查看更多>>摘要：Background: Acute kidney injury (AKI) is a major complication following cardiac surgery that substantially increases mortality. We explored the clinical utility of urinary uromodulin (uUMOD), a marker of renal tubular reserve, for preoperative identification of patients at risk for AKI and perioperative kidney dysfunction.& nbsp;Methods: This prospective observational study included patients who underwent cardiac surgery between December 2019 and January 2021. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria; perioperative kidney dysfunction was accessed using a longitudinal estimated glomerular filtration rate.& nbsp;Results: A total of 409 participants were enrolled. Patients with uUMOD <= 20.7 mu g/mL were associated with a higher risk for AKI (odds ratio, 3.24; 95% confidence interval: 1.87-5.63, P < 0.001), independent of baseline kidney function. The uUMOD exhibits adequate discrimination for predicting AKI, with an area under the receiver operating characteristic curve of 0.713 (95% confidence interval: 0.652-0.773), and has well-fitted calibration (Hosmer-Lemeshow goodness-of-fit test, P = 0.163). The trajectory analysis revealed that decreased uUMOD levels were linked to a higher risk of patients being assigned to a worse perioperative kidney function cluster.& nbsp;Conclusions: Decreased preoperative uUMOD is independently associated with an increased risk of AKI and perioperative kidney dysfunction after cardiac surgery.& nbsp;
查看更多>>摘要：Background: Interleukin-36 (IL-36) family is associated with several fibrosis-related disorders and connective tissue diseases. However, their expression in idiopathic pulmonary fibrosis (IPF) and connective tissue disease-interstitial lung disease (CTD-ILD) is unknown.Methods: We included 19 CTD-ILD patients, 16 IPF patients, and 27 healthy control subjects. Determination of serum concentrations of IL-36 alpha, IL-36 gamma and IL-36 receptor antagonist (IL-36Ra) was performed by ELISA. The value of biomarkers for the diagnosis and assessment of ILD was assessed by lung function tests and high -resolution computed tomography.Results: Serum concentrations of IL-36 alpha and IL-36 gamma in patients with CTD-ILD and IPF were significantly higher than that in healthy controls, whereas serum IL-36Ra concentrations were not significantly different between the 3 groups. Increased IL-36 levels correlated with disease severity in IPF patients. ROC curve analysis showed that the AUC was 0.9931 for IL-36 alpha and 0.8194 for IL-36 gamma in IPF group. In CTD-ILD group, the AUC was 0.9825 for IL-36 alpha and 0.7973 for IL-36 gamma.Conclusions: We demonstrated an imbalance in the agonist and antagonist profiles of IL-36 cytokines in ILD. IL-36 cytokines may be a new diagnostic or therapeutic target in ILD, especially in IPF.
查看更多>>摘要：Gastrointestinal (GI) disorders refer to gastrointestinal tract conditions, ranging from dyspepsia to inflammatory bowel diseases (IBDs) and malignant tumors. Biomarkers, which are assessable indicators of the presence or severity of the disorders, are indispensable agents to diagnose GI conditions. Diagnostic biomarkers, including serological biomarkers, antibodies, immunological biomarkers, fecal biomarkers, and genetic biomarkers (Non-encoding RNAs), are investigated and categorized in this review. Furthermore, we have discussed the essential biological functions and diagnostic roles and the advantages and disadvantages of these biomarkers, besides novel genetic biomarkers such as miRNA-146a and their role in GI diseases.
查看更多>>摘要：MicroRNAs are small non-coding RNAs that are 18-24 nucleotides in length. Among the most widely studied microRNAs, microRNA21 (miR21) is highly expressed in many mammalian cell types. It regulates numerous biological functions such as differentiation, proliferation, apoptosis, and migration. Therefore, sensitive and specific detection of miR-21 is crucial in medical approaches. Several methods such as ISH, northern blotting, RTPCR, microarray, and next-generation are conventionally used to detect miR-21. Due to the limitations and problems related to routine methods, the development of advanced and modern methods has been one of the investigation goals of researchers in recent years. Nanotechnology-based methods have been among the most critical methods in the last two decades. Biosensors are one of the primary modern methods that largely overcome the limitations of routine procedures. The present study introduces and discusses routine methods for the detection of miR-21and the related up-to-date biosensors developed in recent years (2019-2021).
Tada, HayatoKojima, NobukoYamagami, KanTakamura, Masayuki...
6页
查看更多>>摘要：Background and aim: Clinical manifestations and genetic backgrounds of Japanese patients with sitosterolemia have been unclear.Materials and methods: We searched PubMed for studies using the keywords "sitosterolemia" or "phytosterolemia" and "Japan". Moreover, we added information from the members of the Committee on Primary Dyslipidemia under the Research Program on Rare and Intractable Disease of the Ministry of Health, Labour and Welfare (MHLW) of Japan.Results: We identified 36 patients with sitosterolemia caused by biallelic pathogenic mutations in the ATP binding cassette subfamily G member 5 (ABCG5) or ATP-binding cassette subfamily G member 8 (ABCG8) from 31 families in Japan. The diagnosed age ranged from 0 to 64 years (median 13 years). The median sitosterol and LDL cholesterol levels were 100 mu g/ml (IQR: 50-183), and 193 mg/dl (IQR: 108-295), respectively. All the patients exhibited cutaneous and/or tendon xanthomas, up to 9 (25%) patients exhibited premature coronary artery disease, 5 (16%) patients exhibited arthritis, and 8 (22%) patients exhibited blood abnormalities. Ezetimibe was administered to all the patients, including infantile cases, while statins, colestimide, evolocumab, probucol, and LDL apheresis were also used.Conclusion: We are providing a demographic overview of the clinical and genetic backgrounds of Japanese patients with sitosterolemia.
查看更多>>摘要：Background and aims: Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder caused by SMN1 gene mutations. About 40% of SMN1 subtle mutations produced premature termination codons (PTC). This study aims to determine the capacity of these PTCs to trigger nonsense-mediated mRNA decay (NMD) pathway.Methods: Three nonsense mutations in SMN1, including c.43C > T, c.683T > A and c.844C > T, were investigated by using a minigene system and in vivo splicing assays. Two strategies were supplied: administration of cycloheximide (NMD inhibitor) and knockdown of UPF1 (a key NMD factor) in the cells carrying different minigenes. Results: The wild-type minigene exclusively produced correctly spliced transcripts (FL-SMN1). Both the 683T > A and 844C > T expressed remarkably lower FL-SMN1 than the wild-type cells. After cycloheximide treatment, the FL-SMN1 levels in both the 683T > A and 844C > T were increased significantly compared with that of untreated cells. UPF1 knockdown in both the mutant 683T > A and 844C > T caused a dramatically augmentation of FL- SMN1 as compared to that in the cells treated with non-specific control siRNAs.Conclusion: Our data provide evidence that c.683T > A and c.844C > T, but not c.43C > T, in SMN1 leading to SMA trigger NMD using a minigene system. Therefore, NMD should be taken into consideration when exploring the pathogenetic mechanisms for these mutations.
查看更多>>摘要：Background: The ABO(H) secretor status is controlled by FUT2-encoded alpha(1,2)fucosyltransferase (Se enzyme) activity. Three SNPs of FUT2, 302C > T (rs200157007), 385A > T (rs1047781), and 428G > A (rs601338), cause three major variants of nonsecretor (se) or weak-secretor (Se-w) alleles. Evidence has been accumulating that suggests the secretor status is associated with various conditions including infectious diseases but a robust multiplex method for assaying relatively large-scale samples to determine the genotype of these three SNPs simultaneously has not been developed yet.& nbsp;Methods: By combined usage of two Eprobes and a dual-labeled fluorescence probe, we developed a real-time PCR, followed by triplex probe-based fluorescent melting-curve analysis (FMCA) for genotyping of 302C > T, 385A > T, and 428G > A of FUT2 in a single tube.& nbsp;Results: Three genotypes of each of three variants of FUT2 were accurately determined by the triplex probe-based FMCA. We then validated this method using genomic DNA samples of 47 Bangladeshis, and the results obtained by using this method were fully concordant with those by previous Sanger sequencing.& nbsp;Conclusions: Since the present single triplex probe-based FMCA is robust, fast, and cost-effective, we are able to effectively estimate the secretor status of subjects on a large scale in many populations around the world.
查看更多>>摘要：Background: Exosomal cargos such as nucleic acids and proteins have been attracting major interest as promising diagnostic biomarkers of cancers. The aim of this study was to characterize the mRNA profiles of serum exosomes and to identify non-small cell lung cancer (NSCLC) related mRNAs with higher sensitivity and specificity to diagnose and predict prognosis of NSCLC.& nbsp;Methods: mRNA microarray analysis was conducted to screen differentially expressed mRNAs in the serum exosomes of NSCLC patients. Selected exosomal mRNA candidate PLA2G10 and PLA2G10 protein were quantified by RT-qPCR and ELISA assay, respectively, in the sample cohorts of healthy, benign lung tumor and NSCLC. Receiver operating characteristic (ROC) analyses were performed to evaluate the diagnostic power of exosomal PLA2G10 mRNA and protein. Kaplan-Meier plots were used to estimate patients' overall and disease-free survival.& nbsp;Results: Serum exosomal PLA2G10 mRNA levels were elevated in NSCLC patients, and were closely related to more aggressive characteristics (higher stages, lymphatic node metastasis and distant metastasis) and poor overall and disease-free survival of NSCLC patients. Intriguingly, PLA2G10 protein was proved to be incorporated in exosomes, and its expression patterns and relationship with clinical pathological factors were similar to exosomal PLA2G10 mRNA. Additionally, the levels of exosomal PLA2G10 mRNA and protein were positively correlated and their combination could improve the diagnostic power to discriminate less and more malignance of NSCLC.& nbsp;Conclusions: Increased levels of serum exosomal PLA2G10 mRNA and protein were associated with more aggressive features of NSCLC, suggesting their potential as diagnostic and prognostic biomarkers of NSCLC.
查看更多>>摘要：Background: Non-small-cell lung cancer (NSCLC) is one of the main types of lung cancer. Due to lack of effective biomarkers for early detection of NSCLC, the therapeutic effect is not ideal. This study aims to reveal potential biomarkers for clinical diagnosis.Methods: The plasma metabolic profiles of the patients were characterized by liquid chromatography-mass spectrometry (LC-MS). Differential metabolites were screened by p less than 0.05 and VIP greater than 1. Multivariate statistical analysis was used to search for potential biomarkers. Receiver operating characteristic (ROC) curve was used to evaluate the predictors of potential biomarkers. Pathway enrichment analysis was performed on metabolomics data by Ingenuity Pathway Analysis (IPA) and transcriptomics data from GEO were used for validation.Results: A plasma metabolite biomarker panel including 13(S)-hydroxyoctadecadienoic acid (13(S)-HODE) and arachidonic acid was chose. The area under the ROC curve were 0.917, 0.900 and 0.867 for the panel in the different algorithm like Partial Least Squares Discrimination Analysis (PLS-DA), Support Vector Machine (SVM), Random Forest (RF). The candidate biomarkers were associated with the Akt pathway. Genes involved in the biological pathway had significant changes in the expression levels.Conclusion: 13(S)-HODE and arachidonic acid may be potential biomarkers of NSCLC. The Akt pathway was associated with this biomarker panel in NSCLC. Further studies are needed to clarify the mechanisms of disruption in this pathway.
查看更多>>摘要：Background: Heterozygous variants of KCNQ2 can cause KCNQ2 associated neurodevelopmental disorder, mainly are benign (familial) neonatal or infantile epilepsy (B(F)NE or B(F)IE) and developmental epileptic encephalopathy(DEE). Moreover, some intermediate phenotypes, including intellectual disability (ID), and myokymia are related to the gene. Methods: We collected a non-syndromic ID male patient with a novel KCNQ2 missense variant. Whole cell electrophysiology, western blotting, and immunofluorescence were adopted to analyze the variant's functional alterations. Results: The patient presented with global developmental delay since his infancy. He still had profound ID but did not have epilepsy at the adolescence. The de novo KCNQ2 variant p.R75C (NM_172107) in the NH2 domain identified here showed a slightly hyperpolarized shift of activation curves and larger current density in homomeric configurations, which could be abolished in co-expression with Kv7.2 or Kv7.3 wild-type. Western blotting and immunocytochemistry supported that the expression of variant p.R75C is lower than the Kv7.2 wild-type. The findings indicated variant p.R75C causes mild gain-of-function (GOF) of Kv7.2 channel. Conclusions: We report a non-syndromic ID patient with a KCNQ2 mild GOF variant, adding evidence for this rare clinical phenotype in the disorder. We propose that individuals with KCNQ2 GOF variants are prone to have cognitive impairments.
NSTL
Elsevier