Ghrelin regulates the endoplasmic reticulum stress signalling pathway in gestational diabetes mellitus.

OBJECTIVE: We aimed to investigate the effects and mechanisms of the ghrelin-regulated endoplasmic reticulum stress (ERS) signalling pathway in gestational diabetes mellitus (GDM). METHODS: Pregnant female C57BL/6 mice were randomly divided into a normal group, GDM group (high-fat diet + STZ), GDM + ghrelin group (acyl ghrelin), and GDM + ghrelin + ghrelin inhibitor group ([D-lys3]-GHRP-6). We measured body weight, the intake of water and food, glucose, cholesterol, triglyceride and fasting insulin levels in each group. HE staining was used to observe the morphological changes in the pancreas. The TUNEL method was used to detect the apoptosis rate of islet cells. qPCR and Western boltting were performed to detect the relative expression levels of PERK, ATF6, IREIα, GRP78, CHOP and caspase-12, which are related to the ERS signalling pathway in the pancreas. Then, NIT-1 cells were cultured to verify whether ghrelin regulates ERS under high-glucose or tunicamycin conditions. RESULTS: Compared with the GDM group, the GDM + ghrelin group showed improved physical conditions and significantly decreased the fasting blood glucose, glucose tolerance, cholesterol, triglyceride and fasting insulin levels. Damaged islet areas were inhibited by ghrelin in the GDM group. The GDM + ghrelin group showed reduced ß-cell apoptosis compared to the GDM and GDM + ghrelin + ghrelin inhibitor groups. ERS-associated factors (PERK, ATF6, IREIα, GRP78, CHOP and caspase-12) mRNA and protein levels were obviously lower in the GDM + ghrelin group than in the GDM group, while expression levels were restored in the inhibitor group. Ghrelin treatment improved the high-glucose or tunicamycin-induced apoptosis, increased insulin levels and upregulation of GRP78, CHOP and caspase-12 in NIT-1 cells. CONCLUSION: Ghrelin suppressed ERS signalling and apoptosis in GDM mice and in NIT-1 cells. This study established a link between ghrelin and GDM, and the targeting of ERS with ghrelin represents a promising therapeutic strategy for GDM.

Privately vertically mining of sequential patterns based on differential privacy with high efficiency and utility.

Sequential pattern mining is one of the fundamental tools for many important data analysis tasks, such as web browsing behavior analysis. Based on frequent patterns, decision-makers can obtain both economic gains and social values. Sequential data, on the other hand, frequently contain sensitive information, and directly analyzing these data will raise user concerns from a privacy perspective. Differential privacy (DP), as the most popular privacy model, has been employed to address this privacy concern. Most existing DP-Solutions are designed to combine horizontal sequence pattern mining algorithms with differential privacy. Due to the inefficiency of horizontal algorithms, their DP-Solutions cannot ensure high efficiency and accuracy while offering a high privacy guarantee. Therefore, we proposed privVertical, a new private sequence pattern mining scheme combining the vertical mining algorithm with differential privacy to achieve the above objective. Unlike DP-solutions based on horizontal algorithms, privVertical can promote efficiency by avoiding performing costly database scans or costly projection database constructions. Moreover, to promote accuracy, a differentially private hash MapList (called privHashMap) is designed to record frequent concurrency items and their noisy support based on the Sparse Vector Technique. PrivHashMap is used to pre-pruning excessive infrequent candidate sequences in private mining, and Sparse Vector Technique is used to promote the accuracy of PrivHashMap. After pruning these invalid candidate sequences, less noise is required to achieve the same level of privacy, increasing the accuracy of private mining. Theoretical privacy analysis proves privVertical satisfies [Formula: see text]-differential privacy. Experiments show that privVertical achieves higher accuracy and efficiency while achieving the same privacy level.

Echinacea purpurea-derived homogeneous polysaccharide exerts anti-tumor efficacy via facilitating M1 macrophage polarization.

Echinacea purpurea modulates tumor progression, but the underlying mechanism is poorly defined. We isolated and purified a novel homogeneous polysaccharide from E. purpurea (EPPA), which was shown to be an arabinogalactan with a mean molecular mass (Mr) of 3.8 × 104 Da and with α- (1 → 5) -L-Arabinan as the backbone and α-L-Araf-(1→, →6)-ß-D-Galp-(1→, and →4)-α-D-GalpA-(1→ as the side chains. Interestingly, oral administration of EPPA suppresses tumor progression in vivo and shapes the immune cell profile (e.g., facilitating M1 macrophages) in tumor microenvironment by single-cell RNA sequencing (scRNA-seq) analysis. More importantly, EPPA activates the inflammasome through a phagocytosis-dependent mechanism and rewires transcriptomic and metabolic profile, thereby potentiating M1 macrophage polarization. Collectively, we propose that EPPA supplementation could function as an adjuvant therapeutic strategy for tumor suppression.

The draft genome and multi-omics analyses reveal new insights into geo-herbalism properties of Citrus grandis 'Tomentosa'.

Citrus grandis 'Tomentosa' (CGT) (Huajuhong, HJH) is a widely used medicinal plant, which is mainly produced in Guangdong and Guangxi provinces of South China. Particularly, HJH from Huazhou (HZ) county of Guangdong province has been well-regarded as the best national product for geo-herbalism. But the reasons for geo-herbalism property in HJH from HZ county remains a mystery. Therefore, a multi-omics approach was applied to identify the nature of the geo-herbalism in CGT from three different regions. The comprehensive screening of differential metabolites revealed that the Nobiletin content was significantly different in HZ region compared to other regions, and could be employed as a key indicator to determine the geo-herbalism. Furthermore, the high-quality genome (N50 of 9.12 Mb), coupled with genomics and transcriptomics analyses indicated that CGT and Citrus grandis are closely related, with a predicted divergence time of 19.1 million years ago (MYA), and no recent WGD occurred in the CGT, and the bioactive ingredients of CGT were more abundant than that of Citrus grandis. Interestingly, Nobiletin (Polymethoxyflavones) content was identified as a potential indicator of geo-herbalism, and O-methyltransferase (OMT) genes are involved in the synthesis of Polymethoxyflavones. Further multi-omics analysis led to the identification of a novel OMT gene (CtgOMT1) whose transient overexpression displayed significantly higher Nobiletin content, suggesting that CtgOMT1 was involved in the synthesis of Nobiletin. Overall, our findings provide new data resources for geo-herbalism evaluation, germplasm conservation and insights into Nobiletin biosynthesis pathways for the medicinal plant C. grandis 'Tomentosa'.

An increase in prostate cancer diagnosis during inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND: In recent years, some studies showed that inflammatory bowel disease (IBD) might be associated with an increased risk of prostate cancer (PC), whereas some other studies indicated that IBD was not associated with the increased risk of PC. In the present study, we aimed to conduct a systematic review and meta-analysis to evaluate the association of IBD and PC risk. METHODS: Web of Science and PubMed were systematically searched on for link of PC risk and IBD published from January 1976 to February 2019. The pooled multivariate odd ratio (OR) or relative risk (RR) and 95% confidence intervals (CI) were obtained by the use of STATA 12.0 software. RESULTS: The meta-analysis indicated that IBD showed a 78% increase in PC risk (95% CI: 1.32-2.41). Sensitivity analyses showed no changes in the direction of effect after excluding any one study (supplementary figure 1). A significant heterogeneity was detected between different studies (Q test, P<0.001). Moreover, Begg's test, Egger's tests and funnel plots indicated no significant publication bias between included studies [Begg's test (P=0.371); Egger's test (p=0.100)]. CONCLUSION: The present meta-analysis demonstrated that IBD was associated with an increased diagnosis of PC. In addition, large scale prospective studies are essential to determine whether IBD increase the PC risk.

Network Pharmacology Analysis of Damnacanthus indicus C.F.Gaertn in Gene-Phenotype.

Damnacanthus indicus C.F.Gaertn is known as Huci in traditional Chinese medicine. It contains a component having anthraquinone-like structure which is a part of the many used anticancer drugs. This study was to collect the evidence of disease-modulatory activities of Huci by analyzing the published literature on the chemicals and drugs. A list of its compounds and direct protein targets is predicted by using Bioinformatics Analysis Tool for Molecular Mechanism of TCM. A protein-protein interaction network using links between its directed targets and the other known targets was constructed. The DPT-associated genes in net were scrutinized by WebGestalt. Exploring the cancer genomics data related to Huci through cBio Portal. Survival analysis for the overlap genes is done by using UALCAN. We got 16 compounds and it predicts 62 direct protein targets and 100 DPTs and they were identified for these compounds. DPT-associated genes were analyzed by WebGestalt. Through the enrichment analysis, we got top 10 identified KEGG pathways. Refined analysis of KEGG pathways showed that one of these ten pathways is linked to Rap1 signaling pathway and another one is related to breast cancer. The survival analysis for the overlap genes shows the significant negative effect of these genes on the breast cancer patients. Through the research results of Damnacanthus indicus C.F.Gaertn, it is shown that medicine network pharmacology may be regarded as a new paradigm for guiding the future studies of the traditional Chinese medicine in different fields.