ABSTRACT
MicroRNA-494 (miR-494) is a small non-coding RNA located in chromosome 14q32.31 and regulates post-transcriptional gene expression by promoting the degradation of its target mRNAs via binding to the 3' untranslated regions (3'UTR). It has been reported that miR-494 plays an important role in the occurrence, development and prognosis of various diseases. Several signaling pathways modulated by miR-494 including the PTEN/PI3K/AKT, nuclear factor κ-B (NF-κB), mitogen-activated protein kinase (MAPK), transforming growth factor-β (TGF-β)/SMAD, and Wnt/β-catenin are associated with physiological regulation and pathological process in many diseases. The stably expression of miR-494 in the blood stream suggests its potential as a biological marker for disease diagnosis, treatment, and prognosis. Based on recent research, we summarize the role and molecular mechanism of miR-494 in disease development and progression. We also discuss its potential as a marker for clinical diagnosis and prognosis of various diseases.
Subject(s)
MicroRNAs/metabolism , NF-kappa B/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction , Transforming Growth Factor beta/metabolismABSTRACT
Objective@#To compare the efficiency of the target gene panel method and whole-exome sequencing (WES) in detecting idiopathic hypogonadotropic hypogonadism (IHH), and select a more suitable gene detection method.@*METHODS@#We selected 24 genes closely related to the molecular pathogenesis of IHH to make up the gene panel, detected the mutation sites in 73 patients with IHH using the panel method, and verified the results of sequencing with the Sanger method. Using the key words "idiopathic hypogonadotropic hypogonadism", we searched databases for relevant literature, calculated the positive rate of IHH detected by WES and compared it with that detected with the panel method.@*RESULTS@#Of the 73 cases of IHH detected with the panel method, 7 were found with pathogenic mutations, including 2 cases of FGFR1, 2 cases of CHD7, 2 cases of KISS1R, and 1 case of NR5A1 mutation. Sanger sequencing showed that the positive rate of the panel method was 9.7%. Of the 1 336 articles retrieved, 5 met the inclusion criteria and were included, in which WES revealed a positive rate of about 30%.@*CONCLUSIONS@#For detection of the diseases with clear mutated genes, the panel method is relatively inexpensive and has a high sequencing depth, while for detection of the diseases with complicated genetic patterns and unclear mutated genes, WES is more efficient. Further studies are needed for choice of the two methods for different purpose of detection./.
Subject(s)
Humans , Male , Hypogonadism/genetics , Exome SequencingABSTRACT
Objective To study the mechanisms on drug susceptibility and resistance of clinically multidrug-resistant Escherichia coli isolates,to provide information on related treatment.Methods The susceptibility of E.coli strains that isolated from different kinds of samples in the last 3 years on drugs was analyzed by agar dilution test,with strains that exhibiting resistances to cefotuxime,ciprofloxacin and amikacin simultaneously collected for further analysis.Resistant genes which mediate resistance to β-lactamases,fluoroquinolone and aminoglycoside as well as phylogenic type were detected by PCR amplification while genetic relation was analyzed by PFGE.Transferability of resistant plasmids was identified by conjugation test.Results In total,137 multidrug-resistant E.coli isolates were collected.Only 1％ of the isolates exhibited resistance to both imipenem and meropenem while 4％ of the strains were resistant to piperacillin/tazobactam.Most (85％) of the isolates were positive to ESBL and majority of them produced CTX-M.Target substitution and production of methylases were the main mechanisms causing resistance to fluoroquinolones and aminoglycosides respectively.Conclusion The main source of clinical multidrug-resistance was collected from urine samples.Carbapenem and enzyme inhibitor-containing antibiotics seemed to be the available antibiotics that were sentitive to the clinically multidrug-resistant E.coli isolates.
ABSTRACT
To develop a HBV infection mouse model by hydrodynamic-based transfection and further to optimize the method of development of HBV infection mouse model. We first developed a construct which contained inverted terminal repeat elements (ITR) of adeno-associated virus (AAV) and 1. 3 copies of HBV genome (ayw subtype). The pAAV-HBV1. 3 DNA was then injected hydrodynamically into the tail veins of C57BL/6 mice in 5 seconds. The virus load in serum and liver was assayed by ELISA and Real-time PCR. The expression of virus antigen and the pathologic changes of liver were analyzed by HE and immunohistochemical staining. Meanwhile, to develop HBV transfected immunosuppressied mouse, mice were injected intraperitoneally triple with 0.2 ml dexamethason (50 mg/kg) every two days before HBV transfection. The levels of HBsAg and HBeAg were assayed by ELISA. Our data showed: (1) HBsAg and HBeAg were positive (100%) in serum and liver of experimental normal mouse at day 10 after HBV transfection, and became negative at day 30 and day 60. Meanwhile the viral load in serum and liver in experimental group was significantly higher than that in control group at day 10, 30 and 60 after HBV transfection (P < 0.01, P < 0.05, respectively). (2) HBsAg and HBeAg in serum in immunosuppressed mouse model were positive until 60 days. In conclusion, a HBV infection mouse model was developed successfully by hydrodynamic-based transfection. By suppressing the immune status of mice injected with dexamethasone, the expression of HBV antigens was extended longer than that in normal adult mice. These models pave a way for HBV research and evaluation of HBV vaccine and drug development.