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Convolutional Neural Networks (CNNs) have been widely applied in various edge computing devices based on intelligent sensors. However, due to the high computational demands of CNN tasks, the limited computing resources of edge intelligent terminal devices, and significant architectural differences among these devices, it is challenging for edge devices to independently execute inference tasks locally. Collaborative inference among edge terminal devices can effectively utilize idle computing and storage resources and optimize latency characteristics, thus significantly addressing the challenges posed by the computational intensity of CNNs. This paper targets efficient collaborative execution of CNN inference tasks among heterogeneous and resource-constrained edge terminal devices. We propose a pre-partitioning deployment method for CNNs based on critical operator layers, and optimize the system bottleneck latency during pipeline parallelism using data compression, queuing, and "micro-shifting" techniques. Experimental results demonstrate that our method achieves significant acceleration in CNN inference within heterogeneous environments, improving performance by 71.6% compared to existing popular frameworks.
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Benign fibrous histiocytoma (BFH) within the intracerebral region is remarkably rare. Our report details 2 cases of unusual BFH instances that exhibit no adhesion to the dura mater or cerebral falx, accompanied by a comprehensive literature review. While magnetic resonance imaging demonstrates specific characteristics for BFH, it does not readily differentiate BFH from more common brain neoplasms like gliomas and metastatic tumors. The definitive diagnosis of BFH depends primarily on histopathological and immunohistochemical examinations. Total surgical resection is considered an efficacious therapeutic approach, emphasizing the necessity for prolonged postoperative surveillance to detect any potential tumor recurrence or metastasis.
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Neoplasias Encefálicas , Histiocitoma Fibroso Benigno , Imageamento por Ressonância Magnética , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Histiocitoma Fibroso Benigno/patologia , Histiocitoma Fibroso Benigno/diagnóstico por imagem , Histiocitoma Fibroso Benigno/cirurgiaRESUMO
The technique of cloning has wide applications in animal husbandry and human biomedicine. However, the very low developmental efficiency of cloned embryos limits the application of cloning. Ectopic XIST-expression-induced abnormal X chromosome inactivation (XCI) is a primary cause of the low developmental competence of cloned mouse and pig embryos. Knockout or knockdown of XIST improves cloning efficiency in both pigs and mice. The transcription factor Yin yang 1(YY1) plays a critical role in XCI by triggering the transcription of X-inactive specific transcript (XIST) and facilitating the localization of XIST RNA on the X chromosome. This study aimed to investigate whether RNA interference to suppress the expression of YY1 can inhibit erroneous XIST expression, rescue abnormal XCI, and improve the developmental ability of cloned pig embryos. The results showed that YY1 binds to the 5' regulatory region of the porcine XIST gene in pig cells. The microinjection of YY1 siRNA into cloned pig embryos reduced the transcript abundance of XIST and upregulated the mRNA level of X-linked genes at the 4-cell and blastocyst stages. The siRNA-mediated knockdown of YY1 altered the transcriptome and enhanced the in vitro and in vivo developmental efficiency of cloned porcine embryos. These results suggested that YY1 participates in regulating XIST expression and XCI in cloned pig embryos and that the suppression of YY1 expression can increase the developmental rate of cloned pig embryos. The present study established a new method for improving the efficiency of pig cloning.
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Desenvolvimento Embrionário , RNA Longo não Codificante , Animais , Blastocisto/metabolismo , Clonagem de Organismos/métodos , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/metabolismo , Suínos , Inativação do Cromossomo X , Fator de Transcrição YY1/genética , Fator de Transcrição YY1/metabolismoRESUMO
The technique of pig cloning holds great promise for the livestock industry, life science, and biomedicine. However, the prenatal death rate of cloned pig embryos is extremely high, resulting in a very low cloning efficiency. This limits the development and application of pig cloning. In this study, we utilized embryo biopsy combined with microproteomics to identify potential factors causing the developmental arrest in cloned pig embryos. We verified the roles of two potential regulators, PDCD6 and PLK1, in cloned pig embryo development. We found that siRNA-mediated knockdown of PDCD6 reduced mRNA and protein expression levels of the pro-apoptotic gene, CASP3, in cloned pig embryos. PDCD6 knockdown also increased the cleavage rate and blastocyst rate of cloned porcine embryos. Overexpression of PLK1 via mRNA microinjection also improved the cleavage rate of cloned pig embryos. This study provided a new strategy to identify key factors responsible for the developmental defects in cloned pig embryos. It also helped establish new methods to improve pig cloning efficiency, specifically by correcting the expression pattern of PDCD6 and PLK1 in cloned pig embryos.
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Clonagem de Organismos , Técnicas de Transferência Nuclear , Gravidez , Feminino , Animais , Suínos , Clonagem de Organismos/métodos , Embrião de Mamíferos , Blastocisto/metabolismo , Desenvolvimento Embrionário/genética , Biópsia , RNA Mensageiro/metabolismoRESUMO
Ectopic expression of Xist on the putative active X chromosome is a primary cause of the low developmental efficiency of cloned mouse and pig embryos. Suppression of abnormal Xist expression via gene knockout or RNA interference (RNAi) can significantly enhance the developmental competence of cloned mouse and pig embryos. RLIM is a Xist expression activator, whereas REX1 is an Xist transcription inhibitor, as RLIM triggers Xist expression by mediating the proteasomal degradation of REX1 to induce imprinted and random X chromosome inactivation in mice. This study aimed to test whether the knockdown of RLIM and overexpression of REX1 can repress aberrant Xist expression and improve the developmental ability of cloned male pig embryos. Results showed that injection of anti-RLIM small interfering RNA significantly decreased Xist messenger RNA abundance, increased REX1 protein level, and enhanced the preimplantation development of cloned male porcine embryos. These positive effects were not observed in cloned male pig embryos injected with REX1 expression plasmid, which might be due to the low expression efficiency of injected REX1 plasmid and/or the short half-life of expressed REX1 protein. The findings from this study indicated that RLIM participated in the ectopic activation of Xist expression in cloned pig embryos by targeting REX1 degradation. Furthermore, this study provided a new method to improve cloned pig embryo development by the inhibition of Xist expression via RNAi of RLIM.
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Regulação da Expressão Gênica no Desenvolvimento , RNA Longo não Codificante/genética , Ubiquitina-Proteína Ligases/genética , Animais , Clonagem de Organismos , Técnicas de Silenciamento de Genes , Masculino , Técnicas de Transferência Nuclear , RNA Longo não Codificante/metabolismo , Suínos , Ubiquitina-Proteína Ligases/metabolismoRESUMO
The regulation of food intake is a promising way to combat obesity. It has been implicated that various fatty acids exert different effects on food intake and body weight. However, the underlying mechanism remains poorly understood. The aim of the present study was to investigate the effects of linoleic acid (LA) and stearic acid (SA) on agouti-related protein (AgRP) expression and secretion in immortalized mouse hypothalamic N38 cells and to explore the likely underlying mechanisms. Our results demonstrated that LA inhibited, while SA stimulated AgRP expression and secretion of N38 cells in a dose-dependent manner. In addition, LA suppressed the protein expression of toll-like receptor 4 (TLR4), phosphorylation levels of JNK and IKKα/ß, suggesting the inhibition of TLR4-dependent inflammation pathway. However, the above mentioned inhibitory effects of LA were eliminated by TLR4 agonist lipopolysaccharide (LPS). In contrast, SA promoted TLR4 protein expression and activated TLR4-dependent inflammation pathway, with elevated ratio of p-JNK/JNK. While TLR4 siRNA reversed the stimulatory effects of SA on AgRP expression and TLR4-dependent inflammation. Moreover, we found that TLR4 was also involved in LA-enhanced and SA-impaired leptin/insulin signal pathways in N38 cells. In conclusion, our findings indicated that LA elicited inhibitory while SA exerted stimulatory effects on AgRP expression and secretion via TLR4-dependent inflammation and leptin/insulin pathways in N38 cells. These data provided a better understanding of the mechanism underlying fatty acids-regulated food intake and suggested the potential role of long-chain unsaturated fatty acids such as LA in reducing food intake and treating obesity.
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Proteína Relacionada com Agouti , Ingestão de Alimentos/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Ácido Linoleico/farmacologia , Ácidos Esteáricos/farmacologia , Receptor 4 Toll-Like/metabolismo , Proteína Relacionada com Agouti/agonistas , Proteína Relacionada com Agouti/antagonistas & inibidores , Proteína Relacionada com Agouti/biossíntese , Animais , Hipotálamo/citologia , Hipotálamo/metabolismo , Quinase I-kappa B/metabolismo , Inflamação/metabolismo , Leptina/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Fosforilação , RNA Interferente Pequeno/genética , Transdução de Sinais , Receptor 4 Toll-Like/genéticaRESUMO
Glioma is the most common primary brain tumor, yet the high cost of diagnostic imaging has made early detection of asymptomatic glioma a formidable challenge. Thus, the development of a convenient, sensitive, and cost-effective diagnostic strategy, such as enzyme-linked immunosorbent assay (ELISA) based on glioma-specific and World Health Organization (WHO) grade-specific autoantibody serum markers, is necessary. To this end, a comparative proteomic analysis based on two-dimensional western blotting was carried out with the sera of glioma patients and normal controls. Of the 11 novel glioma-expressed autoantibodies, the autoantibody against glial fibrillary acidic protein (GFAP) showed the highest differential expression. To investigate the potential clinical utility of the GFAP autoantibody as an early diagnostic marker for glioma, an ELISA-based assay was developed and validated with sera from glioma patients with WHO grades II (n = 19), III (n = 17), and IV (n = 24). The GFAP autoantibody level directly correlated with WHO grade and tumor volume. Sera from patients of non-glioma brain tumors, as well as non-brain tumors, showed much lower levels of GFAP autoantibody than those of the glioma patients, indicating that elevated GFAP autoantibody is specific to glioma patients. Analysis of the receiver operating characteristics curve suggested that the new ELISA has good distinguishing power and sensitivity for diagnosing glioma patients. This is the first ELISA assay developed for an autoantibody of a glioma antigen and may prove valuable for the clinical detection of glioma.
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Autoanticorpos/sangue , Biomarcadores Tumorais/imunologia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/imunologia , Proteína Glial Fibrilar Ácida/imunologia , Glioma/diagnóstico , Glioma/imunologia , Autoanticorpos/imunologia , Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/sangue , Ensaio de Imunoadsorção Enzimática , Glioma/sangue , HumanosRESUMO
Y-box-binding protein 1 (YB-1) is a multifunctional RNA binding protein involved in virtually every step of RNA metabolism. However, the functions and mechanisms of YB-1 in one of the most aggressive cancers, glioblastoma, are not well understood. In this study, we found that YB-1 protein was markedly overexpressed in glioblastoma and acted as a critical activator of both mTORC1 and mTORC2 signaling. Mechanistically, YB-1 bound the 5'UTR of CCT4 mRNA to promote the translation of CCT4, a component of the CCT chaperone complex, that in turn activated the mTOR signaling pathway by promoting mLST8 folding. In addition, YB-1 autoregulated its own translation by binding to its 5'UTR, leading to sustained activation of mTOR signaling. In patients with glioblastoma, high protein expression of YB-1 correlated with increased expression of CCT4 and mLST8 and activated mTOR signaling. Importantly, the administration of RNA decoys specifically targeting YB-1 in a mouse xenograft model resulted in slower tumor growth and better survival. Taken together, these findings uncover a disrupted proteostasis pathway involving a YB-1/CCT4/mLST8/mTOR axis in promoting glioblastoma growth, suggesting that YB-1 is a potential therapeutic target for the treatment of glioblastoma.
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Glioblastoma , Proteína 1 de Ligação a Y-Box , Regiões 5' não Traduzidas , Animais , Linhagem Celular Tumoral , Chaperonina com TCP-1 , Glioblastoma/genética , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/genética , Proteína 1 de Ligação a Y-Box/genética , Proteína 1 de Ligação a Y-Box/metabolismo , Homólogo LST8 da Proteína Associada a mTOR/genética , Homólogo LST8 da Proteína Associada a mTOR/metabolismoRESUMO
OBJECTIVE: This study was performed to evaluate the diagnostic performance of ultrasound-magnetic resonance imaging (MRI) fusion combined with contrast-enhanced ultrasound and to explore its role in improving the total tumor resection rate. METHODS: Between January 2018 and December 2018, 16 patients in the observation group and 23 patients in the control group were enrolled in this study. The tumor depth and brain shift distance were analyzed, as well as the peak intensity and microvessel density of different grades of gliomas in the observation group. Finally, we compared the difference in total resection rate between the observation and control groups. RESULTS: Using ultrasound during operations, we found a significant negative correlation between brain shift distance and tumor depth, with correlation coefficient r=-0.868(P<0.05). In glioma, the peak intensity and microvessel density increased synchronously with glioma grade(r=0.806, P<0.05). The total resection rate of lesions was significantly higher in the observation group than in the control group (P<0.05). CONCLUSIONS: The application of ultrasound-MRI fusion combined with contrast-enhanced ultrasound can improve the total resection rate of lesions, thus playing an important role in clinical practice.
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Neoplasias Encefálicas/cirurgia , Glioma/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Neuronavegação , Procedimentos Neurocirúrgicos/métodos , Resultado do Tratamento , UltrassonografiaRESUMO
Anaplastic oligodendroglioma (AO) is an uncommon intracranial tumor and prognosis is poor. In this study, we assessed the factors affecting the prognosis of AO patients. Seventy AO patients were recruited from 2001 to 2006 in Shanghai Huashan Hospital of Fudan University; all were treated surgically. Kaplan-Meier survival analysis and Cox regression analysis were used to analyze the prognostic effects of 14 different factors, which were selected from clinical, radiological, pathological, and treatment variables. The results showed that chemotherapy, age, primary or secondary tumors, preoperative Karnofsky Performance Scale (KPS) scores, the presence of epilepsy at initial presentation, radiological contrast infusion, and neurological parameters all correlated with the prognosis of the patients. Furthermore, Cox multivariate analysis also showed that the age (P < 0.048), primary or secondary tumors (P < 0.010), and chemotherapy (P < 0.010) were significantly correlated with the prognosis of the patients. Age and chemotherapy correlated with the prognosis of AO. The patients younger than 50 years old and who received regular chemotherapy were likely to achieve a good outcome. Moreover, individualized treatment after molecular biological typing of AO may improve the prognosis of AO.
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Neoplasias Encefálicas/diagnóstico , Oligodendroglioma/diagnóstico , Adolescente , Adulto , Fatores Etários , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/terapia , Criança , Tratamento Farmacológico , Feminino , Humanos , Avaliação de Estado de Karnofsky , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Oligodendroglioma/mortalidade , Oligodendroglioma/terapia , Prognóstico , Radioterapia , Estudos Retrospectivos , Tomógrafos Computadorizados , Adulto JovemRESUMO
BACKGROUND: Intracranial angiomatous meningioma (AM) is a rare subtype of meningioma. Here, we investigated the clinical and pathological features of AMs. MATERIALS AND METHODS: We performed a retrospective study of 23 intracranial AMs verified by postoperative pathology at Huashan Hospital North between 2013 and 2018. Clinical data, radiological and pathological findings, and information on treatment and outcomes were collected and analyzed. Additionally, the literature on intracranial AMs was reviewed. RESULTS: The sample comprised 13 men and 10 women with AMs. The mean age was 54.2 years, and the mean duration of symptoms was 14.9 months. Headache and epilepsy were the most common symptoms. The most common AMs locations were the cerebral convexity and parasagittal/falx region. The rates of vascular signs, homogeneous enhancement, and peritumoral brain edema (PTBE) on magnetic resonance images were high. Histologically, besides typical meningioma cells, AMs had an abundant vascular component and low Ki-67 index. The extent of PTBE was related to microvessel density (MVD) of tumors, but not to the expression of MMP9 or VEGF. Simpson grade I resection was achieved in 15 cases, and grade II resection was achieved in 7 cases. Twenty-one cases were followed up, and they all had favorable outcomes without recurrence. CONCLUSION: AM is a type of meningioma with a rich blood supply and distinct clinical and pathological features. It showed a slight male predominance and was common at the cerebral convexity or parasagittal/falx region. Histologically, it showed benign biological characteristics despite frequent and severe PTBE, and the extent of PTBE was related to MVD of tumors. Simpson I resection is the best treatment, and the prognosis is usually good after total tumor removal, while gamma knife is recommended for small residual tumor.
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Gliomas are the most common and lethal tumor of the central nervous system (CNS). At present, standard treatment involves chemotherapy and radiotherapy after surgery, but the prognosis for most gliomas remains poor due to tumor heterogeneity and drug resistance. Microtubule-associated protein 2 (MAP2), a microtubule-stabilizing protein, plays a critical role in many cellular processes and may correlate with the proliferation, apoptosis, and drug sensitivity of tumor cells, especially their sensitivity to microtubule-targeting drugs (MTDs). In this study, we investigated the role of MAP2 in gliomas and its relationship to the chemosensitivity of vincristine (VCR), an MTD commonly used in glioma chemotherapy. We downregulated MAP2 expression in glioma cells using RNA interference, observed the resultant changes in the biological characteristics of the cells, and tested their drug sensitivity to VCR by MTT assay. The results show downregulation of MAP2 in glioma cells significantly inhibited cell viability and migration, induced apoptosis, and increased sensitivity to VCR in vitro. Our findings suggest that MAP2 may be a useful molecular marker in MTD chemotherapy and a potential therapeutic target in gliomas.
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Resistencia a Medicamentos Antineoplásicos/fisiologia , Glioma/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Vincristina/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Moduladores de Tubulina/farmacologiaRESUMO
Pig cloning technique is valuable in agriculture, biomedicine, and life sciences. However, the full-term developmental efficiency of cloned pig embryos is only about 1%, which limits pig cloning application. The quality of recipient oocytes greatly affects the developmental competence of cloned pig embryos. Thus, this study investigated the effects of a recipient oocyte source (in vivo matured [IVVM] oocytes vs. slaughter house-derived in vitro matured [IVTM] oocytes), and follicular liquid treatment (slaughter house-derived immature follicle-derived fluid [IFF] vs. in vivo-matured follicle-derived fluid [MFF]) during the in vitro maturation (IVM) of oocytes on the development of the cloned pig embryos. Our results showed that using IVVM oocytes to replace IVTM oocytes as recipient oocytes, and using 10% MFF IVM medium to replace 10% IFF IVM medium could enhance the development of the cloned pig embryos. IFF and MFF contained different levels of oocyte quality-related proteins, resulting in different oocyte quality-related gene expression levels and reactive oxygen species levels between the 10% MFF medium-cultured oocytes and 10% IFF medium-cultured oocytes. This study provided useful information for enhancing the pig cloning efficiency by improving the quality of recipient oocytes.
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Líquido Folicular , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Técnicas de Maturação in Vitro de Oócitos/métodos , Oócitos/efeitos dos fármacos , Oócitos/fisiologia , Animais , Blastocisto/efeitos dos fármacos , Blastocisto/fisiologia , Clonagem de Organismos , Técnicas de Cultura Embrionária , Embrião de Mamíferos/efeitos dos fármacos , Embrião de Mamíferos/fisiologia , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Fertilização in vitro/métodos , Técnicas de Transferência Nuclear , Reação em Cadeia da Polimerase em Tempo Real , SuínosRESUMO
The TBestDB database contains approximately 370,000 clustered expressed sequence tag (EST) sequences from 49 organisms, covering a taxonomically broad range of poorly studied, mainly unicellular eukaryotes, and includes experimental information, consensus sequences, gene annotations and metabolic pathway predictions. Most of these ESTs have been generated by the Protist EST Program, a collaboration among six Canadian research groups. EST sequences are read from trace files up to a minimum quality cut-off, vector and linker sequence is masked, and the ESTs are clustered using phrap. The resulting consensus sequences are automatically annotated by using the AutoFACT program. The datasets are automatically checked for clustering errors due to chimerism and potential cross-contamination between organisms, and suspect data are flagged in or removed from the database. Access to data deposited in TBestDB by individual users can be restricted to those users for a limited period. With this first report on TBestDB, we open the database to the research community for free processing, annotation, interspecies comparisons and GenBank submission of EST data generated in individual laboratories. For instructions on submission to TBestDB, contact tbestdb@bch.umontreal.ca. The database can be queried at http://tbestdb.bcm.umontreal.ca/.
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Bases de Dados de Ácidos Nucleicos , Etiquetas de Sequências Expressas/química , Animais , Sequência de Bases , Análise por Conglomerados , Sequência Consenso , Eucariotos/genética , Fungos/genética , Genômica , Internet , Interface Usuário-ComputadorRESUMO
The organelle genome database GOBASE is now in its twelfth release, and includes 350,000 mitochondrial sequences and 118,000 chloroplast sequences, roughly a 3-fold expansion since previously documented. GOBASE also includes a fully reannotated genome sequence of Rickettsia prowazekii, one of the closest bacterial relatives of mitochondria, and will shortly expand to contain more data from bacteria from which organelles originated. All these sequences are now accessible through a single unified interface. Enhancements to the functionality of GOBASE include addition of pages for RNA structures and a page compiling data about the taxonomic distribution of organelle-encoded genes; incorporation of Gene Ontology terms; addition of features deduced from incomplete annotations to sequences in GenBank; marking of type examples in cases where single genes in single species are oversampled within GenBank; and addition of graphics illustrating gene structure and the position of neighbouring genes on a sequence. The database has been reimplemented in PostgreSQL to facilitate development and maintenance, and structural modifications have been made to speed up queries, particularly those related to taxonomy. The GOBASE database can be queried at http://gobase.bcm.umontreal.ca/ and inquiries should be directed to gobase@bch.umontreal.ca.
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Cloroplastos/genética , Bases de Dados Genéticas , Genoma Bacteriano , Mitocôndrias/genética , Evolução Molecular , Genômica , Internet , Rickettsia prowazekii/genética , Interface Usuário-ComputadorRESUMO
BACKGROUND: Schwannomas have been reported in several unusual intracranial locations. Here we report 2 cases of extremely rare schwannomas originating in the fourth ventricle, without attachment to the surrounding structures. The clinical course, radiologic and pathological features, treatment, and follow-up are described. CASE DESCRIPTION: Case 1 was a 49-year-old man who presented with symptoms of paroxysmal dizziness and vomiting. Magnetic resonance imaging (MRI) showed a mixed solid-cystic mass occupying the inferior half of the fourth ventricle. Complete excision of the tumor was performed via midline suboccipital craniectomy. The histological diagnosis was intraventricular schwannoma. Case 2 was an 18-year-old man with chronic vertigo and progressive gait unsteadiness. MRI revealed a heterogeneously enhancing lesion completely filling the fourth ventricle. An Ommaya tube was placed in the ventricle to relieve symptoms of hydrocephalus, followed by tumor resection performed via a suboccipital craniotomy. Histopathological examination confirmed the diagnosis of schwannoma. CONCLUSIONS: Fourth ventricular schwannomas are rare but should be considered in the differential diagnosis of contrast-enhancing intraventricular tumors in both children and adults. Although their etiopathological origin may differ from that of extra-axial schwannomas, their imaging, histology, and clinical course appear to be identical, and these tumors should be managed similarly.
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Neoplasias do Ventrículo Cerebral/diagnóstico , Neoplasias do Ventrículo Cerebral/cirurgia , Neurilemoma/diagnóstico , Neurilemoma/cirurgia , Adolescente , Neoplasias do Ventrículo Cerebral/patologia , Diagnóstico Diferencial , Quarto Ventrículo/diagnóstico por imagem , Quarto Ventrículo/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Neurilemoma/patologiaRESUMO
OBJECTIVE: To analyze the correlation between the prognosis of medulloblastoma (MB) and relevant clinical factors. METHODS: Seventy-three MB patients, 48 males and 25 females, aged 13.6 (2 approximately 40), underwent surgical treatment and part of them underwent radiotherapy and/or chemotherapy. Follow-up was conducted among 55 cases for 40.0 months (2 months approximately 8 years and 5 months). The correlation between the prognosis and the clinical factors, such and sex, age, tumor location, extent of tumor resection, brainstem invasion, radiotherapy, chemotherapy, ventriculoperitoneal shunt and glial differentiation was analyzed. RESULTS: Six patients died postoperatively, and average survival time of the other 49 patients was 61 months. Twenty patients had a survival time of 3 years after operation, and the 3-year survival rate was 63.98%; and 8 patients survived for 5 years after operation with a 5-year survival rate of 43%. The prognosis Analysis showed that only radiotherapy was the only influencing factor of survival time. Those undergoing whole brain/posterior fossa plus spinal axis radiotherapy showed a better prognosis than those undergoing whole brain/posterior fossa radiotherapy. CONCLUSION: The prognosis of MB is not good; yet, surgical resection with regular radiotherapy and chemotherapy is helpful for the prognosis of MB.
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Neoplasias do Sistema Nervoso Central/terapia , Meduloblastoma/terapia , Adolescente , Adulto , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/patologia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Meduloblastoma/mortalidade , Meduloblastoma/patologia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
N-Acyl amino acids (NAAAs) are conjugate products of fatty acids and amino acids, which are available in animal-derived food. We compared the effects of N-arachidonoylglycine (NAGly), N-arachidonoylserine (NASer), and N-oleoylglycine (OLGly) on in vivo food intake and in vitro [Ca2+]i of Agouti-related protein (AgRP) neurons to identify the role of these compounds in energy homeostasis. Hypothalamic neuropeptide expression and anxiety behavior in response to OLGly were also tested. To further identify the underlying mechanism of OLGly on food intake, we first detected the expression level of potential OLGly receptors. The cannabinoid receptor type 1 (CB1R) antagonist was cotreated with OLGly to analyze the activation of AgRP neuron, including [Ca2+]i, expression levels of PKA, CREB, and c-Fos, and neuropeptide secretion. Results demonstrated that only OLGly (intrapertioneal injection of 6 mg/kg) can induce hyperphagia without changing the expression of hypothalamic neuropeptides and anxiety-like behavior. Moreover, 20 µM OLGly robustly enhances [Ca2+]i, c-Fos protein expression in AgRP neuron, and AgRP content in the culture medium. OLGly-induced activation of AgRP neuron was completely abolished by the CB1R-specific antagonist, AM251. In summary, this study is the first to demonstrate the association of OLGly-induced hyperphagia with activation of the AgRP neuron by CB1R. These findings open avenues for investigation and application of OLGly to modulate energy homeostasis.
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Proteína Relacionada com Agouti/metabolismo , Glicina/análogos & derivados , Hiperfagia/metabolismo , Neurônios/metabolismo , Ácidos Oleicos/efeitos adversos , Receptor CB1 de Canabinoide/metabolismo , Proteína Relacionada com Agouti/genética , Animais , Glicina/efeitos adversos , Glicina/metabolismo , Humanos , Hiperfagia/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ácidos Oleicos/metabolismo , Receptor CB1 de Canabinoide/genéticaRESUMO
Laminarin, a type of ß-glucan isolated from brown seaweeds, exhibits verity of physiological activities, which include immunology modulation and antitumor function. To investigate the effect of laminarin on energy homeostasis, mice were orally administrated with laminarin to test food intake, fat deposition, and glucose homeostasis. Chronically, laminarin treatment significantly decreases high-fat-diet-induced body weight gain and fat deposition and reduces blood glucose level and glucose tolerance. Acutely, laminarin enhances serum glucagon-like peptide-1 (GLP-1) content and the mRNA expression level of proglucagon and prohormone convertase 1 in ileum. Subsequently, laminarin suppresses the food intake of mice, the hypothalamic AgRP neuron activity, and AgRP expression but activates pancreatic function. Furthermore, laminarin-induced appetite reduction was totally blocked by Exendin (9-39), a specific competitive inhibitor of GLP-1 receptor. Then, STC-1 cells were adopted to address the underlying mechanism, by which laminarin promoted GLP-1 secretion in vitro. Results showed that laminarin dose-dependently promoted GLP-1 secretion and c-Fos protein expression in STC-1 cells, which were independent of Dectin-1 and CD18. Interestingly, BAPTA-AM, a calcium-chelating agent, potently attenuated laminarin-induced [Ca2+]i elevation, c-Fos expression, and GLP-1 secretion. In summary, our data support that laminarin counteracts diet-induced obesity and stimulates GLP-1 secretion via [Ca2+]i; this finding provides an experimental basis for laminarin application to treat obesity and maintain glucose homeostasis.
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Although the widely used anticoagulant drug heparin has been shown to have many other biological functions independent of its anticoagulant role, its effects on energy homeostasis are unknown. Here, we demonstrate that heparin level is negatively associated with nutritional states and that heparin treatment increases food intake and body weight gain. By using electrophysiological, pharmacological, molecular biological, and chemogenetic approaches, we provide evidence that heparin increases food intake by stimulating AgRP neurons and increasing AgRP release. Our results support a model whereby heparin competes with insulin for insulin receptor binding on AgRP neurons, and by doing so it inhibits FoxO1 activity to promote AgRP release and feeding. Heparin may be a potential drug target for food intake regulation and body weight control.