Combined exposure to multiple air pollutants and incident ischemic heart disease in individuals with and without type 2 diabetes: A cohort study from the UK Biobank.

BACKGROUND: Air pollution and type 2 diabetes (T2D) are both associated with an increased risk of ischemic heart disease (IHD). Little is known about the combined effects of multiple air pollutants on IHD risk, especially among individuals with T2D. We sought to assess the association of combined exposure to multiple air pollutants with incident IHD and examine the modification effect of T2D. METHODS: This study included 388780 individuals (20036 individuals with T2D) free of cardiovascular disease and cancer from the UK Biobank. The combined exposure to multiple air pollutants, including particulate matter (PM) with diameters ≤ 2.5 µm (PM2.5), PM with diameters between 2.5 and 10 µm (PMcoarse), PM with diameters ≤ 10 µm (PM10), nitrogen dioxide (NO2), and nitrogen dioxides (NOx), was assessed by creating a weighted air pollution score (APS), with a higher APS representing a higher level of air pollution exposure. Hazard ratios (HR) and 95 % confidence intervals (CI) for incident IHD were assessed by multivariable-adjusted Cox proportional hazard models. RESULTS: During a median of 12.9 years of follow-up, 27333 incident IHD cases were observed. Compared with the lowest tertile of the APS, the multivariable-adjusted HR (95 % CI) of IHD risk for the highest tertile was 1.13 (1.03-1.23) among individuals with T2D, while the HR was 1.06 (1.03-1.10) among individuals without T2D. Additionally, the associations between APS and IHD incidence showed a linear relationship among individuals with T2D (nonlinearity: P = 0.37), whereas a non-linear relationship was observed among individuals without T2D (nonlinearity: P = 0.02). For the joint analysis, individuals in the highest tertile of APS and with T2D had a 54 % higher risk of IHD compared to individuals in the lowest tertile of APS and without T2D, with a significant additive interaction (Pinteraction < 0.01). The proportion of relative excess risk was 17 % due to the interaction in categorical analyses. CONCLUSIONS: The combined exposure to multiple air pollutants has been associated with an elevated risk of incident IHD, and the association is more pronounced among individuals with T2D.

Zijuan tea- based kombucha: Physicochemical, sensorial, and antioxidant profile.

Zijuan tea is a representative anthocyanin-rich tea cultivar in China. In this study, Zijuan tea was used to produce a novel kombucha beverage (ZTK). The physicochemical, sensory properties, and antioxidant activity of ZTK were compared with that of black tea kombucha (BTK) and green tea kombucha (GTK). Results indicated that after fermentation, the color of ZTK changed from yellowish-brown to salmon-pink, because its anthocyanins (4.5 mg/L) appeared red in acidic conditions. Meanwhile no significant changes of color were observed in BTK and GTK. The dynamic changes of pH, biomass, and concentrations of sugars, amino acids, and main organic acids were similar in three kombucha beverages, except catechins showing different trends. Moreover, ZTK showed the highest overall acceptability score, antioxidant activity, and concentration of volatiles among the three kombucha beverages. Therefore, Zijuan tea is suitable for the preparation of kombucha beverage with attractive color and health benefits.

Quercetin is protective against short-term dietary advanced glycation end products intake induced cognitive dysfunction in aged ICR mice.

Dietary advanced glycation end products (dAGEs) might be potential toxins involved in the pathogenesis of Alzheimer's disease (AD). Quercetin is a flavonoid possessing neuroprotective effects. We aimed to explore whether a 21 days of dAGEs intake would result in cognitive dysfunction in aged ICR mice, and the protective effects of quercetin, with potential mechanisms explored. Fourteen-month old ICR mice were randomly assigned into four groups, that is, Control, AGEs, quercetin, and AGE diet supplemented with quercetin. Key markers involved in Aß, tau, and neuroinflammation from hippocampus and cortex were measured via western blot. Gut microbiota and short chain fatty acids profiles from intestinal contents were measured via 16S rRNA gene sequencing and gas chromatography (GC), respectively. Quercetin alleviated cognitive impairment induced by dAGEs in aged mice. This might be associated with that quercetin reduced cathepsin B, tau phosphorylation, and neuroinflammation, and elevated α-diversity index (ACE, Chao1, and Shannon index), and reduced phylum Verrucomicrobia of gut microbiota. PRACTICAL APPLICATIONS: Alzheimer's disease (AD) has been regarded as the commonest cause of progressive dementia for the elderly. This study is the very first to demonstrate that even a short-term dietary advanced glycation end product (dAGEs) intake induced impaired cognitive function in aged ICR mice, and querectin is capable of reversing dAGEs-induced cognitive dysfunction. Reduced tau phosphorylation, neuroinflammation, and altered gut microbiota profiles may be involved in querectin's protective effects against dAGEs-induced cognitive impairment. Our study suggested that quercetin supplementation might be beneficial for improving cognitive function in elderly subjects with high consumption of dAGEs such as grilling, frying, and broiling of food.

Co-administration of Shexiang Baoxin Pill and Chemotherapy Drugs Potentiated Cancer Therapy by Vascular-Promoting Strategy.

Effective delivery of chemotherapeutic agents to tumors is a critical objective of improved cancer therapy. Traditional antiangiogenic therapy aims at eradicating tumor blood vessels, but the subsequently reduced blood perfusion may limit the drug amount delivered into the tumor and potentially lead to tumor hypoxia, which has been proved to be unable to meet the therapeutic expectations. "Shexiang Baoxin Pill" (SBP) is a well-known traditional Chinese medicine (TCM) used in clinical treatment of cardiovascular diseases, which has the pharmacological effect of pro-angiogenesis demonstrated recently. In this study, we disclosed our finding that SBP could enhance the effective treatment performance of gemcitabine (GEM) while minimizing the toxic side effects caused by GEM. Mechanistically, SBP increased tumor angiogenesis, blood perfusion, vascular permeability, and vessel dilation, which subsequently favored the delivery of GEM to the tumor lesion. Moreover, combined treatment with SBP and GEM could modify tumor microenvironment and consequently overcome multidrug resistance, and this combination therapy is also suitable for combination of SBP with some other chemotherapeutic drugs as well. These results suggest that combining SBP with chemotherapeutic agents achieves better treatment efficiency, which can open an avenue for expanding the combined treatment of anti-cancer chemotherapeutic drugs with TCM.

Microencapsulation of borage oil with blends of milk protein, ß-glucan and maltodextrin through spray drying: physicochemical characteristics and stability of the microcapsules.

BACKGROUND: Borage oil is a rich commercial source of γ-linolenic acid (18:3n-6). However, borage oil is rich in omega-6 polyunsaturated fatty acids and vulnerable to oxidation. Thus, selecting appropriate wall materials is critical to the encapsulation of borage oil. The present study investigated the influence of wall materials on the physicochemical characteristics and stability of microencapsulated borage oil by spray drying. Blends of milk protein [sodium caseinate (CAS) or whey protein concentrate], ß-glucan (GLU) and maltodextrin (MD) were used as the wall materials for encapsulating borage oil. RESULTS: The microencapsulation of borage oil with different wall materials attained high encapsulation efficiencies. The microencapsulated borage oil prepared with CAS-MD achieved the optimal encapsulation efficiency of 96.62%. The oxidative stabilities of borage oil and microencapsulated borage oil were measured by accelerated storage test at 45 °C and 33% relative humidity for 30 days. The microencapsulated borage oil presented lower peroxide values than those of borage oil, and the microcapsules prepared with CAS-10GLU-MD (consisting of CAS 50 g kg-1 , GLU 100 g kg-1 and MD 475 g kg-1 of microencapsulation) conferred borage oil with high protection against lipid oxidation. CONCLUSION: The results of the present study demonstrate that the CAS-GLU-MD blend is appropriate for microencapsulating borage oil. © 2017 Society of Chemical Industry.

Pathway and rate-limiting step of glyphosate degradation by Aspergillus oryzae A-F02.

Aspergillus oryzae A-F02, a glyphosate-degrading fungus, was isolated from an aeration tank in a pesticide factory. The pathway and rate-limiting step of glyphosate (GP) degradation were investigated through metabolite analysis. GP, aminomethylphosphonic acid (AMPA), and methylamine were detected in the fermentation liquid of A. oryzae A-F02, whereas sarcosine and glycine were not. The pathway of GP degradation in A. oryzae A-F02 was revealed: GP was first degraded into AMPA, which was then degraded into methylamine. Finally, methylamine was further degraded into other products. Investigating the effects of the exogenous addition of substrates and metabolites showed that the degradation of GP to AMPA is the rate-limiting step of GP degradation by A. oryzae A-F02. In addition, the accumulation of AMPA and methylamine did not cause feedback inhibition in GP degradation. Results showed that degrading GP to AMPA was a crucial step in the degradation of GP, which determines the degradation rate of GP by A. oryzae A-F02.

Atractylenolide I stimulates intestinal epithelial repair through polyamine-mediated Ca2+ signaling pathway.

BACKGROUND: An impairment of the integrity of the mucosal epithelial barrier can be observed in the course of various gastrointestinal diseases. The migration and proliferation of the intestinal epithelial (IEC-6) cells are essential repair modalities to the healing of mucosal ulcers and wounds. Atractylenolide I (AT-I), one of the major bioactive components in the rhizome of Atractylodes macrocephala Koidz. (AMR), possesses multiple pharmacological activities. This study was designed to investigate the therapeutic effects and the underlying molecular mechanisms of AT-I on gastrointestinal mucosal injury. METHODS: Scratch method with a gel-loading microtip was used to detect IEC-6 cell migration. The real-time cell analyzer (RTCA) system was adopted to evaluate IEC-6 cell proliferation. Intracellular polyamines content was determined using high performance liquid chromatography (HPLC). Flow cytometry was used to measure cytosolic free Ca2+ concentration ([Ca2+]c). mRNA and protein expression of TRPC1 and PLC-γ1 were determined by real-time PCR and Western blotting assay respectively. RESULTS: Treatment of IEC-6 cells with AT-I promoted cell migration and proliferation, increased polyamines content, raised cytosolic free Ca2+ concentration ([Ca2+]c), and enhanced TRPC1 and PLC-γ1 mRNA and protein expression. Depletion of cellular polyamines by DL-a-difluoromethylornithine (DFMO, an inhibitor of polyamine synthesis) suppressed cell migration and proliferation, decreased polyamines content, and reduced [Ca2+]c, which was paralleled by a decrease in TRPC1 and PLC-γ1 mRNA and protein expression in IEC-6 cells. AT-I reversed the effects of DFMO on polyamines content, [Ca2+]c, TRPC1 and PLC-γ1 mRNA and protein expression, and restored IEC-6 cell migration and proliferation to near normal levels. CONCLUSION: Our data demonstrate that AT-I stimulates intestinal epithelial cell migration and proliferation via the polyamine-mediated Ca2+ signaling pathway. Therefore, AT-I may have the potential to be further developed as a promising therapeutic agent to treat diseases associated with gastrointestinal mucosal injury, such as inflammatory bowel disease and peptic ulcer.

Effects of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper limb motor dysfunction in patients with subacute cerebral infarction.

Studies have confirmed that low-frequency repetitive transcranial magnetic stimulation can decrease the activity of cortical neurons, and high-frequency repetitive transcranial magnetic stimulation can increase the excitability of cortical neurons. However, there are few studies concerning the use of different frequencies of repetitive transcranial magnetic stimulation on the recovery of upper-limb motor function after cerebral infarction. We hypothesized that different frequencies of repetitive transcranial magnetic stimulation in patients with cerebral infarction would produce different effects on the recovery of upper-limb motor function. This study enrolled 127 patients with upper-limb dysfunction during the subacute phase of cerebral infarction. These patients were randomly assigned to three groups. The low-frequency group comprised 42 patients who were treated with 1 Hz repetitive transcranial magnetic stimulation on the contralateral hemisphere primary motor cortex (M1). The high-frequency group comprised 43 patients who were treated with 10 Hz repetitive transcranial magnetic stimulation on ipsilateral M1. Finally, the sham group comprised 42 patients who were treated with 10 Hz of false stimulation on ipsilateral M1. A total of 135 seconds of stimulation was applied in the sham group and high-frequency group. At 2 weeks after treatment, cortical latency of motor-evoked potentials and central motor conduction time were significantly lower compared with before treatment. Moreover, motor function scores were significantly improved. The above indices for the low- and high-frequency groups were significantly different compared with the sham group. However, there was no significant difference between the low- and high-frequency groups. The results show that low- and high-frequency repetitive transcranial magnetic stimulation can similarly improve upper-limb motor function in patients with cerebral infarction.

Quality evaluation of peony seed oil spray-dried in different combinations of wall materials during encapsulation and storage.

This study aimed at evaluating the performance of peony seed oil microencapsulated by spray drying during encapsulation and storage. Four different combinations of gum arabic (GA), corn syrup (CS), whey protein concentrate (WPC) and sodium caseinate (CAS) were used to encapsulate peony seed oil. The best encapsulation efficiency was obtained for CAS/CS followed by the CAS/GA/CS combination with the encapsulation ratio of 93.71 and 92.80 %, respectively, while the lowest encapsulation efficiency was obtained for WPC/GA/CS (85.96 %). Scanning electron microscopy and confocal laser scanning microscopy revealed that the particles were spherical in shape and did not exhibit apparent cracks or fissures, and gum arabic was uniformly distributed across the wall of the microcapsules. Oxidative stability study indicated that the CAS/GA/CS combination presented the best protection against lipid oxidation and the smallest loss of polyunsaturated fatty acid content among all of the formulas as measured by gas chromatography. Therefore, CAS/GA/CS could be promising materials encapsulate peony seed oil with high encapsulation efficiency and minimal lipid oxidation.

Synergistic anti-tumor activity and mechanisms of total glycosides from Cimicifuga dahurica in combination with cisplatin.

OBJECTIVE: To determine the effect and mechanism of combination treatment of the total glycosides from Cimicifuga dahurica (TGCD) and cisplatin (CDDP) in vitro in human colon cancer cells (HCT-8) and in vivo in mouse hepatoma cells (H22)-bearing mice. METHODS: H22 tumor-bearing imprinting control region (ICR) mice were treated with TGCD, CDDP, and TGCD + CDDP for 10 days. Tumor volume and tumor weight were evaluated. TGCD and CDDP in different concentrations were added separately and in combination to cultures of different cancer cell lines, including the HCT-8. Effects of TGCD and CDDP on cell proliferation were detected by 3-(4,5-dimethyl-2-thiazole)-2-5-biphenly-tetrazole bromide (MTT) method and effects on cell apoptosis were tested by flfl ow cytometry and western blotting at 24 h after treatment. RESULTS: Combination index values (CI<0.8) suggested the synergistic effects of the TGCD + CDDP. This combination resulted in the highest increase in the percentage of apoptotic HCT-8 cells, caused cell cycle arrest in G2/M phase and increased expression of cleaved caspase-3, -8, and -9, Bax, phospho-c-Jun N-terminal kinase (p-JNK), and phospho-p38 mitogen-activated protein kinase (p-p38 MAPK), as well as decreased expression of Bcl-2, JNK, p38 MAPK, Poly (ADP-ribose) polymerase 1 (PARP1), caspase-3, and caspase-8 compared with single-agent treated and control groups. TGCD + CDDP treatment reduced tumor weight by 86.1%±7.2% compared with 64.5%±6.8% by CDDP or 46.9%±6.9% by the TGCD alone in vivo. CONCLUSIONS: TGCD enhanced the anticancer activity of CDDP in an additive-to-synergistic manner by activating multiple signaling pathways (including apoptosis). These fifi ndings suggest the potential benefifi t of combined treatment of the TGCD and CDDP against cancer of the colon and liver.

Optimization of liquid-state fermentation conditions for the glyphosate degradation enzyme production of strain Aspergillus oryzae by ultraviolet mutagenesis.

This study aimed to obtain strains with high glyphosate-degrading ability and improve the ability of glyphosate degradation enzyme by the optimization of fermentation conditions. Spore from Aspergillus oryzae A-F02 was subjected to ultraviolet mutagenesis. Single-factor experiment and response surface methodology were used to optimize glyphosate degradation enzyme production from mutant strain by liquid-state fermentation. Four mutant strains were obtained and named as FUJX 001, FUJX 002, FUJX 003, and FUJX 004, in which FUJX 001 gave the highest total enzyme activity. Starch concentration at 0.56%, GP concentration at 1,370 mg/l, initial pH at 6.8, and temperature at 30°C were the optimum conditions for the improved glyphosate degradation endoenzyme production of A. oryzae FUJX 001. Under these conditions, the experimental endoenzyme activity was 784.15 U/100 ml fermentation liquor. The result (784.15 U/100 ml fermentation liquor) was approximately 14-fold higher than that of the original strain. The result highlights the potential of glyphosate degradation enzyme to degrade glyphosate.

[Sijunzi Decoction Promote the Repair of Intestinal Epithelial Cell Injury via Activating TLR-2/My D88 Signaling Pathway].

Objective: To study the effect and mechanism of Sijunzi decoction( SJZD) containing serum on the repairing of gastrointestinal mucosal damage. Methods: SJZD containing serum was prepared by serum pharmacological method. Cell migration model was established by tips scratch method, Real-time-cell-analyzer( RTCA) was used to mensurate IEC-6 cell proliferation, the mRNA and protein expression of TLR-2 and My D88 mRNA were detected by qRT-PCR and Western blot analysis,respectively. Results: Medium dose( 10%) and high dose( 20%) of SJZD containing serum stimulated IEC-6 cell migration at 8 h after cell damage; medium dose( 10%)and high dose( 20%) of SJZD containing serum increased IEC-6 cell proliferation at 12 h after cell damage; low dose( 5%),medium dose( 10%) and high dose( 20%) of SJZD containing serum enhanced IEC-6 proliferation both at 24 h and 36 h after cell damage. Medium dose( 10%) and high dose( 20%) of SJZD containing serum upregulated TLR-2 and My D88 mRNA and protein expression,respectively. Conclusion: Sijunzi decoction can repair the injury of gastrointestinal mucosal barrier,the mechanism may be related to its effect on activating TLR-2 / My D88 signaling pathway,and promoting IEC-6 cell migration and proliferation.

[The Interaction of Oil Microcapsule Wall Materials between Whey Protein and Acacia].

The interaction between whey protein and acacia which were used as wall material was studied on the formation of the oils microcapsules by the FTIR Spectroscopy and Computer Aided Analysis. The results indicated that whey protein changed obviously in amide A and amide I by high pressured homogenization and spray-drying. The amide A moved from 3 406.5 cm(-1) to 3 425.4 cm(-1) which was possibly due to covalent cross-linking between whey protein and acacia. Furthermore the amide I moved from 1 648.6 cm(-1) to 1 654.7 cm(-1) for intramolecular hydrogen bonding of protein had been weaken. After Gaussian fitting on amide I , it was found that the content of secondary structure of α-helix content and ß-folding in whey protein reduced from 19.55% to 17.50% and from 30.59% to 25.63%, respectively. This suggests that protein intramolecular hydrogen bonding force was abated, resulting in abating the rigid structure of the protein molecules and enhancing of the toughness structure. The protein molecules showed some flexibility. The result of SDS-PAGE electrophoresis showed that whey protein--gum Arabic complexes produced covalent products in larger molecular weight. During the spray-drying process, covalent cross-linking produced between whey protein and gum Arabic which improved emulsifying activity of the complex whey protein and gum Arabic produced covalent cross-linking and improved the complex emulsifying activity. Observing the surface structure of the fish oil microcapsule by SEM, the compound of whey protein and acacia as wall material was proved better toughness, less micropore, and more compact structure.

Fetal pulmonary vascular remodeling in a rat model induced by hypoxia and indomethacin.

OBJECTIVE: This study sought to determine the effect of combined treatment of hypoxia plus indomethacin on pulmonary vascular remodeling in fetal rats. METHODS: Hypoxia and indomethacin were used to treat pregnant rats during 19-21 days of gestation. The adventitia, media, and intima of pulmonary arteries from fetal rats were assessed. Western blots were used for determining the abundance of smooth muscle specific alpha-actin protein (α-SMA), elastin, and endothelial nitric oxide synthase (eNOS) in lung tissues. Plasma brain-type natriuretic peptide (BNP) levels, reflecting the increased right ventricular load or pulmonary arterial pressure, were detected. RESULTS: The ratio of left ventricular free wall plus septum to right ventricular weight significantly increased in hypoxia plus indomethacin-treated group. The medial thickness percentage of pulmonary arteries of < 100 µm and ≥100 µm in diameter from hypoxia plus indomethacin-treated group was higher than that from control or single treatment group. Vascular elastin area percentage and immunostaining density of eNOS from the combined-treated group were higher than other groups. The relative abundance of α-SMA, elastin, and eNOS and plasma BNP levels in hypoxia plus indomethacin-treated group also significantly increased compared with other groups. CONCLUSIONS: Hypoxia and indomethacin had synergistic effect on fetal pulmonary vascular remodeling. This rat model induced by combined treatments can mimic human persistent pulmonary hypertension of the newborn.