Correlation between dietary theobromine intake and low cognitive performance in older adults in the United States: A cross-sectional study based on the National Health and Nutrition Examination Survey.

BACKGROUND AND OBJECTIVES: Few studies have investigated the effects of dietary theobromine intake on the cognitive performance of older adults. Therefore, we investigated these effects in older adults in the United States. METHODS AND STUDY DESIGN: In this cross-sectional study, we used data (2011-2014) from the National Health and Nutrition Examination Survey. Intake of theobromine intake was obtained through two 24-h dietary recall interviews and was adjusted by energy. Cognitive performance was assessed using the animal fluency test, Consortium to Establish a Registry for Alzheimer's Disease Word Learning subtest (CERAD), and Digit Symbol Substitution Test (DSST). Logistic regression and restricted cubic spline models were constructed to evaluate the correlation between the dietary intake of theobromine from different sources and the likelihood of low cognitive performance. RESULTS: The fully adjusted model revealed that compared with the lowest quintile, the odds ratios (with 95% confidence intervals) of cognitive performance in the CERAD test were 0.42 (0.28-0.64), 0.34 (0.14-0.83), 0.25 (0.07-0.87), and 0.35 (0.13-0.95) for the highest quintile of total theobromine intake and that from chocolate, coffee, and cream, respectively. Dose-response relationship analysis indicated nonlinear correlations between the likelihood of low cognitive performance and die-tary theobromine (total intake and that from chocolate, coffee, and cream). An L-shaped relationship was ob-served between total theobromine intake and cognitive performance in the CERAD test. CONCLUSIONS: The dietary intakes of theobromine (total and that from chocolate, coffee, and cream) may protect older adults, particularly men, against low cognitive performance.

The extract from Hyssopus cuspidatus Boriss. Prevents bronchial airway remodeling by inhibiting mouse bronchial wall thickening and hASMC proliferation and migration.

ETHNOPHARMACOLOGICAL RELEVANCE: Bronchial asthma, a non-communicable chronic respiratory disease, affects people of all ages. An important pathological feature of bronchial asthma is airway remodeling. Hyssopus cuspidatus Boriss. has been used to treat bronchial asthma for over 100 years in Uygur medicine. The ethanol extract of Hyssopus cuspidatus Boriss.(JAX2) can improve airway inflammation in asthma. However, the anti-asthmatic airway-remodeling effect of JAX2 is unclear. AIM OF THE STUDY: The current study investigated the anti-airway remodeling effect of JAX2 and elucidated its mechanism of action. MATERIALS AND METHODS: The present study established an ovalbumin-induced mouse model of asthma and platelet-derived growth factor-BB-induced human airway smooth muscle cells (hASMCs) proliferation model, with dexamethasone (DEX) and feining tablets (FNP) designated as positive control drugs. Pathological changes in lung tissues were observed using hematoxylin and eosin staining. Interleukin (IL)-5, IL-10, IL-13, and IL-33 levels in the bronchoalveolar lavage fluid (BALF) and serum of mice were determined using enzyme-linked immunosorbent assay (ELISA). Changes in the expression and distribution of TGF-ß1, p-ERK1/2, Smad2/3, and p-Smad3 in lung tissues were determined using immunohistochemistry. Western blotting (WB) was used to determine the protein levels of p-ERK1/2 in lung tissues and cells. MTS assay was used to determine the effects of JAX2 on cell proliferation. IL-5, IL-10, IL-13, MMP-2, and MMP-9 levels in the cell supernatant were determined using ELISA. HASMCs migration was observed using the scratch and transwell methods. The effect of JAX2 on the hASMCs cycle was determined using flow cytometry. RESULTS: JAX2 significantly improved the pathological status of lung tissues in asthmatic mice. It could also significantly reduce IL-5, IL-13, and IL-33 levels in the BALF and serum of asthmatic mice in a dose-dependent manner and significantly increase IL-10 levels. TGF-ß1, p-ERK1/2, Smad2/3, and p-Smad3 expression in lung tissues were decreased in a dose-dependent manner. The protein level of p-ERK1/2 in lung tissues was also reduced. JAX2 could significantly inhibit the proliferation and migration of PDGF-BB-induced hASMCs. IL-5, IL-13, MMP-9, and MMP-2 levels decreased significantly, and IL-10 levels increased significantly in a dose-dependent manner in the cell supernatant. JAX2 could block hASMCs in the G0/G1 phase, thereby inhibiting cell proliferation. p-ERK1/2 protein levels were found to decrease in a dose-dependent manner. CONCLUSIONS: JAX2 significantly inhibits airway remodeling in asthma. Its mechanism of action may be inhibiting the proliferation and migration of hASMCs, releasing inflammatory factors and metalloproteinases, activating the ERK1/2 signal pathway, and promoting the secretion of anti-inflammatory factors.

Association between mixed dietary B vitamin intake and insulin resistance in US middle-aged and older adults without diabetes: The Bayesian kernel machine regression approach.

BACKGROUND AND OBJECTIVES: In daily life, the intake of dietary nutrients is mixed. However, evidence for the association between mixed dietary B vitamin intake and insulin resistance is limited. In this study, we estimated the joint effect of intake of various dietary B vitamins on insulin resistance. METHODS AND STUDY DESIGN: This cross-sectional study used data from the National Health and Nutrition Examination Survey 2011-2018. We included 1,628 middle-aged and 1,058 older adults without diabetes. Multivariable logistic regression and Bayesian kernel machine regression models were constructed. RESULTS: In the multivariable logistic regression, when all B vitamins were included in the model, the ORs (95% CIs) of insulin resistance were 3.06 (1.00-9.37) and 0.42 (0.19- 0.93) for the highest quartile of vitamin B-1 and B-12 intake in the middle-aged group when the lowest quartile was the reference. In the older group, no significant association was observed. In the Bayesian kernel machine regression analysis, a negative trend was noted between mixed B vitamin intake and insulin resistance in both examined groups. The univariate exposure-response function indicated that vitamin B-12 intake was negatively associated with insulin resistance in the middle-aged group, and that vitamin B-6 and dietary folate equivalent intakes were negatively associated with insulin resistance in older group. The bivariate exposure-response function indicated a potential interaction effect between dietary intake of vitamin B-12 and those of vitamin B-1, B-2, niacin, and dietary folate equivalent on insulin resistance in older people. CONCLUSIONS: Our results suggest that mixed dietary B vitamin intake tends to decrease the OR of insulin resistance both in middle-aged and older people.

Threshold effects and interactive effects of total zinc and selenium intake on cognitive function in older adults.

BACKGROUND & AIMS: The aim of this study was to assess threshold effects and interactive effects of total zinc and selenium intake on cognitive function in older adults. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Zinc and selenium intake were obtained through two 24-h dietary recalls. Cognitive performance was evaluated by the Digit Symbol Substitution Test (DSST). Smooth curve fitting, two-piecewise multivariable linear regression models, binary logistic regression model, multiplicative interactions model, and additive interactions model were used to evaluate the association between zinc, selenium intake and their interactive effect on cognitive function. RESULTS: A total of 2450 participants aged 60 years or older were included. Zinc and selenium intake was non-linearly associated with cognitive function. The inflection point for zinc intake was 8.94 mg/d in males and 7.58 mg/d in females. When zinc intake was below inflection point, zinc intake was positively associated with the DSST test in males (ß = 1.02, 95% CI, 0.44 to 1.60) and females (ß = 0.94, 95% CI, 0.26 to 1.62). When zinc intake above inflection point, there is no association between zinc intake and the DSST test in both sexs. The inflection point for selenium intake was 186.33 µg/d in males and 68.40 µg/d in females. Among males, the ß (95% CIs) was 0.03 (0.01,0.06) to the left side of the inflection point and -0.06 (-0.10, -0.02) to the right of the inflection point. Among females, the ß (95% CIs) was 0.13 (0.04,0.22) to the left side of the inflection point and 0.01 (-0.01,0.04) to the right of the inflection point. Besides, zinc and selenium have significant interaction on DSST test only in females (P = 0.028, RERI = 0.418). CONCLUSIONS: The present study demonstrated that zinc and selenium intake was non-linearly associated with cognitive function in different sex. There was an interactive effect between zinc and selenium intake on improving cognitive function, especially in females.

1H NMR-based metabolomics approach to investigating the renal protective effects of Genipin in diabetic rats.

Diabetic nephropathy is one of the various complications of diabetes mellitus, affecting patients for lifetime. Earlier studies have revealed that genipin can not only improve diabetes, but also induce cytotoxicity. Therefore, it is not clear which effect of genipin on kidneys occurs, when it is used in the treatment of diabetes. In the present study, we performed nuclear magnetic resonance (NMR)-based metabolomics analysis of urine and kidney tissue samples obtained from diabetic rats to explore the change of endogenous metabolites associated with diabetes and concomitant kidney disease. Nine significant differential metabolites that were closely related to renal function were screened. They were mainly related to three metabolic pathways: synthesis and degradation of ketone bodies, glycine, serine and threonine metabolism, and butanoate metabolism, which are involved in methylamine metabolism, energy metabolism and amino acid metabolism. In addition, after the intervention of genipin, the metabolic levels of all the metabolites tended to be normal, indicating a protective effect of genipin on kidneys. Our results may be helpful for understanding the antidiabetic effect of genipin.

[Study on TLC identification and UPLC determination method of atractylenolide in Atractylodes macrocephala].

This research is to establish TLC and UPLC methods for simultaneous determination of 3 atractylenolides in Atractylodes macrocephala. Silica gel GF254 plate was used for identification of A. macrocephala, and UPLC-PDA gradient elution method was used to simultaneously determine atractylenolide Ⅰ, Ⅱ and Ⅲ. The Waters BEH C18 column（2.1 mm×100 mm,1.7 µm）with acetonitrile-water as mobile phase and the wavelength of UV detector of 235 nm were performed. The quality control study showed that the characteristic for identification by TLC was distinct and highly specific. The method of content determination was in accordance with the regulations. The quantitative evaluation of atractylenolide Ⅰ,Ⅱ and Ⅲ was in good linear range（r>0.999 9）, and the average recovery was 93.48%（RSD 1.4%）,94.97%（RSD 1.6%）,92.71%（RSD 1.2%）,respectively. TLC identification was in good specificity and repeatability, and the UPLC-PDA method for the simultaneous determination of 3 atractylenolides was simple and reliable for the quality control of A.macrocephala.

Coffee and caffeine consumption and depression: A meta-analysis of observational studies.

OBJECTIVE: The results from observation studies on the relationship between coffee intake and risk of depression and the relationship between caffeine consumption and depression remain controversial. We conducted a meta-analysis with a dose-response analysis to quantitatively summarize the evidence about the association between coffee and caffeine intakes and risk of depression. METHOD: Relevant articles were identified by researching PubMed, Web of Science, China National Knowledge Infrastructure and WANFANG DATA in English or Chinese from 1 January 1980 to 1 May 2015. Case-control, cohort or cross-sectional studies evaluating coffee or caffeine consumption and depression were included. A random-effects model was used to combine study-specific relative risk and 95% confidence interval. Dose-response relationship was assessed by restricted cubic spline functions. RESULTS: Data were obtained from 11 observation articles; 330,677 participants from seven studies in seven articles were included in the coffee-depression analysis, while 38,223 participants from eight studies in seven articles were involved in the caffeine-depression analysis. Compared with the lowest level consumption, the pooled relative risk (95% confidence interval) for coffee-depression and caffeine-depression was 0.757 [0.624, 0.917] and 0.721 [0.522, 0.997], respectively. For dose-response analysis, evidence of a linear association was found between coffee consumption and depression, and the risk of depression decreased by 8% (relative risk = 0.92, 95% confidence interval = [0.87, 0.97], p = 0.002) for each cup/day increment in coffee intake; a nonlinear association was found between caffeine consumption and depression, the risk of depression decreased faster and the association became significant when the caffeine consumption was above 68 mg/day and below 509 mg/day. CONCLUSIONS: Coffee and caffeine consumption were significantly associated with decreased risk of depression.

The Relationship between Serum Zinc Level and Preeclampsia: A Meta-Analysis.

The association between serum zinc level and preeclampsia (PE) remains controversial. A systematic literature search was performed in PubMed, Web of Science and Embase for relevant available articles. The articles were limited to those in English from January 1990 to April 2015. Observational studies evaluating the association between serum zinc level and PE were included. The I² was used to assess heterogeneity and the random effect model (REM) was adopted as the pooling method. The pooled standard mean difference (SMD) with 95% confidence interval (CI) was used to estimate the association between serum zinc level and PE. Seventeen observational studies were included. Compared with healthy pregnancy controls, PE patients have lower serum zinc level in 14 studies about total PE (SMD (95% CI): -0.587 (-0.963, -0.212), Z = 3.06, p for Z = 0.002; I² = 88.4%, p for I² < 0.0001). In subgroup analysis, a lower serum zinc level in PE patients compared with healthy pregnancy controls was observed in studies conducted in Asia, studies with zinc level measured in serum, and studies involving fasting participants. The SMD did not differ significantly between studies with healthy pregnancy controls matched by individual age (yes or no), and by individual gestational age (yes or no), respectively. Results from this meta-analysis indicate that serum zinc level in PE patients is significantly lower than that in healthy pregnancy controls. A moderate amount of zinc supplementation during pregnancy is advocated to reduce the incidence of PE.

Hedyotis diffusa Willd extract inhibits the growth of human glioblastoma cells by inducing mitochondrial apoptosis via AKT/ERK pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Hedyotis diffusa Willd (Rubiaceae) (HDW) has been widely applied for the treatment of tumors, inflammation and toxication in traditional Chinese medicine. The antitumor effect of HDW on glioblastoma has been rarely reported. We aim to evaluate the activity of this extract and explore the underlying mechanism in U87 human glioblastoma cell line. MATERIALS AND METHODS: Cytotoxicity of HDW extract on U87 cells was measured by MTT assay. Apoptosis, cell cycle arrest and mitochondrial membrane potential (MMP) collapse induced by HDW extract were determined by flow cytometry. Caspase activity was analyzed based on colorimetric assay with a microplate spectrophotometer. Protein expression was examined by Western blot. RESULTS: HDW extract suppressed U87 cells growth in a dose- and time-dependent manner. Flow cytometry showed that HDW extract induced significant apoptosis, S/G2-M phase arrest and MMP collapse in U87 cells. Furthermore, dose-dependent activation of caspase-3, Bcl-2, Bax and ERK was observed with HDW extract treatment. Decreased Bcl-2/Bax ratio and Akt suppression were readily found as well. CONCLUSIONS: Induction of mitochondria-mediated apoptosis played an essential role in antitumor activity of HDW extract in U87 cells, in which ERKs and Akt signaling proteins were also involved. These findings contributed to the feasibility of using HDW extract in glioblastoma treatment and the understanding of the molecular mechanism.

[Study on molecular characteristics of four components contained in Hedysari Radix polysaccharide by gel permeation chromatography-multiangle laser light scattering technology (GPC-MALLS)].

OBJECTIVE: To determine such molecular characteristic parameters as absolute molecular weight, molecular weight distribution, root-mean-square turning radius (Rg) and polydispersity index (Mw/Mn) of four components contained in Hedysari Radix polysaccharide 3 (HPS-3) and map weight-average molecular weight (Mw) with root-mean-square turning radius (Rg), in order to calculate conformations of the four components at solution state. METHOD: The gel permeation chromatography-multi angle laser light scatting (GPC-MALLS) was adopted, with 0.1 mol x L(-1) NaNO3 contained 0.02% NaN3 as the mobilephase, Ultrahydrogel 1000 connected in series with Ultrahydrogel500. RESULT: Among the four components of HPS-3, HPS-3-C showed the highest weight average molecular weight of 1.986 x 10(5) g x mol(-1), followed by HPS-3-B 1.113 x 10(5) g x mol(-1) and HPS-3-D 8.457 x 10(4) g x mol(-1) HPS-3-A showed the lowest weight average molecular weight of 1. 223 x 10(4) g x mol(-1) but the highest square radius of gyration, that is 55.5 nm. HPS-3-D had the widest range of molecular weight distribution in four components, with the polydispersity index (Mw/Mn) of 2.543. In the mobile phase, HPS-3-A was globular structure, HPS-3-C was random coil, HPS-3-B and HPS-3-D were both highly branched structure. CONCLUSION: The results provided necessary basis for further studies on molecular characteristics of the four components contained in HPS-3 and their relationship with bioactivity.

Study on pharmacokinetics and tissue distribution of pteryxin in mice by ultra-pressure liquid chromatography with tandem mass spectrometry.

Pteryxin is a coumarin compound naturally occurring in the roots of Radix Peucedani, a commonly used as traditional Chinese medicine for the treatment of certain respiratory diseases and hypertension. An UPLC-MS/MS method was established to quantify pteryxin in mouse plasma and tissue homogenates. Isoimperatorin was used as internal standard (IS). The method was based on protein precipitation with methanol for sample preparation. Pteryxin and IS were separated using a UPLC™ BEH C18 column and eluted with a mobile phase consisting of methanol and water (70:30, v/v) at a flow-rate of 0.2 mL/min. MS/MS detection was carried out by monitoring the fragmentation of m/z 409.3-287.2 for pteryxin and m/z 271.3-185.2 for IS on a triple-quadrupole mass spectrometer. The total run time was only 6 min. The results showed that it had good linearity over a wide concentration range (r > 0.999), and pteryxin was rapidly distributed and then eliminated from mouse plasma (t(½) =1.463 h). The major distribution tissues of pteryxin in mice were liver, and pteryxin was enabled to cross the blood-brain barrier owing to its low polarity. There was no long-term accumulation of pteryxin in mouse tissues.