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1.
Exp Cell Res ; 389(2): 111855, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31978385

RESUMO

Takeda-G-protein-receptor-5 (TGR5) is a G-protein-coupled receptor (GPCR) activated by bile acids, and mortalin is a multipotent chaperone of the HSP70 family. In the present study, TGR5 was detected by immunohistochemistry (IHC) in extrahepatic cholangiocarcinoma (ECC) specimens, and TGR5 expression in ECC tissues and adjacent tissues was compared. In vitro TGR5 was overexpressed and knocked down in human intrahepatic cholangiocarcinoma (ICC) cell line RBE and human extrahepatic cholangiocarcinoma (ECC) cell line QBC-939 to observe its effects on the biological behavior of cholangiocarcinoma (CC) cells, including proliferation, apoptosis and migration. In vivo xenograft model was constructed to explore the role of TGR5 in CC growth. Proteins that interacted with TGR5 were screened using an immunoprecipitation spectrometry approach, and the identified protein was down-regulated to investigate its contribution to CC growth. The present study demonstrated that TGR5 is highly expressed in CC tissues, and strong TGR5 expression may indicate high malignancy in CC. Furthermore, TGR5 promotes CC cell proliferation, migration, and apoptosis resistance. TGR5 boosts CC growth in vivo. In addition, TGR5 combines with mortalin and regulates mortalin expression in the CC cell line. Mortalin participates in the TGR5-induced increase in CC cell proliferation. In conclusion, TGR5 is of clinical significance based on its implications for the degree of malignancy in patients with CC. Mortalin may be a downstream component regulated by TGR5, and TGR5 promotes cholangiocarcinoma at least partially by interacting with mortalin and upregulating its expression. Both TGR5 and mortalin are positive regulators, and may serve as potential therapeutic targets for CC.

2.
Exp Cell Res ; 386(1): 111710, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31693873

RESUMO

Physiological cyclic stretch (CS), caused by artery deformation following blood pressure, plays important roles in the homeostasis of endothelial cells (ECs). Here, we detected the effect of physiological CS on endothelial microvesicles (EMVs) and their roles in leukocyte recruitment to ECs, which is a crucial event in EC inflammation. The results showed compared with the static treatment, pretreatment of 5%-CS-derived EMVs with ECs significantly decreased the adherence level of leukocytes. Comparative proteomic analysis revealed 373 proteins differentially expressed between static-derived and 5%-CS-derived EMVs, in which 314 proteins were uniquely identified in static-derived EMVs, 34 proteins uniquely in 5%-CS-derived EMVs, and 25 proteins showed obvious differences. Based on the proteomic data, Ingenuity Pathways Analysis predicted intercellular adhesion molecule 1 (ICAM1) in EMVs might be the potential molecule involved in EC-leukocyte adhesion. Western blot and flow cytometry analyses confirmed the significant decrease of ICAM1 in 5%-CS-derived EMVs, which subsequently inhibited the phosphorylation of VE-cadherin at Tyr731 in target ECs. Moreover, leukocyte adhesion was obviously decreased after pretreatment with ICAM1 neutralizing antibody. Our present research suggested that physiological stretch changes the components of EMVs, which in turn inhibits leukocyte adhesion. ICAM1 expressed on CS-induced EMVs may play an important role in maintaining EC homeostasis.

3.
Zhen Ci Yan Jiu ; 44(8): 589-93, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31475493

RESUMO

OBJECTIVE: To observe the clinical effect of early acupuncture treatment of limb paralysis in patients with traumatic brain injury (TBI) and changes of serum interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels, so as to explore its mechanism underlying improvement of TBI. METHODS: A total of 70 TBI inpatients were equally divided into a medication group and an acupuncture plus medication group according to a random number table. The medication contained intravenous drip of Mannitol Injection (125 mL, once every 8 h ) and Oxiracetam Injection (4 g, once a day). Starting 72 h after TBI, acupuncture therapy was applied to main points as Fenglong (ST40), Zusanli (ST36), Guanyuan (CV4), Baihui (GV20), Shuigou (GV26) and Fengchi (GB20), etc. The treatment was given once a day for total 28 days. Before and after the treatment, plasma IL-6, BDNF and NGF contents were detected using radioimmunoassay, the volume of the injured brain tissue was detected by using CT scan. The neurological deficit severity was evaluated by using Glasgow Coma Scale (GCS), and the degree of activity of daily living (ADL) ability was assessed by using simplified Fugl-Meyer assessment (FMA) scale, and modified Barthel index (BI), separately. RESULTS: After the treatment, the GCS score on day 28, FMA and ADL-BI scores on day 28 and 60 were significantly increased in both medication and acupuncture plus medication groups in comparison with their own pre-treatment (P<0.05). The focal volume values of the injured brain were significantly decreased on day 14 and 28 in both groups compared with their own pre-treatment (P<0.05). The therapeutic effect of acupuncture plus medication was obviously superior to that of simple medication in lowering focal injured volume on day 14 and 28, and in increasing FMA and ADL-BI scores on day 28 and 60 (P<0.05). Compared with pre-treatment, the levels of plasma IL-6 on day 3, 7 and 14 were significant decreased, and those of plasma BDNF and NGF on day 3, 7 and 14 considerably increased in both groups in comparison with their own pre-treatment (P<0.05). The therapeutic effect of acupuncture plus medication was evidently superior to that of simple medication in lowering IL-6 on day 3 and 7, and in increasing BDNF and NGF levels on day 3, 7 and 14 (P<0.05). CONCLUSION: Early acupuncture treatment can significantly improve the TBI patient's limb motor function and daily life activities, which may be related with its effects in reducing the inflammation and increasing BDNF and NGF levels.


Assuntos
Terapia por Acupuntura , Lesões Encefálicas Traumáticas , Paralisia/terapia , Lesões Encefálicas Traumáticas/complicações , Fator Neurotrófico Derivado do Encéfalo , Humanos , Interleucina-6 , Paralisia/etiologia
4.
Exp Cell Res ; 376(1): 77-85, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30690026

RESUMO

Cyclic stretch regulates proliferation of vascular smooth muscle cells (VSMCs) during hypertension-induced vascular remodeling, but the underlying mechanisms remain to be studied. Connective tissue growth factor (CTGF) has been reported associated with several cellular function such as proliferation,migration and adhesion. Herein, the role of CTGF in VSMCs was investigated in response to mechanical cyclic stretch. Here we show that CTGF is up-regulated both in vivo and in vitro during hypertension. Overexpression of CTGF markedly promoted VSMC proliferation, whereas CTGF knockdown attenuated cyclic stretch-induced proliferation. Furthermore, 3'UTR reporter assays revealed that microRNA-19b-3p (miR-19b-3p) directly regulates CTGF expression. Under pathological condition (e.g. 15% cyclic stretch), miR-19b-3p expression was significantly down-regulated; conversely miR-19b-3p overexpression blocked VSMC proliferation. Taken together, these findings indicate that pathological cyclic stretch induces vascular remodeling by promoting VSMC proliferation via miR-19b-3p/CTGF pathway, and point to CTGF as a potential therapeutic target for hypertension.

5.
J Cell Biochem ; 120(4): 5256-5267, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30320897

RESUMO

Endothelial progenitor cells (EPCs) are vital to the recovery of endothelial function and maintenance of vascular homeostasis. EPCs mobilize to sites of vessel injury and differentiate into mature endothelial cells (ECs). Locally mobilized EPCs are exposed to cyclic stretch caused by blood flow, which is important for EPC differentiation. MicroRNAs (miRNAs) have emerged as key regulators of several cellular processes. However, the role of miRNAs in cyclic stretch-induced EPC differentiation remains unclear. Here, we investigate the effects of microRNA-129-1-3p (miR-129-1-3p) and its novel target Runt-related transcription factor 2 (Runx2) on EPC differentiation induced by cyclic stretch. Bone marrow-derived EPCs were exposed to cyclic stretch with a magnitude of 5% (which mimics physiological mechanical stress) at a constant frequency of 1.25 Hz for 24 hours. The results from a miRNA array revealed that cyclic stretch significantly decreased miR-129-1-3p expression. Furthermore, we found that downregulation of miR-129-1-3p during cyclic stretch-induced EPC differentiation toward ECs. Meanwhile, expression of Runx2, a putative target gene of miR-129-1-3p, was increased as a result of cyclic stretch. A 3'UTR reporter assay validated Runx2 as a direct target of miR-129-1-3p. Furthermore, small interfering RNA (siRNA)-mediated knockdown of Runx2 inhibited EPC differentiation into ECs and attenuated EPC tube formation via modulation of vascular endothelial growth factor (VEGF) secretion from EPCs in vitro. Our findings demonstrated that cyclic stretch suppresses miR-129-1-3p expression, which in turn activates Runx2 and VEGF to promote endothelial differentiation of EPCs and angiogenesis. Therefore, targeting miR-129-1-3p and Runx2 may be a potential therapeutic strategy for treating vessel injury.

6.
Stem Cells ; 36(12): 1863-1874, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30171660

RESUMO

Efficient recruitment and angiogenesis of endothelial progenitor cells (EPCs) are critical during a thrombus event. However, the details of EPC recruitment and the regulation of angiogenesis have not been fully determined. The aim of this study was to determine the role of the long noncoding (lnc)RNA Wilms tumor 1 associated protein pseudogene 1 (WTAPP1) in regulation of the migration and angiogenesis of EPCs. EPCs were isolated from human peripheral blood and characterized by flow cytometry, after which lentivirus-mediated lncRNA WTAPP1 overexpression and knockdown were performed. Scratch assay, Transwell assay, and in vitro and in vivo tube formation assays were performed to measure cell migration, invasion, and angiogenic abilities, respectively. Moreover, a microarray screen, bioinformatic prediction, and quantitative PCR and Western blot of miRNAs interacting with lncRNA WTAPP1 were conducted. Western blot was carried out to elucidate the relationship among WTAPP1, miR-3120-5P, and MMP-1 in the autophagy pathway. WTAPP1 positively regulated migration, invasion, and in vitro and in vivo tube formation in EPCs by increasing MMP-1 expression and activating PI3K/Akt/mTOR signaling. Furthermore, WTAPP1 contains a putative miR-3120-5P binding site. Suppression of WTAPP1 by miR-3120-5P decreased the level of MMP-1. In addition, we demonstrated that suppression of the autophagy pathway is involved in the effects of WTAPP1 on EPC migration and angiogenesis. The lncRNA WTAPP1, a molecular decoy for miR-3120-5p, regulates MMP-1 expression via the PI3K/Akt and autophagy pathways, thereby mediating cell migration and angiogenesis in EPCs. Acting as a potential therapeutic target, the lncRNA WTAPP1 may play an important role in the pathogenesis of DVT. Stem Cells 2018;36:1863-12.


Assuntos
Movimento Celular/fisiologia , Células Progenitoras Endoteliais/fisiologia , Metaloproteinase 1 da Matriz/metabolismo , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Autofagia , Células Progenitoras Endoteliais/citologia , Células Progenitoras Endoteliais/metabolismo , Humanos , Masculino , Metaloproteinase 1 da Matriz/genética , Camundongos , Camundongos Nus , MicroRNAs/genética , Neovascularização Fisiológica/fisiologia , Transdução de Sinais
7.
Neurosci Lett ; 684: 200-204, 2018 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-30114476

RESUMO

Sex differences occur in nociceptive pain, and estrogens are involved in the sex differences. Our previous study shows sex differences exist in acidosis-induced nociception in rats, with females being more sensitive than males to acetic acid. However, the mechanisms underlying the sex differences remain unclear. We report here17ß-estradiol (E2) up-regulates expression of acid-sensing ion channel 3 (ASIC3), which can mediate the acidosis-induced events. The recombinant plasmid of pCDNA3.1-ASIC3-GFP and pCDNA3.1-estrogen receptor α (ERα) were cotransfected to 293 T cells by lipid transfection method. And western blot assays showed expression of ASIC3. We found that E2 markedly increases ASIC3 protein expression in a dose- and time- dependent manner in 293 T cells expressing ASIC3 and ERα. The up-regulating effect of E2 on ASIC3 protein expression is almost completely blocked by the addition of MPP, a specific ERα antagonist. We also observed that sex differences occur in ASIC3 expression in rat dorsal root ganglia (DRG) and in acetic acid-induced nociceptive responses. ASIC3 protein expression in female rat DRG is higher than those in male rat DRG. And female rats are more sensitive to acetic acid-induced nociception than males. ASIC3 protein expression in DRG decreases significantly after ovariectomy, but not after orchiectomy. These results suggest that E2 up-regulates ASIC3 expression through ERα, which may contribute to sex differences in acetic acid-induced nociception.


Assuntos
Canais Iônicos Sensíveis a Ácido/biossíntese , Estradiol/farmacologia , Estrogênios/farmacologia , Caracteres Sexuais , Regulação para Cima/fisiologia , Canais Iônicos Sensíveis a Ácido/genética , Animais , Relação Dose-Resposta a Droga , Feminino , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Expressão Gênica , Células HEK293 , Humanos , Masculino , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos
8.
J Thorac Dis ; 10(3): 1548-1553, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29707305

RESUMO

Background: Closed thoracic drainage tube (CTDT) is a conventional treatment after esophagectomy, even after minimally invasive esophagectomy. Here, we report a single-center, retrospective study to explore the safety and necessity of CTDT after thoracoscopic-esophagectomy. Methods: From October 2015 and August 2016, 50 patients were enrolled and underwent thoracoscopic-esophagectomy in semi-prone position by same surgical team. Perioperative demographic and surgical parameters, and patients' satisfaction with or without CTDT after thoracoscopic-esophagectomy were collected and analyzed. Results: All eligible patients (18 patients without CTDT and 32 patients with CTDT) were successfully underwent thoracoscopic procedures without conversion to open approach or major intraoperative complications and perioperative death. The two groups, with similar demographic parameters, had no statistically difference in thoracic operation time, blood loss, ICU stay, postoperative mobilization and oral feeding, and hospital stay. Also, the incidence of postoperative complications was similar with or without CTDT after esophagectomy. But, no-CTDT group had better post-operative satisfaction, including less pain scale scoring and better Norton scoring. Conclusions: This study demonstrated that the treatment of no-CTDT after the minimally invasive thoracoscopic-esophagectomy is safe and feasible, might reduce the work intensity of medical stuff and lead to a better patients' experience.

9.
Ying Yong Sheng Tai Xue Bao ; 29(1): 133-140, 2018 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-29692021

RESUMO

With the common urea split application (CU) as the control, a field experiment was conducted to examine the effects of loss-controlled urea by split application (LCUS) and loss-controlled urea by basal application (LCUB) on ammonia volatilization (NH3), nitrogen (N) nutrition status, grain yield and N utilization efficiency in rice plants. The results showed that the ratio of NH3 volatilization loss to total N application were 15.8%, 13.4% and 19.7% under the conditions of CU, LCUS and LCUB treatments, respectively. Compared to CU, LCUS significantly reduced the NH3 emission by 4.4 kg N·hm-2, with a decrease of 18.0%, while the LCUB significantly increased the NH3 emission by 7.2 kg N·hm-2, which increased by 24.7%. Compared to CU, LCUS increased the chlorophyll contents of leaf, the N content and N accumulation of seed and straw and grain yield, and significantly increased the N recovery efficiency by 7.6%, while significantly reduced the amount of N translocation, apparent N translocation rate and the rate of contribution to N in spike, respectively. However, compared to CU, LCUB significantly reduced the chlorophyll contents of leaf, the N content and accumulation of seed and straw as well as N utilization efficiency, but the grain yield, the amount of N translocation, apparent N translocation rate and the rate of contribution to N in spike were not affected. In conclusion, LCUS could maintain stable production, as well as decrease NH3 emission, improve N nutrition status and increase N utilization efficiency in rice plants.


Assuntos
Amônia/química , Oryza/crescimento & desenvolvimento , Ureia , Agricultura , Fertilizantes , Nitrogênio , Solo , Volatilização
10.
World J Gastroenterol ; 24(9): 1004-1012, 2018 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-29531464

RESUMO

AIM: To investigate the role of long noncoding RNA (lncRNA) RP4 in colorectal cancer. METHODS: Lentivirus-mediated lncRNA RP4 overexpression and knockdown were performed in the colorectal cancer cell line SW480. Cell proliferation, tumor growth, and early apoptosis were evaluated by a cell counting kit-8 assay, an in vivo xenograft tumor model, and annexin V/propidium iodide staining, respectively. Analysis of the lncRNA RP4 mechanism involved assessment of the association of its expression with miR-7-5p and the SH3GLB1 gene. Western blot analysis was also performed to assess the effect of lncRNA RP4 on the autophagy-mediated cell death pathway and phosphatidylinositol-3-kinase (PI3K)/Akt signaling. RESULTS: Cell proliferation, tumor growth, and early apoptosis in SW480 cells were negatively regulated by lncRNA RP4. Functional experiments indicated that lncRNA RP4 directly upregulated SH3GLB1 expression by acting as a competing endogenous RNA (ceRNA) for miR-7-5p. This interaction led to activation of the autophagy-mediated cell death pathway and de-repression of PI3K and Akt phosphorylation in colorectal cancer cells in vivo. CONCLUSION: Our results demonstrated that lncRNA RP4 is a ceRNA that plays an important role in the pathogenesis of colorectal cancer, and could be a potential therapeutic target for colorectal cancer treatment.


Assuntos
Neoplasias Colorretais/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Nus , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Fatores de Tempo , Carga Tumoral
11.
Onco Targets Ther ; 11: 967-973, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29503571

RESUMO

Background: The mucinous component is a special histologic factor in gastric adenocarcinoma. The aim of this study was to assess the prognostic significance of mucinous component in gastric adenocarcinoma according to proportion. Patients and methods: Candidate patients with gastric adenocarcinoma were given radical D2 gastrectomies from September 2008 to May 2015 in our division. Clinicopathologic data and prognosis were monitored and analyzed among gastric adenocarcinoma patients with various proportions of mucinous component. Results: A total of 690 gastric adenocarcinomas with various proportions of mucinous component from 6,025 gastric adenocarcinoma patients were included. Higher numbers of patients with mucinous component came from: young patients, females, those with drinking history, at lower locations, Borrmann type III and IV, T4 stage, and positive for dissected lymph nodes. Tumors and pathological molecular markers showed more positivity in CEA, CA19-9, S100, and CD34. As the various proportions increased, more mucinous component seemed to be accompanied by more Borrmann type III and IV, T4 stage, and more positive expression of CEA and CA19-9. However, no significant difference in 5-year overall survival rate was observed among various proportions or existence of mucinous component. Also, proportion or existence of mucinous component was not an independent prognostic factor in multivariate analysis. Conclusion: Mucinous component was not a prognostic factor for gastric adenocarcinoma after radical D2 gastrectomy, no matter what proportion the component comprised. However, gastric adenocarcinoma with mucinous component showed specific clinicopathological characteristics, such as more advanced tumor stage, different age and sex, and more positive rate of molecular markers, which might provide a new strategy for optimal individual diagnosis and therapies.

12.
Zookeys ; (726): 1-14, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29362544

RESUMO

Three species of the subfamily Neanurinae (Collembola: Neanuridae) are recorded from Tianmu Mountain, Zhejiang Province, east China. Two of them, Lobellina fusasp. n. and Paralobella tianmunasp. n., are new to science and described in this paper. Lobellina fusasp. n. can be recognized by the presence of six teeth on mandible and the fusion of dorsointernal tubercles on the head. Paralobella tianmunasp. n. is characterized by a mandible with seven teeth, the lateral tubercle of Abd. II-III respectively with 7 (6+s) chaetae. Crossodonthina bidentata Luo & Chen, 2009 is widely distributed in the mountain from 300 to 1500 m a.s.l.

13.
Chemistry ; 24(10): 2365-2369, 2018 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-29315875

RESUMO

Three new proton conductors with simple structures based on isolated olyoxometalate anions as well as protonated imidazole and benzimidazole, namely, NNU-6-8, have been successfully prepared by hydrothermal reaction. We could control the number of proton sources by selecting different types and changing the charges of POM anions. The single crystal sample of NNU-6 along a-axis shows a highest proton conductivity of 1.91×10-2  S cm-1 , which is two and three orders of magnitude higher than that of 2.42×10-4 and 8.90×10-5  S cm-1 along b- and c-axes, respectively, due to the more unobstructed H-bonding network and stronger π-π stacking between benzimidazole rings as proton-transferring pathway along a-axis than that along b and c axes. It is a straightforward model to understand the metaphysical proton-conducting process, and this is the first time to put forward the idea that π-π stacking could assist proton transfer and be in favor of proton conduction, which has been demonstrated by calculating potential energy surfaces of proton transfer between benzimidazole molecules.

14.
J Thorac Dis ; 9(1): 117-122, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28203413

RESUMO

BACKGROUND: One-lung ventilation (OLV) anesthesia intubation route is often used in patients undergoing thoracoscopic-esophagectomy in semi-prone position. Recently, the two-lung ventilation (TLV) approach becomes popular. However, limited studies have compared the two ventilation approaches in parallel. Here, we report a single-center, retrospective study of comparing TLV and OLV approach in patients undergoing thoracoscopic-esophagectomy in semi-prone position. METHODS: From January 2013 to November 2014, 147 patients were enrolled into the current study and were given thoracoscopic-esophagectomy in semi-prone position either by OLV or TLV. Intraoperative respiratory functional data and perioperative surgical parameters of the two approaches were collected and analyzed. RESULTS: Of the 147 patients, 64 patients received OLV and 83 patients received TLV, and all of them were successfully under gone thoracoscopic procedures without conversion to open thoracotomy. There was no incidence of major intraoperative complications or perioperative death. There were no statistically different in postoperative respiratory complications, either. However, TLV approach resulted in better intraoperative respiratory function (PaCO2, PaO2, SaO2), shorter preparation time for anesthesia induction, less blood loss, shorter thoracoscopic operating time and less postoperative hospital stay (P<0.05). The incidence of postoperative respiratory complications and quantity of the resected thoracic lymph node showed no difference between the two ventilation approach (P>0.05). CONCLUSION: This study demonstrated that TLV intubation approach is superior to OLV approach during the thoracoscopic-esophagectomy in semi-prone position. According to this, TLV approach is a technically feasible, convenient and safe anesthesia induction approach for esophageal cancer surgery.

15.
Zootaxa ; 4139(2): 183-96, 2016 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-27470797

RESUMO

Three new species, two of Vitronura and one of Lobellina of subfamily Neanurinae (Neanuridae, Collembola) from Central China are described. In addition a key for valid Lobellina species is included.


Assuntos
Artrópodes/classificação , Estruturas Animais/anatomia & histologia , Estruturas Animais/crescimento & desenvolvimento , Animais , Artrópodes/anatomia & histologia , Artrópodes/crescimento & desenvolvimento , Tamanho Corporal , China , Feminino , Masculino , Tamanho do Órgão
16.
Fish Shellfish Immunol ; 54: 456-65, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27150048

RESUMO

Interferon regulatory factors (IRFs) play a key role in mediating the host response against pathogen infection and other important biological processes. This is the first report of an IRF family member in blunt snout bream Megalobrama amblycephala. The complete cDNA of M. amblycephala (Ma) IRF1 gene has 1422 nucleotides (nt.), with an open reading frame of 858 nt, encoding a polypeptide of 285 amino acids. The putative MaIRF1 polypeptide shared significant structural homology with known IRF1 homologs: a conserved IRF domain was found at the N-terminal and an IRF association domain 2 at the C-terminal. Phylogenetic analysis showed that MaIRF1 amino acid sequence clustered with other teleost IRF1s, with a grass carp ortholog exhibiting the highest similarity. MaIRF1 mRNA expression patterns were studied using quantitative real-time PCR in healthy fish tissues and after a challenge with Aeromonas hydrophila bacterium. It was constitutively expressed in all examined tissues: the highest in blood, the lowest in muscle. The expression after A. hydrophila challenge was up-regulated in liver, spleen and kidney, but down-regulated in intestine and gills. At the protein level, similar expression patterns were observed in liver and gills. Patterns differed in intestine (up-regulation), spleen (down-regulation) and kidney (expression mostly unchanged). This study indicates that MaIRF1 gene plays an important role in the blunt snout bream immune system, hence providing an important base for further studies.


Assuntos
Cyprinidae/genética , Cyprinidae/imunologia , Doenças dos Peixes/imunologia , Fator Regulador 1 de Interferon/genética , Fator Regulador 1 de Interferon/metabolismo , Aeromonas hydrophila/fisiologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , Cyprinidae/classificação , DNA Complementar/genética , DNA Complementar/metabolismo , Regulação para Baixo , Doenças dos Peixes/microbiologia , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/microbiologia , Fator Regulador 1 de Interferon/química , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Regulação para Cima
17.
Bioorg Med Chem Lett ; 26(9): 2268-72, 2016 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-27013393

RESUMO

With the aim of searching novel P-CABs, seven bisabolangelone oxime derivatives were designed, synthesized, characterized and evaluated the H(+),K(+)-ATPase inhibitory activities guided by computer aided drug design methods. The binding free energy calculations were in good agreement with the experiment results with the correlation coefficient R of -0.9104 between ΔGbind and pIC50 of ligands. Compound 5 exhibited the best inhibitory activity (pIC50=6.36) and most favorable binding free energy (ΔGbind=-47.67 kcal/mol) than other derivatives. The binding sites of these compounds were found to be the hydrophobic substituted groups with the Cys813 residue by the decomposed binding free energy analysis.


Assuntos
Inibidores Enzimáticos/farmacologia , ATPase Trocadora de Hidrogênio-Potássio/efeitos dos fármacos , Potássio/metabolismo , Sesquiterpenos/farmacologia , Desenho de Drogas , Avaliação Pré-Clínica de Medicamentos , Oximas/química , Sesquiterpenos/química
18.
Ying Yong Sheng Tai Xue Bao ; 26(5): 1391-6, 2015 May.
Artigo em Chinês | MEDLINE | ID: mdl-26571656

RESUMO

Maize cultivar Shandan 609 was used to determine the effects of drought stress on photosystem II, dry matter accumulation, protective enzyme activity and proline content at seedling stage in pot experiment. Two drought treatments (moderate drought and severe drought) were tested. The results showed that dry matter accumulation, leaf area and plant height of cultivar shaandan 609 decreased significantly with the increasing drought stress. The less grouped PS II units (L-band > 0), severely damaged OEC (K-band > 0), and the inhibited acceptor side (ψo significantly decreased) resulted in the overall dropped performance of PS II (PI(ABS)). Under the condition of moderate and severe drought stress, the activities of superoxide, peroxidase, catalase and proline content increased significantly, which were 1.3, 1.1, 1.2, 5.8 and 1.1, 3.3, 1.5, 15.0 times of control (CK), respectively. Those results indicated that damage of PS II acceptor and donor side under drought stress led to the decline of PS II performance, which was likely to cause the decline of dry mater accumulation of maize cultivar Shandan 609, while protective enzymes and proline as protective substance in plant played a positive role in drought resistance.


Assuntos
Secas , Complexo de Proteína do Fotossistema II/fisiologia , Zea mays/fisiologia , Catalase/metabolismo , Peroxidases/metabolismo , Folhas de Planta , Prolina/metabolismo , Plântula/fisiologia , Estresse Fisiológico , Superóxidos/metabolismo
19.
J Alzheimers Dis ; 41(1): 243-60, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24625800

RESUMO

Targeting on the amyloid-ß (Aß) is a promising immunotherapeutic strategy for Alzheimer's disease (AD). However, Aß(1-15) sequence alone induces low antibody response and poor protection against AD. We describe here the immunological characterization and protective efficacy of several recombinant chimeric vaccines with hexavalent foldable Aß(1-15) (6Aß15) fused to PADRE or toxin-derived carrier proteins. Immunization with these chimeric antigens generated robust Th2 immune responses with high anti-Aß42 antibody titers in different mice, which recognized neurotoxic Aß42 oligomers, but did not stimulate Aß42-specific T cell responses. These 6Aß15 chimeric vaccines markedly reduced Aß pathology and prevented development of behavioral deficits in immunized older AD mice. Importantly, toxin-derived carrier proteins as molecular adjuvants of chimeric vaccines could substantially boost immune responses and overcome Aß- and old age-associated hypo-responsiveness, and elicit long-term Aß-specific antibody response, which in turn inhibited Aß-mediated pathology and improved acquisition and retention of spatial memory in immunized AD mice. These data indicate that toxin fragments as molecular adjuvants are promising new tools for the rational design and development of prototype chimeric vaccines for AD and this type of chimeric vaccine design has the added advantage of overcoming hypo-responsiveness in elderly AD patients with pre-existing memory Th cells from tetanus toxin.


Assuntos
Doença de Alzheimer/prevenção & controle , Vacinas contra Alzheimer/uso terapêutico , Encéfalo/imunologia , Placa Amiloide/prevenção & controle , Vacinação , Envelhecimento , Doença de Alzheimer/imunologia , Doença de Alzheimer/patologia , Vacinas contra Alzheimer/imunologia , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/imunologia , Animais , Anticorpos/metabolismo , Toxinas Botulínicas Tipo A/imunologia , Encéfalo/patologia , Modelos Animais de Doenças , Escherichia coli , Imunotoxinas/imunologia , Vacinas Antimaláricas/imunologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Placa Amiloide/imunologia , Placa Amiloide/patologia , Distribuição Aleatória , Memória Espacial/fisiologia , Linfócitos T/imunologia , Vacinas de Subunidades , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/uso terapêutico
20.
Artigo em Chinês | MEDLINE | ID: mdl-24024439

RESUMO

OBJECTIVE: To understand the pathological changes of tissues and organs in Microtus fortis infected with Schistosoma japonicum for further insight into the biological dynamic variation and explore immune mechanisms of M. fortis against S. japonicum infection. METHODS: The healthy M. fortis and mouse were infected with cercariae of S. japonicum through abdominal skin. On the day 12, 20 and 40, the M. fortis and mouse were sacrificed by cervical dislocation and dissected. The liver and kidney slices of M. fortis and mouse of the different groups were prepared and stained with hematoxylin eosin stain (HE) by conventional techniques, respectively. RESULTS: We did not find obvious lesions on the internal organs of mouse 12 d and 20 d after the infection and the lesions of M. fortis 40 d after the infection. However, white nodules appeared on the liver, kidney and spleen of the M. fortis 12 d and 20 d after the infection, and there were a lot of S. japonicum worms on pathological sections of inflamed liver and kidney tissues, and the boundary between worms and normal organization was clear. There were no parasites on pathological section of liver and kidney of mouse 12 d and 20 d after the infection. CONCLUSION: Among M. fortis, there are severe immune responses and the immune responses have an individual difference 12 days after S. japonicum infection.


Assuntos
Arvicolinae , Modelos Animais de Doenças , Schistosoma japonicum/fisiologia , Esquistossomose Japônica/parasitologia , Animais , Arvicolinae/parasitologia , Feminino , Humanos , Rim/parasitologia , Rim/patologia , Fígado/parasitologia , Fígado/patologia , Masculino , Camundongos , Schistosoma japonicum/crescimento & desenvolvimento , Schistosoma japonicum/isolamento & purificação , Esquistossomose Japônica/patologia , Baço/parasitologia , Baço/patologia
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