Human chorionic gonadotropin increases β-cleavage of amyloid precursor protein in SH-SY5Y cells

Elevated levels of amyloid-β (Aβ) peptides, the main component of amyloid plaques in Alzheimer's disease, are the result of excessive β- and γ-cleavage of the amyloid precursor protein (APP) and/or impaired Aβ clearance in the brain. It has been suggested that high concentrations of luteinizing hormone (LH) in women contribute to increased Aβ generation after menopause, but the mechanism for this is incompletely understood. We investigated the effect of human chorionic gonadotropin (hCG), an LH receptor agonist, on APP β-cleavage in the SH-SY5Y neuroblastoma cell line. Treatment of these cells with hCG-induced elevated β-cleavage in a dose-dependent manner: administration of 30 mIU but not 10 mIU/ml of hCG significantly increased sAPPβ levels in the cell medium 1.7-fold as measured by ELISA. These results support the notion that LH contributes to elevated Aβ levels at least in part by increasing β-cleavage of APP by β-site APP cleaving enzyme.NHMRC grant: 104596

The Traditional Chinese Medicine and Relevant Treatment for the Efficacy and Safety of Atopic Dermatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background. Atopic dermatitis (AD) has become a common skin disease that requires systematic and comprehensive treatment to achieve adequate clinical control. Traditional Chinese medicines and related treatments have shown clinical effects for AD in many studies. But the systematic reviews and meta-analyses for them are lacking. Objective. The systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were conducted to evaluate the efficacy and safety of traditional Chinese medicines and related treatments for AD treatment. Methods. Randomized controlled trials (RCTs) were searched based on standardized searching rules in eight medical databases from the inception up to December 2016 and a total of 24 articles with 1,618 patients were enrolled in this meta-analysis. Results. The results revealed that traditional Chinese medicines and related treatments did not show statistical differences in clinical effectiveness, SCORAD amelioration, and SSRI amelioration for AD treatment compared with control group. However, EASI amelioration of traditional Chinese medicines and related treatments for AD was superior to control group. Conclusion. We need to make conclusion cautiously for the efficacy and safety of traditional Chinese medicine and related treatment on AD therapy. More standard, multicenter, double-blind randomized controlled trials (RCTs) of traditional Chinese medicine and related treatment for AD were required to be conducted for more clinical evidences providing in the future

A Continuous, Fluorescence-based Assay of µ-Opioid Receptor Activation in AtT-20 Cells

Opioids are widely prescribed analgesics, but their use is limited due to development of tolerance and addiction, as well as high variability in individual response. The development of improved opioid analgesics requires high-throughput functional assays to assess large numbers of potential opioid ligands. In this study, we assessed the ability of a proprietary "no-wash" fluorescent membrane potential dye to act as a reporter of µ-opioid receptor (MOR) activation and desensitization via activation of G-protein-coupled inwardly rectifying potassium channels. AtT-20 cells stably expressing mouse MOR were assayed in 96-well plates using the Molecular Devices FLIPR membrane potential dye. Dye emission intensity decreased upon membrane hyperpolarization. Fluorescence decreased in a concentration-dependent manner upon application of a range of opioid ligands to the cells, with high-efficacy agonists producing a decrease of 35% to 40% in total fluorescence. The maximum effect of morphine faded in the continued presence of agonist, reflecting receptor desensitization. The effects of opioids were prevented by prior treatment with pertussis toxin and blocked by naloxone. We have demonstrated this assay to be an effective method for assessing ligand signaling at MOR, which may potentially be scaled up as an additional high-throughput screening technique for characterizing novel opioid ligands.NHMRC Grant Numbers: 1011979 & 104596

The Pseudorabies Virus DNA Polymerase Accessory Subunit UL42 Directs Nuclear Transport of the Holoenzyme

Pseudorabies virus (PRV) DNA replication occurs in the nuclei of infected cells and requires the viral DNA polymerase. The PRV DNA polymerase comprises a catalytic subunit, UL30, and an accessory subunit, UL42, that confers processivity to the enzyme. Its nuclear localization is a prerequisite for its enzymatic function in the initiation of viral DNA replication. However, the mechanisms by which the PRV DNA polymerase holoenzyme enters the nucleus have not been determined. In this study, we characterized the nuclear import pathways of the PRV DNA polymerase catalytic and accessory subunits. Immunofluorescence analysis showed that UL42 localizes independently in the nucleus, whereas UL30 alone predominantly localizes in the cytoplasm. Intriguingly, the localization of UL30 was completely shifted to the nucleus when it was coexpressed with UL42, demonstrating that nuclear transport of UL30 occurs in an UL42-dependent manner. Deletion analysis and site-directed mutagenesis of the two proteins showed that UL42 contains a functional and transferable bipartite nuclear localization signal (NLS) at amino acids 354–370 and that K354, R355, and K367 are important for the NLS function, whereas UL30 has no NLS. Coimmunoprecipitation assays verified that UL42 interacts with importins α3 and α4 through its NLS. In vitro nuclear import assays demonstrated that nuclear accumulation of UL42 is a temperature- and energy-dependent process and requires both importins α and β, confirming that UL42 utilizes the importin α/β-mediated pathway for nuclear entry. In an UL42 NLS-null mutant, the UL42/UL30 heterodimer was completely confined to the cytoplasm when UL42 was coexpressed with UL30, indicating that UL30 utilizes the NLS function of UL42 for its translocation into the nucleus. Collectively, these findings suggest that UL42 contains an importin α/β-mediated bipartite NLS that transports the viral DNA polymerase holoenzyme into the nucleus in an in vitro expression system

Effects of soluble epoxide hydrolase inhibitor on the expression of fatty acid synthase in peripheral blood mononuclear cell in patients with acute coronary syndrome

Abstract Background Researches have shown that soluble epoxide hydrolase inhibitors (sEHi) can protect against the development of atherosclerosis. Simultaneously, emerging evidences have implicated the association between fatty acid synthase (FAS) and acute coronary syndrome (ACS). We tested the hypothesis that sEHi could reduce the occurrence of ACS by regulating FAS. Methods Hospitalized ACS patients were selected as the ACS group (n = 65) while healthy normal subjects as the control group (n = 65). The blood levels of lipoproteins, fasting glucose, myocardial enzyme and high-sensitivity C-reactive protein (hs-CRP) were measured within 24 hours after admission. The peripheral blood mononuclear cells (PBMCs) were isolated and cultured. Trans-4-[4-(3-Adamantan-1-ylureido)cyclohexyloxy] benzoic acid (t-AUCB), a kind of sEHi, was then added to cells in various concentrations (0, 10, 50, 100 μmol/L). The expression of FAS, interleukin-6 (IL-6) mRNA and protein was detected by real-time PCR or Western blot, respectively. Results (1) Compared with the control group, the serum concentration of hs-CRP in the ACS group was increased (PPPPP Conclusions sEH inhibition regulated FAS and inhibited inflammation in cultured PBMCs from ACS patients, a mechanism that might prevent rupture of atherosclerotic lesions and protect against development of ACS.</p

The Current Research and Application of Solid-state Fermentation of Wheat Bran

Wheat bran is the main by-product during the milling process of wheat flour,which is rich in bioactive substances.It could be used as the substrate for microbial growth in the process of solid-state fermentation and in various industrial production fields.The current research and application of solidstate fermented wheat bran in metabolites production,microbial inoculums preparation,whole-grain food processing,and feed substitution were reviewed in this study,and their prospects were also put forward,in order to provide a theoretical reference for the further and systematic research of wheat bran solid-state fermentation

Physical function, ADL, and depressive symptoms in Chinese elderly: Evidence from the CHARLS

BackgroundDepressive symptoms are a serious public health problem that affects the mental health of older adults. However, current knowledge of the association between ADL disability and physical dysfunction and depressive symptoms in Chinese adults is insufficient. We intend to analyze the association between physical function, ADL, and depressive symptoms in older Chinese adults.MethodsThe data obtained from the China Health and Retirement Longitudinal Survey (2015 and 2018) (CHARLS). This includes 3,431 in 2015 and 3,258 in 2018 over the age of 60. Comparing 2015 and 2018 data, multivariate logistic regression models were used to explore the relationship between physical function, ADL, and depressive symptoms in urban and rural older adults, adjusting for sociodemographic factors associated with depression in older adults.ResultsThe prevalence of depressive symptoms among older adults in China was 33.8 percent in 2015 and 50.6 percent in 2018. In baseline data from 2015 and 2018, residence, gender, marital status, drinking, physical function, ADL, and self-rated health were all found to be significantly associated with depressive symptoms in older adults. The differences in physical function, ADL and depressive symptoms among older adults in 2015 and 2018 were further analyzed based on urban and rural stratification. Both physical dysfunction and ADL disability were significantly associated with depressive symptoms in rural older adults in 2015 and 2018. And in urban areas, ADL was found to be significantly associated with depressive symptoms in urban older adults. Multivariate logistic regression analysis demonstrated that ADL disability was significantly associated with depressive symptoms among older adults in both urban and rural areas. Physical dysfunction was only significant in rural areas with depressive symptoms. The alpha level was instead set to 0.05 for all statistical tests.ConclusionRural, female, 60–70 years of age, primary school or below, married, non-smoking, non-drinking, physical dysfunction, ADL disability and self-rated poor health make-up a higher proportion of depressed older adults. ADL disability and physical dysfunction were more likely to be associated with depressive symptoms in rural Chinese older adults. Therefore, the physical and mental health of rural elderly should be of concern. The rural older adults should receive additional support from the government and society

Endoscopic video defogging using luminance blending.

Endoscopic video sequences provide surgeons with direct surgical field or visualisation on anatomical targets in the patient during robotic surgery. Unfortunately, these video images are unavoidably hazy or foggy to prevent surgeons from clear surgical vision due to typical surgical operations such as ablation and cauterisation during surgery. This Letter aims at removing fog or smoke on endoscopic video sequences to enhance and maintain a direct and clear visualisation of the operating field during robotic surgery. The authors propose a new luminance blending framework that integrates contrast enhancement with visibility restoration for foggy endoscopic video processing. The proposed method was validated on clinical endoscopic videos that were collected from robotic surgery. The experimental results demonstrate that their method provides a promising means to effectively remove fog or smoke on endoscopic video images. In particular, the visual quality of defogged endoscopic images was improved from 0.5088 to 0.6475

Decreased expression of long non-coding RNA WT1-AS promotes cell proliferation and invasion in gastric cancer

AbstractTumor recurrence and metastasis remain the major obstacles for the successful treatment of patients diagnosed with gastric cancer. In recent years, long non-coding RNAs (lncRNAs) have been considered as key regulators of tumor behavior. In this study, we investigated the expression and biological role of a newly-identified cancer-related lncRNA, WT1-AS. We found that WT1-AS expression was significantly down-regulated in tumor tissues compared to matched adjacent non-tumor tissues. The WT1-AS expression level was also associated with tumor size and the clinicopathological stage. Cell proliferation, migration, and invasion were inhibited, and the proportion of G0/G1 cells increased when WT1-AS was ectopically-expressed in gastric cancer cells. Furthermore, ectopic expression of WT1-AS was demonstrated to inhibit tumor growth and metastasis in vivo. Finally, we found that WT1-AS overexpression could decrease ERK protein phosphorylation. Our study indicates that WT1-AS is significantly down-regulated in gastric cancers and may be correlated with tumor progression

Comparison of Dynamics of Udder Skin Microbiota From Grazing Yak and Cattle During the Perinatal Period on the Qinghai-Tibetan Plateau

he perinatal period has an important impact on the health of ruminants, and the imbalance of udder skin microbiota might be an important inducement of bovine mastitis. However, it is not clear how the perinatal period affects the microbial structure and stability of the udder skin of yak and cattle. Here, we used 16S rRNA gene high-throughput sequencing to analyze the udder skin microbiota of yak and cattle during the perinatal period. We found that the diversity and richness of microbiota of bovine udder skin during 1–2 weeks postpartum were significantly lower than those in the 1–2 weeks prenatal and 1-month postpartum period (Wilcoxon, p &lt; 0.05). Besides, we found sharing of 2,533 OTUs in the udder skin microbiota of yak and cattle during the perinatal period, among which the core microbiota at the genera level was mainly composed of Staphylococcus, Moraxella, and Acinetobacter. However, the genus Acinetobacter was significantly abundant in the udder skin of cattle during 1–2 weeks postpartum. The NMDS and LEfSe results showed that the perinatal period had more effects on the composition and stability of microbial community in the udder skin of cattle compared to yak, particularly during 1–2 weeks postpartum. In addition, the average content of total whey proteins and immunoglobulin G of whey protein were significantly higher in the yak colostrum when compared to those found in the cattle (p &lt; 0.05). In conclusion, the structure of udder skin microbiota of yak during the perinatal period is more stable than that of cattle in the same habitat, and 1–2 weeks postpartum may be a potential window period to prevent cattle mastitis