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1.
Cell Physiol Biochem ; 53(3): 439-452, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31436397

RESUMO

BACKGROUND/AIMS: Among the assisted reproductive techniques, the in vitro maturation of oocytes (IVM) is less developed than other techniques, but its implementation would entail a qualitative advance. This technique consists in the extraction of immature oocytes from antral ovarian follicles with the patient under low hormone stimulation or without hormone to mature exogenously in culture media supplemented with different molecules to promote maturation. In this sense, we are interested in the role that cannabinoids could have as IVM promoters because cannabinoid's molecular pathway is similar to the one by which oocyte's meiosis resumption is activated. With the intention of advancing in the possible use of cannabinoids as supplements for the media for in vitro maturation of oocytes, we intend to deepen the study of the function of the phytocannabinoid Δ-9-tetrahydrocannabinol (THC) in the IVM process. METHODS: By immunocytochemistry, we detected the location pattern of cannabinoid receptor type 1 (CB1) and type 2 (CB2) during oocyte maturation in presence or absence of THC, as well as, the staining pattern of p-AKT and p-ERK. We used a genetic/ pharmacological approach generating knockout oocytes for CB1 and/or CB2 and they were incubated with THC during the oocyte maturation to visualize the physiological effects of THC, observing the rate of blastocyst achieved by oocyte. RESULTS: This study confirms that the incubation of oocytes with THC during IVM accelerated some events of that process like the phosphorylation pattern of ERK and AKT and was able to increase the blastocyst rate in response to IVF. Moreover, it seems that both CB1 and CB2 are necessary to maintain a healthy oocyte maturation. CONCLUSION: Our data suggest that THC may be useful IVM supplements in clinic as is more feasible and reliable than any synthetic cannabinoid.


Assuntos
Blastocisto/efeitos dos fármacos , Dronabinol/farmacologia , Oócitos/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Blastocisto/citologia , Blastocisto/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Fertilização In Vitro , Técnicas de Maturação in Vitro de Oócitos , Meiose/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oócitos/citologia , Oócitos/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor CB1 de Canabinoide/genética , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/genética , Receptor CB2 de Canabinoide/metabolismo
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1265-1271, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418391

RESUMO

OBJECTIVE: To explore the effect of bone morphogenetic protein 4(BMP4) on the cell cycle and apoptosis of hemaropoictic stem and progenitor cells (HSPC) in conditions of 5-fluorouracil (5-FU)-inducing bone marrow suppression and stress hemogenesis, and its possible mechanism. METHODS: The C57BL transgenic mice with BMP4 overexpression were established and were enrolled in transgenic group (BMP4 group), at the same time the wild type mice matching in age, sex and body weight were selected and were enrolled in control group (WT group). The bone marrow suppression was induced by injection with 5-FU in dose of 150 mg/kg, then the nucleated cells were isolated from bone marrow. After the HSPCs were markered with C-kit/sca-1 fluorescent antibodies, the changes of cell cycle and apoptosis of HSPC were detected by Aunexin V/PI and Ki67/DAPI double staining; the cell cycle-essociated hemotopoietic regulatory factors were detected by RT-qPCR. RESULTS: Under physiologic status, there were no significant differences in cell cycle and apoptotic rate of HSPC between WT group and BMP-4 group. After the bone marrow was suppressed, the ratio of HSPC at G0 phase in BMP4 group significantly decreased(P<0.05); the apoptosis rate of HSPC significantly increased(P<0.05); the mRNA expression levels of hypoxia-inducing factor Hif-1α and chemotactic factor CXCL12 in stroma of BMP4 group were down-regulated significanfly(P<0.05). CONCLUSION: Under non-physiologic conditions such as stress hemogenesis or bone marrow suppression, the up-regulation of BMP4 can promote HSPC into cell cycle and apoptosis of HSPC, moreover, the BMP4 may play a regulatory role for cell cycle of HSPC through direct or indirect down-regulation of Hif-1α and CXCL-12 expressions.


Assuntos
Células-Tronco Hematopoéticas , Animais , Antineoplásicos , Apoptose , Proteína Morfogenética Óssea 4 , Ciclo Celular , Camundongos , Camundongos Endogâmicos C57BL
3.
Pharm Res ; 36(10): 141, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31367840

RESUMO

PURPOSE: The purpose of the present study was to investigate changes of blood-brain barrier (BBB) and brain parenchymal protein expression due to type II diabetes mellitus (T2DM) induced by a high-fat diet (HFD) by using SWATH-based quantitative proteomics. METHODS: Mice were fed a HFD for 2 or 10 weeks, and then SWATH-based quantitative proteomic analysis, western blot analysis, immunohistochemistry and functional transport studies were performed. RESULTS: In brain capillaries, expression levels of BBB transporters (Glut1, P-glycoprotein) and tight-junction proteins (claudin-5, occludin) were significantly reduced in HFD mice at 2 weeks, but recovered to the levels in the normal diet (ND) group at 10 weeks. P-glycoprotein function at the BBB was reduced at 2 weeks. In the cerebral cortex and hippocampus, neurofilament, which is important for neuronal function, was decreased in HFD mice at 2 weeks, but recovered at 10 weeks. CONCLUSION: Our results suggest that changes in the status of insulin resistance influence expression of BBB transporters, which in turn may alter the expression of cognitive function-related proteins.


Assuntos
Encéfalo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Resistência à Insulina , Insulina/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/irrigação sanguínea , Capilares/metabolismo , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Filamentos Intermediários/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteômica , Proteínas de Junções Íntimas/metabolismo
4.
J Nanobiotechnology ; 17(1): 87, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387604

RESUMO

BACKGROUND: Adoptive T cell-transfer (ATC) therapy is a highly promising cancer-treatment approach. However, in vivo-administered T cells tend to disperse, with only a small proportion reaching the tumour. To remedy this, magnetic targeting of T cells has been recently explored. Magnetic nanoparticles (MNPs) functionalised with antibodies were attached to effector T cells and magnetically recruited to tumour sites under MRI guidance. In this study, we investigated whether 3-aminopropyl-triethoxysilane (APS)-coated MNPs directly attached to CD8+ T cell membranes could also magnetically target and accumulate tumour-specific CD8+ T cells in solid tumours using an external magnetic field (EMF). As it has been shown that T cells associated with APS-coated MNPs are retained in lymph nodes (LNs), and tumour-draining LNs are the most common sites of solid-tumour metastases, we further evaluated whether magnetic targeting of APS-MNP-loaded CD8+ T cells could cause them to accumulate in tumour-draining LNs. RESULTS: First, we show that antigen-specific CD8+ T cells preserve their antitumor activity in vitro when associated with APS-MNPs. Next, we demonstrate that the application of a magnetic field enhanced the retention of APS-MNP-loaded OT-I CD8+ T cells under flow conditions in vitro. Using a syngeneic mouse model, we found similar numbers of APS-MNP-loaded OT-I CD8+ T cells and OT-I CD8+ T cells infiltrating the tumour 14 days after cell transfer. However, when a magnet was placed near the tumour during the transfer of tumour-specific APS-MNP-loaded CD8+ T cells to improve tumour infiltration, a reduced percentage of tumour-specific T cells was found infiltrating the tumour 14 days after cell transfer, which was reflected in a smaller reduction in tumour size compared to tumour-specific CD8+ T cells transferred with or without MNPs in the absence of a magnetic field. Nonetheless, magnet placement near the tumour site during cell transfer induced infiltration of activated tumour-specific CD8+ T cells in tumour-draining LNs, which remained 14 days after cell transfer. CONCLUSIONS: The use of an EMF to improve targeting of tumour-specific T cells modified with APS-MNPs reduced the percentage of these cells infiltrating the tumour, but promoted the retention and the persistence of these cells in the tumour-draining LNs.


Assuntos
Transferência Adotiva , Linfócitos T CD8-Positivos/transplante , Linfonodos/patologia , Linfócitos do Interstício Tumoral/imunologia , Nanopartículas de Magnetita/química , Neoplasias Experimentais/terapia , Animais , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Proliferação de Células , Sobrevivência Celular , Feminino , Linfonodos/imunologia , Ativação Linfocitária , Linfócitos do Interstício Tumoral/patologia , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/patologia , Propilaminas/química , Silanos/química
5.
Am J Orthod Dentofacial Orthop ; 156(2): 193-202, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31375229

RESUMO

OBJECTIVES: To evaluate whether the effects on the mandibular condylar cartilage (MCC) and subchondral bone are transient of botulinum neurotoxin (Botox) injection into the masseter muscle. METHODS: Botox (0.3 U) was injected into the right masseter of 6-week-old female mice (C57BL/6; n = 16). In addition, 16 mice were used as control and received no injections. Experimental and matching control mice were killed 4 or 8 weeks after the single Botox injection. Mandibles and mandibular condyles were analyzed by means of microscopic computed tomography (microCT) and histology. Sagittal sections of condyles were stained for tartrate-resistant acid phosphatase (TRAP), toluidine blue, 5-ethynyl-2'-deoxyuridine (EdU), and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling. RESULTS: Bone volume fraction was significantly decreased on the subchondral bone of the Botox-injected side, compared with the control side and control mice, 4 and 8 weeks after injection. Furthermore, histologic analysis revealed decrease in mineralization, cartilage thickness, TRAP activity, and EdU-positive cells in the MCC of the Botox-injected side 4 and 8 weeks after injection. CONCLUSIONS: The effects on the MCC and subchondral bone of Botox injection into the masseter muscle persisted for 8 weeks after injection and were not considered to be transient.


Assuntos
Toxinas Botulínicas Tipo A/farmacologia , Côndilo Mandibular/efeitos dos fármacos , Músculo Masseter/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Injeções , Masculino , Mandíbula , Côndilo Mandibular/diagnóstico por imagem , Côndilo Mandibular/patologia , Músculo Masseter/diagnóstico por imagem , Músculo Masseter/patologia , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Articulação Temporomandibular
6.
Dokl Biochem Biophys ; 486(1): 168-170, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31367813

RESUMO

In the present study, we analyzed the uptake of radiolabeled dopamine by intact synaptosomes and purified synaptic vesicles isolated from the dorsal striatum of mice with constitutive inactivation of all three synuclein-coding genes and wild-type mice. Synuclein deficiency substantially compromised the uptake of this neurotransmitter by synaptic vesicles but had no effect on synaptosomal dopamine uptake.


Assuntos
Dopamina/metabolismo , Vesículas Sinápticas/metabolismo , Sinucleínas/deficiência , Animais , Transporte Biológico/genética , Inativação Gênica , Camundongos , Camundongos Endogâmicos C57BL , Sinucleínas/genética
7.
Dokl Biochem Biophys ; 486(1): 171-174, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31367814

RESUMO

Under conditions of the experimental model of Parkinson's disease at the preclinical (early) and clinical stage-injection of mice with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 5 and 10 weeks-the toxic effects of MPTP was evaluated (the content of catecholamines and their metabolites in the heart, which receives the most extensive sympathetic innervation, was determined). The obtained data indicated the beginning of desympathization of the heart at the preclinical stage of PD and its progression at the clinical stage of the disease.


Assuntos
Catecolaminas/metabolismo , Neurotoxinas/toxicidade , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiologia , Animais , Coração/efeitos dos fármacos , Coração/inervação , Masculino , Camundongos , Camundongos Endogâmicos C57BL
8.
Biol Res ; 52(1): 48, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31466525

RESUMO

BACKGROUND: Light exposure is a common stress factor in in vitro manipulation of embryos in the reproductive center. Many studies have shown the deleterious effects of high-intensity light exposure in different animal embryos. However, no transcriptomic studies have explored the light-induced injury and response in preimplantation embryos. RESULTS: Here, we adopt different time-courses and illumination intensities to treat mouse embryos at the 2-cell stage and evaluate their effects on blastulation. Meanwhile, single-cell transcriptomes from the 2-cell to blastocyst stage were analyzed after high-intensity light exposure. These data show that cells at each embryonic stage can be categorized into different light conditions. Further analyses of differentially expressed genes and GO terms revealed the light-induced injury as well as the potential repair response after high-intensity lighting. Maternal-to-zygote transition is also affected by the failure to remove maternal RNAs and deactivate zygotic genome expression. CONCLUSION: Our work revealed an integrated response to high-intensity lighting, involving morphological changes, long-lasting injury effects, and intracellular damage repair mechanisms.


Assuntos
Técnicas de Cultura Embrionária , Desenvolvimento Embrionário , Luz/efeitos adversos , Análise de Sequência de RNA , Análise de Célula Única , Animais , Blastocisto , Feminino , Camundongos , Camundongos Endogâmicos C57BL
9.
Zhonghua Xin Xue Guan Bing Za Zhi ; 47(8): 634-639, 2019 Aug 24.
Artigo em Chinês | MEDLINE | ID: mdl-31434435

RESUMO

Objective: To investigate the effects of tanshinone ⅡA on atherosclerosis plaque formation and adventitial mast cells activation in high-fat-diet induced Apo E(-/-) mice model. Methods: Sixteen 8-week-old Apo E(-/-)male mice and eight 8-week-old C57BL/6 male mice were randomly allocated into following group: the control group (C57BL/6 + carboxymethyl cellulose per gavage), the atherogenic group (Apo E(-/-)+carboxymethyl cellulose per gavage) and the tanshinoneⅡA intervention group (Apo E(-/-)+30 mg/kg tanshinone ⅡA per gavage). All three groups were fed with high-fat-diet for 26 weeks. Tanshinone ⅡA/carboxymethyl cellulose was applied by the method of gavage administration 6 weeks before execution. After 26 weeks, tumor necrosis factor-α (TNF-α) andinterleukin (IL)-6 levels in serum were assessed by ELISA. Carotid artery was removed, fixed with paraformaldehyde, embedded with paraffin and sectioned. Percentage of stenosis was evaluated on HE stained sections. Plaque progression was assessed by Movat staining. Toluidine blue staining was used to evaluate mast cells infiltration and activation. Immunochemistry staining was used to assess 5-HT, TNF-α and IL-6 expression. mRNA expression of mast cell marker Fcer1a in adventitial tissue was detected by real time-PCR. Results: After high-fat-diet for 26 weeks, the mice in the atherogenic group showed advanced atherosclerosis, tanshinoneⅡA intervention reduced the percentage of carotid artery stenosis caused by atherosclerotic plaque formation ((58.48±8.07)% vs. (80.31±4.08)%, P<0.05). Compared with the atherogenic group, tanshinone ⅡA intervention group had lower level of TNF-α ((12.39±1.62)pg/ml vs. (17.44±1.42)pg/ml) and IL-6 ((116.24±12.16)pg/ml vs. (166.05±19.09)pg/ml) in serum, lower TNF-α ((20 145±1 556) vs. (25 288±1 671)) and IL-6 ((25 688±1 604) vs. (35 286±4 198)) expression in adventitia (all P<0.05). TanshinoneⅡA intervention also decreased the number of mast cells infiltration and activation, reduced 5-HT expression and mast cell marker Fcer1a mRNA relative expression in adventitia (all P<0.05). Conclusions: Tanshinone ⅡA could attenuate induced by high-fat-diet carotid artery atherosclerosis in Apo E(-/-) mice. The protective effect of tanshinoneⅡA is probably mediated through reducing the number and activation percentage of mast cells, decreasing the release of inflammatory cytokines and inflammation of carotid artery in adventitia.


Assuntos
Túnica Adventícia , Aterosclerose , Animais , Apolipoproteínas E , Artérias Carótidas , Masculino , Mastócitos , Camundongos , Camundongos Endogâmicos C57BL
10.
Zhonghua Nei Ke Za Zhi ; 58(8): 584-591, 2019 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-31365980

RESUMO

Objective: To investigate the effects of probiotics and synbiotics on inflammation and microbiota of acute colitis in mice. Methods: C57BL/6J mice were divided into 4 groups randomly. Each group had 10 mice and was given 2.5% dextran sulfate sodium (DSS) drinking water for 5 days other than the blank control group. Except for model control group, other two groups were administrated with probiotics and synbiotics, respectively. Probiotics was composed of Lactobacillus acidophilus, Lactobacillus rhamnosus and Bifidobacterium lactis, while synbiotics was composed of the aforementioned probiotics, inulin and galactooligosaccharide. Feces of different periods and mucosa samples were collected to analyze the differences of enteric flora by 16s rDNA sequencing. Results: (1) Pathological scores in probiotics group and synbiotics group were 5.40±2.79 and 7.25±2.87, respectively, which were significantly lower than those in the model control group with scores 27.00±7.94. Model control group, probiotics group and synbiotics group showed lower flora diversity, increased Bacteroides and decreased Faecalibacterium than blank control group. The mucosal microbiota was different from fecal flora in abundance and species for each group, and Mucispirillum was more common in mucosa. Conclusions: Probiotics and synbiotics alleviate the inflammation of acute colitis in mice. Imbalance of beneficial genera to harmful genera is the characteristic of acute colitis. Supplementation of probiotics and synbiotics contributes to regulating the balance of intestinal microbiota.


Assuntos
Colite/tratamento farmacológico , Colo/microbiologia , Fármacos Gastrointestinais/administração & dosagem , Microbiota/efeitos dos fármacos , Probióticos/administração & dosagem , Simbióticos/administração & dosagem , Animais , Colite/induzido quimicamente , Colo/efeitos dos fármacos , Modelos Animais de Doenças , Fezes/microbiologia , Fármacos Gastrointestinais/uso terapêutico , Inflamação , Camundongos , Camundongos Endogâmicos C57BL , Probióticos/uso terapêutico
11.
Zhonghua Shao Shang Za Zhi ; 35(6): 459-463, 2019 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-31280541

RESUMO

Objective: To investigate the significance of intestinal fatty acid binding protein (IFABP) in the evaluation of intestinal barrier dysfunction of mice at the early stage of severe burn injury. Methods: Thirty-six 8-week-old C57BL/6 male mice were collected and divided into normal control group (n=6) and scald group (n=30) according to random number table. Back of each mouse in scald group was placed into hot water of 90 ℃ for 10 s, causing full-thickness scald (hereinafter refer to as burn) of 30% total body surface area, while mice in normal control group were not inflicted with burns. Six mice in normal control group were taken, and 6 mice in scald group at 1, 2, 6, 12, and 24 h post injury were taken respectively. The portal vein blood of each mouse was extracted and the plasma was separated to measure intestinal permeability with fluorescin isothiocyanate-dextran fluorescence probe tracing method and plasma IFABP content by enzyme-linked immunosorbent assay. The distal ileum tissue of mice in normal control group and scald group at each time point post injury was collected to observe the morphology of the intestinal mucosa tissue by hematoxylin-eosin staining. Data were processed with one-way analysis of variance and Student-Newman-Keuls test, and pearson correlation test was used to analyze the correlation between intestinal permeability and plasma IFABP content of burned mice. Results: (1) At 1, 2, 6, 12, and 24 h post injury, the intestinal permeability of mice in scald group was 2.7±0.8, 5.4±2.5, 7.3±4.2, 12.4±6.1, 1.4±0.7, respectively, obviously higher than 1.0±0.4 of normal control group (P<0.05 or P<0.01). The intestinal permeability of mice in scald group showed an increasing trend post injury, reaching the peak at 12 h post injury, and rapidly falling back at 24 h post injury. (2) At 1, 2, 6, 12, and 24 h post injury, the plasma IFABP content of mice in scald group was (64±11), (59±12), (76±18), (111±22), and (66±10) ng/mL, obviously higher than (35±8) ng/mL in normal control group (P<0.05 or P<0.01). The plasma IFABP content of mice in scald group showed an increasing trend post injury, reaching the peak at 12 h post injury, and rapidly decreasing at 24 h post injury. (3) Uniform thickness of mucosa, intact epithelia, regularly arranged villi, and no inflammatory cell infiltration were observed in ileum of mice in normal control group. In ileum of mice in scald group, shortened villi of mucosa with different degrees, edema of lamina propria, and infiltration of neutrophils were observed at 1 and 2 h post injury; obviously damaged and partially exfoliated ileal mucosa, disorderly arranged and broken villi, degenerated and necrotic epithelial cells, dilated central lacteal, and infiltration of lymphocytes and neutrophils were observed at 6 and 12 h post injury; the damage of ileal mucosa was alleviated, and basically intact epithelia, dilated central lacteal, and infiltration of inflammatory cells were observed at 24 h post injury. (4) There was a significantly positive correlation between the intestinal permeability and the plasma IFABP content of burned mice (r=0.841, P<0.05). Conclusions: The plasma IFABP can be used as a good biological indicator for the evaluation of intestinal barrier dysfunction of mice at the early stage of severe burn injury.


Assuntos
Queimaduras/terapia , Proteínas de Ligação a Ácido Graxo/uso terapêutico , Mucosa Intestinal/fisiopatologia , Lesões dos Tecidos Moles/terapia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
12.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 44(6): 628-633, 2019 Jun 28.
Artigo em Chinês | MEDLINE | ID: mdl-31304923

RESUMO

OBJECTIVE: To investigate the effects of equal concentration of Helicobacter pylori suspension on gastric mucosal infection in mice by different gavage methods. 
 Methods: Six-week-old male C57BL/6 mice were infected by a suspension of Brucella broth containing the same amount of NCTC11637 Helicobacter pylori suspension by A, B, C, and D methods. For method A, the mice were intragastrically administered with Helicobacter pylori suspension (0.2 mL per mouse), once two day for 5 times; for method B, the mice were intragastrically administered with Helicobacter pylori (0.2 mL per mouse) once a day for 5 times; for method C, the mice were perfused with 0.4 mL per mouse of Helicobacter pylori suspension on the first day, then once a day and 0.2 mL per mouse for 3 times; for method D, the mice were administrated with 0.4 mL per mouse Helicobacter pylori suspension on the first day, 0.2 mL per mouse every other day for 3 times. For method E, the mice received equal amounts of normal saline. The mice were killed at 2, 4, and 6 weeks after gavage. The gastric mucosa was detected by rapid urease test for Helicobacter pylori infection, and gastric mucosa was taken for HE staining to observe the degree of infection.
 Results: After 2 weeks of gavage, the infection rates of the mice in A, B, C, and D group were 33.3%, 50.0%, 66.7%, and 33.3%, respectively. The degree of inflammation infection was as following order: C group>B group>D group>A group>E group. The infection rates of mice after 4 weeks of gavage in the A, B, C, and D groups were 50.0%, 83.3%, 83.3%, and 66.7%, respectively. The degree of inflammation infection was as following order: C group>B group>D group>A group>E group. After 6 weeks of gavage, the infection rate in A, B, C, and D groups was 100%, while the degree of inflammation infection was as following order: C group>D group>B group>A group>E group.
 Conclusion: At the acute stage of Helicobacter pylori infection, different gavage methods show different infection rates in mice, and the degree of inflammation is different. At the chronic stage, different gavage methods display the same infection rate in mice with different degree. The gavage method that 0.4 mL Helicobacter pylori suspension on the first day, then once a day and 0.2 mL for 3 times is most conducive to Helicobacter pylori colonization in the gastric mucosa of mice. This method can induce the the most seriou inflammatory infection and is beneficial to the successful establishment of the Helicobacter pylori infection model.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Animais , Mucosa Gástrica , Masculino , Camundongos , Camundongos Endogâmicos C57BL
13.
J Agric Food Chem ; 67(32): 9039-9049, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31353898

RESUMO

This study focused on the effects of oxidized tyrosine products (OTPs) and major component dityrosine (DT) on the brain and behavior of growing mice. Male and female mice were treated with daily intragastric administration of either tyrosine (Tyr; 420 µg/kg body weight), DT (420 µg/kg body weight), or OTPs (1909 µg/kg body weight) for 35 days. We found that pure DT and OTPs caused redox state imbalance, elevated levels of inflammatory factors, hippocampal oxidative damage, and neurotransmitter disorders while activating the mitochondrial apoptosis pathway in the hippocampus and downregulating the genes associated with learning and memory. These events eventually led to growing mice learning and memory impairment, lagging responses, and anxiety-like behaviors. Furthermore, the male mice exhibited slightly more oxidative damage than the females. These findings imply that contemporary diets and food-processing strategies of the modern world should be modified to reduce oxidized protein intake.


Assuntos
Transtornos da Memória/etiologia , Aprendizagem Espacial , Tirosina/análogos & derivados , Tirosina/efeitos adversos , Tirosina/química , Animais , Comportamento Animal , Feminino , Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Humanos , Masculino , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , Transtornos da Memória/psicologia , Camundongos , Camundongos Endogâmicos C57BL , Oxirredução , Estresse Oxidativo , Tirosina/metabolismo
14.
J Agric Food Chem ; 67(32): 8868-8874, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31319027

RESUMO

Chenodeoxycholic acid (CDCA), a primary bile acid, has been demonstrated to play important roles as a signaling molecule in various physiology functions. However, the role of CDCA in regulating intestinal barrier function remains largely unknown. This study aimed to investigate the effects of CDCA on the lipopolysaccharide (LPS)-impaired intestinal epithelial barrier function and explore the underlying mechanisms. In IPEC-J2 cells, CDCA reversed the LPS-induced increase in transepithelial electrical resistance and decrease in tight junction protein expression. In addition, we found that farnesoid X receptor (FXR) but not Takeda G-protein receptor 5 was responsible for the CDCA-improved epithelial barrier function impaired by LPS. Furthermore, CDCA blocked LPS-induced activation of the myosin light chain kinase (MLCK) pathway in a FXR-dependent manner and elicited similar effects to MLCK inhibition. In mice, CDCA supplementation restored LPS-induced elevation of intestinal permeability and MLCK expression and reduction of tight junction protein expression, thus alleviating LPS-induced intestinal barrier impairment. In conclusion, CDCA protected against the LPS-induced impairment of the intestinal epithelial barrier function via the FXR-MLCK pathway.


Assuntos
Ácido Quenodesoxicólico/administração & dosagem , Enteropatias/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Lipopolissacarídeos/efeitos adversos , Quinase de Cadeia Leve de Miosina/metabolismo , Substâncias Protetoras/administração & dosagem , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Células CACO-2 , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Enteropatias/induzido quimicamente , Enteropatias/genética , Enteropatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Quinase de Cadeia Leve de Miosina/genética , Receptores Citoplasmáticos e Nucleares/genética , Transdução de Sinais/efeitos dos fármacos , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/genética , Junções Íntimas/metabolismo
15.
J Agric Food Chem ; 67(32): 8847-8854, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31328515

RESUMO

Microbiome has been revealed as a key element involved in maintaining the circadian rhythms. Oolong tea polyphenols (OTP) has been shown to have potential prebiotic activity. Therefore, this study focused on the regulation mechanisms of OTP on host circadian rhythms. After 8 weeks of OTP administration, a large expansion in the relative abundance of Bacteroidetes with a decrease in Firmicutes was observed, which reflected the positive modulatory effect of OTP on gut flora. In addition, Kyoto Encyclopedia of Genes and Genomes pathways of ATP-binding cassette transporters, two-component system, and the biosynthesis of amino acids enriched the most differentially expressed genes after OTP treatment. Of the differentially expressed proteins identified, most were related to metabolism, genetic information processing, and environmental information processing. It underscores the ability of OTP to regulate circadian rhythm by enhancing beneficial intestinal microbiota and affecting metabolic pathways, contributing to the improvement of host microecology.


Assuntos
Camellia sinensis/química , Transtornos Cronobiológicos/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Transtornos Cronobiológicos/microbiologia , Transtornos Cronobiológicos/fisiopatologia , Modelos Animais de Doenças , Feminino , Humanos , Intestinos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Chá/química
16.
J Agric Food Chem ; 67(32): 8794-8809, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31345023

RESUMO

Oxidative stress may play a critical role in the progression of liver disorders. Increasing interest has been given to the associations among diet, oxidative stress, gut-liver axis, and nonalcoholic fatty liver disease. Here, we investigated the effects of processed meat proteins on biomarkers of lipid homeostasis, hepatic metabolism, antioxidant functions, and gut microbiota composition in glutaredoxin1 deficient (Glrx1-/-) mice. The wild-type (WT) and Glrx1-/- mice were fed a soy protein diet (SPD), a dry-cured pork protein diet (DPD), a braised pork protein diet (BPD), and a cooked pork protein diet (CPD) at a dose of 20% of protein for 3 months. Serum and hepatic total cholesterol, serum endotoxin, hepatic liver droplet %, and antioxidant capacity were significantly increased in the CPD fed WT mice. In addition, CPD fed Glrx1-/- mice significantly increased total cholesterol, triacylglycerol, and pro-inflammatory cytokines which are accompanied by higher steatosis scores, intrahepatic lipid accumulation, and altered gene expression associated with lipid metabolism. Furthermore, hepatic gene expression of Nrf2/keap1 signaling pathway and its downstream signaling targets were determined using RT-qPCR. Glrx1 deficiency increased Nrf2 activity and expression of its target genes (GPx, catalase, SOD1, G6pd, and Bbc3), which was exacerbated by intake of CPD. Metagenomic analyses revealed that Glrx1-/- mice fed meat protein diets had higher abundances of Mucispirillum, Oscillibacter, and Mollicutes but lower abundances of Bacteroidales S24-7 group_norank, Blautia, and Anaerotruncus than their wild-type counterparts. In summary, Glrx1 deficiency induced an increase in serum biomarkers for lipid homeostasis, gut microbiota imbalance, and upregulation of Nrf2/Keap1 and antioxidant defense genes, which was aggravated by cooked meat protein diet.


Assuntos
Glutarredoxinas/genética , Inflamação/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Lipogênese , Fígado/metabolismo , Produtos da Carne/efeitos adversos , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Colesterol/sangue , Citocinas/metabolismo , Feminino , Microbioma Gastrointestinal , Glutarredoxinas/deficiência , Humanos , Inflamação/genética , Inflamação/imunologia , Inflamação/microbiologia , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 2 Relacionado a NF-E2/genética , Carne Vermelha , Transdução de Sinais , Triglicerídeos/sangue
17.
J Agric Food Chem ; 67(31): 8510-8519, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31294559

RESUMO

Acrylamide, mainly formed in Maillard browning reaction during food processing, causes defects in liver circadian clock and mitochondrial function by inducing oxidative stress. Resveratrol is a polyphenol that has powerful antioxidant and anti-inflammatory activity. However, the preventive effects of resveratrol on acrylamide-triggered oxidative damage and circadian rhythm disorders are unclear at the current stage. The present research revealed that resveratrol pretreatment prevented acrylamide-induced cell death, mitochondrial dysfunction, and inflammatory responses in HepG2 liver cells. Acrylamide significantly triggered disorders of circadian genes transcription and protein expressions including Bmal1 and Cry 1 in primary hepatocytes, which were prevented by resveratrol pretreatment. Moreover, we found that the beneficial effects of resveratrol on stimulating Nrf2/NQO-1 pathway and mitochondrial respiration complex expressions in acrylamide-treated cells were Bmal1-dependent. Similarly, the inhibitory effects of resveratrol on inflammation signaling NF-κB were Cry1-dependent. In conclusion, these results demonstrated resveratrol could be a promising compound in suppressing acrylamide-induced hepatotoxicity and balancing the circadian clock.


Assuntos
Fatores de Transcrição ARNTL/imunologia , Acrilamida/toxicidade , Transtornos Cronobiológicos/imunologia , Criptocromos/imunologia , Hepatócitos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Resveratrol/farmacologia , Fatores de Transcrição ARNTL/genética , Animais , Transtornos Cronobiológicos/tratamento farmacológico , Transtornos Cronobiológicos/genética , Transtornos Cronobiológicos/fisiopatologia , Ritmo Circadiano/efeitos dos fármacos , Criptocromos/genética , Células Hep G2 , Hepatócitos/imunologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/genética , Mitocôndrias/imunologia
18.
Gene ; 714: 143996, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31348980

RESUMO

The uniquely human α7-nAChR gene (CHRFAM7A) is evolved from the fusion of two partially duplicated genes, FAM7 and α7-nAChR gene (CHRNA7), and is inserted on same chromosome 15, 5' end of the CHRNA7 gene. Transcription of CHRFAM7A gene produces a 1256-bp open reading frame encoding dup-α7-nAChR, where a 27-aminoacid residues from FAM7 replaced the 146-aminoacid residues of the N-terminal extracellular ligand binding domain of α7-nAChR. In vitro, dup-α7-nAChR has been shown to form hetero-pentamer with α7-nAChR and dominant-negatively regulates the channel functions of α7-nAChR. However, the contribution of CHRFAM7A gene to the biology of α7-nAChR in the brain in vivo remains largely a matter of conjecture. CHRFAM7A transgenic mouse was created and differentially expressed proteins were profiled from the whole brain using iTRAQ-2D-LC-MS/MS proteomic technology. Proteins with a fold change of ≥1.2 or ≤0.83 and p < 0.05 were considered to be significant. Bioinformatics analysis showed that over-expression of the CHRFAM7A gene significantly modulated the proteins commonly involved in the signaling pathways of α7-nAChR-mediated neuropsychiatric disorders including Parkinson's disease, Alzheimer's disease, Huntington's disease, and alcoholism, suggesting that the CHRFAM7A gene contributes to the pathogenesis of neuropsychiatric disorders mostly likely through fine-tuning the functions of α7-nAChR in the brain.


Assuntos
Camundongos Transgênicos/genética , Receptor Nicotínico de Acetilcolina alfa7/genética , Animais , Encéfalo/metabolismo , Cromatografia Líquida/métodos , Cromossomos Humanos Par 15/genética , Perfilação da Expressão Gênica/métodos , Genes Duplicados/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteômica/métodos , Transdução de Sinais/genética , Espectrometria de Massas em Tandem/métodos
19.
Cancer Immunol Immunother ; 68(8): 1303-1315, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31278476

RESUMO

Our previous work has demonstrated the high efficiency of CD8+ natural killer T (NKT)-like cells in killing antigen-bearing dendritic cells. To evaluate their role in the tumor microenvironment, we performed in vitro and in vivo antitumor experiments to investigate whether CD8+NKT-like cells could kill Yac-1 and B16 cells like NK cells and kill EL4-OVA8 cells in an antigen-specific manner like cytotoxic T lymphocytes (CTLs). Unlike NK1.1-CTLs, CD8+NKT-like cells also exhibit the capability to kill myeloid-derived suppressor cells (MDSCs) in an antigen-specific manner, indicative of their potential role in clearing tumor antigen-bearing MDSCs to improve the antitumor microenvironment. In vitro blocking experiments showed that granzyme B inhibitor efficiently suppressed the cytotoxicity of CD8+NKT-like cells against tumor cells and MDSCs, while Fas ligand (FasL) or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) inhibition failed to produce similar effects. Transcriptomic and phenotypic analyses of CD8+NKT-like cells, NK cells, and NK1.1-CTLs indicated that CD8+NKT-like cells expressed both T-cell activation markers and NK cell markers, thus bearing features of both the activated T cells and NK cells. Taken together, CD8+NKT-like cells could exert NK- and CTL-like antitumor effects through the elimination of both tumor cells and MDSCs in a granzyme B-dependent manner.


Assuntos
Células Matadoras Naturais/imunologia , Células Supressoras Mieloides/imunologia , Células T Matadoras Naturais/imunologia , Neoplasias Experimentais/terapia , Linfócitos T Citotóxicos/imunologia , Animais , Antígenos CD8/metabolismo , Citotoxicidade Imunológica , Feminino , Granzimas/metabolismo , Humanos , Ativação Linfocitária , Melanoma Experimental , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neoplasias Experimentais/imunologia , Transcriptoma , Microambiente Tumoral
20.
DNA Cell Biol ; 38(8): 887-894, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31295021

RESUMO

Circular RNAs (circRNAs), as with other noncoding RNAs, have emerged as novel molecules of interest in gene regulation and in the development of many diseases. However, the expression and function of circRNAs in inflammation-induced lymphangiogenesis (LG) are still unknown. Microarray profiling in inflamed human lymphatic endothelial cells identified 82 differentially expressed circRNAs, including 6 downregulated and 76 upregulated circRNAs. One of the top 10 upregulated circRNAs, cZNF609, was selected for subsequent quantitative real-time PCR validation, and was found to be significantly upregulated in inflamed corneas from both mouse and human eyes. The expression of miR-184 was significantly lower in inflamed corneas than in control ones, which suggested that cZNF609 might serve as a sponge for miR-184. The expression of heparanase, a potential target gene of miR-184, was significantly increased in inflamed corneas. Therefore, circRNAs may serve as potential regulators of corneal LG. These findings lay a foundation for functional research on circRNAs in corneal LG pathogenesis.


Assuntos
Córnea/fisiologia , Endoftalmite/genética , Linfangiogênese/genética , RNA , Animais , Células Cultivadas , Córnea/patologia , Endoftalmite/etiologia , Células Endoteliais , Humanos , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs , Análise de Sequência com Séries de Oligonucleotídeos
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