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1.
J Am Chem Soc ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32049531

RESUMO

The ubiquitous biomembrane interface, with its dynamic lateral fluidity, allows membrane-bound components to rearrange and localize for high-affinity multivalent ligand-receptor interactions in diverse life activities. Inspired by this, we herein engineered a fluidic multivalent nanointerface by decorating a microfluidic chip with aptamer-functionalized leukocyte membrane nanovesicles for high-performance isolation of circulating tumor cells (CTCs). This fluidic biomimetic nanointerface with active recruitment-binding affords significant affinity enhancement by four orders of magnitude, exhibiting 7-fold higher capture efficiency compared to a monovalent aptamer functionalized-chip in blood. Meanwhile, this soft nanointerface inherits the biological benefits of a natural biomembrane, min-imizing background blood cell adsorption and maintaining excellent CTC viability (97.6%). Using the chip, CTCs were successfully detected in all cancer patient samples tested (17/17), suggesting the high potential of this fluidity-enhanced multivalent strategy in clinical applications. We expect this bioengineered interface strategy will lead to the design of innovative biomimetic platforms in the biomedical field by leveraging natural cell-cell interaction with a natural biomaterial.

2.
Cytogenet Genome Res ; 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32036363

RESUMO

This study aims to investigate the value of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in fetuses with increased nuchal translucency (defined as NT above the 95th centile for the crown-rump length). A total of 374 singleton pregnancies with gestational ages ranging from 11 to 13 + 6 weeks were investigated. Ultrasound displayed increased NT and no detectable structural malformations in these fetuses. Pregnancies were divided into 4 groups according to the NT values: 95th centile-3.4 mm (114 cases); 3.5-4.4 mm (150 cases); 4.5-5.4 mm (55 cases); and ≥5.5 mm (55 cases). The possible chromosomal anomalies were all analyzed by CMA first. Furthermore, 24 cases with increased NT but negative CMA results were investigated by WES, and the outcomes were followed up. Among all the 374 cases, causative genetic defects were detected in 100/374 (26.7%) of the cases along with 9 variants of unknown significance (VOUS) by CMA. CMA testing yielded 30 pathogenic variants (30/55), accounting for a detection rate of 54.5%, and 1 VOUS in the group of NT ≥5.5 mm, indicating the highest detection rate in the 4 groups. The 24 cases of the CMA negative sub-cohort with WES analysis further yielded 2 VOUS and 3 likely pathogenic variants, including 2 dominant de novo mutations in SOS1 and ECE1 and 1 recessive inherited compound heterozygous mutation in PIGN, which are associated with cardiac defects. All 3 cases opted for termination of pregnancy (TOP). In addition, 2 cases with increased NT were negative by both CMA and WES analysis, and fetal demise occurred. In conclusion, for the investigation of fetuses with increased NT exome sequencing is suggested to be considered in cases with negative CMA findings. However, appropriate genetic counseling should be given to optimizing its utilization in prenatal diagnosis.

3.
Breast Cancer ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-32030658

RESUMO

BACKGROUND: To date, anatomic tumor length is a key criterion for cancer staging and can be used to evaluate the effectiveness of therapies. This article describes growth pattern that can be used as a new characteristic to represent disease burden and tumor features and predict lymphatic metastasis. METHODS: Patients with breast cancer were included in this 10-year (1999-2008) hospital-based multicenter retrospective study. The pathologic length/height ratio was used to illustrate the correlation between tumor features, behaviors and treatments in breast malignancies. The most appropriate ratio was chosen based on the comprehensive evaluation of p value and changing trend of each characteristic. RESULTS: The sample consisted of 4211 women diagnosed with breast cancer. Among them, 2037 patients with complete pathologic length, width and height information were included in the final analysis. There were 2.34 ± 4.77 metastatic lymph nodes for spheroid tumors and 3.21 ± 5.82 for ellipsoid tumors when the cutoff point was 2. In addition, the proportion of ellipsoidal tumors gradually increased from 54.36 to 56.67% in the upper outer quadrant (UOQ) and from 6.7 to 9.03% in the central region with an increase in the cutoff point. The proportion of ER + PR + ellipsoid tumors significantly decreased from 50.1 to 45.35% and that of ER-PR ellipsoid tumors significantly increased from 32.73 to 36.24% with an increase in the cutoff point. Additionally, the best length/weight ratio to distinguish spheroid and ellipsoid tumors was 2. CONCLUSION: This study described for the first time how growth pattern is correlated with tumor malignancy and how it influences the selection of therapeutic strategies for patients.

4.
Food Chem ; 312: 126084, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31901820

RESUMO

The pit mud (PM) prokaryotic communities with obvious difference between old and young PM is essential for solid-fermentation of Chinese Strong-Flavor Baijiu. The bottom-PM (BPM) is considered more important. In this study, the multidimensional prokaryotic communities of old and young BPMs were investigated. The old BPM presented stratified difference within the depth of 0-7 cm, especially, the surface 0-1 cm was characteristic of dominant Caproiciproducens (34.79%). The young BPM showed significant difference between quarter/center and deep corner (1-7 cm), the former were characteristic of abundant Lactobacillus (12.80%-42.72%), while the deep corner was distinctive of dominant Caproiciproducens (17.85%-64.45%). The lactic acid, pH and soluble Ca2+ were considered as the 3 most significant environmental factors through redundancy analysis (RDA). This study may help illuminate the BPM aging process, and allow the future artificial regulation of young BPM.

5.
Cell Rep ; 30(4): 1235-1245.e4, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31995761

RESUMO

DNA-protein crosslinks (DPCs) are a frequent form of DNA lesion and are strongly inhibitive in diverse DNA transactions. Despite recent developments, the biochemical detection of DPCs remains a limiting factor for the in-depth mechanistic understanding of DPC repair. Here, we develop a sensitive and versatile assay, designated ARK, for the quantitative analysis of DPCs in cells. ARK uses sequential chaotropic and detergent-based isolation of DPCs and substantially enhances sample purity, resulting in a 5-fold increase in detection sensitivity and a 10-fold reduction in background reading. We validate the ARK assay with genetic mutants with established deficiencies in DPC repair and demonstrate its robustness by using common DPC-inducing reagents, including formaldehyde, camptothecin, and etoposide. In addition, we show that the Fanconi anemia pathway contributes to the repair of DPCs. Thus, ARK is expected to facilitate various studies aimed at understanding both fundamental biology and translational applications of DNA-protein crosslink repair.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31991885

RESUMO

This large-scale study aimed to test, among Chinese adolescents, the association between problematic Internet use (PIU), non-medical use of prescription drugs (NMUPD), and depressive symptoms, as well as the mediating effects of NMUPD on the associations above. This study used the data from the 2017 National School-based Chinese Adolescents Health Survey, and 24,345 students' questionnaires qualified for the analyses. Generalized linear mixed models and path models were performed. In the models without mediation, PIU was associated with depressive symptoms (unstandardized ß estimate = 0.26, 95% CI = 0.25-0.27); frequent use of opioid or sedative was also related to depressive symptoms (unstandardized ß estimate for opioid = 2.77, 95% CI = 1.90-3.63; unstandardized ß estimate for sedative = 4.45, 95% CI = 3.02-5.88). Additionally, the results of the path models indicated that opioid misuse partially mediated the association between PIU and depressive symptoms. PIU and opioid/sedative misuse were related to the increased risk of depressive symptoms, respectively. The association above might be complicated, and PIU may elevate the risk of opioid or sedative misuse and depressive symptoms, which in turn could worsen the situation of PIU and vice versa. Multidisciplinary health intervention programs to prevent adolescents involving in PIU, as well as NMPUD, are recommended to be provided.

7.
Sleep Breath ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898191

RESUMO

OBJECTIVES: To examine the efficacy of a 24-week Baduanjin exercise program on self-reported sleep quality and quality of life in community-dwelling elderly subjects with sleep disturbances. METHODS: Community-dwelling elderly men and women meeting criteria for sleep disturbances (i.e., Pittsburgh Sleep Quality of Index (PSQI) score ≥ 5) were recruited and randomized to a Baduanjin exercise intervention group or a control group. Participants in the intervention group completed five 45-min exercise sessions per week for 24 weeks, while those in control group were instructed to maintain their usual lifestyle behaviors. RESULTS: A total of 139 participants were enrolled and randomized. Sixty-two of 67 participants in the intervention group (response rate of 92.5%) and 57 of 72 participants (response rate of 79.6%) in the control group completed intervention and follow-up. The intervention group reported significant improvements in overall sleep quality after 24 weeks compared with those randomized to control (PSQI endpoint-to-baseline change = - 2.6 ± 4.0 vs. - 0.5 ± 4.2, time × group interaction p = 0.007). Intervention group participants had higher response rates at both week 12 (23.9% vs. 9.7%, p = 0.025) and week 24 (40.3% vs. 15.3%, p = 0.001) when compared with the control group. There was a trend that the intervention group had increased quality of life (The Short Form Health Survey [SF-36] endpoint=tobaseline change 6.3 ± 10.9 vs. 2.2 ± 10.9, time × group interaction p = 0.06) when compared with the control group. CONCLUSIONS: Baduanjin exercise is an effective and feasible approach to improve self-reported sleep quality but less likely the quality of life in community-dwelling elderly men and women with sleep disturbances. TRIAL REGISTRATION: Effect of Baduanjin Exercise on the Elderly's Sleep; http://www.chictr.org.cn/listbycreater.aspx; ChiCTR1800014706, registered 1 January 2018.

8.
Mol Cell Proteomics ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900314

RESUMO

Adenosine monophosphate-activated protein kinase (AMPK) is an obligate heterotrimer that consists of a catalytic subunit (α) and two regulatory subunits (ß and γ). AMPK is a key enzyme in the regulation of cellular energy homeostasis. It has been well studied and is known to function in many cellular pathways. However, the interactome of AMPK has not yet been systematically established, although protein-protein interaction is critically important for protein function and regulation. Here, we used tandem-affinity purification, coupled with mass spectrometry (TAP-MS) analysis, to determine the interactome of AMPK and its functions. We conducted a TAP-MS analysis of all seven AMPK subunits. We identified 138 candidate high-confidence interacting proteins(HCIPs) of AMPK, which allowed us to build an interaction network of AMPK complexes. Five candidate AMPK-binding proteins were experimentally validated, underlining the reliability of our dataset. Furthermore, we demonstrated that AMPK acts with a strong AMPK-binding protein, Artemis, in non-homologous end joining. Collectively, our study established the first AMPK interactome and uncovered a new function of AMPK in DNA repair.

9.
Nanotechnology ; 31(16): 165707, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-31899897

RESUMO

The core-shell CeO2:Er,Yb@W18O49 heterojunction is successfully synthesized via the facile solvothermal method. The octahedral CeO2:Er,Yb nanocrystal's core exhibits green (2H11/2, 4S3/2 â†’ 4I15/2), red (4F9/2 â†’ 4I15/2) and NIR (4I11/2 â†’ 4I15/2 and 4I13/2 â†’ 4I15/2) emission under 980 nm laser diode excitation, and the multiband emissions are absorbed by the W18O49 nanowire's shell, re-exciting its higher energy localized surface plasmon resonances (LSPR). With the excitation of 980 nm, the photocatalytic property of CeO2:Er,Yb@W18O49 for hydrogen (H2) evolution from ammonia borane (BH3NH3), a three-fold increase compared to W18O49, is researched. The application of natural sunlight for the production of H2 is studied, and an obvious H2 production enhancement compared to the use of W18O49 (two-fold) is also observed. This remarkable enhancement in the catalytic activity of CeO2:Er,Yb@W18O49 heterostructures is ascribed to the re-excitation of LSPR by multiband emissions of CeO2:Er,Yb.

10.
J Trace Elem Med Biol ; 59: 126470, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31958698

RESUMO

BACKGROUND: Metabolic disorders of glucose and lipid were associated with some mineral elements, and data were warranted from various contexts to make the association more explicit. OBJECTIVE: To investigate the relationships between the serum concentrations of six mineral elements (calcium, cobalt, copper, iron, magnesium, and selenium) and the risk of hyperglycemia and dyslipidemia in adults. METHODS: The basic information and the over-night fasting serum samples of adults were randomly collected at a health examination center. The serum concentrations of glucose and lipids were measured with an automatic biochemical analyzer, and the mineral elements were measured with an inductively coupled plasma mass spectrometer. Data were analyzed between the hyperglycemia group (HGg) and the normal glucose group (NGg) as well as between the dyslipidemia group (DLg) and the normal lipid group (NLg). RESULTS: A total of 1466 adults aged 22-81 years (male/female = 1.8) were included, 110 in the HGg and 1356 in the NGg, or 873 in the DLg and 593 in the NLg. The serum element concentration medians [P50 (P25-P75)] significantly different between the HGg and the NGg were 0.83 (0.75-0.94) vs. 0.76 (0.68-0.87) mg/L for copper and 100 (90-110) vs. 94 (87-103) µg/L for selenium (P < 0.001), while those between the DLg and the NLg were 99 (92-110) vs. 97 (90-106) mg/L for calcium, 0.78 (0.69-0.88) vs. 0.75 (0.66-0.85) mg/L for copper, 1.7 (1.4-2.0) vs. 1.6 (1.3-2.0) mg/L for iron, 24 (22-28) vs. 23 (22-27) mg/L for magnesium, and 97 (89-106) vs. 92 (84-100) µg/L for selenium (P < 0.05). When the copper and selenium between the HGg and the NGg were analyzed by logistic regression with age, gender, body mass index, and mineral elements adjusted, only the highest quartile of selenium concentration had association with the increased risk of hyperglycemia [quartile (Q) 4 against Q1: OR = 2.9, 95 % CI = 1.5-5.5, P < 0.001). When the five differed mineral elements between the DLg and the NLg were similarly analyzed, only iron and selenium had associations with the increased risk of dyslipidemia (e.g., Q4 against Q1: OR = 1.4, 95 % CI = 1.1-2.0 for iron and OR = 2.9, 95 % CI = 2.1-4.0 for selenium, P < 0.05). CONCLUSION: In contrast to those of calcium, cobalt, copper, iron, and magnesium, the higher serum concentration of selenium increased the risk of both hyperglycemia and dyslipidemia in the study population of adult Chinese.

11.
Int J Pharm ; 576: 119027, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31953090

RESUMO

We developed a safe and efficacious drug delivery system for treatment of brain diseases. A novel in-situ gel system was prepared using soybean oil, stearic acid and N-methyl-2-pyrrolidinone (NMP) (10:1:3, v/w/v). This system had low viscosity as a sol in vitro and turned into a solid or semi-solid gel in situ after administration. The poorly water-soluble drug flunarizine hydrochloride (FNZ) was incorporated into this "organogel" system. Organogel-FNZ was characterized by light microscopy, differential scanning calorimetry (DSC) and rheology. Drug release in vitro was investigated. The initial "burst" effect did not occur in organogel-FNZ, which is different from other gels formed in situ. Pharmacokinetic studies were undertaken in rats using gel administration (14 mg kg-1), intravenous administration (5 mg kg-1) and administration using drops (14 mg kg-1). Organogel-FNZ could reduce the clearance rate and prolong the duration of action, in the plasma and brain tissues of rats. The peak serum concentration, area under the curve and absolute bioavailability of the organogel-FNZ group were higher than those of the intraocular- drops group. Organogel-FNZ is a promising drug-delivery system for treatment of brain diseases by intraocular administration.

12.
J Cell Biochem ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31904151

RESUMO

Although many methods and new therapeutic drugs have been developed, the overall survival rate and long-term survival rate of patients with gastric cancer (GC) are still not satisfactory. In this study, we investigated the effects of microRNA miR-133a-3p and transcription factor FOXP3 on proliferation and autophagy of GC cells and their interactions. Our results showed that knockdown of FOXP3 increased the proliferation and autophagy of GC cells. The relationship between FOXP3 and autophagy has not been reported previously. In addition, FOXP3 could directly bind the promoter region of TP53 and inhibit its expression. miR-133a-3p increased the proliferation and autophagy via decreasing the protein level of FOXP3 by targeting its 3'-UTR. Our research provides new insights into the development of GC and provides new ideas and theoretical basis for the clinical treatment of GC and the development of new drug targets.

13.
Appl Microbiol Biotechnol ; 104(1): 77-100, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31776606

RESUMO

Sophorolipids (SLs), mainly synthesized by yeasts, were a sort of biosurfactant with the highest fermentation level at present. In recent years, SLs have drawn extensive attention for their excellent physiochemical properties and physiological activities. Besides, issues such as economics, sustainability, and use of renewable resources also stimulate the shift from chemical surfactants towards green or microbial-derived biosurfactants. SLs' large-scale production and application were restricted by the relatively high production costs. Currently, waste streams from agriculture, food and oil refining industries, etc., have been exploited as low-cost renewable substrates for SL production. Advanced cultivation method, uncommonly used substrates, and new genetically modified SL-producing mutants were also designed and applied to improve the productivity or the special properties of SLs. In this review, a systematic and detailed description of primary and secondary metabolism pathways involved in SL biosynthesis was summarized firstly. Furthermore, based on the pathways of SL biosynthesis from different carbon substrates, we reviewed the current knowledge and advances in the exploration of cost-effective and infrequently used hydrophilic and hydrophobic substrates for large or specialized SL production.

14.
Anal Chem ; 92(1): 1582-1588, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31815436

RESUMO

Bispecific antibodies (BsAbs) have drawn increasing interest in the biopharmaceutical industry due to their advantage to bind two distinct antigens simultaneously. The knob-into-hole approach is an effective way to produce bispecific antibodies by driving heterodimerization with mutations in the CH3 domain of each half antibody. To better understand the conformational impact by the knob and hole mutations, we combined size-exclusion chromatography (SEC), differential scanning calorimetry (DSC), and hydrogen-deuterium exchange mass spectrometry (H/D exchange MS), to characterize the global and peptide-level conformational changes. We found no significant alteration in structure or conformational dynamics induced by the knob-into-hole framework, and the conformational stability is similar to the wild-type (WT) IgG4 molecules (except for some small difference in the CH3 domain) expressed in E. coli. Functional studies including antigen-binding and neonatal fragment crystallizable (Fc) receptor (FcRn) binding demonstrated no difference between the knob-into-hole and WT IgG4 molecules in E. coli.

15.
Plant Cell Environ ; 43(1): 261-274, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31674679

RESUMO

Iron (Fe) is an essential micronutrient for plant growth development and plays a key role in regulating numerous cellular processes. In rice, OsHRZ1, an Fe-binding ubiquitin ligase, is a putative sensor of Fe homeostasis that negatively regulates iron acquisition. Despite its apparent importance, only a single basic-Helix-Loop-Helix (bHLH) transcription factor, OsPRI1, has been identified as a direct target of OsHRZ1. In this study, we identified and functionally characterized OsPRI2 and OsPRI3, two paralogs of OsPRI1, observing that they directly interact with OsHRZ1. Additional analyses suggested that OsHRZ1 promotes the degradation of OsPRI2 and OsPRI3. The translocation of Fe from roots to shoots was impaired in plants with loss-of-function mutations in OsPRI2 or OsPRI3, causing the downregulation of Fe-deficiency-responsive genes. In contrast, overexpression of OsPRI2 and OsPRI3 promotes Fe accumulation and activates the expression of Fe-deficiency-responsive genes. We also provide evidence that OsPRI2 and OsPRI3 bind to the promoters of OsIRO2 and OsIRO3, two key regulators of Fe homeostasis. Moreover, OsPRI2 and OsPRI3 directly induce expression of the metal-nicotianamine transporter, OsYSL2, by associating with the promoter in response to Fe deficiency. Our results provide insights into the complex network regulating Fe homeostasis in rice.

16.
Chemistry ; 26(5): 1091-1102, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31743947

RESUMO

Spin-orbit charge-transfer intersystem crossing (SOCT-ISC) is useful for the preparation of heavy atom-free triplet photosensitisers (PSs). Herein, a series of perylene-Bodipy compact electron donor/acceptor dyads showing efficient SOCT-ISC is prepared. The photophysical properties of the dyads were studied with steady-state and time-resolved spectroscopies. Efficient triplet state formation (quantum yield ΦT =60 %) was observed, with a triplet state lifetime (τT =436 µs) much longer than that accessed with the conventional heavy atom effect (τT =62 µs). The SOCT-ISC mechanism was unambiguously confirmed by direct excitation of the charge transfer (CT) absorption band by using nanosecond transient absorption spectroscopy and time-resolved electron paramagnetic resonance (TREPR) spectroscopy. The factors affecting the SOCT-ISC efficiency include the geometry, the potential energy surface of the torsion, the spin density for the atoms of the linker, solvent polarity, and the energy matching of the 1 CT/3 LE states. Remarkably, these heavy atom-free triplet PSs were demonstrated as a new type of efficient photodynamic therapy (PDT) reagents (phototoxicity, EC50 =75 nm), with a negligible dark toxicity (EC50 =78.1 µm) compared with the conventional heavy atom PSs (dark toxicity, EC50 =6.0 µm, light toxicity, EC50 =4.0 nm). This study provides in-depth understanding of the SOCT-ISC, unveils the design principles of triplet PSs based on SOCT-ISC, and underlines their application as a new generation of potent PDT reagents.

17.
J Chem Phys ; 151(21): 214308, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31822095

RESUMO

We employ few-cycle pulses to strong-field-ionize di-iodomethane (CH2I2) and femtosecond extreme ultraviolet (XUV) transient absorption spectroscopy to investigate the subsequent ultrafast dissociative ionization and vibrational wave packet dynamics. Probing in the spectral region of the I 4d core-level transitions, the time-resolved XUV differential absorption spectra reveal the population of several electronic states of CH2I2 + by strong-field ionization. Global analysis reveals three distinct time scales for the observed dynamics: 20 ± 2 fs, 49 ± 6 fs, and 157 ± 9 fs, ascribed to relaxation of the CH2I2 + parent ion from the Franck-Condon region, dissociation of high-lying excited states of CH2I2 + to I+ (3P2), CH2I, and I2 + (2Π3/2,g), and dissociation of CH2I2 + to I (2P3/2) and CH2I+, respectively. Oscillatory features in the time-resolved XUV differential absorption spectra point to the generation of vibrational wave packets in both the residual CH2I2 and the CH2I2 + parent ion. Analysis of the oscillation frequencies and phases reveals, in the case of neutral CH2I2, C-I symmetric stretching induced by bond softening and I-C-I bending driven by a combination of bond softening and R-selective depletion. In the case of CH2I2 +, both the fundamental and first overtone frequencies of the I-C-I bending mode are observed, indicating large-amplitude I-C-I bending motion, in good agreement with results obtained from ab initio simulations of the XUV transition energy along the I-C-I bend coordinate. These results show that femtosecond XUV absorption spectroscopy is well-suited for studying ultrafast photodissociation and vibrational wave packet dynamics.

18.
Food Funct ; 10(12): 7900-7912, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31789332

RESUMO

Hyperuricemia (HUA) is a metabolic disorder that occurs due to the overproduction or under-excretion of uric acid (UA) and is directly linked to the development of many life-threatening diseases. There is a growing interest among many researchers regarding how to overcome the encumbrance of HUA because conventional drugs are associated with multiple side effects. Thus, the present project has been designed to utilize flavonoids and chlorogenic acid-enriched stevia residue extract (STVRE) to combat HUA. The results show that supplementation with STVRE (200 and 400 mg per kg bw) inhibits the XOD enzyme in serum, duodenum, jejunum, and ileum tissues. Moreover, UA levels in the STVRE groups were also significantly (p < 0.05) decreased in serum, duodenum, jejunum, and ileum tissues and juices. STVRE also improved the intestinal morphology and oxidative biomarkers in duodenum, jejunum, and ileum tissues. Protein and mRNA expressions of ABCG2 were upregulated, whereas GLUT9 was downregulated in the STVRE-treated groups as compared with the model control group. The supplementation of STVRE significantly attenuated hyperuricemia and oxidative stress, upregulated ABCG2 and downregulated GLUT9 (protein and mRNA) expression in hyperuricemic mice. The results of our study revealed that the by-product of stevia has the potential to combat hyperuricemia, and can be used as a functional ingredient in the development of nutraceutical products.

19.
Animals (Basel) ; 9(12)2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31817629

RESUMO

This study determined the associations of FADS2 c.1571G>A with milk FAs content and revealed that cows with the GG genotype had improved levels of delta-6 desaturase substrates (linoleic acid, C18:2n-6; p < 0.001) and decreased levels of desaturase products (gamma-linolenic acid, C18:3n-6; p < 0.001), indicating a reduction in FADS2 expression or delta-6 desaturase activity caused by this polymorphism. Computer alignment demonstrated that c.1571G>A occurred within a potential miR-744 binding site. When the c.1571G allele was present, the luciferase activity of reporter constructs was significantly suppressed by miR-744, while no such effect was observed with the A allele. Overexpression of miR-744 in bovine mammary epithelial cells (with the 1571GG genotype) downregulated FADS2 expression at both mRNA and protein levels. In contrast, inhibition of endogenous miR-744 with a specific inhibitor dramatically upregulated FADS2 expression. Taken together, these lines of evidence indicated that the c.1571A minor allele abolished the ability of miR-744 to bind FADS2, with a consequent increase in FADS2 expression levels and synthesis of omega-6 LC-PUFAs.

20.
Nat Prod Res ; : 1-7, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31809578

RESUMO

Two new heptaketides, pleosporalins H and I (1 and 2), as well as seven biosynthetically related known polyketides (3-9) were isolated from the endophytic fungus, Pleosporales sp. F46 by employing the one strain-many compounds (OSMAC) approach. The planar, relative and absolute structures of these compounds were identified by extensive spectroscopic analysis including HRMS, NMR, optical rotations and ECD calculations. The cytotoxic efficiencies of all isolated compounds 1-9 were evaluated against four cancer cell lines A549, CT-26, MCF-7 and MDA-MB-231.

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