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1.
Immunity ; 56(1): 180-192.e11, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36563676

RESUMO

The reinvigoration of anti-tumor T cells in response to immune checkpoint blockade (ICB) therapy is well established. Whether and how ICB therapy manipulates antibody-mediated immune response in cancer environments, however, remains elusive. Using tandem mass spectrometric analysis of modification of immunoglobulin G (IgG) from hepatoma tissues, we identified a role of ICB therapy in catalyzing IgG sialylation in the Fc region. Effector T cells triggered sialylation of IgG via an interferon (IFN)-γ-ST6Gal-I-dependent pathway. DC-SIGN+ macrophages represented the main target cells of sialylated IgG. Upon interacting with sialylated IgG, DC-SIGN stimulated Raf-1-elicited elevation of ATF3, which inactivated cGAS-STING pathway and eliminated subsequent type-I-IFN-triggered antitumorigenic immunity. Although enhanced IgG sialylation in tumors predicted improved therapeutic outcomes for patients receiving ICB therapy, impeding IgG sialylation augmented antitumorigenic T cell immunity after ICB therapy. Thus, targeting antibody-based negative feedback action of ICB therapy has potential for improving efficacy of cancer immunotherapies.


Assuntos
Carcinoma Hepatocelular , Interferon Tipo I , Neoplasias Hepáticas , Humanos , Imunoglobulina G , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Imunoterapia/métodos
2.
Mol Ther ; 31(1): 105-118, 2023 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-36183166

RESUMO

Epigenetic reprogramming is a promising therapeutic strategy for aggressive cancers, but its limitations in vivo remain unclear. Here, we showed, in detailed studies of data regarding 410 patients with human hepatocellular carcinoma (HCC), that increased histone methyltransferase DOT1L triggered epithelial-mesenchymal transition-mediated metastasis and served as a therapeutic target for human HCC. Unexpectedly, although targeting DOT1L in vitro abrogated the invasive potential of hepatoma cells, abrogation of DOT1L signals hardly affected the metastasis of hepatoma in vivo. Macrophages, which constitute the major cellular component of the stroma, abrogated the anti-metastatic effect of DOT1L targeting. Mechanistically, NF-κB signal elicited by macrophage inflammatory response operated via a non-epigenetic machinery to eliminate the therapeutic efficacy of DOT1L targeting. Importantly, therapeutic strategy combining DOT1L-targeted therapy with macrophage depletion or NF-κB inhibition in vivo effectively and successfully elicited cancer regression. Moreover, we found that the densities of macrophages in HCC determined malignant cell DOT1L-associated clinical outcome of the patients. Our results provide insight into the crosstalk between epigenetic reprogramming and cancer microenvironments and suggest that strategies to influence the functional activities of inflammatory cells may benefit epigenetic reprogramming therapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , NF-kappa B , Linhagem Celular , Macrófagos/patologia , Microambiente Tumoral , Histona-Lisina N-Metiltransferase/genética
3.
J Stroke Cerebrovasc Dis ; 32(9): 107296, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37567132

RESUMO

OBJECTIVES: The risk factors for post-carotid artery stenting severe hemodynamic instability remain elusive. This study aimed to identify the predictors of severe hemodynamic instability during and persisted after carotid artery stenting. MATERIALS AND METHODS: Consecutive patients who underwent carotid artery stenting for extracranial carotid artery stenosis at a single-center between September 2018 and July 2021 were retrospectively assessed. The predictive factors of severe hemodynamic instability intraoperation and post-operation were analyzed. RESULTS: Among the 139 patients included, 63 experienced severe hemodynamic instability, with 45 and 18 cases occurring intra and postoperatively, respectively. Persistent was observed in 21 patients. Smoke exposure (odds ratio [OR], 2.38; p=0.039), carotid bifurcation stenosis (OR, 0.91; p=0.018), and large-diameter balloon (>4 mm) dilatation (OR, 11.95; p<0.001) were identified as independent risk factors for hemodynamic instability at any stage of carotid artery stenting. Intraoperatively, large-diameter balloon (>4 mm) dilatation was associated with an increased risk of hemodynamic instability occurrence (OR, 4.67; p=0.01), whereas general anesthesia (OR, 0.19; p=0.001) and a longer distance from the stenosis to the carotid bifurcation (OR, 0.89; p=0.01) were negatively associated with hemodynamic instability. Furthermore, smoking exposure (OR, 3.73; p=0.03), large diameter balloon dilatation (OR, 6.12; p=0.032), distance from stenosis to bifurcation (OR, 0.85; p=0.047) and long-stent (40 mm) implantation (OR, 0.84 [95% confidence interval, 0.74-0.95]; p=0.007) could independently predict persistent hemodynamic instability. CONCLUSION: Patients with a smoking history, lesions near the carotid bulb, or dilatation using a large-diameter balloon were most likely to suffer severe hemodynamic instability. General anesthesia can protect against severe hemodynamic instability only intraoperatively. Long-term stent implantation may reduce persistent hemodynamic instability.


Assuntos
Angioplastia com Balão , Estenose das Carótidas , Humanos , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/terapia , Estenose das Carótidas/complicações , Hemodinâmica , Constrição Patológica/complicações , Estudos Retrospectivos , Angioplastia com Balão/efeitos adversos , Stents , Artérias Carótidas/cirurgia , Resultado do Tratamento
4.
Int Wound J ; 20(10): 4422-4428, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37488776

RESUMO

With the outbreak and pandemic of coronavirus disease-2019 (COVID-19), a huge number of people died of it. Apart from lung injuries, multiple organs have been confirmed to be impaired. In COVID-19 time, primary wound healing processes always prolong, however, its possible underlying mechanisms are still unclear. Therefore, to overcome this clinical problem, clarifying its underlying mechanisms clearly is necessary and urgently needed. In this review, we summarized that COVID-19 can prolong primary wound healing by inducing excessive inflammation and oxidative stress, disturbing immune system and haematological system, as well as influencing the functions and viability of epidermal stem cells (ESCs). Otherwise, we summarized that the strict control measures of blocking up COVID-19 pandemic can also have side effects on primary wound healing process.


Assuntos
COVID-19 , Cicatrização , Humanos , Pandemias , Células Epidérmicas
5.
BMC Neurol ; 22(1): 43, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35120481

RESUMO

BACKGROUND: The aim of this study was to develop a screening score system of non-contrast transthoracic echocardiography (TTE) for patent foramen ovale (PFO) in patients with embolic stroke of undetermined source (ESUS). METHODS: We performed a retrospective analysis of 218 consecutive patients with a recent ESUS from 2015 to 2018, who received TTE and transcranial Doppler (TCD) as routine examinations. PFO was diagnosed by the bubble test of TCD. Significant differences of the non-contrast TTE findings and patient characteristics between PFO group and non-PFO group were selected into a score. RESULTS: PFO was diagnosed in 35.8% (78/218) of the patients. Compared with non-PFO group, a larger median aortic root diameter (ARd) (34 mm vs. 32 mm, p = 0.005), a lower median peak E wave velocity (Em) (61.5 cm/s vs. 68 cm/s, p = 0.005) and a lower incidence rate of mitral regurgitation (34.6% vs. 50.7%, p = 0.022) were seen in PFO group. ARd>33 mm and Em < 72 cm/s were the best thresholds to predict PFO in ROC analysis. A four-point score system (MEAD) including TTE criteria (including ARd>33 mm, Em < 72 cm/s and without mitral regurgitation) and no history of diabetes predicted PFO with an area under curve of 0.67 (95%CI 0.57-0.72, p < 0.001). MEAD score ≥ 3 was the best threshold to predict PFO with an accuracy of 0.64 (95% CI 0.57-0.7), a sensitivity of 0.65 (95% CI 0.53-0.75) and a specificity of 0.63 (95% CI 0.55-0.71). CONCLUSION: The MEAD score measured with non-contrast TTE can be used to select patients for bubble test of TCD to increase the diagnostic yield of PFO after ESUS.


Assuntos
AVC Embólico , Forame Oval Patente , Acidente Vascular Cerebral , Ecocardiografia , Forame Oval Patente/complicações , Forame Oval Patente/diagnóstico por imagem , Forame Oval Patente/epidemiologia , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Ultrassonografia Doppler Transcraniana
6.
Cerebrovasc Dis ; 50(6): 700-706, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34289485

RESUMO

INTRODUCTION: Neurological impairment is associated with collateral status in acute ischaemic stroke (AIS). We aimed to validate the association between admission National Institutes of Health Stroke Scale (aNIHSS) score and infarct core volume (ICV) and target infarct core/penumbra volume mismatch (TMM) on CT perfusion (CTP) in AIS patients. METHODS: Patients with acute middle cerebral artery or internal carotid artery occlusion from 2011 to 2020 were included. All patients underwent pretreatment CTP at admission. ICV and TMM were analyzed with MIStar software on CTP maps. aNIHSS scores and clinical characteristics of patients were obtained from our prospectively recorded stroke database. RESULTS: We recruited 182 patients with a median age of 69.5 years; 85 (63.7%) were male, and the median aNIHSS score was 14. Of those, 149 (81.8%) had an ICV < 70 mL, and 139 (76.3%) had TMM. Lower aNIHSS was associated with an ICV < 70 mL, with an area under the curve (AUC) of 0.74, and TMM with an AUC of 0.76. Among all 15 items of the aNIHSS, the gaze score was the only item independently associated with an ICV < 70 mL (adjusted odds ratio [OR] = 0.42, 95% confidence interval [CI]: 0.22-0.79, p = 0.008) and TMM (adjusted OR = 0.5, 95% CI: 0.28-0.9, p = 0.021). One or both aNIHSS ≤ 16 and gaze score = 0 predicted TMM with a sensitivity of 0.79 and a specificity of 0.62. CONCLUSION: aNIHSS may be a useful tool to predict an ICV < 70 mL and TMM on CTP in AIS patients.


Assuntos
Infarto , AVC Isquêmico , Índice de Gravidade de Doença , Idoso , Feminino , Humanos , Infarto/diagnóstico , Infarto/diagnóstico por imagem , AVC Isquêmico/diagnóstico por imagem , Masculino , National Institutes of Health (U.S.) , Imagem de Perfusão , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X , Estados Unidos
7.
Acta Radiol ; 62(1): 73-79, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32228031

RESUMO

BACKGROUND: The methods used for grading leptomeningeal collateral flow (LMF) on single-phase computed tomography angiography (CTA) are heterogeneous and limited by temporal resolution. PURPOSE: To compare the reliability of relative filling time delay (rFTD) on CT perfusion source images (CTP-SI) and the currently used single-phase CTA collateral assessment methods and evaluate their ability to predict clinical outcomes in acute ischemic stroke patients. MATERIAL AND METHODS: We analyzed consecutive middle cerebral artery or internal carotid artery occlusion patients who received multimodal CT before treatment and within 12 h of stroke symptom onset from October 2015 to December 2018. Patients were dichotomized using the 90-day mRS into good (0-1) versus adverse (2-6) outcomes. CTP-SI was used to identify the rFTD score. CTA images were reconstructed to assess collateral status using the collateral score (Cs) and region leptomeningeal collateral score (rLMCs). Two observers independently assessed images. RESULTS: The baseline characteristics (n = 54) were median age of 67 years and 68.5% of the participants were men. The baseline median NIHSS was 14. Good clinical outcomes were observed in 19 (35.2%) patients. The k value was higher for rFTDs (k = 0.779, P < 0.001) than Cs (k = 0.666, P < 0.001) and rLMCs (k = 0.763, P < 0.001). Higher rFTDs were correlated with lower rLMCs (Spearman's rho -0.68, P < 0.001) and Cs (rho -0.66, P < 0.001). In multivariate logistic regression, rFTD was associated with functional outcomes (P = 0.044). CONCLUSION: The rFTDs method is comparable to single-phase CTA-based assessments in assessing LMFs in acute ischemic stroke patients. Higher rFTDs is independently associated with adverse long-term functional outcomes.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Angiografia Cerebral/métodos , Circulação Colateral/fisiologia , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Doença Aguda , Idoso , Isquemia Encefálica/complicações , Isquemia Encefálica/fisiopatologia , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/fisiopatologia , Angiografia por Tomografia Computadorizada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/fisiopatologia , Imagem Multimodal/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Acidente Vascular Cerebral/fisiopatologia
8.
Br J Haematol ; 191(1): 62-76, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32314355

RESUMO

Multiple myeloma stem-like cells (MMSCs) are responsible for initiation and relapse, though novel treatment paradigms that effectively eradicate MMSCs are yet to be developed. Selective inhibition of the cell cycle regulatory kinase Wee1 by MK1775 is being explored as a potential anti-cancer therapeutic. We report that higher expression of Wee1 is correlated with poor survival in multiple myeloma (MM). The MM models and patient-derived CD138+ plasma cells are particularly sensitive to the growth-inhibitory effects of the Wee1 inhibitor MK1775. MK1775 induces Mus81-Eme1 endonuclease-mediated DNA damage in S-phase cell cycle that results in a blockade of replication and then apoptosis. Furthermore, MK1775 strongly suppresses the features of stemness in vitro, in vivo and in primary CD138+ cells by decreasing ALDH1+ cell fraction and the expression of ALDH1. In addition, co-treatment of MK1775 with bortezomib is synergistic in vitro and in vivo. Bortezomib, although it enhances ALDH1+ cells, when combined with MK1775 abrogates this stimulatory effect on stemness. Considering MM as an invariably incurable malignancy due to the presence of heterogenic myeloma stem-like cells, our study presents inhibition of Wee1 as a promising targeted therapy for MM and provides a compelling rationale to further investigate the activity of MK1775 against myeloma in clinical settings.


Assuntos
Bortezomib/farmacologia , Proteínas de Ciclo Celular/antagonistas & inibidores , Mieloma Múltiplo , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirazóis/farmacologia , Pirimidinonas/farmacologia , Animais , Bortezomib/agonistas , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Sinergismo Farmacológico , Humanos , Camundongos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/enzimologia , Proteínas de Neoplasias/metabolismo , Proteínas Tirosina Quinases/metabolismo , Pirazóis/agonistas , Pirimidinonas/agonistas , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Biochem Biophys Res Commun ; 524(3): 549-554, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32014255

RESUMO

Cisplatin is a main chemotherapeutic drug used to treat non-small-cell lung cancer patients. However, these patients commonly face cisplatin resistance. The roles and underlying mechanisms of gemcitabine, irinotecan, pemetrexed and docetaxel used as single agents or combined with cisplatin for overcoming cisplatin-resistant non-small-cell lung cancer were explored in this study. MTT assays showed that gemcitabine alone exhibited stronger cytotoxicity on cisplatin-resistant A549 cells than irinotecan, pemetrexed and docetaxel. Meanwhile, gemcitabine combined with cisplatin showed a synergistic inhibitory effect on cisplatin-resistant cells. RNA sequencing and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analysis showed that cell cycle signaling pathways and trx-interacting protein were factors in the efficacy of the cotreatment. Flow cytometry and Western blot results showed that when cisplatin-resistant A549 cells were cotreated with gemcitabine and cisplatin, G0/G1 phase arrest occurred, and trx-interacting protein was upregulated. Silencing trx-interacting protein attenuated the response of the resistant cells to the drug combination. A trx-interacting protein agonist together with cisplatin showed an additive cytotoxic effect on the resistant cells compared with cisplatin alone. The gemcitabine and cisplatin combination, compared to gemcitabine or PBS alone, markedly suppressed the growth of cisplatin-resistant A549 tumors in vivo, accompanied by an increase in trx-interacting protein and a decrease in Ki67 expression. Therefore, we concluded that gemcitabine and cisplatin, as an FDA-approved combination, is a viable therapy for cisplatin-resistant non-small-cell lung cancer ex vivo and in vivo.


Assuntos
Proteínas de Transporte/genética , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Cisplatino/farmacologia , Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Células A549 , Animais , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Transporte/metabolismo , Morte Celular/efeitos dos fármacos , Desoxicitidina/farmacologia , Feminino , Fase G1/efeitos dos fármacos , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Gencitabina
10.
BMC Neurol ; 20(1): 139, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32299387

RESUMO

BACKGROUND: Endovascular therapy is widely used in acute large vessel occlusion. This study investigated whether imaging of lateral lenticulostriate arteries (LSAs) before thrombectomy would potentially be helpful for predicting prognosis of patients with acute M1 segment of middle cerebral artery occlusion (MCAO). METHODS: 59 consecutive patients with acute M1 segment of MCAO treated with mechanical thrombectomy at two comprehensive stroke centers were analyzed. Patients were categorized into LSA+ (appearing of lateral LSAs) and LSA- (sparing of lateral LSAs) group according to preprocedural digital substraction angiography (DSA). Baseline data and clinical outcomes were compared. A good clinical outcome was defined as a modified Rankin Scale score of 0 to 2 at 3 months. The association between clinical and imaging parameters and functional outcome was evaluated with logistic regression analysis. RESULTS: LSA+ was shown in 36 patients (61%). LSA+ group had a significantly higher proportion of good outcome (72.2% vs. 8.7%, OR 27.3,95% CI 5.38-138.4, P < 0.001), lower risk of symptomatic intracranial haemorrhages (sICH) (8.3% vs. 47.8%,OR 0.10,95% CI 0.02-0.42, P = 0.001) and lower mortality in hospital (5.6% vs. 34.8%, OR 0.11,95% CI 0.02-0.58, P < 0.004) compared with LSA- group. Patients in LSA+ group had lower baseline NIHSS score(P < 0.01) and NIHSS score at 14 days(P < 0.01) and smaller infarct core volume (P = 0.016) on computed tomography perfusion imaging (CTP) compared to the LSA- group. Multivariate logistic regression analysis showed that a small infarct core volume (OR 6.74,95% CI 1.148-39.569, P = 0.035) and LSA+(OR 22.114,95% CI 3.339-146.470, P = 0.001) were associated with a good clinical outcome. CONCLUSIONS: Our data suggest that appearance of lateral LSAs before mechanical thrombectomy would be potentially helpful for predicting favorable prognosis of patients with acute M1 segment of MCAO.


Assuntos
Infarto da Artéria Cerebral Média/cirurgia , Artéria Cerebral Média/diagnóstico por imagem , Trombectomia/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hemorragias Intracranianas/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
11.
BMC Med Genet ; 20(1): 194, 2019 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823746

RESUMO

BACKGROUND: Von Hippel-Lindau (VHL) syndrome is a familial autosomal dominant hereditary neoplastic disease caused by mutations in the VHL gene. Approximately 503 kinds of VHL gene mutations have been reported. Different types of mutations manifest various clinical phenotypes, from benign to malignant tumours or coexisting cysts. Thus, a gene mutation test is essential in the diagnosis of VHL syndrome. CASE PRESENTATION: We reported two cases in which a novel mutation site in the c530-536delGACTGGA region in exon 3 of the VHL gene resulted in the development of VHL syndrome. According to the ACMG guidelines, this variation is pathogenic and consistent with autosomal dominant inheritance. This variation has not been reported anywhere in the databases or literature. CONCLUSION: This report will add a new mutation site to VHL gene databases. The newly added gene mutation and its associated clinical phenotypes will help improve the accuracy of VHL diagnosis and benefit the community of VHL gene mutation carriers.


Assuntos
Mutação , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Doença de von Hippel-Lindau/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
J Stroke Cerebrovasc Dis ; 26(7): 1635-1640, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28478979

RESUMO

BACKGROUND: Intravenous thrombolysis and intra-arterial thrombectomy are now the standard therapies for patients with acute ischemic stroke. In-house strokes have often been overlooked even at stroke centers and there is no consensus on how they should be managed. Perioperative stroke happens rather frequently but treatment protocol is lacking, In China, the issue of in-house strokes has not been explored. The aim of this study is to explore the current management of in-house stroke and identify the common risk factors associated with perioperative strokes. METHOD: Altogether, 51,841 patients were admitted to a tertiary hospital in Shanghai and the records of those who had a neurological consult for stroke were reviewed. Their demographics, clinical characteristics, in-hospital complications and operations, and management plans were prospectively studied. Routine laboratory test results and risk factors of these patients were analyzed by multiple logistic regression model. RESULT: From January 1, 2015, to December 31, 2015, over 1800 patients had neurological consultations. Among these patients, 37 had an in-house stroke and 20 had more severe stroke during the postoperative period. Compared to in-house stroke patients without a procedure or operation, leukocytosis and elevated fasting glucose levels were more common in perioperative strokes. In multiple logistic regression model, perioperative strokes were more likely related to large vessel occlusion. CONCLUSION: Patients with perioperative strokes had different risk factors and severity from other in-house strokes. For these patients, obtaining a neurological consultation prior to surgery may be appropriate in order to evaluate the risk of perioperative stroke.


Assuntos
Acidente Vascular Cerebral/etiologia , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Glicemia/análise , China , Feminino , Humanos , Leucocitose/complicações , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Fatores de Tempo , Adulto Jovem
13.
Cell Physiol Biochem ; 38(4): 1472-82, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27035834

RESUMO

BACKGROUND/AIMS: Neuroserpin (NSP) is known for its neuroprotective role in cerebral ischemic animal models and patients. Our laboratory conducted a series of investigations on the neuroprotection of NSP in different cells in the brain. In the present study, we further observe the effects of NSP on neurons and microglia-mediated inflammatory response following oxygen-glucose deprivation (OGD), and explore possible mechanisms related to neuroprotection of OGD in the central nervous system (CNS). METHODS: Neurons and microglia from neonatal rats were treated with OGD followed by reoxygenation (OGD/R). To confirm the effects of NSP, the neuronal survival, neuronal apoptosis, and lactate dehydrogenase (LDH) release were measured in cultured neurons. Furthermore, the levels of IL-1ß and nitric oxide (NO) release were also detected in cultured microglia. The possible mechanisms for the neuroprotective effect of NSP were explored using Western blot analysis. RESULTS: NSP administration can reverse abnormal variations in neurons and microglia-mediated inflammatory response induced by OGD/R processes. The neuronal survival rate, neuronal apoptosis rate, and LDH release were significantly improved by NSP administration in neurons. Simultaneously, the release of IL-1ß and NO were significantly reduced by NSP in microglia. Western blot showed that the expression of ERK, P38, and JNK was upregulated in microglia by the OGD/R treatment, and these effects were significantly inhibited by NSP. CONCLUSION: These data verified the neuroprotective effects of NSP on neurons and microglia-mediated inflammatory response. Inhibition of the mitogen-activated protein kinase (MAPK) signaling pathways might play a potential role in NSP neuroprotection on microglia-mediated inflammatory response, which needs further verification.


Assuntos
Apoptose/efeitos dos fármacos , Neuropeptídeos/farmacologia , Fármacos Neuroprotetores/farmacologia , Serpinas/farmacologia , Animais , Western Blotting , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Glucose/farmacologia , Imuno-Histoquímica , Interleucina-1beta/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , L-Lactato Desidrogenase/metabolismo , Microglia/citologia , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Óxido Nítrico/metabolismo , Oxigênio/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Neuroserpina
14.
Appl Environ Microbiol ; 82(8): 2336-2346, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26850304

RESUMO

Buchnera aphidicolais an obligate endosymbiont that provides aphids with several essential nutrients. Though much is known about aphid-Buchnera interactions, the effect of the host plant on Buchnera population size remains unclear. Here we used quantitative PCR (qPCR) techniques to explore the effects of the host plant on Buchnera densities in the cotton-melon aphid, Aphis gossypii Buchneratiters were significantly higher in populations that had been reared on cucumber for over 10 years than in populations maintained on cotton for a similar length of time. Aphids collected in the wild from hibiscus and zucchini harbored more Buchnera symbionts than those collected from cucumber and cotton. The effect of aphid genotype on the population size of Buchnera depended on the host plant upon which they fed. When aphids from populations maintained on cucumber or cotton were transferred to novel host plants, host survival and Buchnera population size fluctuated markedly for the first two generations before becoming relatively stable in the third and later generations. Host plant extracts from cucumber, pumpkin, zucchini, and cowpea added to artificial diets led to a significant increase in Buchnera titers in the aphids from the population reared on cotton, while plant extracts from cotton and zucchini led to a decrease in Buchnera titers in the aphids reared on cucumber. Gossypol, a secondary metabolite from cotton, suppressed Buchnera populations in populations from both cotton and cucumber, while cucurbitacin from cucurbit plants led to higher densities. Together, the results suggest that host plants influence Buchnera population processes and that this may provide phenotypic plasticity in host plant use for clonal aphids.


Assuntos
Afídeos/microbiologia , Carga Bacteriana , Buchnera/crescimento & desenvolvimento , Plantas/parasitologia , Densidade Demográfica , Animais , Reação em Cadeia da Polimerase em Tempo Real
15.
J Stroke Cerebrovasc Dis ; 25(12): 2814-2820, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27544864

RESUMO

BACKGROUND/OBJECTIVE: We sought to assess the different patterns of cerebral hemodynamic changes in staged carotid angioplasty and stenting (CAS). METHODS: We prospectively recruited a cohort of patients with regular angioplasty or staged angioplasty from October 2013 to August 2015. The hemodynamic changes, including peak systolic, end-diastolic, and mean flow velocities in the ipsilateral middle cerebral artery (MCA) and the contralateral anterior cerebral artery (ACA), were recorded by transcranial Doppler ultrasound. RESULTS: Between October 2013 to August 2015, 25 patients (age range from 48 to 78 years, 96% male) with CAS were recruited, of whom 13 patients received staged angioplasty and 12 patients received regular angioplasty. Patients in the staged angioplasty group showed a higher degree of stenosis in the internal carotid artery. After the procedure, the peak systolic, diastolic, and mean flow velocities in the ipsilateral MCA in the staged angioplasty group were significantly higher than those in the regular angioplasty group (P = .028, .036, and .027, respectively). In the staged angioplasty group, first, the peak systolic, end-diastolic, and mean flow velocities in the contralateral ACA decreased significantly soon after balloon dilation in stage I (P = .042, .033, and .034, respectively). Second, the peak systolic, diastolic, and mean flow velocities in the ipsilateral MCA increased after stent placement in stage II (P = .006, .042, and .003, respectively). CONCLUSIONS: Two-stage hemodynamic changes were observed in staged angioplasty. The velocities in the ipsilateral MCA started to increase significantly after the collateral flow diminished.


Assuntos
Angioplastia/instrumentação , Artéria Cerebral Anterior/fisiopatologia , Artéria Carótida Interna/fisiopatologia , Estenose das Carótidas/terapia , Circulação Cerebrovascular , Hemodinâmica , Artéria Cerebral Média/fisiopatologia , Stents , Idoso , Angiografia Digital , Artéria Cerebral Anterior/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo , Artéria Carótida Interna/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/fisiopatologia , Circulação Colateral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Ultrassonografia Doppler Transcraniana
17.
J Stroke Cerebrovasc Dis ; 24(1): 100-3, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25440345

RESUMO

BACKGROUND: We aimed to test the outcome-predictive power of routine fasting glucose (FG) obtained at second day after onset in intravenous thrombolysis (IVT) acute ischemic stroke (AIS) patients. METHODS: We identified AIS patients presenting to our institution between December 2011 and July 2013 within 4.5 hours of onset, who received admission glucose (AG) before IVT, FG, and glycated hemoglobin (HbA1c) the second day after admission, from our prospectively recorded stroke database. Multivariate logistic regression was used to assess the association of FG and 90-day modified Rankin Scale (mRS). RESULTS: Between December 2011 and July 2013, a total of 166 AIS patients received intravenous plasminogen activator. Of those, 119 patients who have AG before IVT, FG, and HbA1c the second day were included in the study. FG independently predicted 90-day clinical unfavorable outcome (mRS, 3-6 with an odds ratio of 1.576; 95% confidence interval [CI], 1.053-2.358; P = .027). This association was not significant in AG (P = .714), HbA1c (P = .655), and history of diabetes (P = .547). In receiver operating characteristic analysis, increased FG was associated with 90-day mRS (3-6) with an area under curve of .72, (95% CI, .65-.9; P = .001). CONCLUSIONS: FG is a powerful predictor associated with the outcome in IVT-treated AIS patients independent of AG and HbA1c.


Assuntos
Glicemia/metabolismo , Isquemia Encefálica/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Idoso , Jejum/metabolismo , Feminino , Fibrinolíticos/uso terapêutico , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Ativador de Plasminogênio Tecidual/uso terapêutico , Falha de Tratamento
18.
J Stroke Cerebrovasc Dis ; 24(7): 1609-13, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25959501

RESUMO

BACKGROUND: We sought to assess the association of left ventricle mass (LVM) indices with the functional outcome of acute ischemic stroke (AIS) patients after intravenous tissue plasminogen activator (IV-tPA). METHODS: Consecutive AIS patients with IV-tPA were recruited. LVM indices including LVM/weight, LVM/surface, and LVM/heightˆ(2.7) on echocardiogram during hospitalization were retrospectively reviewed. Outcome was 90-day modified Rankin scale (mRS) scores. Multivariate logistic regression was performed to analyze the association of LVM indices with outcome. RESULTS: Between August 2010 and May 2014, 55 AIS patients (age range from 27 to 78 years, 69.1% men) with echocardiogram after thrombolysis were recruited. Lower baseline National Institutes of Health Stroke Scale (NIHSS; P = .009) and higher LVM indices (LVM/weight [P = .012], LVM/surface [P = .039], and LVM/heightˆ(2.7) [P = .045]) were significantly associated with 90-day favorable outcome (mRS, 0-2). In multivariate logistic regression analysis, LVM/weight independently predicted good outcome with an odds ratio of 3.89 (95% confidence interval, 1.05-14.42, P = .042) after adjustment for baseline NIHSS, onset-to-treatment time, hypertension, hemorrhagic transformation, and systolic left ventricle inner diameters. CONCLUSIONS: Higher LVM indices on echocardiogram are significantly associated with favorable outcome in stroke patients with IV-tPA, among which LVM/weight seems to be the most effective.


Assuntos
Fibrinolíticos/administração & dosagem , Ventrículos do Coração/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/administração & dosagem , Adulto , Idoso , Angiografia Cerebral/métodos , Avaliação da Deficiência , Feminino , Fibrinolíticos/efeitos adversos , Ventrículos do Coração/fisiopatologia , Humanos , Hipertrofia Ventricular Esquerda/fisiopatologia , Infusões Intravenosas , Modelos Logísticos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Ativador de Plasminogênio Tecidual/efeitos adversos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia , Função Ventricular Esquerda
19.
J Stroke Cerebrovasc Dis ; 23(8): 1995-2000, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25106829

RESUMO

BACKGROUND: Spinal dural arteriovenous fistula (SDAVF) is a rare disorder with the presenting of nonspecific clinical symptoms and signs at onset, which can be a challenge to diagnose promptly and leads to the overusing of spinal digital subtraction angiography (SpDSA) in clinical practice. The purpose of this study was to find specific characteristics of SDAVF by comparing the clinical and radiologic data between the SpDSA-identified patients with SDAVF and SpDSA-negative patients, who were suspected with spinal vascular diseases before admission. METHODS: From 2006 to 2011, patients presented to Huashan hospital with spinal symptoms and who received SpDSA were retrospectively analyzed. Comparisons of clinical and magnetic resonance imaging data were performed between SpDSA-identified SDAVF and SpDSA-negative patients. We derived a diagnostic criteria score and assessed likely clinical usefulness to predict the SDAVF using the score to stratify all patients with suspected. RESULTS: Four independent predictors (age ≥50 years, length of intramedullary lesion ≥5 vertical segments, perimedullary dilated vessels, and subcervical lesion) tested out by multivariable logistic regression and receiver operating characteristic analysis were significantly associated with SDAVF. A 4-point score (AVFS) including those criteria predicted the SpDSA-identified SDAVF with an area under the curve of .91 (95% confidence interval [CI] .84-.97, P < .001). A threshold of AVFS of 3 or more predicted SDAVF with a sensitivity of 85% (95% CI 62%-96%) and a specificity of 97% (95% CI 86%-99%). CONCLUSION: The AVFS score may be useful in routine clinical practice to identify high-risk individuals with SDAVF who need further confirmation with SpDSA.


Assuntos
Angiografia Digital/métodos , Malformações Vasculares do Sistema Nervoso Central/diagnóstico , Malformações Vasculares do Sistema Nervoso Central/patologia , Imageamento por Ressonância Magnética , Doenças da Medula Espinal/patologia , Medula Espinal/irrigação sanguínea , Fatores Etários , Idoso , Angiografia Digital/normas , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
J Stroke Cerebrovasc Dis ; 23(5): 1094-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24355568

RESUMO

BACKGROUND: Massive ipsilateral edema in patients with cerebral dural arteriovenous fistula (DAVF) is poorly documented. The present study better characterizes this condition through assessment of venous anatomy and potential underlying mechanisms. METHODS: One hundred and two consecutive patients diagnosed with DAVF and admitted to the Huashan Hospital from 2006 to 2012 were retrospectively reviewed for the clinical and radiologic data, and those with ipsilateral edema were recruited. An edema scale was calculated from the locations with edema on magnetic resonance imaging. We created a reflux anatomic venous scale (RAVS, including veins of Labbe, Sylvian, and Troland) based on DSA. Two experienced interventional neuroradiologists independently assessed the images and then reached consensus. The Spearman nonparametric rank correlation was performed to analyze the correlation between edema scale and RAVS. RESULTS: Seven patients (mean 61 ± 13 years; 4 men:3 women) with ipsilateral intracranial edema were finally included. DAVF in transverse sinus with reflux flow initially in vein of the Labbe was seen in all patients. Increased edema scale was significantly correlated with increased RAVS (Spearman rho = .856, P = .014). CONCLUSION: The present study indicated that severe ipsilateral edema, with reflux flow initially in vein of the Labbe, was associated with the increased number of reflux anatomic veins in transverse sinus DAVF.


Assuntos
Edema Encefálico/etiologia , Malformações Vasculares do Sistema Nervoso Central/complicações , Veias Cerebrais/fisiopatologia , Circulação Cerebrovascular , Idoso , Angiografia Digital , Edema Encefálico/diagnóstico , Edema Encefálico/fisiopatologia , Malformações Vasculares do Sistema Nervoso Central/diagnóstico , Malformações Vasculares do Sistema Nervoso Central/fisiopatologia , Angiografia Cerebral/métodos , Veias Cerebrais/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Flebografia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
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