Translational research : the journal of laboratory and clinical medicine
-
Oligodendrocyte progenitor cells (OPCs) in the infant brain give rise to mature oligodendrocytes that myelinate CNS axons. OPCs are particularly vulnerable to oxidative stress that occurs in many forms of brain injury. One common cause of infant brain injury is neonatal intraventricular hemorrhage (IVH), which releases blood into the CSF and brain parenchyma of preterm infants. ⋯ The effects of hemoglobin and PLZ on OPC proliferation were not statistically significant, but showed trends towards hemoglobin reducing OPC proliferation and PLZ increasing OPC proliferation (P=0.06 for both effects). Collectively, our results indicate that hemoglobin induces mitochondrial dysfunction in OPCs and that antioxidant therapy reduces these effects. Therefore, antioxidant therapy may hold promise for white matter diseases in which hemoglobin plays a role, such as neonatal IVH.
-
Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor highly expressed in coronary plaques, particularly in macrophages, and in activated platelets. Thus, a possible role in the pathogenesis of acute coronary syndrome (ACS) has been suggested. We evaluated systemic BDNF levels according to the different clinical presentations of ACS. ⋯ At multivariate regression analysis BDNF levels independently predicted the presence of MØI (odds ratio [OR] = 2.856; 95% confidence interval [CI] [1.151-7.090], P = 0.024) and the absence of healed plaques (OR = 0.438, 95% CI [0.185-0.992], P= 0.050). Among ACS patients, BDNF levels were higher in patients with STEMI. Moreover, BDNF levels were independently associated with MØI and with the absence of healed plaques along the culprit vessel, suggesting a possible role of BDNF in promoting plaque inflammation, destabilization and occlusive thrombosis.
-
Gastric cancer (GC) is a highly prevalent malignancy featured by dismal oncological outcomes. Accumulating pieces of evidence have consensus over the therapeutic significance of extracellular vesicles (EVs) and its role in carcinogenesis. Here, we planned to uncover EVs' role in GC by shuttling microRNA-1290 (miR-1290) and to identify the possible molecular mechanism associated with Grhl2, PD-L1, and ZEB1. ⋯ Moreover, we also developed a mouse model of GC and injected the EVs derived from miR-1290-inhibitor-treated GC cells into the tumor-bearing mice for further validation of mechanism in vivo. Intriguingly, the pivotal role of EVs-shuttled miR-1290 as an oncomiR was demonstrated in vivo. Collectively, we found that miR-1290 in EVs secreted from GC cells contributed to immune escape through the Grhl2/ZEB1/PD-L1 axis.
-
The liver is a vital organ that controls glucose and lipid metabolism, hormone regulation, and bile secretion. Liver injury can occur from various insults such as viruses, metabolic diseases, and alcohol, which lead to acute and chronic liver diseases. Recent studies have demonstrated the implications of long noncoding RNAs (lncRNAs) in the pathogenesis of liver diseases. ⋯ Its expression, however, is increased in liver diseases with various etiologies. In this review, we focused on the roles of H19 in the pathogenesis of liver diseases. This comprehensive review is aimed to provide useful perspectives and translational applications of H19 as a potential therapeutic target of liver diseases.
-
An elevated blood angiotensin I-converting enzyme (ACE) supports diagnosis of sarcoidosis and Gaucher disease. However, some ACE mutations increase ACE shedding, and patients with these mutations are therefore at risk of being incorrectly diagnosed with sarcoidosis because of elevated serum ACE levels. We applied a novel approach called "ACE phenotyping" to identify possible ACE mutations in 3 pulmonary clinic patients that had suspected sarcoidosis based on elevated blood ACE levels. ⋯ We also performed a comprehensive analysis of the existing database of all ACE mutations to estimate the proportion of mutations increasing ACE shedding. The frequency of ACE mutations resulting in increased blood ACE levels may be much higher than previously estimated. ACE phenotyping, together with whole exome sequencing, is a diagnostic approach that could prevent unnecessary invasive and/or costly diagnostic procedures, or potentially harmful treatment for patients misdiagnosed on the basis of elevated blood ACE levels.