Effects of dietary supplementation of fish oil plus vitamin D3 on gut microbiota and fecal metabolites, and their correlation with nonalcoholic fatty liver disease risk factors: a randomized controlled trial.

We previously reported that fish oil plus vitamin D3 (FO + D) could ameliorate nonalcoholic fatty liver disease (NAFLD). However, it is unclear whether the beneficial effects of FO + D on NAFLD are associated with gut microbiota and fecal metabolites. In this study, we investigated the effects of dietary supplementation of FO + D on gut microbiota and fecal metabolites and their correlation with NAFLD risk factors. Methods: A total of 61 subjects were randomly divided into three groups: FO + D group (2.34 g day-1 of eicosatetraenoic acid (EPA) + docosahexaenoic acid (DHA) + 1680 IU vitamin D3), FO group (2.34 g day-1 of EPA + DHA), and corn oil (CO) group (1.70 g d-1 linoleic acid). Blood and fecal samples were collected at the baseline and day 90. Gut microbiota were analyzed through 16S rRNA PCR analysis, and fecal co-metabolites were determined via untargeted ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Results: The relative abundance of Eubacterium (p = 0.03) and Lactobacillus (p = 0.05) increased, whereas that of Streptococcus (p = 0.02) and Dialister (p = 0.04) decreased in the FO + D group compared with the CO group. Besides, changes in tetracosahexaenoic acid (THA, C24:6 n-3) (p = 0.03) levels were significantly enhanced, whereas 8,9-DiHETrE levels (p < 0.05) were reduced in the FO + D group compared with the CO group. The changes in 1,25-dihydroxyvitamin D3 levels in the fecal samples were inversely associated with insulin resistance, which was determined using the homeostatic model assessment model (HOMA-IR, r = -0.29, p = 0.02), and changes in 8,9-DiHETrE levels were positively associated with adiponectin levels (r = -0.43, p < 0.05). Conclusion: The present results indicate that the beneficial effects of FO + D on NAFLD may be partially attributed to the impact on gut microbiota and fecal metabolites.

Effects of Dietary Zinc on Growth Performance, Digestive Enzyme Activities, Antioxidant Status, and Immune Responses of Sea Cucumber Apostichopus japonicus.

Zinc is an essential micronutrient for organisms involved in regulating various biological processes. This study evaluated the effects of dietary zinc on growth performance, digestive enzyme activities, antioxidant status, and immune responses of sea cucumber Apostichopus japonicus. Five experimental diets were formulated with graded levels of zinc (0, 20, 40, 60, and 80 mg/kg, respectively), and the actual dietary zinc values were 31.4, 51.0, 68.2, 91.9, and 110.8 mg/kg diet, respectively. Sea cucumbers were fed with diets for 2 months. The results showed the growth performance, amylase, and trypsin activities of sea cucumber increased significantly with zinc supplementation, and the best growth performance and enzyme activities were observed at 40 mg/kg zinc diet. Zinc supplementation significantly increased activities of superoxide dismutase, catalase, anti-superoxide anion, and inhibiting hydroxyl radical, while significantly reduced the malondialdehyde content. Furthermore, the higher zinc supplementation levels resulted in significantly upregulated immune-related genes of hsp90, p105, rel, and lsz, suggesting that excessive zinc caused oxidative stress. The broken-line regression analysis of specific growth rate indicated dietary zinc requirement in juvenile sea cucumber was ~ 66.3 mg/kg diet. Overall, dietary zinc contributes to the growth and immune resistance of juvenile sea cucumber, and our study will provide insights into the rational use of dietary zinc in aquaculture.

Melanin theranostic nanoplatform as an efficient drug delivery system for imaging-guided renal fibrosis therapy.

As renal fibrosis nanotherapeutics, the endogenous biomaterial melanin not only has natural biocompatibility and biodegradability but also has inherent photoacoustic imaging ability and certain anti-inflammatory effects. These properties determine that melanin can not only as a carrier of medication but also track the biodistribution and renal uptake of drugs in vivo by photoacoustic imaging in real-time. Curcumin is a natural compound with biological activity, which has excellent ROS scavenging ability and good anti-inflammatory property. These materials appear more advantages in the development of nanoscale diagnostic and therapeutic platforms for future clinical translation. Herein, this study developed curcumin-loaded melanin nanoparticles (MNP-PEG-CUR NPs) as an efficient medication delivery system for photoacoustic imaging guidance renal fibrosis treatment. The nanoparticles are about 10 nm in size, exhibit good renal clearance efficiency, excellent photoacoustic imaging ability, and good in vitro and in vivo biocompatibility. These preliminary results indicated that MNP-PEG-CUR have clinically applicable potential as a therapeutic nanoplatform for renal fibrosis.

A meta-analysis of prospective cohort studies of flavonoid subclasses and stroke risk.

Epidemiological studies indicate that higher intakes of flavonoids are associated with reduced stroke risk, however, which subtypes play significant roles to protect against stroke remain unclear. A systematic literature search in PubMed and Web of Science databases was performed up to Oct. 2021. Flavonoids or their subtypes (flavanol, flavanone, flavone, flavan-3-ol, isoflavone, or anthocyanin) were paired with stoke as the search term. Multivariate-adjusted relative risks (RRs) with 95% confidence intervals (CIs) for the highest versus the lowest category were pooled by using a random-effects model. Dose-response analysis was implemented by using a restricted cubic spline regression model. Ten independent prospective cohort studies with 387,076 participants and 9,564 events were included. Higher intakes of flavanones were inversely associated with stroke risk (RR = 0.85; 95%CI: 0.78, 0.93). Dose-response analysis showed that 50 mg/day increment of flavanones was associated with 11% reduction in stroke risk (RR = 0.89; 95%CI: 0.84, 0.94). Flavan-3-ols was marginally inversely associated with stroke risk (RR = 0.92; 95%CI: 0.82, 1.02). Dose-response analysis showed that 200 mg/day increment of flavan-3-ols was associated with 14% reduction in stroke risk (RR = 0.86; 95%CI: 0.75, 0.98). The non-significant association was observed with respect to other flavonoid subclasses. This study demonstrated higher intakes of flavanones and flavan-3-ols were associated with a lower risk of stroke. Dietary intakes of lemon and citrus rich in flavanones and flavan-3-ols might have beneficial functions for the protection against stroke. The findings of these associations of the present study need to be confirmed in other regions and ethnic origins.

Effects of Supplementary Selenium and Vitamin E on the Growth Performance, Antioxidant Enzyme Activity, and Gene Expression of Sea Cucumber Apostichopus japonicus.

A 60-day feeding experiment was conducted to evaluate the effects of single selenomethionine (Se) and its mixture with vitamin E (VE) on the growth, antioxidant enzyme activities, and gene expression of juvenile sea cucumber Apostichopus japonicus. The design of the experiment contained two factors and 5 × 2 levels by means of adding various levels of Se and VE in the feed, i.e., combination of 0, 0.3, 0.6, 0.9, or 1.2 mg Se kg-1 and 0 or 200 mg VE kg-1. The results revealed that the specific growth rate and weight gain rate were the highest in the group with 0.3 mg Se kg-1 and 200 mg VE kg-1, followed by the group with 0.6 mg Se kg-1 without VE. Se significantly improved the activities of amylase and protease with VE also imposed positive effect on the amylase activity. Glutathione peroxidase (GPX) activity was highest in the group with 1.2 mg Se kg-1 and lowest with the basal diet. The activity of catalase (CAT) was increased while glutathione reductase (GR) activity was decreased in response to the addition of Se. No significant interactive effects of Se and VE on the enzyme activities were found except superoxide dismutase (SOD) activity. While relative expressions of GPX, CAT, and SOD genes were significantly responsive to the addition of dietary Se, VE significantly promoted the gene expression of SOD. The results suggested that Se and VE might have beneficial effects on the growth and antioxidant responses of A. japonicus.

Vitamin D Decreases Plasma Trimethylamine-N-oxide Level in Mice by Regulating Gut Microbiota.

As a metabolite generated by gut microbiota, trimethylamine-N-oxide (TMAO) has been proven to promote atherosclerosis and is a novel potential risk factor for cardiovascular disease (CVD). The objective of this study was to examine whether regulating gut microbiota by vitamin D supplementation could reduce the plasma TMAO level in mice. For 16 weeks, C57BL/6J mice were fed a chow (C) or high-choline diet (HC) without or with supplementation of vitamin D3 (CD3 and HCD3) or a high-choline diet with vitamin D3 supplementation and antibiotics (HCD3A). The results indicate that the HC group exhibited higher plasma trimethylamine (TMA) and TMAO levels, lower richness of gut microbiota, and significantly increased Firmicutes and decreased Bacteroidetes as compared with group C. Vitamin D supplementation significantly reduced plasma TMA and TMAO levels in mice fed a high-choline diet. Furthermore, gut microbiota composition was regulated, and the Firmicutes/Bacteroidetes ratio was reduced by vitamin D. Spearman correlation analysis indicated that Bacteroides and Akkermansia were negatively correlated with plasma TMAO in the HC and HCD3 groups. Our study provides a novel avenue for the prevention and treatment of CVD with vitamin D.

Safety and efficacy of zotarolimus-eluting stents in the treatment of diabetic coronary lesions in Chinese patients: The RESOLUTE-DIABETES CHINA Study.

BACKGROUND: The RESOLUTE-DIABETES CHINA study was specifically designed to investigate the safety and efficacy of Resolute zotarolimus-eluting stents (ZES; Medtronic, Santa Rosa, CA, USA) in the treatment of diabetic coronary lesions in the Chinese population. METHODS: In all, 945 patients with de novo native coronary lesions and type 2 diabetes mellitus were recruited at 32 cardiac centers across the Chinese mainland and were implanted with Resolute ZES. The primary endpoint was target vessel failure (TVF); secondary endpoints were clinical outcomes, namely all-cause death, stroke, bleeding, target lesion revascularization (TLR), target vessel revascularization (TVR), non-TVR, and stent thrombosis (ST). The follow-up period for all endpoints was 12 months after the procedure. RESULTS: In all, 933 patients (98.73%) had clinical follow-up at 12 months. The rate of TVF was 11.60%, whereas the rate of occurrence of secondary endpoints was 5.47%, with four patients (0.43%) having subacute or late ST. There were no significant differences in TVF rates comparing patients with different HbA1c levels or receiving different glucose control treatments (all P > 0.05). Patients with multivessel lesions had higher TVF rates (95% confidence intervals) than those with single-vessel lesions (16.76% [12.10%-22.97%) vs 9.72% [7.79%-12.11%], respectively; P = 0.006). There were no significant differences in TVF rates in patients with or without small vessels, bifurcated lesions, or chronic total occlusions (all P > 0.05). [Correction added on 17 January 2019, after first online publication: in the second sentence of Results section, "TLF" was changed to "TVF".]. CONCLUSIONS: Resolute ZES may perform well in the Chinese diabetic population, especially in those with poor glucose control, complex lesions, and certain unfavorable clinical features. Further studies are needed to determine why ZES perform well in this population.

Ultrahigh performance liquid chromatography analysis of volatile carbonyl compounds in virgin olive oils.

The enzymatic and chemical oxidation reaction in olive oil produces many volatile carbonyl compounds that contribute to the complex flavor of olive oil. A novel ultrahigh performance liquid chromatography (UHPLC) method with dynamic headspace sampling and 2,4-dinitrophenylhydrazine (DNPH) derivatization were established to determine the volatile carbonyls in virgin olive oil. Quantification of nine characteristic carbonyls (acetone, hexanal, E-2-hexenal, octanal, E-2-octenal, nonanal, E-2-nonenal, E,E-2,4-nonadienal, and E,E-2,4-decadienal) was achieved using cyclopentanal as an internal standard. This method provides comparable linearity (R(2) = 0.9917-1.0000) and repeatability (less than 7.6% relative standard deviations) with solid phase microextraction gas chromatography (SPME-GC). The relative standard deviations (%RSD) of all applied carbonyl standards were lower than 7.6%. The limits of detection (LOD) and quantification (LOQ) were in the ranges of 1.6-150.1 and 4.8-906.1 µg/kg. The recoveries obtained for olive oil samples were in the range of 81.0-115.3%. To show the potential of this method on the quantification of other volatile carbonyls that were not included in this study, GC-electron ionization mass spectrometry (GC-EI/MS) was employed to identify the derivatized carbonyls (carbonyl (2,4-DNPH) hydrazones) while peak assignments were made on the basis of elution sequences and peak areas. This method provided feasibility of using LC to determine volatile carbonyls in oil matrices, which can be applied to exam the degree of lipid oxidation and evaluate the sensory properties of VOO and other edible oils.

Tanshinone IIA protects against cardiac hypertrophy via inhibiting calcineurin/NFATc3 pathway.

Pathological cardiac hypertrophy induced by adrenergic overactivation can subsequently develop to heart failure which remains as a leading cause of mortality worldwide. Tanshinone IIA is a lipid-soluble pharmacologically active compound extracted from the rhizome of the Chinese herb Salvia miltiorrhiza, a well-known traditional Chinese medicine used for the treatment of cardiovascular disorders. However, little is know about the effect of Tanshinone IIA on cardiac hypertrophy. The present study was aimed to investigate whether Tanshinone IIA prevents cardiac hypertrophy induced by isoproterenol (ISO) and to clarify its possible mechanisms. Cardiomyocytes hypertrophy was induced by ISO 10 µM for 48 h with or without Tanshinone IIA 10, 30, 100 µM pretreatment, and evaluated by determining the cell size and the expression of ANP, BNP, ß-MHC, Calcineurin, and NFATc3 by real-time PCR and western blot. We found that Tanshinone IIA pretreatment attenuated the enlargement of cell surface area induced by ISO in cultured cardiomyocytes. The mRNA level of ANP, BNP and ß-MHC was obviously elevated in ISO-treated cardiac cells, which was effectively inhibited by Tanshinone IIA. Moreover, we found that Tanshinone IIA pretreatment could prevent the augment of intracellular calcium transient in ISO-treated cardiomyocytes. The further study revealed that Calcineurin, NFATc3, ANP, BNP and ß-MHC proteins were upregulated by ISO in ventricular myocytes, and Tanshinone IIA pretreatment significantly attenuate the increased expression of Calcineurin, NFATc3, ANP, BNP and ß-MHC proteins. In summary, Tanshinone IIA attenuated cardiomyocyte hypertrophy induced by ISO through inhibiting Calcineurin/NFATc3 pathway, which provides new insights into the pharmacological role and therapeutic mechanism of Tanshinone IIA in heart diseases.

[Efficacy comparison with low and high dose nadroparin for patients with acute coronary syndrome underwent percutaneous coronary intervention].

OBJECTIVE: To evaluate the safety and optimal prior percutaneous coronary intervention (PCI) nadroparin dose in patients with acute coronary syndrome (ACS). METHODS: A total of 236 ACS patients were randomly treated with subcutaneously nadroparin 0.075 ml/10 kg (group I, n = 120) and 0.1 ml/10 kg (group II, n = 116) respectively (bid for 48 hours). PCI was the performed 1 h after final nadroparin injection. No additional nadroparin was applied during PCI. Plasmic anti-Xa level was assayed before and at 1, 2, 4 and 8 hours after final nadroparin administration. Adverse clinical events (death, myocardial infarction, need for revascularization) and bleeding events were recorded up to 30 days post PCI. RESULTS: Baseline clinical characteristics as well as the MACE and severe bleeding events between the two groups were similar (all P > 0.05). Plasmic anti-Xa level of group II was significantly higher than that of group I post nadroparin application (P < 0.01). CONCLUSION: Anticoagulation effects and MACE as well as severe bleeding events up to 30 days post PCI were similar with either 0.075 ml/10 kg or 0.1 ml/10 kg nadroparin dose in ACS patients.