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Two new monoterpenoid indole alkaloids 3-hydroxylochnerine (1) and 10-hydroxyvinorine (2) were isolated from the roots of Rauvolfia yunnanensis. Their structures were elucidated based on the analysis of spectroscopic data and ECD calculation. Both compounds exhibited potent antimicrobial activity against Bacillus subtilis and Escherichia coli, and their activities were comparable to the well-known antibacterial drug berberine.
Assuntos
Anti-Infecciosos , Rauwolfia , Alcaloides de Triptamina e Secologanina , Alcaloides de Triptamina e Secologanina/química , Rauwolfia/química , Estrutura Molecular , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Alcaloides IndólicosRESUMO
BACKGROUND: Sodium butyrate (NaB) is produced through the fermentation of dietary fiber that is not absorbed and digested by the small intestine. PURPOSE: Here, we aimed to investigate the effects of NaB on the proliferation, invasion, and metastasis of CRC cells and their potential underlying molecular mechanism(s). METHODS: The cell counting kit-8 (CCK-8) assay and EdU assay were used to detect cell proliferation ability, flow cytometry was used to investigate the induction of apoptosis and cell cycle progression, and the scratch-wound healing and transwell assays were used to evaluate cell migration and invasion, respectively. The human CRC genome information for tissues and CRC cells treated with NaB obtained from the NCBI GEO database was reannotated and used for differential RNA analysis. Functional and pathway enrichment analyses were performed for differentially expressed lncRNAs and mRNAs. A protein-protein interaction (PPI) network for the hub genes was constructed using the Cytoscape software. Targeted miRNAs were predicted based on the lnCeDB database, and a ceRNA network was constructed using the Cytoscape software. The Kaplan-Meier method was used to analyze patient prognosis using the clinical information and exon-seq data for CRC obtained from the Broad Institute's GDAC Firehose platform. RESULTS: NaB decreased the proliferation ability of CRC cells in a dose- and time-dependent manner. The number of apoptotic CRC cells increased with the increase in NaB concentrations, and NaB induced a G1 phase block in CRC cells. Moreover, NaB suppressed the migratory and invasive capabilities of CRC cells. There were 666 differentially expressed mRNAs and 30 differentially expressed lncRNAs involved in the CRC inhibition by NaB. The PPI network and ceRNA network were constructed based on the differentially expressed mRNAs and lncRNAs. Three differentially expressed mRNAs, including HMGA2, LOXL2, and ST7, were significantly correlated with the prognosis of CRC. CONCLUSION: NaB induces the apoptosis and inhibition of CRC cell proliferation, invasion, and metastasis by modulating complex molecular networks. RNA prediction and molecular network construction need to be the focus of further research in this direction.
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Ácido Butírico/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/genética , Mapas de Interação de Proteínas , Apoptose , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Bases de Dados Genéticas , Relação Dose-Resposta a Droga , Fase G1/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , MicroRNAs/metabolismo , Invasividade Neoplásica , Prognóstico , RNA Longo não Codificante/metabolismoRESUMO
This study aims to explore the effects of the phosphatase and tension homolog (PTEN) expression level on autophagic status and on the resistance of breast cancer to trastuzumab treatment. PTEN and LC3I/II were knocked down with shRNA expression vectors, which were transfected into estrogen receptor (ER)-positive breast cancer cell lines. After trastuzumab treatment, the changes in the autophagy signal transduction pathways and autophagic proteins (LC3I/II, p62, LAMP, and cathepsin B) in these stably transfected cells were detected using western blot. The cells were also orthotopically implanted into nude mice to explore the influence of PTEN knockdown on tumor size, cell viability, and autophagic proteins after trastuzumab treatment. Similar determinations were performed using the LC3I/II overexpressed shPTEN breast cancer cells (LC3I/II-shPTEN). Downregulation of PTEN and autophagic proteins LC3-I and LC3-II was observed in resistant human breast cancer samples. Knockdown of PTEN and PTEN+ LC3I/II with shRNA in breast cancer cells resulted in increased resistance to trastuzumab. Consistently, trastuzumab treatment could not effectively reduce tumor size. Significant decreases in the levels of autophagic proteins LC3I/II, LAMP, p62, cathepsin B, and PI3K-Akt-mTOR and the signaling pathway protein Akt were found in PTEN knockdown cells, compared to the PTEN normal group, after trastuzumab administration, both in vitro and in vivo. However, these findings were reversed with the LC3I/II-shPTEN treatment. Therefore, the loss of PTEN may promote the development of primary resistance to trastuzumab in breast cancer via autophagy defects.
Assuntos
Autofagia/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Proteínas Associadas aos Microtúbulos/biossíntese , PTEN Fosfo-Hidrolase/genética , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Proteínas Associadas aos Microtúbulos/genética , Proteínas de Ligação a RNA/biossíntese , Receptor ErbB-2/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/biossíntese , Trastuzumab/administração & dosagem , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Laparoscopic total mesorectal excision (LaTME) and transanal total mesorectal excision (TaTME) are popular mid and low rectal cancer trends. However, there is currently no systematic comparison between LaTME and TaTME of mid and low rectal cancer. Therefore, we systematically study the perioperative and pathological outcomes of LaTME and TaTME in mid and low rectal cancer. METHODS: Articles included searching through the Embase, Cochrane Library, PubMed, Medline, and Web of science for articles on LaTME and TaTME. We calculated pooled standard mean difference (SMD), relative risk (RR), and 95% confidence intervals (CIs). The protocol for this review has been registered on PROSPERO (CRD42022380067). RESULTS: There are 8761 participants included in 33 articles. Compared with TaTME, patients who underwent LaTME had no statistical difference in operation time (OP), estimated blood loss (EBL), postoperative hospital stay, over complications, intraoperative complications, postoperative complications, anastomotic stenosis, wound infection, circumferential resection margin, distal resection margin, major low anterior resection syndrom, lymph node yield, loop ileostomy, and diverting ileostomy. There are similarities between LaTME and TaTME for 2-year DFS rate, 2-year OS rate, distant metastasis rat, and local recurrence rate. However, patients who underwent LaTME had less anastomotic leak rates (RR 0.82; 95% CI: 0.70-0.97; I2â =â 10.6%, Pâ =â .019) but TaTME had less end colostomy (RR 1.96; 95% CI: 1.19-3.23; I2â =â 0%, Pâ =â .008). CONCLUSION: This study comprehensively and systematically evaluated the differences in safety and effectiveness between LaTME and TaTME in the treatment of mid and low rectal cancer through meta-analysis. Patients who underwent LaTME had less anastomotic leak rate but TaTME had less end colostomy. There is no difference in other aspects. Of course, in the future, more scientific and rigorous conclusions need to be drawn from multi-center RCT research.
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Laparoscopia , Neoplasias Retais , Cirurgia Endoscópica Transanal , Humanos , Animais , Ratos , Reto/cirurgia , Reto/patologia , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Fístula Anastomótica/cirurgia , Margens de Excisão , Cirurgia Endoscópica Transanal/efeitos adversos , Cirurgia Endoscópica Transanal/métodos , Neoplasias Retais/patologia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Complicações Pós-Operatórias/etiologia , Resultado do TratamentoRESUMO
In this article, we explored systematically the spore morphology of Pteridaceae by observation of the species distributed in Shandong Province using scanning electron microscopy (SEM). The results showed that the spore morphology of all the species in the family is tetrahedral and trilete. The characters of spore ornamentation are intraspecies stable, but significantly different among species and genera. Spore morphology is significant in exploring the phylogenetic relationships of Pteridaceae as well as in generic and specific delimitations.
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Pteridaceae , China , Microscopia Eletrônica de Varredura , Filogenia , EsporosRESUMO
Background: Millions of people suffer from Alzheimer's disease (AD) and Parkinson's disease (PD) worldwide. Due to their complex pathology, no effective pharmacological treatment has been found to date, despite extensive research. Developing new, effective therapeutic agents to cure these disease remains a major challenge. Although the cause of AD and PD remains illusive, numerous studies indicates that oxidative stress and neuro-inflammation lead to neurodegeneration in the central nervous system and play vital role in AD and PD morbidity and progression. Flavonoids, which are found widely in nature, exhibit anti-oxidative, anti-inflammatory, anti-mutative, anti-microbial, and neuroprotective properties, so have potential to treat these two kinds of diseases. Methods: In this review, we focus on the anti-oxidative and neuroprotective action of flavonoids in attenuating Alzheimer's and Parkinson's disease, and how they might be harnessed in the development of new pharmacological agents to treat these two diseases. Result: Some flavonoid compounds, like hesperidin, naringin, naringenin, tangeretin, nobiletin, silibinin, Epigallocatechin-3-gallate, displayed to be effective in both AD and PD. Conclusion: Considerable studies have demonstrated the anti-AD and anti-PD effects of flavonoids through various in vitro and in vivo models. However, more rigorous studies are needed to be done for flavonoids to develop into effective drugs and apply them to clinical practice.
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BACKGROUND: Uncontrolled seizures in patients with gliomas have a significant impact on quality of life and morbidity, yet the mechanisms through which these tumors cause seizures remain unknown. Here, we hypothesize that the active metabolite d-2-hydroxyglutarate (d-2-HG) produced by the IDH-mutant enzyme leads to metabolic disruptions in surrounding cortical neurons that consequently promote seizures. METHODS: We use a complementary study of in vitro neuron-glial cultures and electrographically sorted human cortical tissue from patients with IDH-mutant gliomas to test this hypothesis. We utilize micro-electrode arrays for in vitro electrophysiological studies in combination with pharmacological manipulations and biochemical studies to better elucidate the impact of d-2-HG on cortical metabolism and neuronal spiking activity. RESULTS: We demonstrate that d-2-HG leads to increased neuronal spiking activity and promotes a distinct metabolic profile in surrounding neurons, evidenced by distinct metabolomic shifts and increased LDHA expression, as well as upregulation of mTOR signaling. The increases in neuronal activity are induced by mTOR activation and reversed with mTOR inhibition. CONCLUSION: Together, our data suggest that metabolic disruptions in the surrounding cortex due to d-2-HG may be a driving event for epileptogenesis in patients with IDH-mutant gliomas.
Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/patologia , Glioma/patologia , Glutaratos , Humanos , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Mutação , Qualidade de Vida , Convulsões , Serina-Treonina Quinases TORRESUMO
We observed nuclear swelling in glutamate (Glu)-treated astrocytes that was concomitant with but independent of astrocytic cell swelling. We confirmed Glu-induced nuclear swelling with nuclei isolated from astrocytes. Ammonia is metabolically related to Glu and could induce a nuclear swelling in intact astrocytes but shrinkage in isolated nuclei. Other compounds such as glutamine, aspartate, taurine, glycine, and ATP did not cause any nuclear swelling in isolated nuclei of astrocytes. Surprisingly, Glu and ammonia did not induce nuclear swelling in microglia, C6, HEK 293, or Hep G2 cell lines in cultures and their isolated nuclei. The Glu- and ammonia-induced nuclear size changes appear to be a specific response of astrocytes to these two closely related metabolic compounds.
Assuntos
Amônia/farmacologia , Astrócitos/ultraestrutura , Núcleo Celular/ultraestrutura , Ácido Glutâmico/farmacologia , Amônia/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Células Cultivadas , Ácido Glutâmico/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Microscopia de Força AtômicaRESUMO
OBJECTIVE: To explore the sensitivity and specificity of Golgi protein 73 (GP73) monoclonal antibody in the diagnosis of hepatocellular carcinoma (HCC). METHODS: Self-prepared GP73 monoclonal antibody was used as the primary antibody for detecting the serum GP73 levels in healthy controls(n=31)and HCC patients (n=59). The baseline level of the healthy controls was determined by semiquantitative analysis. The results were compared with those from GP73 polyclonal antibody and alpha-fetoprotein (AFP). RESULTS: The GP73 level of healthy controls was 1.2 (0.9-1.7) relative unit (RU), which was significantly lower than that of HCC patients [5.7 (2.5-7.8) RU] (P<0.001) with monoclonal antibody. Using polyclonal antibody, the GP73 level of HCC patients was also significantly higher than healthy controls [7.8 (3.0-12.4) RU vs. 1.1 (1.0-2.0) RU, P<0.001]. The sensitivity and specificity of GP73 monoclonal antibody in diagnosis of HCC were 84.7% and 93.5%; on the contrary, those of GP73 polyclonal antibody were 78.0% and 93.5%, respectively. The sensitivity and specificity of AFP (67.8% and 74.2%, respectively) in the HCC patients were markedly lower than those of GP73. Logistic regression analysis showed that the odds ratio (OR) of GP73 monoclonal antibody was 7.18 and that of GP73 polyclonal antibody was 1.51. CONCLUSIONS: Our self-prepared monoclonal antibody can effectively detect GP73 serum level in HCC patients, and has higher sensitivity and specificity than AFP. It may be superior to the currently used GP73 polyclonal antibody. The results lay the foundation for the further development of ELISA methods by using this monoclonal antibody.
Assuntos
Anticorpos Monoclonais , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Proteínas de Membrana/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/sangue , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Hepáticas/sangue , Masculino , Proteínas de Membrana/imunologia , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND: The incidence of nasopharyngeal carcinoma is increasing gradually, but the pathogenesis is not completely clear. MicroRNA, a highly conserved endogenous noncoding small molecule RNA, plays an essential role in the regulation of gene expression and is a hotspot in cancer research worldwide. OBJECTIVES: Although previous studies have confirmed that the abnormal expression of microRNAs is closely related to the progression of nasopharyngeal carcinoma, the role of miRNA-331-3p in nasopharyngeal carcinoma has not been studied. The purpose of this study was to explore the role and mechanism of miRNA-331-3p in the progression of nasopharyngeal carcinoma. MATERIALS AND METHODS: Real-time quantitative reverse transcription polymerase chain reaction was performed to detect the expression of miRNA-331-3p in nasopharyngeal carcinoma clinical samples and cell lines (CNE-1 and 5-8F cells). After overexpression of miRNA-331-3p in CNE-1 cells, cell proliferation was measured by Cell Counting Kit-8 assay, cell invasion was detected by Transwell assay, and apoptosis was tested by flow cytometry. In addition, the dual-luciferase reporter assay was used to identify the target gene of miRNA-331-3p and Western blotting was performed to measure the relative protein expression. RESULTS: The expression of miRNA-331-3p in nasopharyngeal carcinoma clinical samples and cells was decreased significantly. Overexpression of miRNA-331-3p markedly inhibited the proliferation and invasion of CNE-1 cells and promoted cell apoptosis. Moreover, overexpression of miRNA-331-3p reduced the expression of target gene elF4B, leading to inhibition of the phosphorylation of Phosphoinositide 3-kinase (PI3K) and Serine/ threonine kinase (AKT). CONCLUSION: miRNA-331-3p inhibited cell proliferation and induced cell apoptosis in nasopharyngeal carcinoma by targeting elF4B gene and then blocked the PI3K-AKT signaling pathway. SIGNIFICANCE: The role of miRNA-331-3p in the development of NPC and its mechanism provide new ideas for the treatment of nasopharyngeal carcinoma.
Assuntos
Apoptose , Proliferação de Células , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Fatores de Iniciação em Eucariotos/antagonistas & inibidores , MicroRNAs/genética , Carcinoma Nasofaríngeo/patologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Linhagem Celular Tumoral , Movimento Celular , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Fatores de Iniciação em Eucariotos/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: Targeting glutamine metabolism in cancer has become an increasingly vibrant area of research. Mutant IDH1 (IDH1 mut ) gliomas are considered good candidates for targeting this pathway because of the contribution of glutamine to their newly acquired function: synthesis of 2-hydroxyglutarate (2HG). METHODS: We have employed a combination of 13C tracers including glutamine and glucose for investigating the metabolism of patient-derived IDH1 mut glioma cell lines through NMR and LC/MS. Additionally, genetic loss-of-function (in vitro and in vivo) approaches were performed to unravel the adaptability of these cell lines to the inhibition of glutaminase activity. RESULTS: We report the adaptability of IDH1 mut cells' metabolism to the inhibition of glutamine/glutamate pathway. The glutaminase inhibitor CB839 generated a decrease in the production of the downstream metabolites of glutamate, including those involved in the TCA cycle and 2HG. However, this effect on metabolism was not extended to viability; rather, our patient-derived IDH1 mut cell lines display a metabolic plasticity that allows them to overcome glutaminase inhibition. CONCLUSIONS: Major metabolic adaptations involved pathways that can generate glutamate by using alternative substrates from glutamine, such as alanine or aspartate. Indeed, asparagine synthetase was upregulated both in vivo and in vitro revealing a new potential therapeutic target for a combinatory approach with CB839 against IDH1 mut gliomas.
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Ischemia occurs in the brain as the result of stroke and other related injuries and few therapies are effective. If more is understood then potential treatments could be investigated. It was previously reported that 14-3-3gamma could be up-regulated by ischemia in astrocyte to protect cells from ischemia-induced apoptosis. In this study, we attempted to uncover the mechanism responsible for this 14-3-3gamma up-regulation in primary culture of astrocytes under ischemic-like conditions. It was found that in vitro ischemia may activate PI3K/Akt and MAPK signaling pathways. Astrocyte cultures were treated with LY294002 (PI3K inhibitor), U0126 (ERK inhibitor), SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor). Only SP600125 could inhibit the ischemia-induced 14-3-3gamma up-regulation in astrocytes. At the same time, we observed an ischemia-induced nuclear translocation of p-c-Jun, a major downstream component of JNK. Inhibition of AP-1 with curcumin also inhibited 14-3-3gamma up-regulation indicating that ischemia-induced up-regulation of 14-3-3gamma in astrocyte involves activation of the JNK/p-c-Jun/AP-1 pathway.
Assuntos
Proteínas 14-3-3/biossíntese , Astrócitos/metabolismo , Isquemia Encefálica/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Transdução de Sinais/fisiologia , Fator de Transcrição AP-1/metabolismo , Astrócitos/enzimologia , Câmaras de Exposição Atmosférica , Isquemia Encefálica/enzimologia , Células Cultivadas , Inibidores Enzimáticos/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/fisiologia , Proteínas Proto-Oncogênicas c-jun/antagonistas & inibidores , RNA/biossíntese , RNA/isolamento & purificação , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição AP-1/antagonistas & inibidores , Regulação para CimaRESUMO
Hematite, a type of inorganic-sorptive medium, was used for the removal of U (VI) from aqueous solutions. Variables of the batch experiments including solution pH, contact time, initial concentration, temperature, calcium and magnesium ions were studied. The results indicated that the adsorption capacities are strongly affected by the solution pH, contact time and initial concentration. A higher pH favors higher U (VI) removal. The adsorption was also affected by temperature and calcium and magnesium ions, but the effect is very weak. The maximum adsorption capacity (q(m)) only increased from 3.36 mgg(-1) to 3.54 mgg(-1) when the temperature was increased from 293 K to 318 K. A two-stage kinetic behavior was observed in the adsorption of uranium (VI): very rapid initial adsorption in a few minutes, followed by a long period of slower uptake. It was found that an increase in temperature resulted in a higher uranium (VI) loading per unit weight of the sorbent. The adsorption of uranium by hematite had good efficiency, and the equilibrium time of adsorbing uranium (VI) was about 6h. The isothermal data were fitted with both Langmuir and Freundlich equations, but the data fitted the former better than the latter. The pseudo-first-order kinetic model, pseudo-second-order kinetic model and intraparticle diffusion model were used to describe the kinetic data, but the pseudo-second-order kinetic model was the best. The thermodynamic parameter Delta G(0) were calculated, the negative Delta G(0) values of uranium (VI) at different temperatures confirmed the adsorption processes were spontaneous.
Assuntos
Compostos Férricos/química , Urânio/química , Urânio/isolamento & purificação , Adsorção , Microscopia Eletrônica de Varredura , Água/químicaRESUMO
BACKGROUND: Recent studies have shown that the short-chain fatty acids (SCFAs) produced by the gut microbiota play a positive role in the development of colorectal cancer (CRC). AIMS: This study aims to elucidate the "food-microorganism-SCFAs" axis and to provide guidance for prevention and intervention in CRC. METHODS: The PubMed, Embase and Cochrane databases were searched from their inceptions to August 2018, and 75 articles and 25 conference abstracts were included and analysed after identification and screening. RESULTS: The concentrations of SCFAs in CRC patients and individuals with a high risk of CRC were higher than those in healthy individuals. The protective mechanism of SCFAs against CRC has been described in three aspects: epigenetics, immunology and molecular signalling pathways. Many food and plant extracts that were fermented by microorganisms produced SCFAs that play positive roles with preventive and therapeutic effects on CRC. The "food-microorganism-SCFAs" axis was constructed by summarizing the pertinent literature. CONCLUSIONS: This study provides insight into the basic research and practical application of SCFAs by assessing the protective effect of SCFAs on CRC.
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Neoplasias Colorretais/prevenção & controle , Ácidos Graxos Voláteis/fisiologia , Comportamento Alimentar/fisiologia , Microbioma Gastrointestinal/fisiologia , Pesquisa Biomédica/métodos , Pesquisa Biomédica/tendências , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/microbiologia , Ácidos Graxos Voláteis/uso terapêutico , Alimentos , Humanos , Padrões de Prática Médica/tendências , Probióticos/uso terapêutico , Fatores de Risco , Transdução de Sinais/fisiologiaRESUMO
The unexpected finding of astrocytes to release glutamate as gliotransmitter challenges the traditional concepts on astrocyte being "passive" in CNS communications. Glutamate is the major excitatory transmitter in transferring information between neurons, but is now also known to activate astrocyte through transporters and receptors. Together with the sensitive swelling response, astrocytes could respond directly to glutamate and neuronal activity. Other new functions of astrocytes include modulation of synaptic plasticity and cerebral blood flow (CBF). The classic glutamate deplenishment through glutamine synthesis and CO(2) production does not account for the total glutamate internalized into astrocytes. This leads us to speculate there are many hidden functions of glutamate in neurons and astrocytes waiting to be discovered. In this review, we attempted to reexamine some of these new and older functions of glutamate and to reevaluate the roles of glutamate intoning these two cell types.
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Astrócitos/metabolismo , Ácido Glutâmico/metabolismo , Neurônios/metabolismo , Animais , Astrócitos/citologia , Encéfalo/irrigação sanguínea , Encéfalo/citologia , Humanos , Plasticidade Neuronal , Neurônios/citologiaRESUMO
Caspase recruitment domain-containing protein 9 (Card9) is located upstream of the nuclear factor kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) inflammatory pathways. This study investigated the therapeutic effect and potential mechanism of pioglitazone in rats with severe acute pancreatitis (SAP). SAP was induced by a retrograde infusion of 5.0% sodium taurocholate into the biliopancreatic duct of Sprague Dawley rats (n=54), which were then treated with pioglitazone. Blood and pancreatic tissues were harvested at 3, 6, and 12 h after SAP induction. Pancreatic pathological damage was evaluated by hematoxylin and eosin staining. Serum amylase, serum pro-inflammatory cytokines, and pancreatic myeloperoxidase (MPO) activities were determined by enzyme-linked immunosorbent assay. The expression of Card9 mRNA and protein in pancreatic tissues was detected by real-time polymerase chain reaction and western blotting. Pioglitazone had a therapeutic effect in treating rats with SAP by decreasing the level of amylase activity, ameliorating pancreatic histological damage, decreasing serum pro-inflammatory cytokine levels and tissue MPO activity, and downregulating the expression of NF-κB, p38MAPK, and Card9 mRNAs and proteins (P<0.05). The present study demonstrated that the inhibition of Card9 expression could reduce the severity of SAP. Card9 has a role in the pathogenic mechanism of SAP.
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Anti-Inflamatórios/farmacologia , Pancreatite/tratamento farmacológico , Pancreatite/patologia , Tiazolidinedionas/farmacologia , Amilases/sangue , Amilases/efeitos dos fármacos , Animais , Anti-Inflamatórios/uso terapêutico , Western Blotting , Proteínas Adaptadoras de Sinalização CARD/análise , Proteínas Adaptadoras de Sinalização CARD/efeitos dos fármacos , Citocinas/sangue , Citocinas/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Masculino , NF-kappa B/análise , Peroxidase/análise , Pioglitazona , Distribuição Aleatória , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Tiazolidinedionas/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Proteínas Quinases p38 Ativadas por Mitógeno/análiseRESUMO
OBJECTIVE: To investigate the clinical effects of 360 degree circular decompression and transpedicle screw fixation to treat the ossification of thoracic posterior longitudinal ligament by posterior approach. METHODS: From December 2009 to November 2013, 18 patients with ossification of thoracic posterior longitudinal ligament ossification were treated with 360 degree circle decompression and transpedicle screw fixation by posterior approach. There were 8 males and 10 females,ranging in age from 32 to 67 years old, with an average of 51 years old. Four patients were accompanied with ligamentum flavum ossification. Longitudinal ossifications in 5 cases were located in the upper thoracic vertebra and 13 cases in the middle and lower thoracic vertebra. Five cases were typical type, 4 cases were segmental type, 6 cases were continuous type and 3 cases were mixed type. All the patients had the posterior spinal canal decompression combined with longitudinal ligament resection, interbody fusion with bone graft and internal fixation surgeries. The operation time,blood loss and complications were recorded. JOA score were applied to evaluate the neurological function recovery pre-surgery, 2 days post-surgery and the latest follow-up. The surgery effects were evaluated by Epstein-Schwall method. RESULTS: The operation time ranged from 3 to 6 hours (mean, 4.2 hours). The blood loss ranged from 800 to 4 000 ml (mean, 1 800 ml). All the patients were followed up, and the duration ranged from 6 months to 3 years, with a mean of 1.8 years. The JOA score increased from preoperative 4.30 ± 2.60 to 7.60 ± 2.40 2 days after surgery, and 7.80 ± 1.90 at the latest follow-up (t = 4.61, P < 0.001). The JOA scores between 2 days after surgery and the latest follow-up had no significant differences (t = 0.28,P = 0.78). The neurological recovery rate was 74% 2 days after surgery and 71% at the latest follow-up. There were 4 cases got an excellent result,10 good,3 fair and 1 poor according to Epstein-Schwall evaluation method. Four patients had cerebrospinal fluid leakage, 3 patients had intercostal nerve paralysis or pain, and 1 patient had superficial incision infection. The neurological function in 3 patients became worse in the second day posteratively , and among them, 2 patients were recovered at the latest follow-up and 1 patient had no changes. All the patients got fusion of bone graft and no internal fixation loosening and fractures occurred. CONCLUSION: 360 degree circular decompression and transpedicle screw fixation can resect different types of thoracic longitudinal ligament ossification, and can achieve a good clinical effect.
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Descompressão Cirúrgica/métodos , Fixação Interna de Fraturas/métodos , Ossificação do Ligamento Longitudinal Posterior/cirurgia , Vértebras Torácicas/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Caspase recruitment domain-containing protein 9 (Card9) is located upstream of the nuclear factor kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) inflammatory pathways. This study investigated the therapeutic effect and potential mechanism of pioglitazone in rats with severe acute pancreatitis (SAP). SAP was induced by a retrograde infusion of 5.0% sodium taurocholate into the biliopancreatic duct of Sprague Dawley rats (n=54), which were then treated with pioglitazone. Blood and pancreatic tissues were harvested at 3, 6, and 12 h after SAP induction. Pancreatic pathological damage was evaluated by hematoxylin and eosin staining. Serum amylase, serum pro-inflammatory cytokines, and pancreatic myeloperoxidase (MPO) activities were determined by enzyme-linked immunosorbent assay. The expression of Card9 mRNA and protein in pancreatic tissues was detected by real-time polymerase chain reaction and western blotting. Pioglitazone had a therapeutic effect in treating rats with SAP by decreasing the level of amylase activity, ameliorating pancreatic histological damage, decreasing serum pro-inflammatory cytokine levels and tissue MPO activity, and downregulating the expression of NF-κB, p38MAPK, and Card9 mRNAs and proteins (P<0.05). The present study demonstrated that the inhibition of Card9 expression could reduce the severity of SAP. Card9 has a role in the pathogenic mechanism of SAP.
Assuntos
Animais , Masculino , Pancreatite/patologia , Pancreatite/tratamento farmacológico , Tiazolidinedionas/farmacologia , Anti-Inflamatórios/farmacologia , Distribuição Aleatória , Western Blotting , Reprodutibilidade dos Testes , Citocinas/efeitos dos fármacos , Citocinas/sangue , Resultado do Tratamento , Proteínas Adaptadoras de Sinalização CARD/análise , Reação em Cadeia da Polimerase em Tempo Real , Pioglitazona , Amilases/efeitos dos fármacos , Amilases/sangue , Anti-Inflamatórios/uso terapêuticoRESUMO
An energy-efficient application-specific integrated circuit (ASIC) featured with a work-on-demand protocol is designed for wireless body sensor networks (WBSNs) in medical applications. Dedicated for ultra-low-power wireless sensor nodes, the ASIC consists of a low-power microcontroller unit (MCU), a power-management unit (PMU), reconfigurable sensor interfaces, communication ports controlling a wireless transceiver, and an integrated passive radio-frequency (RF) receiver with energy harvesting ability. The MCU, together with the PMU, provides quite flexible communication and power-control modes for energy-efficient operations. The always-on passive RF receiver with an RF energy harvesting block offers the sensor nodes the capability of work-on-demand with zero standby power. Fabricated in standard 0.18-¿m complementary metal-oxide semiconductor technology, the ASIC occupies a die area of 2 mm × 2.5 mm. A wireless body sensor network sensor-node prototype using this ASIC only consumes < 10-nA current under the passive standby mode, and < 10 ¿A under the active standby mode, when supplied by a 3-V battery.