The versatility and paradox of GDF 11.
Aging; Aging/metabolism; Animals; Biomarker; Biomarkers/metabolism; BMP signaling; Bone Morphogenetic Proteins/*metabolism; Development; Embryonic Development; Erythropoiesis; Growth differentiation factor 11; Growth Differentiation Factors/*metabolism; Humans; Neurogenesis; Pancreas/growth & development/metabolism; Retina/growth & development/metabolism
In addition to its roles in embryonic development, Growth and Differentiation Factor 11 (GDF 11) has recently drawn much interest about its roles in other processes, such as aging. GDF 11 has been shown to play pivotal roles in the rescue of the proliferative and regenerative capabilities of skeletal muscle, neural stem cells and cardiomyocytes. We would be remiss not to point that some controversy exists regarding the role of GDF 11 in biological processes and whether it will serve as a therapeutic agent. The latest studies have shown that the level of circulating GDF 11 correlates with the outcomes of patients with cardiovascular diseases, cancer and uremia. Based on these studies, GDF 11 is a promising candidate to serve as a novel biomarker of diseases. This brief review gives a detailed and concise view of the regulation and functions of GDF 11 and its roles in development, neurogenesis and erythropoiesis as well as the prospect of using this protein as an indicator of cardiac health and aging.
Jamaiyar A; Wan W; Janota D M; Enrick M K; Chilian W M; Yin L
Pharmacology & therapeutics
2017
2017-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.pharmthera.2017.02.032" target="_blank" rel="noreferrer noopener">10.1016/j.pharmthera.2017.02.032</a>
Stable isotope-based flux studies in nonalcoholic fatty liver disease.
*Citric acid cycle; *Fatty acid oxidation; *Fibrosis; *NAFLD; *Oxidative stress; *Stable isotopes; Animals; Humans; Isotopes/metabolism; Mass Spectrometry/*methods; Non-alcoholic Fatty Liver Disease/*metabolism
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is associated with the worldwide epidemics of obesity, diabetes and cardiovascular diseases. NAFLD ranges from benign fat accumulation in the liver (steatosis) to non-alcoholic steatohepatitis (NASH), and cirrhosis which can progress to hepatocellular carcinoma and liver failure. Mass spectrometry and magnetic resonance spectroscopy-coupled stable isotope-based flux studies provide new insights into the understanding of NAFLD pathogenesis and the disease progression. This review focuses mainly on the utilization of mass spectrometry-based methods for the understanding of metabolic abnormalities in the different stages of NAFLD. For example, stable isotope-based flux studies demonstrated multi-organ insulin resistance, dysregulated glucose, lipids and lipoprotein metabolism in patients with NAFLD. We also review recent developments in the stable isotope-based technologies for the study of mitochondrial dysfunction, oxidative stress and fibrogenesis in NAFLD. We highlight the limitations of current methodologies, discuss the emerging areas of research in this field, and future directions for the applications of stable isotopes to study NAFLD and its complications.
McCullough Arthur; Previs Stephen; Kasumov Takhar
Pharmacology & therapeutics
2018
2018-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.pharmthera.2017.07.008" target="_blank" rel="noreferrer noopener">10.1016/j.pharmthera.2017.07.008</a>
Alcohol abuse and disorder of granulopoiesis.
*stem cells; Alcohol abuse; Bacterial infection; Bone marrow; Cell signaling; Granulopoiesis; Immune defense; Leukopenia; Progenitor cells; The granulopoietic response
Granulocytes are the major type of phagocytes constituting the front line of innate immune defense against bacterial infection. In adults, granulocytes are derived from hematopoietic stem cells in the bone marrow. Alcohol is the most frequently abused substance in human society. Excessive alcohol consumption injures hematopoietic tissue, impairing bone marrow production of granulocytes through disrupting homeostasis of granulopoiesis and the granulopoietic response. Because of the compromised immune defense function, alcohol abusers are susceptible to infectious diseases, particularly septic infection. Alcoholic patients with septic infection and granulocytopenia have an exceedingly high mortality rate. Treatment of serious infection in alcoholic patients with bone marrow inhibition continues to be a major challenge. Excessive alcohol consumption also causes diseases in other organ systems, particularly severe alcoholic hepatitis which is life threatening. Corticosteroids are the only therapeutic option for improving short-term survival in patients with severe alcoholic hepatitis. The existence of advanced alcoholic liver diseases and administration of corticosteroids make it more difficult to treat serious infection in alcoholic patients with the disorder of granulopoieis. This article reviews the recent development in understanding alcohol-induced disruption of marrow granulopoiesis and the granulopoietic response with the focus on progress in delineating cell signaling mechanisms underlying the alcohol-induced injury to hematopoietic tissue. Efforts in exploring effective therapy to improve patient care in this field will also be discussed.
Shi Xin; DeLucia Angelo L; Bao Jianxin; Zhang Ping
Pharmacology & therapeutics
2019
2019-03
<a href="http://doi.org/10.1016/j.pharmthera.2019.03.001" target="_blank" rel="noreferrer noopener">10.1016/j.pharmthera.2019.03.001</a>