Oat Peptides Alleviate Dextran Sulfate Sodium Salt-Induced Colitis by Maintaining the Intestinal Barrier and Modulating the Keap1-Nrf2 Axis.

The prevalence of inflammatory bowel disease (IBD) is progressively rising each year, emphasizing the significance of implementing rational dietary interventions for disease prevention. Oats, being a staple agricultural product, are abundant in protein content. This study aimed to investigate the protective effects and underlying mechanisms of oat peptides (OPs) in a mouse model of acute colitis induced by dextran sulfate sodium salt (DSS) and a Caco-2 cell model. The findings demonstrated that intervention with OPs effectively mitigated the symptoms associated with DSS-induced colitis. The physicochemical characterization analysis demonstrated that the molecular weight of the OPs was predominantly below 5 kDa, with a predominant composition of 266 peptides. This study provides further evidence of the regulatory impact of OPs on the Keap1-Nrf2 signaling axis and elucidates the potential role of WGVGVRAERDA as the primary bioactive peptide responsible for the functional effects of OPs. Ultimately, the results of this investigation demonstrate that OPs effectively mitigate DSS-induced colitis by preserving the integrity of the intestinal barrier and modulating the Keap1-Nrf2 axis. Consequently, these findings establish a theoretical foundation for the utilization of OPs as dietary supplements to prevent the onset of IBD.

The Effect of Trait Mindfulness on Subjective Well-Being of Kindergarten Teachers: The Sequential Mediating Roles of Emotional Intelligence and Work-Family Balance.

Purpose: Teaching is a tough and stressful profession. Teachers' pressure and job burnout have become a common and serious problem, which makes teachers' subjective well-being feel a serious impact. The kindergarten environment is challenging and unique. The educational objects faced by kindergarten teachers are usually immature, which brings challenges to the teaching of kindergarten teachers. At the same time, in China, kindergarten teachers also need to undertake daily administrative management and other tasks. Therefore, focusing on the subjective well-being of kindergarten teachers in developing countries during the stage of the COVID-19 pandemic has important implications for promoting teacher well-being globally. Patients and Methods: The study included 321 kindergarten teachers from 13 kindergartens in Jinan, Shandong Province, China. A cross-sectional study design was used with a cluster random sampling technique. For the present study, Five-Factor Mindfulness Questionnaire, Emotional Intelligence Scale, Work-Family Balance Scale and Subjective Well-being Scale were utilized. Results: Findings of the study show that trait mindfulness can directly predict subjective well-being. Emotional intelligence played a mediating role in the relationship between trait mindfulness and subjective well-being. Work-family balance played a mediating role between trait mindfulness and subjective well-being. Emotional intelligence and work-family balance play a sequential mediating effect between trait mindfulness and subjective well-being. Conclusion: This study explores the influence mechanism of trait mindfulness on kindergarten teachers' subjective well-being from the perspective of metacognition. An important conclusion of this study is that emotional intelligence and work-family balance play a sequential mediating effect between trait mindfulness and subjective well-being. We believe the findings of this study have important implications for enriching existing theory and educational practice. This finding has important implications for improving the subjective well-being of kindergarten teachers in developing countries, especially in the context of the current severe impact of the COVID-19 pandemic on education systems.

Alterations in the Gut Microbiota and Metabolomics of Seafarers after a Six-Month Sea Voyage.

Maintaining the health of seafarers is a difficult task during long-term voyages. Little is known about the corresponding changes in the gut microbiome-host interaction. This study recruited 30 seafarers undertaking a 6-month voyage and analyzed their gut microbiota using 16S rRNA gene sequencing. Fecal untargeted metabolomics analysis was performed using liquid chromatography-mass spectrometry. Significant changes in the composition of the gut microbiota and an increased ratio of Firmicutes/Bacteroidetes at the end (day 180) of the 6-month voyage, relative to the start (day 0), were observed. At the genus level, the abundances of Holdemanella and Plesiomonas were significantly increased, while the abundance of Bacteroides was decreased. Predicted microbial functional analysis revealed significant decreases in folate biosynthesis and biotin metabolism. Furthermore, 20 differential metabolites within six differentially enriched human metabolic pathways (including arginine biosynthesis, lysine degradation, phenylalanine metabolism, sphingolipid metabolism, pentose and glucuronate interconversions, and glycine, serine, and threonine metabolism) were identified by comparing the fecal metabolites at day 0 and day 180. Spearman correlation analysis revealed close relationships between the 14 differential microbiota members and the six differential fecal metabolites that might affect specific human metabolic pathways. This study adopted a multi-omics approach and provides potential targets for maintaining the health of seafarers during long-term voyages. These findings are worthy of more in-depth exploration in future studies. IMPORTANCE Maintaining the health of seafarers undertaking long-term voyages is a difficult task. Apart from the alterations in the gut microbiome and fecal metabolites after a long-term voyage, our study also revealed that 20 differential metabolites within six differentially enriched human metabolic pathways are worthy of attention. Moreover, we found close relationships between the 14 differential microbiota members and the six differential fecal metabolites that might impact specific human metabolic pathways. Accordingly, preventative measures, such as adjusting the gut microbiota by decreasing potential pathobionts or increasing potential probiotics as well as offsetting the decrease in B vitamins and beneficial metabolites (e.g., d-glucuronic acid and citrulline) via dietary adjustment or nutritional supplements, might improve the health of seafarers during long-term sea voyages. These findings provide valuable clues about gut microbiome-host interactions and propose potential targets for maintaining the health of seafarers engaged in long-term sea voyages.

The efficacy and safety of Zengxiao Jiandu decoction combined with definitive concurrent chemoradiotherapy for unresectable locally advanced non-small cell lung cancer: a randomized, double-blind, placebo-controlled clinical trial.

Background: Traditional Chinese medicine (TCM) makes a synergistic and attenuative effect when combined with chemoradiotherapy. However, strong evidence-based studies are lacking. The study sought to investigate whether Zengxiao Jiandu decoction as an adjunctive therapy is superior to definitive concurrent chemoradiotherapy (DCCRT) alone in unresectable, locally advanced (LA), stage III non-small cell lung cancer (NSCLC). Methods: Patients with unresectable LA-NSCLC were randomly assigned to receive DCCRT either combined with Zengxiao Jiandu decoction (TCM arm) or placebo therapy (Control arm), by computer-generated random assignment lists using a central randomization system. The patients were routinely followed-up every 3 months for the first 2 years after the therapy, and every 6 months for the subsequent 3 years, or earlier if clinically indicated. The primary endpoint was grade ≥3 chemoradiotherapy-related toxicities, while secondary endpoints included the completion rate of chemoradiotherapy, the clinical objective response rate (ORR), and survival. The placebo achieved full consistency in color, aroma, taste and appearance with the Zengxiao Jiandu decoction. Results: From February 2019 to December 2020, 163 patients were randomly allocated to TCM arm (n=82) or Control arm (n=81). Fifty-nine (72.0%) patients in TCM arm finished chemoradiotherapy per protocol and 79 (96.3%) received protocol-specified Zengxiao Jiandu decoction. Forty-two patients in Control arm finished chemoradiotherapy per protocol. The incidence of grade ≥3 chemoradiotherapy-related toxicities was higher in Control arm than TCM arm (44.4% vs. 31.7%, P=0.094). Grade ≥3 radiation pneumonitis occurred more frequently in Control arm than TCM arm (13.6% vs. 3.7%, P=0.024). The completion rate of the protocol-specified chemotherapy was significantly higher in TCM arm than Control arm (79.3% vs. 64.2%, P=0.033), but the completion rates of the definitive-dose radiotherapy were similar. There were no significant differences in ORR between the 2 arms. The progression-free survival (PFS) of TCM arm was significantly better than Control arm (median PFS, 12.0 vs. 9.0 months, P=0.035). However, Zengxiao Jiandu decoction was not found to produce any significant benefit in overall survival. Conclusions: The Zengxiao Jiandu decoction adjunctive therapy, as compared to DCCRT alone, reduced grade ≥3 radiation pneumonitis, improved the completion rate of DCCRT, and prolonged PFS for unresectable LA-NSCLC. Trial Registration: Chinese Clinical Trial Registry ChiCTR2000031667.

Icariside II Restores Vascular Smooth Muscle Cell Contractile Phenotype by Enhancing the Focal Adhesion Signaling Pathway in the Rat Vascular Remodeling Model.

Vascular smooth muscle cell (VSMC) phenotypic transition represents the fundamental pathophysiological alteration in the vascular remodeling process during the initiation and progression of cardiovascular diseases. Recent studies have revealed that Icariside II (ICS-II), a flavonol glycoside derived from the traditional Chinese medicine Herba Epimedii, exhibited therapeutic effects in various cardiovascular diseases. However, the therapeutic efficacy and underlying mechanisms of ICS-II regarding VSMC phenotypic transition were unknown. In this study, we investigated the therapeutic effects of ICS-Ⅱ on vascular remodeling with a rat's balloon injury model in vivo. The label-free proteomic analysis was further implemented to identify the differentially expressed proteins (DEPs) after ICS-II intervention. Gene ontology and the pathway enrichment analysis were performed based on DEPs. Moreover, platelet-derived growth factor (PDGF-BB)-induced primary rat VSMC was implemented to verify the restoration effects of ICS-II on the VSMC contractile phenotype. Results showed that ICS-II could effectively attenuate the vascular remodeling process, promote SMA-α protein expression, and inhibit OPN expression in vivo. The proteomic analysis identified 145 differentially expressed proteins after ICS-II intervention. Further, the bioinformatics analysis indicated that the focal adhesion signaling pathway was enriched in the ICS-II group. In vitro studies showed that ICS-II suppressed VSMC proliferation and migration, and promoted VSMC contractile phenotype by modulating the focal adhesion signaling pathway. Taken together, our results suggest that ICS-II attenuates the vascular remodeling process and restores the VSMC contractile phenotype by promoting the focal adhesion pathway.

Icariside II Attenuates Vascular Remodeling Via Wnt7b/CCND1 Axis.

ABSTRACT: Angioplasty often fails due to the abnormal proliferation of vascular smooth muscle cells (VSMCs). Success rates of angioplasty may increase following the administration of an agent that effectively ameliorates aberrant vascular remodeling. Icariside II (ICS-II) is a natural flavonol glycoside extract from the Chinese herbal medicine Epimedii that possesses several medicinal qualities that are beneficial in humans. Nevertheless, the role of ICS-II in addressing aberrant vascular remodeling have yet to be clarified. The current investigation studies the molecular effects of ICS-Ⅱ on balloon-inflicted neointimal hyperplasia in rats in vivo and on platelet-derived growth factor-induced vascular proliferation in primary rat aortic smooth muscle cells (VSMCs) in vitro. ICS-II was found to be as effective as rapamycin, the positive control used in this study. ICS-II inhibited neointimal formation in injured rat carotid arteries and notably reduced the expression of Wnt7b. ICS-Ⅱ significantly counteracted platelet-derived growth factor-induced VSMCs proliferation. Cell cycle analysis showed that ICS-II triggered cell cycle arrest during the G1/S transition. Western blot analysis further indicated that this cell cycle arrest was likely through Wnt7b suppression that led to CCND1 inhibition. In conclusion, our findings demonstrate that ICS-II possesses significant antiproliferative qualities that counteracts aberrant vascular neointimal hyperplasia. This phenomenon most likely occurs due to the suppression of the Wnt7b/CCND1 axis.

Pharmacokinetic and metabolic profiling studies of sennoside B by UPLC-MS/MS and UPLC-Q-TOF-MS.

Sennoside B is a specific dianthrone compound extracted from senna, which is widely used as a stimulant laxative but has potential side effects. This study aimed to obtain the metabolic and pharmacokinetic data of sennoside B. The metabolic profiles of sennoside B were obtained from rat plasma, urine, bile and feces by an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). As a result, 14 metabolites were structurally identified and the proposed metabolic pathways of sennoside B included hydrolysis to aglycones, release of rhein-type anthrone, and extensive conjugation. As the only compound detected in the plasma samples after intravenous and intragastric administrations, the prototype was selected as the plasma marker in the pharmacokinetic study. A simple and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the quantitation of sennoside B in rat plasma. The linear range of sennoside B was 5-1000 ng/mL (R2 ≥ 0.991) and the lowest limit of quantification (LLOQ) was 5 ng/mL. The intra- and inter- precisions of the assay were less than 10%, whereas accuracy ranged from 85.80% to 103.80%. The extraction recovery, matrix effect and stability of sennoside B were within acceptable limits. The established method was well validated and successfully applied to the pharmacokinetic study of sennoside B. The oral absolute bioavailability of sennoside B was calculated as 3.60% and the value apparent volume of distribution of intravenous and intragastric administrations were 32.47 ±â€¯10.49 L/kg and 7646 ±â€¯1784 L/kg, respectively. The maximum plasma concentrations were 212.6 ±â€¯50.9 µg/L and 14.06 ±â€¯2.73 µg/L for intravenous and intragastric dosing groups, respectively. According to the current results of pharmacokinetic and metabolic profiling studies, metabolites with high abundance in tissues would be the next object in the pharmacokinetic study of sennoside B.

Design of Phase-Changeable and Injectable Alginate Hydrogel for Imaging-Guided Tumor Hyperthermia and Chemotherapy.

The objective of the present study was to construct an alginate (AG)-based phase-changeable and injectable hydrogel for imaging-guided tumor hyperthermia and chemotherapy. Based on the binding between the α-l-guluronic blocks of AG and calcium ions, the AG/MoS2/Bi2S3-poly(ethylene glycol) (MBP)/doxorubicin (DOX) solution formed a cross-linked hydrogel to simultaneously encapsulate MBP nanosheets and DOX within the hydrogel matrix. The in situ formed hydrogel can act as a reservoir to control the release of entrapped drug molecules, and the doped MBP nanosheets and DOX can realize computed tomography/photoacoustic dual-modal imaging-guided in vivo tumor photothermal therapy and chemotherapy, respectively. The AG/MBP/DOX hydrogel exhibited excellent photothermal conversion properties with mass extinction coefficient of 45.1 L/g/cm and photothermal conversion efficiency of 42.7%. Besides, the heat from the photothermal transformation of MBP can promote drug diffusion from the hydrogel to realize on-demand drug release. Additionally, the hydrogel system can restrain MBP and DOX from entering into the blood stream during therapy, and therefore substantially decrease their side effects on normal organs. More importantly, the drug loading of the AG hydrogel was general and can be extended to the encapsulation of antibiotics, such as amoxicillin, for the prevention of postoperative infections.

Bulk pancreatic cancer cells can convert into cancer stem cells(CSCs) in vitro and 2 compounds can target these CSCs.

Increasing evidence has confirmed the existence of cancer stem cells (CSCs) in both hematological malignancies and solid tumors. However, the origin of CSCs is still uncertain, and few agents have been capable of eliminating CSCs till now. The aim of this study was to investigate whether bulk pancreatic cancer cells could convert into CSCs under certain conditions and explore whether metformin and curcumin can kill pancreatic CSCs. Aspc1, Bxpc3 and Panc1 pancreatic cancer cells were cultured in stem cell culture medium (serum-free Dulbecco's modified Eagle medium/Nutrient Mixture F-12 containing basic fibroblast growth factor, epidermal growth factor, B27 and insulin) for 5 days and it was found that all the pancreatic cancer cells aggregated into spheres and expressed pancreatic cancer stem cell surface markers. Then characteristics of Panc1 sphere cells were analyzed and cytotoxicity assays were performed. The results show that Panc1 sphere cells exhibited CSC characteristics and were more resistant to conventional chemotherapy and more sensitive to metformin and curcumin than their parent cells. These findings suggested that bulk pancreatic cancer cells could acquire CSC characteristics under certain conditions, which may support the "yin-yang" model of CSCs (interconversion between bulk cancer cells and CSCs). These results also showed that metformin and curcumin could be candidate drugs for targeting pancreatic CSCs.

A novel fatty acid lipophilic index and risk of CHD in US men: the health professionals follow-up study.

Few epidemiological studies have examined the association between an overall fatty acid (FA) profile and CHD risk. The aim of the present study was to examine a novel index that summarises individual FA levels based on FA affinity and fluidity in relation to CHD risk in men. In a prospective nested case­control study, FA in plasma and erythrocytes were measured in 459 CHD cases and 879 matched controls. Lipophilic index (LI) was computed by summing the products between FA levels and melting point of each FA to reflect the overall FA lipophilicity. Among controls, higher plasma LI was significantly correlated with adverse profiles of blood lipids, inflammatory markers and adiponectin. After multivariate adjustment for age, smoking, BMI and other CHD risk factors, plasma LI was significantly associated with an increased risk of CHD: the relative risk was 1·61 (95% CI 1·03, 2·53; P for trend»0·04) comparing extreme quintiles. This association was attenuated to 1·21 (95% CI 0·48, 3·09; P for trend»0·77) after adjusting for plasma levels of total trans-FA, long-chain n-3 FA and polyunsaturated:saturated fat ratio. Erythrocyte LI was not significantly associated with CHD risk. The present data indicate that a novel LI is associated with an adverse profile of cardiovascular risk markers and increased risk of CHD in men; its usefulness as a complement of individual FA in assessing disease risk needs to be elucidated in future studies.

Effects of flaxseed supplementation on erythrocyte fatty acids and multiple cardiometabolic biomarkers among Chinese with risk factors of metabolic syndrome.

PURPOSE: We investigated effects of ground whole flaxseed supplementation on erythrocyte polyunsaturated fatty acids (PUFAs) and serum biomarkers of inflammation, endothelial dysfunction, oxidative stress, and thrombosis in Chinese with risk factors of metabolic syndrome (MetS). METHODS: This study was a secondary analysis of a 12-week, randomized, parallel-group trial in participants screened for MetS. The analysis included only those with 2 or more components of MetS before receiving either lifestyle counseling (LC, n = 90) or LC + 30 g/day flaxseed supplementation (LCF, n = 83). RESULTS: Compared to the LC group, those in the LCF group experienced significant increases in total erythrocyte n-3 PUFAs, α-linolenic acid, eicosapentenoic acid, and docosapentenoic acid (all P < 0.001), while total n-6 PUFAs (P < 0.05) and n-6/n-3 ratio decreased (P < 0.001). Arachidonic acid increased significantly in the LC group (P < 0.001), and serum high-sensitivity C-reactive protein, interleukin-18, soluble intracellular adhesion molecular-1, E-selectin, and plasminogen activator inhibitor-1 declined significantly in both groups (all P < 0.05), but no between-group differences were observed. There was no significant change in serum interleukin-6, tumor necrosis factor-α, soluble vascular adhesion molecular-1, monocyte chemoattractant protein-1, and oxidized low-density lipoprotein in either group. CONCLUSIONS: These data suggest that flaxseed supplementation increases erythrocyte n-3 PUFAs, decreases n-6 PUFAs and n-6/n-3 ratio in participants with risk factors of MetS, but has no additional benefits beyond the lifestyle consulting for the multiple biomarkers tested in the current study.

Low wintertime vitamin D levels in a sample of healthy young adults of diverse ancestry living in the Toronto area: associations with vitamin D intake and skin pigmentation.

BACKGROUND: Vitamin D plays a critical role in bone metabolism and many cellular and immunological processes. Recent research indicates that concentrations of serum 25-hydroxyvitamin D [25(OH)D], the main indicator of vitamin D status, should be in excess of 75 nmol/L. Low levels of 25(OH)D have been associated with several chronic and infectious diseases. Previous studies have reported that many otherwise healthy adults of European ancestry living in Canada have low vitamin D concentrations during the wintertime. However, those of non-European ancestry are at a higher risk of having low vitamin D levels. The main goal of this study was to examine the vitamin D status and vitamin D intake of young Canadian adults of diverse ancestry during the winter months. METHODS: One hundred and seven (107) healthy young adults self-reporting their ancestry were recruited for this study. Each participant was tested for serum 25(OH)D concentrations and related biochemistry, skin pigmentation indices and basic anthropometric measures. A seven-day food diary was used to assess their vitamin D intake. An ANOVA was used to test for significant differences in the variables among groups of different ancestry. Linear regression was employed to assess the impact of relevant variables on serum 25(OH)D concentrations. RESULTS: More than 93% of the total sample had concentrations below 75 nmol/L. Almost three-quarters of the subjects had concentrations below 50 nmol/L. There were significant differences in serum 25(OH)D levels (p < 0.001) and vitamin D intake (p = 0.034) between population groups. Only the European group had a mean vitamin D intake exceeding the current Recommended Adequate Intake (RAI = 200 IU/day). Total vitamin D intake (from diet and supplements) was significantly associated with 25(OH)D levels (p < 0.001). Skin pigmentation, assessed by measuring skin melanin content, showed an inverse relationship with serum 25(OH)D (p = 0.033). CONCLUSION: We observe that low vitamin D levels are more prevalent in our sample of young healthy adults than previously reported, particularly amongst those of non-European ancestry. Major factors influencing 25(OH)D levels were vitamin D intake and skin pigmentation. These data suggest a need to increase vitamin D intake either through improved fortification and/or supplementation.