Ferritin-mediated mitochondrial iron homeostasis is essential for the survival of hematopoietic stem cells and leukemic stem cells.

Iron metabolism plays a crucial role in cell viability, but its relationship with adult stem cells and cancer stem cells is not fully understood. The ferritin complex, responsible for intracellular iron storage, is important in this process. We report that conditional deletion of ferritin heavy chain 1 (Fth1) in the hematopoietic system reduced the number and repopulation capacity of hematopoietic stem cells (HSCs). These effects were associated with a decrease in cellular iron level, leading to impaired mitochondrial function and the initiation of apoptosis. Iron supplementation, antioxidant, and apoptosis inhibitors reversed the reduced cell viability of Fth1-deleted hematopoietic stem and progenitor cells (HSPCs). Importantly, leukemic stem cells (LSCs) derived from MLL-AF9-induced acute myeloid leukemia (AML) mice exhibited reduced Fth1 expression, rendering them more susceptible to apoptosis induced by the iron chelation compared to normal HSPCs. Modulating FTH1 expression using mono-methyl fumarate increased LSCs resistance to iron chelator-induced apoptosis. Additionally, iron supplementation, antioxidant, and apoptosis inhibitors protected LSCs from iron chelator-induced cell death. Fth1 deletion also extended the survival of AML mice. These findings unveil a novel mechanism by which ferritin-mediated iron homeostasis regulates the survival of both HSCs and LSCs, suggesting potential therapeutic strategies for blood cancer with iron dysregulation.

Alpinia officinarum Hance extract ameliorates diabetic gastroparesis by regulating SCF/c-kit signaling pathway and rebalancing gut microbiota.

Diabetic gastroparesis (DGP) is a common complication of type 2 diabetes mellitus (T2DM). Alpinia officinarum Hance (AOH) is one of the most commonly used both as a food and folk medicines, which is rich in diarylheptanoids and flavonoids. The gastroprotection and hypoglycemic effect make AOH has great potential in developing of anti-DGP complementary medicine. However, the molecular mechanisms of AOH that act against DGP are yet to be elucidated. In this study, we evaluated the therapeutic effects, the potential molecular mechanism, and the changes of gut microbiota of AOH in DGP. The 5 components of the AOH were analyzed, and the potential signaling pathway of AOH improving DGP was predicted by molecular docking. Subsequently, DGP rat model was constructed using high-fat-irregular-diet, AOH intervention significantly reduced blood glucose levels, increased gastrointestinal propulsion rate, and improved gastric histological morphology in DGP rats. Meanwhile, AOH has been shown to regulate the SCF/c-kit signaling pathway and rebalance the gut microbiota, which may be closely related to its role in improving DGP. Taken together, AOH may play a protective role on DGP through multiple mechanisms, which might pave the road for development and utilization of AOH.

Exploring the Underlying Mechanism of Alpinia officinarum Hance Ameliorating Diabetic Gastroparesis through Combining Network Pharmacology, Molecular Docking, and in Vivo Experimental Verification.

BACKGROUND: Alpinia officinarum Hance (AOH) has a long history in China as a Chinese medicine and exerts the pharmacological effects of antidiabetic and gastrointestinal protection. In traditional Chinese medicine theory, AOH is often combined with other Chinese medicines for the treatment of diabetic gastroparesis (DGP). However, the molecular mechanisms, potential targets, and bioactive ingredients of AOH that act against DGP are yet to be elucidated. In this study, network pharmacology, molecular docking, and experimental study were used to predict the therapeutic effects and the potential molecular mechanism of AOH in DGP. METHODS: Network pharmacology analysis was performed to acquire information on the active chemical ingredients, DGP-related target proteins in AOH, and potential signaling pathway. In addition, molecular docking approach was used to simulate the binding of drugs and targets. Finally, DGP-mice model was used for experimental verification in vivo. Results: Through the network pharmacological research, AKT1 was found to be the core protein in AOH for the treatment of DGP and was mainly involved in the PI3K-AKT signaling pathway. Additionally, the interactions between bioactive compounds and target proteins (PIK3CA and AKT1) were analyzed using molecular docking, which verified the results of network pharmacology. Further in vivo studies indicated that AOH could reduce fasting blood glucose levels, improve gastric emptying rate, and ameliorate biochemical indicators in DGP mice. Moreover, AOH could increase the expressions and phosphorylation levels of PI3K and AKT in the stomach to regulate oxidative stress. CONCLUSIONS: The study has shown that AOH may play a protective role on DGP through mediation of the PI3K-AKT signaling pathway to regulate oxidative stress.

Effect of synbiotic supplementation on immune parameters and gut microbiota in healthy adults: a double-blind randomized controlled trial.

Synbiotics are increasingly used by the general population to boost immunity. However, there is limited evidence concerning the immunomodulatory effects of synbiotics in healthy individuals. Therefore, we conducted a double-blind, randomized, placebo-controlled study in 106 healthy adults. Participants were randomly assigned to receive either synbiotics (containing Bifidobacterium lactis HN019 1.5 × 108 CFU/d, Lactobacillus rhamnosus HN001 7.5 × 107 CFU/d, and fructooligosaccharide 500 mg/d) or placebo for 8 weeks. Immune parameters and gut microbiota composition were measured at baseline, mid, and end of the study. Compared to the placebo group, participants receiving synbiotic supplementation exhibited greater reductions in plasma C-reactive protein (P = 0.088) and interferon-gamma (P = 0.008), along with larger increases in plasma interleukin (IL)-10 (P = 0.008) and stool secretory IgA (sIgA) (P = 0.014). Additionally, synbiotic supplementation led to an enrichment of beneficial bacteria (Clostridium_sensu_stricto_1, Lactobacillus, Bifidobacterium, and Collinsella) and several functional pathways related to amino acids and short-chain fatty acids biosynthesis, whereas reduced potential pro-inflammatory Parabacteroides compared to baseline. Importantly, alternations in anti-inflammatory markers (IL-10 and sIgA) were significantly correlated with microbial variations triggered by synbiotic supplementation. Stratification of participants into two enterotypes based on pre-treatment Prevotella-to-Bacteroides (P/B) ratio revealed a more favorable effect of synbiotic supplements in individuals with a higher P/B ratio. In conclusion, this study suggested the beneficial effects of synbiotic supplementation on immune parameters, which were correlated with synbiotics-induced microbial changes and modified by microbial enterotypes. These findings provided direct evidence supporting the personalized supplementation of synbiotics for immunomodulation.

Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial.

Dietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas with dietary fibers or probiotics on functional constipation symptoms, and to identify modulations of gut microbiota of relevance. We conducted a 4-week double-blinded randomized placebo-controlled trial in 250 adults with functional constipation. Intervention: A: polydextrose; B: psyllium husk; C: wheat bran + psyllium husk; D: Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001; Placebo: maltodextrin. Oligosaccharides were also included in group A to D. 16S rRNA sequencing was used to assess the gut microbiota at weeks 0, 2, and 4. A total of 242 participants completed the study. No time-by-group effect was observed for bowel movement frequency (BMF), Bristol stool scale score (BSS), and degree of defecation straining (DDS), while BSS showed mean increases of 0.95-1.05 in group A to D (all P < 0.05), but not significantly changed in placebo (P = 0.170), and 4-week change of BSS showed similarly superior effects of the interventions as compared placebo. Group D showed a marginal reduction in plasma 5-hydroxytryptamine. Group A resulted in a higher Bifidobacterium abundance than placebo at week 2 and 4. Fourteen genera showed intervention-specific increasing or decreasing trends continuously, among which Anaerostipes showed increasing trends in groups B and C, associated with BMF increase. Random forest models identified specific baseline microbial genera panels predicting intervention responders. In conclusion, we found that the dietary fibers or probiotics may relieve hard stool, with intervention-specific changes in gut microbiota relevant to constipation relief. Baseline gut microbiota may predispose the intervention responsiveness. ClincialTrials.gov number, NCT04667884.

What is the context?Supplementation of dietary fibers, such as psyllium husk or wheat bran (10 ~ 15 g/day) may relieve constipation symptoms, but bloating and flatulence are major concerns on a high fiber intake.Functional constipation patients had alternated gut microbiota profiles, while meta-analysis suggested that multispecies probiotics may increase bowel movement frequency and relieve hard stool in functional constipation.Dietary fibers or probiotics may lead to before-after changes of gut microbiota in patients with functional constipation, but time-series continued changes of gut microbiota during the intervention are unknown.Elevation of 5-hydroxytryptamine synthesis in enterochromaffin cells may affect bowel movement. And the elevated plasma 5-hydroxytryptamine was observed in functional constipation patients.What is new? Daily supplement of three prebiotic formulas with dietary fibers (polydextrose, psyllium husk, wheat bran, together with oligosaccharides), or a probiotic formula with Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001 effectively relieved hard stool in functional constipation patients after 4 weeks intervention.We identified continued increasing or decreasing gut microbial genera over the intervention. Dietary fiber ­ gut microbiota (Anaerostipes)­constipation relieve (bowel movement frequency) evidence axis was identified in this human trial.Probiotic supplementation marginally reduced plasma 5-hydroxytryptamine, possibly associated with changes in BMF-related gut microbial genera.Intervention-specific baseline gut microbiota well predicted the responsiveness of constipation symptom relief.What is the impact? We provided references for the dosage and duration of dietary fiber/probiotics recommendations for adults with functional constipation, and advanced the microbial genera evidences of the fibers/probiotics-microbiota-laxation theory in humans.

Investigation of the Potential Mechanism of Alpinia officinarum Hance in Improving Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking.

Objective: We used network pharmacology, molecular docking, and cellular analysis to explore the pharmacodynamic components and action mechanism of Alpinia officinarum Hance (A. officinarum) in improving type 2 diabetes mellitus (T2DM). Methods: The protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the potential targets and mechanism of A. officinarum toward improving T2DM. The first 9 core targets and potential active compounds were docked using Discovery Studio 2019. Finally, IR-HepG2 cells and qPCR were applied to determine the mRNA expression of the top 6 core targets of the PPI network. Results: A total of 29 active ingredients and 607 targets of A. officinarum were obtained. T2DM-related targets overlapped with 176 targets. The core targets of the PPI network were identified as AKT serine/threonine kinase 1 (AKT1), an activator of transcription 3 (STAT3), tumor necrosis factor (TNF), tumor protein p53 (TP53), SRC proto-oncogene, nonreceptor tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), albumin (ALB), mitogen-activated protein kinase 1 (MAPK1), and peroxisome proliferator-activated receptor gamma (PPARG). A. officinarum performs an antidiabetic role via the AGE-RAGE signaling pathway, the HIF-1 signaling pathway, the PI3K-AKT signaling pathway, and others, according to GO and KEGG enrichment analyses. Molecular docking revealed that the binding ability of diarylheptanoid active components in A. officinarum to core target protein was higher than that of flavonoids. The cell experiments confirmed that the A. officinarum extracts improved the glucose uptake of IR-HepG2 cells and AKT expression while inhibiting the STAT3, TNF, TP53, SRC, and EGFR mRNA expression. Conclusion: A. officinarum Hance improves T2DM by acting on numerous components, multiple targets, and several pathways. Our results lay the groundwork for the subsequent research and broaden the clinical application of A. officinarum Hance.

Effects of low-dose B vitamins plus betaine supplementation on lowering homocysteine concentrations among Chinese adults with hyperhomocysteinemia: a randomized, double-blind, controlled preliminary clinical trial.

PURPOSE: To test the hypothesis that daily supplementation with low-dose B vitamins plus betaine could significantly reduce plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia and free from background mandatory folic acid fortification. METHODS: One hundred apparently healthy adults aged 18-65 years with hyperhomocysteinemia were recruited in South China from July 2019 to June 2021. They were randomly assigned to either the supplement group (daily supplementation: 400 µg folic acid, 8 mg vitamin B6, 6.4 µg vitamin B12 and 1 g betaine) or the placebo group for 12 weeks. Fasting venous blood was collected at baseline, week 4 and week 12 to determine the concentrations of homocysteine, folate, vitamin B12 and betaine. Generalized estimation equations were used for statistical analysis. RESULTS: Statistically significant increments in blood concentrations of folate, vitamin B12 and betaine after the intervention in the supplement group indicated good participant compliance. At baseline, there were no significant differences in plasma homocysteine concentration between the two groups (P = 0.265). After 12-week supplementation, compared with the placebo group, there was a significant reduction in plasma homocysteine concentrations in the supplement group (mean group difference - 3.87; covariate-adjusted P = 0.012; reduction rate 10.1%; covariate-adjusted P < 0.001). In the supplement group, the decreased concentration of plasma homocysteine was associated with increments of blood concentrations of both folate (ß = -1.680, P = 0.004) and betaine (ß = -1.421, P = 0.020) after 12 weeks of supplementation. CONCLUSIONS: Daily supplementation with low-dose B vitamins plus betaine for 12 weeks effectively decreased plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov as NCT03720249 on October 25, 2018. Website: https://clinicaltrials.gov/ct2/show/NCT03720249 .

Fermented noni (Morinda citrifolia L.) fruit juice improved oxidative stress and insulin resistance under the synergistic effect of Nrf2/ARE pathway and gut flora in db/db mice and HepG2 cells.

Oxidative stress interferes with blood glucose homeostasis, leading to insulin resistance (IR) and hyperglycemia, which eventually induce type 2 diabetes (T2DM). Fermented noni (Morinda citrifolia L.) fruit juice (FNJ) is a traditional folk medicine in Polynesia as well as a functional food supplement with a variety of health benefits. In this study, the efficacy and mechanism of FNJ in improving oxidative stress and IR were investigated under the synergistic effect of Nrf2/ARE pathway and gut flora in vivo and in vitro. In vitro, insulin resistant HepG2 cells were established with 50 mM high glucose, and 25 µM rosiglitazone (ROSI) was used as a positive control. In vivo, male C57BLKS mice in the CON group were fed a normal diet and C57BLKS/J-db/db (db/db) mice were treated with 10 mg kg-1 d-1 ROSI and 6.5 and 13 mL kg-1 d-1 FNJ for 8 weeks, respectively. The results showed that 3-5% FNJ markedly improved IR by increasing glucose uptake and consumption and ameliorated oxidative stress via up-regulating the expression of related antioxidant enzymes such as SOD and GPx and attenuating ROS and MDA in IR-HepG2 cells. In vivo, db/db mice exhibited hyperglycemia, hyperinsulinemia, and oxidative stress, whereas FNJ significantly inverted those conditions. Moreover, FNJ supplementation notably increased the gut microbiota diversity of T2DM mice and remodeled the gut microbial composition to suppress microbial disorder. Specifically, FNJ increased the ratio of F/B and lowered the Proteobacteria abundance at the phylum level. The db/db mice were enriched in Enterobacteriaceae, Klebsiella, and Klebsiella-pneumonia, while FNJ feeding significantly up-regulated Rikenellaceae. In addition, western blotting and qPCR experiments showed that FNJ promoted the expression of Nrf2, HO-1, IRS1, PI3K, AKT, and GLUT4 and reduced the JNK level both in vivo and vitro. These results confirmed that FNJ had a protective effect on oxidative stress and IR by activating Nrf2/ARE signaling pathway and regulating gut flora in db/db mice and IR-HepG2 cells.

Polyphenols in Highland Barley Tea Inhibit the Production of Advanced Glycosylation End-Products and Alleviate the Skeletal Muscle Damage.

SCOPE: Highland barley tea is a kind of caffeine-free cereal tea. Previous studies have shown that it is rich in polyphenol flavonoids. Here, the effect of Highland barley tea polyphenols (HBP) on the production of advanced glycosylation end-products and alleviate the skeletal muscle damage is systematically investigated. METHODS AND RESULTS: HBP effectively inhibits the formation of AGEs in vitro, and 12 phenolic compounds are identified. In addition, d-galactose is used to construct a mouse senescence model and intervenes with different doses of HBP. It is found that high doses of HBP effectively inhibit AGEs in serum and flounder muscle species and increased muscle mass in flounder muscle; also, high doses of HBP increase the expression of the mitochondrial functional protein SIRT3 and decrease the expression of myasthenia-related proteins. Furthermore, cellular experiments show that AGEs can significantly increase oxidative stress in skeletal muscle. CONCLUSION: These data indicate that the relationship between the biological activity and HBP properties is relevant since Highland barley can be a potential functional food to prevent AGEs-mediated skeletal muscle damage.

Microcomb-driven silicon photonic systems.

Microcombs have sparked a surge of applications over the past decade, ranging from optical communications to metrology1-4. Despite their diverse deployment, most microcomb-based systems rely on a large amount of bulky elements and equipment to fulfil their desired functions, which is complicated, expensive and power consuming. By contrast, foundry-based silicon photonics (SiPh) has had remarkable success in providing versatile functionality in a scalable and low-cost manner5-7, but its available chip-based light sources lack the capacity for parallelization, which limits the scope of SiPh applications. Here we combine these two technologies by using a power-efficient and operationally simple aluminium-gallium-arsenide-on-insulator microcomb source to drive complementary metal-oxide-semiconductor SiPh engines. We present two important chip-scale photonic systems for optical data transmission and microwave photonics, respectively. A microcomb-based integrated photonic data link is demonstrated, based on a pulse-amplitude four-level modulation scheme with a two-terabit-per-second aggregate rate, and a highly reconfigurable microwave photonic filter with a high level of integration is constructed using a time-stretch approach. Such synergy of a microcomb and SiPh integrated components is an essential step towards the next generation of fully integrated photonic systems.

A diarylheptanoid compound from Alpinia officinarum Hance ameliorates high glucose-induced insulin resistance by regulating PI3K/AKT-Nrf2-GSK3ß signaling pathways in HepG2 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Alpinia officinarum Hance, a perennial natural medicine-food herb, has been traditionally used to treat colds, stomachache, and diabetes for thousands of years. 1,7-Diphenyl-4E-en-3-heptanone (DPH5), a diarylheptanoid isolated from the rhizome of A. officinarum has been reported to be safe and to have antioxidant and hypoglycemic effects, suggesting its potential in the treatment of insulin resistance (IR). AIM OF THE STUDY: Aim of to investigate the protective effect of DPH5 on IR and elucidate its underlying mechanism of action. MATERIALS AND METHODS: HepG2 cells were used as the research objects. Glucose uptake and reactive oxygen species (ROS) levels in high glucose-induced insulin-resistant HepG2 cells were assessed using flow cytometry. Glucose consumption and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed using the corresponding assay kits. The expression of mRNA and proteins related to insulin signaling, glucose metabolism, and antioxidant factor, including insulin receptor substrate-1 (IRS1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), translocation of glucose transporter-4, glycogen synthase kinase-3ß (GSK3ß), glucokinase (GCK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), nuclear factor-erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NADPH quinoneoxidoreductase (NQO1), and glutathione peroxidase (GSH-Px) was determined using real-time quantitative polymerase chain reaction and western blotting. Furthermore, molecular docking was performed to determine the spatial mechanism of DPH5 on the key targets PI3K, AKT, Nrf2, and GSK3ß. RESULTS: DPH5 could improve IR that manifested as increased glucose uptake and glucose consumption in insulin-resistant HepG2 cells. Moreover, DPH5 could enhance antioxidant capacity by activating Nrf2/HO-1 elements, including increasing Nrf2, HO-1, SOD, NQO1, and GSH-Px expression and reducing MDA, ROS, and JNK levels, thereby improving oxidative stress and ultimately alleviating IR. Additionally, DPH5 could promote the expression of IRS1, PI3K, AKT, GSK3ß, GCK, and PK, and downregulate the expression of PEPCK and G6pase, thereby accelerating glucose utilization and enhancing insulin sensitivity. The mechanism underlying the effect of DPH5 in alleviating IR was related to the PI3K/AKT- and Nrf2/HO-1-mediated regulation of the GSK3ß signaling pathway, and the results were further confirmed using the specific inhibitors LY294002 and ML385. Results from molecular docking indicated that there were different regulatory sites and interacting forces between DPH5 and PI3K, AKT, Nrf2, and GSK3ß; however, the binding force was relatively strong. CONCLUSIONS: DPH5 improved oxidative stress and glucose metabolism via modulating the PI3K/AKT-Nrf2-GSK3ß pathway, thereby ameliorating IR. Overall, our findings suggest the potential of DPH5 as a natural medicine to treat type-2 diabetes mellitus.

Mechanism of Yangxinshi Intervention on Cardiac Fibrosis in Diabetic Cardiomyopathy Based on Network Pharmacology.

BACKGROUND: Cardiac fibrosis (CF) is major myocardial change in diabetic cardiomyopathy (DCM). Yangxinshi as a Chinese medicine formula is used to treat cardiovascular diseases. However, the exact effective mechanism of Yangxinshi on CF is still uncertain. Hence, based on the pharmacological network, predicting the active components, potential targets and pathways of Yangxinshi on diabetic fibrosis require to be further studied. MATERIALS AND METHODS: By using Cytoscape 3.6.0 Bisogenet plug-in, the active components of Yangxinshi were obtained and screened through TCMSP, and the PPI network of DCM-CF was constructed and then screened by CytoNCA plug-in. GO analysis and KEGG pathway enrichment analysis were carried out by Cluego plug-in. Combined with the results of network pharmacological analysis, cells in vitro were performed to verify the CF stimulated with high glucose or intervence with Yangxinshi, and the expressions of Cbl-b, p-smad2, and α-SMA were detected. RESULTS: Yangxinshi might play a key role in reversing cardiac fibrosis in individuals with DCM by regulating the signal pathway of CBL and promoted the expression of Cbl-b and inhibited the expression of p-smad2 and α-SMA, verifying some predictive work via network pharmacology. CONCLUSION: Based on network pharmacology, this study demonstrates that the beneficial effect of Yangxinshi on CF is related to the Cbl-b/smad2 pathway, providing an idea for the therapeutic effect of Yangxinshi on cardiac fibrosis in DCM.

Efficacy of Bilberry and Grape Seed Extract Supplement Interventions to Improve Glucose and Cholesterol Metabolism and Blood Pressure in Different Populations-A Systematic Review of the Literature.

Intervention with fruit extracts may lower glucose and lipid levels, as well as blood pressure. We reviewed the efficacy of bilberry and grape seed extracts to affect these outcomes across populations with varying health status, age and ethnicity, across intervention doses and durations, in 24 intervention studies with bilberry and blackcurrant (n = 4) and grape seed extract (n = 20). Bilberry and blackcurrant extract lowered average levels of glycated hemoglobin (HbA1c), at least in Chinese subjects, especially in those who were older, who were diagnosed with Type 2 Diabetes Mellitus (T2DM) and who were participating in longer-term studies. We also found good evidence that across studies and in subjects with hypercholesterolemia, T2DM or metabolic syndrome, intervention with bilberry and blackcurrant extract, and to some extent grape seed extract, significantly lowered total and low density lipoprotein (LDL) cholesterol levels after four weeks. Intervention with grape seed extract may reduce systolic and diastolic blood pressure in subjects with hypertension or metabolic syndrome. Differential responsiveness in cholesterol and blood pressure outcomes between stratified populations could not be explained by age, dose or study duration. In conclusion, bilberry and blackcurrant extract appears effective in lowering HbA1c and total and LDL cholesterol, whereas grape seed extract may lower total and LDL cholesterol, and blood pressure, in specific population groups.

Association of serum 25-Hydroxyvitamin D with Vitamin D intervention and outdoor activity among children in North China: an observational study.

BACKGROUND: Living at high latitudes is one of the risk factors for vitamin D deficiency in children. However, evidence on vitamin D improvement for this pediatric population to date is limited. This study aims at evaluating the association of different vitamin D intervention methods and outdoor activity on the vitamin D status of children in North China. METHODS: In this observational study, a total of 55,925 children aged 1 month to 18 years old were recruited from pediatric outpatient departments from July 2016 to June 2017. Data on demographics, anthropometric measurements, vitamin D intervention (either prescribed by physicians or given by parents) and outdoor activity were recorded. The serum levels of 25-hydroxycholecalciferol (25(OH)D) were determined by high performance liquid chromatography tandem-mass spectrometry. Logistic regression analysis was performed to assess the association of vitamin D intervention or outdoor activity with blood vitamin D status, adjusted for age, gender, BMI for age, and seasons. RESULTS: The overall rate of hypovitaminosis D was 65.60%. Of the children's outdoor activity, 35.63, 31.95, and 32.42% were below 30 min/d, 30-60 min/d and over 60 min/d, respectively. Furthermore, the proportion of therapeutic intervention, supplementation intervention and no vitamin D intervention among the children was 16.48, 32.87, and 50.65%, respectively. After adjusted for confounding factors, vitamin D intervention was associated with a lower risk of hypovitaminosis D, with OR (95% CI) of 0.191 (0.180, 0.202) in children with therapeutic doses and 0.423 (0.404, 0.443) in those with supplementation doses, compared with children without vitamin D intervention. In addition, longer outdoor time was associated with a lower risk of hypovitaminosis D [0.479 (0.456, 0.504) for 60 min/d, 0.737 (0.701, 0.776) for 30-60 min/d], independent of vitamin D intervention. CONCLUSIONS: High prevalence of vitamin D deficiency was found in children living at high latitudes. Vitamin D intervention and outdoor activity are all negatively associated with children's vitamin D deficiency. Routine vitamin D intervention combined with increased outdoor time might be an effective approach to prevent hypovitaminosis D among children, especially those at school, living at high latitudes.

The Wound Healing Effect of Callicarpa nudiflora in Scalded Rats.

Callicarpa nudiflora has been widely used in Li nationality medicine and treated burns and scalds in China. Our objective was to preliminarily elucidate healing effect and action mechanism of Callicarpa nudiflora water extract (CNE) on the scald wounds using an experimental rat mode. The second-degree scald wounds were induced by hot water on dorsal surface of Sprague-Dawley (SD) rats, and then they were randomly divided into 5 groups as follows: control (CON), Vaseline, Silver sulfadiazine (SSD), and Vaseline supplemented with 10% and 20% CNE groups. These ointments were employed locally once daily for 21 days. The macroscopic analysis showed CNE significantly accelerated the wound healing process and lowered the wound areas on days 15, 18, and 21 especially in 20% CNE group compared to CON group. Histopathological evaluation showed the mildly hypertrophic epidermis and the intact dermis in the 20% CNE-treated group were obviously distinguished from CON group on day 21. The CNE-treated groups had no obvious effect for TNF-α and IL-10 expressions on the second day and 14th day, while TGF-ß1 expression level was decreased on the 21th day and VEGF level was increased on the 7th day in the 20% CNE group. Furthermore, the expression level of Samd3 was strongly inhibited in 20% CNE group. These findings suggested that the CNE can enhance the wound healing and skin repair in deep second-degree scald rats and thus support its traditional use.

A combination of Pueraria lobata and Silybum marianum protects against alcoholic liver disease in mice.

BACKGROUND: Excess alcohol exposure leads to alcoholic liver disease (ALD). Pueraria lobata (PUE) and Silybum marianum (SIL) are two well-known hepatoprotective herbal remedies with various activities. The possible effect of combination of PUE and SIL on ALD has not been elucidated yet. PURPOSE: We aimed to demonstrate that the combination of PUE and SIL prevents against alcoholic liver injury in mice using a model of chronic-plus-single-binge ethanol feeding. STUDY DESIGN: Male C57BL/6 mice were randomly divided into five groups (n = 8-10), namely the control group (CON), ethanol-induced liver injury group (ETH), 150 mg/kg PUE treated group (PUE), 60 mg/kg SIL treated group (SIL), 210 mg/kg PUE+SIL treatment group (PUE+SIL). Except control group, all animals were fed a modified Lieber-DeCarli ethanol liquid diet for 10 days. While, control group received Lieber-DeCarli control diet containing isocaloric maltose dextrin substituted for ethanol. On day 11, the mice orally received a single dose of 31.5% (v/v) ethanol (5 g/kg BW) or an isocaloric maltose solution. RESULTS: Ethanol exposure caused liver injury, as demonstrated by remarkably increased plasma parameters, histopathological changes, the increased lipid accumulation, oxidative stress and inflammation in liver. These alterations were ameliorated by the treatments of PUE, SIL and PUE+SIL. While, the PUE+SIL treatment showed the most effective protection, which was associated with reducing alcohol-induced hepatic steatosis via upregulating LKB1/AMPK/ACC signaling, and inhibiting hepatic inflammation via LPS-triggered TLR4-mediated NF-κB signaling pathway. Our results also indicated that the hepatoprotective effects of SIL+PUE might mainly attribute to the protection of SIL and PUE alone in alcohol-induced hepatic steatosis and hepatic inflammation, respectively. CONCLUSION: These findings also suggest that the combination of PUE and SIL has a potential to be developed as a functional food for the management of ALD.

Measurement of pharmacokinetics and tissue distribution of three bioactive constituents from Zanthoxylum armatum DC in rat plasma and tissues through UFLC-MS/MS.

The compounds of N-Methylanhydrotetrahydroberberrubine A, dictamnine and eudesmin were the primary bioactive components in the roots of Zanthoxylum armatum DC (Z. armatum). To clarify the pharmacokinetics and distribution of these three compounds, an ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was employed to determine the contents of these three compounds in rat plasma and seven tissues. The separation was achieved on a Kinetex XB-C18 100A column (2.1 × 50 mm, 2.6 µm, Phenomenex). The optimized mobile phase system was set with 0.1‰ formic acid aqueous solution (A) and acetonitrile (containing 0.1‰ formic acid) (B) with a programmed elution of 0.00 to 0.50 min, 2% B; 0.51-4.00 min, 30%-60% B; and 4.01-5.00 min, 2% B. All analytes were measured with optimized multiple reaction monitoring (MRM) in the positive ion ESI mode. Berberine hydrochloride was selected as the internal standard (IS). The MS/MS transitions of N-Methylanhydrotetrahydroberberrubine A, dictamnine, eudesmin and IS were 339.9135.1, 200.1 → 129.1, 387.4 → 369.0 and 337.1 → 321.1, respectively. The lower limits quantification (LLOQ) of the three analytes was 0.5-20 ng/ml. The linear ranges were 0.5-400 ng/ml for N-Methylanhydrotetrahydroberberrubine A and dictamnine and 20-4000 ng/ml for eudesmin. The present analysis showed that the two alkaloids were quickly absorbed, with Tmax in 0.167-0.292 h, and eudesmin was absorbed in 2.5 h. Moreover, all compounds were found at high concentrations in the gastrointestinal track. These results are helpful for further investigation of the clinical application of Z. armatum.

Effects and possible mechanisms of Alpinia officinarum ethanol extract on indomethacin-induced gastric injury in rats.

CONTEXT: Alpinia officinarum Hance (Zingiberoside) has a long history in treating gastrointestinal diseases, but its mechanisms of action are not yet known. OBJECTIVE: To investigate the effects and underlying mechanisms of the ethanol extract of A. officinarum rhizomes in an indomethacin-induced gastric injury rat model. MATERIAL AND METHODS: Indomethacin (0.3 g/kg) was orally administered to Sprague-Dawley rats to induce gastric damage; after 7 h, the rats were treated with 0.03, 0.09, or 0.18 g/kg of the plant extract, galangin (0.2 g/kg), or bismuth potassium citrate (0.08 g/kg), once a day for 6 days. Rats in the control group received an equivalent volume of vehicle solution for 6 days. Gastric damage was evaluated by gross ulcer and histological indexes. Cyclooxygenase and non-cyclooxygenase pathway proteins were quantified by western blotting and ELISA. RESULTS: Alpinia officinarum extract ameliorated gastric injury in a dose-dependent manner, and 0.18 g/kg dose exhibited the best performance by reducing the gross ulcer (from 20.23 ± 1.38 to 1.66 ± 0.37) and histological (from 4.67 ± 1.03 to 0.33 ± 0.51) indexes, decreasing serum TNF-α level (14.17%), increasing serum VEGF level (1.58 times), increasing cyclooxygenase-1 level (1.25 times, p < 0.001) in the gastric mucosa, and reversing indomethacin-induced changes in the expression of non-cyclooxygenase pathway proteins (p < 0.05). Galangin was less effective as an antiulcer agent than the whole extract, indicating that other components also contributed to the protective effect. CONCLUSIONS: Alpinia officinarum extract and galangin exert antiulcer effects through cyclooxygenase and non-cyclooxygenase pathways validating use of galangin as a treatment for gastric damage.

A new diarylheptanoid from Alpinia officinarum promotes the differentiation of 3T3-L1 preadipocytes.

A new diarylheptanoid, namely trans-(4R,5S)-epoxy-1,7-diphenyl-3-heptanone (1), and a new natural product, 7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl-hepta-4E,6E-dien-3-one (2), were obtained from the aqueous extract of Alpinia officinarum Hance, together with three other diarylheptanoids, 5-hydroxy-1,7-diphenyl-3-heptanone (3), 1,7-diphenyl-4E-en-3-heptanone (4) and 5-methoxy-1,7-diphenyl-3-heptanone (5). The structures were characterised mainly by analysing their physical data including IR, NMR and HRMS. This study highlights that the 4,5-epoxy moiety in 1 is rarely seen in diarylheptanoids. In addition, the five isolates were tested for their differentiation activity of 3T3-L1 preadipocytes. The results showed that these compounds could dose-dependently promote adipocyte differentiation without cytotoxicity (IC50 > 100 µM).

Evaluation of the chemical composition, antioxidant and anti-inflammatory activities of distillate and residue fractions of sweet basil essential oil.

In this study, the chemical composition and antioxidant and anti-inflammatory activities of sweet basil (Ocimum basilicum L. Lamiaceae family) were evaluated. Sweet basil is a food-related plant that is widely used in traditional Chinese medicine. Sweet basil crude oil was processed via molecular distillation and further characterized using gas chromatography-mass spectrometry (GC-MS) to screen for new compounds. The GC-MS analysis identified thirty-eight compounds. The major constituents of the residue fraction were estragole (17.06%), methyl eugenol (11.35%) and linoleic acid (11.40%), while the distillate fraction primarily contained methyl eugenol (16.96%), α-cadinol (16.24%) and α-bergamotene (11.92%). The antioxidant (DPPH and ABTS assays) and anti-inflammatory (in Raw264.7 cells) activities were evaluated. The residue fraction markedly scavenged the DPPH (IC50 = 1.092 ± 0.066 mg/mL) and ABTS (IC50 = 0.707 ± 0.042 mg/mL) radicals. Meanwhile, the distillate fraction distinctly suppressed the production of cytokines (TNF-α, IL-ß, IL-6) and their gene expression in LPS-induced Raw264.7 cells and suppressed NO and iNOS in an in vitro model when compared with the crude oil. In conclusion, the fractions obtained from sweet basil crude oil showed different antioxidant and anti-inflammatory properties, and they could be used as an effective source of natural antioxidant and anti-inflammatory agents after molecular distillation. Thus, the properties of essential oils in natural herbal medicines may be maximized to provide a valuable therapeutic strategy for treating various disorders caused by extreme oxidative stress.