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1.
Genes (Basel) ; 10(10)2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31569414

RESUMO

Nucleosomes are the basic units of eukaryotes. The accurate positioning of nucleosomes plays a significant role in understanding many biological processes such as transcriptional regulation mechanisms and DNA replication and repair. Here, we describe the development of a novel method, termed ZCMM, based on Z-curve theory and position weight matrix (PWM). The ZCMM was trained and tested using the nucleosomal and linker sequences determined by support vector machine (SVM) in Saccharomyces cerevisiae (S. cerevisiae), and experimental results showed that the sensitivity (Sn), specificity (Sp), accuracy (Acc), and Matthews correlation coefficient (MCC) values for ZCMM were 91.40%, 96.56%, 96.75%, and 0.88, respectively, and the average area under the receiver operating characteristic curve (AUC) value was 0.972. A ZCMM predictor was developed to predict nucleosome positioning in Homo sapiens (H. sapiens), Caenorhabditis elegans (C. elegans), and Drosophila melanogaster (D. melanogaster) genomes, and the accuracy (Acc) values were 77.72%, 85.34%, and 93.62%, respectively. The maximum AUC values of the four species were 0.982, 0.861, 0.912 and 0.911, respectively. Another independent dataset for S. cerevisiae was used to predict nucleosome positioning. Compared with the results of Wu's method, it was found that the Sn, Sp, Acc, and MCC of ZCMM results for S. cerevisiae were all higher, reaching 96.72%, 96.54%, 94.10%, and 0.88. Compared with the Guo's method 'iNuc-PseKNC', the results of ZCMM for D. melanogaster were better. Meanwhile, the ZCMM was compared with some experimental data in vitro and in vivo for S. cerevisiae, and the results showed that the nucleosomes predicted by ZCMM were highly consistent with those confirmed by these experiments. Therefore, it was further confirmed that the ZCMM method has good accuracy and reliability in predicting nucleosome positioning.

2.
Opt Express ; 27(15): 20720-20733, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31510161

RESUMO

Under the framework of computational integral imaging, an optical 3D objects security and high-quality reconstruction method based on pixel-evaluating mapping (PEM) algorithm is proposed. In this method, the pixel crosstalk caused by noneffective pixel overlap is effectively reduced by a pixel-evaluated mask, which can improve the image quality of the reconstructed 3D objects. Meanwhile, compared with the other computational integral imaging reconstruction methods, our proposed PEM algorithm can obtain more accurate pixel mapping weight parameters, thereby the reconstructed 3D objects provide higher quality. In addition, the nonlinear feedback shift register cellular automata algorithm is proposed to increase the security of the proposed method. We have experimentally verified the proposed 3D objects encryption and reconstruction algorithm. The experimental results show that the proposed method is superior to the other computational reconstruction methods.

3.
Curr Mol Med ; 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31530264

RESUMO

Stearic acid (SA), a saturated long-chain fatty acid consisting of 18 carbon atoms, is widely found in feed ingredients such as corn, soybeans, and wheat. However, the roles of SA in the renewal of intestinal epithelial cells remain unclear. In the present study, we found that 0.01-0.15 mM SA promoted IPEC-J2 cell differentiation. In addition, the results showed that the viability of IPEC-J2 cells was inhibited by SA in a time- and dose-dependent manner. Flow cytometry and western blot analysis suggested that SA induced apoptosis and blocked autophagic flux in cells. In addition, the amounts of triglyceride were significantly increased upon challenge with SA. Moreover, the decrease in the viability of cells induced by SA could be attenuated by 4-PBA, an inhibitor of ER stress. In summary, SA accelerated IPEC-J2 cell differentiation at 0.01-0.15 mM. Furthermore, SA induced IPEC-J2 cell apoptosis and impaired autophagic flux by causing ER stress.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31553089

RESUMO

This study was conducted to determine the effects of oral administration with glutamate on metabolism of suckling piglets based on 1 H-Nuclear magnetic resonance (1 H NMR) spectroscopy through the level of metabolism. Forty-eight healthy [(Yorkshire × Landrace) × Duroc] piglets born on the same day with a similar birth bodyweight (1.55 ± 0.20 kg) were obtained from six sows (8 piglets per sow). The piglets from each sow were randomly assigned into four treatments (2 piglets per treatment). The piglets were given 0.09 g/kg body weight (BW) of sodium chloride (CN group), 0.03 g/kg BW monosodium glutamate (LMG group), 0.25 g/kg BW monosodium glutamate (MMG group) and 0.50 g/kg BW monosodium glutamate (HMG group) twice a day respectively. An 1 H NMR-based metabolomics' study found that the addition of monosodium glutamate (MSG) significantly reduced serum citrate content in 7-day-old piglets, while HMG significantly increased serum trimethylamine content and significantly reduced unsaturated fat content in 7-day-old piglets (p < .05). The content of glutamine, trimethylamine, albumin, choline and urea nitrogen was significantly increased and the creatinine content decreased significantly in the 21-day-old HMG (p < .05). Analysis of serum hormones revealed that glucagon-like peptide-1 (GLP-1) content in the 21-day-old HMG was highest (p < .05). The cholecystokinin (CCK) content in the HMG of 7-day-old piglets was lower than that in the LMG (p < .05), and the CCK content in the serum of the 21-day-old MMG was highest (p < .05). The serum leptin levels in the 21-day-old HMG were the lowest (p < .05). The serum insulin content in the 7-day-old MMG was highest (p < .05). This study suggests that MSG plays an important role in the metabolism of sugar, fat and protein (amino acids). These results provide a theoretical basis for designing piglet feed formulations.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31542233

RESUMO

Serine Threonine Tyrosine Kinase 1 (STYK1) presents oncogenic properties in many studies, and emerging evidence suggests that ferroptosis serve as a novel tumor suppressor. However, the interplay between STYK1 and ferroptosis in NSCLC remains unclear. Our aim is to illustrate the expression of ferroptotic regulator Glutathione peroxidase 4 (GPX4) in NSCLC and the relationship between STYK1 and ferroptosis. Herein, results based on ONCOMINE database, clinical specimens, and cellular manipulation revealed GPX4 was upregulated in NSCLC tissues and cell lines, and high GPX4 expression predicted worse prognosis. High STYK1 expression predicted worse OS and was related to high GPX4 in NSCLC tissues; overexpression of STYK1 in lung cancer cell line SW900 upregulated the expression of GPX4, promoted proliferation, and attenuated diverse mitochondrial abnormalities specific to ferroptosis, whereas knockdown of GPX4 exacerbated such attenuations without affecting cell proliferation. Taken together, ferroptosis as an anti-tumor factor is inhibited in NSCLC, and targeting ferroptosis could be a novel therapeutic strategy for the management of NSCLC; furthermore, regulating ferroptosis could be another cancerous mechanism of STYK1.

6.
Acta Biomater ; 96: 491-504, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31302299

RESUMO

The combination of multi-targeting magnetic nanoprobes and multi-targeting strategies has potential to facilitate magnetic resonance imaging (MRI) and magnetic induction hyperthermia of the tumor. Although the thermo-agents based on magnetic iron oxide nanoparticles (MION) have been successfully used in the form of intratumoral injection in clinical cure of glioblastoma, the tumor-targeted thermotherapy by intravenous administration remains challenging. Herein, we constructed a c(RGDyK)- and d-glucosamine-grafted bispecific molecular nanoprobe (Fe3O4@RGD@GLU) with a magnetic iron oxide core of size 22.17 nm and a biocompatible shell of DSPE-PEG2000, which can specially target the tumor vessel and cancer cells. The selection of c(RGDyK) could make the nanoprobe enter the neovascularization endotheliocyte through αvß3-mediated endocytosis, which drastically reduced the dependence on the enhanced permeability and retention (EPR) effect in tumor. This dual-ligand nanoprobe exhibited strong magnetic properties and favorable biocompatibility. In vitro studies confirmed the anti-phagocytosis ability against macrophages and the specific targeting capability of Fe3O4@RGD@GLU. Then, the imaging effect and anti-tumor efficacy were compared using different targeting strategies with untargeted nanoprobes, dual-targeted nanoprobes, and magnetic targeting combined with dual-targeted nanoprobes. Moreover, the combination strategy of magnetic targeting and active targeting promoted the penetration depth of nanoprobes in addition to the increased accumulation in tumor tissue. Thus, the dual-targeted magnetic nanoprobe together with the combined targeting strategy could be a promising method in tumor imaging and hyperthermia through in vivo delivery of theranostic agents. STATEMENT OF SIGNIFICANCE: Magnetic induction hyperthermia based on iron oxide nanoparticles has been used in clinic for adjuvant treatment of recurrent glioblastoma. Nonetheless, this application is limited to intratumoral injection, and tumor-targeted hyperthermia by intravenous injection remains challenging. In this study, we developed a multi-targeted strategy by combining magnetic targeting with active targeting of dual-ligand magnetic nanoprobes. This combination mode acquired optimum contrast imaging effect through MRI and tumor-suppressive effect through hyperthermia under an alternating current magnetic field. The design of the nanoprobe was suitable for targeting most tumor lesions, which enabled it to be an effective theranostic agent with extensive uses. This study showed significant enhancement of the penetration depth and accumulation of nanoprobes in the tumor tissue for efficient imaging and hyperthermia.

7.
J Anim Physiol Anim Nutr (Berl) ; 103(5): 1530-1537, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31350808

RESUMO

Weaning process widely affects the small intestinal structure and function in piglets, while the responses of large intestine to weaning stress are still obscure. The purpose of this study was to determine the developmental changes (i.e., short chain fatty acids (SCFAs) concentrations, growth parameters, crypt-related indices and antioxidant capacity) in colon of piglet during weaning. Forty piglets were weaned at day 21 and euthanized to collect colonic tissues and digesta samples on day 0, 1, 3, 7 and 14 post-weaning (n = 8). Piglet growth performance was improved (p < .001) on day 7 and 14 post-weaning. The concentrations of acetate, propionate, butyrate, valerate, isobutyrate, isovalerate and total SCFAs were higher (p < .001) during the late post-weaning period. The mRNA abundances of SCFAs transporters were greater (p < .001) on day 7 and 14. The absolute and relative weights, absolute length and perimeter of colon were greater (p < .001) on day 7 and 14. Similarly, post-weaning increases (p < .001) in colonic crypt depth and Ki67 positive cells numbers per crypt were observed during the same period. Colonic crypt fission indices decreased (p < .01), while total crypt numbers increased (p < .001) on day 14 after weaning. Moreover, total SCFAs concentration was significantly associated with colonic growth parameters and Ki67 cells/crypt (p < .001). In addition, catalase content was decreased on day 3, 7, and 14, whereas, the concentrations of total superoxide dismutase (T-SOD) and manganese-containing superoxide dismutase (MnSOD) were higher (p < .05) on day 1 and 3 post-weaning. These results showed that weaning process has a significant effect on colonic growth and development, which might be associated with the change of SCFAs concentrations in colon.

8.
J Mater Sci Mater Med ; 30(7): 83, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31273466

RESUMO

Infection and encrustation limit the use of ureteral stent and to data no device can completely solve these complications. The Cu-bearing stainless steel is a novel material with properties of inhibiting infection and decreasing encrustation in vitro. In this work, ureteral stents were fabricated and implanted into the bladder of New Zealand rabbits, aiming to further investigate the effects of material on bacterial survival and growth as well as the implant related encrustation. Less adherent microbes and deposited crystals on Cu-bearing stainless steel stents were found, with significant differences in comparison with stainless steel stents, which further support the development of biofunctional ureteral stents.

9.
BMC Vet Res ; 15(1): 234, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286936

RESUMO

BACKGROUND: Enterotoxigenic Escherichia coli K88 (E. coli K88) are considered as a major cause of diarrhea and death in newly weaned piglets. Oral passive immunization with chicken egg yolk immunoglobulins (IgY) have attracted considerable attention for treatment of gastrointestinal infection due to its high specificity. In this study it was estimated the protective effect of anti-K88 fimbriae IgY against E. coli K88 adhesion to piglet intestinal mucus in vitro and to investigate the potential use of IgY for controlling E. coli-induced diarrhea in weaned piglets in vivo. RESULTS: E. coli K88 was incubated with IgY for 24 h, and the bacterial growth profiles showed that specific IgY with a concentration higher than 5 mg/mL was observed to significantly inhibit the growth of E. coli K88 compared to nonspecific yolk powder in a liquid medium. Moreover, pretreatment with 50 mg/mL of IgY was found to significantly decrease the adhesion ability of E. coli K88 to porcine jejunal and ileal mucus, further supported by the observations from our immunofluorescence microscopic analysis. In vivo, administration of IgY successfully protected piglets from diarrhea caused by E. coli K88 challenge. Additionally, IgY treatment efficiently alleviated E. coli-induced intestinal inflammation in piglets as the gene expression levels of inflammatory cytokines TNF-α, IL-22, IL-6 and IL-1ß in IgY-treated piglets remained unchanged after E. coli K88 infection. Furthermore, IgY significantly prevented E. coli K88 adhering to the jejunal and ileal mucosa of piglets with E. coli infection and significantly decreased E. coli and enterotoxin expression in colonic contents. CONCLUSION: Outcome of the study demonstrated that IgY against the fimbrial antigen K88 was able to significantly inhibit the growth of E. coli K88, block the binding of E. coli to small intestinal mucus, and protect piglets from E. coli-induced diarrhea. These results indicate that passive immunization with IgY may be useful to prevent bacterial colonization and to control enteric diseases due to E. coli infection. The study has great clinical implication to provide alternative therapy to antibiotics in E coli induced diarrhea.


Assuntos
Aderência Bacteriana/efeitos dos fármacos , Diarreia/etiologia , Diarreia/prevenção & controle , Escherichia coli Enterotoxigênica/efeitos dos fármacos , Infecções por Escherichia coli/complicações , Imunoglobulinas/farmacologia , Animais , Antígenos de Bactérias/imunologia , Citocinas/genética , Diarreia/microbiologia , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/patologia , Infecções por Escherichia coli/prevenção & controle , Proteínas de Escherichia coli/imunologia , Proteínas de Fímbrias/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Imunização Passiva , Imunoglobulinas/uso terapêutico , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Ligação Proteica/efeitos dos fármacos , Suínos
10.
Dig Dis Sci ; 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31332625

RESUMO

BACKGROUND: Endoscopic variceal sequential ligation (EVSL) is currently endorsed in our hospital, as the preferred endoscopic treatment for prevention of variceal rebleeding and achieving adequate hemostasis. There is currently a lack of consensus surrounding EVSL-induced changes in esophageal motor function and abnormal reflux. AIMS: To explore alterations in esophageal motor function and risk of abnormal gastroesophageal reflux in liver cirrhosis patients with esophageal varices, after EVSL. METHODS: Twenty-one liver cirrhosis patients with esophageal varices were studied using manometry and 24-h pH monitoring 1 day prior to and 1 month following EVSL. The EVSL consisted of performing esophageal variceal ligation using a multi-band ligator, which was repeated every 4 weeks until the varices were eradicated. RESULTS: The amplitude and duration of peristaltic contraction waves and the percentage of abnormal esophageal contraction waveforms were unaltered in both the proximal (P > 0.05) and the distal (P > 0.05) esophagus after EVSL. However, the lower esophageal sphincter pressure was decreased following EVSL (16.1 ± 7.9 mmHg vs 21.1 ± 6.3 mmHg (P < 0.05)). Various quantitative parameters including percentage of total monitoring time with pH < 4.0, total number of reflux episodes, number of reflux episodes > 5 min, and DeMeester scores were not increased in post-EVSL patients. Abnormal reflux monitored by 24-h pH monitoring occurred in ten (47.6%) pre-EVSL patients and 11 (52.4%) post-EVSL patients. CONCLUSIONS: Although EVSL affects esophageal motility by relatively decreasing LES pressure, it does not induce substantial motor abnormalities nor increase risk of abnormal gastroesophageal reflux disease in cirrhosis patients.

11.
Cell Signal ; 62: 109331, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31154001

RESUMO

Upon occurrence of kidney injury, tubular cells arrested in G2/M stage may promote interstitial fibroblast activation and kidney fibrosis through producing large amounts of pro-fibrotic cytokines. MTORC1 signaling is essential for controlling cell growth, however, the role and mechanisms for mTORC1 in regulating tubular cell cycle progression during kidney fibrosis are not clear. Here we reported that p-S6 abundance was increased at 15 min, reached peak at 1 h and declined from 3 h to 24 h, while the abundance of p-4E-BP1 and p-Histone H3 was increased from 15 min to 24 h in tubular epithelial cells at the similar pattern after serum stimulation. The phosphorylation of 4E-BP1 was prohibited in NRK-52E cells by the transfection of 4E-BP1 plasmid with four phospho-sites mutation (4E-BP1A4). 4E-BP1A4 transfection led to less G2/M cell arrest as well as the production of pro-fibrotic cytokine and extracellular matrix in NRK-52E cells. In addition, aristolochic acid (AA)-induced tubular cell G2/M arrest induced by treatment was also largely attenuated in NRK-52E cells transfected with 4E-BP1A4. In mouse kidneys with UUO nephropathy, p-4E-BP1 abundance was markedly elevated in the mitotic tubular cells. Therefore, these data indicates that suppressing 4E-BP1 phosphorylation may inhibit tubular cell G2/M-arrest and kidney fibrosis.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31176866

RESUMO

Cysteine oxygenase (CDO) is a mononuclear nonhemoglobin enzyme that catalyzes the production of taurine through the cysteine (Cys) pathway and plays a key role in the biosynthesis of taurine in mammals. However, the function of CDOs in bony fish remains poorly understood. In this study, we cloned CDO genes (CaCDO1 and CaCDO2) from Carassius auratus. The cDNA sequences of both CaCDO1 and CaCDO2 encoded putative proteins with 201 amino acids, which included structural features typical of the CDO protein family. Multiple sequence alignment and phylogenetic analysis showed that CaCDO1 and CaCDO2 shared high sequence identities and similarities with C. carpio homologs. Quantitative real-time polymerase chain reaction (qRT-PCR) results revealed that CaCDO1 and CaCDO2 were both broadly expressed in all selected tissues and developmental stages in C. auratus but had differing mRNA levels. In addition, compared to those of the taurine-free group, the in vivo mRNA expression levels of both CaCDO1 and CaCDO2 significantly decreased with increasing dietary taurine levels from 1.0 to 9.0 g/kg. Furthermore, in vitro taurine treatments showed similar inhibitory effects on the expression of CaCDO1 and CaCDO2 in the intestines of C. auratus. Our results also showed that the mRNA expression of CaCDO2 in the intestines was higher than that of CaCDO1 in response to in vivo and in vitro taurine supplementation. Overall, these data may provide new insights into the regulation of fish CDO expression and provide valuable knowledge for improving dietary formulas in aquaculture.


Assuntos
Cisteína Dioxigenase/genética , Cisteína Dioxigenase/metabolismo , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Carpa Dourada/genética , Carpa Dourada/metabolismo , Taurina/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , DNA Complementar/genética , Regulação da Expressão Gênica no Desenvolvimento , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Carpa Dourada/crescimento & desenvolvimento , Isoenzimas/genética , Isoenzimas/metabolismo , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Taurina/farmacologia , Distribuição Tecidual
13.
J Anim Physiol Anim Nutr (Berl) ; 103(5): 1503-1511, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31144409

RESUMO

This study was conducted to test the hypothesis that dietary supplementation with anti-E. coli, chicken egg yolk immunoglobulins (IgY), may affect early weaned piglet (EWP) intestinal functions and enteric micro-organisms. One hundred and forty-eight ([Landrace × Yorkshire] × Duroc) piglets, weaned at age day 21, were randomly assigned to receive one of three diets for 14 days. Treatment group one (control group) was fed the base diet. Treatment group two (antibiotics group) was fed the base diet which was supplemented with 100 ppm colistin sulphate and 15 ppm enramycin; treatment group three (IgY group) was fed the base diet which was supplemented with 500 mg/kg anti-E. coli IgY. The study evaluated the effects on EWPs of IgY on growth, serum biochemical, inflammatory profiles and also digestion content intestinal bacterial populations. Results showed no significant difference in diarrhoea rates between IgY-fed EWPs and antibiotic-treated EWPs. Serum biochemical analysis showed that EWPs fed an IgY-containing diet had both lower (p < 0.05) cholesterol and low-density lipoprotein compared to antibiotic-treated EWPs. Escherichia coli populations measured in IgY-fed EWP ileal contents, compared to the control group, were significantly reduced (p < 0.05). Enterococcus, Lactobacillus, Clostridium and Bifidobacterium populations were unaffected by the IgY treatment. Larger (p < 0.05) Enterococcus populations and lower (p < 0.05) expression levels of heat-stable enterotoxin b (STb) were observed in IgY-fed EWP caecal digesta compared to the control group. Enteric Lactobacillus significantly decreased (p < 0.05) in EWPs fed antibiotics while it was unaffected by IgY treatment. Dietary supplementation with anti-E. coli IgY has the potential to suppress enteric E. coli growth, but not Lactobacillus, Clostridium and Bifidobacterium. This promotes and maintains a healthy EWP intestinal environment. These findings suggest that IgY may be used as an alternative to antibiotics in EWP diets.

14.
Rev Sci Instrum ; 90(3): 033108, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30927815

RESUMO

Broadband laser ranging (BLR) is an appropriate method to obtain absolute distance in dynamic experiments. In this article, we first analyze the performance limit for BLR and indicate that the measuring range can be hardly increased while keeping the distance or time resolution unchanged. Then, multi-reference BLR is proposed, which can break this limit and greatly increase the measuring range. Its validity is demonstrated by an experiment with an explosively driven aluminum surface flying over 100 mm. This method would improve the capability of BLR.

15.
Intern Med J ; 49(10): 1299-1306, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30985051

RESUMO

BACKGROUND: Elevated D-dimer levels have been associated with poor outcomes in patients with cardiovascular disease. AIM: To study this association in elderly patients with chronic heart failure (CHF). METHODS: We analysed 1355 elderly patients who were admitted with CHF. All patients had D-dimer levels measured within the first 24 h following admission. A multivariate logistic regression model was used to assess the variables associated with chronic kidney disease. We used Cox regression analysis to assess the multivariable relationship between the D-dimer and subsequent all-cause death. RESULTS: In the multiple logistic regression analysis, the D-dimer was identified as a risk factor for chronic kidney disease (odds ratio = 1.278, 95% confidence interval 1.138 to 1.436, P < 0.001). The optimal cut-off level for D-dimer to predict all-cause death was found to be >885 ng/mL. In the multivariate Cox proportional-hazards model, a D-dimer level >885 ng/mL remained significantly associated with all-cause death (hazard ratio = 2.003, 95% confidence interval 1.334 to 3.010, P = 0.001). Additional analyses revealed that higher D-dimer levels were associated with an increased risk of all-cause death irrespective of the subtype of heart failure (including heart failure with reduced ejection fraction and heart failure with preserved ejection fraction). CONCLUSION: In elderly patients with CHF, measurement of D-dimer levels may help to risk stratify these patients, and high D-dimer levels might be regarded as a warning sign to intensify therapy.

16.
J Anim Sci ; 2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30852589

RESUMO

Bile acid, a cholesterol metabolite, promotes gastrointestinal tract digestion and absorption of cholesterol, lipids, and fat-soluble vitamins. It is a signaling regulatory molecule that influences a variety of endocrinal and metabolic activities. This study investigated the effects of hyodeoxycholic acid (HDCA) as a dietary supplement on endocrine cell differentiation and function and weaned piglet serum biochemical indices. Sixteen piglets [Duroc × (Landrace × Yorkshire)] were individually housed and weaned at 21 d of age (BW of 6.14 ± 0.22 kg). Uniform weight animals were randomly assigned to 1 of 2 treatments (8 replicate pens per treatment and 1 piglet per pen). The treatments were 1) base diet (control) and 2) base diet supplemented with 2 g/kg of HDCA. Control and HDCA piglet numbers of chromogranin A (CgA)-positive cells per crypt did not differ. HDCA CgA-positive cells numbers decreased (P < 0.05) in the jejunal villi showed a tendency to decrease (P < 0.10) in the ileal villi and showed tendency toward an increase (P < 0.10) in the duodenal villi compared with the controls. The HDCA diet led to a decline in glucagon-like peptide 2 (P < 0.01) concentrations, but did not affect plasma glucagon-like peptide 1. HDCA supplementation increased (P < 0.05) the mRNA expression of jejunal Insm1, Sst, PG, and Gast, but decreased (P < 0.05) duodenal expression of Insm1, jejunal Pdx1, and ileal NeuroD1. HDCA elevated globulin and immunoglobulin A (P < 0.05) serum concentrations and decreased the albumin/globulin ratio (P < 0.05). Total protein and immunoglobulin G serum levels tended to increase compared with the control group. These results indicate that dietary HDCA at 2 g/kg may regulate enteroendocrine cell differentiation and play a role in increasing weaned piglet humoral immunity.

17.
Mol Med Rep ; 19(4): 2660-2670, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30720126

RESUMO

Adipose­derived stem cells (ADSCs) and bone marrow­derived stem cells (BMSCs) are considered to be prospective sources of mesenchymal stromal cells (MSCs), that can be used in cell therapy for atherosclerosis. The present study investigated whether ADSCs co­cultured with M1 foam macrophages via treatment with oxidized low­density lipoprotein (ox­LDL) would lead to similar or improved anti­inflammatory effects compared with BMSCs. ADSCs, peripheral blood monocytes, BMSCs and ox­LDL were isolated from ten coronary heart disease (CHD) patients. After three passages, the supernatants of the ADSCs and BMSCs were collected and systematically analysed by liquid chromatography­quadrupole time­of­flight­mass spectrometry (6530; Agilent Technologies, Inc., Santa Clara, CA, USA). Cis­9, trans­11 was deemed to be responsible for the potential differences in the metabolic characteristics of ADSCs and BMSCs. These peripheral blood monocytes were characterized using flow cytometry. Following peripheral blood monocytes differentiation into M1 macrophages, the formation of M1 foam macrophages was achieved through treatment with ox­LDL. Overall, 2x106 ADSCs, BMSCs or BMSCs+cis­9, trans­11 were co­cultured with M1 foam macrophages. Anti­inflammatory capability, phagocytic activity, anti­apoptotic capability and cell viability assays were compared among these groups. It was demonstrated that the accumulation of lipid droplets decreased following ADSCs, BMSCs or BMSCs+cis­9, trans­11 treatment in M1 macrophages derived from foam cells. Consistently, ADSCs exhibited great advantageous anti­inflammatory capabilities, phagocytic activity, anti­apoptotic capability activity and cell viability over BMSCs or BMSCs+cis­9, trans­11. Additionally, BMSCs+cis­9, trans­11 also demonstrated marked improvement in anti­inflammatory capability, phagocytic activity, anti­apoptotic capability activity and cell viability in comparison with BMSCs. The present results indicated that ADSCs would be more appropriate for transplantation to treat atherosclerosis than BMSCs alone or BMSCs+cis­9, trans­11. This may be an important mechanism to regulate macrophage immune function.


Assuntos
Tecido Adiposo/citologia , Células da Medula Óssea/metabolismo , Células Espumosas/metabolismo , Inflamação/etiologia , Inflamação/metabolismo , Lipoproteínas LDL/efeitos adversos , Células-Tronco Mesenquimais/metabolismo , Idoso , Apoptose , Células da Medula Óssea/citologia , Sobrevivência Celular , Citocinas/metabolismo , Feminino , Células Espumosas/citologia , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Metabolismo dos Lipídeos , Macrófagos/metabolismo , Masculino , Células-Tronco Mesenquimais/citologia , Metaboloma , Metabolômica/métodos , Pessoa de Meia-Idade
18.
J Anim Sci ; 2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30753616

RESUMO

Bile acid, a cholesterol metabolite, promotes gastrointestinal tract digestion and absorption of cholesterol, lipids, and fat-soluble vitamins. It is a signaling regulatory molecule that influences a variety of endocrinal and metabolic activities. This study investigated the effects hyodeoxycholic acid (HDCA) as a dietary supplement on endocrine cell differentiation and function and weaned piglet serum biochemical indices. Sixteen piglets (Duroc × [Landrace × Yorkshire]) were individually housed and weaned at 21 days of age (body weight of 6.14 ± 0.22 kg). Uniform weight animals were randomly assigned to one of two treatments (eight replicate pens per treatment and one piglet per pen). The treatments were 1) base diet (control); and 2) base diet supplemented with 2 g/kg of HDCA. Control and HDCA piglet numbers of CgA-positive cells per crypt did not differ. HDCA CgA-positive cells numbers decreased (P < 0.05) in the jejunal villi, showed a tendency to decrease (P < 0.10) in the ileal villi, and showed tendency toward an increase (P < 0.10) in the duodenal villi compared to the controls. The HDCA diet led to a decline in GLP-2 (P < 0.01) concentrations, but did not affect plasma GLP-1. HDCA supplementation increased (P < 0.05) the mRNA expression of jejunal Insm1, Sst, PG, and Gast, but decreased (P < 0.05) duodenal expression of Insm1, jejunal Pdx1, and ileal NeuroD1. HDCA elevated GLO and IgA (P < 0.05) serum concentrations and decreased the A/G ratio (P < 0.05). TP and IgG serum levels tended to increase compared to the control group. These results indicate that dietary HDCA at 2 g/kg may regulate enteroendocrine cell differentiation and play a role in increasing weaned piglet humoral immunity.

19.
Environ Pollut ; 247: 524-533, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30708314

RESUMO

Prothioconazole (PTC) is a widely used triazolinthione fungicide with low toxicity and short residual period. However, its desulfurization metabolite, prothioconazole-desthio (PTC-d), is more persistent and has higher toxicity in terrestrial animals. In this study, the toxicokinetics (TK) and tissue distribution of PTC and PTC-d in Chinese lizards (Eremias argus) were measured following single oral dose (100 mg kg-1 body weight) treatments. TK parameters indicated that PTC was more rapidly absorbed than PTC-d, as indicated by its shorter time to reach peak concentrations in most tissues. Furthermore, the relative bioavailability of PTC in lizards was lower than that of PTC-d. Compared with PTC, PTC-d preferentially accumulated in lizards, as reflected by longer half-life of PTC-d. During the distribution process, PTC-d generated in vivo was transported from other tissues and was deposited in the skin and tail, where PTC-d may be excreted by exuviation or tail detachment. Preferential enrichment of S-enantiomer of both PTC and PTC-d were observed in all tissues. Hepatic cytochrome P450 gene expression measurement revealed that cyp1a5 and cyp3a28 exhibited the strongest responses in both treatment groups. In addition, the opposite responses of cyp2k4 in different treatment groups may indicate that this enzyme caused differences in the rates of metabolism of the two chemicals. This study compared the TK profile of PTC and its desulfurization metabolite PTC-d in lizards and demonstrated that the desulfurization of PTC could increase its ecological risk due to the higher bioavailability and persistence of PTC-d.


Assuntos
Fungicidas Industriais/toxicidade , Lagartos/metabolismo , Triazóis/toxicidade , Animais , Hidrocarboneto de Aril Hidroxilases/genética , Hidrocarboneto de Aril Hidroxilases/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Fungicidas Industriais/metabolismo , Fígado/metabolismo , Lagartos/genética , Estereoisomerismo , Distribuição Tecidual , Toxicocinética , Triazóis/metabolismo
20.
Ecotoxicol Environ Saf ; 171: 247-255, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-30612012

RESUMO

Enantioselective toxicokinetics, accumulation, and toxicity of myclobutanil were investigated by oral exposure of myclobutanil enantiomers to lizards. After a single oral administration, the absorption half-lives ( [Formula: see text] ) and elimination half-lives (t1/2k) were in the range of 0.133-14.828 and 3.641-17.682 h, respectively. The absorption and elimination half-lives of (+)-myclobutanil showed no significant differences from those of (-)-myclobutanil in lizard blood, whereas preferential enrichment of (-)-enantiomer was observed in the liver, fat, skin, intestine, lung and kidney. In the bioaccumulation experiments, the residue of (-)-myclobutanil was detected in most tissues at 7, 14, and 28 days, while (+)-myclobutanil was found only in lizard skin, at a concentration lower than that of (-)-myclobutanil. Thus, (-)-myclobutanil was preferentially accumulated in lizards. The transcriptional responses of metabolic enzyme genes indicated that cytochrome P450 1a1 (cyp1a1), cyp2d3, cyp2d6, cyp3a4 and cyp3a7 played a crucial role in the metabolism of (+)-myclobutanil, whereas cyp1a1, cyp2d3, cyp2d6, cyp2c8, and cyp3a4 contributed to the metabolism of (-)-myclobutanil. The difference in metabolism pathways may be a reason for the enantioselectivity of myclobutanil in lizard. Myclobutanil also affected the expression of antioxidant enzyme genes, and the (+)-myclobutanil treatment might produce higher oxidative stress in lizard liver when compared with its antipode. Hepatic histopathological changes such as hepatocellular hypertrophy, nuclear pyknosis, vacuolation, and non-zonal macrovesicular lipid accumulation were observed in the liver of lizards for both (+)-myclobutanil and (-)-myclobutanil treatments. Thus, myclobutanil could affect lizard liver upon multiple exposure. The findings of this study provide specific insights into the enantioselective metabolism and toxicity of chiral triazole fungicides in lizards.


Assuntos
Fungicidas Industriais/toxicidade , Lagartos/metabolismo , Nitrilos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Transcrição Genética/efeitos dos fármacos , Triazóis/toxicidade , Administração Oral , Animais , Antioxidantes/metabolismo , Citocromos/genética , Fungicidas Industriais/farmacocinética , Rim/metabolismo , Fígado/efeitos dos fármacos , Lagartos/genética , Nitrilos/farmacocinética , Estresse Oxidativo/genética , Pele/metabolismo , Estereoisomerismo , Distribuição Tecidual , Toxicocinética , Triazóis/farmacocinética
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