Prioritization of therapeutic targets for cancers using integrative multi-omics analysis.

BACKGROUND: The integration of transcriptomic, proteomic, druggable genetic and metabolomic association studies facilitated a comprehensive investigation of molecular features and shared pathways for cancers' development and progression. METHODS: Comprehensive approaches consisting of transcriptome-wide association studies (TWAS), proteome-wide association studies (PWAS), summary-data-based Mendelian randomization (SMR) and MR were performed to identify genes significantly associated with cancers. The results identified in above analyzes were subsequently involved in phenotype scanning and enrichment analyzes to explore the possible health effects and shared pathways. Additionally, we also conducted MR analysis   to investigate metabolic pathways related to cancers. RESULTS: Totally 24 genes (18 transcriptomic, 1 proteomic and 5 druggable genetic) showed significant associations with cancers risk. All genes identified in multiple methods were mainly enriched in nuclear factor erythroid 2-related factor 2 (NRF2) pathway. Additionally, biosynthesis of ubiquinol and urate were found to play an important role in gastrointestinal tumors. CONCLUSIONS: A set of putatively causal genes and pathways relevant to cancers were identified in this study, shedding light on the shared biological processes for tumorigenesis and providing compelling genetic evidence to prioritize anti-cancer drugs development.

Total Sn-2 Palmitic Triacylglycerols and the Ratio of OPL to OPO in Human Milk Fat Substitute Modulated Bile Acid Metabolism and Intestinal Microbiota Composition in Rats.

In this study, the impact of sn-2 palmitic triacyclglycerols (TAGs) in combination with their ratio of two major TAGs (1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL) to 1,3-dioleoyl-2-palmitoylglycerol (OPO)) in human milk fat substitute (HMFS) on bile acid (BA) metabolism and intestinal microbiota composition was investigated in newly-weaned Sprague-Dawley rats after four weeks of high-fat feeding. Compared to those of control group rats, HMFS-fed rats had significantly increased contents of six hepatic primary BAs (CDCA, αMCA, ßMCA, TCDCA, TαMCA and TßMCA), four ileal primary BAs (UDCA, TCA, TCDCA and TUDCA) and three secondary BAs (DCA, LCA and ωMCA), especially for the HMFS with the highest sn-2 palmitic acid TAGs of 57.9% and OPL to OPO ratio of 1.4. Meanwhile, the inhibition of ileal FXR-FGF15 and activation of TGR5-GLP-1 signaling pathways in HMFS-fed rats were accompanied by the increased levels of enzymes involved in BA synthesis (CYP7A1, CYP27A1 and CYP7B1) in the liver and two key thermogenic proteins (PGC1α and UCP1) in perirenal adipose tissue, respectively. Moreover, increasing sn-2 palmitic TAGs and OPL to OPO ratio in HMFS also altered the microbiota composition both on the phylum and genus level in rats, predominantly microbes associated with bile-salt hydrolase activity, short-chain fatty acid production and reduced obesity risk, which suggested a beneficial effect on host microbial ecosystem. These observations provided important nutritional evidence for developing new HMFS products for infants.

The triacylglycerol structure and composition of a human milk fat substitute affect the absorption of fatty acids and calcium, lipid metabolism and bile acid metabolism in newly-weaned Sprague-Dawley rats.

In this study, the effect of sn-2 palmitic triacylglycerols (sn-2 palmitic TAGs) and the ratio between the two major sn-2 palmitic TAGs (OPL to OPO ratio) in a human milk fat substitute (HMFS) on growth, fatty acid and calcium absorptions, and lipid and bile acid metabolic alterations was investigated in Sprague-Dawley rats. After 4 weeks of high-fat feeding, rats fed with the HMFS containing a sn-2 palmitic acid content of 57.87% and an OPL to OPO ratio of 1.4 showed the lowest TAG accumulation in their livers and hypertrophy of perirenal adipocytes, compared to the groups fed with fats containing a lower sn-2 palmitic acid content or a lower OPL to OPO ratio. Meanwhile, synergistically improved absorption of fatty acids and calcium and increased levels of total bile acids (BAs), especially for the tauro-conjugated BAs (TCDCA, TUDCA, TαMCA, TßMCA, TDCA and TωMCA), were observed in rats by both increasing the sn-2 palmitic acid content and the OPL to OPO ratio in HMFS. In addition, the levels of total BAs and tauro-conjugated BAs were negatively correlated with serum TAG, TC, and LDL-c levels and positively correlated with HDL-c levels according to Spearman's correlation analysis (P < 0.05). Collectively, these findings present new nutritional evidence for the potential effects of the TAG structure and composition of a human milk fat substitute on the growth and lipid and bile acid metabolism of the host in infancy.

Proteomic Analyses of 3-Monochloropropanediol 1-Monooleate and 1-Monostearate Induced Testicular Toxicity in a 90 Day Sprague-Dawley Rats' Study.

3-Monochloropropane 1,2-diol (3-MCPD) esters are toxicants formed during food thermal processing, and their testicular toxicities were widely reported. In this 90 day in vivo study, Sprague-Dawley rats were treated with 3-MCPD 1-monooleate at 10 and 100 mg/kg body weight (bw)/day or 1-monostearate at 15 and 150 mg/kg bw/day. Histological results indicated that testicular impairment was observed, and the level of serum testosterone was decreased dose dependently, while the levels of serum transforming growth factor beta and interferon-γ in rats' serum were increased dose dependently. To address the molecular mechanisms leading to testicular toxicities of 3-MCPD esters, testes samples were investigated with a mass spectrometry proteomic approach. The deregulated proteins affected by 3-MCPD esters include many enzymes related with the inflammatory necrosis pathways. While verifying the results in cellular level, 3-MCPD 1-monooleate and 3-MCPD 1-monostearate showed almost similar testicular cytotoxicity, and they could activate RIPK1 and MLKL pathways at the cellular level. All of these results showed the possible mechanisms about the toxicity of 3-MCPD esters in rats' testes and play a vital role in understanding the toxic effects of 3-MCPD esters both in vivo and in vitro.

The association study between CYP24A1 gene polymorphisms and risk of liver, lung and gastric cancer in a Chinese population.

Recently, four single nucleotide polymorphisms (rs2585428, rs4809960, rs6022999 and rs6068816) in CYP24A1 gene were extensively studied for their associations with cancer risk. However, these studies included only a few types of cancer, which calls for further investigations. In view of this, we here conducted a case-control study to explore the associations between these four CYP24A1 gene polymorphisms and risk of liver, lung and gastric cancer in a Chinese population. A total of 480 liver cancer patients, 550 lung cancer patients, 460 gastric cancer patients and 800 normal controls were recruited in this study. The genotyping of CYP24A1 gene polymorphisms was applied with Sanger sequencing assay. Single-locus analysis demonstrated that rs6022999 was significantly associated with risk of liver and lung cancer, while rs6068816 was significantly associated with the risk of gastric cancer. Haplotype analysis revealed that haplotype GTAT was associated with an increased risk of liver cancer and a decreased risk of lung cancer, and haplotype ATGC was associated with a decreased risk of lung cancer. The further meta-analysis of rs6068816 and lung cancer risk showed that rs6068816 was not associated with lung cancer risk in Chinese population, which confirmed our present finding. Conclusively, rs6022999 may be a genetic biomarker for liver and lung cancer susceptibility in Chinese population, and rs6068816 may be used to predict gastric cancer risk in Chinese population.

Human Chorionic Gonadotropin Priming Does Not Improve Pregnancy Outcomes of PCOS-IVM Cycles.

Background: Influence of pre-retrieval human chorionic gonadotropin (HCG) priming on outcomes of in vitro maturation (IVM) remains controversial. This study aimed to evaluate the effect of HCG priming before oocyte retrieval on clinical outcomes of IVM cycles in patients with polycystic ovarian syndrome (PCOS). Methods: This was a retrospective cohort study analyzing data from the first IVM cycles of unstimulated PCOS patients in a reproductive center of university affiliated hospital from January 2006 to December 2017. Patients received HCG injection before oocyte retrieval were assigned to HCG priming group and those without HCG administration were categorized as none HCG priming (Non-HCG) group. Main outcomes included oocyte maturation rate, number of embryos available, clinical pregnancy rate, and live birth rate. Candidate factors of clinical pregnancy rate was explored by univariate analysis and multivariate logistic regression analysis. Results: There were 324 patients meeting the inclusion and exclusion criteria. Among them, 129 women received HCG priming and 195 other did not. Women in HCG group had significantly lower basal FSH level (5.17 ± 1.63 vs. 5.80 ± 2.38) than Non-HCG group. Both FSH levels were <10 IU/L and the absolute difference was 0.63 IU/L. Other basic characteristics were similar between groups with or without HCG priming. Oocyte maturation rate was trend to be higher in HCG group (52.68 vs. 48.56%) but no statistical significance was found (P = 0.097). No significant difference in clinical pregnancy rate was found between HCG and Non-HCG groups (31.37 vs. 35.67%). Miscarriage rates (31.25 vs. 34.43%) and live birth rates were also similar between groups. HCG priming was not correlated with clinical pregnancy rate in both univariate analysis (P = 0.468) and multivariate logistic regression analysis (P = 0.538; OR = 1.212; 95%CI: 0.657-2.237). Conclusion: HCG priming before oocyte retrieval may not improve clinical outcomes of IVM in patients with PCOS.

Ninety-Day Nephrotoxicity Evaluation of 3-MCPD 1-Monooleate and 1-Monostearate Exposures in Male Sprague Dawley Rats Using Proteomic Analysis.

Fatty acid esters of 3-monochloropropane 1,2-diol (3-MCPD esters) are processing-induced food toxicants, with the kidney as their major target organ. For the first time, this study treated Sprague Dawley (SD) rats with 3-MCPD 1-monooleate at 10 and 100 mg/kg BW/day and 1-monostearate at 15 and 150 mg/kg BW/day for 90 days and examined for their potential semi-long-term nephrotoxicity and the associated molecular mechanisms. No bodyweight difference was observed between groups during the study. Both 3-MCPD 1-monooleate and 1-monostearate resulted in a dose-dependent increase of serum urea creatinine, uric acid and urea nitrogen levels, and histological renal impairment. The proteomic analysis of the kidney samples showed that the 3-MCPD esters deregulated proteins involved in the pathways for ion transportation, apoptosis, the metabolism of xenobiotics, and enzymes related to endogenous biological metabolisms of carbohydrates, amino acids, nitrogen, lipids, fatty acids, and the tricarboxylic acid (TCA) cycle, providing partial explanation for the nephrotoxicity of 3-MCPD esters.

Lack of association between interleukin-22 gene polymorphisms and cancer risk: a case-control study and a meta-analysis.

BACKGROUND: Interleukin-22 (IL22) has been implicated in inflammation and tumorigenesis. The association between IL22 gene polymorphisms and cancer risk has been widely explored. However, the limited sample sizes of previous studies may produce inadequate statistical power and conflicting results, which calls for further investigations. In this study, we recruited a total of 1490 cancer patients (480 liver cancer patients, 550 lung cancer patients, and 460 gastric cancer patients) and 800 normal controls to explore the associations between IL22 gene polymorphisms (rs1179251, rs2227485, rs2227511, and rs2227473) and cancer risk. METHOD: The genotyping was performed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Sanger sequencing. RESULTS: Our results showed that none of the four IL22 gene polymorphisms was associated with the risk of liver, lung or gastric cancer in Hubei Han Chinese population. To improve the statistical strength, a meta-analysis was further conducted. The results further confirmed our present findings and showed that rs1179251, rs2227485, and rs2227473 were not associated with cancer risk in total or stratified analysis. CONCLUSION: Consequently, the rs1179251, rs2227485, rs2227511, and rs2227473 polymorphisms may not be associated with cancer risk. However, further investigations using larger samples in different ethnic populations are required.

Risk of preterm delivery in singletons conceived by in vitro fertilization.

To evaluate the preterm delivery and other obstetrics complications similar in singleton pregnancies achieved through IVF compared to spontaneous pregnancies. Retrospective case-control study included 1663 women with singleton pregnancies following IVF-ICSI (study group) and 3326 women with singleton spontaneous pregnancies (control group) who delivered between January 2015 and January 2018 at the Peking University Third Hospital. The control group matched 1:2 by age, BMI, parity, and gravidity. Maternal outcomes included preterm delivery and complications. There was significantly higher incidence of gestational diabetes, hypertensive disorders, and placenta previa in IVF-ICSI pregnancies versus controls (p < .05). IVF-ICSI resulted in significantly higher rate of preterm birth than in spontaneous pregnancies (p < .05) and the difference remained significant for deliveries that occurred before 28, 32, and 34 weeks gestation (p < .05). Multivariate logistic regression analysis revealed that female-factor infertility, hypertensive disorder, placenta previa, and PROM were significant prognostic factors associated with increased risk of prematurity. IVF-ICSI is associated with increased risk of obstetric complications including preterm delivery in singleton pregnancies. Female-factor infertility is an independent prognostic factor for preterm birth. This information is important for patient counseling and helps to refine the recommendation to optimize maternal health before embarking on fertility treatments.

Chemical compositions of chrysanthemum teas and their anti-inflammatory and antioxidant properties.

Seventeen commercial chrysanthemum teas (Chrysanthemum morifolium and Coreopsis tinctoria) were extracted with hot-H2O, and examined and compared to the 75% methanol extracts for their chemical compositions using UPLC/Q-TOF-MS analysis. For the first time, 6, 8-C,C-diglucosylapigenin and eriodicyol-7-O-glucoside were detected in the Snow chrysanthemum, and acetylmarein was detected in HangJu, GongJu and HuaiJu. The extracts were also examined for their radical scavenging and anti-inflammatory activities in vitro. The hot-H2O extract of Kunlunmiju 1 had the greatest total phenolic content, and relative DPPH and oxygen radical absorbance capacity values of 12.72 mg gallic acid equivalents/g, 105.48 and 1222.50 µmol Trolox equivalents/g, respectively. In addition, all the hot-H2O extracts suppressed the lipopolysaccharide-induced interleukin-6, IL-1ß and cyclooxygenase-2 mRNA expressions, and H2O2-induced intracellular reactive oxygen species production in cultured cells. The results from this research may be used to promote the consumption of chrysanthemum as a functional tea.

Synthesis of 2-Monochloropanol Fatty Acid Esters and Their Acute Oral Toxicities in Swiss Mice.

A novel synthetic route was designed, developed, and utilized to synthesize six high-purity 2-monochloropropanediol fatty acid esters (2-MCPD esters), a group of potential processing-induced food contaminants. A chlorine atom was introduced to C-2 of a diethyl malonate molecule, which was reduced by NaBH4 and followed by esterification using fatty acids. The reaction products were isolated and purified using silica gel columns to obtain three 2-MCPD monoesters and three diesters at about 50-54% and 56-59% yields, respectively. In addition, 2-MCPD monopalmitate and dipalmitate were examined for their acute oral toxicities in Swiss mice. The LD50 values of 2-MCPD mono- and dipalmitate were greater than 5000 mg/kg body weight (BW), along with detectable nephrotoxicity and testicular toxicity. The results of this study may promote future investigation of MCPD ester toxicology and detection.

Risk of miscarriage in women with endometriosis undergoing IVF fresh cycles: a retrospective cohort study.

BACKGROUND: Endometriosis is thought to affect the effectiveness of ART by an increased risk of miscarriage. We aimed to investigate the impact of endometriosis in women achieving singleton pregnancies through IVF fresh cycles and risk of miscarriage. METHODS: This retrospective cohort study included all women undergoing a first IVF cycle and achieving singleton pregnancies after fresh embryo transfer in a tertiary university hospital reproductive medical center between January 2008 and June 2016. Women with endometriosis were compared with women with no endometriosis. Women in the endometriosis group were all with a history of laparoscopy or laparotomy for endometriosis and/or with ovarian endometrioma. The control group was matched 1:2 according to age and study period. RESULTS: Among the cohort, we identified 1006 women with endometriosis as study group and 2012 unaffected women matched in a 1:2 ratios as control group. The miscarriage rate between women with and without endometriosis was similar (22.4 and 20.1%, P = 0.085). The odds ratio after adjusting for the risk factors for miscarriage was 1.14 (95% confidence interval 0.95-1.37). In the study group, the women with and without endometrioma did not show a significant risk of miscarriage, (19.8 and 23.8%, P = 0.152, OR 0.79, 95% CI 0.58-1.09). The miscarriage rate in women with endometrioma ≥30 mm (37.3 ± 7.1 mm) and < 30 mm (19.3 ± 5.5 mm) was not significantly different, (24.7 and 18.5%, P = 0.229, OR 1.44, 95% CI 0.79-2.63). After adjustment for risk factors for miscarriage, the presence of endometrioma and the size of endometrioma, regression model confirmed no significant increase for the risk of miscarriage in the subgroup analyses. CONCLUSIONS: The risk of miscarriage did not statistically increase in women with endometriosis who achieved pregnancy through IVF fresh cycles.

Factors inducing decreased oocyte maturation rate: a retrospective analysis of 20,939 ICSI cycles.

PURPOSE: Decreased oocyte maturation rate (OMR) is associated with worse clinical outcomes in IVF/ICSI cycles. The clinical features inducing decreased OMR remain unknown. The study is designed to explore the factors influencing the incidence of decreased OMR and its effects on clinical outcomes. METHODS: This is a retrospective case-control study analyzing data from 20,939 ICSI cycles in a reproductive center of university affiliated hospital from January 2015 to December 2017. Patients with a decreased OMR (< 30%) were characterized as Group A and those with an OMR ≥ 30% constituted Group B. Candidate factors of decreased OMR and clinical outcomes were compared between the two groups. RESULTS: There were 1.3% cycles with an OMR < 30% and 22.16% of all oocytes retrieved (12.87 per cycle in average) were immature. Primary infertility, longer duration of infertility, larger BMI, more previous assisted reproductive times, less oocytes retrieved were risk factors for decreased OMR. Compared with long agonist protocol, patients received antagonist protocol for COH had a higher incidence of decreased OMR. The fertilization rate and subsequent embryo development of oocytes in Group A were worse than Group B. Implantation rate and clinical pregnancy rate were both lower in Group A than Group B. CONCLUSION: Primary infertility, duration of infertility, BMI, previous assisted reproductive times, number of oocytes retrieved and COH protocol were found to be factors inducing decreased OMR. Patients with decreased OMR had worse clinical outcomes.

Dietary sn-2 palmitic triacylglycerols reduced faecal lipids, calcium contents and altered lipid metabolism in Sprague-Dawley rats.

In this study, the impact of dietary sn-2 palmitic triacylglycerol (sn-2 PTAG) on faecal lipids, calcium excretion and lipid metabolic alternation was investigated in Sprague-Dawley (SD) rats fed with high-fat diet containing either palm olein (PO, sn-2 palmitic acid (PA) of 14.8%), sn-2 PTAG50 (sn-2 PA of 56.4%) or sn-2 PTAG70 (sn-2 PA of 72.4%), respectively. After 4-week feeding period, SD rats fed with sn-2 PTAGs showed reduced faecal soap fatty acids, neutral lipid and calcium excretion compared to those of PO-fed rats, whereas a significant difference was only observed for the sn-2 PTAG70-fed rats (p < .05). Moreover, dietary sn-2 PTAG70 also showed a significant effect on decreasing serum triacylglycerol (TAG) level, reducing perirenal adipocyte size and regulating lipid metabolism in small intestine and perirenal adipose tissue of SD rats. Significantly increased mRNA levels of genes involved in intestinal lipid anabolism as well as lipid catabolism were both observed in the sn-2 PTAG70-fed rats (p < .05). Meanwhile, dietary sn-2 PTAG70 also significantly up-regulated lipolysis, mitochondrial fatty acid oxidation and thermogenesis-related gene and protein levels in perirenal adipose tissue, which might be correlated with the reduced perirenal adipocyte size. Taken together, our findings indicated that sn-2 PTAG70 may have some beneficial effects on intestinal lipid utilisation and lipid metabolic activity for energy supply in visceral adipose tissue.

Endometrial miR-543 Is Downregulated During the Implantation Window in Women With Endometriosis-Related Infertility.

BACKGROUND: Differentially expressed microRNAs (miRNAs) and their target mRNAs may lead to alterations in normal physiological status of the tissues and initiate pathological processes. The aim of this study was to investigate the expression of the most relevant miRNAs in the eutopic endometrial tissue during the window of implantation in women with endometriosis-related infertility. METHODS: In the study, 76 infertile women with a regular menstrual cycle were recruited from the Center for Reproductive Medicine, Peking University Third Hospital between January 2014 and June 2016. We performed a combined messenger RNA and miRNA microarray and bioinformatics analysis of eutopic endometrium in 6 women with and without endometriosis-related infertility at the time of implantation window. Quantitative real-time polymerase chain reaction arrays were utilized to examine the expression levels of selected miRNAs (from 35 patients with endometriosis and 35 disease-free individuals at different menstrual stages). RESULTS: Five differentially expressed miRNAs (miR-142-5p, miR-146a-5p, miR-1281, miR-940, and miR-4634) were significantly upregulated, whereas miR-543 was significantly downregulated in the eutopic endometrium during the window of implantation in patients with endometriosis. Further analysis showed that miR-543 was significantly upregulated at the peri-implantation phase compared with that at proliferative phase in the endometrium of disease-free patients (P < .05). However, the expression level of miR-543 was significantly decreased in patients with endometriosis (P < .05), especially downregulated at the window of implantation phase (P < .05). CONCLUSIONS: miR-543 plays an important role during embryo implantation process and is associated with endometrial receptivity. Downregulation of miR-543 may affect embryo implantation, resulting in the pathogenesis of endometriosis-related infertility.

Reproductive outcomes in women with unicornuate uterus undergoing in vitro fertilization: a nested case-control retrospective study.

BACKGROUND: Unicornuate uterus, a congenital uterine malformation resulting from unilateral maldevelopment of Mullerian duct, is more prevalent in women with infertility. Owing to relative rarity of the condition, the evidence on the associated reproductive outcomes is derived from small heterogeneous studies that report different clinical endpoints and often do not account for the anatomical variations of unicornuate uterus. The aim of this study was to evaluate the embryological and clinical outcomes following IVF-ICSI treatment in women with unicornuate uterus without rudimentary functional cavity (ESHRE-ESGE class IVb). METHODS: Retrospective nested case-control study comprised 342 women with unicornuate uterus and 1026 matched controls who underwent IVF-ICSI cycles between October 2012 and October 2016. Cumulative live birth rate upon one complete IVF cycle, including transfers of all resulting embryos was considered as a primary outcome measure. RESULTS: Baseline characteristics were comparable between the unicornuate uterus and control groups except for higher rate of primary infertility in unicornuate uterus. Ovarian response to stimulation did not differ between the groups. Transfer of day-3 embryos in fresh cycle resulted in lower clinical pregnancy rate (35.9% vs. 43.9%, p = 0.028) and live-birth rate (26.9% vs. 35.2%, p = 0.017) per transfer, but the difference was not observed when either cleavage frozen-thaw embryos or blastocysts were transferred. Implantation rate was lower and miscarriage rate was higher in women with unicornuate uterus but the difference between the groups did not reach statistical significance. Transfer of cleavage embryos resulted in significantly higher miscarriage rate and lower live-birth rate in fresh versus frozen-thaw cycles in each group, whereas fresh and frozen-thaw blastocyst embryos had comparable outcomes. Upon completion of one IVF-ICSI cycle, the cumulative pregnancy rate (53.1% vs. 65.7, p < 0.001) and cumulative live birth rate (42.4% vs. 54.6%, p < 0.001) were significantly lower in women with unicornuate uterus compared to those in women with normal uterus. Cumulative outcomes were superior when embryos were cultured to blastocyst stage. CONCLUSIONS: Women with unicornuate uterus have lower clinical pregnancy and live birth rate after IVF-ICSI treatment compared to women with normal uterus. The treatment outcomes are improved with blastocyst culture, which warrants evaluation in prospective setting.

Grafting C8-C16 alkyl groups altered the self-assembly and curcumin -loading properties of sodium caseinate in water.

The data presented here are related to the research article entitled "Synthesis and characterization of alkylated caseinate, and its structure-curcumin loading property relationship in water" (Zhang et al., 2018) [1]. This data article reports the detailed spectra information for 1H NMR, 13C NMR and UPLC-Q-TOF MS of the N-succinimidyl fatty acid esters with various alkyl chain lengths (Cn-NHSs, n = 8, 12, 14 and 16). 1H NMR, 13C NMR and UPLC-Q-TOF MS spectra for C16-NHS are shown as an example. Then the stacked 1H NMR spectra of the obtained alkylated caseinates (Cn-caseinates, n = 8, 12, 14 and 16) are provided. The surface hydrophobicity index (S0) of Cn-caseinates with different substitution degrees (SD) of alkyl groups is shown. Additionally, Visual appearances for the formed aqueous dispersions of curcumin-loaded native caseinate (NaCas) and Cn-caseinates self-assemblies are shown. X-ray diffraction patterns of curcumin, C16-caseinate, its physical mixture and curcumin-loaded C16-caseinate self-assemblies are examined. The re-dispersibility and short-term storage stability of the curcumin-loaded NaCas and C16-caseinate self-assemblies are also studied.

Gypenosides Reduced the Risk of Overweight and Insulin Resistance in C57BL/6J Mice through Modulating Adipose Thermogenesis and Gut Microbiota.

This study investigated whether and how gypenosides from jiaogulan tea at 100 and 300 mg/kg/day levels could reduce the development of overweight and insulin resistance in C57 BL/6J mice fed a high-fat diet in 12 weeks. The 300 mg/kg/day gypenosides supplement significantly reduced final body weight, plasma total cholesterol, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) index by 19.9%, 40%, and 36%, respectively, compared with the high-fat diet control group. Gypenosides also increased brown adipocyte tissue activity and white adipose tissue browning. The expression of genes involved in mitochondrial activity and fatty acid ß-oxidation were also increased in both brown and white adipocyte tissues. In addition, gypenosides at 100 and 300 mg/kg/day levels decreased the ratio of Firmicutes to Bacteroidetes by 20% and 58.6%, respectively, and increased Akkermansia muciniphila abundance in the gut microbiota.

Inhibitory Effect of Piceatannol on TNF-α-Mediated Inflammation and Insulin Resistance in 3T3-L1 Adipocytes.

Piceatannol, a bioactive component in grape and blueberry, was examined for its potential in decreasing the inflammatory activities in adipocytes using a cocultured adipocyte and macrophage system, and suppressing tumor necrosis factor-α (TNF-α)-mediated inflammation and the related insulin resistance using a 3T3-L1 adipocyte model. Piceatannol at 10 µM significantly reduced the release of inflammatory cytokines of TNF-α and monocyte chemoattractant protein-1 (MCP-1) by 19 and 31% in the cocultured system, respectively. Pretreatment with piceatannol also inhibited TNF-α-induced expression of interleukin-6 (IL-6) and MCP-1 at both mRNA and protein levels in the 3T3-L1 adipocytes. Piceatannol also partially improved the malfunction of insulin-stimulated glucose uptake, which was reduced by TNF-α in 3T3-L1 adipocytes. Furthermore, the inhibitions were mediated by significant blocking of IκBα phosphorylation and nuclear factor-κB (NF-κB) activation through suppressing nuclear translocation of NF-κB p65 along with c-Jun N-terminal kinase (JNK)-mitogen activated protein kinase (MAPK) activation. In addition, the Akt-dependent forkhead box O1 (FoxO1) signaling pathway was involved in the restoration of insulin-stimulated glucose uptake through suppressing the down-regulation of phosphorylation of Akt and FoxO1 expressions. These results suggested the potential of piceatannol in improving chronic inflammatory condition and insulin sensitivity in obese adipose tissues.

[Maternal and fetal outcomes with aortic dissection in pregnant patients with Marfan syndrome].

OBJECTIVE: To evaluate the clinical characteristics of aortic dissection in pregnant patients with Marfan syndrome and the maternal and fetal outcomes in cardiovascular surgery. METHODS: Seven pregnant women with Marfan syndrome with aortic dissection were identified, who were treated in Beijing Anzhen Hospital Affiliated to Capital Medical University between January 2012 and September 2014. Patient charts were reviewed for cardiovascular surgery, occurrence of complications, clinical features and the maternal and fetal outcomes. RESULTS: (1) Among 7 patients, 4 cases were diagnosed as type A aortic dissection and 3 were cases diagnosed as type B aortic dissection. The diagnosis mainly depends on CT angiography. New York Heart Association (NYHA) classify into 5 of level II, 1 of level III, 1 of leveI IV. Except for 1 patient with cardiac tamponade lead to heart failure, the remaining 6 cases had no complications. (2) Three patients underwent heart surgery with cardiopulmonary bypass in second trimester and two patients underwent heart surgery in third trimester. Two patients terminated pregnancy before heart surgery (one of whom underwent artificial abortion, one of whom underwent cesarean section in second trimester). (3) The methods of cardiovascular surgeries were as follow: 3 of Bentall+Sun', 1 of Bentall+Sun'+ right coronary artery bypass grafting, 1 of Bentall, 1 of the whole chest aorta replacement surgery, and 1 of femoral artery catheter chest aorta with membrane mesh stent implantation. The diameter of aortic roots measured during operation were 5 cm in 2 cases, 7 cm in 2 cases and 10 cm in 2 cases respectively. Among the 7 cases, 3 were conducted cesarean sections during cardiovascular surgery, 1 was terminated pregnancy due to intrauterine fetal death after cardiovascular surgery, and 1 was conducted cesarean section due to severe early-onset preeclampsia at 30 weeks of pregnancy after cardiovascular surgery. (4) Among the 7 cases, 3 were conducted cesarean sections during cardiovascular surgery, the order of which was implemented cesarean section under general anesthesia firstly and then operated cardiovascular surgery with cardiopulmonary bypass and heparinization. Two were conducted cardiovascular surgery after termination of pregnancy by early artificial abortion operation or hysterotomy. 1 was conducted Bentall surgery at 18 weeks of pregnancy, after that the patient was receiving warfarin until the fetal brain hemorrhage was examined by ultrasound at 31 weeks of pregnancy; the patient was conducted cesarean section due to intrauterine fetal death. 1 was conducted heart surgery at 24 weeks of pregnancy and continue the pregnancy to 30 weeks, was conducted cesarean section due to severe early-onset preeclampsia at 30 weeks of pregnancy. (5) Among 7 patients, three patients underwent heart surgery with cardiopulmonary bypass combined with cesarean section. Two patients terminated pregnancy after heart surgery. Two patients terminated pregnancy before heart surgery. Six patients were alive and one patient died of multiple organ failure. (6) 3 cases of newborn with birth body mass between 1 080 to 1 490 g.1 case of birth died after 14 d. 2 cases for newborns were alive without exception. CONCLUSION: Aortic dissection poses serious risk for pregnant women with Marfan syndrome and the fetus, and the mortality rates for both the mother and the fetus are high. Early diagnosis and appropriate treatment should be based on maternal and fetal conditions (such as aortic dissection, gestational age). When fetus is mature, cardiovascular surgery should be carried out with cesarean section. A multi-disciplinary team between obstetric and cardiovascular surgery is crucial to the outcome of these critical patients.