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1.
Ecotoxicol Environ Saf ; 192: 110201, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32028152

RESUMO

OBJECTIVE: This study focused on the oxidative stress effect of di-n-butyl phthalate (DBP) on development of the urinary system. METHODS: We examined the mRNA expression of genital tubercle (GT) in control and DBP induced hypospadias group by Affymetrix Rat 230 2.0 Array. Real-time PCR and Western Blot were used to detect the protein and mRNA expression levels of inositol-1,4,5-triphate-receptor (IP3R) and epithelial-mesenchymal-transition (EMT)-related molecular markers, such as E-cadherin, ß-Catenin, Snail, N-cadherin, in the GT of hypospadiac male rats and controls. The results of array were further confirmed in vitro. The changes of intracellular calcium concentration in urethral epithelial cells were detected by Fluo-3-AM before and after DBP treatment. The levels of reactive oxygen species (ROS) in urethral epithelial cells were measured by DCFH-DA with different concentrations of DBP (0, 1, 10, 100 µmol/L) treatment. RESULTS: The mRNA expression profiles of GT in control and DBP induced hypospadias group showed high expression of IP3R and the abnormalities of EMT. Compared to the control group, the expression levels of IP3R, E-cadherin and ß-Catenin increased at both the protein and mRNA levels. However the expression levels of Snail and N-cadherin decreased. The intracellular calcium concentration increased significantly after DBP treatment. The effect of DBP on urethral epithelial cells was linked to the generation of oxidative stress. CONCLUSION: DBP can influence the development of GT through its oxidative stress effect, which significantly increases the concentration of calcium and inhibits EMT in urethral epithelial cells, and block the fusion process of urethral groove, causing the occurrence of hypospadias. This study provides a new understanding of DBP's molecular mechanisms on hypospadias and may lead to new treatment strategies for the disease.

2.
Int J Infect Dis ; 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32045695

RESUMO

OBJECTIVES: To analyze the effects of one dose of live attenuated hepatitis A vaccine in a developing country. METHODS: The reported cases of hepatitis A virus (HAV)infection from 2005 to 2018 in Henan province, China, were analyzed. Data of vaccinated children were assessed on the childhood immunization information management system. Questionnaire survey and blood sample collection were randomly conducted in six counties and districts of Henan province to analyze the prevalence of HAV lgG among the population aged 0-70 years. RESULTS: In 2008, Henan province began to expand its program on immunization, and children aged 18 months were given one dose of live attenuated hepatitis A vaccine (HepA-L). From 2005 to 2007, the HAV incidence remained steady at above 5000 cases per year and increased to 7489 in 2007. Since 2008, the HAV incidence decreased cumulatively from 4576 to 237 in 2018, indicating a 94.8% decrease, which was particularly pronounced among adolescents (98.2%). The proportion of hepatitis A cases in patients younger than 10 years continually decreased from 41.6% in 2012 to 3.8% in 2018. The reduction of reported cases older than 40 years was slower than that of children. In 2012, the proportion of hepatitis A cases older than 40 years was 27.6%, and continually increased to 69.2% (164/237) in 2018. The results of serological investigation showed that the 0-1.5-year age group had the lowest anti-HAV IgG prevalence (38.6%), which increased to 75.0% in the 4-6-year age group, covered by this immunization program. CONCLUSIONS: The data indicated a large decrease in HAV infections in Henan province from 2008 onward in response to the introduction of a planned immunization program of HepA-L.

3.
BMC Musculoskelet Disord ; 21(1): 17, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31918703

RESUMO

BACKGROUND: The management of thoracolumbar burst fractures traditionally involves posterior pedicle screw fixation, but it has some drawbacks. The aim of this study is to evaluate the clinical and radiological outcomes of patients with thoracolumbar burst fractures. They were treated by a modified technique that monoaxial pedicle screws instrumentation and distraction-compression technology assisted end plate reduction. METHODS: From March 2014 to February 2016, a retrospective study including 42 consecutive patients with thoracolumbar burst fractures was performed. The patients had undergone posterior reduction and instrumentation with monoaxial pedicle screws. The fractured vertebrae were also inserted screws as a push point. The distraction -compression technology was used as assisting end plate reduction. All patients were followed up at a minimum of 2 years. These parameters including segmental kyphosis, severity of fracture, neurological function, canal compromise and back pain were evaluated in preoperatively, postoperatively and at the final follow-up. RESULTS: The average follow-up period was 28.9 ± 4.3 months (range, 24-39mo). No patients had postoperative implant failure at recent follow-up. The mean Cobb angle of the kyphosis was improved from 14.2°to 1.1° (correction rate 92.1%). At final follow-up there was 1.5% loss of correction. The mean preoperative wedge angle was improved from 17.1 ± 7.9°to 4.4 ± 3.7°(correction rate 74.3%). The mean anterior and posterior vertebral height also showed significant improvements postoperatively, which were maintained at the final follow-up(P < 0.05). The mean visual analogue scale (VAS) scores was 8 and 1.6 in preoperation and at the last follow-up, and there was significant difference (p < 0.05). CONCLUSION: Based on our experience, distraction-compression technology can assist reduction of collapsed endplate directly. Satisfactory fracture reduction and correction of segmental kyphosis can be achieved and maintained with the use of monoaxial pedicle screw fixation including the fractured vertebra. It may be a good treatment approach for thoracolumbar burst fractures.

5.
Obesity (Silver Spring) ; 28(1): 122-131, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31773909

RESUMO

OBJECTIVE: This study aimed to investigate the effects of liraglutide on the body weight set point (BWSP) in diet-induced obese rats and to determine the relationship between BWSP and hypothalamic arcuate nucleus (ARC) microglial activation. METHODS: Diet-induced obesity (DIO) rats were divided into three groups: continuous high-fat diet (HFD) plus saline, HFD with liraglutide, and HFD with liraglutide pair feeding. Body weight, BWSP, inflammatory cytokines, suppressor of cytokine signaling 3, orexigenic/anorexigenic proteins, apoptosis, and microglia in the ARC were assessed. The effect of liraglutide on the Notch-1 signaling pathway and its relationships with  nuclear factor-κB and p38 mitogen-activated protein kinase were also investigated in a lipopolysaccharide (LPS)-induced microglia activation model. RESULTS: Liraglutide reduced BWSP; reversed adverse changes in hypothalamic inflammation, suppressor of cytokine signaling 3, and apoptosis; and diminished microgliosis in DIO rats. The BWSP showed a linear correlation with ARC microglial density. Liraglutide inhibited LPS-induced M1 microglial polarization and promoted microglial polarization to the M2 phenotype, diminishing inflammatory cytokine expression. Liraglutide inhibited Notch-1 signaling pathway activation and decreased nuclear factor-κB and p38 mitogen-activated protein kinase pathway activation in LPS-stimulated microglia. CONCLUSIONS: Liraglutide can reduce BWSP in DIO rats. There is a linear correlation between hypothalamic microgliosis and BWSP. Liraglutide reduces excessive microglial activation and inflammation, which may contribute to BWSP reduction.

6.
J Chromatogr A ; 1611: 460618, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31672267

RESUMO

In this study, a monolithic enzyme reactor based on a strategy of green synthesis was successfully prepared in a capillary with trypsin immobilized by "thiol-ene" click reaction. A polymer of poly(butyl methacrylate-co-α-methacrylic acid-co-ethylene glycol dimethacrylate) was prepared in a mixture of 1-butyl-3-methylimidazolium tetrafluoroborate and choline chloride/ethylene glycol as the support of enzyme reactor. After "thiol-ene" reaction was used for enzyme immobilization, the Michaelis constants and maximum reaction rate of the resulting immobilized enzyme reactors (IMER) were determined by capillary electrophoresis to be 2.1 mmol/L and 0.028 µmol/min, respectively. The enzymatic hydrolysis of the enzyme reactor under different experimental conditions were investigated. A on-line digestion of bovine serum albumin (BSA) on the new IMER can be achieved within 50 s, up to 864 times faster than in-solution digestion (12 h). BSA can be well digested and the numbers of identified peptides were 73 with the coverage rates of 82.7%. The IMER was further used for the analysis of protein extracts from rat liver, and 1034 protein groups were identified. All these results demonstrated that such a click reaction based IMER would be of great prospect in the high throughput analysis for proteome with high confidence.

7.
J Org Chem ; 85(2): 774-787, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31829008

RESUMO

A palladium-catalyzed alkenylation involving remote δ-position C(alkenyl)-H activation of cycloalkenes reacting with electron-deficient alkenes is described. This method features excellent site selectivity and stereoselectivity to efficiently afford only E-selective highly substituted 1,3-diene derivatives with extra-ligand-free and good functional group tolerance including estrone and free N-H tryptamine under weakly alkaline conditions. Mechanistic studies suggest that picolinamide as a bidentate directing group enables the formation of unique alkenyl palladacycle intermediates.

8.
Anal Chim Acta ; 1096: 184-192, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31883586

RESUMO

A monolithic chip incorporated with graphene oxide (GO) based on deep eutectic solvents (DESs) was developed for solid phase extraction (SPE). The carboxylated GO was modified with p-aminostyrene (pAS) by amidation, and the obtained GO (pAS-COOH-GO) was covalently incorporated into poly(butyl methacrylate-co-ethylene glycol dimethyl methacrylate) monolithic chip. Due to the high viscosity characteristics of DESs, a uniform pAS-COOH-GO incorporated monolithic chip with good permeability can be achieved. A systematic study of the preparation parameters on the performance of the resulting monolith was carried out, including the content of pAS-COOH-GO, DESs composition and porogen ratio. The resulting pAS-COOH-GO incorporated monolith was characterized by nitrogen adsorption, scanning electron microscopy, and transmission electron microscopy. The GO-doped monolithic chip can be used for SPE of polycyclic aromatic hydrocarbons (phenanthrene, anthracene, fluoranthene, pyrene, benzo(a)anthracene, benzo(a) pyrene, dibenzo(a,h)anthracene and inden(1,2,3,-cd)pyrene). The recoveries were all higher than 90%, which was about twice as high as that of the monolithic chip prepared without GO. By comparing the SPE results with that of GO free monolithic chip, good enrichment effects were demonstrated on the pAS-COOH-GO incorporated monolithic chip.

9.
Biosci Biotechnol Biochem ; 84(1): 134-142, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31490096

RESUMO

Plumbagin (PLB), an alkaloid obtained from the roots of the plants of Plumbago genus, is an inhibitor of NADPH oxidase 4 (NOX4). This study aimed to investigate the beneficial effect of PLB against oxygen-glucose deprivation/reoxygenation (OGDR)-induced neuroinjury in human SH-SY5Y neuronal cultures. Our results showed that OGD/R stimulated NOX4 protein expression and reactive oxygen species (ROS) production in SH-SY5Y cells, whereas increased 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) production, resulting in the activation of the NLRP3 inflammasome. And PLB pretreatment reduced the ROS production by regulating the expression of NOX4 and downregulated NF-κB signaling which was induced by OGDR. Furthermore, PLB inhibited OGDR induced NLRP3 inflammasome activation but not PARP1. Overall, PLB improved OGDR induced neuroinjury by inhibiting NOX4-derived ROS-activated NLRP3 inflammasome.


Assuntos
Hipóxia Celular/efeitos dos fármacos , Glucose/deficiência , Inflamassomos/metabolismo , NADPH Oxidase 4/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Naftoquinonas/farmacologia , Neurônios/metabolismo , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Isquemia Encefálica/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Raízes de Plantas/química , Plumbaginaceae/química
10.
Gynecol Endocrinol ; : 1-7, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31793358

RESUMO

Prenatal diagnosis of Down syndrome (DS) is based on calculated risk involving maternal age, biochemical and ultrasonographic markers, and, more recently, cell-free DNA (cfDNA). The present study was designed to identify Down Syndrome biomarkers in maternal serum. We quantified the changes in maternal serum protein levels between 10 non-pregnant women, 10 pregnant women with healthy fetuses, and 10 pregnant women with DS fetuses using isobaric tags for relative and absolute quantification (iTRAQ). We subsequently conducted a Gene Ontology (GO) analysis. A total of 470 proteins were identified, 11 of which had significantly different serum levels between the DS fetus group and Healthy fetuses group. Our data shows the identified proteins may be relevant to DS and constitute potential DS biomarkers.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31828048

RESUMO

Background: Streptococcus pneumoniae, a main causative agent associated with invasive and non-invasive infection in elderly population, is a major global health problem. After pneumococcal conjugate vaccines (PCV) and pneumococcal polysaccharide vaccines (PPV) were introduced, the distribution of S. pneumoniae serotypes has changed. There was currently limited data on epidemiology and status of antimicrobial resistance of S. pneumoniae in Shanghai. Objective: To determine the serotype distribution, antimicrobial susceptibility and molecular epidemiology of S. pneumoniae isolated from adults in Shanghai. Method: A total of 75 S. pneumoniae isolates consecutively collected from 2015 through 2017 were serotyped by conventional multiplex-PCR. The antimicrobial susceptibility was determined by broth microdilution method. The multilocus sequence type (MLST) was performed to estimate the molecular epidemiology. Results: The predominant serotypes among the isolates were 19F (20.00%), 3 (16.00%), 23F (9.33%), 14 (8.00%), and19A (5.33%). The prevalence of pneumococcal strains with serotypes targeted by vaccines PCV7, PCV10, PCV13, and PPV23 was 44, 45.33, 66.67, and 80%, respectively. Penicillin non-susceptible S. pneumoniae (PNSSP) accounted for 16% of the isolates examined and resistance to erythromycin, azithromycin, tetracycline, clindamycin, cefaclor and trimethoprim-sulfamethoxazole were found in 92.00, 90.67, 86.67, 81.33, 54.67, and 54.67% of isolates, with most isolates (78.67%) presenting multidrug-resistance. The top three sequence types (STs) were ST271 (17.33%), ST180 (9.33%), and ST81 (8.00%). The international resistance clone complexes Spain23F-1 (n = 4), Netherland3-31 (n = 8), and Taiwan19F-14 (n = 14) were identified. Conclusions: The S. pneumoniae isolates showed high genetic diversity in Shanghai and the prevalence of antimicrobial resistance was also high among S. pneumoniae isolates, most of which were multidrug-resistant. The spread of international resistance clones might contribute to the increase of resistant isolates. The PPV23 could protect against most pneumococcal capsular serotypes causing infection of adults in Shanghai.

12.
Small ; 15(51): e1904486, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31755651

RESUMO

Magnesium (Mg) alloys have been promised for biomedical implants in orthopedic field, however, the fast corrosion rate and mode challenge their clinical application. To push Mg alloys materials into practice, a composite coating with biodegradable and high compatible components to improve anticorrosion property of an Mg alloy (i.e., AZ31) is designed and fabricated. The inner layer is micro-nano structured Mg(OH)2 through hydrothermal treatment. Then stearic acid (SA) is introduced to modify Mg(OH)2 for better reducing the gap below a surface-degradation polymer layer of poly(1,3-trimethylene carbonate). Benefited by the SA modification effect, this sandwiched coating avoids corrosive medium penetration via enhancing the adhesion strength at the interface between outer and inner layers. Both in vitro and in vivo tests indicate that the composite coating modified AZ31 perform a better anticorrosion behavior and biocompatibility compared to bare AZ31. Strikingly, a 1.7-fold improvement in volume of newly formed bone is observed surrounding the composite coating modified implant after 12 week implantation. The sandwiched biocompatible coating strategy paves a hopeful way for future translational application of Mg alloys orthopedic materials in clinics.

13.
Math Biosci Eng ; 16(6): 6753-6768, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31698586

RESUMO

In this paper, we study a ratio-dependent predator-prey system with diffusion and cross-diffusion under the homogeneous Neumann boundary condition. By applying the maximum principle and Harnack's inequality, we present a priori estimates of the positive steady state of the system. The existence and non-existence of non-constant positive steady states are established. Our findings show that under certain hypotheses, non-constant positive steady states can exist due to the emergence of cross-diffusion, which reveals that cross-diffusion can induce stationary patterns but the random diffusion fails.

14.
Ann Clin Microbiol Antimicrob ; 18(1): 34, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31706307

RESUMO

BACKGROUND: The increased prevalence of Klebsiella pneumoniae infections and resistance rates are a current cause for concern. However, data for resistance rates in K. pneumoniae strains from primary hospitals and the resistance distribution among the different isolate sample sources are scarce. METHODS: All the K. pneumoniae strains were isolated from patients who visited a primary health care center located in Central Zhejiang Province from January 2011 to December 2017. The specimens included blood, sputum, cervical secretions and urine. The species were identified by the Vitek 2 Compact Bacterial Identification and Monitoring System or VITEK-MS and the extended spectrum ß-lactamase (ESBL) and drug resistance profiles were identified using the AST-GN13 Gram negative susceptibility card (VITEK-2). The genotype of strains from urine sources was analyzed by detecting TEM and SHV genes. Finally, the drug resistance rates among the isolates from different sample sources were analyzed using the Chi square test with SPSS software. RESULTS: A total of 5319 K. pneumoniae strains were isolated in this study. Among the 20 antimicrobial drugs studied, the resistance rates of K. pneumoniae strains varied from 1.4% (ertapenem) to 23.1% (nitrofurantoin). The antibiotic resistance rates varied significantly among the isolate samples sources for all, with the highest rates for all antibiotics except for nitrofurantoin found in urine samples. In addition, the ESBL-positive rate in urine samples was 27.1%, significantly higher than that of cervical secretions (20.2%), blood (16.5%) and sputum (15.2%). Compared to the ESBL-negative strains, higher resistance rates were detected in the ESBL-positive strains. The most common genotype of isolates from urine was SHV (28%, 23/82), following by TEM (14.6%, 12/82). CONCLUSION: The highest resistance rates of K. pneumoniae strains to most antibiotics found in urine samples are partly due to the ESBLs, indicating that a special attention should be paid in the treatment of urinary tract infection.

15.
Anal Chem ; 91(23): 15267-15274, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31691556

RESUMO

N-doping strategy has been explored to enhance the activity of carbon nanozymes because the reconstructed electronic structures in N-doped carbon nanozymes are advantageous for the catalytic process. However, carbon nanozymes with high N content are still difficult to obtain due to the instability of N element under high calcination temperatures. To address this challenge, here we proposed a new N-doping strategy to fabricate highly active and specific peroxidase-like carbon nanozymes by using a high N-containing polymer (i.e., polyethylenimine (PEI)) as the N source and a natural clay mineral (i.e., montmorillonite (MMT)) as a template, respectively. We showed that the assembly of MMT with PEI protected N loss under high calcination temperatures and thus retained more catalytically active N sites. The mechanism study showed that the hydroxyl radical could be the key intermediate involved in the peroxidase-like catalysis. We then used the optimized carbon nanozyme with high and specific peroxidase-like activity (i.e., CP600-6) to detect H2O2, glucose, and ascorbic acid. Moreover, we successfully determined the total antioxidant capacity (TAC) in real samples including four commercial beverages, fresh orange juice, and three kinds of vitamin C tablets. The current study not only provides a new strategy for fabricating peroxidase-like nanozymes but also develops a facile TAC assay for future use in evaluation of antioxidant food quality and oxidative stress in healthcare.

16.
Mikrochim Acta ; 186(12): 812, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31745668

RESUMO

A boronate affinity monolith with improved affinity and selectivity for glycoproteins was prepared starting from two monomers. The first is 3-aminopropyltriethoxysilane-methacrylic acid (APTES-MAA), and the other is a polyhedral oligomeric silsesquioxane (POSS) monomer. In the next step, 3-(acrylamido)benzeneboronic acid was adopted as boronate affinity ligand, and ethylene glycol dimethacrylate as the crosslinker, and iso-propanol and octanol as binary porogens. The synergistic effect of APTES-MAA and POSS warrants good affinity and selectivity for glycoproteins, which results in a number of attractive features including (a) a wide operation pH range (from 5 to 8); (b) higher enrichment factors ranging from 19.3 to 20.6; (c) greater recoveries of glycoproteins between 95.8 and 107.1%; (d) lower relative standard deviations of ≤4.2%. Compared to the corresponding APTES-MAA/POSS-free monolith, the new boronate material had 1.7-fold increased glycoprotein recovery from complex samples. Glycoproteins in 500-fold diluted serum samples can be enriched by the boronate monolith. Graphical abstractSchematic representation of the preparation of 3-aminopropyltriethoxysilane-methacrylic acid/polyhedral oligomeric silsesquioxanes boronate affinity monolith. This sorbent exhibits high selectivity and wide pH operation range for capturing glycopeptides.

17.
Urol J ; 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31630384

RESUMO

PURPOSE: To investigate the clinical implications of CD3+CD69+ T-cells and CD8+CD28+ T-cells in the peripheral blood of patients prior to radical prostatectomy. MATERIALS AND METHODS: A total of 91 prostate cancer (PCa) patients and 50 benign prostatic hyperplasia (BPH) patients were enrolled from January 2016 to December 2017. The proportions of CD3+CD69+ T-cells and CD8+CD28+ T-cells in the peripheral blood of PCa and BPH patients were detected by flow cytometry, and the association of these T-cell populations with pathological Grade Group and pathological TNM classification was evaluated. Data analysis was performed with SAS version 9.4 software. RESULTS: The proportions of CD3+CD69+ and CD8+CD28+ T-cells in peripheral blood were higher in PCa patients than those in BPH patients. Multivariate analysis identified a higher CD3+CD69+ T-cell proportion as a risk factor for PCa (odds ratio (OR)=4.783, P=0.0013), but the diagnostic efficacy of the CD3+CD69+ T-cell proportion (area under the curve (AUC)=0.6833, P=0.0003) for PCa was still inferior to that of the tPSA level (AUC=0.7531, P<0.0001). The AUCs for CD3+CD69+ T-cell and CD8+CD28+ T-cell proportions for PCa were 0.6959 (P=0.0372) and 0.6935 (P=0.0395), respectively, among men with tPSA levels of 4.0-10.0 ng/ml. A lower CD3+CD69+ T-cell proportion was associated with higher pathological Grade Group (P=0.0074). CONCLUSION: The proportions of CD3+CD69+ T-cells and CD8+CD28+ T-cells in peripheral blood are potential diagnostic indicators for PCa. The preoperative proportion of CD3+CD69+ T-cells in peripheral blood may have prognostic value in terms of the pathological Grade Group in PCa.

18.
Front Pharmacol ; 10: 1060, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31619999

RESUMO

Triphala is a famous herbal formula originated in Asia and is popular in America. Due to the high abundance of polyphenols, its oral liquid is unstable and easy to cause precipitate, which results in the loss of activities. However, complex composition and unclear precipitation mechanism hinders the improvement of stability. In this study, the accumulation of precipitation in the storage and its effect on activity were investigated. Then, an integrated chain of evidence was proposed based on the physical phase, chemical profile, and sediment elements. The results showed that antioxidant activity decreased from IC50 115 to 146 µl before and after 90 days of storage, and the anti-fatigue activity decreased from 30.54 to 28.47 min. Turbiscan Lab Expert observed that particle size increased from 106 to 122 nm, and the turbiscan stability index increased from 0 to 14, which indicated that its stability is continuously decreasing. High performance liquid chromatography (HPLC) fingerprint coupled with multivariate statistical analysis identified that these chemical markers changed significantly, such as gallic acid, catechins, and ellagic acid. Loss of catechins tends to be involved in the formation of phlobaphene precipitation. The fact that the new-born ellagic acid in precipitation (0.47 mg/ml) is significantly higher than that reduced in solution (0.25 mg/ml) indicates that it is not only derived from colloid aging. Microscopic observation combined with energy spectrum analysis further confirmed the existence of the multi-precipitates. The crystalline precipitate is ellagic acid, and the other is phlobaphene. In conclusion, based on the evidence chain analysis, this study revealed a systematic change of the whole polyphenol solution system. It provides a novel perspective to understand the sedimentation formation of polyphenol solution, which is an important theoretical contribution to the preparation of polyphenol solutions.

19.
Toxicology ; 428: 152300, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31568847

RESUMO

Maternal exposure to di-n-butyl phthalate (DBP) induces hypospadias via regulation of autophagy in uroepithelial cells. Here, we use gene express analysis to explore the underlying molecular mechanisms. Pregnant rats received DBP orally at a dose of 750 mg/kg/day during gestational days 14-18. Gene expression analysis showed an increased expression of the hedgehog interacting protein (HhIP) gene. In DBP-induced hypospadiac male offspring, immunohistochemistry (IHC) staining and Western blot analysis confirmed increased expression of the HhIP protein and inhibited hedgehog signaling. in vitro experiments suggest the involvement of the reactive oxygen species (ROS)-HhIP-Gli1-autophagy axis in DBP-treated primary rat urethral epithelial cells. Taken together, our findings show that prenatal exposure to DBP induces abnormal hedgehog signaling and autophagy in uroepithelial cells that may play important roles in the development of hypospadias.

20.
Cell Death Dis ; 10(6): 391, 2019 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-31564717

RESUMO

Psychosocial stress is a critical inducing factor of inflammatory bowel diseases (IBD), while autophagy is a novel central issue of IBD development. The present study investigated the potential role of autophagy in stress-related IBD in patients and animal model. The correlation between psychosocial stress and intestinal autophagy was determined in 23 patients with IBD. Corticotropin-releasing hormone (CRH), a well-established inducer of psychosocial stress, was administrated in dextran sulfate sodium (DSS)-induced IBD mice and lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDM). In IBD patients, the autophagy markers beclin-1, LC3-II/I ratio, Atg16L1, and Atg4B were significantly enhanced. The psychosocial stress score was positively associated with the levels of beclin-1 and the LC3II/I ratio in intestinal biopsy specimens. In IBD mouse model, CRH significantly aggravated intestinal inflammation, increased Paneth cell metaplasia, and enhanced intestinal autophagy (beclin-1, Atg16L1, PIK3R4, and Atg4B upregulation; GAA, CTSD, and PPKAA1 downregulation). Additionally, the CRH-induced gut microbial dysbiosis was evidenced by a marked increase in the number of detrimental bacteria. In LPS-stimulated BMDM, CRH substantially increased M1/M2 polarization and thus promoted inflammation. In both IBD mice and LPS-treated BMDM, blockade of autophagy by chloroquine abrogated the unbeneficial effects of CRH, whereas autophagy inducer rapamycin resulted in a pronounced protective effect against IBD lesion. Our data demonstrate that psychosocial stress may link the enhanced intestinal autophagy by modulating gut microbiota and inflammation to aggravate IBD. These data indicate autophagy as a promising therapeutic target for psychosocial stress-related IBD.

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