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1.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(6): 605-609, 2020 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-32521984

RESUMO

Robotic-assisted transanal total mesorectal excision (R-TaTME) has unique advantage in low rectal cancer. Single incision plus oneport (SIPOP) laparoscopic operation can synchronously cooperate with robotic-assisted transanal operation, in order to the difficulty of operation, improve the quality of operation and shorten the time of operation. A retrospective analysis was conducted on the clinical and pathological data of one patient who underwent SIPOP synchronously combined with R-TaTME + sigmoid-anal anastomosis + ileostomy at the Department of General Surgery, Army Characteristic Medical Center on September 11, 2019. This 71-year-old patient was male with body mass index of 24.08 kg/m(2) and received preoperative chemotherapy. Rectal adenocarcinoma was confirmed by colonoscopy biopsy, and distance from tumor lower edge to anal verge was 3 cm. MRI indicated T2N1 stage. The operation was completed successfully, and the transabdominal and robotic transanal surgery totaled 117 minutes, with 15 minutes for the robotic transanal preparation step. There was about 20 ml of intraoperative blood loss and no blood transfusion was performed. The patient was discharged 6 days after operation. No intraoperative or postoperative complications occurred. The postoperative TNM staging was stage I (pyT2N0cM0). No recurrence or metastasis was found at postoperative 7 month. It is a safe, effective and feasible technique for patients with low rectal cancer.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias Retais/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Cirurgia Endoscópica Transanal/métodos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Idoso , Canal Anal/cirurgia , Anastomose Cirúrgica , Antineoplásicos/administração & dosagem , Colo Sigmoide/cirurgia , Humanos , Ileostomia , Laparoscopia/métodos , Masculino , Mesentério/cirurgia , Terapia Neoadjuvante , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia , Reto/cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/instrumentação , Cirurgia Endoscópica Transanal/instrumentação
2.
Zhonghua Bing Li Xue Za Zhi ; 48(12): 921-927, 2019 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-31818064

RESUMO

Objective: To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy. Methods: This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer's protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS. Results: There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109). Conclusion: There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Quinase do Linfoma Anaplásico/genética , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico , Humanos , Hibridização in Situ Fluorescente , Variações Dependentes do Observador , Patologistas , Estudos Retrospectivos
5.
Ann Oncol ; 30(6): 990-997, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30916311

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) often presents with multiple nodules within the liver, with limited effective interventions. The high genetic heterogeneity of HCC might be the major cause of treatment failure. We aimed to characterize genomic heterogeneity, infer clonal evolution, investigate RNA expression pattern and explore tumour immune microenvironment profile of multifocal HCC. PATIENTS AND METHODS: Whole-exome sequencing and RNA sequencing were carried out in 34 tumours and 6 adjacent normal liver tissue samples from 6 multifocal HCC patients. Protein expression of Ki67, AFP, P53, Survivin and CD8 was detected by immunohistochemistry. Fluorescence in situ hybridization was carried out to validate the amplification status of sorafenib-targeted genes. RESULTS: We deciphered genomic and transcriptional heterogeneity among tumours in each multifocal HCC patient including mutational profiles, copy number alterations, tumour evolutionary trajectory and tumour immune microenvironment profiles. Of note, sorafenib-targeted alterations were identified in the trunk of phylogenetic tree in only one out of the six patients, which may explain the relative low treatment response rate to sorafenib in clinical practice. Moreover, we demonstrated RNA expression patterns and tumour immune microenvironment profiles of all nodules. We found that RNA expression pattern was associated with Edmondson-Steiner grading. Based on the differential expression of 66 reported immune markers, unsupervised hierarchical clustering analysis of 34 nodules identified immune subsets: one low expression cluster with seven nodules and one high expression cluster with 11 nodules. CD8+ T cells were more enriched in nodules of the high expression cluster. CONCLUSIONS: Our study provided a detailed view of genomic and transcriptional heterogeneity, clonal evolution and immune infiltration of multifocal HCC. The heterogeneity of druggable targets and immune landscape might help interpret the clinical responsiveness to targeted drugs and immunotherapy for multifocal HCC patients.

6.
Artigo em Chinês | MEDLINE | ID: mdl-29495173

RESUMO

Objective: To investigate the relationship between workplace bullying and posttraumatic stress disorder (PTSD) in nursing staff, and to analyze the role of psychological capital between workplace bullying and PTSD. Methods: From December 2014 to June 2015, convenience sampling was used to collect 496 nurses from 5 grade A tertiary hospitals in a province of China. Their workplace bullying, psychological capital, and PTSD status were assessed using the Negative Acts Questionnaire, Psychological Capital Questionnaire, and Posttraumatic Stress Disorder Self-Rating Scale, respectively. The correlation between variables was analyzed using a structural equation model. Results: Among these nurses, the scores of negative acts, psychological capital, and PTSD were 37.15±12.83, 78.81±16.54, and 34.56±12.52, respectively. The score on each dimension of negative acts was positively correlated with that on each dimension of PTSD (P<0.01) ; the score on each dimension of psychological capital was negatively correlated with that on each dimension of PTSD and negative acts (P<0.01). Negative acts had a positive predictive effect on PTSD (ß=0.539, P<0.01) , which was reduced after inclusion of psychological capital (ß=0.513, P<0.01). The path coefficient was 0.62 for the effect of negative acts on PTSD, -0.18 for the effect of negative acts on psychological capital, and -0.11 for the effect of psychological capital on PTSD (P<0.05) . Conclusion: Workplace bullying is a predictive factor for PTSD, and psychological capital plays a mediating role between workplace bullying and PTSD. The manager should reduce workplace bullying to improve the psychological capital in nursing staff and to prevent and reduce PTSD.


Assuntos
Bullying , Recursos Humanos de Enfermagem no Hospital , Transtornos de Estresse Pós-Traumáticos , Local de Trabalho , Adulto , China , Humanos , Masculino , Inquéritos e Questionários , Centros de Atenção Terciária
7.
Eur Rev Med Pharmacol Sci ; 21(21): 4891-4895, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29164572

RESUMO

OBJECTIVE: To investigate the relationship between the expression of glucose transporter-1 (GLUT-1) and the clinicopathological features and prognosis of patients with nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Sixty-three patients with NPC (the NPC group) and 24 patients with chronic nasopharyngitis (the control group) who were treated between December 2014 and February 2016 were selected for this study. Pathological nasopharyngeal tissues were collected from patients. The expression of GLUT-1 was detected by immunohistochemistry. The expression of GLUT-1 was correlated with clinicopathological features and survival time. RESULTS: The positive GLUT-1 expression rate in the NPC group was 58.73% (37/63), which was significantly higher than in the control group (29.17%, 7/24) (p<0.01). The positive GLUT-1 expression rate was significantly correlated with clinical stage, lymph node metastasis, and Epstein-Barr (EB) virus infection (p<0.05). The 3-year survival rate of GLUT-1-positive NPC patients was 75.00% and was significantly lower than that of GLUT-1-negative NPC patients (88.89%) (p<0.05). CONCLUSIONS: GLUT-1 was highly expressed in the nasopharyngeal tissues of patients with NPC, and its expression was associated with clinical stage, lymph node metastasis, and EB virus infection.


Assuntos
Carcinoma/metabolismo , Carcinoma/patologia , Transportador de Glucose Tipo 1/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Adulto , Idoso , Carcinoma/complicações , Carcinoma/genética , Estudos de Casos e Controles , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/patologia , Feminino , Transportador de Glucose Tipo 1/genética , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/complicações , Neoplasias Nasofaríngeas/genética , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida
8.
Microsc Res Tech ; 80(12): 1344-1350, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28921824

RESUMO

The famous lacquer wares excavated from the Jiuliandun Tombs of the middle and late Warring States period (476-221 BC) were analyzed using scanning electron microscopy/energy as well as dispersive X-ray spectrometry (SEM/EDS), Raman spectroscopy (RS), optical microscopy (OM), and X-ray diffraction (XRD). The results showed a multilayer structure in the lacquer film, including a Qihui layer (a layer made of lacquer and various plasters), undercoat layer (or finishing coat) and colored paint layer mixed with various inorganic particles, such as quartz (SiO2 ) and hydroxyapatite [Ca5 (PO4 )3 (OH)], as fillers in the Qihui layers or orpiment (As2 S3 ) and cinnabar (HgS), which were used as a yellow or red pigment, respectively. With the help of elemental mapping images, a double-layer structure of the lacquer plaster was observed, corresponding to a mixture of lacquer liquid and bone ash [Ca5 (PO4 )3 (OH)], with large-diameter particles in the ground lacquer layer near the wooden body and small quartz (SiO2 ) particles in upper lacquer layer. Specifically, quartz particles detected in the undercoat layer as fillers could be beneficial for improving the moshardness value, cost reduction and abrasive resistance of the lacquer film. In fact, the mixed method that used urushi and inorganic particles to form lacquer plaster was an important technological innovation and deeply influenced lacquering technologies worldwide. The results of this study will not only contribute to understanding the importance of lacquer skills in the Chinese Warring States but also provide information for cultural relic conservation as well as modern lacquer manufacturing for their protection and duplication.

9.
Zhonghua Bing Li Xue Za Zhi ; 46(4): 228-234, 2017 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-28376587

RESUMO

Objective: To investigate the multidirectional differentiation potential in epithelioid sarcoma (ES), with special emphasis on its mesothelial and lymphatic endothelial markers expression. Methods: Ten cases of distal-type ES were included. The clinical, histological, and immunohistochemical(including mesothelial and lymphatic endothelial markers expression)features and follow-up data were evaluated. Results: The patients aged between 8 to 66 years. Five cases were male and five were female. The tumors were located at the palm (2 cases), wrist (3 cases), upper arm (2 cases), poplitealfossa (1 case), lower leg (1 case) and thigh (1 case), respectively. Clinically, most cases presented as painful, firm subcutaneous nodules. Histologically, the tumors were mainly composed of epithelioid, rhabdoid, spindle, or transitional cells, with abundant eosinophilic cytoplasm, oval and vesicular nucleus, and one or more prominent nucleoli. They were arranged in nodular, diffuse nodular or sheet like growth patterns, frequently with necrosis at the center with vague granulomatous configuration. Immunohistochemically, all tumors expressed cytokeratins, epithelial membrane antigen, CD34, desmin, mesothelial markers such as Calretinin, WT1, D2-40, M2A, vascular and lymphatic endothelial markers FLI-1, and VEGFR-3. The tumor cells did not express CD31, FⅧRAg, HHF35, HMB45, Melan A, MyoD1, myogenin, S-100 protein and SMA. All 10 patients underwent radical resection or extended excision, with additional radiotherapy or chemotherapy. During the follow-up from October 2012 to August 2016, seven cases showed recurrences and metastases within 2 months to 2 years. Five patients died of the disease due to widespread metastases. Conclusions: ES may show a wide spectrum of morphology, and display a multidirectional differentiating capabilities including towards mesothelial and lymphatic endothelial cells. As such, its diagnosis and differential diagnosis are particularly important as it is easily confused with other tumors with similar morphology or immune phenotype.


Assuntos
Endotélio Linfático/patologia , Sarcoma/patologia , Adolescente , Adulto , Idoso , Braço , Biomarcadores Tumorais , Diferenciação Celular , Criança , Desmina/análise , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Queratinas/análise , Masculino , Pessoa de Meia-Idade , Mucina-1/análise , Proteínas de Neoplasias/análise , Proteínas S100/análise , Sarcoma/química , Sarcoma/diagnóstico , Coxa da Perna , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/análise
10.
Zhonghua Bing Li Xue Za Zhi ; 46(3): 176-181, 2017 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-28297758

RESUMO

Objective: To analyze the clinical and pathological features of Kaposiform hemangioendothelioma (KHE), and to investigate the role of master transcriptional factor Prox-1 in the regulation of lymphatic differentiation. Methods: Nine cases of KHE (during the period from October 2009 to June 2016) were collected with clinical and pathological data. H&E stained section review and immunohistochemietry using the Dako EnVision method were performed. Results: There were 6 female and 3 male patients with age ranging from 2 months to 8 years (median 3 years and 4 months). The patients presented with either single subcutaneous soft tissue mass, or bone tumors, with the duration of disease onset ranging from 1 month to 1 year. The sites of involvement included the skins of neck (2 cases), nose root (1 case), inguinal (1 case), thigh root (1 case), humerus (2 cases), lumbar vertebrae(1 case), and mesentery (1 case). These tumors were histologically composed of nodules of densely packed spindle or ovoid cells and deformed small blood vessels in an invasive growth pattern. The tumor cells were immunohistochemically positive for both blood vessels and lymphatic endothelial markers, including Prox-1, the master transcriptional factor, and VEGFR-3. With followed-up from 1 to 60 months (median 26 months), two patients died of the disease, while the remaining patients were alive without recurrence. Conclusions: KHE is a rare vascular tumor with at least partial lymphatic endothelial differentiation, in which Prox-1 may act as a master regulator for such differentiation. KHE is an aggressive tumor of intermediate malignant potential, with local invasion and recurrence tendency, and long term follow-up is required.


Assuntos
Neoplasias Ósseas/patologia , Hemangioendotelioma/genética , Hemangioendotelioma/patologia , Proteínas de Homeodomínio/genética , Síndrome de Kasabach-Merritt/genética , Síndrome de Kasabach-Merritt/patologia , Sarcoma de Kaposi/genética , Sarcoma de Kaposi/patologia , Neoplasias Cutâneas/patologia , Proteínas Supressoras de Tumor/genética , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/genética , Biomarcadores Tumorais , Criança , Pré-Escolar , Feminino , Marcadores Genéticos , Fator 1-alfa Nuclear de Hepatócito , Proteínas de Homeodomínio/metabolismo , Humanos , Masculino , Recidiva Local de Neoplasia , Proteínas Supressoras de Tumor/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Neoplasias Vasculares/genética , Neoplasias Vasculares/patologia
11.
Oncogene ; 35(17): 2197-207, 2016 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-26257057

RESUMO

Enhanced sensitivity to Wnts is an emerging hallmark of a subset of cancers, defined in part by mutations regulating the abundance of their receptors. Whether these mutations identify a clinical opportunity is an important question. Inhibition of Wnt secretion by blocking an essential post-translational modification, palmitoleation, provides a useful therapeutic intervention. We developed a novel potent, orally available PORCN inhibitor, ETC-1922159 (henceforth called ETC-159) that blocks the secretion and activity of all Wnts. ETC-159 is remarkably effective in treating RSPO-translocation bearing colorectal cancer (CRC) patient-derived xenografts. This is the first example of effective targeted therapy for this subset of CRC. Consistent with a central role of Wnt signaling in regulation of gene expression, inhibition of PORCN in RSPO3-translocated cancers causes a marked remodeling of the transcriptome, with loss of cell cycle, stem cell and proliferation genes, and an increase in differentiation markers. Inhibition of Wnt signaling by PORCN inhibition holds promise as differentiation therapy in genetically defined human cancers.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Proteínas de Membrana/genética , Proteínas Wnt/genética , Aciltransferases , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas de Membrana/antagonistas & inibidores , Camundongos , Processamento de Proteína Pós-Traducional , Células-Tronco/efeitos dos fármacos , Proteínas Wnt/antagonistas & inibidores , Via de Sinalização Wnt/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Neuroscience ; 277: 637-46, 2014 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-25090922

RESUMO

OBJECT: To investigate whether resting-state functional connectivity (FC) differed in the default mode network (DMN) in stroke patients with and without post-stroke cognitive impairment (PSCI vs. Non-PSCI) and to explore the relationship between DMN connectivity and the cognitive performance in stroke patients. METHODS: We totally enrolled twenty healthy controls and 18 stroke patients. The stroke patients were divided into two subgroups on the basis of the cognitive assays. Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) scores were recorded 10 days and 3 months after the stroke. Independent component analysis was used to isolate the DMN. One-way analysis of variance was performed to detect different FC among groups. Pearson correlation analyses were conducted to determine the relationships between FC strength and the MoCA and MMSE scores. RESULTS: Compared to healthy controls, both Non-PSCI patients and PSCI patients showed significantly decreased FC in the posterior cingulate cortex/precuneus (PCC/PCu), as well as increased FC in the medial prefrontal cortex (MPFC) and left hippocampus. However, Non-PSCI patients showed more significantly increased FC in the MPFC and hippocampus than PSCI patients did. The FC in the PCC/PCu was related to the MoCA score measured at a 10-day follow-up, and the FC in the left hippocampus predicted the MoCA score measured at 3 months follow-up. CONCLUSIONS: Our findings may be helpful for facilitating further understanding of the potential mechanism underlying PSCI, and suggests that resting-state DMN connectivity could serve as neuroimaging biomarkers for future interventional studies.


Assuntos
Encéfalo/fisiopatologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/fisiopatologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Análise de Variância , Mapeamento Encefálico , Transtornos Cognitivos/etiologia , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Prognóstico , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Descanso , Processamento de Sinais Assistido por Computador , Acidente Vascular Cerebral/complicações
14.
Neuroscience ; 267: 102-13, 2014 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-24607345

RESUMO

Obesity and eating disorders are prevailing health concerns worldwide. It is important to understand the regulation of food intake and energy metabolism. Thiamine (vitamin B1) is an essential nutrient. Thiamine deficiency (TD) can cause a number of disorders in humans, such as Beriberi and Wernicke-Korsakoff syndrome. We demonstrated here that TD caused anorexia in C57BL/6 mice. After feeding a TD diet for 16days, the mice displayed a significant decrease in food intake and an increase in resting energy expenditure (REE), which resulted in a severe weight loss. At the 22nd day, the food intake was reduced by 69% and 74% for male and female mice, respectively in TD group. The REE increased by ninefolds in TD group. The loss of body weight (17-24%) was similar between male and female animals and mainly resulted from the reduction of fat mass (49% decrease). Re-supplementation of thiamine (benfotiamine) restored animal's appetite, leading to a total recovery of body weight. The hypothalamic adenosine monophosphate-activated protein kinase (AMPK) is a critical regulator of food intake. TD inhibited the phosphorylation of AMPK in the arcuate nucleus (ARN) and paraventricular nucleus (PVN) of the hypothalamus without affecting its expression. TD-induced inhibition of AMPK phosphorylation was reversed once thiamine was re-supplemented. In contrast, TD increased AMPK phosphorylation in the skeletal muscle and upregulated the uncoupling protein (UCP)-1 in brown adipose tissues which was consistent with increased basal energy expenditure. Re-administration of thiamine stabilized AMPK phosphorylation in the skeletal muscle as well as energy expenditure. Taken together, TD may induce anorexia by inhibiting hypothalamic AMPK activity. With a simultaneous increase in energy expenditure, TD caused an overall body weight loss. The results suggest that the status of thiamine levels in the body may affect food intake and body weight.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Anorexia/etiologia , Hipotálamo/enzimologia , Deficiência de Tiamina/complicações , Deficiência de Tiamina/patologia , Análise de Variância , Animais , Composição Corporal , Peso Corporal , Calorimetria , Dieta/efeitos adversos , Ingestão de Alimentos/fisiologia , Metabolismo Energético/fisiologia , Feminino , Regulação da Expressão Gênica/fisiologia , Canais Iônicos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/metabolismo , Neuropeptídeo Y/metabolismo , Proteína Desacopladora 1
15.
Neurol Res ; 36(3): 224-33, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24512016

RESUMO

The herbal extract 3-n-butylphthalide (NBP) is used in clinical practice for ischemic patients in China. It has been shown to have various neuroprotective effects both in vitro and in vivo. In the present study, the effects of NBP on learning and memory decline in the senescence-accelerated mouse prone-8 (SAMP8) animal model were investigated. Intragastric NBP administration to 4-month-old SAMP8 mice for 2 months significantly improved spatial learning and memory ability. Moreover, the loss of choline acetyltransferase (ChAT)-positive neurons in the medial septal nucleus and the vertical limb of the diagonal band in SAMP8 mice was slowed down, as was the decline in the protein and mRNA expression of ChAT in the hippocampus, cerebral cortex, and forebrain. These results demonstrated that NBP treatment starting at the age of 4 months protected from the learning/memory deficits with aging of SAMP8 mice, and that this effect might be mediated by preventing the decline of the central cholinergic system.


Assuntos
Envelhecimento/fisiologia , Benzofuranos/farmacologia , Cognição/efeitos dos fármacos , Animais , Córtex Cerebral/efeitos dos fármacos , Colina O-Acetiltransferase/metabolismo , Hipocampo/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Prosencéfalo/efeitos dos fármacos , Núcleos Septais/efeitos dos fármacos , Núcleos Septais/metabolismo
16.
Alcohol Clin Exp Res ; 38(3): 683-93, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24224909

RESUMO

BACKGROUND: Endoplasmic reticulum (ER) stress plays a key role in cell apoptosis pathways. Caspase-12, a proapoptotic gene induced by ER stress, is also the key molecule in ER-related apoptosis. The purpose of this study is to evaluate the protective activity and possible mechanism of resveratrol (ResV) against ethanol (EtOH)-induced apoptosis in human hepatocyte Chang cell line. METHODS: The human hepatocyte Chang cell line was used to test the hypothesis that ResV may alleviate the liver cell apoptosis induced by EtOH. ER stress-inducible proteins and silent mating type information regulation 2 homolog 1 (SIRT1) were assayed by Western blot. Cell viability was studied by MTT assay and apoptosis was measured by Annexin-V and propidium iodide assay. Caspase-12 activation was examined by immunofluorescence staining. Alcohol dehydrogenase-2 (ADH-2) and aldehyde dehydrogenase-2 (ALDH-2) were measured by polymerase chain reaction amplified product length polymorphism. Phosphodiesterase (PDE) activity was assayed in cell lysates using a cyclic nucleotide PDE assay. RESULTS: EtOH exposure significantly increased the expression of ER stress markers and activated signaling pathways associated with ER stress. These include GRP78, p-IRE1α, p-eIF2α, p-PERK, ATF4 as well as cleaved caspase-3/12, CHOP/GADD153, and Bax in human hepatocyte Chang cell line. The expression of these proteins were significantly down-regulated by ResV (10 µM) in a SIRT1-dependent manner. ResV can inhibit EtOH-, tunicamycin-, thapsigargin-induced caspase-12 activation. ADH-2 and ALDH-2 activities are lower in this cell line. PDE activity increased by EtOH was inhibited by ResV (10 µM). CONCLUSIONS: The results indicate that (i) EtOH-induced activation of caspase-12 could be one of the underlying mechanisms of hepatocyte apoptosis; (ii) EtOH-induced cell apoptosis was alleviated via ResV (10 µM) by inhibiting ER stress and caspase-12 activation in a SIRT1-dependent manner; and (iii) SIRT1 activated indirectly by ResV (10 µM) attenuates EtOH-induced hepatocyte apoptosis partly through inhibiting PDE activity.


Assuntos
Apoptose/efeitos dos fármacos , Caspase 12/metabolismo , Hepatócitos/efeitos dos fármacos , Diester Fosfórico Hidrolases/metabolismo , Estilbenos/farmacologia , Álcool Desidrogenase/genética , Aldeído Desidrogenase/genética , Aldeído-Desidrogenase Mitocondrial , Inibidores de Caspase/farmacologia , Linhagem Celular , Depressores do Sistema Nervoso Central/farmacologia , Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Etanol/farmacologia , Hepatócitos/enzimologia , Humanos , Inibidores de Fosfodiesterase/farmacologia , Resveratrol , Sirtuína 1/metabolismo
17.
SAR QSAR Environ Res ; 24(10): 795-817, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23941641

RESUMO

Cyclin-dependent kinase 2 (CDK2) has been identified as an important target for developing novel anticancer agents. Molecular docking, three-dimensional quantitative structure-activity relationship (3D-QSAR) and pharmacophore modelling were combined with the ultimate goal of studying the structure-activity relationship of CDK2 inhibitors. The comparative molecular similarity indices analysis (CoMSIA) model constructed based on a set of 3-aminopyrazole derivatives as CDK2 inhibitors gave statistically significant results (q (2) = 0.700; r (2) = 0.982). A HypoGen pharmacophore model, constructed using diverse CDK2 inhibitors, also showed significant statistics ([Formula: see text]Cost = 61.483; RMSD = 0.53; Correlation coefficient = 0.98). The small residues and error values between the estimated and experimental activities of the training and test set compounds proved their strong capability of activity prediction. The structural insights obtained from these two models were consistent with each other. The pharmacophore model summarized the important pharmacophoric features required for protein-ligand binding. The 3D contour maps in combination with the comprehensive pharmacophoric features helped to better interpret the structure-activity relationship. The results will be beneficial for the discovery and design of novel CDK2 inhibitors. The simplicity of this approach provides expansion to its applicability in optimizing other classes of small molecular CDK2 inhibitors.


Assuntos
Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Relação Quantitativa Estrutura-Atividade , Antineoplásicos/química , Antineoplásicos/farmacologia , Humanos , Simulação de Acoplamento Molecular , Pirazóis/química , Pirazóis/farmacologia
18.
Eur Rev Med Pharmacol Sci ; 17(11): 1447-54, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23771533

RESUMO

BACKGROUND: Vascularized bone-grafting pedicled on 1,2 intercompartmental supraretinacular artery (1,2 ICSRA) has been recommended as a treatment alternative for established scaphoid nonunion complicated with proximal pole avascular necrosis (AVN). Previous reports focused the studies on the union rate and the revascularization of the transferred graft. However, the postoperative wrist stiffness still a challenging problem and remaining to be solved. The purpose of our study was to determine whether the combination of vascularized bone-grafting pedicled on 1,2 ICSRA and wrist external fixator immobilization provides a more effective strategy for treating established scaphoid nonunion complicated with AVN and improving postoperative range of motion (ROM) of the injured wrist. PATIENTS AND METHODS: We retrospectively reviewed a consecutive series of 11 patients who had cases of established scaphoid nonunion involving AVN of the proximal pole were treated with vascularized bone-grafting pedicled on 1,2 1,2 ICSRA, internal fixation, and wrist external fixator immobilization. Procedure of wrist arthrolysis was performed before vascularized bone graft transferring. Preoperative and postoperative evaluation included measurement of clinical (wrist ROM and grip strength), radiographic (intrascaphoid angle, scapholunate angle) and functional (Mayo wrist score) parameters. RESULTS: Osseous union was achieved in all of the 11 cases within an average period of 11.4 weeks. On an average 6.1 years follow-up, there were three excellent, six good and two fair results. Significant improvements were found for Mayo wrist score, wrist ROM, and grip strength (p < 0.01). Intrascaphoid angle and scapholunate angle were significantly improved postoperatively, and there was no significant difference between the postoperative values and the values at the last follow-up. Early functional rehabilitation of the injured wrist under the protection of the fixator did not result in displacement of the transferred graft. CONCLUSIONS: The results of the present investigation support the use of the vascularized bone graft pedicled on 1,2 ICSRA in the treatment of scaphoid nonunion complicated with proximal pole AVN. Procedures of wrist arthrolysis and early institution of wrist functional rehabilitation under the protection of the external fixator play important role in the restoration of range of motion of the injured wrist.  


Assuntos
Transplante Ósseo , Fixadores Externos , Fraturas não Consolidadas/cirurgia , Osso Escafoide/lesões , Adulto , Feminino , Fraturas não Consolidadas/complicações , Humanos , Masculino , Amplitude de Movimento Articular , Estudos Retrospectivos , Osso Escafoide/cirurgia , Traumatismos do Punho/fisiopatologia , Traumatismos do Punho/cirurgia
19.
Genet Mol Res ; 10(1): 177-85, 2011 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-21341209

RESUMO

Osteogenesis imperfecta is normally caused by an autosomal dominant mutation in the type I collagen genes COL1A1 and COL1A2. The severity of osteogenesis imperfecta varies, ranging from perinatal lethality to a very mild phenotype. Although there have been many reports of COL1A1 and COL1A2 mutations, few cases have been reported in Chinese people. We report on five unrelated families and three sporadic cases. The mutations were detected by PCR and direct sequencing. Four mutations in COL1A1 and one in COL1A2 were found, among which three mutations were previously unreported. The mutation rates of G>C at base 128 in intron 31 of the COL1A1 gene and G>A at base 162 in intron 30 of the COL1A2 gene were higher than normal. The patients' clinical characteristics with the same mutation were variable even in the same family. We conclude that mutations in COL1A1 and COL1A2 also have an important role in osteogenesis imperfecta in the Chinese population. As the Han Chinese people account for a quarter of the world's population, these new data contribute to the type I collagen mutation map.


Assuntos
Colágeno Tipo I/genética , Osteogênese Imperfeita/etiologia , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Criança , Pré-Escolar , Colágeno/genética , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Mutação , Reação em Cadeia da Polimerase , Adulto Jovem
20.
Neoplasma ; 57(6): 522-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20845990

RESUMO

UNLABELLED: The study was aimed at detecting the expression of a newly found oncogene, astrocyte elevated gene-1 (AEG-1), in renal cell carcinoma (RCC) and its correlation with histopathologic features and the survival of patients. Real-time reverse transcription-PCR and Western blot showed markedly higher expression of AEG-1 in 8 cases of RCC tissue compared with the paired normal tissue from the same patient. The expression level of AEG-1 was also increased in four RCC cell lines in contrast with normal tubular epithelial human kidney cells 2 (HK-2) at both mRNA and protein levels. Furthermore, immunohistochemistry analysis showed highly expressed AEG-1 in 96 of 102 (94.1%) cases of paraffin-embedded archival RCC tissue. Statistical analysis showed a significant correlation of AEG-1 expression with tumor grade (P <0.001), clinical staging (P = 0.003), T classification (P = 0.003) as well as metastasis classification (P=0.032). The means for survival time of low AEG-1 expression group was 76.98m
while high AEG-1expression group was 60.94m. Our results suggest that AEG-1 protein is overexpressed in RCC and plays an important role in tumor differentiation and progression.
High AEG-1 expression is closely associated with poor prognosis. KEYWORDS: Astrocyte elevated gene-1, AEG-1, renal cell carcinoma, prognosis.


Assuntos
Carcinoma de Células Renais/química , Moléculas de Adesão Celular/análise , Núcleo Celular/patologia , Neoplasias Renais/química , Carcinoma de Células Renais/patologia , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/fisiologia , Linhagem Celular Tumoral , Progressão da Doença , Humanos , Imuno-Histoquímica , Neoplasias Renais/patologia , Estadiamento de Neoplasias
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