Bile acids (BA) are liver derived compounds that undergo host and microbial metabolism. BA metabolites have multiple physiological roles including maintaining intestinal immune homeostasis. Dietary ...components influence BA metabolism/excretion through several mechanisms. This study aimed to evaluate the effects of daily strawberry intake (4 weeks) on bile acid metabolism in humans.
Thirty overweight/obese adults (age: 53 ± 7 years, BMI: 31 ± 4 kg/m2) were recruited for this randomized, double-blind, placebo-controlled, crossover trial. Participants were randomized to 1 of 2 study sequences in a 1:1 ratio with 4 weeks washout period between two treatments. Participants consumed a strawberry beverage containing 25 g freeze-dried strawberry powder (∼1.75 servings of fresh strawberries) or energy-matched control beverage in random order twice a day for 4 weeks. Fasting blood samples were collected at weeks 0, 4, 8, and 12. Plasma samples (500 μL) were extracted using solid-phase C18 cartridges. An ultra-high performance liquid chromatography tandem mass spectrometry method was developed to quantitate bile acids and their metabolites (sulfates, glucuronides) in plasma. The method was validated in terms of linearity, sensitivity, recovery, and matrix effect. The data were analyzed using a paired student t-test with statistical significance set at P < 0.05.
Twenty-nine glucuronidated and sulfated BAs were identified in plasma samples. Concentrations of primary BAs were not affected between the study treatments, whereas a significant decrease (P < 0.05) was observed in total secondary BAs (52 compounds) after 4 weeks of strawberry intake (11.2 ± 1.1 μmol/L) compared to placebo (18.3 ± 3.2 μmol/L). Individual secondary BAs including lithocholic acid (LCA), sulfo-glycolithocholic acid, and C24 oxidized LCA were significantly decreased after 4-week strawberry intake compared to placebo (P < 0.05).
Our results indicate that regular strawberry intake could lower pro-inflammatory LCA and other secondary BAs, suggesting a potential role of strawberry in ameliorating colonic inflammation and promoting gut health.
This work was funded by the California Strawberry Commission and various donor funds to the Center for Nutrition Research, IIT.
•We report a BODIPY-based turn-on fluorescent bisphenol A sensor.•We tested the superior selectivity toward BPA against several bisphenol analogs and phenol.•We demonstrated the stability and ...robustness of this probe for analyzing BPA in real, complex water samples.
Due to the prevalent use of polycarbonate plastics and epoxy resins in packaging materials and paints for ships, there has been a widespread global contamination of environmental water sources with bisphenol A (BPA). BPA, an endocrine disruptor, has been found to cause tremendous health problems. Therefore, there is an urgent need for detecting BPA in a convenient and sensitive manner to ensure water safety. Herein, we develop a fluorescent turn-on BPA probe, named Bisphenol Orange (BPO), which could conveniently detect BPA in a wide variety of real water samples including sea water, drain water and drinking water. BPO shows superior selectivity toward BPA and up to 70-fold increase in fluorescence emission at 580nm when mixed with BPA in water. Mechanistic studies suggest a plausible water-dependent formation of hydrophobic BPA clusters which favorably trap and restrict the rotation of BPO and recover its inherent fluorescence.
Background
Clinical rejection (CR) defined as decision to treat clinically suspected rejection with change in immunotherapy based on clinical presentation with or without diagnostic biopsy findings ...is an important part of care in heart transplantation. We sought to assess the utility of donor fraction cell‐free DNA (DF cfDNA) in CR and the utility of serial DF cfDNA in CR patients in predicting outcomes of clinical interest.
Methods
Patients with heart transplantation were enrolled in two sequential, multi‐center, prospective observational studies. Blood samples were collected for surveillance or clinical events. Clinicians were blinded to the results of DF cfDNA.
Results
A total of 835 samples from 269 subjects (57% pediatric) were included for this analysis, including 28 samples associated with CR were analyzed. Median DF cfDNA was 0.43 (IQR 0.15, 1.36)% for CR and 0.10 (IQR 0.07, 0.16)% for healthy controls (p < .0001). At cutoff value of 0.13%, the area under curve (AUC) was 0.82, sensitivity of 0.86, specificity of 0.67, and negative predictive value of 0.99. There was serial decline in DF cfDNA post‐therapy, however, those with cardiovascular events (cardiac arrest, need for mechanical support or death) showed significantly higher levels of DF cfDNA on Day 0 (2.11 vs 0.31%) and Day 14 (0.51 vs 0.22%) compared to those who did not have such an event (p < .0001).
Conclusion
DF cfDNA has excellent agreement with clinical rejection and, importantly, serial measurement of DF cfDNA predict clinically significant outcomes post treatment for rejection in these patients.
Zebrafish is a popular animal model for research on eye development because of its rapid ex utero development and good fecundity. By 3 days post fertilization (dpf), the larvae will show the first ...visual response. Many genes have been identified to control a proper eye development, but we are far from a complete understanding of the underlying genetic architecture. Whole genome gene expression profiling is a useful tool to elucidate genetic regulatory network for eye development. However, the small size of the embryonic eye in zebrafish makes it challenging to obtain intact and pure eye tissues for expression analysis. For example, the anterior-posterior length of the eye between day 2 and 3 is only approximately 200-300 microm, while the diameter of the lens is less 100 microm. Also, the retinal pigment epithelium (RPE) underlying the retina is just a single-layer epithelium. While gene expression profiles can be obtained from the whole embryo, they do not accurately represent the expression of these tissues. Therefore pure tissue must be obtained for a successful gene expression profiling of eye development. To address this issue, we have developed an approach to microdissect intact retina and retina with RPE attached from 1-3 dpf, which cover major stages of eye morphogenesis. All procedures can be done with fine forceps and general laboratory supplies under standard stereomicroscopes. For retinal dissection, the single-layer RPE is removed and peeled off by brushing action and the preferential adherence of the RPE remnants to the surface of the culture plate for dissection. For RPE-attached retinal dissection, the adherence of RPE to the dissection plate is removed before the dissection so that the RPE can be completely preserved with the retina. A careful lifting action of this tissue can efficiently separate the presumptive choroid and sclera. The lens can be removed in both cases by a chemically etched tungsten needle. In short, our approach can obtain intact eye tissues and has been successfully utilized to study tissue-specific expression profiles of zebrafish retina and retinal pigment epithelium.
It is well known that angiotensin-(1–7) (Ang-(1–7)) counterbalances vasoconstrictive and proliferative functions of angiotensin II (Ang II), some of those actions are via inhibition of Ang II induced ...activation of mitogen-activated protein kinases(MAPK). This study investigated the effects of Ang-(1–7) on Ang II-mediated cell signaling pathways in mouse bone marrow-derived dendritic cells (DC). The expression of receptor Mas and angiotensin-converting enzyme-related carboxypeptidase (ACE2) mRNA was examined by reverse transcription-polymerase chain reaction (RT-PCR); activation of MAPK was detected by immunoblotting after incubation of dendritic cells with Ang II in the presence or absence of Ang-(1–7), valsartan, PD123319, and
d-Ala
7-Ang-(1–7). Ang II rapidly (5
min, 10
−7
mol/L) stimulated phosphorylation of extracellular signal-related kinase (ERK1/2); this effect was partially inhibited by Ang II type 1 (AT1) receptor antagonist valsartan and significantly attenuated by Ang II type 2 (AT2) receptor antagonist PD123319. Ang-(1–7) alone also induced phosphorylation of ERK1/2; co-treatment of Ang-(1–7) and Ang II markedly enhanced ERK1/2 phosphorylation, the enhancement was eliminated by the Ang-(1–7) receptor antagonist
d-Ala
7-Ang-(1–7). Both Ang-(1–7) and Ang II had no effect on p38 and c-Jun N-terminal kinase (JNK) phosphorylation. In conclusion, Ang II stimulates ERK1/2 phosphorylation via AT2 receptor in mouse DC, Ang-(1–7) enhances this effect. Generation of Ang-(1–7) by DC could thereby counteract on the pro-inflammatory function of locally generated Ang II.
Background
To determine prevalence, clinical implication, and risk factors for aortic root dilation (ARD) in pediatric heart transplant recipients.
Methods
Serial echocardiograms were reviewed in all ...pediatric heart transplant recipients from 1999 to 2014 to assess maximal systolic diameter at the aortic annulus, aortic sinus, aortic sino‐tubular (ST) junction, and ascending aorta. ARD was defined by a sinus/annulus ratio >1.56, ST junction/annulus ratio >1.28, and/or ascending aorta/annulus ratio >1.35.
Results
A total of 147 subjects (53% male) were evaluated; 50% had congenital heart disease (CHD). Of the 74 with CHD, 38 had prior aortic arch reconstruction. The median age at transplant was 3 years (7 days–20.3 years) with a median duration of follow‐up of 3.88 years (3 months–15 years). Prevalence of ARD significantly increased in the cohort from 15.6% at the initial echocardiogram to 49.6% at later follow‐up (P<.0001). The median duration to development of ARD was 7.6 months. There were no significant differences in prevalence of ARD or days to maximum ratio based on the pretransplant diagnosis. Aortic regurgitation was very rare (7 with ≤mild) and did not correlate with ARD or require any interventions.
Conclusion
During intermediate follow‐up, ARD commonly develops in children post–heart transplant, and prevalence increases with time after transplant. Within 1 year after transplant, almost 50% had developed abnormalities in aortic root size that were not apparent at the initial posttransplant echocardiogram. Preexisting CHD or need for prior arch reconstruction did not increase the risk of ARD.
While a number of machine learning (ML) models have been used to estimate RE, systematic evaluation and comparison of these models are still limited. In this study, we developed three traditional ML ...models and a deep learning (DL) model, stacked autoencoders (SAE), to estimate RE in northern China’s grasslands. The four models were trained with two strategies: training for all of northern China’s grasslands and separate training for the alpine and temperate grasslands. Our results showed that all four ML models estimated RE in northern China’s grasslands fairly well, while the SAE model performed best (R2 = 0.858, RMSE = 0.472 gC m−2 d−1, MAE = 0.304 gC m−2 d−1). Models trained with the two strategies had almost identical performances. The enhanced vegetation index and soil organic carbon density (SOCD) were the two most important environmental variables for estimating RE in the grasslands of northern China. Air temperature (Ta) was more important than the growing season land surface water index (LSWI) in the alpine grasslands, while the LSWI was more important than Ta in the temperate grasslands. These findings may promote the application of DL models and the inclusion of SOCD for RE estimates with increased accuracy.
•We observed the new VR bands of V1044 Her on May 22, 23 and 24, 2015.•Photometric orbital parameters and starspot parameters of V1044 Her are derived.•The orbital period of V1044 Her exists a cyclic ...variation.•The cyclic variation of V1044 Her can caused by LITF or magnetic cyclic
We present new CCD photometric observations of V1044 Her obtained on May 22, 23 and 24, 2015. From our data, we derived five new light curve minimum times. Combining our new results with previously available CCD light minimum times, we derived an updated ephemeris and discovered that the period of this binary system exhibits an oscillation. The cyclic variation may be caused by the light-time effect via the presence of a third body or magnetic activity cycle. We calculated the corresponding period of the third body to be 14.1 ± 1.4 years or magnetic cycle to be 12.2 ± 0.7 years. We analyzed our new asymmetric light curves to obtain photometric solutions and starspot parameters using the Wilson and Devinney program. The final results show that V1044 Her is a contact binary system with a degree of contact factor f = 3.220( ± 0.002)%.
To assess the association of single nucleotide polymorphisms (SNPs) of endotheline receptor gene with the severity of coronary heart disease (CHD).
A total of 553 CHD patients, including 324 patients ...with mult-vessel disease based on result of selected coronary angiography, and 553 age- and sex-frequency matched controls were selected. Clinical data were collected. Genotypes of rs501120, rs899997, rs1878406 and rs7173743 were determined with TaqMan-MGB probes.
The distribution of genotypes of the 4 SNPs showed no significant difference between the two groups. However, the frequency of A allele of rs501120 and T allele of rs1878406 were significantly higher in the CHD group compared with the control group (P< 0.05). For rs7173743 and rs899997, no significant difference was detected between the two groups. After adjusting for conventional risk factors by logistic regression analysis, the results suggested that the distribution of rs1878406 TT+TC genotype in severe multi-vessel disease group is significantly hig
Transforming growth factor alpha (TGFα) belongs to the epidermal growth factor (EGF) family and is known to play an important role during eyelid morphogenesis. In this study, we showed that ectopic ...expression of TGFα in the stroma of Kera-rtTA/tet-O-TGFα bitransgenic mice results in precocious eye opening, abnormal morphogenesis of the meibomian gland, tendon and tarsal plate malformation and epithelium hyperplasia. TGFα did not change proliferation and differentiation of meibocytes, but promoted proliferation and inhibited differentiation of the tarsal plate tenocytes. These results suggest that proper formation of the tendon and tarsal plate in the mouse eyelid is required for normal morphogenesis of the meibomian gland.
•Kera-rtTA/tet-O-TGFα (KR/TG) mice were generated and induced to overexpress TGFα in eyelid stroma.•Eyelid morphogenesis is perturbed in KR/TG mice.•TGFα affect proliferation apoptosis and differentiation of the tendon and tarsal plate tenocytes but not meibomian gland epithelial cells.•Preliminary mechanism of tenocytes hyperplasia by excess TGFα.
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