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1.
IEEE Trans Cybern ; 50(4): 1395-1404, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30640642

RESUMO

Complementarity between activities reveals that doing any one of them increases the returns to doing the others. In other words, complementarity leads to the synergistic effect that the whole is greater than the sum of its parts. Identifying and exploiting complementarity can benefit many cybernetic activities, where human-machine interactions are inherent and dominant. One such activity is requirements tracing that helps stakeholders to track the status of their goals. Although various kinds of support for human analysts in requirements tracing have been proposed, little is known about the nature of complementarity when different tracing practices are involved. In this paper, we explore the role of complementarity by considering together the tagging-to-trace (T2T) and learning-to-trace (L2T) activities. We present a novel approach to examining which T2T and L2T practices enhance the qualities of each other. Our approach also uncovers the environmental factors which the complementarity is sensitive to. Applying our approach to the logs of 140 analyst-tracing units offers operational insights into the rigorous detection of complementarity and shows the importance of understanding the cybernetic conditions under which the requirements tracing practices may in fact be complementary.

2.
Plant J ; 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31820831

RESUMO

Phycobilisomes are large light-harvesting complexes attached to the stromal side of thylakoids in cyanobacteria and red algae. They can be remodeled or degraded in response to changing light and nutritional status. Both the core and the peripheral rods of phycobilisomes contain biliproteins. During biliprotein biosynthesis, open-chain tetrapyrrole chromophores are attached covalently to the apoproteins by dedicated lyases. Another set of non-bleaching (Nb) proteins has been implicated in phycobilisome degradation, among them NblA and NblB. We report in vitro experiments with lyases, biliproteins and NblA/B which imply that the situation is more complex than currently discussed: lyases can also detach the chromophores and NblA and NblB can modulate lyase-catalyzed binding and detachment of chromophores in a complex fashion. We show: (i) NblA and NblB can interfere with chromophorylation as well as chromophore detachment of phycobiliprotein, they are generally inhibitors but in some cases enhance the reaction; (ii) NblA and NblB promote dissociation of whole phycobilisomes, cores and, in particular, allophycocyanin trimers; (iii) while NblA and NblB do not interact with each other, both interact with lyases, apo- and holo-biliproteins; (iv) they promote synergistically the lyase-catalyzed chromophorylation of the ß-subunit of the major rod component, CPC; and (v) they modulate lyase-catalyzed and lyase-independent chromophore transfers among biliproteins, with the core protein, ApcF, the rod protein, CpcA, and sensory biliproteins (phytochromes, cyanobacteriochromes) acting as potential traps. The results indicate that NblA/B can cooperate with lyases in remodeling the phycobilisomes to balance the metabolic requirements of acclimating their light-harvesting capacity without straining the overall metabolic economy of the cell.

3.
Am J Transl Res ; 11(9): 6040-6054, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632572

RESUMO

Cyclooxygenase-2 (COX2) and tumor-associated macrophages (TAMs) are associated with invasion, angiogenesis, and poor prognosis in many human cancers. However, the role of TAMs in human gastric cancer (GC) remains elusive. In the present study, we first measured COX2 expression and TAM infiltration in human GC tissues using double immunohistochemical staining. Then, we indirectly cocultured M2-polarized macrophages derived from human THP-1 cells with GC cells as an in vitro model. Transwell assays, siRNA transfection, treatment with a COX2 inhibitor and Western blotting were used to investigate the relationship among TAMs, invasion and COX2 expression as well as the underlying molecular mechanism. Double IHC staining showed that TAMs were aggregated near GC tumor nests and had high COX2 expression; moreover, the number of TAMs that infiltrated the tumor nest was correlated with the depth of invasion, COX2 expression and poor prognosis in human GC. In an in vitro assay, after treatment with phorbol myristate acetate (PMA), the THP-1 cells differentiated into M2 macrophages and induced COX2/MMP9-dependent invasiveness in GC cells. Pretreatment of GC cells with COX2 siRNA or a COX2 inhibitor (Celecoxib) can negate these promoting effects. The results of this study and those of our previous studies indicate that coculture with M2-polarized macrophages can induce the COX2-dependent release of matrix metalloproteinase-9 (MMP9), which subsequently increases the invasiveness of GC cells. Our data may provide a basis for targeting TAMs or for polarizing TAMs through immune regulation to halt GC progression, which could soon become a nonsurgical treatment for human gastric cancer.

4.
Surg Endosc ; 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31317331

RESUMO

OBJECTIVE: The study aimed to compare the oncologic outcomes and long-term survival of laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Substantial evidence demonstrated that LPD is technically safe and feasible with perioperative outcomes equivalent to that of OPD. However, for patients with malignancy, especially PDAC, the oncologic outcomes and long-term survival of patients who underwent LPD remains to be elucidated. METHODS: Studies on LPD for the treatment of PDAC published before December 25, 2018 were searched online. The oncologic outcomes (e.g., numbers of lymph nodes retrieved, negative margin (R0) resection), and long-term survival (postoperative survival from 1 to 5 year) of LPD were compared to that of ODP. RESULTS: After screening 1507 studies, six comparative cohort studies, which reported the oncologic outcomes and long-term survival of patients with PDAC were included. No significant difference was found between LPD and OPD regarding lymph nodes harvested (OR 1.96, 95% CI - 1.17 to 5.09, p = 0.22), R0 rate (OR 1.44, 95% CI 1.00 to 2.06, p = 0.05), number of positive lymph nodes (OR - 0.44, 95% CI - 1.06 to 0.17, p = 0.16), rate of adjuvant treatment (OR 1.04, 95% CI 0.68 to 1.59, p = 0.86) and time to adjuvant treatment (OR - 6.21, 95% CI - 16.00 to 3.59, p = 0.21). LPD showed similar 1-year (OR 1.20, 95% CI 0.87 to 1.65, p = 0.28), and 2-year survival (OR 1.25, 95% CI 0.94 to 1.66, p = 0.13) to that of OPD. The 3-year (OR 1.50, 95% CI 1.12 to 2.02, p = 0.007), 4-year (OR 1.73, 95% CI 1.02 to 2.93, p = 0.04), and 5-year survival (OR 2.11, 95% CI 1.35 to 3.31, p = 0.001) were significantly longer in LPD group. CONCLUSION: For the treatment of PDAC, the oncologic outcomes of LPD were equivalent to that of OPD; LPD seemed promising regarding the postoperative long-term survival.

5.
Polymers (Basel) ; 11(1)2019 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-30960099

RESUMO

In the present study, a glucose oxidase (GluOx) direct electron transfer was realized on an aminated polyethylene glycol (mPEG), carboxylic acid functionalized multi-walled carbon nanotubes (fMWCNTs), and ionic liquid (IL) composite functional polymer modified glassy carbon electrode (GCE). The amino groups in PEG, carboxyl groups in multi-walled carbon nanotubes, and IL may have a better synergistic effect, thus more effectively adjust the hydrophobicity, stability, conductivity, and biocompatibility of the composite functional polymer film. The composite polymer membranes were characterized by cyclic voltammetry (CV), ultraviolet-visible (UV-Vis) spectrophotometer, fluorescence spectroscopy, electrochemical impedance spectroscopy (EIS), and transmission electron microscopy (TEM), respectively. In 50 mM, pH 7.0 phosphate buffer solution, the formal potential and heterogeneous electron transfer constant (ks) of GluOx on the composite functional polymer modified GCE were -0.27 V and 6.5 s-1, respectively. The modified electrode could recognize and detect glucose linearly in the range of 20 to 950 µM with a detection limit of 0.2 µM. The apparent Michaelis-Menten constant (Kmapp) of the modified electrode was 143 µM. The IL/mPEG-fMWCNTs functional polymer could preserve the conformational structure and catalytic activity of GluOx and lead to high sensitivity, stability, and selectivity of the biosensors for glucose recognition and detection.

6.
Sci Rep ; 9(1): 4353, 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30867507

RESUMO

The conformational lock was a bio-thermodynamic theory to explain the characteristics of interfaces in oligomeric enzymes and their effects on catalytic activity. The previous studies on superoxide dismutases (Cu, Zn-SODs) showed that the dimeric structure contributed to the high catalytic efficiency and the stability. In this study, steered molecular dynamics simulations were used firstly to study the main interactions between two subunits of Cu, Zn-SODs. The decomposition process study showed that there were not only four pairs of hydrogen bonds but also twenty-five residue pairs participating hydrophobic interactions between A and B chains of SOD, and van der Waals interactions occupied a dominant position among these residue pairs. Moreover, the residue pairs of hydrogen bonds played a major role in maintaining the protein conformation. The analysis of the energy and conformational changes in the SMD simulation showed that there were two groups (two conformational locks) between A and B chains of SOD. The first group consisted of one hydrogen-bond residues pair and seven hydrophobic interactions residues pairs with a total average energy of -30.10 KJ/mol, and the second group of three hydrogen-bond residues pair and eighteen hydrophobic interactions residues pairs formed with a total average energy of -115.23 KJ/mol.

7.
Protein Expr Purif ; 156: 66-71, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30629973

RESUMO

Naturally-occurring orange carotenoid protein (OCP) is synthesized in cyanobacteria and red algae for photoprotection. Holo-OCP can be produced with three plasmids in E. coli, which needs two inducers (arabinose and isopropyl ß-D-thiogalactoside) to initiate two processes: one for generation of carotenoid and the other for generation of apo-OCP, so takes about two days. Afterwards, a two-plasmid method using two plasmids in E. coli is established, in which E. coli cells are induced only by isopropyl ß-D-thiogalactoside, so can yield different holo-OCPs from several cyanobacteria within three days. In this work, we optimized the two-plasmid method as follows: (1) re-organization of the two plasmids, letting carotenoid-generating gene, crtW, be arranged together with apo-OCP-generating gene, ocp, in a single plasmid, which causes that both carotenoid and apo-protein were properly produced, (2) modification of several amino acids at the N-terminus of apo-OCP, in this way increasing the yield and purity of holo-OCP. After these optimizations, we can generate much more amount of holo-OCP within shorter time of only 16 h, and pure holo-OCP be conveniently prepared after routine purification. Comparing with the reported data, the general yield of holo-OCP is increased by ∼10-fold under similar conditions. The high quality of the prepared holo-OCPs is verified by fluorescence quenching of the phycobilisomes.


Assuntos
Carotenoides/química , Proteínas Recombinantes , Escherichia coli , Regulação Bacteriana da Expressão Gênica , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/genética
8.
Mol Med Rep ; 19(3): 2153-2163, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30628711

RESUMO

Hypoxia­induced apoptosis occurs in various diseases. Cobalt chloride (CoCl2) is a hypoxia mimic agent that is frequently used in studies investigating the mechanisms of hypoxia. Nuclear respiratory factor­1 (NRF­1) is a transcription factor with an important role in the expression of mitochondrial respiratory and mitochondria­associated genes. However, few studies have evaluated the effects of NRF­1 on apoptosis, particularly with regard to damage caused by CoCl2. In the present study, the role of NRF­1 in mediating CoCl2­induced apoptosis was investigated using cell viability analysis, flow cytometry, fluorescence imaging, western blotting analysis, energy metabolism analysis and reverse transcription­quantitative polymerase chain reaction. The present results revealed that the apoptosis caused by CoCl2 could be alleviated by NRF­1. Furthermore, overexpression of NRF­1 increased the expression of B­cell lymphoma­2, hypoxia inducible factor­1α and NRF­2. Also, cell damage induced by CoCl2 may be associated with depolarization of mitochondrial membrane potential, and NRF­1 suppressed this effect. Notably, the oxygen consumption rate (OCR) was reduced in CoCl2­treated cells, whereas overexpression of NRF­1 enhanced the OCR, suggesting that NRF­1 had protective effects. In summary, the present study demonstrated that NRF­1 protected against CoCl2­induced apoptosis, potentially by strengthening mitochondrial function to resist CoCl2­induced damage to H9C2 cells. The results of the present study provide a possible way for the investigation of myocardial diseases.


Assuntos
Apoptose/efeitos dos fármacos , Cobalto/farmacologia , Mitocôndrias/efeitos dos fármacos , Fator 1 Nuclear Respiratório/genética , Animais , Apoptose/genética , Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/genética , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/genética , Citometria de Fluxo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Mitocôndrias/patologia , Consumo de Oxigênio/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo
9.
Biochem Biophys Res Commun ; 508(2): 440-444, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30502082

RESUMO

Hyperuricemia contributes to vascular injury and dysfunction, yet the potential mechanisms are not well understood. Uric acid (UA) has been found to stimulate macrophage migration inhibitory factor (MIF) up-regulation in renal tubules from rats subjected to UA-induced nephropathy. Given that MIF is able to induce vascular smooth muscle cell (VSMC) de-differentiation (from contractile state to a secretory state), we thus hypothesized that UA-induced vascular injury is via up-regulating of MIF in VSMCs, which enhancing vascular inflammation and VSMC transition. Within a mouse model of UA injection (500 mg/kg, twice/day, 14 days), we measured circulating and vascular MIF levels under UA stimulation at 6 h, day 1, and 14. We tested the efficacy of MIF inhibitor (10 mg/kg, twice/day, 14 days) on UA-induced vascular inflammation and remodeling. High plasma level of UA induced vascular MIF release into the plasma at acute phase. In the chronic phase, the protein level of MIF is up-regulated in the vessels. MIF inhibitor suppressed vascular inflammatory responses, repressed VSMC de-differentiation, and attenuated vascular remodeling and dysfunction following UA stimulation. Knockdown of MIF in cultured VSMCs repressed UA-induced de-differentiation. Our results provided a novel mechanism for MIF-mediated vascular injury in response to UA stimulation, and suggested that anti-MIF interventions may be of therapeutic value in hyperuricemic patients.


Assuntos
Fatores Inibidores da Migração de Macrófagos/antagonistas & inibidores , Remodelação Vascular/fisiologia , Animais , Desdiferenciação Celular/efeitos dos fármacos , Desdiferenciação Celular/fisiologia , Células Cultivadas , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Humanos , Hiperuricemia/patologia , Hiperuricemia/fisiopatologia , Oxirredutases Intramoleculares/antagonistas & inibidores , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/fisiologia , Fatores Inibidores da Migração de Macrófagos/genética , Fatores Inibidores da Migração de Macrófagos/fisiologia , Masculino , Camundongos , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , RNA Interferente Pequeno/genética , Ratos , Ratos Sprague-Dawley , Ácido Úrico/toxicidade , Remodelação Vascular/efeitos dos fármacos , Vasculite/induzido quimicamente , Vasculite/prevenção & controle
10.
Exp Ther Med ; 16(5): 3875-3882, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30344664

RESUMO

Effects of toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway on expression of angiotensinogen and AT1a receptor were investigated, to explore the role of TLR4/NF-κB signaling pathway in cardiovascular disease. Neonatal rat left ventricular myocytes (NRVMs) were cultured and cardiomyocytes were identified by immunocytochemical staining of sarcomeric α-actin. NRVMs were treated with lipopolysaccharide (LPS) at a dose of 10, 100 and 1,000 ng/ml, and RT-PCR was performed 24 h later to detect the expression of TLR4, angiotensinogen (ATG) and AT1a at mRNA level. NRVMs were cultured and pretreated with caffeic acid phenethylester (CAPE) for 30 min. Then NRVMs were stimulated with LPS (1,000 ng/ml) for 24 h. Nuclear translocation of NF-κB p65 was detected by immunocytochemistry. Expression of TLR4, angiotensinogen and AT1a receptor after CAPE stimulation was detected by RT-PCR. TLR4 mRNA was highly expressed in in vitro cultured NRVMs, and the expression level was significantly increased by LPS (10-1,000 ng/ml) stimulation in a dose-dependent manner (P<0.05). LPS stimulation also significantly increased the expression levels of angiotensinogen and AT1a receptor in a dose-dependent manner (P<0.05). NF-κB was activated and nuclear translocation of NF-κB p65 occurred after stimulation with LPS (1,000 ng/ml) for 24 h, while CAPE (20 µg/ml) inhibited the nuclear translocation of NF-κB p65 and inhibited LPS-induced expression of angiotensinogen and AT1a receptor. With LPS stimulation, TLR4 signaling positively regulates the expression of TLR4 and upregulates the expression of angiotensinogen and AT1a receptor in NRVMs. CAPE, an inhibitor of NF-κB, inhibited NF-κB p65 activation and inhibited the upregulation of TLR4, angiotensinogen and AT1a receptors induced by LPS. These results suggest that NF-κB plays a key regulatory role in the above-mentioned effects induced by LPS. Intervention with TLR4/NF-κB signaling may become a new target for prevention and treatment of cardiovascular diseases.

11.
Vet Res Commun ; 40(2): 73-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27094043

RESUMO

OBJECTIVE: This study aims to investigate the immunoprotection of recombinant Eg.P29 (rEg.P29) vaccine and analyze the underlying mechanism in sheep. METHODS: Three groups of male sheep were immunized subcutaneously with rEg.P29 and PBS, Freund's complete adjuvant as controls, respectively. After prime-boost vaccination, the sheep were challenged with encapsulated Echinococcus granulosus eggs. The percentage of protection in sheep was determined 36 weeks after the infection. Humoral immune response was analyzed for specific IgG, IgG1, IgG2, IgM and IgE levels. Moreover, cytokines including interferon (IFN)-γ, interleukin (IL)-2, IL-4,and IL-10 were also evaluated. RESULTS: Immunization with rEg.P29 induced protective immune responses up to 94.5 %, compared with immunoadjuvant group. The levels of specific IgG, IgG1, IgG2, and IgE as well as IFN-γ, IL-2, and IL-4 significantly increased after two immunizations (P < 0.05); however, the levels of IgM and IL-10 did not show difference. CONCLUSION: rEg.P29 showed Immunoprotection and induced Th1 and Th2 immune responses; hence, rEg.P29 is a potential vaccine for E. granulosus infection.


Assuntos
Antígenos de Helmintos/imunologia , Equinococose/veterinária , Doenças dos Ovinos/prevenção & controle , Animais , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/genética , Citocinas/sangue , Equinococose/imunologia , Equinococose/patologia , Equinococose/prevenção & controle , Echinococcus granulosus/genética , Echinococcus granulosus/imunologia , Humanos , Masculino , Ovinos , Doenças dos Ovinos/imunologia , Doenças dos Ovinos/patologia , Vacinas Sintéticas/imunologia , Zoonoses/prevenção & controle
12.
Radiat Environ Biophys ; 55(2): 195-202, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26980623

RESUMO

The purpose of this study was to investigate the role of Sestrin2 in response to radiation-induced injury to the heart and on the cardiomyopathy development in the mouse. Mice with genetic deletion of the Sestrin2 (Sestrin2 knockout mice [Sestrin2 KO]) and treatment with irradiation (22 or 15 Gy) were used as independent approaches to determine the role of Sestrin2. Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson's trichrome was used to assess myocardial fibrosis. Immunohistochemistry and Western blot were used to detect the capillary density. After 22 or 15 Gy irradiation, the LV ejection fraction (EF) was impaired in wt mice at 1 week and 4 months after irradiation when compared with sham irradiation. Compared to wt mice, Sestrin2 KO mice had significant reduction in reduced LVEF at 1 week and 4 months after irradiation. A significant increase in LV end-diastolic pressure and myocardial fibrosis and a significant decrease in capillary density were observed in irradiation-wt mice, as well as in irradiation-Sestrin2 KO mice. Sestrin2 involved in the regulation of cardiomyopathy (such as myocardial fibrosis) after irradiation. Overexpression of Sestrin2 might be useful in limiting radiation-induced myocardial injury.


Assuntos
Cardiomiopatias/etiologia , Cardiomiopatias/metabolismo , Miocárdio/metabolismo , Proteínas Nucleares/metabolismo , Lesões por Radiação/etiologia , Lesões por Radiação/metabolismo , Animais , Capilares/metabolismo , Capilares/efeitos da radiação , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Fibrose , Técnicas de Inativação de Genes , Coração/fisiopatologia , Coração/efeitos da radiação , Hemodinâmica/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/patologia , Proteínas Nucleares/deficiência , Proteínas Nucleares/genética , Peroxidases , Lesões por Radiação/patologia , Lesões por Radiação/fisiopatologia , Análise de Sobrevida , Fatores de Tempo , Função Ventricular Esquerda/efeitos da radiação
13.
J Physiol ; 594(7): 1875-90, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26732231

RESUMO

KEY POINTS: Despite the clinical importance of pre-emptive analgesia, the mechanisms by which it attenuates pain associated with central sensitization are poorly understood. We find that fentanyl and the α2-adrenoceptor agonist dexmedetomidine (Dex) differ significantly in their modulatory actions on noxious mechanical and noxious heat-evoked nociception in vivo. Unlike fentanyl, Dex modified descending control of nociception by decreasing the threshold for descending inhibition and/or increasing the threshold for descending facilitation. Dex exhibited after-actions on activities of thalamus in prolongation of noxious heat-evoked paw withdrawal latency that persisted for at least 7 days. This study provides insight into the organization of thalamic modulation in pre-emptive analgesia. ABSTRACT: We investigated and compared the antinociceptive effects of intraperitoneal administration of fentanyl (2-60 µg kg(-1)) and dexmedetomidine (Dex, 1-10 µg kg(-1); a highly selective α2-adrenoceptor agonist) in the regulation of nociception assessed by measuring noxious paw withdrawal reflexes in rats. Fentanyl elevated noxious mechanical paw withdrawal threshold and prolonged paw withdrawal heat latency within 1-1.5 h (P < 0.05). Dex failed to affect the mechanical paw withdrawal threshold, yet significantly prolonged the paw withdrawal heat latency in a bi-phasic manner; a short transient 1-1.5 h period followed by a second, slowly developing increase in latency that persisted for at least 7 days (P < 0.05). Lesion of the dorsolateral funiculus (DLF) did not influence fentanyl-induced antinociceptive effects, indicating peripheral and spinal antinociceptive mechanisms. By contrast, the Dex-induced second, but not the first, phase of the prolonged paw withdrawal heat latency was significantly blocked by the lesion of either DLF or thalamic ventromedial (VM) nuclei, and was attenuated by intracerebral administration of either atipamezole (α2-adrenoceptor antagonist) or WAY-100635 (5-HT1A receptor antagonist) into the VM nuclei (P < 0.05). Upon intramuscular 5.8% saline-induced muscle nociception, pre-emptive injection of fentanyl enhanced mechanical hyperalgesia and blocked heat hypoalgesia, whereas Dex significantly prevented the occurrence of mechanical hyperalgesia and enhanced heat hypoalgesia. It is suggested that Dex, but not fentanyl, significantly enhances descending inhibition and/or decreases descending facilitation to modulate pain and nociception. The present study provides novel insight into thalamus-mediated mechanisms in pre-emptive analgesia.


Assuntos
Analgésicos não Entorpecentes/farmacologia , Analgésicos Opioides/farmacologia , Dexmedetomidina/farmacologia , Fentanila/farmacologia , Hiperalgesia/tratamento farmacológico , Núcleos Talâmicos/efeitos dos fármacos , Analgésicos não Entorpecentes/administração & dosagem , Analgésicos não Entorpecentes/uso terapêutico , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Animais , Dexmedetomidina/administração & dosagem , Dexmedetomidina/uso terapêutico , Fentanila/administração & dosagem , Fentanila/uso terapêutico , Imidazóis/farmacologia , Masculino , Inibição Neural , Nociceptividade , Limiar da Dor , Piperazinas/farmacologia , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Núcleos Talâmicos/fisiologia
14.
Artigo em Chinês | MEDLINE | ID: mdl-30129713

RESUMO

Objective: To screen for the Echinococcus granulosus 01883(Eg-01883) specifically expressed at the protoscolex period, clone and express this molecule as well as analyse its immunogenicity. Methods: Eg-01883, which is highly expressed at the protoscolex period but not in oncosphere, was screened by analysing the published mRNA sequences of E. granuolosus. Total RNA of E. granuolosus was extracted, Eg-01883 was cloned by RT-PCR, and the recombinant plasmid pET28a-Eg-01883 was constructed. Expression of the recombinant protein rEg-01883 was induced by isopropyl-ß-D-thiogalactoside (IPTG). ICR mice were randomized into 3 groups (n=12 in each group). Mice in the immunization group received subcutaneous injections of 10 µg rEg-01883 in 100 µl PBS emulsified in Freund's adjuvant at multiple sites, followed by immune enhancement after 2 weeks. Mice in the adjuvant group were injected with PBS and adjuvant. Mice in the control group received no treatment. Blood was obtained through caudal vein before immunization, and at 1, 2, and 4 weeks after the first immunization, and through the eyeball at 6 weeks after immunization. Serum levels of IgG, IFN-γ and IL-4 were determined by ELISA. The immunogenicity of rEg-01883 was identified by Western blotting. Results: Eg-01883 was screened, cloned, expressed and purified to obtain the recombinant protein rEg-01883, which mainly existed as the inclusion body. ELISA results showed that immunization with rEg-01883 induced production of specific IgG antibody. The serum IgG level in the immunization group increased from 1 week after the first immunization, peaked at 6 weeks(2.344±0.153), which was significantly higher than those of the adjuvant group(0.206 1±0.006) and the control group (0.241±0.01) (P<0.01). At 6 weeks after the first immunization, the serum levels of IFN-γ (43.23 pg/ml) and IL-4(24.88 pg/ml) in the immunization group were significantly higher than those in the adjuvant group(21.77 pg/ml, 13.27 pg/ml) and the control group(17.40 pg/ml, 12.25 pg/ml)(P<0.05). Western blot showed that the recombinant protein rEg-01883 could be recognized by His-Tag antibodies, serum of immunized mice, and serum of mice with secondary infection. Conclusion: The recombinant protein rEg-01883 shows good immunogenicity in ICR mice.


Assuntos
Echinococcus granulosus , Imunização , Adjuvantes Imunológicos , Animais , Anticorpos Anti-Helmínticos , Antígenos de Helmintos , Western Blotting , Ensaio de Imunoadsorção Enzimática , Camundongos , Camundongos Endogâmicos ICR , Proteínas Recombinantes , Vacinação
15.
IEEE Trans Cybern ; 46(9): 1962-73, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25910273

RESUMO

Developers often spend valuable time navigating and seeking relevant code in software maintenance. Currently, there is a lack of theoretical foundations to guide tool design and evaluation to best shape the code base to developers. This paper contributes a unified code navigation theory in light of the optimal food-foraging principles. We further develop a novel framework for automatically assessing the foraging mechanisms in the context of program investigation. We use the framework to examine to what extent the clustering of software entities affects code foraging. Our quantitative analysis of long-lived open-source projects suggests that clustering enriches the software environment and improves foraging efficiency. Our qualitative inquiry reveals concrete insights into real developer's behavior. Our research opens the avenue toward building a new set of ecologically valid code navigation tools.

16.
IEEE Trans Cybern ; 46(8): 1784-95, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-25910274

RESUMO

Group size is a key factor in collaborative software development and many other cybernetic applications where task assignments are important. While methods exist to estimate its value for proprietary projects, little is known about how group size affects distributed and decentralized cybernetic applications and in particular open source software (OSS) development. This paper presents a novel approach in which we frame developers' collective resolution of OSS change tasks as a social information foraging problem. This new perspective enables us to predict the optimal group size and quantify group size's effect on individual performance. We test the theory with data mined from two projects: 1) Firefox and 2) Mylyn. This paper not only uncovers the mismatch of optimal and actual group sizes, but also reveals the association of optimality with improved productivity. In addition, the social-level productivity gain is observed as project evolves. We show this paper's impact by extending the frontiers of knowledge in two areas: 1) social coding and 2) recommendation systems.

17.
Heart Vessels ; 31(8): 1218-29, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26290166

RESUMO

We decided to assess the prognostic value of NLRP3 inflammasome level in acute coronary syndrome (ACS) patients and whether it was related to coronary atherosclerotic severity. Study population included one-hundred and twenty-three (123) subjects. Peripheral blood monocyte NLRP3 protein level was correlated with clinical presentation, angiographic characteristics and its scoring systems as well as GRACE and TIMI risk scores. Follow-up for major adverse cardiac events (MACE) was carried out at 180 days. Peripheral blood monocyte NLRP3 was found to be elevated in ACS patients (P < 0.05) and showed positive correlation with GRACE score (r = 0.619), TIMI score (r = 0.580), SYNTAX score (r = 0.550), Clinical SYNTAX score (r = 0.564) and Gensini score (r = 0.516). NLRP3 was also increased with increasing number of vessels, the number of lesions present and the presence bifurcation lesions (P < 0.05). Multivariate Cox regression analysis showed NLRP3 to be an independent predictor of MACE (P = 0.043). Kaplan-Meier analysis and receiver operating characteristic curves for NLRP3 showed good predictive value for MACE. There is a positive correlation of NLRP3 level with severity of coronary atherosclerosis. NLRP3 level is a promising prognostic utility and is efficient in event prediction for MACE.


Assuntos
Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/mortalidade , Doença da Artéria Coronariana/sangue , Creatinina/sangue , Lipídeos/sangue , Proteína 3 que Contém Domínio de Pirina da Família NLR/sangue , Idoso , Estudos de Casos e Controles , Angiografia Coronária , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença
18.
Tumour Biol ; 37(5): 5869-78, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26586399

RESUMO

The purpose of this study was to evaluate the radiation-enhancing effect of sodium glycididazole, and the corresponding mechanisms of action on laryngeal cancer cells. Two laryngeal cancer cell lines (Hep-2 and UT-SCC-19A) were irradiated with X-rays in the presence or absence of sodium glycididazole. Cell survival, DNA damage and repair, cell apoptosis, cell cycle distribution, expression of proteins related to cell cycle checkpoint, and apoptosis were measured. Significantly increased DNA damages, decreased cells in the G1 phase, arrested cells at G2/M phase, decreased DNA repair protein XRCC1 foci formation, and enhanced cell apoptosis were observed in laryngeal cell lines treated by sodium glycididazole combined with irradiation compared with the irradiation alone. The combined treatment downregulated the protein expressions of ataxia-telangiectasia mutated (ATM), p-ATM, CHK2, and P53 but upregulated the protein expressions of MDM2 and Cdk2. This study indicates that sodium glycididazole enhances the radiosensitivity of laryngeal cancer cells through downregulation of ATM signaling pathway in vitro and in vivo.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Imidazóis/farmacologia , Neoplasias Laríngeas/metabolismo , Radiossensibilizantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Modelos Animais de Doenças , Células Hep G2 , Humanos , Hipóxia/tratamento farmacológico , Hipóxia/metabolismo , Neoplasias Laríngeas/patologia , Camundongos , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiação , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Coron Artery Dis ; 26(5): 409-21, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25946654

RESUMO

OBJECTIVES: Despite recent advances in the understanding of the role of NLRP3 inflammasomes in coronary atherosclerosis, further work on their activation and clinical implications remains to be performed. In this study, we aimed to evaluate the effect of the dose of rosuvastatin on NLRP3 and cathepsin-B expression in peripheral blood monocytes in patients with acute coronary syndrome. METHODS: A total of 123 participants were enrolled in this study; these included acute myocardial infarction (AMI) patients (n=53), unstable angina patients (UA, n=40), and normal controls (n=30). AMI and UA patients were divided into high-dose rosuvastatin (20 mg) and low-dose rosuvastatin (5 mg) groups. NLRP3, cathepsin-B, and downstream cytokine expressions were appropriately evaluated using real-time PCR, flow cytometry, western blotting and enzyme-linked immunosorbent assay. The concentrations of serum inflammatory markers were also evaluated for correlation with NLRP3 levels. RESULTS: AMI and UA patients had higher NLRP3, cathepsin-B, interleukin-18 (IL-18), pro-IL-18, IL-1ß, and pro-IL-1ß expressions as compared with the control group (P<0.05). This corresponded with higher levels of serum total cholesterol, serum low-density lipoprotein cholesterol, and oxidized low-density lipoprotein in UA and AMI patients (P<0.05). Rosuvastatin at a concentration of 20 mg led to a significant decrease (P<0.05) in the expressions of NLRP3, cathepsin-B, and their downstream cytokines as compared with 5 mg rosuvastatin (P>0.05) from baseline to 4 weeks. This study also showed a positive correlation between NLRP3, cathepsin-B, and downstream inflammatory mediators. CONCLUSION: NLRP3 is involved in inflammation that leads to atherosclerosis. A high dose of rosuvastatin can modulate the inflammatory process of atherosclerosis by downregulating the expression of NLRP3, cathepsin-B, and their downstream mediators. These findings provide insight into the pathogenesis and management of acute coronary syndrome, with NLRP3 as the potential target.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Angina Instável/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Proteínas de Transporte/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inflamassomos/sangue , Mediadores da Inflamação/sangue , Monócitos/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Rosuvastatina Cálcica/administração & dosagem , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/imunologia , Adulto , Idoso , Angina Instável/sangue , Angina Instável/diagnóstico , Angina Instável/genética , Angina Instável/imunologia , Biomarcadores/sangue , Proteínas de Transporte/genética , Proteínas de Transporte/imunologia , Catepsina B/sangue , China , Citocinas/sangue , Feminino , Humanos , Inflamassomos/genética , Inflamassomos/imunologia , Mediadores da Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/genética , Infarto do Miocárdio/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Fatores de Tempo , Adulto Jovem
20.
Proc Natl Acad Sci U S A ; 111(39): 14042-6, 2014 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-25197073

RESUMO

Low-threshold lasers realized within compact, high-quality optical cavities enable a variety of nanophotonics applications. Gallium nitride materials containing indium gallium nitride (InGaN) quantum dots and quantum wells offer an outstanding platform to study light-matter interactions and realize practical devices such as efficient light-emitting diodes and nanolasers. Despite progress in the growth and characterization of InGaN quantum dots, their advantages as the gain medium in low-threshold lasers have not been clearly demonstrated. This work seeks to better understand the reasons for these limitations by focusing on the simpler, limited-mode microdisk cavities, and by carrying out comparisons of lasing dynamics in those cavities using varying gain media including InGaN quantum wells, fragmented quantum wells, and a combination of fragmented quantum wells with quantum dots. For each gain medium, we use the distinctive, high-quality (Q ∼ 5,500) modes of the cavities, and the change in the highest-intensity mode as a function of pump power to better understand the dominant radiative processes. The variations of threshold power and lasing wavelength as a function of gain medium help us identify the possible limitations to lower-threshold lasing with quantum dot active medium. In addition, we have identified a distinctive lasing signature for quantum dot materials, which consistently lase at wavelengths shorter than the peak of the room temperature gain emission. These findings not only provide better understanding of lasing in nitride-based quantum dot cavity systems but also shed insight into the more fundamental issues of light-matter coupling in such systems.

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