Low expression of microRNA-328 can predict sepsis and alleviate sepsis-induced cardiac dysfunction and inflammatory response.

Sepsis often leads to cardiac dysfunction and inflammation. This study investigated the clinical value of microRNA-328 (miR-328) in sepsis and its role in cardiac dysfunction and inflammation caused by sepsis. The expression level of miR-328 in the serum of the subjects was detected by qRT-PCR. Receiver operating characteristic (ROC) curve measured the diagnostic value of miR-328 in sepsis. Rat sepsis model was established to detect left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and maximal rate of increase/decrease of left ventricular pressure (±dp/dtmax). Myocardial injury markers serum cardiac troponin I (cTnI), myocardial kinase isoenzyme (CK-MB), and inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). miR-328 expression was assessed in serum of sepsis patients and in rat models of sepsis. The AUC of ROC curve was 0.926, sensitivity 87.60%, and specificity 86.36%. Compared with the sham group, LVSP and +dp/dtmax were decreased in the rat model of sepsis. LVEDP, -dp/dtmax, cTnI, CK-MB, tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß were upregulated in the rat model of sepsis. The low expression of miR-328 reversed these indicators. miR-328 is a diagnostic marker for patients with sepsis, and decreasing the expression level of miR-328 can ameliorate cardiac dysfunction and cardiac inflammation in sepsis.

Low expression of microRNA-328 can predict sepsis and alleviate sepsis-induced cardiac dysfunction and inflammatory response

Sepsis often leads to cardiac dysfunction and inflammation. This study investigated the clinical value of microRNA-328 (miR-328) in sepsis and its role in cardiac dysfunction and inflammation caused by sepsis. The expression level of miR-328 in the serum of the subjects was detected by qRT-PCR. Receiver operating characteristic (ROC) curve measured the diagnostic value of miR-328 in sepsis. Rat sepsis model was established to detect left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and maximal rate of increase/decrease of left ventricular pressure (±dp/dtmax). Myocardial injury markers serum cardiac troponin I (cTnI), myocardial kinase isoenzyme (CK-MB), and inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). miR-328 expression was assessed in serum of sepsis patients and in rat models of sepsis. The AUC of ROC curve was 0.926, sensitivity 87.60%, and specificity 86.36%. Compared with the sham group, LVSP and +dp/dtmax were decreased in the rat model of sepsis. LVEDP, -dp/dtmax, cTnI, CK-MB, tumor necrosis factor-α, interleukin (IL)-6, and IL-1β were upregulated in the rat model of sepsis. The low expression of miR-328 reversed these indicators. miR-328 is a diagnostic marker for patients with sepsis, and decreasing the expression level of miR-328 can ameliorate cardiac dysfunction and cardiac inflammation in sepsis.

MS/MS-based newborn and family screening detects asymptomatic patients with very-long-chain acyl-CoA dehydrogenase deficiency.

OBJECTIVES: To determine whether asymptomatic persons with biochemical evidence of very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency identified through expanded newborn screening with tandem mass spectometry have confirmed disease. STUDY DESIGN: We characterized 8 asymptomatic VLCAD-deficient individuals by enzyme and/or mutational analysis and compared them with clinically diagnosed, symptomatic patients with regard to mutations, enzyme activity, phenotype, and age of disease onset. RESULTS: VLCAD molecular analyses in 6 unrelated patients revealed the previously reported V243A mutation, associated with hepatic or myopathic phenotypes, on 7/12 alleles. All other mutations were also missense mutations. Residual VLCAD activities of 6% to 11% of normal were consistent with milder phenotypes. In these identified individuals treated prospectively with dietary modification as preventive measures, clinical symptoms did not develop during follow-up. CONCLUSIONS: MS/MS-based newborn screening correctly identifies VLCAD-deficient individuals. Based on mutational and enzymatic findings, these infants probably are at risk of future disease. Because life-threatening metabolic derangement can occur even in otherwise mild phenotypes, we advocate universal newborn screening programs for VLCAD deficiency to detect affected patients and prevent development of metabolic crises. Longer-term follow-up is essential to define outcomes, the definite risk of future disease, and appropriate treatment recommendations.