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1.
Bioorg Med Chem Lett ; 30(8): 127027, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32122737

RESUMO

A series of triazolopyridinone derivatives originating from the antidepressant trazodone was designed and pharmacologically evaluated. Most of the compounds with a multireceptor functional profile exhibited high potency at the D2, 5-HT1A, and 5-HT2A receptors. Compounds S1, S3, S9 and S12 were selected for further evaluation of druggable potential. Among these compounds, S1, as a D2 receptor partial agonist, demonstrated very potent inhibition of quipazine-induced head-twitch response, which validated its 5-HT2A receptor antagonistic efficacy in vivo. S1 also demonstrated a dose-dependent effect on PCP-induced hyperactivity when administered orally. Thus, S1 endowed with a triazolopyridinone scaffold represents a valuable lead for the development of novel atypical antipsychotics.

2.
J Cell Mol Med ; 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32160403

RESUMO

Maresin Conjugates in Tissue Regeneration 1 (MCTR1) is a newly identified macrophage-derived sulfido-conjugated mediator that stimulates the resolution of inflammation. This study assessed the role of MCTR1 in alveolar fluid clearance (AFC) in a rat model of acute lung injury (ALI) induced by lipopolysaccharide (LPS). Rats were intravenously injected with MCTR1 at a dose of 200 ng/rat, 8 hours after administration of 14 mg/kg LPS. The level of AFC was then determined in live rats. Primary rat ATII (Alveolar Type II) epithelial cells were also treated with MCTR1 (100 nmol/L) in a culture medium containing LPS for 8 hours. MCTR1 treatment improved AFC (18.85 ± 2.07 vs 10.11 ± 1.08, P < .0001) and ameliorated ALI in rats. MCTR1 also significantly promoted AFC by up-regulating epithelial sodium channel (ENaC) and Na+ -K+ -adenosine triphosphatase (Na, K-ATPase) expressions in vivo. MCTR1 also activated Na, K-ATPase and elevated phosphorylated-Akt (P-Akt) by up-regulating the expression of phosphorylated Nedd4-2 (P-Nedd4-2) in vivo and in vitro. However, BOC-2 (ALX inhibitor), KH7 (cAMP inhibitor) and LY294002 (PI3K inhibitor) abrogated the improved AFC induced by MCTR1. Based on the findings of this study, MCTR1 may be a novel therapeutic approach to improve reabsorption of pulmonary oedema during ALI/acute respiratory distress syndrome (ARDS).

3.
Lab Invest ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32123295

RESUMO

Gram-negative bacterial infection causes an excessive inflammatory response and acute organ damage or dysfunction due to its outer membrane component, lipopolysaccharide (LPS). Protectin conjugates in tissue regeneration 1 (PCTR1), an endogenous lipid mediator, exerts fundamental anti-inflammation and pro-resolution during infection. In the present study, we examined the properties of PCTR1 on the systemic inflammatory response, organic morphological damage and dysfunction, and serum metabolic biomarkers in an LPS-induced acute inflammatory mouse model. The results show that PCTR1 reduced serum inflammatory factors and ameliorated morphological damage and dysfunction of the lung, liver, kidney, and ultimately improved the survival rate of LPS-induced acute inflammation in mice. In addition, metabolomics analysis and high performance liquid chromatography-mass spectrometry revealed that LPS-stimulated serum linoleic acid (LA), arachidonic acid (AA), and prostaglandin E2 (PGE2) levels were significantly altered by PCTR1. Moreover, PCTR1 upregulated LPS-inhibited fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2), and elongase of very long chain fatty acids 2 (ELOVL2) expression, and downregulated LPS-stimulated phospholipase A2 (PLA2) expression to increase the intrahepatic content of AA. However, these effects of PCTR1 were partially abrogated by a lipoxin A4 receptor (ALX) antagonist (BOC-2). In summary, via the activation of ALX, PCTR1 promotes the conversion of LA to AA through upregulation of FADS1, FADS2, and ELOVL2 expression, and inhibits the conversion of bound AA into free AA through downregulation of PLA2 expression to decrease the serum AA and PGE2 levels.

4.
Circ Cardiovasc Imaging ; 13(3): e009889, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32164451

RESUMO

BACKGROUND: The monocyte chemoattractant protein-1/CCR2 (chemokine receptor 2) axis plays an important role in abdominal aortic aneurysm (AAA) pathogenesis, with effects on disease progression and anatomic stability. We assessed the expression of CCR2 in a rodent model and human tissues, using a targeted positron emission tomography radiotracer (64Cu-DOTA-ECL1i). METHODS: AAAs were generated in Sprague-Dawley rats by exposing the infrarenal, intraluminal aorta to PPE (porcine pancreatic elastase) under pressure to induce aneurysmal degeneration. Heat-inactivated PPE was used to generate a sham operative control. Rat AAA rupture was stimulated by the administration of ß-aminopropionitrile, a lysyl oxidase inhibitor. Biodistribution was performed in wild-type rats at 1 hour post tail vein injection of 64Cu-DOTA-ECL1i. Dynamic positron emission tomography/computed tomography imaging was performed in rats to determine the in vivo distribution of radiotracer. RESULTS: Biodistribution showed fast renal clearance. The localization of radiotracer uptake in AAA was verified with high-resolution computed tomography. At day 7 post-AAA induction, the radiotracer uptake (standardized uptake value [SUV]=0.91±0.25) was approximately twice that of sham-controls (SUV=0.47±0.10; P<0.01). At 14 days post-AAA induction, radiotracer uptake by either group did not significantly change (AAA SUV=0.86±0.17 and sham-control SUV=0.46±0.10), independent of variations in aortic diameter. Competitive CCR2 receptor blocking significantly decreased AAA uptake (SUV=0.42±0.09). Tracer uptake in AAAs that subsequently ruptured (SUV=1.31±0.14; P<0.005) demonstrated uptake nearly twice that of nonruptured AAAs (SUV=0.73±0.11). Histopathologic characterization of rat and human AAA tissues obtained from surgery revealed increased expression of CCR2 that was co-localized with CD68+ macrophages. Ex vivo autoradiography demonstrated specific binding of 64Cu-DOTA-ECL1i to CCR2 in both rat and human aortic tissues. CONCLUSIONS: CCR2 positron emission tomography is a promising new biomarker for the noninvasive assessment of AAA inflammation that may aid in associated rupture prediction.

5.
J Cell Physiol ; 2020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32037554

RESUMO

Endothelial glycocalyx degradation, critical for increased pulmonary vascular permeability, is thought to facilitate the development of sepsis into the multiple organ failure. Maresin conjugates in tissue regeneration 1 (MCTR1), a macrophage-derived lipid mediator, which exhibits potentially beneficial effects via the regulation of bacterial phagocytosis, promotion of inflammation resolution, and regeneration of tissue. In this study, we show that MCTR1 (100 ng/mouse) enhances the survival of mice with lipopolysaccharide (LPS)-induced (15 mg/kg) sepsis. MCTR1 alleviates LPS (10 mg/kg)-induced lung dysfunction and lung tissue inflammatory response by decreasing inflammatory cytokines (tumor necrosis factor-α, interleukin-1ß [IL-1ß], and IL-6) expression in serum and reducing the serum levels of heparan sulfate (HS) and syndecan-1. In human umbilical vein endothelial cells (HUVECs) experiments, MCTR1 (100 nM) was added to the culture medium with LPS for 6 hr. MCTR1 treatment markedly inhibited HS degradation by downregulating heparanase (HPA) protein expression in vivo and in vitro. Further analyses indicated that MCTR1 upregulates sirtuin 1 (SIRT1) expression and decreases NF-κB p65 phosphorylation. In the presence of BOC-2 or EX527, the above effects of MCTR1 were abolished. These results suggest that MCTR1 protects against LPS-induced sepsis in mice by attenuating pulmonary endothelial glycocalyx injury via the ALX/SIRT1/NF-κB/HPA pathway.

6.
Comp Biochem Physiol C Toxicol Pharmacol ; 231: 108724, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32061958

RESUMO

The present study was conducted to evaluate a multi-strain probiotic (MP) on growth performance, immune and antioxidant function, response to hypoxia stress and resistance to Aeromonas hydrophila of grass carp (Ctenopharyngodon idella). Based on the viable cell counts of aerobic Bacillus spp., six experimental diets with MP supplemented at 0, 0.34, 1.68, 3.36, 6.72, 10.1 g kg-1 were formulated and 900 juveniles (7.30 ± 0.01 g) were equally distributed into 30 aquaria with respective diet for 60 days. Results showed that fish with 0.34-1.68 g kg-1 MP had better growth and feed utilization. Further, plasma total protein, albumin and high-density lipoprotein were remarkably increased with dietary MP at >1.68 g kg-1. Dietary MP supplementation at 6.72-10.1 g kg-1 strikingly elevated plasma myeloperoxidase activity and complement C3 content. For fish with MP at 1.68 and 6.72-10.1 g kg-1, their liver malondialdehyde and glutathione peroxidase were remarkably declined and promoted. After hypoxia stress, fish with 3.36-6.72 g kg-1 MP showed significantly higher respiratory burst activity. Challenge test by A. hydrophila confirmed the protection effects of MP through the decreased cumulative mortality rates. For intestinal histomorphology and enzymatic analyses, fish with 1.68 g kg-1 MP displayed significantly higher intestinal villi height, goblet cells and alkaline phosphatase activity. In conclusion, dietary MP supplementation at 1.68 g kg-1 could promote growth, intestinal morphology and antioxidant capacity, while enhancing host immunity requires higher dosages of MP. Broken-line analysis of weight gain revealed that 1.34 g kg-1 is the optimum dosage for the growth of grass carp.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32077667

RESUMO

Cardiovascular disease (CVD) remains the leading cause of death worldwide despite advances in diagnostic technologies and treatment strategies. The underlying cause of most CVD is atherosclerosis, a chronic disease driven by inflammatory reactions. Atherosclerotic plaque rupture could cause arterial occlusion leading to ischemic tissue injuries such as myocardial infarction (MI) and stroke. Clinically, most imaging modalities are based on anatomy and provide limited information about the on-going molecular activities affecting the vulnerability of atherosclerotic lesion for risk stratification of patients. Thus, the ability to differentiate stable plaques from those that are vulnerable is an unmet clinical need. Of various imaging techniques, the radionuclide-based molecular imaging modalities including positron emission tomography (PET) and single-photon emission computerized tomography (SPECT) provide superior ability to noninvasively visualize molecular activities in vivo and may serve as a useful tool in tackling this challenge. Moreover, the well-established translational pathway of radiopharmaceuticals may also facilitate the translation of discoveries from benchtop to clinical investigation in contrast to other imaging modalities to fulfill the goal of precision medicine. The relationship between inflammation occurring within the plaque and its proneness to rupture has been well documented. Therefore, an active effort has been significantly devoted to develop radiopharmaceuticals specifically to measure CVD inflammatory status, and potentially elucidate those plaques which are prone to rupture. In the following review, molecular imaging of inflammatory biomarkers will be briefly discussed.

8.
Virol J ; 17(1): 17, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32014042

RESUMO

BACKGROUND: Anhui Province in China is facing a severe HIV epidemic with an increasing number of newly diagnosed cases. METHODS: In this study, HIV genetic characteristics in the province were investigated. Newly reported HIV-positive individuals from 15 districts of Anhui Province were enrolled and interviewed. Total viral RNA was extracted from plasma isolated from blood samples. We amplified and sequenced an HIV pol fragment of the 1062 bp. The sequences were used for determination of HIV subtypes and the presence of drug resistance mutations. Transmission networks were constructed to explore possible relationships. And all of assembled partial pol genes were submitted to the Stanford HIV Drug Resistance Database website to find the transmitted drug resistance. RESULTS: Partial pol gene sequences were obtained from 486 cases. The results showed that MSM was the most dominant transmission route (253, 52.06%), followed by heterosexual transmission (210, 43.21%) and blood-borne transmission (1, 0.21%). Many subtypes were identified, including CRF01_AE (226, 46.50%), CRF07_BC (151, 31.07%), subtype B (28, 5.76%), CRF08_BC (20, 4.12%), CRF55_01B (15, 3.09%), CRF68_01B (7, 1.44%), CRF67_01B (3, 0.62%), CRF57_BC (2, 0.41%), CRF59_01B (2, 0.41%), CRF79_0107 (2, 0.41%), subtype C (2, 0.41%), CRF64_BC (1, 0.21%), and circulating recombinant forms (URFs) (27, 5.55%). Four transmission subnetworks containing high transmission risk individuals (with degree ≥4) were identified based on CRF01_AE and CRF07_BC sequences, including two CRF01_AE transmission subnetworks constituted by elderly people with average ages of 67.9 and 61.5 years. Infection occurred most likely through heterosexual transmission, while the other two CRF07_BC transmission subnetworks consist mainly of MSMs with average ages of 31.73 and 34.15. The level of HIV-transmitted drug resistance is 3.09%. CONCLUSIONS: The simultaneous spread of multiple HIV subtypes in Anhui province underscores that close surveillance of the local HIV epidemic is necessary. Furthermore, the elderly people were frequently involved, arguing for behaviour intervention in this specific population besides the MSM risk group.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32079407

RESUMO

Recombinant forms contribute substantially to the genetic diversity of HIV-1. Recent studies have also revealed that three major viral strains (CRF07_BC, CRF01_AE, and subtype B) have been cocirculating among MSM in Anhui, suggesting a high probability of generating new recombinants. Here, we reported a novel CRF01_AE and CRF07_BC HIV-1 recombinant form in men who have sex with men (MSM) in Fuyang city of China. Two near full-length sequences (NFLG) named FY184, FY208 were successfully obtained. The genomic composition analysis of the NFLG reveals that it was divided into four segments by three breakpoints, with two regions of CRF07_BC inserted into a CRF01_AE backbone's gag, pol regions. The CRF01_AE regions were originated from a sub-cluster lineage of CRF01_AE, which mainly circulating among MSM in China. The emergence of a novel recombinant of CRF01_AE/CRF07_BC is indicative of the increasing genetic diversity of the HIV epidemic in MSM in Anhui.

10.
Arch Virol ; 165(3): 619-626, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31965315

RESUMO

Human pegivirus 2 (HPgV-2) is a recently recognized pegivirus of the family Flaviviridae. To investigate the epidemic features of HPgV-2 circulating in the human immunodeficiency virus (HIV)-infected population, we tested for antibodies and viral RNA of HPgV-2 and hepatitis C virus (HCV) with retrospective plasma samples collected from 771 HIV infections with multiple risk behaviors in Honghe Prefecture of Yunnan Province. A total of 195 subjects (25.29%) were seroreactive to HPgV-2, and 41 (5.32%) were RNA positive. Although the positive rate of HPgV-2 antibodies in HIV/HCV-coinfected individuals (27.69%) was significantly higher than that of HIV monoinfections (20.82%) (p = 0.036), this is the first report of HPgV-2 viremia in HIV-infected individuals without HCV infection and the presence of two HPgV-2 lineages in China. Our data indicate that HPgV-2 can also be transmitted sexually, which might be facilitated when combined with HCV infection, injecting drug use, and risky sexual behavior, which appear to have a synergistic effect on HPgV-2 infection. Phylogenetic analysis of 26 near-full-length genome sequences showed that the HPgV-2 strains in China are divided into two clusters.


Assuntos
Infecções por Flaviviridae/complicações , Infecções por Flaviviridae/epidemiologia , Flaviviridae/classificação , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Viremia , Anticorpos Antivirais/sangue , China/epidemiologia , Humanos , Incidência , Filogenia , Prevalência , RNA Viral/genética , RNA Viral/isolamento & purificação
11.
Infect Genet Evol ; 77: 104098, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31678241

RESUMO

There is increasing evidence that naturally occurring HIV-1 genetic diversity can have an impact on drug resistance. Recently, our previous study has demonstrated the natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) in HIV-1 CRF65_cpx strains. The aim of this study is to investigate the presence of natural drug-resistance mutations (DRMs) in other HIV-1 subtypes or CRFs circulating in China. A total of 14,403 pol sequences from China were retrieved from the Los Alamos HIV Sequence Database, 10,041 of which were treatment naïve and presented substantial genetic diversity. Besides the natural presence of V179D and K103R/V179D in CRF65_cpx, the natural presence of V179E was found in CRF55_01B. In all but one of the 228 patients infected with CRF55_01B, NNRTI resistance mutation V179E was present and the combination of V179E and E138G was detected in 14 treatment-naïve patients, with a rate of 6.2%. A significant trend for increasing prevalence of E138G mutation in CRF55_01B strains over time was observed (p < .001). Phylogenetic analysis was conducted to clarify the epidemiological relationship of CRF55_01B strains. Most of the sequences containing E138G mutation scattered in the big CRF55_01B cluster, which indicated the rising prevalence of E138G was mainly due to multiple mutation events rather than local transmission clusters of a particular variant containing E138G mutation. Our findings highlight the importance of molecular surveillance of CRF55_01B strains and the urgent need for implementation of effective preventive measures to reduce the transmission of CRF55_01B.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31766855

RESUMO

HIV has remarkable genetic diversity among populations. The diversity has critical impacts on transmission, immune escape, pathogenesis, and clinical management. HIV-1 diversity originates from frequent mutation and recombination during reverse transcription. This work focuses on the quasispecies genetic dynamics within individuals with primary infections. Eleven men who have sex with men from the Beijing PRIMO Clinical Cohort were identified as primary infection and had three or four series of their anticoagulant blood samples collected. Viral RNA was extracted and amplified using single-genome amplification. Products of the gp120 gene that met single-genome amplification requirements were sequenced. Subtype assortment of all collected sequences was performed using both the jumping profile hidden Markov model (jpHMM) and REGA. Quasispecies diversity at each time was estimated using Mega 6. Intrapatient recombination was analyzed using RDP4. According to the Fiebig classification system, YA-81 belongs to stage III and YA-113 belongs to stage IV. The other samples are all associated with the infection stage of V/VI. YA113 had a dual infection with subtype B and a new unique recombinant form involving CRF01_AE and C. The other eight were infected with CRF01_AE, one was infected with B/C recombinant, and the last one with B. Of the 10 single infections, 8 were caused by 1 founder virus. They all displayed a sharp increase of quasispecies diversity during the sampling times. Two were caused by at least two founder viruses. The diversity of these strains starts at a significantly high level and is followed by a relatively steady trend. Critically, the separate subtypes YA113-B and YA113-CRF01_AE/C both showed a similar trend to those infected by a single founder virus. Recombination analysis revealed that 5 of 11 cases underwent detectable intrapatient recombination. These findings indicate that tracing the dynamics of HIV-1 quasispecies during early infection may be relevant and valuable for understanding pathways of viral diversification and immune escape.

13.
Water Environ Res ; 92(1): 94-105, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31332872

RESUMO

To overcome the problems of high excess sludge yield and poor nitrogen removal efficiency in traditional biological treatment processes, a multi-stage A/O biofilm reactor was developed by combining the multi-stage A/O process with novel floating spherical carriers, resulting in repeated coupling of anoxic and aerobic environments. Results showed that the system achieved COD, NH 4 + - N , and TN removal efficiencies of 93.8%, 84.5%, and 75.7%, respectively, with average effluent concentrations lower than: 29.8 COD mg/L, 4.3 NH 4 + - N  mg/L, and 13.2 TN mg/L. The observed sludge yield was 0.139 g MLSS/g COD, which was lower than that of the conventional activated sludge process. Microbial analysis showed that the community structure and cell morphology of microorganisms changed greatly with alternating aerobic-anoxic condition; high-throughput sequencing results proved that functional microorganisms can be enriched on the surface of the carries and therefore improved the nitrogen removal efficiency and meanwhile minimize the sludge yield within the system. PRACTITIONER POINTS: The research innovatively developed a novel floating spherical carrier and coupled it with multi-stage A/O process. The complex redox environments inside the floating spherical carriers improves the nitrogen removal efficiency and the sludge reduction effect. Nitrospirae, Hydrogenophaga promoted the nitrogen removal, Firmicutes, Bacteroidetes and Dechloromonas promoted the in-situ sludge reduction of the system.


Assuntos
Nitrogênio , Esgotos , Biofilmes , Reatores Biológicos , Desnitrificação , Eliminação de Resíduos Líquidos
14.
J Agric Food Chem ; 68(1): 4-16, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31829005

RESUMO

Obesity has an important influence on health conditions, causing a multitude of complications and comorbidities, and drug therapy is considered to be one of the treatment strategies. Nowadays, there is increasing interest in the study of intestinal microbiota regulation of obesity; also, an increasing number of agricultural and sideline products have been found to have anti-obesity potential. In the present review, we summarize an overview of current known and potential anti-obesity oligosaccharides and their molecular structures. We describe their anti-obesity potential activity and the molecular structure associated with this activity, the regulation of intestinal microbiota composition and its mechanism of action, including regulation of the short-chain fatty acid (SCFA) pathway and altering bile acid (BA) pathway. This review will provide new ideas for us to develop new anti-obesity functional foods.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Obesidade/tratamento farmacológico , Oligossacarídeos/administração & dosagem , Animais , Fármacos Antiobesidade/química , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal , Humanos , Obesidade/metabolismo , Obesidade/microbiologia , Oligossacarídeos/química , Prebióticos/administração & dosagem , Prebióticos/análise
15.
Insects ; 10(11)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683768

RESUMO

Ectropis grisescens and Ectropis obliqua are sibling species of tea-chewing pests. An investigation of the distribution of tea geometrids was implemented for enhancing controlling efficiency. E. grisescens is distributed across a wider range of tea-producing areas than Ectropis obliqua in China with sympatric distribution found in some areas. In order to explore reproductive isolation mechanisms in co-occurrence areas, hybridization experiments were carried out. Results showed they can mate but produce infertile hybrids. During experiments, the desynchronized development phenomenon was found in the hybridized generation of sibling tea geometrids. Furthermore, transcriptome analysis of those individuals of fast-growing and slow-growing morphs revealed that the insect hormone biosynthesis pathway was enriched in two unsynchronized development groups of hybrid offspring. More importantly, some genes regulating the synthesis of moulting hormone showed significantly up-regulated expression in fast-growing groups. Above all, metabolism of the juvenile hormone and synthesis of the ecdysone pathway were found to be crucially involved in the desynchronized development phenomenon. This research finding contributes to a better understanding of the mechanisms of insect development and reproductive isolation of two sibling species.

17.
Fish Shellfish Immunol ; 95: 617-623, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31622676

RESUMO

A feeding experiment was conducted to determine the effects of Schizochytrium sp. on growth performance, antioxidant capacity and non-specific immunity in golden pompano (Trachinotus ovatus).Two diets were formulated with or without Schizochytrium sp. supplemented (D1:0% and D2: 3%) to feed fish for 8 weeks. Results showed that growth performance, feed intake and survival rate increased significantly with Schizochytrium sp. supplemented (P < 0.05). Feed coefficient rate (FCR) of golden pompano fed the diet supplemented with Schizochytrium sp. was significantly lower than that of fish fed the control diet (P < 0.05). No significant differences were found in antioxidant capacity both in transcriptional level, including nclear factor erythroid-2-related factor-2 (Nrf2), Kelch-like-ECH-associated protein (keap1), catalase (CAT), glutathione peroxidase (GSH-PX) and heme oxygenase 1 (HO-1) and enzyme activity, such as total antioxidant capacity (T-AOC), malondialdehyde (MDA) and superoxide dismutase (SOD) (P > 0.05). Gut amylase and lipase were significantly higher in dietary Schizochytrium sp. supplemented treatment than that in control group (P < 0.05). The relative peroxisome proliferator-activated receptor-α (PPARα) expression level in liver was significantly higher in Schizochytrium sp supplemented treatment than that in control one (P < 0.05). The mRNA expression of myeloid differentiation factor 88 (MyD88), IL-1R-associated kinases 4 (IRAK4), interferon regulating Factor 3 (IRF3), interferon regulating Factor 3(IRF7) and heat shock protein 70 (HSP70) were significantly lower in Schizochytrium sp. supplemented treatment than that in control one (P < 0.05). In Schizochytrium sp. supplemented diet, golden pompano had significantly longer villi length than that in control diet (P < 0.05); muscle thickness in Schizochytrium sp. supplemented diet was thicker than that in control one (P < 0.05) and there were more goblet cells in Schizochytrium sp. treatment (P < 0.05). After the rearing trial, an air exposure trial was conducted. Results showed that the air-exposure mortality (AEM) and mRNA expression level of Nrf2, keap1, CAT, GSH-PX and HO-1 showed no significant difference (P > 0.05). These results indicated that dietary Schizochytrium sp. improved the growth performance and non-specific immunity of golden pompano while made no difference to antioxidant capacity.

18.
Front Physiol ; 10: 1027, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440171

RESUMO

A nutritional feeding experiment was conducted to evaluate the effects of shrimp paste on feeding attractiveness, growth performance, digestive enzyme activities, immune-related genes and intestinal morphology in hybrid snakehead (Channa maculata ♀ × Channa argus ♂). Two diets were formulated with or without shrimp paste supplementation (D1:0% and D2: 3%) to feed fish for 8 weeks. Results showed that growth performance (FBW, WG and SGR) and feed intake (FI) significantly increased with shrimp paste supplemented (P < 0.05), while FCR and SR of hybrid snakehead fed diets supplemented with shrimp paste or not showed no significant difference (P > 0.05). Gut lipase and amylase activities were significantly higher in diet supplemented with shrimp paste than that in control one (P < 0.05). Hepatic antioxidant statuses of hybrid snakehead fed dietary shrimp paste or not showed no significant differences in total antioxidant capacity, malondialdehyde and superoxide dismutase of fish (P > 0.05). Results showed that fish fed diet with shrimp paste supplemented did not show significant difference in expression of GR, IκB, P65 and IL8 than that in control group (P > 0.05). There are significantly more goblet cells in shrimp paste supplemented diet than that in control diet (P < 0.05). However, villi length and muscle thickness showed no significant difference compared to control diet (P > 0.05). The results indicated that dietary 3% shrimp paste supplementation improved the growth performance of hybrid snakehead by enhancing feed intake (FI) while made no difference to antioxidant capacity and immunity.

19.
Materials (Basel) ; 12(17)2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31450630

RESUMO

This paper studies the effect of high-strength steel fiber reinforced concrete (SFRC) on the axial compression behavior of rectangular-sectional SFRC-filled steel tube columns. The purpose is to improve the integrated bearing capacity of these composite columns. Nine rectangular-sectional SFRC-filled steel tube columns and one normal concrete-filled steel tube column were designed and tested under axial loading to failure. The compressive strength of concrete, the volume fraction of steel fiber, the type of internal longitudinal stiffener and the spacing of circular holes in perfobond rib were considered as the main parameters. The failure modes, axial load-deformation curves, energy dissipation capacity, axial bearing capacity, and ductility index are presented. The results identified that steel fiber delayed the local buckling of steel tube and increased the ductility and energy dissipation capacity of the columns when the volume fraction of steel fiber was not less than 0.8%. The longitudinal internal stiffening ribs and their type changed the failure modes of the local buckling of steel tube, and perfobond ribs increased the ductility and energy dissipation capacity to some degree. The compressive strength of SFRC failed to change the failure modes, but had a significant impact on the energy dissipation capacity, bearing capacity, and ductility. The predictive formulas for the bearing capacity and ductility index of rectangular-sectional SFRC-filled steel tube columns are proposed to be used in engineering practice.

20.
Mol Pharm ; 16(9): 3996-4006, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31369274

RESUMO

Folate receptor α (FRα) is a well-studied tumor biomarker highly expressed in many epithelial tumors such as breast, ovarian, and lung cancers. Mirvetuximab soravtansine (IMGN853) is the antibody-drug conjugate of FRα-binding humanized monoclonal antibody M9346A and cytotoxic maytansinoid drug DM4. IMGN853 is currently being evaluated in multiple clinical trials, in which the immunohistochemical evaluation of an archival tumor or biopsy specimen is used for patient screening. However, limited tissue collection may lead to inaccurate diagnosis due to tumor heterogeneity. Herein, we developed a zirconium-89 (89Zr)-radiolabeled M9346A (89Zr-M9346A) as an immuno-positron emission tomography (immuno-PET) radiotracer to evaluate FRα expression in triple-negative breast cancer (TNBC) patients, providing a novel means to guide intervention with therapeutic IMGN853. In this study, we verified the binding specificity and immunoreactivity of 89Zr-M9346A by in vitro studies in FRαhigh cells (HeLa) and FRαlow cells (OVCAR-3). In vivo PET/computed tomography (PET/CT) imaging in HeLa xenografts and TNBC patient-derived xenograft (PDX) mouse models with various levels of FRα expression demonstrated its targeting specificity and sensitivity. Following PET imaging, the treatment efficiencies of IMGN853, pemetrexed, IMGN853 + pemetrexed, paclitaxel, and saline were assessed in FRαhigh and FRαlow TNBC PDX models. The correlation between 89Zr-M9346A tumor uptake and treatment response using IMGN853 in FRαhigh TNBC PDX model suggested the potential of 89Zr-M9346A PET as a noninvasive tool to prescreen patients based on the in vivo PET imaging for IMGN853-targeted treatment.

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