Association of maternal weight gain in early pregnancy with congenital heart disease in offspring: a China birth cohort study.

OBJECTIVES: Little study has reported the association of maternal weight gain in early pregnancy with fetal congenital heart disease (CHD). We aimed to explore the potential relationship based on a China birth cohort while adjusting by multiple factors. DESIGN: Cohort study. SETTING: China birth cohort study conducted from 2017 to 2021. PARTICIPANTS: The study finally included 114 672 singleton pregnancies in the 6-14 weeks of gestation, without missing data or outliers, loss to follow-up or abnormal conditions other than CHD. The proportion of CHD was 0.65% (749 cases). PRIMARY AND SECONDARY OUTCOME MEASURES: Association between maternal pre-pregnancy weight gain and CHD in the offspring were analysed by multivariate logistic regression, with the unadjusted, minimally adjusted and maximally adjusted methods, respectively. RESULTS: The first-trimester weight gain showed similar discrimination of fetal CHD to that period of maternal body mass index (BMI) change (DeLong tests: p=0.091). Compared with weight gain in the lowest quartile (the weight gain less than 0.0 kg), the highest quartile (over 2.0 kg) was associated with a higher risk of fetal CHD in unadjusted (OR 1.36, 95% CI: 1.08 to 1.72), minimally adjusted (adjusted OR (aOR) 1.29, 95% CI: 1.02 to 1.62) and maximally adjusted (aOR 1.29, 95% CI: 1.02 to 1.63) models. The association remains robust in pregnant women with morning sickness, normal pre-pregnancy BMI, moderate physical activity, college/university level, natural conception or with folic acid (FA) and/or multivitamin supplementation. CONCLUSIONS AND RELEVANCE: Although the association of maternal pre-pregnancy weight gain on fetal CHD is weak, the excessive weight gain may be a potential predictor of CHD in the offspring, especially in those with morning sickness and other conditions that are routine in the cohort, such as normal pre-pregnancy BMI, moderate physical activity, college/university level, natural conception or with FA and/or multivitamin supplementation.

Honokiol attenuates high glucose-induced peripheral neuropathy via inhibiting ferroptosis and activating AMPK/SIRT1/PGC-1α pathway in Schwann cells.

Schwann cells injury induced by high glucose (HG) contributes to the development of diabetic peripheral neuropathy (DPN). Honokiol has been reported to regulate glucose metabolism, however, its effect on DPN and the precise molecular mechanisms remain unclear. This study aimed to investigate the role of AMPK/SIRT1/PGC-1α axis in the protective effects of honokiol on DPN. The biochemical assay and JC-1 staining results demonstrated that honokiol reduced HG-induced oxidative stress and ferroptosis as well as mitochondrial dysfunction in Schwann cells. RT-qPCR and western blotting were utilized to investigate the mechanism of action of honokiol, and the results showed that HG-induced inhibition of AMPK/SIRT1/PGC-1α axis and changes of downstream gene expression profile were restored by honokiol. Moreover, silencing of Sirt1 by siRNA delivery markedly diminished the changes of gene expression profile induced by honokiol in HG-induced Schwann cells. More importantly, we found that administration of honokiol remarkably attenuated DPN via improving sciatic nerve conduction velocity and increasing thermal and mechanical sensitivity in streptozotocin-induced diabetic rats. Collectively, these results demonstrate that honokiol can attenuate HG-induced Schwann cells injury and peripheral nerve dysfunction, suggesting a novel potential strategy for treatment of DPN.

Towards an integrated health risk assessment framework of soil heavy metals pollution: Theoretical basis, conceptual model, and perspectives.

The health risk of soil heavy metals pollution has been gaining increasing public concern. However, many countries have not set their own health risk assessment (HRA) framework and most of the existing studies directly referred to the USEPA risk assessment model and parameters. For those countries that do not propose an original HRA framework, the experience of developed countries is crucial for advancing their own HRA system. This study systematically reviewed the development of HRA framework in some representative developed countries. The theoretical basis, conceptual model, progress, and challenges of HRA researches concerning soil heavy metals pollution were summarized. By recalling and comparing the health risk-related laws and guidance in the USA, UK, and Japan, results showed that the construction of HRA framework varied between these countries, but HRA has become the main method for deriving their soil environmental criteria. We further summarized the evaluation scales, land use types, exposure pathways, and sensitive receptors of HRA studies, and highlighted the key parameters affecting health risk outputs. There has been a shift toward the incorporation of probabilistic modeling, metals bioavailability, and sources emission characteristics into recent HRA studies. Nonetheless, challenges remained on how to minimize the uncertainty of generating probability distribution and detecting metal bioavailability. To facilitate the development of HRA framework, it was advised that developing countries should strengthen the theoretical researches of health risk and localization researches of exposure factors. Future directions are suggested to tend to: 1) promote sensitive analysis to quantify the impact of distribution assumptions on health risk outputs, 2) derive reasonable risk threshold and consistent evaluation protocol for bioavailability-based health risk assessment method, and 3) strive to explore the combined health effect of exposure to heavy metals in soil through source-media-receptor integrated studies.

Effects of fertilizer application on phthalate ester pollution and the soil microbial community in plastic-shed soil on long-term fertilizer experiment.

Due to the use of agricultural film, the pollution of phthalate esters (PAEs) in plastic-shed soils has attracted increasing attention. In this study, we used watermelon as a planting system and investigated the effects of organic fertilizer and chemical fertilizer application on the degradation of PAEs by evaluating soil nutrients and soil bacterial communities in plastic-shed soil. The dibutyl phthalate (DBP) concentration in the organic fertilizer soil was only 58.2% in the zero-fertilization control (CK) soil, but the concentrations of monohexyl phthalate (MEHP) and mono-n-butyl ester (MBP), the metabolites of PAEs, were found to be higher. The concentration of MBP is ten times that of DBP. The results showed that fertilization, especially the application of organic fertilizers, had a significant effect on the degradation of PAEs. There were specific biomarkers in different fertilization treatments. Among the microbiome community, Planifilum had the highest relative abundance in the organic fertilizer (OF) soil, and the highest proportion of Thermodesulfovibrionia was detected in the chemical fertilizer (CF) soil. These biomarkers were significantly correlated with PAEs and their metabolites. The relative abundance of Thermomonosporaceae was significantly positively correlated with DBP. Planifilum and Thermaerobacter, which significantly increased in organic fertilizer soil, showed a significant negative correlation with DBP and a significant positive correlation with MBP. The relative abundances of Planifilum and Geobacillus were elevated in the OF soil and may be able to co-metabolize soil nitrogen and PAEs. PAEs and their metabolites in soils had significant effects on soil microbes, as did the soil nutrients including available phosphorus (AP), alkali-hydrolysable nitrogen (Alkali-N), and organic matter (OM). Our research provides scientific support for the use of fertilizers to reduce PAE contamination but also warns of the potential risks of PAE metabolites.

A Study on the Evaluation of Polyenoic Vegetable Oils and Their Female Health Benefits Based on Time Series Analysis Model: The Case of Peony Seed Oil.

Polyenoic vegetable oils mainly contain polyenoic acids such as linoleic acid and linolenic acid, as well as active ingredients such as VE, phytosterols, mineral elements, and squalene. Among them, schisandra oil, kiwi seed oil, grape seed oil, maitake fruit oil, and evening primrose seed oil all contain up to 80% or more polyenoic acids. Studies have shown that polygenic vegetable oils have the effects of assisting in lowering blood lipids, antioxidation, delaying ageing, anti-inflammation, sun protection, moisturizing, slimming and weight loss, etc. They can be widely used in nutritional and healthy edible oils, health food, skin care, and cosmetic products and have great prospects for development and utilization. This paper explores the application of artificial neural networks in the analysis of data. A nonlinear time series prediction method based on the BP algorithm is proposed. The prediction accuracy is much higher than that of the traditional method.

Distinct Basal Brain Functional Activity and Connectivity in the Emotional-Arousal Network and Thalamus in Patients With Functional Constipation Associated With Anxiety and/or Depressive Disorders.

OBJECTIVE: Functional constipation (FC) is a common gastrointestinal disorder. Anxiety and/or depressive disorders are common in patients with FC (FCAD). Brain dysfunction may play a role in FC, but the contribution of comorbid anxiety and/or depression in patients with FC is poorly understood. METHODS: Sixty-five FC patients and 42 healthy controls (HCs) were recruited, and a hierarchical clustering algorithm was used to classify FC patients into FCAD and patients without anxiety/depressive status (FCNAD) based on neuropsychological assessment. Resting-state functional magnetic resonance imaging measures including fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity were used to investigate brain functional differences. RESULTS: Thirty-seven patients were classified as FCAD, and 28 patients were classified as FCNAD; as compared with HC, both groups showed decreased activity (fALFF) in the perigenual anterior cingulate cortex (pACC), dorsomedial prefrontal cortex (DMPFC), and precuneus; enhanced precentral gyrus-thalamus connectivity and attenuated precuneus-thalamus connectivity in FCAD/FCNAD highlighted the thalamus as a critical connectivity node in the brain network (pFWE < .05). In comparison with FCNAD/HC, the FCAD group also had decreased fALFF in the orbitofrontal cortex (OFC) and thalamus, and increased OFC-hippocampus connectivity. In the FCNAD group, brain activities (pACC/DMPFC) and connection (precuneus-thalamus) had correlations only with symptoms; in the FCAD group, brain activities (OFC, pACC/DMPFC) and connectivities (OFC-hippocampus/precentral gyrus-thalamus) showed correlations with both constipation symptoms and anxiety/depressive status ratings. Mediation analysis indicated that the relationship between abdominal distension and OFC activity was completely mediated by anxiety in FCAD. CONCLUSIONS: These findings provide evidence of differences in brain activity and functional connectivity between FCAD and FCNAD, potentially providing important clues for improving treatment strategies.

Hypoglycemic activity of Origanum vulgare L. and its main chemical constituents identified with HPLC-ESI-QTOF-MS.

Origanum vulgare L. (O. vulgare) is an important medicine food homology in diabetes. The present study aimed to assess the hypoglycemic effect of the leaf extract of O. vulgare in HepG2 and HepG2-GFP-CYP2E1 (E47) cells, and disclose its potential active components by the HPLC-ESI-QTOF-MS method. Firstly, we evaluated the anti-diabetic capacity of the leaf extract of O. vulgare through inhibition of α-glucosidase activity, promotion of glucose uptake, inhibition of glycosylation and relieving of oxidative stress. Secondly, the promoter activity, the mRNA and protein expression of PEPCK and SREBP-1c, and the expression of CPY2E1 and GLUT2 in the O. vulgare mediated anti-diabetic capacity were analyzed in HepG2 and E47 cells. Finally, HPLC-ESI-QTOF-MS analysis was performed to identify the herb's main components under 280 nm irradiation. In vitro assays demonstrated that the extract inhibited α-glucosidase activity, promoted glucose uptake, inhibited glycosylation and relieved oxidative stress, which suggested that O. vulgare leaf extract has a strong hypoglycemic capacity. Moreover, mechanistic analysis also showed that the extract decreased the promoter activity and the mRNA and protein expression of PEPCK and SREBP-1c. In addition, the extract inhibited the expression of CPY2E1 and enhanced the expression of GLUT2. Moreover, the UV chromatogram at 280 nm showed six main peaks, identified as amburoside A (or 4-(3',4'-dihydroxybenzoyloxymethyl) phenyl O-ß-d-glucopyranoside), luteolin 7-O-glucuronide, apigenin 7-O-glucuronide, rosmarinic acid, lithospermic acid and a novel compound, demethylbenzolignanoid, based on accurate MS data. This work supported the ethnopharmacological usage of O. vulgare as an antidiabetic herbal medicine or dietary supplement and identified its main phenolic compounds.

Abnormalities in the thalamo-cortical network in patients with functional constipation.

Functional constipation (FCon) is a common functional gastrointestinal disorder (FGID); neuroimaging studies have shown brain functional abnormalities in thalamo-cortical regions in patients with FGID. However, association between FCon and topological characteristics of brain networks remains largely unknown. We employed resting-state functional magnetic resonance imaging (RS-fMRI) and graph theory approach to investigate functional brain topological organization in 42 patients with FCon and 41 healthy controls (HC) from perspectives of global, regional and modular levels. Results showed patients with FCon had a significantly lower normalized clustering coefficient and small-worldness, implying decreased brain functional connectivity. Regions showed altered nodal degree and efficiency mainly located in the thalamus, rostral anterior cingulate cortex (rACC), and supplementary motor area (SMA), which are involved in somatic/sensory, emotional processing and motor-control. For the modular analysis, thalamus, rACC and SMA had an aberrant within-module nodal degree and nodal efficiency, and thalamus-related network exhibited abnormal interaction with the limbic network (amygdala and hippocampal gyrus). Nodal degree in the thalamus was negatively correlated with difficulty of defecation, and nodal degree in the rACC was negatively correlated with sensation of incomplete evacuation. These findings indicated that FCon was associated with abnormalities in the thalamo-cortical network.

B-vitamin supplementation ameliorates anxiety- and depression-like behavior induced by gestational urban PM2.5 exposure through suppressing neuroinflammation in mice offspring.

PM2.5 exposure is an emerging environmental concern and severe health insult closely related to psychological conditions such as anxiety and depression in adolescence. Adolescence is a critical period for neural system development characterized by continuous brain maturation, especially in the prefrontal cortex. The etiology of these adolescent conditions may derive from fetal origin, probably attributed to the adverse effects induced by intrauterine environmental exposure. Anxiety- and depression-like behavior can be induced by gestational exposure to PM2.5 in mice offspring which act as a useful model system. Recent studies show that B-vitamin may alleviate PM2.5-induced hippocampal neuroinflammation- and function-related spatial memory impairment in adolescent mice offspring. However, cortical damage and related neurobehavioral defects induced by gestational PM2.5 exposure, as well as the potential reversibility by interventions in mice offspring require to be elucidated. Here, we aimed to investigate whether B-vitamin would protect mice offspring from the adverse effects derived from gestational exposure to urban PM2.5 on cortical areas to which anxiety and depression are closely related. Pregnant mice were divided into three groups: control group (treated with PBS alone), model group (treated with both PM2.5 and PBS), and intervention group (treated with both PM2.5 and B-vitamin), respectively. The mice offspring were then applied to comprehensive neurobehavioral, ultrastructural, biochemical, and molecular biological analyses. Interestingly, we observed that gestational PM2.5 exposure led to neurobehavioral defects including anxiety- and depression-like behavior. In addition, neuroinflammation, oxidative damage, increased apoptosis, and caspase-1-mediated inflammasome activation in the prefrontal cortex were observed. Notably, both behavioral and molecular changes could be significantly alleviated by B-vitamin treatment. In summary, our results suggest that the anxiety- and depression-like behavior induced by gestational PM2.5 exposure in mice offspring can be ameliorated by B-vitamin supplementation, probably through the suppression of apoptosis, oxidative damage, neuroinflammation, and caspase-1-mediated inflammasome activation.

Wilforine resensitizes multidrug resistant cancer cells via competitive inhibition of P-glycoprotein.

BACKGROUND AND PURPOSE: Multidrug resistance (MDR) remains the main obstacle in cancer treatment and overexpression of P-glycoprotein (P-gp) is one of the most common causes of chemoresistance. The development of novel P-gp inhibitors from natural products is a prospective strategy to combat MDR cancers. Among the natural sesquiterpene compounds, sesquiterpene pyridine alkaloids exhibit various biological properties. Therefore, in the present study, we evaluated the modulatory effects of wilforine on P-gp expression and function. The molecular mechanisms and kinetic models of wilforine-mediated P-gp inhibition were further investigated. METHODS: The human P-gp stable expression cells (ABCB1/Flp-InTM-293) and human cervical cancer cells (sensitive: HeLaS3; MDR: KBvin) were used. The cell viability was assessed by SRB assay. The inhibitory effect of wilforine on P-gp efflux and the underlying mechanism were evaluated by assays for calcein-AM uptake, rhodamine123 and doxorubicin efflux, ATPase activity, real-time quantitative RT-PCR, apoptosis, and cell cycle analysis. Molecular docking was performed by the docking software CDOCKER with BIOVIA Discovery Studio 4.5 (D.S. 4.5). RESULTS: We found that wilforine significantly inhibited the efflux activity of P-gp in a concentration-dependent manner. Further kinetic analysis demonstrated that wilforine significantly inhibited P-gp efflux function by competitive inhibition and stimulated the basal P-gp ATPase activity. In addition, wilforine re-sensitized MDR cancer cells to chemotherapeutic drugs. The docking model indicated that wilforine was bound to residues of P-gp such as LEU884, LYS887, THR176 and ASN172. CONCLUSION: These results suggest a novel future therapeutic strategy for MDR cancer using wilforine as an adjuvant treatment with chemotherapy.

Dietary thymol supplementation promotes skeletal muscle fibre type switch in longissimus dorsi of finishing pigs.

As one of the key points related to meat quality, skeletal muscle fibre type is determined by energy metabolism and genetic factors, but its transformation could be also greatly influenced by many factors. Thymol, the primary effective ingredients of thyme, is well known for its anti-oxidation and anti-inflammatory, while little is known about its effect on skeletal muscle oxidative metabolism and fibre type switch. Therefore, in order to investigate its effects and possibility to be applied in livestock production, 36 150-day-old fattening Pigs were fed with different diet for six-week experiment. As a result, the drip loss ratio of longissimus dorsi (LD) was significantly reduced (p < .05). Oxidative metabolism-related enzyme activity, the mRNA levels and protein expression of COX5B and PGC1α, mRNA level of myosin heavy chain I (MyHC I) and protein level of MyHC IIa were significantly upregulated (p < .05). While compared with control group, the protein expression of MyHC IIb was significantly decreased (p < .05). The result revealed that thymol could promote the oxidative metabolism in the muscle of pigs and improve the meat quality to a certain extent.

Transcriptome analysis in roots and leaves of wheat seedlings in response to low-phosphorus stress.

Low phosphorus availability is a major abiotic factor constraining wheat growth. The molecular mechanisms of the wheat whole genome under low-phosphorus stress are still unclear. To obtain information on gene expression in wheat seedlings under low-phosphorus stress, transcriptome sequencing was performed on roots and leaves. The results showed that 2,318 (1,646 upregulated and 672 downregulated) transcripts were differentially expressed in the leaves, and 2,018 (1,310 upregulated and 708 downregulated) were differentially expressed in the roots. Further analysis showed that these differentially expressed genes (DEGs) were mainly enriched in carbon fixation in photosynthetic organs and in carbon metabolism, photosynthesis, glyoxylate and dicarboxylate metabolism and plant-pathogen interaction in both leaves and roots. These pathways were mainly associated with environmental adaptation, energy metabolism and carbohydrate metabolism, suggesting that the metabolic processes were strengthened in wheat seedlings under low-phosphorus stress and that more energy and substances were produced to resist or adapt to this unfavourable environment. This research might provide potential directions and valuable resources to further study wheat under low-phosphorus stress.

Effects of maternal dietary supplementation of phytosterol esters during gestation on muscle development of offspring in mice.

The development of muscle in the embryo, which is crucial for postnatal skeletal muscle growth, has been investigated widely. Much has been learned during the past several decades about the role of maternal nutrition in the outcome of pregnancy. Protein and carbohydrate levels during pregnancy have been shown to be important in the development of offspring, especially muscle development. However, the maternal effects of steroids were still not clear. Phytosterol esters (PEs) are produced by the esterification of phytosterols and fatty acids and have many beneficial functions, such as anti-inflammation and hypolipemic functions. Through the effect of regulation on lipid metabolism, can pregnant mice fed with PEs show any programming effect on the muscle development of offspring? In our study, PEs were supplied to the maternal diet, and changes in maternal lipid metabolism and the development of offspring skeletal muscle were detected. As a result, the amniotic fluid total bile acid (TBA) and total cholesterol (TC) levels were decreased; the growth of offspring was significantly faster than that of the control group until 6 weeks of age. Adult offspring had a higher lean mass index and grip strength. In skeletal muscle, the proportion of myosin heavy chain (MHC) 1 was significantly decreased, while the proportion of MHC 2 b was increased. In conclusion, maternal PEs significantly reduced sterols in the amniotic fluid, while skeletal muscle development was promoted in the offspring.

Gestational B-vitamin supplementation alleviates PM2.5-induced autism-like behavior and hippocampal neurodevelopmental impairment in mice offspring.

Gestational exposure to PM2.5 is a worldwide environmental issue associated with long-lasting behavior abnormalities and neurodevelopmental impairments in the hippocampus of offspring. PM2.5 may induce hippocampus injury and lead to autism-like behavior such as social communication deficits and stereotyped repetitive behavior in children through neuroinflammation and neurodegeneration. Here, we investigated the preventive effect of B-vitamin on PM2.5-induced deleterious effects by focusing on anti-inflammation, antioxidant, synaptic remodeling and neurodevelopment. Pregnant mice were randomly divided into three groups including control group (mice subject to PBS only), model group (mice subject to both 30 µL PM2.5 of 3.456 µg/µL and 10 mL/(kg·d) PBS), and intervention group (mice subject to both 30 µL PM2.5 of 3.456 µg/µL and 10 mL/(kg·d) B-vitamin supplementation (folic acid, vitamin B6 and vitamin B12 with concentrations at 0.06, 1.14 and 0.02 mg/mL, respectively)). In the current study B-vitamin significantly alleviated neurobehavioral impairment reflected in reduced social communication disorders, stereotyped repetitive behavior, along with learning and spatial memory impairment in PM2.5-stimulated mice offspring. Next, B-vitamin corrected synaptic loss and reduced mitochondrial damage in hippocampus of mice offspring, demonstrated by normalized synapse quantity, synaptic cleft, postsynaptic density (PSD) thickness and length of synaptic active area. Furthermore, significantly down-regulated expression of pro-inflammatory cytokines including NF-κB, TNF-α and IL-1ß, and lipid peroxidation were found. We observed elevated levels of oxidant-related genes (SOD, GSH and GSH-Px). Moreover, decreased cleaved caspase-3 and TUNEL-positive cells suggested inhibited PM2.5-induced apoptosis by B-vitamin. Furthermore, B-vitamin increased neurogenesis by increasing EdU-positive cells in the subgranular zone (SGZ) of offspring. Collectively, our results suggest that B-vitamin supplementation exerts preventive effect on autism-like behavior and neurodevelopmental impairment in hippocampus of mice offspring gestationally exposed to PM2.5, to which alleviated mitochondrial damage, increased anti-inflammatory and antioxidant capacity and synaptic efficiency, reduced neuronal apoptosis and improved hippocampal neurogenesis may contribute.

Antidiabetic potential of the ethyl acetate extract of Physalis alkekengi and chemical constituents identified by HPLC-ESI-QTOF-MS.

ETHNOPHARMACOLOGICAL RELEVANCE: The edible plant Physalis alkekengi (PA) is used in traditional medicine to treat diabetes. However, the anti-diabetic effects and constituents of the fruit and aerial parts of this plant have not been studied extensively. AIM OF THE STUDY: The purpose of this study was to investigate the antidiabetic potential of Physalis alkekengi and identify its chemical constituents. MATERIALS AND METHODS: In the present study, the in vitro glucose uptake capacity was tested using the 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose (2-NBDG) assay in HepG2 cells. Secondly, the anti-diabetes effects of the ethyl acetate extracts of the aerial parts/fruit (EAP/EAF) of P. alkekengi were evaluated in high-fat diet-fed and streptozotocin-induced diabetic rats (seven groups, n = 7) daily at doses of 300 and 600 mg/kg for 28 days. Fasting blood glucose (FBG) was measured with a glucometer and the levels of total cholesterol (TC), triglyceride (TG), glycated serum protein (GSP), and fasting insulin (FINS) were measured by ELISA. Furthermore, insulin sensitivity index (ISI) and homeostasis model assessment-insulin resistance index (HOMA-IR) were calculated based on FBG and FINS. Changes in blood glucose concentration were assessed after an oral glucose challenge in diabetic rats treated with EAF and EAP extracts. In all assays, rosiglitazone, a current antidiabetic drug and insulin sensitizer, was also tested. Finally, the compounds in EAP were identified by HPLC-ESI-QTOF-MS analysis. RESULTS: EAP increased the uptake of 2-NBDG, a measure of direct glucose uptake, in HepG2 cells. Next, in diabetic rats treated with P. alkegenki extracts for 28 days, the levels of FBG, TC, TG and GSP and were lowered effectively, while FINS was increased significantly. EAP/EAF enhanced insulin sensitivity significantly as measured by ISI and HOMA-IR along with oral glucose tolerance test analysis. The EAP generally exerted the greatest effects. Lastly, a HPLC-ESI-Q-TOF-MS analysis identified 50 compounds, including 26 physalins, 10 flavonoids, and 9 phenolic acids, with 21 compounds found for the first time in P. alkekengi. CONCLUSIONS: The results support the merit of P. alkekengi as an antidiabetic herbal medicine or dietary supplement.

Evaluation of in vitro/in vivo anti-diabetic effects and identification of compounds from Physalis alkekengi.

The aims of the present study were to assess the anti-diabetic effects of Physalis alkekengi L. (PA) in 3T3-L1 pre-adipocyte cells and HepG2-GFP-CYP2E1 (E47) cells and in a pre-diabetic rat model, as well as to identify the active chemical constituents. The in vitro results showed that PA has a strong anti-diabetic capacity to relieve oxidative stress and inhibit α-glucosidase activity. Mechanistic analysis also showed that ethyl acetate extracts of aerial parts and fruit of PA (PAG-EA and PAF-EA) enhanced glucose transporter 4 expression and function as well as enhanced insulin sensitivity by inhibiting the expression of cytochrome P450-2E1 (CYP2E1) mRNA and protein. In vivo, PAG-EA and PAF-EA significantly decreased the levels of fasting blood glucose and fasting insulin, as well as total cholesterol and triglyceride, in the pre-diabetic rats. The results from insulin sensitivity index and homeostasis model assessment-insulin resistance index along with an oral glucose tolerance test also showed that PAG-EA and PAF-EA could significantly enhance the insulin sensitivity, which confirmed the in vitro findings. Moreover, HPLC-ESI-QTOF-MS analysis identified flavonoids, physalins and phenolic acids as the main plant constituents. Our findings support the ethnopharmacological use of PA fruit, along with its aerial parts, as a strong anti-diabetic agent. The EA fraction, especially the constituent polyphenols and flavonoids, may have a good potential to treat diabetes.

Capsinoids activate brown adipose tissue (BAT) with increased energy expenditure associated with subthreshold 18-fluorine fluorodeoxyglucose uptake in BAT-positive humans confirmed by positron emission tomography scan.

Background: Capsinoids are reported to increase energy expenditure (EE) via brown adipose tissue (BAT) stimulation. However, imaging of BAT activation by capsinoids remains limited. Because BAT activation is a potential therapeutic strategy for obesity and related metabolic disorders, we sought to prove that capsinoid-induced BAT activation can be visualized by 18-fluorine fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). Objective: We compared capsinoids and cold exposure on BAT activation and whole-body EE. Design: Twenty healthy participants (8 men, 12 women) with a mean age of 26 y (range: 21-35 y) and a body mass index (kg/m2) of 21.7 (range: 18.5-26.0) underwent 18F-FDG PET and whole-body calorimetry after ingestion of 12 mg capsinoids or ≤2 h of cold exposure (∼14.5°C) in a crossover design. Mean standardized uptake values (SUVs) of the region of interest and BAT volumes were calculated. Blood metabolites were measured before and 2 h after each treatment. Results: All of the participants showed negligible 18F-FDG uptake post-capsinoid ingestion. Upon cold exposure, 12 participants showed avid 18F-FDG uptake into supraclavicular and lateral neck adipose tissues (BAT-positive group), whereas the remaining 8 participants (BAT-negative group) showed undetectable uptake. Capsinoids and cold exposure increased EE, although cold induced a 2-fold increase in whole-body EE and higher fat oxidation, insulin sensitivity, and HDL cholesterol compared with capsinoids. Conclusions: Capsinoids only increased EE in BAT-positive participants, which suggests that BAT mediates EE evoked by capsinoids. This implies that capsinoids stimulate BAT to a lesser degree than cold exposure as evidenced by 18F-FDG uptake below the presently accepted SUV thresholds defining BAT activation. This trial was registered at www.clinicaltrials.gov as NCT02964442.

Dietary fat and carbohydrate quality have independent effects on postprandial glucose and lipid responses.

PURPOSE: The magnitude of postprandial lipemia is influenced not only by the amount but also the type of fat and carbohydrate consumed. The aim of this study was to evaluate differences in postprandial glucose and lipid responses after a mixed meal containing low- or high-glycemic-index (GI) carbohydrate and three different types of fat varying in the degree of saturation in healthy subjects. METHODS: A randomized, controlled, single-blinded crossover study was conducted in 20 healthy Chinese men. Subjects consumed in random order six experimental isocaloric meals that differed in carbohydrate and fat quality, and contained 40 g of either saturated fat (SFA, butter), monounsaturated fat (MUFA, olive oil) or polyunsaturated fat (PUFA, grapeseed oil), and 50 g of either low-GI (basmati rice) or high-GI (jasmine rice) carbohydrate. Glucose, insulin, c-peptide, triglycerides (TG) and non-esterified fatty acids (NEFA) were measured over 4 h. RESULTS: For all substrates evaluated, there were no significant interactions between fat and carbohydrate. The incremental area under the curve (iAUC) for TG was significantly lower after the SFA and PUFA meals compared with the MUFA meal, irrespective of GI. No significant difference was found for NEFA iAUC in all treatments. Glucose, insulin and c-peptide iAUCs were significantly lower after ingestion of low-GI than high-GI meals, independent of the type of fat. CONCLUSIONS: A carbohydrate-rich meal (of either low or high GI) that contains butter or grapeseed oil results in lower postprandial TG concentrations relative to olive oil in healthy Chinese males. Glucose, insulin and c-peptide responses, however, are directly dependent on the GI of the meal and not on the degree of saturation of dietary fat. The trial was registered at clinicaltrials.gov as NCT02585427.

Astragaloside I Stimulates Osteoblast Differentiation Through the Wnt/ß-catenin Signaling Pathway.

Astragaloside I (As-I), one of the main active ingredients in Astragalus membranaceus, is believed to have osteogenic properties, but this hypothesis has not been investigated in detail. In the present work, the As-I-induced osteogenic effects and its underlying mechanism were studied in MC3T3-E1 cells. The results indicated that the cellular levels of ALP and extracellular matrix calcium increased in a dose-dependent manner by As-I. To clarify the mechanisms involved in this process, the effect of As-I on the key osteogenic-related genes was investigated. We found that As-I stimulated the expression of ß-catenin and Runx2 in MC3T3-E1 cells, which play central roles in the Wnt/ß-catenin signaling pathway, suggesting that As-I could promote osteoblastic differentiation by regulating the Wnt/ß-catenin signaling pathway. Moreover, the osteogenic effect of As-I could be inhibited by DKK-1, which is the classical inhibitor of Wnt/ß-catenin-signaling pathway. Furthermore, As-I also increased BMP-2, BGP and OPG/RANKL expression, which are also activated by Wnt/ß-catenin signaling pathway. Taken together, our findings show that As-I stimulates osteoblast differentiation through the Wnt/ß-catenin signaling pathway, which also activates the BMP pathway and RANK pathway, thus highlighting the As-I for pharmaceutical and medicinal applications such as treating bone disease. Copyright © 2016 John Wiley & Sons, Ltd.

Comparison of Formulas Based on Lipid Emulsions of Olive Oil, Soybean Oil, or Several Oils for Parenteral Nutrition: A Systematic Review and Meta-Analysis.

Many studies have reported that olive oil-based lipid emulsion (LE) formulas of soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) may be a viable alternative for parenteral nutrition. However, some randomized controlled clinical trials (RCTs) have raised concerns regarding the nutritional benefits and safety of SMOFs. We searched principally the MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Scopus, EMBASE, and Cochrane Central Register of Controlled Trials databases from inception to March 2014 for the relevant literature and conducted a meta-analysis of 15 selected RCTs that 1) compared either olive oil- or SMOF-based LEs with soybean oil-based LEs and 2) reported plasma concentrations of α-tocopherol, oleic acid, and ω-6 (n-6) and ω-3 (n-3) long-chain polyunsaturated fatty acids (PUFAs) and liver concentrations of total bilirubin and the enzymes alanine transaminase, aspartate transaminase, alkaline phosphatase, and γ-glutamyl transferase. The meta-analysis suggested that SMOF-based LEs were associated with higher plasma concentrations of plasma α-tocopherol, oleic acid, and the ω-3 PUFAs eicosapentaenoic and docosahexaenoic acid. Olive oil- and SMOF-based LEs correlated with lower plasma concentrations of long-chain ω-6 PUFAs and were similar to soybean oil-based LEs with regard to their effects on liver function indicators. In summary, olive oil- and SMOF-based LEs have nutritional advantages over soybean oil-based LEs and are similarly safe. However, their performance in clinical settings requires further investigation.