Translational research : the journal of laboratory and clinical medicine
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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.
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An increasing body of evidence shows a role for macrophages and monocytes (as their precursors) in hypertension, but with conflicting results with regard to whether they are protective or harmful. Therefore, we systematically reviewed the effect of macrophage interventions on blood pressure in animal models, to explore which factors determine the blood pressure increasing vs. decreasing effect. A search in PubMED and EMBASE yielded 9620 records, 26 of which were included. ⋯ Prespecified subgroup analysis did reveal a potential role for the route in which the macrophage-depleting agent is being administrated (intraperitoneal vs intravenous subgroup difference of P = 0.07 (k = 22), or P < 0.001 in studies achieving considerable (ie, >50%) depletion (k = 18)). Along with findings from specific macrophage protein deletion studies-showing that deletion of one single macrophage protein (like TonEBP, endothelin-B, EP4, NOX-2 and the angiotensin II type 1 receptor) can alter blood pressure responses to hypertensive stimuli-the indication that each route has its specific depletion pattern regarding targeted tissues and macrophage phenotypes suggests a determinative role for these features. These hypothesis-generating results encourage more detailed depletion characterization of each technique by direct experimental comparisons, providing a chance to obtain more knowledge on which macrophages are beneficial versus detrimental in hypertension development.
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Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-age women. Reduced progesterone levels are associated with luteal phase deficiency in women with PCOS. The levels of C-X-C motif chemokine ligand-14 (CXCL14) were previously reported to be decreased in human-luteinized granulosa (hGL) cells derived from PCOS patients. ⋯ P38 and Jun N-terminal kinase (JNK) pathways were also activated by CXCL14 and inhibition of p38 and JNK attenuated the increase of phosphorylation of CREB, STAR expression and progesterone production caused by CXCL14. Our findings revealed the novel role of CXCL14 in upregulation of STAR expression and progesterone synthesis through CREB phosphorylation via activation of p38 and JNK pathways in hGL cells. This is likely contributing to the dysfunction in steroidogenesis in granulosa cells from PCOS patients.
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A fraction of the transcriptome is translated into proteins. The rest is classified as non-protein coding RNA (Ribonucleic Acid) but has gained increased attention as functional and regulatory group of transcripts. The gene regulatory role of non-coding RNAs (ncRNAs) has now been widely accepted in diverse biological processes in both physiology and disease. ⋯ The presence of RISC components including microRNAs in the nucleus supports this notion. They may integrate with chromatin modifiers, microprocessing machinery and mRNA stabilizing transcripts to play a multifunctional role in the nucleus. Although a limited number of studies appreciate this novel activity of microRNAs relevant to the cardiovascular system, they provide proof-of-concept that requires consideration while targeting miRNAs with therapeutic potential.