RESUMO
OBJECTIVE: To determine the maximum tolerated dose (MTD) of paclitaxel combined with a fixed dose of cisplatin (75 mg/m2) delivered via hyperthermic intraperitoneal chemotherapy (HIPEC) to patients with ovarian cancer. METHODS: This multicenter Phase I trial employed a Bayesian Optimal Interval (BOIN) design. The MTD was determined to have a target dose-limiting toxicity (DLT) rate of 25%. The starting dose was 175 mg/m2. The Data and Safety Monitoring Board made decisions regarding dose escalation or de-escalation in increments of 25 mg/m2 for subsequent patient cohorts, up to a maximum sample size of 30 or 12 patients treated at a given dose. RESULTS: Twenty-one patients participated in this study. Among the three evaluable patients who received 150 mg/m2 paclitaxel, no DLTs were observed. Among the 12 evaluable patients who received 175 mg/m2 paclitaxel, two reported DLTs: one had grade 4 neutropenia and one had grade 4 anemia, neutropenia, and leukopenia. Four of the six evaluable patients who received 200 mg/m2 paclitaxel reported DLTs: one patient had grade 4 diarrhea, one had grade 3 kidney injury, and two had grade 4 anemia. The isotonic estimate of the DLT rate in the 175 mg/m2 dose group was 0.17 (95% confidence interval, 0.02-0.42), and this dose was selected as the MTD. CONCLUSION: Paclitaxel, when combined with a fixed dose of cisplatin (75 mg/m2), can be safely administered intraperitoneally at a dose of 175 mg/m2 in patients with ovarian cancer who received HIPEC (43 °C, 90 min) following cytoreductive surgery.
Assuntos
Anemia , Neutropenia , Neoplasias Ovarianas , Humanos , Feminino , Cisplatino , Paclitaxel , Quimioterapia Intraperitoneal Hipertérmica , Dose Máxima Tolerável , Teorema de Bayes , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/terapia , Neutropenia/induzido quimicamente , Anemia/etiologia , Relação Dose-Resposta a DrogaRESUMO
This paper introduces professor SUN Shen-tian's clinical thoughts and his characteristics of acupuncture techniques for the treatment of depression based on "psychosomatic medicine". Professor SUN, the master of traditional Chinese medicine, believes that depression refers to comorbidity of "heart mind" and "body", resulting from the "body-mind" disharmony, specially dominated by the emotional disorder. This disease is located in the brain, with the injury of mind and closely related to the heart and liver dysfunction. In pathogenesis, the dysfunction of brain mind and the unhealthy conditions of body and mind are involved. The treatment should focus on "regulating the mind, improving the intelligence, co-modulating the abdominal and brain functions and treating the physical and mental disorders". Baihui (GV 20), Ningshen (Extra) and emotional area on the head are selected as the main points to benefit the intelligence and calming down the mind; the abdominal region 1 and region 8 of "Sun's abdominal acupuncture" are used as the main points of the abdomen to regulate the brain functions. The point prescription is modified according to the symptoms and etiologies. The repeated transcranial acupuncture stimulation and electroacupuncture at low frequency (2 Hz) are crucial to the therapeutic effect. Reliving anxious emotions is specially considered before acupuncture, and the mind is protected and deqi is consolidated during acupuncture.
Assuntos
Terapia por Acupuntura , Acupuntura , Humanos , Depressão/terapia , Pontos de Acupuntura , Terapia por Acupuntura/métodos , Medicina Tradicional ChinesaRESUMO
To summarize SUN Shen-tian's treatment ideas and clinical features. SUN applies meridian syndrome differentiation to the diagnosis and treatment of diseases; advocates that prevention and treatment of diseases should be regulated mind firstly; applies transcranial repetitive acupuncture combined modern cerebral cortex function positioning; emphasizes the application of multiple acupuncture methods and manipulation, and includes the meridian penetrating needling method, the flat needling and penetrating needling method, and the stagnant needle lifting method, pays attention to the importance of achieving qi and manipulation for the effect.
Assuntos
Terapia por Acupuntura , Acupuntura , Meridianos , Moxibustão , Pontos de AcupunturaRESUMO
Agricultural products are a primary pathway for humans to accumulate heavy metals (HMs) via the soil-crop system and should therefore should be included as a crucial part of the food security in our country. Given that previous studies on protection zoning for preventing farmland HM pollution rarely considered agricultural products as a basic element, this study attempted to establish a zoning system for farmland HM prevention, which was based on the perspective of agricultural product pollution. We subsequently took a representative peri-urban area in the black soil region, which was provided with a higher risk of being polluted, as an empirical case. The results indicated that:â the comprehensive quality index of agricultural products (IICQAP) was 1.09, illustrating only a mild HM pollution, with Pb and Ni having the highest accumulation levels; â¡ the human health risk index (QHI) was 0.61, showing no risk for human health; and ⢠the designed zoning method revealed 89.45% of the farmlands to be risk-free at the moment and 10.55% of the farmlands to be under low risk of HM pollution in agricultural products. According to the zoning results, we suggested prioritized protection and an early-warning strategy, respectively, and further recommended prevention methods such as accumulation intervention, crop restructuring, and in-situ passivation. The results served to enrich the theoretical basis for preventing farmland HM pollution, to reinforce the management standards for agricultural products in the black soil region, and also to build a differentiated urban-rural farmland protection system.
Assuntos
Metais Pesados , Poluentes do Solo , China , Monitoramento Ambiental , Fazendas , Humanos , Metais Pesados/análise , Medição de Risco , Solo , Poluentes do Solo/análiseRESUMO
Pancreatic cancer is a highly aggressive and lethal digestive system malignancy. Our previous studies revealed the correlation of high levels of lncRNA SOX2OT expression with patients' poor survival outcomes, the promoting role of SOX2OT in proliferation and cycle progression of pancreatic cancer cells, and the in vivo binding of SOX2OT to RNA binding protein FUS, which destabilized the protein expression of FUS. However, the mechanism of SOX2OT binding and inhibiting FUS protein stability remains unclear. In this study, we performed RNA pull-down, cycloheximide-chase, and ubiquitination assays to determine the effect of SOX2OT on FUS ubiquitination, and explored the specific regulatory mechanism of SOX2OT-FUS axis in pancreatic cancer cell migration, invasion, in vivo tumor growth, and metastasis through RNA sequencing. We found that SOX2OT binds to FUS through its 5' and 3' regions, resulting in FUS ubiquitination and degradation. The SOX2OT-FUS regulatory axis promotes migration, invasion, tumor growth, and metastasis ability of pancreatic cancer cells. The in-depth elaboration of the SOX2OT-FUS regulatory axis in pancreatic cancer may clarify the mechanism of action of SOX2OT and provide new ideas for pancreatic cancer treatment.
RESUMO
OBJECTIVE: To explore the expression and clinical significance of Gal-3 and NFκB pathway related factors in epithelial ovarian carcinoma cells. METHODS: 99 histologic specimens of epithelial ovarian cancer and 20 normal ovarian histologic specimens were collected, and the expressions of Gal-3, IκB and p65 were detected by immunohistochemistry. Their relationship with clinical characteristics was analyzed. RESULTS: The expression of Gal-3 and p65 was negatively correlated with the overall survival rate (P<0.05), while the expression of IκB was positively correlated with the overall survival rate (P<0.05). Expression of Gal-3, p65 and IκB were found associated with EOC platinum resistance (P<0.05), and expression of Gal-3 and p65 correlated with pathologic grading (P<0.05). IκB and Gal-3 were associated with the recurrence of EOC (P<0.05). IκB may be related to clinical stage (P<0.05). Multivariate analysis results showed that abnormal expression of Gal-3 may be an independent prognostic risk factors for the drug resistance to platinum-based chemotherapy (95% CI=5.336~34.112, P<0.05). The expression of Gal-3, p65, and IκB can be clinical immunohistochemical indicators that determine the prognosis of EOC, but the amount of Gal-3 expression was related to the epithelial ovarian cancer's pathologic type and overall survival, which suggested that Gal-3 can be used as a prognostic factor in epithelial ovarian cancer. CONCLUSION: Targeted therapy of Gal-3 may become an effective potential new method against epithelial ovarian cancer.
RESUMO
There is no criteria of placebo acupuncture method and no suitable method for all kinds of acupuncture research currently. In this paper, the methods and theories of placebo acupuncture were collected in recent 10 years at home and abroad. The analysis was conducted in the aspects of the premise of placebo acupuncture design, the common methods and their advantages and disadvantages, the application of various placebo acupuncture methods and the controversy on placebo acupuncture. It is required to further improve the design of placebo acupuncture control, explore the key questions of it and specify the criteria of its method so as to lay the foundation for the establishment of scientific and rational placebo acupuncture control in acupuncture research.
Assuntos
Pontos de Acupuntura , Terapia por Acupuntura/métodos , Efeito Placebo , Humanos , Projetos de PesquisaRESUMO
The purpose of this study was to explore the functional implication of microRNA-218 (miR-218) in diabetic nephropathy (DN) through high-glucose-stimulated renal proximal tubule impairment. Biological function experiments showed that miR-218 and inflammatory factors TNF-α and IL-1ß were highly expressed in renal proximal tubule under high-glucose conditions. Inhibiting miR-218 alleviated renal tubular cell injury, which was represented by miR-218 inhibitor facilitating renal tubular cell vitality whilst reducing its apoptosis and levels of inflammation factors. In addition, we confirmed that miR-218 directly targeted GPRC5A and negatively regulated its expression. Co-transfection assay showed that overexpression of GPRC5A accentuated the mitigated action of miR-218 inhibitor on renal proximal tubule cell injury induced by high-glucose. Accordingly, these data indicated that downregulation of miR-218 can assuage high-glucose-resulted renal tubular cell damage, and its ameliorative effect was achieved by negative regulation of GPRC5A, which provides a novel direction for unearthing the pathogenesis and even further biological treatment of DN.
Assuntos
Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Regulação para Baixo/genética , Glucose/efeitos adversos , Túbulos Renais/lesões , MicroRNAs/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Cultivadas , Nefropatias Diabéticas/urina , Humanos , Interleucina-1beta/metabolismo , Túbulos Renais/citologia , MicroRNAs/genética , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transfecção , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Background: Depression is a common mental disorder worldwide. Psychological treatments and antidepressant medication are the usual treatments for depression. However, a large proportion of patients with depression do not respond to the treatments. In 2005, Vagus nerve stimulation was approved for the adjunctive long-term treatment of chronic or recurrent depression in adult patients experiencing a major depressive episode who had failed to respond to four or more adequate antidepressant treatments. However, the efficacy of VNS for treating depression remains unclear. Accordingly, we performed a systematic review to evaluate the efficacy and safety of VNS. Methods: We conducted a systematic review in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Systematic search was performed in the database of Pubmed, Embase, CENTRAL, and Web of science for identifying the suitable trials. Suicidal rate was considered as the primary outcome in this review. Result: Only two randomized sham controlled add-on studies including 255 cases (134 with VNS treatment and 121 control cases) were included in this review. None of the studies reported suicidal rate. We performed a qualitative analysis and it is suggested that there was no significant statistic difference between VNS and sham VNS on the score of 24-item Hamilton Rating Scale for Depression (HAMD24) (MD: -2.40, 95% CI: -7.90 to 3.10). Similar findings were also reported on improvement percentage of HAMD24 (MD: 1.00, 95%CI: -6.06 to 8.06), Montgomery-Asberg Depression Rating Scale (MADRS) (MD: 4.70, 95%CI: -2.98 to 12.38) and 30 item Inventory of Depressive Symptomalogy-Self-Report (IDS-SR30) (MD: 4.9, 95%CI: -1.89 to 11.69). However, a marginal difference of Beck Depression Inventory self-rating score was detected between the real and sham treatment (MD: 7.80, 95% CI: 0.34 to 15.26). Aminor effect of IDS-SR30was also found in real VNS group (RR: 2.33, 95% CI: 1.07 to 5.10). Conclusion: The efficacy and safety of VNS for depression is still unclear. Further randomized controlled trials are needed to confirm the efficacy and safety of VNS.
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A field experiment with different nitrogen fertilization rates and mitigation measures was conducted in an open-ground vegetable field on the North China Plain to investigate the effects of nitrogen application level and management practices on ammonia volatilization and N2O emission. Reducing the nitrogen fertilization rate by 20% and by 50% decreased ammonia volatilization by 25.7% and 48.0%, respectively, during the spring-sowed cucumber growth period. Amendment with combined inhibitors and biochar decreased ammonia volatilization loss by 10.0% and 6.1%, respectively. Reducing nitrogen fertilization rate by 20% and 50% decreased N2O emission by 28.8% and 61.0% during the spring-sowed cucumber growth period. Addition of combined inhibitors decreased N2O emission by 58.9%, while it was increased by 14.1% with biochar addition. Under the same application method of banding application, replacing 30% nitrogen fertili-zer with organic manure did not show any significant mitigation for ammonia volatilization and N2O emission. For the intensively managed vegetable fields, reducing the nitrogen application rate appropriately was the most effective measure to reduce ammonia volatilization and N2O emission.
Assuntos
Amônia/análise , Fertilizantes , Óxido Nitroso/análise , Verduras , Agricultura , China , Nitrogênio , Solo , VolatilizaçãoRESUMO
OBJECTIVE: To explore the effects of Osthole on apoptosis of HL-60 cells induced by tumor necrosis factor related apoptosis inducing ligand (TRAIL) and its possible mechanism. METHODS: The proliferative inhibition of HL-60 cells treated with different concentrations of Osthole, TRAIL alone and Osthole combined with TRAIL was measured by MTT assay. The HL-60 cells were treated with Osthole, TRAIL alone and Osthole combined with TRAIL at the concentrationAssuntos
Apoptose
, Cumarínicos
, Células HL-60
, Humanos
, Ligante Indutor de Apoptose Relacionado a TNF
RESUMO
Brain-derived neurotrophic factor (BDNF) plays important roles in neural stem cell (NSC) growth. In this study, we investigated whether BDNF exerts its neurotrophic effects through the Wnt/ß-catenin signaling pathway in human embryonic spinal cord NSCs (hESC-NSCs) in vitro. We found an increase in hESC-NSC growth by BDNF overexpression. Furthermore, expression of Wnt1, Frizzled1 and Dsh was upregulated, whereas GSK-3ß expression was downregulated. In contrast, hESC-NSC growth was decreased by BDNF RNA interference. BDNF, Wnt1 and ß-catenin components were all downregulated, whereas GSK-3ß was upregulated. Next, we treated hESC-NSCs with 6-bromoindirubin-3'-oxime (BIO), a small molecule inhibitor of GSK-3ß. BIO reduced the effects of BDNF upregulation/downregulation on the cell number, soma size and differentiation, and suppressed the effect of BDNF modulation on the Wnt signaling pathway. Our findings suggest that BDNF promotes hESC-NSC growth in vitro through crosstalk with the Wnt/ß-catenin signaling pathway, and that this interaction may be mediated by GSK-3ß.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Proliferação de Células , Células-Tronco Embrionárias/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Células-Tronco Neurais/metabolismo , Via de Sinalização Wnt , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Células Cultivadas , Células-Tronco Embrionárias/fisiologia , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Humanos , Células-Tronco Neurais/fisiologia , Regulação para Cima , beta Catenina/metabolismoRESUMO
Fangchinoline (Fan) is a bioactive compound isolated from the Chinese herb Stephania tetrandra S. Moore (Fen Fang Ji). The aim of the present study was to investigate the effect of Fan on the proliferation of SPC-A-1 lung cancer cells, and to define the associated molecular mechanisms. Following treatment with Fan, Cell Counting Kit-8, phase contrast imaging and Giemsa staining assays were used to detect cell viability; flow cytometry was performed to analyze the cell cycle distribution; and reverse transcription-quantitative polymerase chain reaction and western blot assays were used to investigate changes in the expression levels of cell cycle-associated genes and proteins. In the present study, treatment with Fan markedly inhibited the proliferation of SPC-A-1 lung cancer cells and significantly increased the percentage of cells in the G0/G1 phase of the cell cycle in a dose-dependent manner (P<0.05 for 2.5-5 µm; P<0.01 for 10 µm), whereas the percentage of cells in the S and G2/M phases were significantly reduced following treatment (P<0.05 for 5 µm; P<0.01 for 10 µm). Mechanistically, Fan significantly reduced the mRNA expression levels of cyclin D1, cyclin-dependent kinase 4 (CDK4) and CDK6 (P<0.05 for 2.5-5 µm; P<0.01 for 10 µm), which are key genes in the regulation of the G0/G1 phase of the cell cycle. Furthermore, treatment with Fan also decreased the expression of phosphorylated retinoblastoma (Rb) and E2F transcription factor-1 (E2F-1) proteins (P<0.05 for 5 µm; P<0.01 for 10 µm). In summary, the present study demonstrated that Fan inhibited the proliferation of SPC-A-1 lung cancer cells and induced cell cycle arrest at the G0/G1 phase. These effects may be mediated by the downregulation of cellular CDK4, CDK6 and cyclin D1 levels, thus leading to hypophosphorylation of Rb and subsequent suppression of E2F-1 activity. Therefore, the present results suggest that Fan may be a potential drug candidate for the prevention of lung cancer.
RESUMO
Development of the human fetal spinal cord is a very complicated process involving numerous signaling pathways including Wnt signaling pathways. These pathways are critical for the development and function of the mammalian nervous system. ß-Catenin is a key molecule in the canonical Wnt signaling pathway. However, the distributions of ß-catenin during development of the human fetal spinal cord have not been well characterized. Therefore, in this study, we performed immunohistochemical analysis of the ß-catenin distribution in the developing human spinal cord from 35 fetuses at three weeks to eight months of gestation. As early as E3W and E4W, ß-catenin was mainly expressed in the internal limiting membrane of the neural tube and neuroepithelium (E: Embryos; W: Weeks). During developmental stages, ß-catenin was widely expressed in various structures and cells including the neuroepithelium, internal limiting membrane, mantle layer, marginal layer, basal plate, alar plate, ependyma, gray matter, white matter, neurons with multiple processes, glial cells, and nerve fibers. This study clarifies the morphological developmental characteristics of the human fetal spinal cord as well as the distribution and expression pattern of ß-catenin in chronological and spatial aspects. Our results suggest that the Wnt÷ß-catenin signaling pathway might play a crucial role in various stages of the formation and differentiation of the human fetal spinal cord.
Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Medula Espinal/embriologia , Medula Espinal/metabolismo , beta Catenina/metabolismo , Diferenciação Celular , Citoplasma/metabolismo , Humanos , Imuno-Histoquímica , Tubo Neural/metabolismo , Neuritos/metabolismo , Neuroglia/metabolismo , Neurônios/metabolismo , Fatores de Tempo , Via de Sinalização WntRESUMO
In order to search for new anionic architectures and develop useful organic-inorganic hybrid materials in halometallate systems, two new crystalline organic-inorganic hybrid compounds have been prepared, i.e. catena-poly[triethyl(2-hydroxyethyl)azanium [[bromidocadmate(II)]-di-µ-bromido]], {(C8H20NO)[CdBr3]}n, (1), and catena-poly[triethyl(2-hydroxyethyl)azanium [[bromidomercurate(II)]-di-µ-bromido]], {(C8H20NO)[HgBr3]}n, (2), and the structures determined by X-ray diffraction analysis. The compounds are isostructural, crystallizing in the space group P21/n. The metal centres are five-coordinated by bromide anions, giving a slightly distorted trigonal-bipyramidal geometry. The crystal structures consist of one-dimensional edge-sharing chains of MBr5 trigonal bipyramids, between which triethylcholine counter-cations are intercalated. O-H···Br hydrogen-bonding interactions are present between the cations and anions.
Assuntos
Colina/análogos & derivados , Complexos de Coordenação/química , Mercúrio/química , Colina/química , Cristalografia por Raios X , Ligação de Hidrogênio , Compostos Inorgânicos , Estrutura Molecular , Compostos OrgânicosRESUMO
PURPOSE: The development of the human embryonic spinal cord is very complicated, and many cell types are involved in the process. However, the morphological characteristics of neuronal and glial cells during the development of the human fetal spinal cord have not been described. We investigated the systemic distributions and expression pattern of the cell type-specific markers Neuron-specific nuclear protein (NeuN) and glial fibrillary acidic protein (GFAP) during the development of the human fetal spinal cord, in order to clarify the detailed developmental changes of neuronal and glial cells in chronological and spatial aspects. METHODS: A total of 35 fetuses, aged 3 weeks to 8 months of gestation (E3W-E8M), were studied. The markers used for immunohistochemical study were NeuN and GFAP. RESULTS: The intracellular makers NeuN and GFAP were widely detected expression in different structures and cells during the development of the human fetal spinal cord, including the following: central canal, neuroepithelial layer, internal limiting membrane, mantle layer, marginal layer, basal plate, alar plate, ependymal layer, gray matter, white matter, neuron, astrocytes, and nerve fibers. However, there was an absence of GFAP in astrocytes during early fetal spinal cord development until E9W, and the appearance of GFAP-positive reactivity was later than that of neurons. CONCLUSIONS: We consider that NeuN and GFAP can be used to identify neuronal and glial cells during the development of the human fetal spinal cord, and their distribution differs both chronologically and spatially. These characteristic expression patterns would give us a clue to better understand the developmental characteristics of the human spinal cord.
Assuntos
Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Proteína Glial Fibrilar Ácida/metabolismo , Fosfopiruvato Hidratase/metabolismo , Medula Espinal/embriologia , Medula Espinal/metabolismo , Fatores Etários , Feminino , Feto , Idade Gestacional , Humanos , Masculino , Medula Espinal/citologiaRESUMO
BACKGROUND: After more than 10 years without a case of wild poliovirus (WPV) in China, an outbreak occurred in 2011 in Xinjiang Uyghur Autonomous Region. METHODS: Acute flaccid paralysis (AFP) case surveillance was strengthened with epidemiological investigations and specimen collection and serological surveys were conducted among hospitalized patients. RESULTS: There were 21 WPV cases and 23 clinical compatible polio cases reported. WPV was isolated from 14 contacts of AFP cases and 13 in the healthy population. Incidence of WPV and clinical compatible polio cases were both highest among children <1 years, however, 24/44 (54.5%) polio cases were reported among adults aged 15-39 years. CONCLUSIONS: High coverage of routine immunization should be maintained among children until WPV transmission is globally eradicated. Expansion of AFP case surveillance and use of serologic surveys to estimate population immunity should be conducted rapidly to guide preparedness and response planning for future WPV outbreaks.
Assuntos
Surtos de Doenças , Poliomielite/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Criança , Pré-Escolar , China/epidemiologia , Busca de Comunicante , Surtos de Doenças/prevenção & controle , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Poliomielite/diagnóstico , Poliomielite/prevenção & controle , Vigilância em Saúde Pública , Estudos Retrospectivos , Adulto JovemRESUMO
To investigate the effects of gambognic acid (GA) on TRAIL-induced apoptosis of cancer cells, human colon HT-29 cancer cells were treated with GA to promote apoptosis. Inhibition of the cell proliferation was measured with MTT assay and cell apoptosis was detected with formation of DNA ladders in agarose gel electrophoresis, and activation of caspase activity. The content of cytosolic reactive oxygen species (ROS) was measured with flow cytometry. The activities of Caspase-3, -8, -9 were detected using spectrophotometric assay. The levels of c-FLIP, CHOP, DR4 and DR5 in cells were tested by Western blot. Combination of GA (1 µg · mL(-1)) and TRAIL (40 ng · mL(-1)) significantly reduced proliferation and increased apoptosis of HT-29 cells over those induced by each agent alone. Percentage of apoptotic cells was increased to 45.5%. GA markedly enhanced the intracellular ROS generation. Expression of CHOP, DR4 and DR5 was up-regulated to 7.38, 5.41, and 4.85 times of the control group, respectively. GA promoted activation of Caspase-3, -8, and -9 by TRAIL (P<0.05). Furthermore, the expression of anti-apoptotic protein c-FLIP was down-regulated to 0.22 ± 0.08 times of the control group. In conclusion, GA sensitizes HT-29 cells to TRAIL-induced apoptosis by promoting ROS-activated ERS pathways, up-regulating of DR4 and DR5, and inhibiting c-FLIP expression.
Assuntos
Apoptose , Neoplasias do Colo/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Xantonas/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Células HT29 , Humanos , Espécies Reativas de Oxigênio/metabolismo , Regulação para CimaRESUMO
To investigate the epidemiology of hand, foot, and mouth disease (HFMD) and the genetic characteristics of enterovirus A71 (EV-A71) in Linyi of Shandong Province, China during 2007-2012. The number of reported HFMD cases were obtained from the National Notifiable Disease Reporting System (NNDRS) were analyzed by descriptive epidemiology method; the VP1 region of EV-A71 isolated from HFMD patients in Linyi was amplified and sequenced. Finally, the genetic variability and phylogenecity of VP1 sequences of EV-A71 were analyzed by MEGA 5.0. The results showed that HFMD incidence was reported in each year from 2007 to 2012 in Linyi, and the highest incidence and mortality were reported in 2009, when there were total 14697 cases and 9 of death. The reported incidence was 140.28/100000, and the mortality was 0.086/100000. The peak incidence usually occurred between April and July, and the summit occurred in May. Scattered children accounted for 77.37%-92.00% of all cases. The peak age was 2.5 years during 2007-2009 and 1.5 years during 2010-2012. A total of 1365 laboratory-confirmed HFMD cases were reported in the 6 consecutive years, accounting for 2.98% of the gross number. Among these reports, the ratio of EV-A71 was 44.18%, and the ratio of coxsackievirus A16 (CVA16) was 46.59%. All EV-A71 strains isolated in Linyi during 2007-2012 belonged to the C4a evolutionary branch of C4 genotype. In conclusion, HFMD outbreaks occurred every year in Linyi during 2007-2012. Incidence varied significantly among different counties. The peak incidence in each year lasted from April to July. Most of the patients were children under 3 years of age, and scattered children took the highest proportion. Co-circulation of EV-A71 and CVA16 was the major cause of HFMD in each year. Since the first report of HFMD prevalence caused by EV-A71 (C4a) in 2007, the virus has been prevalent continuously in Linyi for 6 years.
Assuntos
Enterovirus/genética , Doença de Mão, Pé e Boca/epidemiologia , Doença de Mão, Pé e Boca/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Enterovirus/classificação , Enterovirus/isolamento & purificação , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , Adulto JovemRESUMO
BACKGROUND: After being polio free for more than 10 years, an outbreak following importation of wild poliovirus (WPV) was confirmed in Xinjiang Uygur Autonomous Region, China, in 2011. METHODS: A cross-sectional study was conducted prior to supplementary immunization activities (SIAs), immediately after the confirmation of the WPV outbreak. In selected prefectures, participants aged ≤ 60 years old who visited hospitals at county-level or above to have their blood drawn for reasons not related to the study, were invited to participate in our study. Antibody titers ≥ 8 were considered positive. RESULTS: Among the 2,611 participants enrolled, 2,253 (86.3%), 2,283 (87.4%), and 1,989 (76.2%) were seropositive to P1, P2 and P3 respectively, and 1744 (66.8%) participants were seropositive to all the three serotypes. Lower antibody seropositivities and geometric mean titers were observed in children <1 year of age and in adults aged 15-39 years. CONCLUSION: Serosurveys to estimate population immunity in districts at high risk of polio importation might be useful to gauge underlying population immunity gaps to polio and possibly to guide preparedness and response planning. Consideration should be given to older children and adults during polio risk assessment planning and outbreak response.