Translational research : the journal of laboratory and clinical medicine
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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.
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Acute kidney injury (AKI) diagnosis relies on plasma creatinine concentration (Crpl), a relatively insensitive, surrogate biomarker of glomerular filtration rate that increases only after significant damage befalls. However, damage in different renal structures may occur without increments in Crpl, a condition known as subclinical AKI. Thus, detection of alterations in other aspects of renal function different from glomerular filtration rate must be included in an integral diagnosis of AKI. ⋯ Predisposed animals showed a reduced response to the FST (namely, reduced furosemide-induced diuresis and K+ excretion), whereas nonpredisposed animals showed no alteration, compared to the controls. Computational modeling of epithelial transport of solutes and water along the nephrons applied to experimental data suggested that proximal tubule transport was only minimally reduced, the sodium-chloride symporter was upregulated by 50%, and the renal outer medullary potassium channel was downregulated by 85% in predisposed animals. In conclusion, serial coupling of the FST and computational modeling may be used to detect and localize subclinical tubular alterations.
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This study aimed to assess the angiographic characteristics, feasibility and safety of the provocative test with acetylcholine (AChT), and the influence on further treatment and prognosis of Middle European patients in 5-year follow-up, especially focusing on those with a history of myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA). The AChPOL Registry was an ongoing prospective single-center registry that included patients undergoing AChT from December 2010 to March 2013 for further diagnostic evaluation of a suspicious variant angina or coronary microvascular spasm, based on the COVADIS criteria. AChT was injected in incremental doses of 25, 50, and 75µg into the right coronary artery and 25, 50, and 100 µg into the left coronary artery, and the patients were followed up for 5 years. ⋯ Interestingly, patients with a history of MINOCA had higher rates of MI and recurrent chest pain requiring hospitalization in the follow-up. We showed that AChT was safe in Middle European patients. In the follow-up patients with microvascular spasm and a history of MINOCA had the highest risk of MI and recurrent chest pain requiring hospitalization.
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Lung cancer (LC) is the leading cause of cancer-related death worldwide and miRNAs play a key role in LC development. To better diagnose LC and to predict drug treatment responses we evaluated 228 articles encompassing 16,697 patients and 12,582 healthy controls. Based on the criteria of ≥3 independent studies and a sensitivity and specificity of >0.8 we found blood-borne miR-20a, miR-10b, miR-150, and miR-223 to be excellent diagnostic biomarkers for non-small cell LC whereas miR-205 is specific for squamous cell carcinoma. ⋯ In conclusion, we report diagnostic miRNA biomarkers for in-depth clinical evaluation. Furthermore, in an effort to avoid unnecessary toxicity we propose predictive biomarkers. The biomarker candidates support personalized treatment decisions of LC patients and await their confirmation in randomized clinical trials.
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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.