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Abstract: Background: Brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of coronary artery disease (CAD). The human BDNF Val66Met polymorphism has been shown to be associated with altered susceptibility to neuropsychiatric disorders. However it is unknown whether this polymorphism plays a role in cardiovascular disease. Methods: Genotyping of BDNF Val66Met polymorphism was carried out in 513 controls, 628 unstable angina pectoris (UAP) and 276 stable angina pectoris (SAP) patients. The plasma concentrations of BDNF and high-sensitivity C-reactive protein (hsCRP) were measured by ELISA. The general clinical data in patients and controls were obtained. Results: There was a significant association between genotype and allele frequency of the BDNF Val66Met polymorphism and UAP (all P <0.05). Multivariate logistic regression analysis revealed that the BDNFMet/Met genotype had a protective effect on the occurrence of UAP after controlling for known risk factors of CAD (OR 0.53, P =0.005). Subjects with BDNFMet/Met genotype also had decreased plasma hsCRP levels compared with the Val carriers (P <0.01). Conclusion: The BDNFMet/Met genotype has a protective effect on the occurrence of UAP, which might in part be due to the decreased plasma hsCRP level in BDNFMet/Met carriers. To our knowledge, this is the first study that demonstrates the link between BDNF Val66Met polymorphism and CAD. [Copyright &y& Elsevier]

The kinetics of cytoskeletal networks, with actin as a key factor, play a key role in regulating the morphology and function of dendritic spines. Drebrin is a neuron growth and brain development-related actin-binding protein and is present in 70% of the dendritic spines of excitatory synapses. It regulates the development and formation of dendritic spines and well-developed dendritic spines pave the way for presynaptic elements. Well-developed and mature synapses are prerequisite for maintaining nervous system physiology. Abnormal morphology of dendritic spines and loss of synapses are seen in many neurologic diseases associated with cognitive decline. However, the mechanisms governing these pathologic changes and their correlation with drebrin remain unclear. Exploring the relationship between drebrin and cognitive function may provide insight into the early prevention of cognitive impairment and in the diagnosis and treatment of Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

Abstract: Background: Long-term lamivudine treatment induces emergence of lamivudine-resistant hepatitis B virus (HBV) in a significant number of patients with chronic HBV infection. Rapid and quantitative methods to determine the percentage of lamivudine-resistant mutants in total HBV are important during lamivudine therapy. Methods: We established a quantitative real-time PCR method with selective primers and TaqMan probe to detect the percentage of lamivudine-resistant mutants in total HBV without the need of external DNA standards. This percentage was calculated as the PCR efficiency raised to the differences between threshold cycle number (ΔCt) of mutant and control reactions. Clones of the HBV polymerase gene containing the different YMDD variants were diluted in series and tested. Serum samples from 145 lamivudine-treated and 98 untreated patients with chronic hepatitis B virus infection were analyzed using this method and compared with DNA sequencing. Results: As little as 0.1% mutant plasmids in 106–109 copies/ml of wild-type plasmids were detected. Among the 145 patients treated with lamivudine, 42 of them had mutants with percentages of 5–100%. In six discordant results between real-time PCR and DNA sequencing, real-time PCR detected mutants with percentages of 5–20%, which were concordant with subclone sequencing. Five of 98 lamividine-untreated patients had mutants of 10–20% in wild-type virus populations. Compared to DNA sequencing, real-time PCR was fast and cost-effective. Conclusion: This real-time PCR is a rapid, sensitive and cost-effective method for relative quantitation of YMDD mutants of HBV. [Copyright &y& Elsevier]

• Urinary extracellular vesicles miRNAs' expression pattern of RCC patients was examined. • uEV miR-135b-5p, miR-196b-5p, miR-200c-3p, and miR-203a-3p were upregulated in RCC patients. • A three-uEV miRNA panel could discriminate RCC patients from controls with the AUC of 0.785. • An uEV-miRNA panel could also distinguish early-stage RCC patients with the AUC of 0.786. The potential of urinary-derived extracellular vesicle (uEV) microRNAs (miRNAs) as noninvasive molecular biomarkers for identifying early-stage renal cell carcinoma (RCC) patients is rarely explored. The present study aims to explore the possibility of uEV miRNAs as novel molecular biomarkers for distinguishing early-stage RCC. uEVs were extracted by ExoQuick-TC™ kit and miRNA concentrations were measured by RT-qPCR. ROC curves and bioinformatics analysis were employed to predict the diagnostic efficacy and regulatory mechanisms of dysregulated miRNAs. Through a multiphase case-control study on uEV miRNAs screening, training, and validation in RCC cells (ACHN, Caki-1) and control cells (HK-2) and in uEVs of 125 RCC patients and 128 age- and sex-matched controls, we successfully identified four uEVs miRNAs (miR-135b-5p, miR-196b-5p, miR-200c-3p, and miR-203a-3p) were significantly and stably upregulated in RCC in vitro and in vivo. When adjusted with estimated glomerular filtration rate (eGFR), the AUC of the three-uEV miRNA panel (miR-135b-5p, miR-200c-3p, and miR-203a-3p) was 0.785 (95 % CI = 0.729–0.842, P < 0.0001) for discriminating RCC patients from controls. Notably, this panel exhibited similar performance in distinguishing early-stage (stage Ⅰ) RCC patients, with an AUC of 0.786 (95 %CI = 0.727–0.844, P < 0.0001). Bioinformatics analysis predicted that candidate miRNAs were involved in cancer progressing. Our study identified a four uEV miRNAs panel (miR-135b-5p, miR-196b-5p, miR-200c-3p, and miR-203a-3p) may serve as an auxiliary noninvasive indication of early-stage RCC. [ABSTRACT FROM AUTHOR]

Backgrounds Guillain-Barré syndrome (GBS) is a postinfectious immune-mediated peripheral neuropathy. Interleukin (IL)-27 and IL-35 have been recognized as novel members of IL-12 family. We evaluated the serum and cerebral spinal fluid (CFS) concentrations of IL-27 and IL-35 in GBS and analyze their correlations with clinical characteristics. Methods Serum samples from 50 patients with GBS including 9 acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 33 acute motor axonal neuropathy (AMAN) and 8 unclassified and 35 age- and sex-matched healthy controls were collected. Thirty CSF samples from these patients and 25 patients with other noninflammatory neurological disorders (ONNDs) as disease controls were collected after lumbar puncture. Serum and CSF IL-27 and IL-35 concentrations were measured using human IL-27 or IL-35 ELISA. Results Serum IL-27 concentrations were elevated ( p = 0.002) whereas serum IL-35 concentrations were decreased ( p = 0.031) in patients with GBS comparing with healthy controls, particularly in patients exhibiting AMAN ( p = 0.012). Additionally, serum IL-35 concentrations were negatively correlated with disease severity and outcomes in patients with AMAN ( r = − 0.358, p = 0.041; r = − 0.416, p = 0.016). Conclusions IL-27 might be pathogenic, whereas IL-35 be protective in GBS. Additionally, serum IL-35 concentrations may be important biomarkers for the severity and outcomes of AMAN. [ABSTRACT FROM AUTHOR]