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1.
J Med Virol ; 96(5): e29640, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38699969

RESUMO

After the termination of zero-COVID-19 policy, the populace in China has experienced both Omicron BA.5 and XBB waves. Considering the poor antibody responses and severe outcomes observed among the elderly following infection, we conducted a longitudinal investigation to examine the epidemiological characteristics and antibody kinetics among 107 boosted elderly participants following the Omicron BA.5 and XBB waves. We observed that 96 participants (89.7%) were infected with Omicron BA.5, while 59 (55.1%) participants were infected with Omicron XBB. Notably, 52 participants (48.6%) experienced dual infections of both Omicron BA.5 and XBB. The proportion of symptomatic cases appeared to decrease following the XBB wave (18.6%) compared to that after the BA.5 wave (59.3%). Omicron BA.5 breakthrough infection induced lower neutralizing antibody titers against XBB.1.5, BA.2.86, and JN.1, while reinfection with Omicron XBB broadened the antibody responses against all measured Omicron subvariants and may alleviate the wild type-vaccination induced immune imprinting. Boosted vaccination type and comorbidities were the significant factors associated with antibody responses. Updated vaccines based on emerging severe acute respiratory syndrome coronavirus 2 variants are needed to control the Coronavirus Disease 2019 pandemic in the elderly.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Infecções Irruptivas , Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , China/epidemiologia , Idoso , Anticorpos Antivirais/sangue , Masculino , Feminino , Anticorpos Neutralizantes/sangue , SARS-CoV-2/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Estudos Longitudinais , Vacinação
2.
J Org Chem ; 89(7): 4904-4915, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38500413

RESUMO

The palladium-catalyzed highly regioselective asymmetric allylic alkylation of 3'-indolyl-3-oxindole derivatives with Morita-Baylis-Hillman (MBH) carbonates was developed to facilely construct chiral 3,3'-bisindole derivatives under mild reaction conditions. The regioselectivity (α/γ) of MBH carbonates was efficiently switched in the presence of chiral oxalamide phosphine or spiroketal-based diphosphine/Pd(0) complexes as a chiral catalyst. A series of multifunctional 3,3'-bisindole derivatives with all-carbon quaternary stereogenic centers were obtained in high yields with good to excellent enantio-, diastereo-, and regioselectivity. The present process is endowed with some salient features such as broad substrate scope, N-protecting group-free, excellent stereoselectivity, as well as adjustable regioselectivity.

5.
Appl Opt ; 62(3): 725-734, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36821278

RESUMO

Optomechanical components such as the lens barrels and frames of IR spectrometers produce strong internal stray radiation, which reduces the instrument's SNR and dynamic range. An IR internal stray radiation calculation method based on an analytical model of the view factor is proposed. The mathematical model of the view factor calculation method of typical optomechanical components is established. For any IR optical systems, the internal stray radiation can be quickly and accurately calculated by adjusting the coordinate systems in the calculation method. Based on the proposed method, the internal stray radiation of a double-pass long-wave IR spectrometer was calculated. The calculation results are consistent with the simulation results. The RMS value of the relative error between the calculated value and the simulated value is around 11%. To verify the proposed method, an experiment was conducted to test the internal stray radiation of the long-wave IR spectrometer. The internal stray radiation test results agree with the calculated and simulated results, and the relative error between the test results and the calculation results is within 9%.

6.
iScience ; 25(9): 104886, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-35966041

RESUMO

The emergence of the SARS-CoV-2 Omicron BA.1 (B.1.1.529) variant has raised questions regarding resistance to neutralizing antibodies elicited by natural infection or immunization. We examined the neutralization activity of sera collected from previously SARS-CoV-2-infected individuals and SARS-CoV-2 naive individuals who received BBIBP-CorV or CoronaVac to BA.1 and the earlier variants Alpha, Beta, and Delta. Both sera from convalescent patients over three months after infection and two-dose BBIBP-CorV or CoronaVac vaccine recipients barely inhibited BA.1, less effectively neutralized Beta and Delta, and moderately neutralized Alpha. However, administering a single dose of BBIBP-CorV or CoronaVac in previously infected individuals or a third dose booster vaccination of BBIBP-CorV or CoronaVac in previously vaccinated individuals enhances neutralizing activity against BA.1 and other variants, albeit with a lower antibody titer for BA.1. Our data suggest that a booster vaccination is important to broaden neutralizing antibody responses against the variants.

7.
Appl Opt ; 61(8): 2125-2139, 2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35297906

RESUMO

The spaceborne dispersive spectrometer is widely used in environmental, resource, and ocean observations. The coded spectrometer has higher energy advantages than the dispersion spectrometer, so it has great application prospects. In the current study, we developed an off-axis short-wave infrared coded optical system (SICOS) based on curved prism dispersion, and we further explored the design and optimization of the SICOS structure. Finite element analyses of a space-based short-wave infrared coded spectrometer based on curved prism dispersion (SSICS-CPD), including static simulation, modal analysis, sinusoidal vibration mechanical analysis, and random vibration mechanical analysis, were carried out. Simulation results showed that the SICOS support structure had excellent mechanical and thermal stability. As off-axis optical systems cannot meet the requirements of optical position accuracy through centering processing, a point source microscope and three-coordinate measuring machines were employed to complete the high-precision and rapid assembly of the SSICS-CPD. In addition, verification tests of surface shape error, stress relief, random vibration, and optical design parameters were carried out to validate the high stability and imaging performance of the SSICS-CPD. Results showed that the average modulation transfer function in the full field was 0.43 at 16.67 lp/mm, the spectral smile was <0.2 pixels, and the spectral keystone was <0.1 pixels. The design, analysis, assembly, and verification of the SSICS-CPD provide a useful reference for the development of other spaceborne prism dispersion spectrometers.

8.
Appl Opt ; 60(25): 7563-7573, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34613222

RESUMO

In view of the functional requirements of high reliability and stability support of optical components of space remote sensors, a rigid-flexible, dual-mode coupling support structure for space-based rectangular curved prisms (SRCPs) was designed. In-depth studies of the support principle and engineering realization of the SRCPs and optimization of the flexible adhesive structure were performed. Static and dynamic simulations were conducted on the mirror subassembly by means of finite element analysis, and test verification was also performed. The tests revealed that the surface shape error of the mirror subassembly after mechanical testing was 0.021λ, the displacement of the mirror body was 0.008 mm, the inclination angle was ∼0.8'', the mass of the mirror subassembly was 4.79 kg, the fundamental frequency was 283 Hz, and the maximum amplification of the total rms acceleration was 4.37. All indexes were superior to those of the design requirements. On this basis, bonding tests and mechanical tests of a rectangular curved prism reflector, a rectangular curved prism, and a rectangular plane reflector employing this proposed support structure were continued. The test results verified the reliability, stability, and universal applicability of the proposed rigid-flexible, dual-mode peripheral bonding support structure.

9.
Front Neurol ; 12: 644910, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054692

RESUMO

Background: Dopa-responsive dystonia (DRD) is a movement disorder that is highly clinically and genetically heterogeneous. Our study summarizes clinical characteristics and long-term outcomes in patients with dopa-responsive dystonia with the aim of obtaining further knowledge on this disorder. Methods: Patients who met DRD genetic diagnostic criteria through whole-exome sequencing and took levodopa for over 3 years were included in our study. Detailed information was collected on these patients, including family history, age at onset, age and dosage at starting levodopa, current medication and dosage, levodopa duration, diurnal fluctuation, and other clinical features. The Burke-Fahn-Marsden Dystonia Rating Scale-Motor (BFMDRS-M) score was used to evaluate patients' dystonia and variation after levodopa. According to the long-term outcomes, patients were further graded as good (dystonia improved by more than 50% after levodopa, and no further motor symptoms appeared) and poor (dystonia improved by <50% after levodopa, or new motor symptoms appeared). Results: A total of 20 DRD patients were included (11 with GCH1 variants, 9 with TH variants). During long-term levodopa treatment, three patients with TH variants (3/20, 15%) developed motor symptoms, including body jerks and paroxysmal symptoms, and responded well to increasing levodopa doses. The patient with homozygous mutation c.1481C>T/p. Thr494Met harbored more serious symptoms and poor response to levodopa and showed decreased cardiac uptake in MIBG. Conclusions: Most DRD patients showed satisfactory treatment outcomes after long-term levodopa, whereas few patients with TH variants presented motor symptoms, which is considered to be related to dopamine insufficiency. For patients with motor symptoms after long-term levodopa, increasing the dose slowly might be helpful to relieve symptoms.

10.
Inorg Chem ; 60(9): 6550-6558, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33861587

RESUMO

A versatile microporous metal-organic framework (MOF), {[Cu(TIA)]·1.5CH3OH}n (Cu-1), was successfully obtained via the solvothermal reaction of cuprous(II) salt with the bifunctional ligand 3-(1H-1,2,4-triazol-1-yl)isophthalic acid. Single-crystal X-ray diffraction studies indicate that Cu-1 contains an apo three-dimensional skeleton and two types of one-dimensional channels. The framework of Cu-1 has excellent acid-alkali resistance and thermal stability, which is stable in a pH = 2-13 aqueous solution and an 260 °C air environment. In addition, the microporous copper MOF shows very high uptakes of CO2 (180 cm3·g-1) and C2H2 (113 cm3·g-1) at 273 K and displays excellent adsorption selectivity for small molecular gases. The ideal adsorbed solution theory selectivity values for C2H2/C2H4, CO2/CH4, and CO2/N2 are 2, 9, and 22 at 298 K, respectively. At the same time, breakthrough experiments for CO2/CH4, CO2/N2, and C2H2/C2H4 were further conducted to verify the efficient separation performances.

11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 104-108, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554805

RESUMO

OBJECTIVE: To investigate the correlation between FOXP3, CD11c protein expression and the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: This study included 48 patients with DLBCL who were admitted to Jiujiang No.1 People's Hospital and TCM-Integrated Hospital of Southern Medical University from January 2015 to January 2019. The DLBCL tissues removed during the operation were collected as test specimens. The expression of FOXP3 and CD11c protein were detected by immunohistochemistry. The deadline for postoperative follow-up was December 31, 2019, and the patient's short-term efficacy (complete remission, partial remission) and progression-free survival were recorded. RESULTS: FOXP3 protein was positively expressed in the nucleus, mostly focally or diffusely distributed, the FOXP3+ rate was 54.17% (26/48). While, the CD11c protein was positively expressed on the cell membrane, mostly diffusely distributed, and the CD11c+ rate was 60.47% (29/48). The expression of FOXP3 and CD11c protein was no significant relationship with age, sex, site of involvement, and lactate dehydrogenase level in DLBCL patients, but was a significant relationship with clinical stage and international prognostic index score, the difference was statistically significant (P<0.05). That was, the lower the clinical stage of DLBCL patients and international prognostic index score, the higher the positive expression rate of FOXP3 and CD11c protein (r=0.637, r=0.709). One year after surgery, the total effective rate of DLBCL patients with FOXP3+ or CD11c+ expression was significantly higher than that of patients with FOXP3- or CD11c-,expression (P<0.05). By the end of the follow-up, the median progression-free survival of DLBCL patients with FOXP3+ or CD11c+ expression was significantly longer than that of patients with FOXP3- or CD11c+ expression (P<0.05). CONCLUSION: In some patients with DLBCL, FOXP3 and CD11c expresse positively, and the positive expression rate is related to the clinical stage and international prognostic index score. The positive expression of FOXP3 and CD11c indicate a good prognosis.


Assuntos
Linfoma Difuso de Grandes Células B , Fatores de Transcrição Forkhead , Humanos , Imuno-Histoquímica , Prognóstico , Proteômica
12.
BMC Complement Altern Med ; 19(1): 147, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234859

RESUMO

BACKGROUND: Ethanol withdrawal (EtOHW) anxiety is a crucial risk factor for alcoholic relapse. The neuropeptide nociceptin/orphanin FQ (N/OFQ) acts upon its receptor (NOP) to antagonize corticotropin-releasing factor (CRF) and elicit anxiolytic actions. Semen Ziziphi Spinosae (SZS), a prototypical hypnotic-sedative herb in Oriental medicine, exhibits anxiolytic effects during nicotine withdrawal by improving amygdaloid CRF/CRF1 receptor (CRFR1) signaling. Therefore, we evaluated the effects of SZS on EtOHW anxiety and the involvement of amygdaloid CRF/CRFR1 and N/OFQ/NOP pathways. METHODS: Male Sprague Dawley rats received intraperitoneal injections of 2 g/kg EtOH (20% v/v) once daily for 28 d followed by a 3-d withdrawal. During EtOHW, the rats were given once-daily intragastric treatments of a methanol extract of SZS (MESZS, 60 or 180 mg/kg/d). Anxiety-like behaviors were measured with the open field (OF) and elevated plus maze (EPM) tests, and plasma corticosterone (CORT) levels were examined by an enzyme-linked immunosorbent assay. mRNA and protein expression levels of the neuropeptides and their receptors were determined by quantitative polymerase chain reaction and Western blot assays. RESULTS: MESZS increased the distance traveled in the center zone of the OF and dose-dependently elongated the duration of staying in the center zone in EtOHW rats. MESZS increased both the number of entries into and the time spent in the open arms of the EPM by EtOHW rats. And, MESZS inhibited the over secretion of plasma CORT during EtOHW. EtOHW enhanced CRF and CRFR1 gene and protein expression in the central nucleus of the amygdala (CeA), which were inhibited by 180 mg/kg/d MESZS. EtOHW increased amygdaloid NOP mRNA and protein expression but spared N/OFQ mRNA expression, and 180 mg/kg/d MESZS further promoted these increases. Additionally, a post-MESZS intra-CeA infusion of either CRF or the selective NOP antagonist UFP-101 abolished the expected anxiolytic effect of 180 mg/kg/d MESZS. CONCLUSIONS: These results suggest that MESZS ameliorates EtOHW anxiety by improving both CRF/CRFR1 and N/OFQ/NOP transmissions in the CeA.


Assuntos
Ansiolíticos/administração & dosagem , Ansiedade/tratamento farmacológico , Núcleo Central da Amígdala/efeitos dos fármacos , Etanol/efeitos adversos , Neuropeptídeos/metabolismo , Síndrome de Abstinência a Substâncias/complicações , Ziziphus/química , Animais , Ansiedade/etiologia , Ansiedade/genética , Ansiedade/metabolismo , Núcleo Central da Amígdala/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de Hormônio Liberador da Corticotropina/genética , Receptores de Hormônio Liberador da Corticotropina/metabolismo
13.
Neuropharmacology ; 157: 107687, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31251995

RESUMO

At present, role of the lateral habenula (LHb) calcium-permeable AMPA receptors (CP-AMPARs) in depression is not understood, particularly in Parkinson's disease-related depression. Here we found that lesions of the substantia nigra pars compacta (SNc) in rats induced depressive-like behaviors, and intra-LHb injection of CP-AMPAR antagonist Naspm produced antidepressant-like effects in SNc sham-lesioned and SNc-lesioned rats, however, the doses inducing these effects in SNc-lesioned rats were lower than that of SNc sham-lesioned rats. Blockade of LHb CP-AMPARs decreased the firing rate of the neurons and increased release of dopamine and serotonin in the medial prefrontal cortex (mPFC) in both groups, but the duration of Naspm action on the firing rate and release of the transmitters were prolonged in SNc-lesioned rats. These changes in SNc-lesioned rats were involved in increased expression of ßCaMKII and p-GluR1-S831 in the LHb. Intra-LHb injection of Naspm inhibited dopaminergic neurons in the anterior ventral tegmental area and serotonergic neurons in the dorsal raphe nucleus and excited dopaminergic neurons in the posterior ventral tegmental area (pVTA) and serotonergic neurons in the median raphe nucleus (MRN), and lesioning the GABAergic rostromedial tegmental nucleus (RMTg) decreased the percentages of excited pVTA dopaminergic neurons and MRN serotonergic neurons. Our findings indicate that blockade of LHb CP-AMPARs produces antidepressant-like effects, which attribute to decreased firing activity of LHb neurons and increased levels of dopamine and serotonin in the mPFC, and provide further evidence that LHb CP-AMPARs regulate the firing activity of pVTA dopaminergic neurons and MRN serotonergic neurons indirectly via the RMTg.


Assuntos
Antidepressivos/farmacologia , Núcleo Dorsal da Rafe/fisiologia , Habenula/fisiologia , Oxidopamina/farmacologia , Parte Compacta da Substância Negra/fisiologia , Receptores de AMPA/antagonistas & inibidores , Espermina/análogos & derivados , Potenciais de Ação/fisiologia , Animais , Comportamento Animal/efeitos dos fármacos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/biossíntese , Dopamina/metabolismo , Neurônios Dopaminérgicos , Habenula/metabolismo , Ácido Ibotênico/farmacologia , Masculino , Inibição Neural/efeitos dos fármacos , Parte Compacta da Substância Negra/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Ratos , Receptores de AMPA/agonistas , Receptores de AMPA/metabolismo , Neurônios Serotoninérgicos , Serotonina/metabolismo , Espermina/farmacologia , Tegmento Mesencefálico/efeitos dos fármacos , Área Tegmentar Ventral/fisiologia
14.
Neuropharmacology ; 137: 275-285, 2018 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-29778944

RESUMO

Although the basolateral amygdala (BLA) and serotonin6 (5-HT6) receptor are involved in modulation of anxiety, their roles in Parkinson' disease (PD)-related anxiety are still unknown. Thus we perform this study to examine the involvement of BLA 5-HT6 receptor on anxiety in unilateral 6-hydroxydopamine-induced PD rats. The lesion of the medial forebrain bundle (MFB) induced anxiety-like behaviors, and decreased the basal firing rate of BLA glutamate neurons and dopamine (DA) levels in tissues of the medial prefrontal cortex (mPFC), amygdala and ventral part of hippocampus (vHip) in rats. Activation of BLA 5-HT6 receptor by local infusion of WAY208466 induced anxiolytic-like effects and increased extracellular γ-aminobutyric acid (GABA) level in the BLA in the lesioned rats. Blockade of BLA 5-HT6 receptor by SB258585 produced anxiolytic-like effects and increased extracellular GABA levels in the BLA in two groups of rats. Activation and blockade of BLA 5-HT6 receptor resulted in increases in DA levels and decreases in noradrenaline levels in tissues of the mPFC, amygdala and vHip in two groups of rats, and induced opposite effects on the firing activity of glutamate neurons between sham-operated and the lesioned rats. The results suggest that decreased DA levels in the limbic brain regions and the enhanced sensitivity of the 5-HT6 receptor on the BLA neurons might be etiological and pathophysiological factors for anxiety in PD. The anxiolytic-like effects may due to elevated extracellular GABA levels in the BLA and altered monoamine levels in the limbic regions, which were induced by WAY208466 and SB258585 through different mechanisms.


Assuntos
Ansiedade/metabolismo , Complexo Nuclear Basolateral da Amígdala/metabolismo , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/psicologia , Receptores de Serotonina/metabolismo , Animais , Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Corpo Estriado/fisiopatologia , Dopamina/metabolismo , Ácido Glutâmico/metabolismo , Masculino , Metilaminas/farmacologia , Vias Neurais/fisiopatologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Norepinefrina/metabolismo , Oxidopamina , Piperazinas/farmacologia , Piridinas/farmacologia , Ratos Sprague-Dawley , Serotoninérgicos/farmacologia , Substância Negra/fisiopatologia , Sulfonamidas/farmacologia , Ácido gama-Aminobutírico/metabolismo
15.
BMC Complement Altern Med ; 17(1): 493, 2017 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-29145840

RESUMO

BACKGROUND: We previously reported that a methanol extract of Glycyrrhizae radix (MEGR) blocked methamphetamine-induced locomotor sensitization and conditioned place preference in rats. In the present study, the effects of MEGR on repeated nicotine-induced locomotor sensitization and enhanced extracellular dopamine (DA) release in the nucleus accumbens (Nacc) were evaluated. METHODS: Male Sprague-Dawley rats received repeated administrations of nicotine (0.4 mg/kg, subcutaneous) or saline twice a day for 7 d and were challenged with nicotine 4 d after the last daily dosing. During the 4-d withdrawal period, the rats were treated once a day with MEGR (60 or 180 mg/kg/d). Extracellular DA levels were measured by in vivo microdialysis, the malondialdehyde levels and the activities of superoxide dismutase and catalase in the Nacc were biochemically evaluated, and the expression of antioxidant proteins was confirmed by Western blot assays. All data were assessed with analysis of variance tests followed by post-hoc comparison tests and p values <0.05 were considered statistically significant. RESULTS: The expression of repeated nicotine-induced locomotor sensitization was dose-dependently attenuated by MEGR, and 180 mg/kg/d MEGR significantly inhibited augmented accumbal DA release induced by a direct local challenge of nicotine. Moreover, 180 mg/kg/d MEGR reversed increases in malondialdehyde production, decreases in superoxide dismutase and catalase activities, and the reduced expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase 1 in the nicotine-sensitized Nacc. CONCLUSIONS: These results suggest that MEGR inhibited nicotine-induced locomotion and dopaminergic sensitization via antioxidant action.


Assuntos
Glycyrrhiza , Nicotina/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Dopamina/metabolismo , Interações Ervas-Drogas , Locomoção/efeitos dos fármacos , Masculino , Metanol , Núcleo Accumbens/química , Núcleo Accumbens/metabolismo , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley
16.
Nan Fang Yi Ke Da Xue Xue Bao ; 37(12): 1695-inside back cover, 2017 Dec 20.
Artigo em Chinês | MEDLINE | ID: mdl-29292268

RESUMO

OBJECTIVE: We report a rare case of a multiple sarcomatoid carcinoma of the jejunum with postoperative lung and brain metastases. The patient underwent jejunum segmental resection for intussusception and gastrointestinal bleeding. Multiple metastasis ofbrain and lung occurred 4 months after the operation, and the patient died for multiple organ failure 8 months after the surgery. Primary sarcomatoid carcinoma was difficult to diagnose at an early stage, and the diagnosis relies on optical microscopic and immunohistochemical observations. Currently no guidelinesare established for treatment for sarcomatoid carcinoma of the jejunum, and surgical resection remains the optimal therapeutic approach. Previous reports documented a poor prognosis of the patients with a median survival time of 5.5 months (0.36-36months), and the primary causes of death were tumor recurrence and metastasis. Ki-67 as a potential prognostic marker and the value of PD-L1-targeted immunotherapy for the treatment await further investigation.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias do Jejuno/patologia , Neoplasias Pulmonares/secundário , Neoplasias Primárias Múltiplas/patologia , Evolução Fatal , Humanos , Neoplasias do Jejuno/cirurgia , Recidiva Local de Neoplasia , Neoplasias Primárias Múltiplas/cirurgia
17.
Brain Res ; 1650: 184-195, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27616337

RESUMO

The role of dorsal hippocampus (DH) serotonin6 (5-HT6) receptors in memory is unknown, particularly in memory impairment of Parkinson's disease. We tested here effects of activation and blockade of DH 5-HT6 receptors on working and hippocampus-dependent memories in rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. The lesion induced working and hippocampus-dependent memory impairments as measured by the T-maze rewarded alternation and hole-board tests, and decreased dopamine (DA) levels in the striatum, medial prefrontal cortex (mPFC), DH and amygdala. Intra-DH injection of 5-HT6 receptor agonist WAY208466 (1.5, 3 and 6µg/rat) did not change choice accuracy and the number of head-dippings when re-exposure to hole-board in sham-operated rats, while 5-HT6 receptor antagonist SB258585 (4µg/rat) increased choice accuracy and decreased the number of head-dippings. In the lesioned rats, both WAY208466 (3 and 6µg/rat) and SB258585 (2 and 4µg/rat) increased choice accuracy and decreased the number of head-dippings. Neurochemical results showed that intra-DH injection of WAY208466 or SB258585 produced significant effects on DA and noradrenaline (NA) levels in the mPFC (WAY208466: sham-operated, NA -44%; lesioned, DA 522%, NA -47%; SB258585: sham-operated, DA 72%, NA 85%; lesioned, DA -68%), DH (WAY208466: lesioned, DA 427%; SB258585: sham-operated, DA 119%, NA 206%) and amygdala (WAY208466: sham-operated, NA -28%; lesioned, DA 302%; SB258585: sham-operated, NA 183%); however, 5-HT levels in these brain regions were not changed. These findings suggest DA depletion plays a key role in working and hippocampus-dependent memory impairments, and 5-HT6 receptors in the DH are involved in the regulation of the memories.


Assuntos
Memória de Curto Prazo/efeitos dos fármacos , Memória/efeitos dos fármacos , Receptores de Serotonina/metabolismo , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/fisiologia , Animais , Modelos Animais de Doenças , Dopamina/farmacologia , Hipocampo/efeitos dos fármacos , Masculino , Neostriado/efeitos dos fármacos , Norepinefrina/farmacologia , Oxidopamina/farmacologia , Doença de Parkinson , Transtornos Parkinsonianos , Córtex Pré-Frontal/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores de Serotonina/fisiologia , Serotonina/farmacologia
18.
Photodiagnosis Photodyn Ther ; 13: 201-204, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26162501

RESUMO

OBJECTIVE: To investigate the anti-tumor and immune efficacy of photodynamic immune-therapy (PIT), the combination of photodynamic therapy and dendritic cells (DC), on murine Heps hepatoma. METHODS: DCs were derived from syngeneic mouse bone marrow and then labeled with DAPI in vitro. The hepatoma model was established by subcutaneous inoculation with Heps cells in one hundred and twenty-eight mice. They were then divided into four groups at random: control group, PDT group, DC group and PIT group. Tumors in the control group were injected with normal saline. Mice in the PDT group were injected with the photosensitizer Deuteporfin 24 h before irradiation. Mice in the DC group were injected with DAPI labeled dendritic cells intratumorally. Mice in the PIT group were further given an injection of DCs after photoirradiation. Tumor growth and survival time were recorded after treatment. Fluorescence of tumor draining lymph nodes was evaluated under fluorescence microscope. Cytotoxic activity of splenocytes was tested by standard lactate dehydrogenase (lactate dehydrogenase, LDH) release assay. RESULTS: (1) Tumor growth was significantly slowed down in the PDT and PIT group compared to the control group (P<0.01). (2) The mean survival time was significantly prolonged in the PDT and PIT group. (3) The number of fluorescent cells in the draining lymph nodes from DC group was higher than that of the PIT group. (4) The anti-tumor activity of splenocytes in the PDT and PIT group was significantly higher than that of the DC and control groups (P<0.01, P<0.01). CONCLUSIONS: The present study suggests that PDT can inhibit tumor growth and induce anti-tumour immune response. The combination of PDT induced by Deuteporfiin and dendritic cell is capable of amplifying the antitumor immune response.


Assuntos
Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/terapia , Células Dendríticas/transplante , Imunoterapia Adotiva/métodos , Neoplasias Hepáticas/imunologia , Fotoquimioterapia/métodos , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Terapia Combinada/métodos , Células Dendríticas/imunologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Camundongos , Fármacos Fotossensibilizantes/uso terapêutico , Taxa de Sobrevida , Resultado do Tratamento
19.
J Hematol Oncol ; 8: 22, 2015 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-25887760

RESUMO

BACKGROUND: During tumor formation and expansion, increasing glucose metabolism is necessary for unrestricted growth of tumor cells. Expression of key glycolytic enzyme alpha-enolase (ENO1) is controversial and its modulatory mechanisms are still unclear in non-small cell lung cancer (NSCLC). METHODS: The expression of ENO1 was examined in NSCLC and non-cancerous lung tissues, NSCLC cell lines, and immortalized human bronchial epithelial cell (HBE) by quantitative real-time reverse transcription PCR (qRT-PCR), immunohistochemistry, and Western blot, respectively. The effects and modulatory mechanisms of ENO1 on cell glycolysis, growth, migration, invasion, and in vivo tumorigenesis and metastasis in nude mice were also analyzed. RESULTS: ENO1 expression was increased in NSCLC tissues in comparison to non-cancerous lung tissues. Similarly, NSCLC cell lines A549 and SPCA-1 also express higher ENO1 than HBE cell line in both mRNA and protein levels. Overexpressed ENO1 significantly elevated NSCLC cell glycolysis, proliferation, clone formation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo by regulating the expression of glycolysis, cell cycle, and epithelial-mesenchymal transition (EMT)-associated genes. Conversely, ENO1 knockdown reversed these effects. More importantly, our further study revealed that stably upregulated ENO1 activated FAK/PI3K/AKT and its downstream signals to regulate the glycolysis, cell cycle, and EMT-associated genes. CONCLUSION: This study showed that ENO1 is responsible for NSCLC proliferation and metastasis; thus, ENO1 might serve as a potential molecular therapeutic target for NSCLC treatment.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Ligação a DNA/metabolismo , Quinase 1 de Adesão Focal/metabolismo , Neoplasias Pulmonares/patologia , Fosfopiruvato Hidratase/metabolismo , Transdução de Sinais/fisiologia , Proteínas Supressoras de Tumor/metabolismo , Animais , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Glicólise/fisiologia , Xenoenxertos , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Camundongos , Camundongos Nus , Invasividade Neoplásica/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno , Transfecção
20.
Neuropharmacology ; 95: 181-91, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25797491

RESUMO

Although the medial subdivision of the central nucleus of the amygdala (CeM) and serotonin-1A (5-HT1A) receptors are involved in the regulation of anxiety, their roles in Parkinson's disease (PD)-associated anxiety are still unknown. Here we assessed the importance of CeM 5-HT1A receptors for anxiety in rats with unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle (MFB). The lesion induced anxiety-like behaviors, increased the firing rate and burst-firing pattern of CeM γ-aminobutyric acid (GABA) neurons, as well as decreased dopamine (DA) levels in the striatum, medial prefrontal cortex (mPFC), amygdala and ventral part of hippocampus (vHip). Intra-CeM injection of the selective 5-HT1A receptor agonist 8-OH-DPAT produced anxiolytic effects in the lesioned rats, and decreased the firing rate of CeM GABAergic neurons in two groups of rats. Compared to sham-operated rats, the duration of the inhibitory effect on the firing rate of GABAergic neurons was shortened in the lesioned rats. The injection increased DA levels in the mPFC and amygdala in two groups of rats and the vHip in the lesioned rats, and increased 5-HT level in the lesioned rats, whereas it decreased NA levels in the mPFC in two groups of rats and the vHip in the lesioned rats. Moreover, the mean density of 5-HT1A receptor and GABA double-labeled neurons in the CeM was reduced after the lesioning. These results suggest that activation of CeM 5-HT1A receptor produces anxiolytic effects in the 6-OHDA-lesioned rats, which involves decreased firing rate of the GABAergic neurons, and changed monoamine levels in the limbic and limbic-related brain regions.


Assuntos
8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Ansiolíticos/farmacologia , Transtornos de Ansiedade/tratamento farmacológico , Núcleo Central da Amígdala/efeitos dos fármacos , Transtornos Parkinsonianos/fisiopatologia , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Transtornos de Ansiedade/fisiopatologia , Núcleo Central da Amígdala/fisiopatologia , Dopamina/metabolismo , Neurônios GABAérgicos/efeitos dos fármacos , Neurônios GABAérgicos/fisiologia , Sistema Límbico/efeitos dos fármacos , Sistema Límbico/fisiopatologia , Masculino , Feixe Prosencefálico Mediano/fisiopatologia , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Oxidopamina , Transtornos Parkinsonianos/psicologia , Piperazinas/farmacologia , Piridinas/farmacologia , Ratos Sprague-Dawley , Receptor 5-HT1A de Serotonina/metabolismo , Antagonistas do Receptor 5-HT1 de Serotonina/farmacologia
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