Gypenoside XIII regulates lipid metabolism in HepG2 hepatocytes and ameliorates nonalcoholic steatohepatitis in mice.

Gypenoside XIII is isolated from Gynostemma pentaphyllum (Thunb.) Makino. In mice, G. pentaphyllum extract and gypenoside LXXV have been shown to improve non-alcoholic steatohepatitis (NASH). This study investigated whether gypenoside XIII can regulate lipid accumulation in fatty liver cells or attenuate NASH in mice. We used HepG2 hepatocytes to establish a fatty liver cell model using 0.5 mM oleic acid. Fatty liver cells were treated with different concentrations of gypenoside XIII to evaluate the molecular mechanisms of lipid metabolism. In addition, a methionine/choline-deficient diet induced NASH in C57BL/6 mice, which were given 10 mg/kg gypenoside XIII by intraperitoneal injection. In fatty liver cells, gypenoside XIII effectively suppressed lipid accumulation and lipid peroxidation. Furthermore, gypenoside XIII significantly increased SIRT1 and AMPK phosphorylation to decrease acetyl-CoA carboxylase phosphorylation, reducing fatty acid synthesis activity. Gypenoside XIII also decreased lipogenesis by suppressing sterol regulatory element-binding protein 1c and fatty acid synthase production. Gypenoside XIII also increased lipolysis and fatty acid ß-oxidation by promoting adipose triglyceride lipase and carnitine palmitoyltransferase 1, respectively. In an animal model of NASH, gypenoside XIII effectively decreased the lipid vacuole size and number and reduced liver fibrosis and inflammation. These findings suggest that gypenoside XIII can regulate lipid metabolism in fatty liver cells and improve liver fibrosis in NASH mice. Therefore, gypenoside XIII has potential as a novel agent for the treatment of NASH.

The association between human milk fatty acid composition in mothers with an elevated body mass index and infant growth changes.

BACKGROUND & AIMS: Few studies have investigated alternations in human milk polyunsaturated fatty acid (PUFA) composition in the context of maternal obesity and its effects on infant growth trajectories. This study explored whether maternal weight status and breastfeeding type influence human milk FA composition and infant anthropometry during the first six months of life. METHODS: Mother-infant dyads were enrolled from the Prediction of Allergies in Taiwanese Children birth cohort study. Data concerning maternal pre-pregnancy weight, infants' breastfeeding practices, and anthropometric data were obtained regularly. We identified and compared between the composition of 30 FAs in the colostrum and 2-month milk, respectively, in obese/overweight (OB/OW) and normal-weight (NW) mothers. Multiple linear regression analyses were performed to determine the association between PUFA composition at different lactation stages and infant anthropometric parameter changes and to identify the independent variables for body mass index (BMI) z-scores by six months of age. RESULTS: We included 338 mother-infant dyads (OB/OW mothers, 16.9 %). OB/OW mothers exhibited lower total n-3 PUFAs (P = 0.035), higher ratios of arachidonic acid (C20:4n-6)/eicosapentaenoic acid (C20:5n-3) + docosahexaenoic acid (C22:6n-3), and n-6/n-3 PUFA in colostrum (P = 0.037 and 0.011, respectively), and their offspring had higher body weight and BMI z-scores. Nevertheless, no PUFA composition or n-6/n-3 PUFA ratios in colostrum and 2-month milk were associated with anthropometric parameter changes by age 6 months. Infant birth weight z-scores were independently associated with BMI outcomes at age 6 months (adjusted ß = 0.16, 95 % confidence interval (0.05-0.35), P = 0.010) CONCLUSION: Neither n-3 nor n-6 PUFA profiles nor n-6/n-3 PUFA ratios at different lactation stages were found to be associated with anthropometric changes by age 6 months, suggesting that human milk PUFA composition may not be an important determinant of early infant growth trajectories.

Gypenoside A from Gynostemma pentaphyllum Attenuates Airway Inflammation and Th2 Cell Activities in a Murine Asthma Model.

Our previous study found that oral administration of Gynostemma pentaphyllum extract can attenuate airway hyperresponsiveness (AHR) and reduce eosinophil infiltration in the lungs of asthmatic mice. Gypenoside A is isolated from G. pentaphyllum. In this study, we investigated whether gypenoside A can effectively reduce asthma in mice. Asthma was induced in BALB/c mice by ovalbumin injection. Asthmatic mice were treated with gypenoside A via intraperitoneal injection to assess airway inflammation, AHR, and immunomodulatory effects. In vitro, gypenoside A reduced inflammatory and oxidative responses in inflammatory tracheal epithelial cells. Experimental results showed that gypenoside A treatment can suppress eosinophil infiltration in the lungs, reduce tracheal goblet cell hyperplasia, and attenuate AHR. Gypenoside A significantly reduced Th2 cytokine expression and also inhibited the expression of inflammatory genes and proteins in the lung and bronchoalveolar lavage fluid. In addition, gypenoside A also significantly inhibited the secretion of inflammatory cytokines and chemokines and reduced oxidative expression in inflammatory tracheal epithelial cells. The experimental results suggested that gypenoside A is a natural compound that can effectively reduce airway inflammation and AHR in asthma, mainly by reducing Th2 cell activation.

Trajectory of vitamin D, micronutrient status and childhood growth in exclusively breastfed children.

This study aimed to compare the trajectory of serum 25(OH)D, micronutrient levels, and anthropometric measurements between exclusively breastfed and mixed-fed children. This is a prospective cohort study. Anthropometric measurements of the children were obtained during scheduled clinical visits. Tests for 25(OHD), ferritin, zinc and complete blood count were performed yearly until 3 years of age. Clinical records and questionnaires on dietary habits were obtained. The results showed that despite official recommendations on vitamin D/iron supplements for breastfed children, less than 10% of our exclusively breastfed children received regular supplements. Thus, after 1 year, the odds for having iron deficiency anemia and vitamin D insufficiency were 9 [95% CI, 4-19] and 6 [95% CI, 2-16], respectively. Longitudinal follow-up showed the prevalence of iron deficiency to decrease from 34% at 1 year to 2% at age 3 years. However, the prevalence of vitamin D insufficiency remained persistently high throughout the first three years of life (60% at 1 to 44% at 3 years). Very few children had zinc deficiency. Anthropometric measurements showed exclusively breastfed children to have lower mean z-scores for body weight and height when compared to mixed-fed children after 12 months. In conclusion, children who were exclusively breastfed for longer than 4 months without proper supplement were more likely to have transient iron deficiency anemia and persistent vitamin D insufficiency. Their growth became relatively slower after infancy. Whether this was associated with underlying inadequate serum vitamin D and iron level remains an important issue to be explored.

Protective Effects of Licochalcone A Improve Airway Hyper-Responsiveness and Oxidative Stress in a Mouse Model of Asthma.

Licochalcone A was isolated from Glycyrrhiza uralensis and previously reported to have antitumor and anti-inflammatory effects. Licochalcone A has also been found to inhibit the levels of Th2-associated cytokines in the bronchoalveolar lavage fluid (BALF) of asthmatic mice. However, the molecular mechanism underlying airway inflammation and how licochalcone A regulates oxidative stress in asthmatic mice are elusive. In this study, we investigated whether licochalcone A could attenuate inflammatory and oxidative responses in tracheal epithelial cells, and whether it could ameliorate oxidative stress and airway inflammation in asthmatic mice. Inflammatory human tracheal epithelial (BEAS-2B) cells were treated with licochalcone A to evaluate oxidative responses and inflammatory cytokine levels. In addition, BALB/c mice were sensitized with ovalbumin (OVA) and injected intraperitoneally with licochalcone A (5 or 10 mg/kg). Licochalcone A significantly inhibited reactive oxygen species, eotaxin, and proinflammatory cytokines in BEAS-2B cells. Licochalcone A also decreased intercellular adhesion molecule 1 levels in inflammatory BEAS-2B cells, blocking monocyte cell adherence. We also found that licochalcone A significantly decreased oxidative responses, reduced malondialdehyde levels, and increased glutathione levels in the lungs of OVA-sensitized mice. Furthermore, licochalcone A decreased airway hyper-responsiveness, eosinophil infiltration, and Th2 cytokine production in the BALF. These findings suggest that licochalcone A alleviates oxidative stress, inflammation, and pathological changes by inhibiting Th2-associated cytokines in asthmatic mice and human tracheal epithelial cells. Thus, licochalcone A demonstrated therapeutic potential for improving asthma.

Association of maternal allergy with human milk soluble CD14 and fatty acids, and early childhood atopic dermatitis.

BACKGROUND: This study aimed to investigate whether maternal allergy is associated with soluble CD14 (sCD14) and fatty acid composition in different stages of lactation and the onset of atopic dermatitis (AD) in early childhood. METHODS: In total, 443 mother-child groups (445 children) were enrolled in the Prediction of Allergies in Taiwanese Children birth cohort study. Colostrum and mature milk at 2 months postpartum (2-month HM) were collected from lactating mothers. Information regarding parental allergy histories and physician-diagnosed atopic diseases was obtained using age-specific questionnaires (0-2 years). We compared sCD14 levels and the composition of 30 fatty acids in the colostrum and 2-month HM, respectively, between allergic and non-allergic mothers and between children with and without AD by the age of 2 years. RESULTS: In total, 185 (41.8%) mothers presented with allergies, and 154 (34.6%) children had physician-diagnosed AD by the age of 2 years. Both in the colostrum and 2-month HM of 289 lactating mothers, sCD14 levels were significantly lower in allergic mothers whose children presented with AD compared with children who did not (P = 0.015 and 0.044, respectively). Among the children with AD who were born to non-allergic mothers, sCD14 levels were lower. However, the result was not statistically significant (P = 0.376 and 0.264, respectively). Our data revealed the lack of associations between fatty acid composition and AD (P > 0.05). CONCLUSION: Decreased sCD14 levels in the colostrum and 2-month HM were associated with AD at 2 years of age, particularly among children born to mothers with allergies.

Water extract of Helminthostachys zeylanica attenuates LPS-induced acute lung injury in mice by modulating NF-κB and MAPK pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Previous studies showed that Helminthostachys zeylanica (L.) Hook. could reduce inflammatory responses in macrophage and brain astrocytes. AIM OF THE STUDY: In the present study, we evaluated whether an ethyl acetate extract (HZE) or a water extract (HZW) of H. zeylanica could reduce inflammatory responses in lung epithelial cells and ameliorate lipopolysaccharide (LPS)-induced acute lung injury in mice. METHODS: Human lung epithelial A549 cells were pre-treated with HZE or HZW (1-10µg/mL), then stimulated with LPS. BALB/c mice received oral HZW for 7 consecutive days, then an intratracheal instillation of LPS to induce lung injury. RESULTS: HZW reduced chemokine and proinflammatory cytokine production in LPS-activated A549 cells. HZW also suppressed ICAM-1 expression and reduced the adherence of acute monocytic leukemia cells to inflammatory A549 cells. HZE had less efficacy than HZW in suppressing inflammatory responses in A549 cells. In vivo, HZW significantly suppressed neutrophil infiltration and reduced the TNF-α and IL-6 levels in bronchoalveolar lavage fluid and serum from LPS-treated mice. HZW also modulated superoxide dismutase activity, glutathione, and myeloperoxidase activity in lung tissues from LPS-treated mice. HZW decreased the phosphorylation of mitogen-activated protein kinase and nuclear factor kappa B, and promoted heme oxygenase-1 expression in inflamed lung tissue from LPS-treated mice. CONCLUSION: Our findings suggested that HZW reduced lung injury in mice by reducing oxidative stress and inflammatory responses. HZW also reduced inflammatory responses in human lung epithelial cells.

Role of Maternal Allergy on Immune Markers in Colostrum and Secretory Immunoglobulin A in Stools of Breastfed Infants.

BACKGROUND: Although protection against infectious diseases has been observed among breastfed infants as compared to formula-fed infants, possible benefits of breastfeeding by allergic mothers for allergy prevention remain controversial. OBJECTIVES: The aims of this study were to determine whether maternal allergy would influence immune markers (secretory immunoglobulin A [sIgA], interleukin-8 [IL-8], soluble CD14 [sCD14]) in colostrum and the associations between maternal allergy and fecal sIgA levels in breastfed infants. METHODS: Study subjects were enrolled from the Prediction of Allergies in Taiwanese Children (PATCH) birth cohort study. Colostrum samples were obtained from 98 lactating mothers. Stool samples were collected from 108 infants within 5 days after birth and at 2 and 4 months of age. We compared concentrations of sIgA, IL-8, and sCD14 in colostrum between mothers with and without a history of allergic disease and allergic sensitization. We also compared fecal sIgA levels between breastfed and formula-fed infants and between infants with allergic and nonallergic mothers. RESULTS: The sIgA concentrations were significantly higher in colostrum from allergic mothers than from nonallergic mothers (P = .01) and from allergic mothers who were immunoglobulin E (IgE) sensitized compared to nonallergic mothers who were not IgE sensitized (P = .023). Breastfed infants had significantly higher fecal sIgA levels as compared to formula-fed infants, regardless of whether their lactating mothers had an allergy (P < .05). CONCLUSION: We found that breastfeeding is associated with increased infants' fecal sIgA levels and may have potential protective effects to the infants during the first 4 months of life, regardless of whether their lactating mothers have allergies.

Superconductivity in the PbO-type structure alpha-FeSe.

The recent discovery of superconductivity with relatively high transition temperature (Tc) in the layered iron-based quaternary oxypnictides La[O(1-x)F(x)] FeAs by Kamihara et al. [Kamihara Y, Watanabe T, Hirano M, Hosono H (2008) Iron-based layered superconductor La[O1-xFx] FeAs (x = 0.05-0.12) with Tc = 26 K. J Am Chem Soc 130:3296-3297.] was a real surprise and has generated tremendous interest. Although superconductivity exists in alloy that contains the element Fe, LaOMPn (with M = Fe, Ni; and Pn = P and As) is the first system where Fe plays the key role to the occurrence of superconductivity. LaOMPn has a layered crystal structure with an Fe-based plane. It is quite natural to search whether there exists other Fe based planar compounds that exhibit superconductivity. Here, we report the observation of superconductivity with zero-resistance transition temperature at 8 K in the PbO-type alpha-FeSe compound. A key observation is that the clean superconducting phase exists only in those samples prepared with intentional Se deficiency. FeSe, compared with LaOFeAs, is less toxic and much easier to handle. What is truly striking is that this compound has the same, perhaps simpler, planar crystal sublattice as the layered oxypnictides. Therefore, this result provides an opportunity to better understand the underlying mechanism of superconductivity in this class of unconventional superconductors.