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This study aimed to investigate the treatment effects and molecular mechanism of 3-aminobenzamide (3-AB) on intracranial aneurysms (IA). The IA model was established in male Sprague-Dawley (SD) rats and sham group was set up without ligation. The rats were intraperitoneally injected with normal saline in sham and model control groups and 10 mg/kg, 20 mg/kg and 40 mg/kg 3-AB for low, middle and high 3-AB groups for 3 months, respectively. The rates in and blood pressures of caudal artery were measured and anterior cerebral artery and olfactory artery were stained with hematoxylin and eosin (HE) for morphology observation. Besides, the effects of 3-AB on inflammatory cells, macrophages, neutrophils and T cells, were evaluated using immunohistochemistry. Gene expressions of TNF-α, MMP-9, MMP-2, iNOS, TLR4, PARP-1 and p65 were measured using qRT-PCR and the protein levels of TLR4, PARP-1 and p-p65 were evaluated using western blotting. Blood pressures of rats in 3-AB treatment groups were decreased in a dose-dependent manner. The damage of cerebral artery wall was alleviated and the inflammatory cells (macrophages, neutrophils and T cells) were reduced to some extent in 3-AB high-dose groups. The gene expression of TNF-α, MMP-9, MMP-2, iNOS, TLR4, PARP-1 and p65, as well as the protein expression of TLR4, PARP-1 and p-p65 in 3-AB treatment groups were decreased in a dose-dependent manner (P < 0.01).3-AB exhibited therapeutic effects on IA through inhibiting the secretions of inflammatory cytokines and MMPs.
Assuntos
Benzamidas/farmacologia , Doenças Arteriais Cerebrais/tratamento farmacológico , Aneurisma Intracraniano/tratamento farmacológico , Animais , Antígenos CD/metabolismo , Pressão Arterial , Doenças Arteriais Cerebrais/metabolismo , Doenças Arteriais Cerebrais/patologia , Doenças Arteriais Cerebrais/prevenção & controle , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Aneurisma Intracraniano/metabolismo , Aneurisma Intracraniano/patologia , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , NF-kappa B/metabolismo , Proteínas de Neoplasias/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
While animal models of controlled cortical impact often display short-term motor dysfunction after injury, histological examinations do not show severe cortical damage. Thus, this model requires further improvement. Mice were subjected to injury at three severities using a Pin-Point™-controlled cortical impact device to establish secondary brain injury mouse models. Twenty-four hours after injury, hematoxylin-eosin staining, Fluoro-Jade B histofluorescence, and immunohistochemistry were performed for brain slices. Compared to the uninjured side, we observed differences of histopathological findings, neuronal degeneration, and glial cell number in the CA2 and CA3 regions of the hippocampus on the injured side. The Morris water maze task and beam-walking test verified long-term (14-28 days) spatial learning/memory and motor balance. To conclude, the histopathological responses were positively correlated with the degree of damage, as were the long-term behavioral manifestations after controlled cortical impact. All animal procedures were approved by the Institutional Animal Care and Use Committee at Shanghai Jiao Tong University School of Medicine.
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Gliomas are the most commonly occurring primary malignant brain tumors in the central nervous system of adults. They are rarely curable and the prognosis for high grade gliomas is generally poor. Recently, long non-coding RNA (lncRNA) human ovarian cancer-specific transcript 2 (HOST2) has been reported to be expressed at high levels in human ovarian cancer, involving tumorigenesis. However, little is still known about whether and how HOST2 regulates glioma development and progression. Therefore, this study aims to investigate the role of HOST2 in human glioma cells. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to determine the expression of lncRNA HOST2, let-7b, and PBX3 in human glioma cells. Cultured human glioma cells were treated with siRNA (si)-lncRNA HOST2, let-7b mimic, si-lncRNA HOST2 + let-7b inhibitor, and si-PBX3. Parameters including cell viability, colony formation, cell migration, and cell invasion were detected by cell counting kit-8 assay, colony formation assay, scratch test, and Transwell assay respectively to determine the effects of down-regulated HOST2 on glioma cells. Tumor formation in nude mice was evaluated by subcutaneous tumor formation experiment. Results showed that HOST2 and PBX3 were highly expressed in glioma tissue whereas let-7b was expressed at much lower levels. In response to treatment with si-lncRNA HOST2, si-PBX3, and let-7b mimic, glioma cell lines exhibited decreased cell viability, suppressed cell migration, invasion, and reduced colony formation of glioma cells. This was accompanied by an attenuated tumor formation with smaller volume and weight in nude mice, suggesting that down-regulated HOST2 could inhibit the tumorigenicity of glioma cells. Lastly, we found that lncRNA HOST2 was highly expressed in glioma tissues and its down-regulation could inhibit the growth and invasion of glioma cells. © 2018 IUBMB Life, 71(1):93-104, 2019.
Assuntos
Glioma/genética , Proteínas de Homeodomínio/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas/genética , RNA Longo não Codificante/genética , Adolescente , Adulto , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Criança , Feminino , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Xenoenxertos , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , RNA Interferente Pequeno/genética , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: With the development of enteral nutrition in patients with neurological disorders in China, related guidelines were published in 2011. The Chinese Society for Parenteral and Enteral Nutrition conducted a survey to evaluate the status quo of enteral nutrition practices in these patients. METHODS AND STUDY DESIGN: This multicenter prospective investigation was conducted from April 2012 to April 2013 and involved 18 tertiary hospitals in China. The survey using standardized questionnaires sought information about the basic protocols for enteral nutrition (devices and staffing) and specific information about patients with neurological conditions who received nutrition by way of enteral feeding. RESULTS: In the 18 hospitals from 13 provinces, 83.3% patients were configured with an enteral nutrition infusion pump, 77.8% had a percutaneous endoscopic gastrostomy (PEG) device, and 88.9% had a clinical nutrition support group. Four hundred four patients participated in this survey (259 men, 145 women; mean age 61.3±14.7 years), 85.7% had suffered a stroke, 83.9% had impaired consciousness, and 98.0% had dysphagia. Of the 10 guidelines for enteral nutrition practices, setting the energy target, choosing the enteral nutrition tube, and monitoring the patient received unsatisfactory ratings were in poor compliance (56.2%, 30.0% and 38.9%, respectively); the remaining seven guidelines were in good compliance (each >75%). CONCLUSION: The survey suggested that configuration of the enteral nutritional devices and staffing was adequate in China's tertiary hospitals. However, some associated practices had not yet reached the desired levels of competency, indicating a need for this to be understood and for improved training.
Assuntos
Nutrição Enteral/métodos , Pesquisas sobre Atenção à Saúde , Doenças do Sistema Nervoso/terapia , Centros de Atenção Terciária , Idoso , China , Ingestão de Energia , Nutrição Enteral/instrumentação , Feminino , Fidelidade a Diretrizes/estatística & dados numéricos , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Apoio Nutricional/métodos , Estudos ProspectivosRESUMO
A bidirectional total synthesis of chloptosin has been achieved in 16 operations (32 individual reactions) and 3% overall yield from the readily available materials. Palladium-catalyzed tryptophan synthesis, diastereoselective selenocyclization and oxidative deselenation successfully served as key steps in construction of the dimeric core amino acid. 2-Bromo-1-ethyl pyridinium tetrafluoroborate was efficiently employed in the peptide couplings with spatial encumbrance in this synthesis.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/farmacologia , Piridazinas/síntese química , Piridazinas/farmacologia , Animais , Antineoplásicos/química , Catálise , Linhagem Celular Tumoral , Humanos , Espectroscopia de Ressonância Magnética , Camundongos , Peptídeos Cíclicos/química , Piridazinas/químicaRESUMO
In the title compound, [Co(C(7)H(2)N(2)O(7))(C(10)H(8)N(2))(2)], the Co(II) atom is coordinated by four N atoms from two 2,2'-bipyridine ligands and two O atoms from a 3,5-dinitro-2-oxidobenzoate ligand, displaying a distorted octa-hedral coordination geometry. The crystal structure involves C-Hâ¯O hydrogen bonds between the 2,2'-bipyridine ligands and the carboxyl-ate and NO(2) groups of the 3,5-dinitro-2-oxidobenzoate ligand.
RESUMO
[reaction: see text] An efficient total synthesis of (2S,2'S,3aR,3'aR,8aR,8'aR)-6,6'-dichloro-3a,3'a-dihydroxy-1,1',2,2',3,3a,3',3'a,8,8a,8',8'a-dodecahydro-5,5'-bipyrrolo[2,3-b]indole-2,2'-dicarboxylic acid, the central amino acid component of chloptosin (1), is described. Starting from m-chloronitrobenzene, this C(2)-symmetrical amino acid was synthesized by using a 14-step route, in which a Zinin benzidine rearrangement, intramolecular Heck reaction, and selenocyclization and oxidative deselenation served as key steps. The absolute stereochemistry of the target was confirmed by X-ray single-crystal studies on a key intermediate (17).