds of patients with diabetes avoid regularly monitoring their blood glucose levels because of the painful and invasive nature of current blood glucose detection. As an alternative to blood sample collection, exhaled breath condensate (EBC) has emerged as a promising noninvasive sample from which to monitor glucose levels. However, this dilute sample matrix requires sensors capable of detecting glucose with high resolution at nanomolar and micromolar concentrations. Recent developments in EBC collection methods and highly sensitive glucose biosensors provide a path toward enabling robust and sensit...
Source: Translational Research : the journal of laboratory and clinical medicine - May 30, 2019 Category: Laboratory Medicine Authors: Tankasala D, Linnes JC Tags: Transl Res Source Type: research

IMM-H004 therapy for permanent focal ischemic cerebral injury via CKLF1/CCR4-mediated NLRP3 inflammasome activation.
This study aims to investigate the effects of IMM-H004 on ischemia stroke injury and further elucidate the molecular mechanisms. The standard pMCAO model of focal ischemia was used in this paper. Drugs were administered at 6 hours after ischemia, and behavioral assessment, euthanasia, and outcome measures were evaluated at 9 hours after ischemia. The effects of IMM-H004 on ischemic stroke injury were determined using 2,3,5-triphenyltetrazolium chloride (TTC) staining, behavioral tests, enzyme-linked immunosorbent assay (ELISA), and Nissl staining. Immunohistologic staining, immunofluorescence staining, quantitative RT-PCR ...
Source: Translational Research : the journal of laboratory and clinical medicine - May 30, 2019 Category: Laboratory Medicine Authors: Ai QD, Chen C, Chu S, Zhang Z, Luo Y, Guan F, Lin M, Liu D, Wang S, Chen N Tags: Transl Res Source Type: research

Biofabrication of thick vascularized neo-pedicle flaps for reconstructive surgery.
Abstract Wound chronicity due to intrinsic and extrinsic factors perturbs adequate lesion closure and reestablishment of the protective skin barrier. Immediate and proper care of chronic wounds is necessary for a swift recovery and a reduction of patient vulnerability to infection. Advanced therapies supplemented with standard wound care procedures have been clinically implemented to restore aberrant tissue; however, these treatments are ineffective if local vasculature is too compromised to support minimally-invasive strategies. Autologous "flaps", which are tissues equipped with their own hierarchical ...
Source: Translational Research : the journal of laboratory and clinical medicine - May 21, 2019 Category: Laboratory Medicine Authors: Stephens CJ, Spector JA, Butcher JT Tags: Transl Res Source Type: research

Biosensors for detection of human placental pathologies: a review of emerging technologies and current trends.
This article presents an overview of the research in the field of biosensors that can potentially predict and diagnose common placental pathologies. A survey of biomarkers in maternal circulation and their characterization methods is presented, including markers of oxidative stress, angiogenic factors, placental debris, and inflammatory biomarkers that are associated with various pathophysiological processes in the context of pregnancy complications. Novel biosensors enabled by microfluidics technology and nanomaterials are then reviewed. Representative designs of plasmonic and electrochemical biosensors for highly sensiti...
Source: Translational Research : the journal of laboratory and clinical medicine - May 20, 2019 Category: Laboratory Medicine Authors: Liu J, Mosavati B, Oleinikov A, Du E Tags: Transl Res Source Type: research

Characterization of upregulated adhesion GPCRs in acute myeloid leukemia.
Abstract The role of adhesion G protein-coupled receptors (aGPCRs) in cancer has become increasingly evident in recent years. Yet, data supporting the contribution of this family of genes to hematological malignancies, particularly acute myeloid leukemia (AML) are limited. Here, we use publicly available genomic data to characterize the expression of the 33 aGPCRs in patients with AML and examine whether upregulation of these genes is associated with the clinical and molecular characteristics of patients. Upregulation in one or more of 8 aGPCR genes (ADGRB1, CELSR2, ADGRD1, ADGRE1, ADGRE2, ADGRE5, ADGRG1, and ADGR...
Source: Translational Research : the journal of laboratory and clinical medicine - May 17, 2019 Category: Laboratory Medicine Authors: Yang J, Wu S, Alachkar H Tags: Transl Res Source Type: research

3D bioprinting for lungs and hollow organs.
Abstract Three-dimensional bioprinting has been gaining attention as a potential method for creating biological tissues, supplementing the current arsenal of tissue engineering techniques. 3D bioprinting raises the possibility of reproducibly creating complex macro- and microscale architectures using multiple different cell types. This is promising for creation of multilayered hollow organs, which has been challenging using more traditional tissue engineering techniques. In this review, the state of the field in bioprinting of epithelialized hollow and tubular organs is discussed. Most of the progress for the pulm...
Source: Translational Research : the journal of laboratory and clinical medicine - May 14, 2019 Category: Laboratory Medicine Authors: Galliger Z, Vogt CD, Panoskaltsis-Mortari A Tags: Transl Res Source Type: research

Pigment epithelium-derived factor inhibits adipogenesis in 3T3-L1 adipocytes and protects against high-fat diet-induced obesity and metabolic disorders in mice.
Abstract Obesity is a major cause of metabolic syndrome and type II diabetes, and it presents with metabolic disorders, such as hyperglycemia, hyperlipidemia, and insulin resistance. Pigment epithelium-derived factor (PEDF), a protein isolated from retinal pigment epithelial cells, has multiple functions, including neuronal protection, antineoplastic effects, and anti-inflammatory activity. The aim of this study is to investigate the antiobesity effects of PEDF. The antiobesity effects of PEDF on fat accumulation, inflammation, energy expenditure, insulin resistance, and obesity-related physiological parameters an...
Source: Translational Research : the journal of laboratory and clinical medicine - May 3, 2019 Category: Laboratory Medicine Authors: Chen CC, Lee TY, Leu YL, Wang SH Tags: Transl Res Source Type: research

Targeting neutrophil extracellular traps enhanced tPA fibrinolysis for experimental intracerebral hemorrhage.
Abstract The minimally invasive surgery plus fibrinolysis has been identified as a promising treatment for spontaneous intracerebral hemorrhage (ICH). However, the fibrinolytic efficacy is not satisfactory. Neutrophil extracellular traps (NETs) have been demonstrated to impair fibrinolysis in sepsis and acute ischemic stroke. Therefore, we decided to explore the presence and potential effect of NETs in ICH fibrinolysis. Intracerebral hemorrhage was induced by autologous arterial blood injection into the basal ganglia in rats. First, at 0.5 hour, 1 hour, and 1.5 hours after blood injection, the brains were collecte...
Source: Translational Research : the journal of laboratory and clinical medicine - April 30, 2019 Category: Laboratory Medicine Authors: Tan Q, Guo P, Zhou J, Zhang J, Zhang B, Lan C, Xian J, Ge M, Feng H, Chen Z Tags: Transl Res Source Type: research

De novo lung biofabrication: clinical need, construction methods, and design strategy.
Abstract Chronic lung disease is the 4th leading cause of death in the United States. Due to a shortage of donor lungs, alternative approaches to support failing, native lungs have been attempted, including mechanical ventilation and various forms of artificial lungs. However, each of these support methods causes significant complications when used for longer than a few days and are thus not capable of long-term support. For artificial lungs, complications arise due to interactions between the artificial materials of the device and the blood of the recipient. A potential new approach is the fabrication of lungs fr...
Source: Translational Research : the journal of laboratory and clinical medicine - April 29, 2019 Category: Laboratory Medicine Authors: Comber EM, Palchesko RN, Ng WH, Ren X, Cook KE Tags: Transl Res Source Type: research

Blood outgrowth endothelial cells overexpressing eNOS mitigate pulmonary hypertension in rats: a unique carrier cell enabling autologous cell-based gene therapy.
Abstract We have investigated a unique cell type, blood outgrowth endothelial cells (BOEC), as a cell-based gene therapy approach to pulmonary hypertension. BOEC are bona fide endothelial cells, obtained from peripheral blood, that can be expanded to vast numbers, and are amenable to both cryopreservation and genetic modification. We established primary cultures of rat BOEC and genetically altered them to over-express human eNOS plus green fluorescent protein (rBOEC/eNOS) or to express GFP only (rBOEC/GFP). We gave monocrotaline to rats on day 0, and they developed severe pulmonary hypertension. As a Prevention mo...
Source: Translational Research : the journal of laboratory and clinical medicine - April 24, 2019 Category: Laboratory Medicine Authors: Somani A, Nair SL, Milbauer LC, Zhu G, Sajja S, Solovey A, Chen Y, Hebbel RP Tags: Transl Res Source Type: research

Emerging strategies to disrupt the central TGF- β axis in kidney fibrosis.
Emerging strategies to disrupt the central TGF-β axis in kidney fibrosis. Transl Res. 2019 Apr 24;: Authors: Rauchman M, Griggs D Abstract Chronic kidney disease (CKD) affects more than 20 million people in the United States and the global burden of this disorder is increasing. Many affected individuals will progress to end stage kidney disease necessitating dialysis or transplantation. CKD is also a major independent contributor to the risk of cardiovascular morbidity and mortality. Tubulointerstitial fibrosis is a final common pathway for most causes of progressive CKD. Currently, there are no ...
Source: Translational Research : the journal of laboratory and clinical medicine - April 24, 2019 Category: Laboratory Medicine Authors: Rauchman M, Griggs D Tags: Transl Res Source Type: research

Bone marrow-liver-thymus (BLT) immune humanized mice as a model to predict cytokine release syndrome.
This study demonstrates that BLT-humanized mice are capable of experiencing CRS, and could be used to screen biologics for this adverse event to enhance patient safety. PMID: 31082370 [PubMed - as supplied by publisher] (Source: Translational Research : the journal of laboratory and clinical medicine)
Source: Translational Research : the journal of laboratory and clinical medicine - April 22, 2019 Category: Laboratory Medicine Authors: Yan H, Semple KM, Gonzaléz CM, Howard KE Tags: Transl Res Source Type: research

Noninvasive assessment of renal fibrosis by magnetic resonance imaging and ultrasound techniques.
Abstract Renal fibrosis is a useful biomarker for diagnosis and guidance of therapeutic interventions of chronic kidney disease (CKD), a worldwide disease that affects more than 10% of the population and is one of the major causes of death. Currently, tissue biopsy is the gold standard for assessment of renal fibrosis. However, it is invasive, and prone to sampling error and observer variability, and may also result in complications. Recent advances in diagnostic imaging techniques, including magnetic resonance imaging (MRI) and ultrasonography, have shown promise for noninvasive assessment of renal fibrosis. Thes...
Source: Translational Research : the journal of laboratory and clinical medicine - April 22, 2019 Category: Laboratory Medicine Authors: Jiang K, Ferguson CM, Lerman LO Tags: Transl Res Source Type: research

Pan-cancer genomic amplifications underlie a WNT hyperactivation phenotype associated with stem cell-like features leading to poor prognosis.
Abstract Cancer stem cells pose significant obstacles to curative treatment contributing to tumor relapse and poor prognosis. They share many signaling pathways with normal stem cells that control cell proliferation, self-renewal, and cell fate determination. One of these pathways known as Wnt is frequently implicated in carcinogenesis where Wnt hyperactivation is seen in cancer stem cells. Yet, the role of conserved genomic alterations in Wnt genes driving tumor progression across multiple cancer types remains to be elucidated. In an integrated pan-cancer study involving 21 cancers and 18,484 patients, we identif...
Source: Translational Research : the journal of laboratory and clinical medicine - April 22, 2019 Category: Laboratory Medicine Authors: Chang WH, Lai AG Tags: Transl Res Source Type: research

Recent advances in 3D printing: vascular network for tissue and organ regeneration.
Abstract Over the past years, the fabrication of adequate vascular networks has remained the main challenge in engineering tissues due to technical difficulties, while the ultimate objective of tissue engineering is to create fully functional and sustainable organs and tissues to transplant in the human body. There have been a number of studies performed to overcome this limitation, and as a result, 3D printing has become an emerging technique to serve in a variety of applications in constructing vascular networks within tissues and organs. 3D printing incorporated technical approaches allow researchers to fabrica...
Source: Translational Research : the journal of laboratory and clinical medicine - April 5, 2019 Category: Laboratory Medicine Authors: Hann SY, Cui H, Esworthy T, Miao S, Zhou X, Lee SJ, Fisher JP, Zhang LG Tags: Transl Res Source Type: research

Exosomes on the border of species and kingdom intercommunication.
Abstract Over the last decades exosomes have become increasingly popular in the field of medicine. While until recently they were believed to be involved in the removal of obsolete particles from the cell, it is now known that exosomes are key players in cellular communication, carrying source-specific molecules such as proteins, growth factors, miRNA/mRNA, among others. The discovery that exosomes are not bound to intraspecies interactions, but are also capable of interkingdom communication, has once again revolutionized the field of exosomes research. A rapidly growing body of literature is shedding light at nov...
Source: Translational Research : the journal of laboratory and clinical medicine - March 29, 2019 Category: Laboratory Medicine Authors: Schuh CMAP, Cuenca J, Alcayaga-Miranda F, Khoury M Tags: Transl Res Source Type: research

Cellular senescence and radiation-induced pulmonary fibrosis.
Abstract Radiation-induced pulmonary fibrosis (RIPF) is a serious treatment complication that affects about 9%-30% cancer patients receiving radiotherapy for thoracic tumors. RIPF is characterized by progressive and irreversible destruction of lung tissues and deterioration of lung function, which can compromise quality of life and eventually lead to respiratory failure and death. Unfortunately, the mechanisms by which radiation causes RIPF have not been well established nor has an effective treatment for RIPF been developed. Recently, an increasing body of evidence suggests that induction of senescence by radiati...
Source: Translational Research : the journal of laboratory and clinical medicine - March 27, 2019 Category: Laboratory Medicine Authors: He Y, Thummuri D, Zheng G, Okunieff P, Citrin DE, Vujaskovic Z, Zhou D Tags: Transl Res Source Type: research

Pathogenesis of fibrostenosing Crohn's disease.
Abstract Crohn's disease (CD) is a chronic inflammatory disease, which could affect any part of the gastrointestinal tract. A severe complication of CD is fibrosis-associated strictures, which can cause bowel obstruction. Unfortunately, there is no specific antifibrotic therapy available. More than 80% of the patients with CD will have to undergo at least 1 surgery in their life and recurrence of strictures after surgery is common. Investigations on the mechanism of fibrostenosing CD have revealed that fibrosis is mainly driven by expansion of mesenchymal cells including fibroblasts, myofibroblasts, and smooth mus...
Source: Translational Research : the journal of laboratory and clinical medicine - March 26, 2019 Category: Laboratory Medicine Authors: Li J, Mao R, Kurada S, Wang J, Lin S, Chandra J, Rieder F Tags: Transl Res Source Type: research

Mechanisms of cardiac collagen deposition in experimental models and human disease.
Abstract The inappropriate deposition of extracellular matrix within the heart (termed cardiac fibrosis) is associated with nearly all types of heart disease, including ischemic, hypertensive, diabetic, and valvular. This alteration in the composition of the myocardium can physically limit cardiomyocyte contractility and relaxation, impede electrical conductivity, and hamper regional nutrient diffusion. Fibrosis can be grossly divided into 2 types, namely reparative (where collagen deposition replaces damaged myocardium) and reactive (where typically diffuse collagen deposition occurs without myocardial damage). D...
Source: Translational Research : the journal of laboratory and clinical medicine - March 26, 2019 Category: Laboratory Medicine Authors: Cowling RT, Kupsky D, Kahn AM, Daniels LB, Greenberg BH Tags: Transl Res Source Type: research

Partial remission and early stages of pediatric type 1 diabetes display immunoregulatory changes. A pilot study.
This study aims to identify new biomarkers at early stages of pediatric T1D that reflect immunoregulatory changes. To that end, pediatric patients with T1D (n = 52) and age-related control subjects (n = 30) were recruited. Immune response-related molecules and lymphocyte subsets were determined starting at T1D onset and until the second year of progression. Results showed that circulating TGF-β levels decreased during PR, and that betatrophin concentration was increased in all the considered stages without differing among studied checkpoints. Moreover, an increase of regulatory T, B and NK subsets was found du...
Source: Translational Research : the journal of laboratory and clinical medicine - March 15, 2019 Category: Laboratory Medicine Authors: Villalba A, Fonolleda M, Murillo M, Rodriguez-Fernandez S, Ampudia RM, Perna-Barrull D, Raina MB, Quirant-Sanchez B, Planas R, Teniente-Serra A, Bel J, Vives-Pi M Tags: Transl Res Source Type: research

Immunomodulatory roles of nitric oxide in cancer: tumor microenvironment says "NO" to antitumor immune response.
Immunomodulatory roles of nitric oxide in cancer: tumor microenvironment says "NO" to antitumor immune response. Transl Res. 2019 Mar 15;: Authors: Peñarando J, Aranda E, Rodríguez-Ariza A Abstract In recent years, an increasing number of studies have shown that there is an important connection between nitric oxide (NO) and the pathology of malignant diseases, but we are far from a complete comprehension of how this simple diatomic molecule contributes to tumorigenesis. The emerging identification of immune-mediated mechanisms regulated by NO may help to unravel the intricate a...
Source: Translational Research : the journal of laboratory and clinical medicine - March 15, 2019 Category: Laboratory Medicine Authors: Peñarando J, Aranda E, Rodríguez-Ariza A Tags: Transl Res Source Type: research

Cardiac fibrosis: potential therapeutic targets.
Abstract Cardiovascular disease is a leading cause of mortality in the world and is exacerbated by the presence of cardiac fibrosis, defined by the accumulation of noncontractile extracellular matrix proteins. Cardiac fibrosis is directly linked to cardiac dysfunction and increased risk of arrhythmia. Despite its prevalence, there is a lack of efficacious therapies for inhibiting or reversing cardiac fibrosis, largely due to the complexity of the cell types and signaling pathways involved. Ongoing research has aimed to understand the mechanisms of cardiac fibrosis and develop new therapies for treating scar format...
Source: Translational Research : the journal of laboratory and clinical medicine - March 9, 2019 Category: Laboratory Medicine Authors: Park S, Nguyen NB, Pezhouman A, Ardehali R Tags: Transl Res Source Type: research

Role of adherens junctions and apical-basal polarity of neural stem/progenitor cells in the pathogenesis of neurodevelopmental disorders: a novel perspective on congenital Zika syndrome.
, BÁtiz LF Abstract Radial glial cells (RGCs) are the neural stem/progenitor cells (NSPCs) that give rise to most of neurons and glial cells that constitute the adult central nervous system. A hallmark of RGCs is their polarization along the apical-basal axis. They extend a long basal process that contacts the pial surface and a short apical process to the ventricular surface. Adherens junctions (AJs) are organized as belt-like structures at the most-apical lateral plasma membrane of the apical processes. These junctional complexes anchor RGCs to each other and allow the recruitment of cytoplasmic proteins ...
Source: Translational Research : the journal of laboratory and clinical medicine - March 5, 2019 Category: Laboratory Medicine Authors: Bustamante FA, Miró MP, VelÁsquez ZD, Molina L, Ehrenfeld P, Rivera FJ, BÁtiz LF Tags: Transl Res Source Type: research

Epigenetic therapy of Prader-Willi syndrome.
Abstract Prader-Willi syndrome (PWS) is a complex and multisystem neurobehavioral disorder. The molecular mechanism of PWS is deficiency of paternally expressed genes from the chromosome 15q11-q13. Due to imprinted gene regulation, the same genes in the maternal chromosome 15q11-q13 are structurally intact but transcriptionally repressed by an epigenetic mechanism. The unique molecular defect underlying PWS renders an exciting opportunity to explore epigenetic-based therapy to reactivate the expression of repressed PWS genes from the maternal chromosome. Inactivation of H3K9m3 methyltransferase SETDB1 and zinc fin...
Source: Translational Research : the journal of laboratory and clinical medicine - March 5, 2019 Category: Laboratory Medicine Authors: Kim Y, Wang SE, Jiang YH Tags: Transl Res Source Type: research

Peptides derived from the extracellular domain of the somatostatin receptor splicing variant SST5TMD4 increase malignancy in multiple cancer cell types.
te MD Abstract Extracellular fragments derived from plasma membrane receptors can play relevant roles in the development/progression of tumor pathologies, thereby offering novel diagnostic or therapeutic opportunities. The truncated variant of somatostatin receptor subtype-5, SST5TMD4, is an aberrantly spliced receptor with 4 transmembrane domains, highly overexpressed in several tumor types, whose C-terminal tail is exposed towards the extracellular matrix, and could therefore be the substrate for proteolytic enzymes. In silico analysis implemented herein predicted 2 possible cleavage sites for metalloproteases M...
Source: Translational Research : the journal of laboratory and clinical medicine - March 2, 2019 Category: Laboratory Medicine Authors: Del Rio-Moreno M, Alors-Perez E, de Souza PB, Prados-Gonzalez ME, CastaÑo JP, Luque RM, Gahete MD Tags: Transl Res Source Type: research

Survival and prognostic factors in patients with gastrointestinal cancers and brain metastases: have we made progress?
Tandberg DD, Kirkpatrick JP, Shi D, Shih HA, Chuong M, Saito H, Aoyama H, Masucci L, Roberge D, Mehta MP Abstract The literature describing the prognosis of patients with gastrointestinal (GI) cancers and brain metastases (BM) is sparse. Our group previously published a prognostic index, the Graded Prognostic Assessment (GPA) for GI cancer patients with BM, based on 209 patients diagnosed from 1985-2005. The purpose of this analysis is to identify prognostic factors for GI cancer patients with newly diagnosed BM in a larger contemporary cohort. A multi-institutional retrospective IRB-approved database of 792 GI ca...
Source: Translational Research : the journal of laboratory and clinical medicine - February 27, 2019 Category: Laboratory Medicine Authors: Sperduto PW, Fang P, Li J, Breen W, Brown PD, Cagney D, Aizer A, Yu J, Chiang V, Jain S, Gaspar LE, Myrehaug S, Sahgal A, Braunstein S, Sneed P, Cameron B, Attia A, Molitoris J, Wu CC, Wang TJC, Lockney N, Beal K, Parkhurst J, Buatti JM, Shanley R, Lou E, Tags: Transl Res Source Type: research

Evolving insights into the cellular and molecular pathogenesis of fibrosis in systemic sclerosis.
Abstract Systemic sclerosis (SSc, scleroderma) is a complex multisystem disease characterized by autoimmunity, vasculopathy, and most notably, fibrosis. Multiple lines of evidence demonstrate a variety of emerging cellular and molecular pathways which are relevant to fibrosis in SSc. The myofibroblast remains the key effector cell in SSc. Understanding the development, differentiation, and function of the myofibroblast is therefore crucial to understanding the fibrotic phenotype of SSc. Studies now show that (1) multiple cell types give rise to myofibroblasts, (2) fibroblasts and myofibroblasts are heterogeneous, ...
Source: Translational Research : the journal of laboratory and clinical medicine - February 23, 2019 Category: Laboratory Medicine Authors: Korman B Tags: Transl Res Source Type: research

The double edge sword of fibrosis in cancer.
Abstract Cancer-associated fibrosis is a critical component of the tumor microenvironment (TME) which significantly impacts cancer behavior. However, there is significant controversy regarding fibrosis as a predominantly tumor promoting or tumor suppressing factor. Cells essential to the generation of tissue fibrosis such as fibroblasts and mesenchymal stem cells (MSCs) have dual phenotypes dependent upon their independence or association with cancer cells. Cancer-associated fibroblasts and cancer-associated MSCs have unique molecular profiles which facilitate cancer cell cross talk, influence extracellular matrix...
Source: Translational Research : the journal of laboratory and clinical medicine - February 21, 2019 Category: Laboratory Medicine Authors: Chandler C, Liu T, Buckanovich R, Coffman LG Tags: Transl Res Source Type: research

B-type natriuretic peptide enhances fibrotic effects via matrix metalloproteinase-2 expression in the mouse atrium in vivo and in human atrial myofibroblasts in vitro.
In this study, we investigated the direct effects of BNP on TNF-α-induced atrial fibrosis mice, as well as its effects on human atrial myofibroblasts. We found that injecting TNF-α-induced mice with recombinant human BNP enhanced atrial fibrosis via matrix metalloproteinase-2 (MMP-2) expression and collagen accumulation. Furthermore, we found that BNP stimulated MMP-2 expression in human atrial myofibroblasts. Treatment of human atrial myofibroblasts with cycloheximide had no effect on this outcome; however, treatment of cells with MG132 enhanced BNP-induced MMP-2 expression, indicating that protein stability a...
Source: Translational Research : the journal of laboratory and clinical medicine - February 19, 2019 Category: Laboratory Medicine Authors: Tsai YT, Lin FY, Lin CS, Loh SH, Li CY, Lin CY, Lin YW, Tsai CS Tags: Transl Res Source Type: research

Role of the intestinal microbiome in liver fibrosis development and new treatment strategies.
Abstract Liver cirrhosis is a major cause of morbidity and mortality worldwide. The most common chronic liver diseases in western countries are alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). Although these diseases have different causes, liver fibrosis develops via shared mechanisms. The liver and intestinal microbiome are linked by the portal vein and have bidirectional interactions. Changes in the intestinal microbiota are believed to contribute to the pathogenesis and progression of liver diseases including ALD, NAFLD, viral hepatitis, and cholestatic disorders, based on s...
Source: Translational Research : the journal of laboratory and clinical medicine - February 16, 2019 Category: Laboratory Medicine Authors: Zhou R, Fan X, Schnabl B Tags: Transl Res Source Type: research

Mutations in ILK, encoding integrin-linked kinase, are associated with arrhythmogenic cardiomyopathy.
Abstract Arrhythmogenic cardiomyopathy is a genetic heart muscle disorder characterized by fibro-fatty replacement of cardiomyocytes leading to life-threatening ventricular arrhythmias, heart failure, and sudden cardiac death. Mutations in genes encoding cardiac junctional proteins are known to cause about half of cases, while remaining genetic causes are unknown. Using exome sequencing, we identified 2 missense variants (p.H33N and p.H77Y) that were predicted to be damaging in the integrin-linked kinase (ILK) gene in 2 unrelated families. The p.H33N variant was found to be de novo. ILK links integrins and the act...
Source: Translational Research : the journal of laboratory and clinical medicine - February 15, 2019 Category: Laboratory Medicine Authors: Brodehl A, Rezazadeh S, Williams T, Munsie NM, Liedtke D, Oh T, Ferrier R, Shen Y, Jones SJM, Stiegler AL, Boggon TJ, Duff HJ, Friedman JM, Gibson WT, FORGE Canada Consortium, Childs SJ, Gerull B Tags: Transl Res Source Type: research

The Cellular basis of fibrotic tendon healing: challenges and opportunities.
Abstract Tendon injuries are common and can dramatically impair patient mobility and productivity, resulting in a significant socioeconomic burden and reduced quality of life. Because the tendon healing process results in the formation of a fibrotic scar, injured tendons never regain the mechanical strength of the uninjured tendon, leading to frequent reinjury. Many tendons are also prone to the development of peritendinous adhesions and excess scar formation, which further reduce tendon function and lead to chronic complications. Despite this, there are currently no treatments that adequately improve the tendon h...
Source: Translational Research : the journal of laboratory and clinical medicine - February 8, 2019 Category: Laboratory Medicine Authors: Nichols AEC, Best KT, Loiselle AE Tags: Transl Res Source Type: research

Ability of a urine gene expression classifier to reduce the number of follow-up cystoscopies in bladder cancer patients.
This study aimed to improve our previous urine gene expression classifiers focusing on the detection of non-high-risk non-muscle-invasive bladder cancer (NMIBC), and develop a new classifier able to decrease the frequency of cystoscopies during bladder cancer (BC) patients' surveillance. A total of 597 urines from BC patients, controls and patients in follow-up for BC (PFBC) were included. The study has 3 phases. In the urinary biomarker discovery phase, 84 urines from BC and control patients were retrospectively included and analyzed by RNA sequencing. In the classifier development phase, a total of 132 selected genes fro...
Source: Translational Research : the journal of laboratory and clinical medicine - February 7, 2019 Category: Laboratory Medicine Authors: Montalbo R, Lozano JJ, Izquierdo L, Ingelmo-Torres M, BaÑos C, Palou J, Van der Heijden AG, Medina R, Schmidbauer J, Prat A, Ribal MJ, Alcaraz A, Mengual L Tags: Transl Res Source Type: research

Translational research in pulmonary fibrosis.
Abstract Pulmonary fibrosis refers to the development of diffuse parenchymal abnormalities in the lung that cause dyspnea, cough, hypoxemia, and impair gas exchange, ultimately leading to respiratory failure. Though pulmonary fibrosis can be caused by a variety of underlying etiologies, ranging from genetic defects to autoimmune diseases to environmental exposures, once fibrosis develops it is irreversible and most often progressive, such that fibrosis of the lung is one of the leading indications for lung transplantation. This review aims to provide a concise summary of the recent advances in our understanding of...
Source: Translational Research : the journal of laboratory and clinical medicine - February 5, 2019 Category: Laboratory Medicine Authors: Mathai SK, Schwartz DA Tags: Transl Res Source Type: research

BM-MSCs-derived ECM modifies multiple myeloma phenotype and drug response in a source-dependent manner.
Abstract Multiple myeloma (MM) malignant plasma cells accumulate in the bone marrow (BM) where their interaction with the microenvironment promotes disease progression and drug resistance. Previously, we have shown that MM cells cocultured with BM-mesenchymal stem cells (MSCs) comodulated cells' phenotype in a MAPKs/translation initiation (TI)-dependent manner. Dissection of the coculture model showed that BM-MSCs secretomes and microvesicles (MVs) participate in this crosstalk. Here, we addressed the role of the BM-MSCs extracellular matrix (ECM). MM cell lines cultured on decellularized ECM of normal donors' (ND...
Source: Translational Research : the journal of laboratory and clinical medicine - January 23, 2019 Category: Laboratory Medicine Authors: Ibraheem A, Attar-Schneider O, Dabbah M, Dolberg Jarchowsky O, Tartakover Matalon S, Lishner M, Drucker L Tags: Transl Res Source Type: research

Selenium and selenoproteins: from endothelial cytoprotection to clinical outcomes.
Abstract The role of the vascular endothelium in inflammation was demonstrated experimentally through biomarkers of endothelial dysfunction and cytoprotection. Selenium is a trace element essential for cell protection against oxidative lesions triggered by reactive oxygen species or inflammatory responses. Preclinical studies have demonstrated a relationship between adhesion molecules as biomarkers of endothelial dysfunction and selenoproteins as biomarkers of selenium status under conditions that mimic different diseases. Most studies in humans indicate an association between selenium deficiency and increased ris...
Source: Translational Research : the journal of laboratory and clinical medicine - January 19, 2019 Category: Laboratory Medicine Authors: Junior EL, Leite HP, Konstantyner T Tags: Transl Res Source Type: research

Mast cell-deficiency protects mice from streptozotocin-induced diabetic cardiomyopathy.
Abstract Mast cells (MCs) have been implicated in the pathogenesis of cardiometabolic diseases by releasing pro-inflammatory mediators. Patients and animals with diabetic cardiomyopathy (DCM) also show inflammatory cell accumulation in the heart. Here, we detected MCs in mouse heart after streptozotocin (STZ)-induced DCM. DCM production caused significant systole and diastole interventricular septum and left ventricular (LV) posterior wall thinning, and systolic LV internal dilation in wild-type (WT) mice. DCM production also led to significant reductions of fractional shortening percentage, heart rate, body weigh...
Source: Translational Research : the journal of laboratory and clinical medicine - January 19, 2019 Category: Laboratory Medicine Authors: He A, Fang W, Zhao K, Wang Y, Li J, Yang C, Benadjaoud F, Shi GP Tags: Transl Res Source Type: research

Alcohol dependence treating agent, acamprosate, prevents traumatic brain injury-induced neuron death through vesicular zinc depletion.
Abstract Acamprosate, also known as N-acetyl homotaurine, is an N-methyl-d-aspartate receptor antagonist that is used for treating alcohol dependence. Although the exact mechanism of acamprosate has not been clearly established, it appears to work by promoting a balance between the excitatory and inhibitory neurotransmitters, glutamate, and gamma-aminobutyric acid, respectively. Several studies have demonstrated that acamprosate provides neuroprotection against ischemia-induced brain injury. However, no studies have been performed evaluating the effect of acamprosate on traumatic brain injury (TBI). In the present...
Source: Translational Research : the journal of laboratory and clinical medicine - January 17, 2019 Category: Laboratory Medicine Authors: Choi BY, Lee SH, Choi HC, Lee SK, Yoon HS, Park JB, Chung WS, Suh SW Tags: Transl Res Source Type: research

Chronic exposure to e-cig aerosols during early development causes vascular dysfunction and offspring growth deficits.
Abstract Increasing popularity of electronic cigarettes (e-cigs), including among women of reproductive age, is attributed to its perceived safety compared to conventional tobacco. However, there is a major knowledge gap surrounding the effects of e-cig aerosols on pregnancy and fetal development. We aimed to evaluate the effects of vaping e-cigs during gestation on offspring growth and to asses if growth deficits are accompanied by altered maternal and fetal vascular hemodynamics. Sprague-Dawley dams were assigned to Pair-Fed Control, Pair-Fed Juice, or Juice+Nicotine groups, and then underwent either a prenatal ...
Source: Translational Research : the journal of laboratory and clinical medicine - January 7, 2019 Category: Laboratory Medicine Authors: Orzabal MR, Lunde-Young ER, Ramirez JI, Howe SYF, Naik VD, Lee J, Heaps CL, Threadgill DW, Ramadoss J Tags: Transl Res Source Type: research

Enhancing responsiveness of pancreatic cancer cells to gemcitabine treatment under hypoxia by heme oxygenase-1 inhibition.
Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and has one of the worst prognoses leading to a meager 5-year survival rate of ∼8%. Chemotherapy has had limited success in extending the life span of patients with advanced PDAC due to poor tumor perfusion and hypoxia-induced resistance. Hypoxia reprograms the gene expression profile and upregulates the expression of multiple genes including heme oxygenase-1 (HO-1), which provide survival advantage to PDAC cells. However, the relationships between HO-1, hypoxia, and response to chemotherapy is unclear. Our results show...
Source: Translational Research : the journal of laboratory and clinical medicine - January 4, 2019 Category: Laboratory Medicine Authors: Abdalla MY, Ahmad IM, Rachagani S, Banerjee K, Thompson CM, Maurer HC, Olive KP, Bailey KL, Britigan BE, Kumar S Tags: Transl Res Source Type: research

Tetraspanin CD151 impairs heterodimerization of ErbB2/ErbB3 in breast cancer cells.
Abstract CD151/Tspan24 (SFS-1, PETA3) is one of the best characterized members of the tetraspanin family, whose involvement in breast cancer (BCa) progression was demonstrated both in vitro and in vivo. We have recently reported that in ErbB2-overexpressing BCa cells grown in 3D laminin-rich extracellular matrix, CD151 regulated basal phosphorylation and homodimerization of ErbB2 and sensitized the cells to Herceptin (trastuzumab). Following from these data, we have here analyzed an involvement of CD151 in regulation of ErbB2/ErbB3 heterodimerization and its impact on cell response to Herceptin. CD151 was found to...
Source: Translational Research : the journal of laboratory and clinical medicine - December 28, 2018 Category: Laboratory Medicine Authors: Mieszkowska M, Piasecka D, Potemski P, Debska-Szmich S, Rychlowski M, Kordek R, Sadej R, Romanska HM Tags: Transl Res Source Type: research

M üller cells in pathological retinal angiogenesis.
Müller cells in pathological retinal angiogenesis. Transl Res. 2018 Dec 27;: Authors: Li X, Liu J, Hoh J, Liu J Abstract Müller cells are the major glial cells spanning the entire layer of the retina and maintaining retinal structure. Under pathological conditions, Müller cells are involved in retinal angiogenesis, a process of growing new blood vessels from pre-existing capillaries. In response to hypoxia, high glucose, and inflammation conditions, multiple signaling pathways are activated in Müller cells, followed by the increased production of proangiogenic factors including vas...
Source: Translational Research : the journal of laboratory and clinical medicine - December 27, 2018 Category: Laboratory Medicine Authors: Li X, Liu J, Hoh J, Liu J Tags: Transl Res Source Type: research

Establishment of vaginal microbiota composition in early pregnancy and its association with subsequent preterm prelabor rupture of the fetal membranes.
This study identifies reduced Lactobacillus spp. abundance and increasing vaginal bacterial diversity as an early risk factor for PPROM and highlights the need for interventional studies designed to assess the impact of modifying vaginal bacterial composition for the prevention of preterm birth. PMID: 30633889 [PubMed - as supplied by publisher] (Source: Translational Research : the journal of laboratory and clinical medicine)
Source: Translational Research : the journal of laboratory and clinical medicine - December 27, 2018 Category: Laboratory Medicine Authors: Brown RG, Al-Memar M, Marchesi JR, Lee YS, Smith A, Chan D, Lewis H, Kindinger L, Terzidou V, Bourne T, Bennett PR, MacIntyre DA Tags: Transl Res Source Type: research

Increased circulating levels of epidermal growth factor-like domain 7 in pregnant women affected by preeclampsia.
Abstract Proper placental development is crucial to establish a successful pregnancy. Defective placentation is the major cause of several pregnancy complications, including preeclampsia (PE). We have previously demonstrated that the secreted factor epidermal growth factor-like domain 7 (EGFL7) is expressed in trophoblast cells of the human placenta and that it regulates trophoblast migration and invasion, suggesting a role in placental development. In the present study, we demonstrate that circulating levels of EGFL7 are undetectable in nonpregnant women, increase during pregnancy and decline toward term. Close t...
Source: Translational Research : the journal of laboratory and clinical medicine - December 25, 2018 Category: Laboratory Medicine Authors: Massimiani M, Lacko LA, Burke Swanson CS, Salvi S, Argueta LB, Moresi S, Ferrazzani S, Gelber SE, Baergen RN, Toschi N, Campagnolo L, Stuhlmann H Tags: Transl Res Source Type: research

The connection of circadian rhythm to inflammatory bowel disease.
nch P Abstract Inflammatory bowel disease (IBD) comprises a group of chronic, immune system-mediated inflammatory diseases that primarily affect the gastrointestinal tract. The pathogenesis of the intestinal lesions in IBD remains elusive, but the inflammation process could be the result of dysfunction of the innate and adaptive immune systems induced by genetic and environmental factors. In recent years, research has demonstrated a connection between environmental stressors that can influence day-night variations, also called circadian rhythms, and digestive health. In this review, we focus on alterations in the ...
Source: Translational Research : the journal of laboratory and clinical medicine - December 19, 2018 Category: Laboratory Medicine Authors: Gombert M, Carrasco-Luna J, Pin-Arboledas G, CodoÑer-Franch P Tags: Transl Res Source Type: research

Safety and efficacy of a bacteriophage cocktail in an in vivo model of Pseudomonas aeruginosa sinusitis.
Abstract Pseudomonas aeruginosa (PA) is a bacterial pathogen that frequently displays antibiotic resistance. Its presence within the sinuses of chronic rhinosinusitis sufferers is associated with poorer quality of life. Obligately lytic bacteriophages (phages) are viruses that infect, replicate within, and lyse bacteria, causing bacterial death. The aims of the current study were to assess the safety and efficacy of a PA phage cocktail (CT-PA) in a sheep model of rhinosinusitis. The sheep rhinosinusitis model was adapted to simulate PA infection in sheep frontal sinuses. To assess efficacy, after a 7-day biofilm f...
Source: Translational Research : the journal of laboratory and clinical medicine - December 19, 2018 Category: Laboratory Medicine Authors: Fong SA, Drilling AJ, Ooi ML, Paramasivan S, Finnie JW, Morales S, Psaltis AJ, Vreugde S, Wormald PJ Tags: Transl Res Source Type: research

Epigenetic regulators of programmed death-ligand 1 expression in human cancers.
Abstract The programmed cell death protein 1-programmed death-ligand 1 (PD-L1) axis has been successfully targeted in clinics and the use of immune check-point inhibitors have shown durable antitumor response in untreated or heavily treated advanced stage cancer. PD-L1 upregulation has been found to correlate with poor prognosis in multiple cancer types and expression of PD-L1 in intratumoral compartment has been suggested to influence immune response and act as a key determinant of checkpoint immunotherapy efficacy. Hence it becomes critical to understand the regulation of PD-L1 expression in cancer. Role of onco...
Source: Translational Research : the journal of laboratory and clinical medicine - November 9, 2018 Category: Laboratory Medicine Authors: Kumar S, Sharawat SK Tags: Transl Res Source Type: research

Novel biomarkers in multiple myeloma.
Abstract Significant advancements have been made in the molecular mechanisms of myelomagenesis, diagnostic methods, prognostication, and the treatment options in multiple myeloma (MM) over the last decade. Despite these, MM remains a heterogeneous disease with differing outcomes. As myeloma treatment landscape continues to expand, personalized treatment that provides maximum benefit to a specific patient becomes more important. In the last few years, serum monoclonal proteins including the serum-free light chain assays, imaging, and cytogenetics have been used to predict the outcomes of MM patients receiving diffe...
Source: Translational Research : the journal of laboratory and clinical medicine - October 13, 2018 Category: Laboratory Medicine Authors: Levin A, Hari P, Dhakal B Tags: Transl Res Source Type: research

Epigenetic alterations caused by aflatoxin b1: a public health risk in the induction of hepatocellular carcinoma.
ro MC Abstract Aflatoxin B1 (AFB1) is currently the most commonly studied mycotoxin due to its great toxicity, its distribution in a wide variety of foods such as grains and cereals and its involvement in the development of + (hepatocellular carcinoma; HCC). HCC is one of the main types of liver cancer, and has become a serious public health problem, due to its high incidence mainly in Southeast Asia and Africa. Studies show that AFB1 acts in synergy with other risk factors such as hepatitis B and C virus leading to the development of HCC through genetic and epigenetic modifications. The genetic modifications ...
Source: Translational Research : the journal of laboratory and clinical medicine - September 15, 2018 Category: Laboratory Medicine Authors: Ferreira RG, Cardoso MV, de Souza Furtado KM, Espíndola KMM, Amorim RP, Monteiro MC Tags: Transl Res Source Type: research