Investigating the shared genetic architecture between primary sclerosing cholangitis and inflammatory bowel diseases: a Mendelian randomization study.

BACKGROUND: Several studies have found that primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) are closely associated. However, the direction and causality of their interactions remain unclear. Thus, this study employs Mendelian Randomization to explore whether there are causal associations of genetically predicted PSC with IBD. METHODS: Genetic variants associated with the genome-wide association study (GWAS) of PSC were used as instrumental variables. The statistics for IBD, including ulcerative colitis (UC), and Crohn's disease (CD) were derived from GWAS. Then, five methods were used to estimate the effects of genetically predicted PSC on IBD, including MR Egger, Weighted median (WM), Inverse variance weighted (IVW), Simple mode, and Weighted mode. Last, we also evaluated the pleiotropic effects, heterogeneity, and a leave-one-out sensitivity analysis that drives causal associations to confirm the validity of the analysis. RESULTS: Genetically predicted PSC was significantly associated with an increased risk of UC, according to the study (odds ratio [OR] IVW= 1.0014, P<0.05). However, none of the MR methods found significant causal evidence of genetically predicted PSC in CD (All P>0.05). The sensitivity analysis results showed that the causal effect estimations of genetically predicted PSC on IBD were robust, and there was no horizontal pleiotropy or statistical heterogeneity. CONCLUSIONS: Our study corroborated a causal association between genetically predicted PSC and UC but did not between genetically predicted PSC and CD. Then, we identification of shared SNPs for PSC and UC, including rs3184504, rs9858213, rs725613, rs10909839, and rs4147359. More animal experiments and clinical observational studies are required to further clarify the underlying mechanisms of PSC and IBD.

Cytomegalovirus Infection Is a Risk Factor in Gastrointestinal Cancer: A Cross-Sectional and Meta-Analysis Study.

BACKGROUND: This study was planned to investigate the association betweenhuman cytomegalovirus (HCMV) infection and gastrointestinal cancer (GIC) risk, by undertaking a meta-analysis and case-control cross-sectional study. SUMMARY: A cross-sectional study analysis of 160 GIC patients and 100 control subjects indicated significantly higher HCMV prevalence in GIC patients based on the HCMV IgM test. However, a similar analysis based on an IgG test revealed no significant relationship. Further meta-analysis of 11 studies, including 1,044 patients and 991 healthy subjects, displayed HCMV infection as an important risk factor for not only colorectal cancer occurrence and development based on a HCMV DNA test, but also for GIC based on a HCMV IgM test. However, the IgG test again displayed no significant relationship between HCMV infection and GIC occurrence. Key Message: Overall, our study revealed that HCMV infection is associated with an increased GIC risk. However, additional studies are warranted to elucidate the molecular mechanism underlying this association.

Akebia saponin D alleviates hepatic steatosis through BNip3 induced mitophagy.

Akebia Saponin D (ASD) is the most abundant constituent of the rhizome of Dipsacus asper Wall. The prior studies have shown that ASD alleviates hepatic steatosis targeted at the modulation of autophagy and exerts hepatoprotective effects through mitochondria. However, it is still unclear which signal transduction pathway that ASD increase autophagy and protect the mitochondria. The purpose of this paper was to explore the mechanisms through which ASD alleviates hepatic steatosis. ASD significantly reduced lipid accumulation in BRL cells. Furthermore, ASD significantly increased the mitophagy acting as increase the colocalization between mitochondria and punctate EGFP-LC3. ASD treatment increased the expression of BNip3, phospho-AMPK, prevented oleic acid (OA) induced LC3-II and phospho-mTOR expression. These effects were similar to the effects cotreatment with rapamycin. ASD treatment could not attenuate the expression of BNip3 blocked by chloroquine (CQ) or siRNA-mediated knockdown of BNip3. These results suggest that Akebia saponin D alleviates hepatic steatosis targeted at BNip3 mediated mitophagy. Activation of BNip3 via ASD may offer a new strategy for treating NAFLD.

Cytomegalovirus infection and atherosclerosis risk: A meta-analysis.

Human cytomegalovirus (HCMV) infection is an important risk factor for atherosclerosis (AS). Numerous studies have been conducted to analyze the association between HCMV infection and risk of AS, but no clear consensus has been reached. So the objective of this paper was aimed to demonstrate the relationship between HCMV and AS by doing a meta-analysis. Relative literature was searched through the electronic databases PubMed, Embase, and CNKI. Data were accurately assessed and analyzed independently by two investigators. Ultimately, the 30 studies, involving 3328 cases and 2090 controls were included in our meta-analysis. The positive ratio of HCMV IgG, IgM, DNA and pp65 were, respectively, 63.26% (923/1459), 25.46% (69/271), 33.69% (381/1131), and 50.32% (158/314) in case patients. Meanwhile the positive ratio of HCMV IgG, IgM, DNA, and pp65 were, respectively, 52.12% (541/1038), 1.55% (3/194), 13.72% (79/576), and 12.26% (28/229) in control subjects. The positive ratio of HCMV infection was higher in atherosclerosis group than that in non-atherosclerosis group. Especially in Asian group, calculated odds ratios for the presence of HCMV infection in IgG-based HCMV tests, IgM-based tests, PCR-based tests, and pp65-based tests, expressed as OR (95% confidence intervals, 95%CI), were 3.07(95%CI 2.09-4.51), 8.92(95%CI 3.17-25.11), 6.75 (95%CI 3.50-13.02), and 5.72(95%CI 1.51-21.58), respectively. The meta-analysis results showed that HCMV infection is significant connected with an increased risk for AS.

VDR Gene variation and insulin resistance related diseases.

BACKGROUND: Vitamin D status may influence the risk of Insulin resistance related diseases such as Type 2 diabetes (T2DM), metabolic syndrome (MetS), and polycystic ovarian syndrome (PCOS). Several studies have assessed vitamin D receptor (VDR) gene polymorphism in relationship with these diseases; however, results remain inconsistent. Our study was conducted to elucidate whether VDR Gene polymorphisms could predict insulin resistance on a large scale. METHODS: A meta-analysis using MEDLINE and EMBASE, was performed up to December 16th, 2016. Studies reporting association of vitamin D gene polymorphism with incident T2DM, MetS and PCOS outcomes were included and sub-group analysis by pigment of skin and latitude were performed. RESULTS: A total of 28 articles based on four gene variation, and comprising 9232 participants with 5193 Insulin resistance related diseases patients were included. No significant associations of the VDR ApaI, BsmI, FokI and TaqI variant with Insulin resistance related diseases were found. However, sub-group analysis analysis showed that PCOS in TaqI (OR = 1.47, 95% CI = 1.03-2.09, P = 0.03) for T allele and MetS for G allele (OR = 1.41, 95% CI = 1.07-1.85, P = 0.01) in BsmI was significant association with VDR gene polymorphism. Simultaneously, sub-group analysis showed VDR ApaI rs7975232(G > T)variant was associated with insulin resistance related diseases in Asians (GG/GT + TT) (OR, 1.62; 95% CI, 1.03-2.53; P = 0.04) and population who lived in middle latitude district (30-60°) (GG/GT + TT) (OR, 1.22; 95% CI, 1.04-1.43; P = 0.02), VDR BsmI rs1544410 (A > G)and VDR Taq1rs731236 (T/C) variant were associated with insulin resistance related diseases in Caucasian (dark-pigmented). CONCLUSION: The results suggested that the association between insulin resistance related diseases and VDR ApaI, BsmI, FokI variant was more obvious in dark-pigmented Caucasians and Asians but not in Caucasian with white skin.

[Structural characterization of Glehniae Radix polysaccharides using partial acid hydrolysis-hydrophilic interaction liquid chromatography-mass spectrometry].

Water-soluble polysaccharides from traditional Chinese medicine have properties of complex structure and high molecular, resulting in hardly complete their structural characterization.However, a "bottom-up" approach could solve this problem.Glehniae Radix extract was extracted with hot water and then precipitated by 40% ethanol to obtain Glehniae Radix polysaccharides (RGP). Subsequently, a partial acid hydrolysis method was carried out and the effects of acid concentration, time and temperature on hydrolysis were investigated. Under the optimum hydrolysis condition (1.5 mol•L⁻¹ trifluoroacetic acid, 4 h, and 80 ℃), RGP were hydrolyzed to characteristic oligosaccharide fragments. Futher, a hydrophilic liquid chromatography- mass spectrometry method was used for the separation and structural characterization of the polysaccharide hydrolysates. According to MS and MS/MS analysis of several standard disaccharides, a method for determining the type of polysaccharide glycosidic linkage by mass spectrometry was established. The results showed that the polysaccharide hydrolysates were linear glucan containing 1, 4-glycosidic bonds. And gluco-oligosaccharides with the degrees of polymerization (DP) of 4-11 were obtained after partial acid hydrolysis.

Akebia Saponin D Decreases Hepatic Steatosis through Autophagy Modulation.

Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of the metabolic syndrome, and the incidence of NAFLD is increasing rapidly. However, appropriate drugs for treatment of NAFLD are lacking. This study aimed to elucidate the protective effects and mechanisms of Akebia saponin D (ASD) against NAFLD in ob/ob mice and Buffalo rat liver cells. ASD significantly decreased hepatic steatosis and hepatocyte apoptosis in ob/ob mice. ASD also significantly activated autophagic flux, as assessed by the decreased expression of light chain 3 (LC3)-II and P62 accumulation of autophagosomes. In Buffalo rat liver cells, ASD prevented oleic acid (OA)-induced lipid droplets and increased autophagic flux acting as increase the number of autolysosomes than autophagosomes in mTagRFP-mWasabi-LC3. ASD treatment also prevented OA-induced expression of LC3-II, P62, Beclin, and phospho-mammalian target of rapamycin. These effects were similar to those of cotreatment with rapamycin. ASD treatment could not prevent OA-increased, autophagy-related protein expression after treatment with chloroquine or small interfering RNA-mediated knockdown of atg7. These results suggest that ASD alleviates hepatic steatosis targeted at the fusion of autophagosomes to lysosomes, and autophagy modulation via ASD may offer a new strategy for treating NAFLD.

[The Component Analysis of Petroleum Ether Extract in Scutellariae barbatae,Hedyotis diffusa and the Herb Pair and the Investigation of Anti-Endometrial Cancer Cells Activity].

Objective: To investigate the chemical components and the activity of anti-endometrial cancer cells of the petroleum ether extract in Scutellariae barbatae and Hedyotis diffusa and the herb pair. Methods: Main composition analysis and identification were determined by the GC-MS technology combined with Kovats retention index( KI). Activity of anti-endometrial cancer cells was researched by MTT assay. Results: Unsaturated fatty acid,esters,sterol and other compounds in Scutellariae barbatae,Hedyotis diffusa and the herb pair were identified by GC-MS. Hedyotis diffusa and the herb pair contained more anthraquinones which distinguished from Scutellariae barbatae. The IC50 values for HEC-1A cells of petroleum ether extract in Scutellariae barbatae and Hedyotis diffusa and the herb pair were 275. 204 µg / m L,105. 826 µg / m L,148. 645 µg / m L. The IC50 values for Ishikawa cells of petroleum ether extract in Scutellariae barbatae and Hedyotis diffusa and the herb pair are 189. 114 µg / m L,77. 974 µg / m L,137. 999 µg / m L. Conclusion: Petroleum ether extract in Scutellariac barbatae and Hedyotis diffusa and the herb pair has inhibition effect on the proliferation of HEC-1A and Ishikawa cells,the Hedyotis diffusa has the strongest activity of anti-endometrial cancer. It is speculated that the strongest activity could be related to the higher content of anthraquinones.

[Study on Optimum Extraction Process of Water Soluble Protein from Coicis Semen].

OBJECTIVE: To optimize the extraction process of water soluble protein from Coicis Semen. METHODS: Coicis Semen was used to extract protein with cysteine hydrochloride aqueous solution in alkaline environment. The single factor test was conducted with the factors of extraction temperature, extraction pH, solid-liquid ratio and extraction time. In combination with single factor test results, a 4 factors 3 levels orthogonal experiment was designed with the factors of extraction temperature, extraction pH, solid-liquid ratio and extraction time. The effect of various factors on the results and the interactions were analyzed by range analysis, variance analysis and partial least squares regression analysis. RESULTS: The optimum extraction process of water soluble protein from Coicis Semen was as follows: the extraction temperature was 40 °C , the extraction pH was 10, the solid-liquid ratio was 1:20 and the extraction time was 4 h. The interaction of temperature and solid-liquid ratio, as well as temperature and extraction time would lower protein extraction rate. CONCLUSION: The optimized extraction process is economical, simple, reasonable and practicable.

Protective effects of Akebia saponin D against rotenone-induced hepatic mitochondria dysfunction.

Akebia saponin D (ASD) is a typical bioactive triterpenoid saponin obtained from the rhizome of Dipsacus asper Wall. Previous studies have found that ASD has a hepatoprotective effect in a mouse model. The purpose of this paper was to explore the molecular mechanism of the hepatoprotective effects of ASD on BRL cells and isolated rat liver mitochondria. We investigated the effects of ASD on rotenone-induced toxicity in BRL cells. The results showed that ASD inhibited the accumulation of reactive oxidant species, ATP deficiency, and mitochondrial membrane potential dissipation; ameliorates mitochondrial respiratory dysfunction, and improved the activity of complex I in a concentration-dependent manner, indicating that ASD likely improved mitochondrial function. ASD suppressed rotenone-induced BRL cell apoptosis and increased Bcl-2/Bax ratio. These results suggest that ASD may exert hepatoprotective effects against rotenone-induced toxicity through mitochondria. This study supports our previous research that ASD possesses hepatoprotective activity in vivo and it is worthy of further study.

Structural characterization and immunomodulatory activity of a mannan from Helvella leucopus.

A new polysaccharide fraction HLP-1 (2.55 × 105 Da) was obtained from the fruiting bodies of Helvella leucopus. Structural characterization of HLP-1 was elucidated by infrared spectroscopy, monosaccharide composition analysis, methylation analysis, nuclear magnetic resonance spectroscopy, scanning electron microscopy and Congo red assay. HLP-1 was a mannan with a backbone of →6)-α-D-Manp(1 â†’ 4)- α-D-Manp(1 â†’6)-α-D-Manp(1 â†’ 3)-α-D-Manp(1 â†’ 4)-α-D-Manp(1 â†’ 3)-α-D-Manp(1→, which branched at the O-6 position and terminated with T-ß-D-Manp. Moreover, HLP-1 could significantly improve the proliferation and neutral red phagocytosis of RAW264.7. Besides, HLP-1 could stimulate the production of nitric oxide (NO), ROS, tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6). HLP-1 induced macrophage activation via NF-κB signal pathway. These findings indicated that HLP-1 was a potential immune enhancement agent applied in functional foods.

Global burden of major gastrointestinal cancers and its association with socioeconomics, 1990-2019.

Background: To understand the impact of common cancers of the gastrointestinal tract and help to formulate evidence-based policy, we evaluate the relationship between the burden of GI tract cancers and socioeconomics. Methods: Data on GI tract cancer burden were obtained from the Global Burden of Disease (GBD) 2019 including mortality and incidence rates. According to the Socio-demographic Index (SDI) level, country and territory, and sex, etc., the data were further stratified. The association between the burden of GI tract cancer and socioeconomics, indicated by SDI, was described. Uncertainty analysis was estimated using bootstrap draw. Results: In 2019, five major cancers of the gastrointestinal tract led to an age-standardized incidence rate (ASIR) of 61.9 (95% CI 56.1-67.6) per 100 000 person-years. From 1990 to 2019, five common tumors of the gastrointestinal tract related age-standardized death rates (ASDRs) decreased by -22.7% (-31.1 to -13.5). For the five common tumors, ASIRs and ASDRs were both higher in males than those in females. Globally, Mongolia, and several East Asia countries exhibited the highest ASIRs in 2019. The high SDI, and high-middle SDI locations recorded the highest incidence rate and death rate of colon and rectum cancer and pancreatic cancer. On the contrary, the low-middle SDI, and low SDI locations possessed the highest incidence rate and death rate of stomach cancer and esophageal cancer. Conclusion: There is a profound association between socioeconomics and burden of common cancers of the gastrointestinal tract. It would be helpful for the high SDI, and high-middle SDI locations to pay special attention to the screening of colon and rectum cancer and pancreatic cancer while the low-middle SDI, and low SDI locations should pay more attention to the screening of stomach cancer and esophageal cancer.

The effect of biopsychosocial holistic care models on the cognitive function and quality of life of elderly patients with mild cognitive impairment: a randomized trial.

BACKGROUND: Cognitive dysfunction is a functional disorder that occurs after brain tissue damage, which can be classified as mild, moderate, or severe according to the degree of illness, especially in the elderly. Mild cognitive impairment (MCI) has many causes and is difficult to treat. It has been reported that biopsychosocial holistic care models can achieve good results in treating MCI. This study aimed to explore the application effect of biopsychosocial holistic care models on elderly patients with MCI. METHODS: A total of 140 patients with MCI diagnosed in Nantong People's Hospital (Nantong, China) from March 2019 to March 2020 were selected as the research cohort. Using a computer-generated randomization list, the participants were randomly allocated to either the observation group or control group, with 70 cases in each group. We compared the cognitive function and quality of life scores of the 2 groups before treatment, 1 month after treatment, and 3 months after treatment. RESULTS: In the first and third months after the intervention, the mini mental state examination (MMSE) score and Montreal Cognitive Assessment (MoCA) score of the observation group were higher than those of the control group, and activities of daily living (ADL) score was lower than that of the control group. The difference between MMSE and MoCA scores between the 2 groups of participants at the third month of treatment was statistically significant (P=0.000). CONCLUSIONS: Biopsychosocial holistic care models can improve the cognitive function and quality of life of elderly MCI patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100046021.

Anti-inflammatory effect of a polysaccharide fraction from Craterellus cornucopioides in LPS-stimulated macrophages.

Immunocytes-involved inflammation is considered to modulate the damage in various diseases. Oxidative stress is initiated by oxidative agents such as LPS and ROS, which are strongly involved in chronic inflammation. Our previous study found that a polysaccharide fraction from Craterellus cornucopioides (CCPP-1) showed good antioxidant activity. However, the anti-inflammatory effect of CCPP-1 was still elusive. The objective of this study was to evaluate the anti-inflammatory activity of CCPP-1 and its potential mechanism in LPS-stimulated RAW264.7 macrophages. The results showed that CCPP-1 could inhibit LPS-induced ROS and NO accumulation. Additionally, CCPP-1 could decrease pro-inflammatory cytokines production (TNF-α, IL-1ß, and IL-18) and inflammatory mediator (iNOS) expression, which might be associated with its capacity to inhibit NF-κB signaling pathway and NLRP3 inflammasome activation. Therefore, this study suggested that CCPP-1 had an ameliorative effect on the inflammation response and was potential to develop into functional food for treating chronic inflammation. PRACTICAL APPLICATIONS: Craterellus cornucopioides is an edible fungus widely distributed in Southwestern China. It was reported that C. cornucopioides polysaccharide (CCPP-1), as important active ingredient, showed good antioxidant activity. However, the anti-inflammatory effect was still elusive. This study showed that CCPP-1 possessed anti-inflammatory activity. The molecular mechanism might be associated with its capacity to inhibit NF-κB signaling pathway and NLRP3 inflammasome activation. Therefore, polysaccharides from C. cornucopioides have potential to develop into functional food to combat inflammatory condition and thus indirectly halt the progression of various inflammatory response-related chronic diseases.

Akebia saponin D ameliorates metabolic syndrome (MetS) via remodeling gut microbiota and attenuating intestinal barrier injury.

Metabolic syndrome (MetS) is a complex, multifactorial disease which lead to an increased risk of cardiovascular disease, type 2 diabetes, and stroke. However, selective, and potent drugs for the treatment of MetS are still lacking. Previous studies have found that Akebia saponin D (ASD) has beneficial effects on metabolic diseases such as obesity, atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). Therefore, our study was designed to determine the effect and mechanism of action of ASD against MetS in a high-fat diet (HFD) induced mouse model. ASD significantly decreased plasma lipid and insulin resistance in these mice, and a targeted approach using metabolomic analyses of plasma and feces indicated that glucose and lipids in these mice crossed the damaged intestinal barrier into circulation. Furthermore, ASD was able to increase lipid excretion and inhibit intestinal epithelial lipid absorption. Results for gut microbiota composition showed that ASD significantly reduced HFD-associated Alistipes, Prevotella, and enhanced the proportions of Butyricimonas, Ruminococcus, and Bifidobacterium. After 14 weeks of ASD/fecal microbiota transplantation (FMT) interventions the developed gut barrier dysfunction was restored. Additionally, RNA-seq revealed that ASD reduced the lipid-induced tight junction (TJ) damage in intestinal epithelial cells via down-regulation of the PPAR-γ-FABP4 pathway in vitro and that use of the PPAR-γ inhibitor (T0070907) was able to partially block the effects of ASD, indicating that the PPAR-γ/FABP4 pathway is a critical mediator involved in the improvement of MetS. Our results demonstrated that ASD not only modifies the gut microbiome but also ameliorates the HFD-induced gut barrier disruption via down-regulation of the PPAR-γ-FABP4 pathway. These findings suggest a promising, and novel therapeutic strategy for gut protection against MetS.

HSD3B1 variant and androgen-deprivation therapy outcome in prostate cancer.

OBJECTIVE: Rate-limiting enzyme 3b-hydroxysteroid dehydrogenase type 1 (3ßHSD1) encoded by HSD3B1 catalyzes the transition of dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT). The HSD3B1 (1245C) variant renders 3bHSD1 of resistant to ubiquitination and degradation, leading to a large amount of protein accumulation in the cell. Multiple clinical studies have shown that this mutation was correlated with resistance to androgen-deprivation therapy in prostate cancer. However, the results were not consistent depending on different treatment strategy and in some researches, the number of observed cases was relatively small. METHODS: To determine the effects of HSD3B1 (1245C) variant on resistance to androgen-deprivation therapy in prostate cancer, we performed a meta-analysis of the available literature. Electronic database searches identified appropriately designed studies that detected HSD3B1 in prostate cancer. We conducted a systematic search of studies in the following databases: PubMed, and EMBASE published until August 10, 2020 using the following search terms: (HSD3B1 AND ((((prostate cancer) OR prostatic neoplasm) OR prostatic carcinoma) OR prostatic cancer). RESULTS: Eight researches were included in this research. The result validated that the HSD3B1 (1245C) variant allele was associated with a shorter PFS (HR, 1.97; 95% CI, 1.39-2.79; P = 0.0001) (homozygous wild-type group) in men with prostate cancer when treated with ADT, however, a higher PFS (HR, 0.68; 95% CI, 0.48-0.96; P = 0.03) when treated with ADT and CYP17A1 inhibitor. CONCLUSION: The HSD3B1 (1245C) variant is a predictor of ADT plus CYP17A1 inhibitor response in prostate cancer.

Targeted Metabolomics for Plasma Amino Acids and Carnitines in Patients with Metabolic Syndrome Using HPLC-MS/MS.

Metabolic syndrome (MetS) is a health disorder characterized by metabolic abnormalities that predict an increased risk to develop cardiovascular disease (CVD) and type 2 diabetes. Biomarkers can provide an insight into the novel mechanism for MetS and can be potentially used for personalized response to therapies. We exploited a targeted HPLC-MS/MS method to characterize plasma amino acids and carnitine metabolic profile in MetS patients. A training set (40 cases and 40 controls) and validation set (80 MetS patients and 80 healthy controls) were carried out to find the metabolic profiles. We discovered two carnitine metabolites including hydroxydecanoyl carnitine and methylglutarylcarnitine. Our results indicated that the decreased level of hydroxydecanoyl carnitine and methylglutarylcarnitine may be associated with the risk of MetS. These biomarkers may improve the risk prediction and provide a novel tool for monitoring of the progression of disease and response to treatment in MetS patients.

Discovery of metabolite profiles of metabolic syndrome using untargeted and targeted LC-MS based lipidomics approach.

Metabolic syndrome (MetS) is an important risk factor for type 2 diabetes, cardiovascular diseases and all-cause morbidity and mortality. Biomarkers can provide insight into the mechanism, facilitate early detection, and monitor progression of MetS and its response to therapeutic interventions. To identify potential biomarkers, we applied a non-targeted and targeted lipidomics method to characterize plasma metabolic profile in MetS patients. Metabolic profiling was performed on a non-target set (40 cases and 40 controls) on UHPLC-Q-TOF/MS and target set (80 MetS patients and 80 healthy controls) on UHPLC-Q-orbitrap MS. Using comprehensive screening and validation workflow, we identified a panel of three metabolites including PC(18:1/P-16:0), PC(o-22:3/22:3), PC(P-18:1/16:1). Our results indicated that the identified biomarkers may improve the risk prediction and provide a novel tool for monitoring of the progression of disease and response to treatment in MetS patients.

Purification, characterization, and bioactivity of two new polysaccharide fractions from Thelephora ganbajun mushroom.

Two new polysaccharide fractions (TZP1-1 and TZP2-1) were obtained from the fruiting bodies of Thelephora ganbajun using DEAE-52 cellulose and Superdex 200 columns chromatography. The physiochemical characterization and biological activities of TZP1-1 and TZP2-1 were investigated. The relative molecular weight of TZP1-1 and TZP2-1 were 2.07 × 106 and 4,886 Da, respectively. TZP1-1 included mannose, rhamnose, galactose, and xylose (4:1:83.9:7.5), while TZP2-1 included mannose, glucose, galactose, and xylose (5.4:1:79.0:8.1). The Congo red experiment results confirmed that TZP2-1 had triple helix conformation. Furthermore, both TZP1-1 and TZP2-1 showed a certain cytotoxicity on HeLa and SH-SY5Y cells, while they exhibited a stronger inhibitory effect on HeLa than SH-SY5Y. Besides, the cytotoxicity of TZP1-1 was better than that of TZP2-1. Moreover, both of them exhibited a moderate inhibitory effect on α-amylase and α-glucosidase. These findings could promote the application of polysaccharides from T. ganbajun. PRACTICAL APPLICATIONS: Thelephora ganbajun is an edible fungus widely distributed in Southwestern China. T. ganbajun polysaccharides as important active ingredients have not been reported. In this current study, two polysaccharides fractions (TZP1-1 and TZP2-1) were characterized, and their cytotoxicities and antidiabetic effect were also assayed. These findings could promote polysaccharides from T. ganbajun to be better application.

Curcumin inhibits the formation of atherosclerosis in ApoE-/- mice by suppressing cytomegalovirus activity in endothelial cells.

BACKGROUND: Curcumin (Cur) is a hydrophobic polyphenol compound derived from the rhizome of the herb Curcuma longa. Cur has a wide spectrum of biological and pharmacological activities. It has been shown that human cytomegalovirus (HCMV) infection was an important risk factor for atherosclerosis (AS) and Cur exhibited an outstanding anti-HCMV effect. However, anti-AS effects of Cur remain unclear when HCMV infected endothelial cells. AIMS: This study will investigate the anti-AS activities and mechanism of Cur,when HCMV infected in vivo and in vitro. MATERIALS AND METHODS: Cur (0.5, 1, and 2 µM) was used to explore the anti-AS activities and mechanism after HCMV infected endothelial cells in vitro. ApoE-/- mice were fed a high fat and cholesterol diet (HD) and given 4000,000 copies/mouse MCMV infection by intraperitoneal and treated with ganciclovir (5 mg/kg/d), Cur (25, 15 mg/kg/d) for 10 weeks in vivo. KEY FINDINGS: As our results showed that Cur inhibited CMV replication and proliferation, reduced the intracellular ROS overproduction, decreased the release of inflammatory cytokines, down-regulated the level of HMGB1-TLRS-NF-κB signaling pathway-related proteins in vitro experiments. Cur reduced the serum levels of LDL-C, TC and TG, significantly decreased the formation of atherosclerotic plaque in the aorta, reduced the lipid deposition in liver and inflammatory damage in heart, lung and kidney in vivo experiments. SIGNIFICANCE: This study showed that Cur prevent AS progression by inhibiting CMV activity and CMV-induced HMGB1-TLRS-NF-κB signaling pathway.