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Aim: We aimed to explore a new approach and theoretical basis for the diagnosis, treatment and prognosis of pre‐eclampsia. Methods: In total, 103 pre‐eclamptic patients (study group: SG) and 100 healthy pregnant women (control group: CG) were enrolled. Reverse transcription quantitative polymerase chain reaction (RT‐qPCR) was used to detect the expression level of serum Hoxb3. Enzyme‐linked immunosorbent assay was used to detect the content of serum sFlt‐1. Pregnancy outcomes in the two groups were recorded, and the correlations of the levels of Hoxb3 and sFlt‐1 with the pregnancy outcomes were analyzed. Results: The relative expression of serum Hoxb3 mRNA in the CG was significantly higher than that in the SG, whereas the content of serum sFlt‐1 in the CG was significantly lower than that in the SG. Compared with the CG, the SG had a significantly lower number of spontaneous deliveries, higher number of cesarean deliveries and significantly higher number of uneventful perinatal births. The incidences of intrauterine growth restriction, intrauterine distress, premature infants and neonatal deaths in perinatal infants in the SG were significantly higher than those in the CG. According to the analysis of receiver operating characteristic curves, the areas under the curves of Hoxb3, sFlt‐1 and their combined detection for diagnosing pre‐eclampsia were 0.799, 0.856 and 0.930, respectively. The areas under the curves for predicting poor perinatal outcomes were 0.724, 0.828 and 0.871, respectively. Conclusion: In conclusion, Hoxb3 and sFlt‐1 have certain reference significance for the risk evaluation of pre‐eclampsia and the adverse pregnancy outcomes of pre‐eclampsia women. [ABSTRACT FROM AUTHOR]

The giant panda (Ailuropoda melanoleuca) is a native species to China. They are rare and endangered and are regarded as the ‘national treasure’ and ‘living fossil’ in China. For the time being, there are only about 2500 giant pandas in the world. Therefore, we still have to do much more efforts to protect the giant pandas. In captive wildlife, the cataract incidence of mammalian always increases with age. Currently, in China, the proportion of elderly giant pandas who suffering from cataract has reached 20%. The eye disorder thus has a strong influence on the physical health and life quality of the elderly giant pandas. To discover the genes associated with the pathogenesis of cataract in the elderly giant panda and achieve the goal of early assessment and diagnosis of cataract in giant pandas during aging, we performed whole genome methylation sequencing in 3 giant pandas with cataract and 3 healthy giant pandas using methylation-dependent restriction-site associated DNA sequencing (MethylRAD). In the present study, we obtained 3.62M reads, on average, for each sample, and identified 116 and 242 differentially methylated genes (DMGs) between the two groups under the context of CCGG and CCWGG on genome, respectively. Further KEGG and GO enrichment analyses determined a total of 110 DMGs that are involved in the biological functions associated with pathogenesis of cataract. Among them, 6 DMGs including EEA1, GARS, SLITRK4, GSTM3, CASP3, and EGLN3 have been linked with cataract in old age. [ABSTRACT FROM AUTHOR]

Lead exposure causes or aggravates hearing damage to human or animal, but the detailed effects of lead exposure on auditory system including injury sites of the cochlea in mammal remain controversy. To investigate the effect of chronic lead exposure on auditory system, 40 adult guinea pigs with normal hearing were randomly divided into five groups. They were fed 2 mmol/L lead acetate in drinking water for 0, 15, 30, 60, and 90 days (n = 8), respectively. Lead concentrations in blood, cochlea, and brainstem were measured. Auditory function was measured by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). The morphology of cochlea and brainstem was observed, and expression of autophagy-related protein in brainstem was also assessed. The blood lead concentration reached a high level at the 15th day and kept stable, but the lead level in brainstem and cochlear tissue increased obviously at the 60th day and 90th day of lead exposure, respectively. There was no significant difference in the morphology of hair cells and stria vascularis (SV) among these five groups, but the number of spiral ganglion neuron (SGN) gradually decreased after 60 days. The differences of ABR thresholds and DPOAE amplitudes were not statistically significant among each group, but I wave latency, III latency, and I-III wave interval of ABR were delayed with the prolonging of time of lead exposure. The expressions of autophagy-related protein ATG5, ATG6, and LC3B in brainstem were increased after 30 days. These results suggest that the key target of lead toxicity was the auditory nerve conduction pathway including SGNs and brainstem, rather than cochlear hair cells and SV. Autophagy may play a very important role in lead toxicity to auditory nervous system. [ABSTRACT FROM AUTHOR]

Background: Individualized therapeutic regimen is a recently intensively pursued approach for targeting diseases, in which the search for biomarkers was considered the first and most important. Thus, the goal of this study was to investigate whether the UGT1A1, ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A genes are underlying biomarkers for gastric cancer, which, to our knowledge, has not been performed.Methods: Ninety-eight tissue specimens were collected from gastric cancer patients between May 2012 and March 2015. A multiplex branched DNA liquidchip technology was used for measuring the mRNA expressions of ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A. Direct sequencing was performed for determination of UGT1A1 polymorphisms. Furthermore, correlations between gene expressions, polymorphisms and clinicopathological characteristics were investigated.Results: The expressions of TYMS, TUBB3 and STMN1 were significantly associated with the clinicopathological characteristics of age, gender and family history of gastric cancer, but not with differentiation, growth patterns, metastasis and TNM staging in patients with gastric cancer. No clinical characteristics were correlated with the expressions of ERCC1, BRCA1, RRM1 and TOP2A. Additionally, patients carrying G allele at -211 of UGT1A1 were predisposed to developing tubular adenocarcinoma, while individuals carrying 6TAA or G allele respectively at *28 or -3156 of UGT1A1 tended to have a local invasion.Conclusions: The UGT1A1 polymorphism may be useful to screen the risk population of gastric cancer, while TYMS, TUBB3 and STMN1 may be potential biomarkers for prognosis and chemotherapy guidance. [ABSTRACT FROM AUTHOR]

Chronic stress induces altered energy metabolism and plays important roles in the etiology of depression, in which the glucocorticoid negative feedback is disrupted due to imbalanced glucocorticoid receptor (GR) functions. The mechanism underlying the dysregulation of GR by chronic stress remains elusive. In this study, we investigated the role of AMP-activated protein kinase (AMPK), the key enzyme regulating cellular energy metabolism, and related signaling pathways in chronic stress-induced GR dysregulation. In cultured rat cortical astrocytes, glucocorticoid treatment decreased the level, which was accompanied by the decreased expression of liver kinase B1 (LKB1) and reduced phosphorylation of AMPK. Glucocorticoid-induced effects were attenuated by glucocorticoid-inducible kinase 1 (SGK1) inhibitor GSK650394, which also inhibited glucocorticoid induced phosphorylation of Forkhead box O3a (FOXO3a). Furthermore, glucocorticoid-induced down-regulation of GR was mimicked by the inhibition of AMPK and abolished by the AMPK activators or the histone deacetylase 5 (HDAC5) inhibitors. In line with the role of AMPK in GR expression, AMPK activator metformin reversed glucocorticoid-induced reduction of AMPK phosphorylation and GR expression as well as behavioral alteration of rats. Taken together, these results suggest that chronic stress activates SGK1 and suppresses the expression of LKB1 via inhibitory phosphorylation of FOXO3a. Downregulated LKB1 contributes to reduced activation of AMPK, leading to the dephosphorylation of HDAC5 and the suppression of transcription of GR. [ABSTRACT FROM AUTHOR]

Abstract: Some of the most serious diseases are characterized by the presence of a specific secondary structure within DNA or RNA, often in the promoter or the coding region of the responsible gene, that enhances or disrupts expression of the protein. Structural elements that impact cellular function may also be formed in other genomic regions such as telomeres. Compounds that interact with such structural elements may be useful in diagnosis or treatment of patients. In this report, we present a FRET melting assay that allows testing of libraries of compounds against four different nucleic acid structures. Compounds are tested to determine whether they stabilize preformed secondary structures (i.e., whether they cause an increase in melting temperature (Tm )). This property is described by the ΔTm parameter, which is the difference between the Tm of the compound-stabilized structure and the Tm of the unbound structure. Model oligonucleotides are labeled with FAM as a fluorescent donor and TAMRA as an acceptor. The intensity of FAM fluorescence is recorded as a function of temperature. Melting temperatures are determined by the FRET method in 96-well plates; this assay could easily be converted into 384-well format. [Copyright &y& Elsevier]