Mechanisms of Pathology-Induced Neural Stem Cell Plasticity and Neural Regeneration in Adult Zebrafish Brain
AbstractPurpose of the ReviewThe purpose of this study is to review the current knowledge on the damage-induced molecular programs that underlie the regenerative ability in zebrafish brain.Recent FindingsNeural stem cells are the reservoir for new neurons during development and regeneration of the vertebrate brains. Pathological conditions such as neurodegenerative diseases hamper neural stem cell plasticity and neurogenic outcome in humans, whereas adult zebrafish brain can enhance proliferation and neurogenic capacity of its neural stem cells despite the incipient pathology. Evidence suggests that zebrafish uses damage-i...
Source: Current Pathobiology Reports - January 16, 2018 Category: Laboratory Medicine Source Type: research
Policing the Intestinal Epithelial Barrier: Innate Immune Functions of Intraepithelial Lymphocytes
AbstractPurpose of ReviewThis review will explore the contribution of intraepithelial lymphocytes (IELs) to mucosal innate immunity and highlight the similarities in IEL functional responses to bacteria, viruses, and protozoan parasite invasion.Recent FindingsIELs rapidly respond to microbial invasion by activating host defense responses, including the production of mucus and antimicrobial peptides to prevent microbes from reaching the epithelial surface. During active infection, IELs promote epithelial cytolysis, cytokine and chemokine production to limit pathogen invasion, replication, and dissemination. Commensal-induce...
Source: Current Pathobiology Reports - January 15, 2018 Category: Laboratory Medicine Source Type: research
Regional Control of Regulatory Immune Cells in the Intestine
AbstractPurpose of ReviewThe intestine contains the largest compartment of immune regulatory cells which include T regulatory cells and IL-10-producing macrophages. These cell populations serve to restrain unnecessary immune responses of the intestine, which may lead to the pathogenesis of Crohn ’s disease or food allergy.Recent FindingsThis review discusses the recent findings pertaining to the functional regulation of these cells which may provide insight into novel therapies. Both T regulatory cells and macrophages are regulated in microbiota-dependent and microbiota-independent manners, i.e., dietary antigens. Often,...
Source: Current Pathobiology Reports - January 12, 2018 Category: Laboratory Medicine Source Type: research
Adipose Tissue Metabolism and Cancer Progression: Novel Insights from Gut Microbiota?
AbstractPurpose of ReviewObesity is strongly associated with the development of several types of cancers. This review aims to discuss the recent key mechanisms and actors underlying the link between adipose tissue metabolism and cancer, and the unequivocal common mechanisms connecting gut microbes to adipose tissue and eventually cancer development.Recent FindingsComplex interactions among systemic and tissue-specific pathways are suggested to link obesity and cancer, involving endocrine hormones, adipokines, fatty acids, inflammation, metabolic alterations, and hypoxia. Emerging evidence also suggests that the gut microbi...
Source: Current Pathobiology Reports - October 24, 2017 Category: Laboratory Medicine Source Type: research
Black, White, and Gray: Macrophages in Skin Repair and Disease
AbstractPurpose of ReviewMacrophages alter their responses during the temporal stages of wound healing. During the inflammatory phase, they perform phagocytosis. During neovascularization, they fuse sprouting endothelial cells. In the proliferation phase, they deposit extracellular matrix, and during wound resolution, macrophages phagocytize excessive cellular components. This review addresses how changing macrophage phenotypes affects skin repair and disease.Recent FindingsMacrophages can determine the outcome of repair and can shift the normal wound healing response into fibrosis or chronic wounds. Emerging single-cell t...
Source: Current Pathobiology Reports - October 14, 2017 Category: Laboratory Medicine Source Type: research
The Regulation of Notch Signaling in Retinal Development and Regeneration
AbstractPurpose of ReviewNotch signaling is an important component of retinal progenitor cell maintenance and Muller glia (MG) specification during development, and its manipulation may be critical for allowing MG to re-enter the cell cycle and regenerate neurons in adults. In mammals, MG respond to retinal injury by undergoing a gliotic response rather than a regenerative one. Understanding the complexities of Notch signaling may allow for strategies that enhance regeneration over gliosis.Recent FindingsNotch signaling is regulated at multiple levels and is interdependent with various other signaling pathways in both the ...
Source: Current Pathobiology Reports - October 6, 2017 Category: Laboratory Medicine Source Type: research
Bioinductive Scaffolds —Powerhouses of Skeletal Muscle Tissue Engineering
AbstractPurpose of ReviewSkeletal muscle tissue engineering is a field of vital importance to many sufferers of volumetric muscle loss (VML) and other muscular pathologies. Bioinductive scaffolds can host cells and modulate their behaviour and thus serve as a platform for muscle tissue growth.Recent FindingsScaffolds for skeletal muscle engineering can be composed of synthetic polymers, naturally derived polymers, decellularized extracellular matrix (ECM) or any combination of these. They lead to active tissue regeneration by modulating the initial inflammatory response, recruiting progenitor cells and determining cell phe...
Source: Current Pathobiology Reports - August 14, 2017 Category: Laboratory Medicine Source Type: research
Future Challenges in the Generation of Hepatocyte-Like Cells From Human Pluripotent Stem Cells
AbstractPurpose of ReviewThe purpose of this review is to provide an updated perspective on directing human pluripotent stem cells (hPSCs) to hepatocyte-like-cells (HLCs) and the associated challenges.Recent FindingsRecent advances in the hepatocyte differentiation field have largely been focused on increasing the reproducibility and definition of culture systems to further their translation to a clinical setting. There have been advances using new extracellular matrices such as human laminins, and recent work using small molecules to drive the differentiation process has dramatically reduced the cost of producing HLCs wit...
Source: Current Pathobiology Reports - July 31, 2017 Category: Laboratory Medicine Source Type: research
The Contractile Phenotype of Dermal Fetal Fibroblasts in Scarless Wound Healing
AbstractPurpose of ReviewInjured skin in the mammalian fetus can heal regeneratively due to the ability of fetal fibroblasts to effectively reorganize the extracellular matrix (ECM). This process occurs without fetal fibroblasts differentiating into highly contractile myofibroblasts which cause scarring and fibrosis in adult wounds. Here, we provide a brief review of fetal wound healing and the evidence supporting a unique contractile phenotype in fetal fibroblasts. Furthermore, we discuss the biomechanical role of the ECM in driving myofibroblast differentiation in wound healing and the implications for new clinical modal...
Source: Current Pathobiology Reports - July 28, 2017 Category: Laboratory Medicine Source Type: research
Mitochondrial Fatty Acid Oxidation Disorders Associated with Cardiac Disease
AbstractPurpose of ReviewTo elucidate the role metabolic pathways have on pathophysiological mechanisms involving the heart, it is essential to understand how biochemical pathways influence pathophysiology, clinical findings, and treatment. In this review, we focus on fatty acid oxidation disorders that affect the heart. We enumerate the defects that arise from each step of fatty acid oxidation leading to cardiomyopathy, conduction defects, arrhythmias, and sudden death.Recent FindingsWith the advent of newborn screening, careful interpretation of diagnostic findings and early treatment, morbidity, and mortality associated...
Source: Current Pathobiology Reports - July 24, 2017 Category: Laboratory Medicine Source Type: research
Liver Disease in Alpha-1 Antitrypsin Deficiency: Current Approaches and Future Directions
AbstractPurpose of ReviewThe aim of the study is to review the liver disease caused by alpha-1 antitrypsin deficiency (A1ATD), including pathogenesis, epidemiology, diagnostic testing, and recent therapeutic developments.Recent FindingsTherapeutic approaches target several intracellular pathways to reduce the cytotoxic effects of the misfolded mutant globular protein (ATZ) on the hepatocyte. These include promoting ATZ transport out of the endoplasmic reticulum (ER), enhancing ATZ degradation, and preventing ATZ globule-aggregation.SummaryA1ATD is the leading genetic cause of liver disease among children. It is a protein-f...
Source: Current Pathobiology Reports - July 10, 2017 Category: Laboratory Medicine Source Type: research
Pathobiology of the Hepatic Glycogen Storage Diseases
AbstractPurpose of the ReviewThe purpose of this study is to review the pathobiology of the hepatic glycogen storage diseases (GSD) and recent developments in their management.Recent FindingsIncreasingly, noninvasive mutation detection has replaced biological and tissue samples as the first line diagnostic method. For type 1 GSD, continuous subcutaneous monitoring has transformed patient monitoring. There is evidence that improved metabolic control can prevent complications such as adenoma formation and renal dysfunction. Improved understanding of the pathophysiology of hepatic adenomata may allow rationalization of their ...
Source: Current Pathobiology Reports - June 6, 2017 Category: Laboratory Medicine Source Type: research
ER Stress and Autophagy in Obesity and Nonalcoholic Fatty Liver Disease
AbstractPurpose of reviewThis review highlights the extent to which dysfunction of the endoplasmic reticulum (ER) and autophagy contribute to the pathogenesis of obesity-associated hepatic steatosis and non-alcoholic fatty liver disease (NAFLD). We addressed the following questions: what is the role of the unfolded protein response (UPR) and autophagy in the liver? What interactions between the UPR and autophagy are present during the progression of obesity-associated NAFLD? What steps within the pathways of the UPR and autophagy could be potential therapeutic targets for the treatment of NAFLD?Recent FindingsRecent studie...
Source: Current Pathobiology Reports - June 2, 2017 Category: Laboratory Medicine Source Type: research
Alagille Syndrome: Genetics and Functional Models
AbstractPurpose of ReviewWe review the genetics of the autosomal dominant, multi-system disorder Alagille syndrome, and provide a summary on how current functional models and emerging biotechnologies are equipped to guide scientists towards novel therapies. The importance of haploinsufficiency as a disease mechanism will be underscored throughout this discussion.Recent FindingsAlagille syndrome, a human disorder affecting the liver, heart, vasculature, kidney, and other systems, is caused by mutations in the Notch signaling pathway ligand, Jagged1 (JAG1) or the receptor,NOTCH2. Current advances in animal modeling,in vitro ...
Source: Current Pathobiology Reports - June 1, 2017 Category: Laboratory Medicine Source Type: research
Aging, Cellular Senescence, and Kidney Fibrosis
AbstractPurpose of ReviewFibrosis is a hallmark of chronic kidney disease, and a primary risk factor for chronic kidney disease is age. Senescent cells accumulate in the kidney during natural aging and after injury. Understanding the effect of senescence on kidney maintenance and how senescence is linked to fibrosis may reveal new therapeutic opportunities.Recent FindingsThe load of senescent cells in the kidney is predictive of biological age and correlates with renal disease and allograft outcome. Senescent cells do not proliferate to repair injury. Instead, they secrete proteins that enhance inflammation and modulate fi...
Source: Current Pathobiology Reports - May 23, 2017 Category: Laboratory Medicine Source Type: research
