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Current Pathobiology Reports

Elizabeth A Mills, Daniel Goldman
Purpose of review: Notch signaling is an important component of retinal progenitor cell maintenance and 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 findings: Notch signaling is regulated at multiple levels, and is interdependent with various other signaling pathways in both the receptor and ligand expressing cells...
December 2017: Current Pathobiology Reports
Melissa A Gilbert, Nancy B Spinner
Purpose of review: We 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 findings: Alagille 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...
September 2017: Current Pathobiology Reports
Aron Parekh, Patricia A Hebda
PURPOSE OF REVIEW: Injured 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 modalities based on the biophysical properties of fetal fibroblasts...
September 2017: Current Pathobiology Reports
Duc-Hung Pham, Changwen Zhang, Chunyue Yin
Purpose of Review: The liver is the largest internal organ and performs both exocrine and endocrine function that is necessary for survival. Liver failure is among the leading causes of death and represents a major global health burden. Liver transplantation is the only effective treatment for end-stage liver diseases. Animal models advance our understanding of liver disease etiology and hold promise for the development of alternative therapies. Zebrafish has become an increasingly popular system for modeling liver diseases and complements the rodent models...
June 2017: Current Pathobiology Reports
Alexandra MacColl Garfinkel, Mustafa K Khokha
PURPOSE OF REVIEW: Given the enormous impact congenital heart disease has on child health, it is imperative that we improve our understanding of the disease mechanisms that underlie patient phenotypes and clinical outcomes. This review will outline the merits of using the frog model, Xenopus, as a tool to study human cardiac development and left-right patterning mechanisms associated with congenital heart disease. RECENT FINDINGS: Patient-driven gene discovery continues to provide new insight into the mechanisms of congenital heart disease, and by extension, patient phenotypes and outcomes...
June 2017: Current Pathobiology Reports
Matthew Dodson, Donna D Zhang
PURPOSE OF REVIEW: The goal of this review is to summarize the current knowledge in the field regarding the non-canonical activation of the NRF2 pathway. Specifically, we address what role p62 plays in mediating this pathway, which pathologies have been linked to the p62-dependent activation of NRF2, as well as what therapeutic strategies could be used to treat diseases associated with the non-canonical pathway. RECENT FINDINGS: It has recently been shown that autophagic dysfunction leads to the aggregation or autophagosomal accumulation of p62, which sequesters KEAP1, resulting in prolonged activation of NRF2...
June 2017: Current Pathobiology Reports
Roberta A Gottlieb, Amandine Thomas
PURPOSE OF REVIEW: Mitochondrial homeostasis and quality control are essential to maintenance of cardiac function and a disruption of this pathway can lead to deleterious cardiac consequences. RECENT FINDINGS: Mitochondrial quality control has been described as a major homeostatic mechanism in cell. Recent studies highlighted that an impairment of mitochondrial quality control in different cell or mouse models is linked to cardiac dysfunction. Moreover, some conditions as aging, genetic mutations or obesity have been associated with mitochondrial quality control alteration leading to an accumulation of damaged mitochondria responsible for increased production of reactive oxygen species, metabolic inflexibility, and inflammation, all of which can have sustained effects on cardiac cell function and even cell death...
June 2017: Current Pathobiology Reports
David M Habiel, Cory M Hogaboam
PURPOSE OF REVIEW: Idiopathic Pulmonary Fibrosis (IPF) is the most common form of interstitial lung diseases of unknown eathiopathogenesis, mean survival of 3-5 years and limited therapeutics. Characterized by a loss of alveolar type II epithelial cells and aberrant activation of stromal cells, considerable effort was undertaken to characterize the origin and activation mechanisms of fibroblasts and myofibroblasts in IPF lungs. In this review, the origin and contribution of fibroblast and myofibroblasts in lung fibrosis will be summarized...
June 2017: Current Pathobiology Reports
Altea Rocchi, Congcong He
PURPOSE OF REVIEW: Physical exercise is a highly effective method to prevent several pathogenic conditions, such as obesity, type 2 diabetes and cardiovascular diseases, largely due to metabolic adaptations induced by exercise in skeletal muscle. Yet how exercise induces the beneficial effects in muscle remains to be fully elucidated. Autophagy is a lysosomal degradation pathway that regulates nutrient recycling, energy production and organelle quality control. The autophagy pathway is upregulated in response to stress during exercise and muscle contraction, and may be an important mechanism mediating exercise-induced health benefits...
June 2017: Current Pathobiology Reports
Arti V Shinde, Nikolaos G Frangogiannis
PURPOSE OF REVIEW: Activated fibroblasts are critically implicated in repair and remodeling of the injured heart. This manuscript discusses recent progress in the cell biology of fibroblasts in the infarcted and remodeling myocardium, highlighting advances in understanding the origin, function and mechanisms of activation of these cells. RECENT FINDINGS: Following myocardial injury, fibroblasts undergo activation and myofibroblast transdifferentiation. Recently published studies have suggested that most activated myofibroblasts in the infarcted and pressure-overloaded hearts are derived from resident fibroblast populations...
June 2017: Current Pathobiology Reports
Rui Kang, Daolin Tang
PURPOSE OF REVIEW: Autophagy is a conserved intracellular degradation system and plays a dual role in cell death, depending on context and phase. Ferroptosis is a new form of regulated cell death that mainly depends on iron accumulation and lipid peroxidation. In this review, we summarize the processes of autophagy and ferroptosis and discuss their crosstalk mechanisms at the molecular level. RECENT FINDINGS: The original study shows that ferroptosis is morphologically, biochemically, and genetically distinct from autophagy and other types of cell death...
June 2017: Current Pathobiology Reports
Namita Chatterjee, Shushan Rana, Cristina Espinosa-Diez, Sudarshan Anand
PURPOSE OF REVIEW: The goals of this review are to examine the usefulness of miRNAs as diagnostic and prognostic biomarkers for cancer and to evaluate the applicability of miRNAs as cancer therapeutics. RECENT FINDINGS: Examination of miRNA milieu from body fluids offers a new alternative for quick, affordable and easy analysis of disease status in patients. Blood-based exosomal miRNAs have increased stability and are an excellent choice for clinical cancer diagnostics and prognostics...
March 2017: Current Pathobiology Reports
Maureen Banach, Jacques Robert
A PURPOSE OF REVIEW: Nonmammalian comparative animal models are important not only to gain fundamental evolutionary understanding of the complex interactions of tumors with the immune system, but also to better predict the applicability of novel immunotherapeutic approaches to humans. After reviewing recent advances in developing alternative models, we focus on the amphibian Xenopus laevis and its usefulness in deciphering the perplexing roles of MHC class I-like molecules and innate (i)T cells in tumor immunity...
March 2017: Current Pathobiology Reports
Luai Huleihel, Michelle E Scarritt, Stephen F Badylak
PURPOSE OF REVIEW: An overview of the role of extracellular RNAs (exRNA) in the regulation of homeostasis, disease progression, and regeneration is provided herein. Several exRNAs have been identified as potential biomarkers for disease and disease progression. In addition, the potential of exRNAs as a therapeutic modality is discussed. RECENT FINDINGS: Fibrotic diseases of the lung, liver, and heart, among other organs share a number of identical exRNAs which play key roles in disease pathogenesis...
March 2017: Current Pathobiology Reports
Andrew J Warburton, David N Boone
PURPOSE OF REVIEW: The goal of this review was to compare and contrast the results and implications from several recent transcriptomic studies that analyzed the expression of lncRNAs in breast cancer. How many lncRNAs are dysregulated in breast cancer? Do dysregulated lncRNAs contribute to breast cancer etiology? Are lncRNAs viable biomarkers in breast cancer? RECENT FINDINGS: Transcriptomic profiling of breast cancer tissues, mostly from The Cancer Genome Atlas, identified thousands of long noncoding RNAs that are expressed and dysregulated in breast cancer...
March 2017: Current Pathobiology Reports
Aditi Dubey, Jean-Pierre Saint-Jeannet
PURPOSE OF REVIEW: Craniofacial disorders are among the most common human birth defects and present an enormous health care and social burden. The development of animal models has been instrumental to investigate fundamental questions in craniofacial biology and this knowledge is critical to understand the etiology and pathogenesis of these disorders. RECENT FINDINGS: The vast majority of craniofacial disorders arise from abnormal development of the neural crest, a multipotent and migratory cell population...
March 2017: Current Pathobiology Reports
Ellen L Mitchell, Zahida Khan
Purpose of Review: The 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 Findings: Therapeutic 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...
2017: Current Pathobiology Reports
Benedicte F Jordan, Florian Gourgue, Patrice D Cani
Purpose of Review: Obesity 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 Findings: Complex 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...
2017: Current Pathobiology Reports
Marko Z Nikolić, Emma L Rawlins
PURPOSE OF REVIEW: The lung research field has pioneered the use of organoids for the study of cell-cell interactions. RECENT FINDINGS: The use of organoids for airway basal cells is routine. However, the development of organoids for the other regions of the lung is still in its infancy. Such cultures usually rely on cell-cell interactions between the stem cells and a putative niche cell for their growth and differentiation. SUMMARY: The use of co-culture organoid systems has facilitated the in vitro cultivation of previously inaccessible stem cell populations, providing a novel method for dissecting the molecular requirements of these cell-cell interactions...
2017: Current Pathobiology Reports
Divya Ail, Muriel Perron
PURPOSE OF REVIEW: Retinal degenerative diseases have immense socio-economic impact. Studying animal models that recapitulate human eye pathologies aids in understanding the pathogenesis of diseases and allows for the discovery of novel therapeutic strategies. Some non-mammalian species are known to have remarkable regenerative abilities and may provide the basis to develop strategies to stimulate self-repair in patients suffering from these retinal diseases. RECENT FINDINGS: Non-mammalian organisms, such as zebrafish and Xenopus, have become attractive model systems to study retinal diseases...
2017: Current Pathobiology Reports
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