LysZX4-NCA, a new endolysin with broad-spectrum antibacterial activity for topical treatment.

The prevalence of multidrug-resistant highly virulent Klebsiella pneumoniae (MDR-hvKP) requires the development of new therapeutic agents. Herein, a novel lytic phage vB_KpnS_ZX4 against MDR-hvKP was discovered in hospital sewage. Phage vB_KpnS_ZX4 had a short latent period (5 min) and a large burst size (230 PFU/cell). It can rapidly reduce the number of bacteria in vitro and improve survival rates of bacteremic mice in vivo from 0 to 80 % with a single injection of 108 PFU. LysZX4, an endolysin derived from vB_KpnS_ZX4, exhibits potent antimicrobial activity in vitro in combination with ethylenediaminetetraacetic acid (EDTA). The antimicrobial activity of LysZX4 was further enhanced by the fusion of KWKLFKI residues from cecropin A (LysZX4-NCA). In vitro antibacterial experiments showed that LysZX4-NCA exerts broad-spectrum antibacterial activity against clinical Gram-negative bacteria, including MDR-hvKP. Moreover, in the mouse model of MDR-hvKP skin infection, treatment with LysZX4-NCA resulted in a three-log reduction in bacterial burden on the skin compared to the control group. Therefore, the novel phages vB_KpnS_ZX4 and LysZX4-NCA are effective reagents for the treatment of systemic and local MDR-hvKP infections.

Adsorption of uranium(VI) by natural vermiculite: Isotherms, kinetic, thermodynamic and mechanism studies.

Human activities such as mining uranium resources, hydrometallurgy, and nuclear fuel preparation inevitably produce wastewater sludge containing radionuclides, posing a severe threat to the environment around the production site. Natural clay minerals have been widely used in groundwater pollution remediation because of their high cation exchange capacity. Through static batch experiments, the optimal pH range of vermiculite for U(VI) adsorption was 6-8,the maximum adsorption capacity was 1.62 × 10-5 mol g-1. The kinetic adsorption results indicated that the adsorption mode was mainly multilayer non-homogeneous chemisorption. In addition, the adsorption of vermiculite on U(VI) was found to be a heat absorption process according to the thermodynamic model fitting, and the spontaneous reactivity of U(VI) adsorption on vermiculite surface was positively correlated with temperature and negatively correlated with the initial concentration of U(VI). Combined with SEM-EDS and FT-IR results, the adsorption process of vermiculite on U(VI) is mainly an ion exchange and complexation reaction, and U(VI) is removed in the form of ≡ SUOU22+ or ≡ SOUO2OH, etc., by XPS means. The results of this study not only investigated the adsorption behavior and mechanism of natural vermiculite in groundwater contaminated with simulated uranium but also provided theoretical support for its feasibility in remediating uranium-polluted groundwater.

Integerrima A-E, phenylethanoid glycosides from the stem of Callicarpa integerrima.

Five new phenylethanoid glycosides integerrima A-E (1-5) were isolated from the stem of Callicarpa integerrima for the first time. Their structures were elucidated by extensive spectroscopic analyses. In addition, cytotoxicity, anti-adipogenic and antioxidant activities were evaluated. All the phenylethanoid glycosides would be nontoxic to the normal human hepatocytes LO-2 and pre-adipocytes 3T3-L1 cell lines, significantly promote the proliferation of normal hepatocytes, thus displaying the potential for hepatoprotective. Integerrima A (1), C (3) and D (4) exhibited selectively moderate cytotoxic activity against the hepatoma cell lines Bel-7402, with the IC50 value at 72.66, 80.43 and 84.88 µmol/L, respectively. Moreover, integerrima D (4) had significant activities on reducing lipid droplet formation, with the inhibition rate of 48.02% on the concentration of 200 µg/mL. Finally, the result of FRAP assays exhibited remarkable antioxidant activity in integerrima E (5), which was close to the positive control ascorbic acid with the concentration of 100 µg/mL.

Screen of high efficiency cellulose degrading strains and effects on tea residues dietary fiber modification: Structural properties and adsorption capacities.

In our study, two high efficiency cellulose degrading strains were screened, isolated and identified as Cochliobolus kusanoi and Aspergillus puulaauensis by 18S rDNA gene sequencing. In addition, the composite microbial system was constructed to develop the synergistic effect among different strains. Under the optimum conditions, the yield of soluble dietary fiber from tea residues by mixed fermentation method (MF-SDF) dramatically increased compared to single strain fermentation. The structural analysis demonstrated that all samples possessed the representative infrared absorption peaks of polysaccharides, whereas MF-SDF revealed more loose structure, lower crystallinity and smaller molecular size. For the adsorption capacities indexes, MF-SDF also owned the highest adsorbing capacity for the water molecule, oil molecule, cholesterol molecule and nitrite ion. Overall, our data showed that mixed fermentation method could be better choices to improve the functional properties of dietary fiber, and screening of cellulose degrading strains could provide new thinkings for the study of dietary fiber modification and realize high-quality utilization of crop residues.

Associations between predicted vitamin D status, vitamin D intake, and risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) severity.

BACKGROUND: Vitamin D may have a role in immune responses to viral infections. However, data on the association between vitamin D and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) severity have been limited and inconsistent. OBJECTIVE: We examined the associations of predicted vitamin D status and intake with risk of SARS-CoV-2 infection and COVID-19 severity. METHODS: We used data from periodic surveys (May 2020 to March 2021) within the Nurses' Health Study II. Among 39,315 participants, 1768 reported a positive test for SARS-CoV-2 infection. Usual vitamin D intake from foods and supplements were measured using a semiquantitative, pre-pandemic food-frequency questionnaire in 2015. Predicted 25-hydroxyvitamin D [25(OH)D] concentration were calculated based on a previously validated model including dietary and supplementary vitamin D intake, UV-B, and other behavioral predictors of vitamin D status. RESULTS: Higher predicted 25(OH)D concentrations, but not vitamin D intake, were associated with a lower risk of SARS-CoV-2 infection. Comparing participants in the highest quintile of predicted 25(OH)D concentrations with the lowest, the multivariable-adjusted OR was 0.76 (95% CI: 0.58, 0.99; P-trend = 0.04). Participants in the highest quartile of UV-B (OR: 0.76; 95% CI: 0.66, 0.87; P-trend = 0.002) and UV-A (OR: 0.76; 95% CI: 0.66, 0.88; P-trend < 0.001) also had a lower risk of SARS-CoV-2 infection compared with the lowest. High intake of vitamin D from supplements (≥400 IU/d) was associated with a lower risk of hospitalization (OR: 0.51; 95% CI: 0.29, 0.91; P-trend = 0.04). CONCLUSIONS: Our study provides suggestive evidence on the association between higher predicted circulating 25(OH)D concentrations and a lower risk of SARS-CoV-2 infection. Greater intake of vitamin D supplements was associated with a lower risk of hospitalization. Our data also support an association between exposure to UV-B or UV-A, independently of vitamin D and SARS-CoV-2 infection, so results for predicted 25(OH)D need to be interpreted cautiously.

Speckle Tracking Echocardiography Verified the Efficacy of Qianyangyuyin Granules in Alleviating Left Ventricular Remodeling in a Hypertensive Rat Model.

BACKGROUND: Global longitudinal strain (GLS) can be assessed by speckle tracking echocardiography (STE) to express the degree of cardiac fibrosis. Qianyangyuyin (QYYY) granules can effectively improve GLS in hypertensive patients. Using a hypertensive rat model, we carried out speckle tracking echocardiography to validate the effect of QYYY in diminishing LV remodeling. METHODS: We randomly divided 16 spontaneously hypertensive rats (SHRs) into SHR, SHR + valsartan (SHR + V), SHR + low-dose QYYY (SHR + QL), and SHR + high-dose QYYY (SHR + QH) groups, with four rats in each group. Another group of 4 Wistar-Kyoto (WKY) rats were selected into a normal control (WKY) group. At the 8th week, conventional echocardiographic parameters were measured by GE Vivid E95 ultrasound (12S probe, 10-12 MHz) and GLS by speckle tracking echocardiography with EchoPAC (version 203) software. HE and Masson's trichrome staining were performed to detect the cardiomyocyte width and collagen volume fraction after rat sacrifice. Collagen I, α-SMA, S100A4, TGF-ß, Smad 3, MYH6, and MYH7 were further analyzed by Western blot. RESULTS: The absolute values of GLS significantly increased in the SHR + QH group compared to the SHR group, while the CVF and CW values significantly decreased. In addition, Collagen I, α-SMA, S100A4, TGF-ß, Smad3, MYH7, and MYH7/MYH6 ratio remarkably reduced in the SHR + QH group. The value of GLS could be repetitively measured and positively correlated with the collagen volume fraction of the myocardium and the cardiomyocyte width of the left ventricular free wall. CONCLUSIONS: GLS is a reliable indicator to evaluate the therapeutic effect on left ventricular remodeling in hypertension. QYYY granules can inhibit the development of cardiac fibrosis in the hypertensive rat model.

Ginsenoside Rb1 exerts antidepressant-like effects via suppression inflammation and activation of AKT pathway.

Depression-like behaviors caused by chronic stress are related to inflammation and microglia activation. Antidepressant therapy may contribute to inhibiting inflammation responses and microglia activation. Ginsenoside Rb1 (GRb1) is known to display antidepressant-like effect on chronic unpredictable mild stress-induced depressive rats. However, the antidepressant-like effects of GRb1 on chronic restraint stress (CRS) mice and the potential anti-inflammatory mechanisms are unclear. Here, we focused on the molecular mechanisms related to inhibition of inflammation response and the protection on microglia. Our results showed that GRb1 had an antidepressant effects via relieving the depression-like behaviors in CRS model. Furthermore, GRb1 increased the protein expressions of brain-derived neurotrophic factor and phospho- protein kinase B/ protein kinase B (p-AKT/AKT), and decreased the protein expressions of interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α) and ionized calcium binding adapter molecule 1 in hippocampus, reduced the levels IL-1ß and TNF-α in serum. Finally, GRb1 lowered the protein expressions of IL-1ß and TNF-α in BV-2 microglia induced by lipopolysaccharides. Taken together, the results indicate that GRb1 prevents CRS-induced depression-like behaviors in mice, which may be related to anti-inflammatory effects in hippocampus, serum and microglia and activation of AKT pathway.

Characterization of the complete chloroplast genome of Taxus wallichiana as the medicinal plant from China.

Taxus wallichiana is a member of the family Taxaceae, which is a unique and endangered species in China and is widely used for ornamental, material and medicinal purposes. The complete chloroplast genome of T. wallichiana was found to possess a total size of 128,168 bp. The GC content of T. wallichiana chloroplast genome sequence is 37.3%, the overall nucleotide composition of chloroplast genome sequence is: A of 30.7%, T of 32.0%, C of 19.0% and G of 18.3%. The total of 116 genes were successfully annotated, which contained 83 protein-coding genes, 29 transfer RNA genes, and 4 ribosomal RNA genes. The ML phylogenetic analysis result showed that T. wallichiana was closely related to Taxus baccata in the phylogenetic relationship using the neighbour-joining (NJ) method in this study.

Meta-analysis of randomized clinical trials of adjuvant chemotherapy for resected biliary tract cancers.

BACKGROUND: This meta-analysis was performed by analyzing randomized controlled trials (RCTs) to assess the potential prognostic value of adjuvant chemotherapy (ACT) for patients with resected biliary tract cancers (BTCs). METHODS: PubMed, EMBASE, and the Cochrane Library were searched for relevant articles published. Only RCTs affected by tumors of gallbladder, intrahepatic, perihilar, and distal bile ducts were considered. Data were pooled using a random-effects model. The primary endpoint of the study was overall survival (OS). RESULTS: The study identified 1192 patients who met the inclusion and exclusion criteria. ACT had nearly reached a significant better OS (HR, 0.88; 95% CI, 0.77-1.01; P = 0.07) and achieved a significant better RFS (HR, 0.83; 95% CI, 0.69-0.99; P = 0.04). The effectiveness of ACT for OS was significantly modified by fluorouracil-based ACT (HR, 0.83; 95% CI, 0.70-0.99; P = 0.04), but not by gemcitabine-based ACT (HR, 0.91; 95% CI, 0.74-1.12; P = 0.36). The survival benefit was also not modified by primary disease site, resection margin status, and lymph node status. CONCLUSIONS: ACT is correlated with favorable relapse-free survival compared with non-ACT for resected BTCs patients. Fluorouracil-based ACT could be viewed as a standard practice for resected BTCs patients regardless of the primary cancer site, lymph node or margin status.

The efficacy and safety of acupuncture for Ramsay Hunt syndrome: A protocol for systematic review.

BACKGROUND: Ramsay Hunt syndrome (RHS), also known as Hunt syndrome, is caused by varicella-zoster virus infection. The virus often invades the facial nerve geniculate ganglion to cause peripheral facial paralysis, accompanied by severe ear pain, auricular herpes zoster, tinnitus, deafness, vertigo, and other inner ear neurologic symptoms. The acupuncture has a long history as a traditional treatment of traditional Chinese medicine for the treatment of Hunt syndrome, with few adverse events and low cost. However, there are few evidences for the efficacy and safety of acupuncture for Hunt syndrome. Hence, we plan this systematic review and meta-analysis protocol to evaluate the efficacy and safety of acupuncture for Hunt syndrome. METHODS: Four English databases will be searched from their inception to February 2019, including Cochrane Library, PubMed, Embase, OVID, and 4 Chinese databases, including Chinese Biomedical Literature Database [CBM], China National Knowledge Infrastructure [CNKI], CQVIP, and Wanfang. No restriction was imposed for language or publication period. Randomized controlled clinical trials (RCTs) compared any form of acupuncture with/without additional treatment against sham or no treatment or same additional treatment. Data will be extracted and evaluated by 2 reviewers independently. RevMan 5.3 software will be used for data analysis when a meta-analysis is allowed. RESULTS: This systematic review and meta-analysis will provide an evidence of acupuncture for RHS. CONCLUSION: This study will determine whether acupuncture is an effective and safe intervention for RHS. PROSPERO registration number: CRD 42019118283.

Occurrence and Distribution of Uranium in a Hydrological Cycle around a Uranium Mill Tailings Pond, Southern China.

Uranium (U) mining activities, which lead to contamination in soils and waters (i.e., leachate from U mill tailings), cause serious environmental problems. However, limited research works have been conducted on U pollution associated with a whole soil-water system. In this study, a total of 110 samples including 96 solid and 14 water samples were collected to investigate the characteristics of U distribution in a natural soil-water system near a U mining tailings pond. Results showed that U concentrations ranged from 0.09 ± 0.02 mg/kg to 2.56 × 104± 23 mg/kg in solid samples, and varied greatly in different locations. For tailings sand samples, the highest U concentration (2.56× 104 ± 23 mg/kg) occurred at the depth of 80 cm underground, whereas, for paddy soil samples, the highest U concentration (5.22 ± 0.04 mg/kg) was found at surface layers. Geo-accumulation index and potential ecological hazard index were calculated to assess the hazard of U in the soils. The calculation results showed that half of the soil sampling sites were moderately polluted. For groundwater samples, U concentrations ranged from 0.55 ± 0.04 mg/L to 3.36 ± 0.02 mg/L with a mean value of 2.36 ± 0.36 mg/L, which was significantly lower than that of percolating waters (ranging from 4.56 ± 0.02 mg/L to 12.05 ± 0.04 mg/L, mean 7.91 ± 0.98 mg/L). The results of this study suggest that the distribution of U concentrations in a soil-water system was closely associated with hydrological cycles and U concentrations decreased with circulation path.

Coffee consumption and plasma biomarkers of metabolic and inflammatory pathways in US health professionals.

BACKGROUND: Coffee consumption has been linked to lower risk of various health outcomes. However, the biological pathways mediating the associations remain poorly understood. OBJECTIVES: The aim of this study was to assess the association between coffee consumption and concentrations of plasma biomarkers in key metabolic and inflammatory pathways underlying common chronic diseases. METHODS: We investigated the associations of total, caffeinated, and decaffeinated coffee consumption with 14 plasma biomarkers, including C-peptide, insulin-like growth factor 1 (IGF-1), IGF binding protein (IGFBP) 1, IGFBP-3, estrone, total and free estradiol, total and free testosterone, sex hormone-binding globulin (SHBG), total adiponectin, high-molecular-weight (HMW) adiponectin, leptin, C-reactive protein (CRP), interleukin 6 (IL-6), and soluble tumor necrosis factor receptor 2 (sTNFR-2). Data were derived from 2 cohorts of 15,551 women (Nurses' Health Study) and 7397 men (Health Professionals Follow-Up Study), who provided detailed dietary data before blood draw and were free of diabetes, cardiovascular disease, or cancer at the time of blood draw. Multivariable linear regression was used to calculate the percentage difference of biomarker concentrations comparing coffee drinkers with nondrinkers, after adjusting for a variety of demographic, clinical, and lifestyle factors. RESULTS: Compared with nondrinkers, participants who drank ≥4 cups of total coffee/d had lower concentrations of C-peptide (-8.7%), IGFBP-3 (-2.2%), estrone (-6.4%), total estradiol (-5.7%), free estradiol (-8.1%), leptin (-6.4%), CRP (-16.6%), IL-6 (-8.1%), and sTNFR-2 (-5.8%) and higher concentrations of SHBG (5.0%), total testosterone (7.3% in women and 5.3% in men), total adiponectin (9.3%), and HMW adiponectin (17.2%). The results were largely similar for caffeinated and decaffeinated coffee. CONCLUSION: Our data indicate that coffee consumption is associated with favorable profiles of numerous biomarkers in key metabolic and inflammatory pathways. This trial was registered at clinicaltrials.gov as NCT03419455.

Accumulation of U(VI) on the Pantoea sp. TW18 isolated from radionuclide-contaminated soils.

Pantoea sp. TW18 isolated from radionuclide-contaminated soils was used for the bioremediation of radionuclides pollution. Accumulation mechanism of U(VI) on Pantoea sp. TW18 was investigated by batch experiments and characterization techniques. The batch experiments revealed that Pantoea sp. TW18 rapidly reached accumulation equilibrium at approximately 4 h with a high accumulation capacity (79.87 mg g-1 at pH 4.1 and T = 310 K) for U(VI). The accumulation data of U(VI) onto Pantoea sp. TW18 can be satisfactorily fitted by pseudo-second-order model. The accumulation of U(VI) on Pantoea sp. TW18 was affected by pH levels, not independent of ionic strength. Analysis of the FT-IR and XPS spectra demonstrated that accumulated U(VI) ions were primarily bound to nitrogen- and oxygen-containing functional groups (i.e., carboxyl, amide and phosphoryl groups) on the Pantoea sp. TW18 surface. This study showed that Pantoea sp. TW18 can be considered as a promising sorbent for remediation of radionuclides in environmental cleanup.

Screening and Identification of the Metabolites of Water Extracts of Raw and Honey-Processed Astragalus in Rat Urine Based on UHPLC/ESI-Q-TOF-MS and Multivariate Statistical Analysis.

Radix Astragali is a famous traditional Chinese medicine and honey-processed Astragalus is a product of Radix Astragali acquired by honey-processing. These two products are widely utilized to treat various diseases. In this study, we screened bioactive components and metabolites of raw and honey-processed Astragalus in rat urine by ultra-performance liquid chromatography equipped with electrospray ionization/quadrupole time-of-flight mass spectrometry (UHPLC/ESI-Q-TOF-MS) combined with multivariate statistical analysis. In total, 62 compounds, including 7 parent compounds and 55 metabolites, were detected and 11 metabolites were characterized for the first time. The identified metabolites indicated that the metabolic reactions of Astragalus in rats included hydroxylation, glucuronidation, deglucosidation, monomethylation, demethylation, sulfation, hydrogenation, and dehydroxylation. The metabolic pathways of raw and honey-processed Astragalus in rat urine also were clarified. Through multivariate statistical analysis of the data of the raw and honey-processed Astragalus groups, we found that 20 compounds were differential components and that 1 metabolite only existed in the honey-processed Astragalus group. The differences in these ingredients between these two groups might provide the basis for interpreting the biologic activity differences in traditional Chinese medicine treatments. Graphical Abstract.

A Novel Rabbit Model for Benign Biliary Stricture Formation and the Effects of Medication Infusions on Stricture Formation.

BACKGROUND: Benign biliary stricture (BBS) is highly refractory. Currently, there is no effective strategy for prevention of BBS recurrence. The aim of this study is to establish a novel BBS rabbit model and to investigate the efficacy of biliary infusion with anti-proliferative medications for treating BBS. METHOD: A BBS model was established via surgical injury and biliary infection. The biliary infusion tube was inserted into the common bile duct via the stump of cystic duct after cholecystectomy. Biliary infusions with Rapamycin, Pirfenidone and Fasudil were performed daily during the 4 weeks following the surgery. The wall thickness and luminal area of the bile duct were assessed. RESULTS: All rabbits formed BBS after surgery. The mortality rate was 13% (8/60) and tube withdrawal rate was 4% (2/48). The thickness of the bile duct wall was significantly reduced; whereas the luminal area of the bile duct was dramatically enlarged in the Rapamycin or the Pirfenidone treated group, compared to the saline treated group. Furthermore, the local treatment significantly decreased the levels of proliferation makers, including PCNA, Collagen I and fibrogenic mediators, including ACTA2 and TGF-beta. CONCLUSION: We have established a novel animal model for BBS formation. We have further demonstrated that biliary infusion with Rapamycin or Pirfenidone limits the biliary strictures through inhibiting the proliferation of the bile duct wall in this model. This may represent a new avenue for preventing biliary restenosis.

Application of pathways activity profiling to urine metabolomics for screening Qi-tonifying biomarkers and metabolic pathways of honey-processed Astragalus.

Honey-processed Astragalus, a widely used Qi-tonifying and immunomodulating herb in traditional Chinese medicine, has strengthened the tonic effects and achieved fewer side effects compared with astragali radix in clinical application. Here, we focus on Qi-tonifying biomarkers and pathways of honey-processed Astragalus using urine metabolomics that provide the basis for building the linkage between metabolites in rat urine and its symptoms. The spleen Qi deficiency model group, normal group, astragali radix group, and honey-processed Astragalus group were implemented to evaluate Qi-tonifying effects. Twelve potential biomarkers were screened by multivariate statistical analysis by using ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Furthermore, pathways activity profiling showed unique pathways that are primarily involved in tryptophan metabolism, tricarboxylic acids cycle, and methionine metabolism. The results demonstrated that metabolomics coupled with pathway activity profiling were promising tools. It might serve as a novel methodological clue to systematically dissect the underlying Qi-tonifying mechanism of honey-processed Astragalus.

Dietary glutamine, glutamate and mortality: two large prospective studies in US men and women.

Background: Emerging studies have related circulating glutamine metabolites to various chronic diseases such as cardiovascular disease and cancer; diet is the major source of nutrients involved in glutamine metabolism. However, it remains unknown whether dietary intakes of glutamine, glutamate,and their ratio are related to total and cause-specific mortality. Methods: We followed 74 082 women from the Nurses' Health Study (1984-2012) and 42 303 men from the Health Professionals Follow-up Study (1986-2012), who were free of cardiovascular disease and cancer at baseline. Diet was updated every 2 to 4 years by using validated food frequency questionnaires. The content of glutamine and glutamate in foods was calculated based on protein fractions generated from gene sequencing methods and adjusted for total energy intake. Results: We documented 30 424 deaths during 2 878 344 person-years of follow-up. After adjustment for potential confounders including lifestyle and dietary factors, higher intakes of glutamine and glutamine-to-glutamate ratio were associated with significantly lower risk of total and cause-specific mortality. Compared with people in the lowest quintile of dietary glutamine-to-glutamate ratio, the pooled hazard ratio (HR) in the highest quintile was 0.87 [95% confidence interval (CI): 0.84, 0.91; P for trend < 0.001) for total mortality, 0.81 (95% CI: 0.75, 0.88; P for trend < 0.001) for cardiovascular mortality, and 0.93 (95% CI: 0.87, 0.99; P for trend = 0.01) for cancer mortality. Conclusions: We found dietary glutamine and glutamine-to-glutamate ratio were inversely related to risk of mortality, particularly cardiovascular mortality, independent of other dietary and lifestyle factors, in US men and women.

Genetic variation of habitual coffee consumption and glycemic changes in response to weight-loss diet intervention: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial.

Background: Coffee consumption has been associated with glucose metabolism and risk of type 2 diabetes.Objective: We examined whether the genetic variation determining habitual coffee consumption affected glycemic changes in response to weight-loss dietary intervention.Design: A genetic risk score (GRS) was calculated based on 8 habitual coffee consumption-associated single nucleotide polymorphisms. We used general linear models to test changes in glycemic traits in groups randomly assigned to high- and low-fat diets according to tertiles of the GRS.Results: We observed significant interactions between the GRS and low compared with high dietary fat intake on 6-mo changes in fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) (P-interaction = 0.023 and 0.022, respectively), adjusting for age, sex, race, physical activity, smoking, alcohol, seasonal variation, and baseline values of the respective outcomes. Participants with a higher GRS of habitual coffee consumption showed a greater reduction in fasting insulin and a marginally greater decrease in HOMA-IR in the low-fat diet intervention group.Conclusions: Our data suggest that participants with genetically determined high coffee consumption may benefit more by eating a low-fat diet in improving fasting insulin and HOMA-IR in a short term. This trial was registered at clinicaltrials.gov as NCT00072995 and NCT03258203.

[Identification of biomarkers in urine of rats with spleen Qi deficiency and biological significance].

To identify biomarkers for spleen Qi deficiency by analyzing small molecule metabolites in urine, in order to expound the relationship between biomarkers and metabolic pathways. The spleen Qi deficiency model was established through dietary restriction and overstrain. All of the rats received D-xylose absorption experiment and blood routine test. Urine samples were collected in the next day. The urine samples were analyzed using UPLC-Q-TOF-MS to obtain the dataset of urine metabolic group. Principal component analysis (PCA), orthogonal partialleast squares-discriminant analysis (OPLS-DA) and other multivariate statistical methods were employed to evaluate the quality of the dataset and screen out potential biomarkers of spleen Qi deficiency. The results of D-xylose absorption and blood routine demonstrated that the spleen Qi deficiency model was successfully established. In positive ion mode and negative ion mode, PCA and OPLS-DA score plots could clearly distinguish model group and blank group. According to S-plot of OPLS-DA, VIP value, t-test and area under receiver operating characteristic curve (ROC), 24 biomarkers, including phenylalanine, succinic acid, aconitic acid, isocitrate acid, betaine, kynurenine, indole, creatine, creatinine, orotic acid, xanthine, and xanthurenic acid, were identified as associated with the spleen Qi deficiency, mainly involving energy metabolism, amino acid metabolism, tryptophan metabolism, purine metabolism and pyrimidine metabolism. Urine metabolomics method combined with online software package for data processing and analysis metabolic pathway can provide new methods and ideas for studies for spleen Qi deficiency and other traditional Chinese medicine symptoms.

[Effect of genistein combined with anastrozole on mammary tumors in ovariectomized rats].

OBJECTIVE: To evaluate the inhibitory effect of genistin combined with anastrozole on the growth and apoptosis of breast tumor tissue, and to study their anti-cancer mechanism by using the model of 7,12-dimethylbenz [alpha] anthracene (DMBA)-induced mammary tumors following ovariectomy in Sprague-Dawley (SD) rats. METHODS: The DMBA induced postmenopausal SD rats were randomly divided into the control group, the genistein group, the anastrozole group, and the genistein combined with anastrozole group. The growth of tumors was observed in each group. The proliferation index and apoptosis index of tumor cells were determined. Moreover, estradiol (E2) and 17beta-HSD1 mRNA levels were determined by ELISA and RT-PCR respectively. RESULTS: The tumor growth was inhibited in the genistein group and the anastrozole group. The inhibitory ratio was significantly higher in the genistein combined with anastrozole group (P < 0.05). Compared with the control group, levels of E2 and 17beta-HSD1 mRNA decreased more significantly in the genistein combined with anastrozole group (P < 0.05). CONCLUSIONS: Genistein could suppress the growth of mammary tumors in postmenopausal rats. It showed synergistic effect when combined with anastrozole, which resulted in reduced levels of E2 and 17beta-HSD1 mRNA. It had inhibitory effect on the growth of breast tumors.