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1.
Biomed Res Int ; 2021: 4873678, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34337013

RESUMO

LIHC (liver hepatocellular carcinoma) mostly occurs in patients with chronic liver disease. It is primarily induced by a vicious cycle of liver injury, inflammation, and regeneration that usually last for decades. The G protein nucleolar 2 (GNL2), as a protein-encoding gene, is also known as NGP1, Nog2, Nug2, Ngp-1, and HUMAUANTIG. Few reports are shown towards the specific biological function of GNL2. Meanwhile, it is still unclear whether it is related to the pathogenesis of carcinoma up to date. Here, our study attempts to validate the role and function of GNL2 in LIHC via multiple databases and functional assays. After analysis of gene expression profile from The Cancer Genome Atlas (TCGA) database, GNL2 was largely heightened in LIHC, and its overexpression displayed a close relationship with different stages and poor prognosis of carcinoma. After enrichment analysis, the data revealed that the genes coexpressed with GNL2 probably participated in ribosome biosynthesis which was essential for unrestricted growth of carcinoma. Cell functional assays presented that GNL2 knockdown by siRNA in LIHC cells MHCC97-H and SMCC-7721 greatly reduced cell proliferation, migration, and invasion ability. All in all, these findings capitulated that GNL2 could be a promising treatment target and prognosis biomarker for LIHC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/terapia , Proteínas de Ligação ao GTP/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Proteínas de Ligação ao GTP/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Prognóstico , Reprodutibilidade dos Testes , Transdução de Sinais/genética
2.
Bioresour Technol ; 337: 125427, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34217022

RESUMO

The present study investigated the effect of brown-rot fungus Gloeophyllum trabeum inoculation on lignocellulose degradation, enzyme activities and fungal community during co-composting of swine manure and wheat straw. G. trabeum inoculation shortened the maturation period of composting from 39 to 30 days. Composting piles inoculated with G. trabeum showed a higher degree of maturity as indicated by 31.6% lower C/N ratio and 29.4% higher GI. The decomposition rate of cellulose, hemicellulose and lignin was increased by 181.1%, 49.4% and 109.4%, respectively, due to higher activities of filter paper enzyme, xylanase, manganese peroxidase and laccase. Redundancy analysis showed that inoculating G. trabeum influenced the succession of fungal communities by changing the main physicochemical parameters, resulting in the increased relative abundance of Aspergillus, Mycothermus and Melanocarpus. Pearson correlation analysis indicated that more dominant fungal genera were involved in the production of lignocellulose-degrading enzymes after G. trabeum inoculation.


Assuntos
Compostagem , Animais , Basidiomycota , Fungos , Lignina , Esterco , Solo , Suínos
3.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(2): 143-147, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33627208

RESUMO

OBJECTIVE: To study the clinical features of children with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, a polygenic and multifactorial autoinflammatory disease with unknown pathogenesis. METHODS: A retrospective analysis was performed on the medical data of 13 children with PFAPA syndrome. RESULTS: All 13 children had disease onset within the age of 3 years, with a mean age of onset of (14±10) months. They all had periodic fever, with 8-18 attacks each year. The mean interictal period of fever was (30±5) days. Pharyngitis, cervical adenitis, and aphthous stomatitis were the three cardinal symptoms, with incidence rates of 100% (13/13), 85% (11/13), and 38% (5/13) respectively. There were increases in white blood cells, C-reactive protein, and erythrocyte sedimentation rate during fever. Of all the 13 children, 6 underwent whole exome sequencing and 7 underwent panel gene detection for autoinflammatory disease, and the results showed single heterozygous mutations in the MEFV gene in 6 children (46%). Recurrent fever in all children gradually returned to normal without antibiotics. Ten children were treated with a single dose of glucocorticoids, and fever was relieved after treatment. Of all the children, 4 were treated with cimetidine, among whom 2 had response; 4 children were treated with colchicine, among whom 2 had response and 2 were withdrawn from the drug due to adverse reactions. Tonsillectomy was performed for 2 children, among whom 1 was followed up for 3 years without recurrence and 1 still had recurrence. CONCLUSIONS: For children with unexplained periodic fever with early onset accompanied by pharyngitis, cervical adenitis, aphthous stomatitis, elevated inflammatory indices, and good response to glucocorticoids, PFAPA syndrome should be considered. This disorder has good prognosis, and early diagnosis can avoid the long-term repeated use of antibiotics.


Assuntos
Linfadenite , Faringite , Estomatite Aftosa , Criança , Pré-Escolar , Febre/etiologia , Humanos , Lactente , Linfadenite/diagnóstico , Faringite/diagnóstico , Faringite/tratamento farmacológico , Pirina , Estudos Retrospectivos , Estomatite Aftosa/diagnóstico , Estomatite Aftosa/tratamento farmacológico , Estomatite Aftosa/genética
4.
Clin Cancer Res ; 26(20): 5494-5505, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32816947

RESUMO

PURPOSE: T-cell recruitment, survival, and proliferation are the important limitations to chimeric antigen receptor (CAR) T cells therapy in the treatment of solid tumors. In this study, we engineered CAR-T cells to coexpress cytokines IL7 and CCL21 (7 × 21 CAR-T), a cytokine combination in order to improve proliferation and chemotaxis of CAR-T cells. EXPERIMENTAL DESIGN: CLDN18.2-specific second-generation CAR-T cells coexpressing cytokines were prepared using retroviral vector transduction. The proliferation and migration of genetically engineered CAR-T cells were evaluated in vitro. The antitumor activities of genetically engineered CAR-T cells were evaluated against multiple solid tumors in C57BL/6 mice in vivo. RESULTS: In vitro, the proliferation and chemotaxis of 7 × 21 CAR-T cells are significantly improved when compared with those of the conventional CAR-T cells. In vivo, 7 × 21 CAR-T cells revealed superior therapeutic effects to either conventional CAR-T cells or 7 × 19 CAR-T cells which coexpress IL7 and CCL19 as previously reported in three different solid tumors without cyclophosphamide precondition. Interestingly, 7 × 21 CAR-T cells could also suppress the tumor growth with heterogeneous antigen expression and even induce tumor complete remission. Mechanistically, IL7 and CCL21 significantly improved survival and infiltration of CAR-T cells and dendritic cells in tumor. In addition, CCL21 also inhibited the tumor angiogenesis as proved by IHC. CONCLUSIONS: Coexpression of IL7 and CCL21 could boost CAR-T cells' antitumor activity, and 7 × 21 CAR-T cells may be served as a promising therapy strategy for solid tumors.

5.
J Mol Cell Biol ; 11(5): 421-432, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30215728

RESUMO

Paired amphipathic helix protein (SIN3B) is a transcription corepressor for many genes. Here we show a different regulation mechanism of integrin αV gene expression by SIN3B in human hepatocellular carcinoma (HCC). We first observed a close relationship between Integrin αV and SIN3B expressions in HCC patients and tumor cell lines with different metastatic potentials. Overexpression of SIN3B significantly accelerated the cell migration rate of SMMC-7721, but failed when integrin αV expression was silenced. Interestingly, SIN3B stimulated integrin αV subunit promoter activity only in the presence of sulfatide. Importantly, SIN3B was identified in the complex with sulfatide by mass spectrometry. Fat blot assay indicated that SIN3B specifically interacted with sulfatide. Molecular modeling suggested that sulfatide induced the conformational change of SIN3B from compacted α-helices to a relaxed ß-sheet in PAH2 domain. The data of immunoprecipitation and ChIP assay indicated that altered SIN3B lost the binding affinity with MAD1 and HDAC2, which reduced the recruitment of HDAC2 on integrin αV gene promoter and prevented the deacetylation of the histone 3. In conclusion, this study demonstrated that SIN3B promoted the transcriptional activation of the integrin αV subunit gene promoter by reducing interaction with HDAC2.


Assuntos
Carcinoma Hepatocelular/patologia , Integrina alfaV/metabolismo , Neoplasias Hepáticas/patologia , Proteínas Repressoras/metabolismo , Acetilação , Carcinoma Hepatocelular/metabolismo , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Histona Desacetilase 2/química , Histona Desacetilase 2/metabolismo , Histonas/metabolismo , Humanos , Integrina alfaV/genética , Neoplasias Hepáticas/metabolismo , Simulação de Dinâmica Molecular , Regiões Promotoras Genéticas , Ligação Proteica/efeitos dos fármacos , Estrutura Secundária de Proteína , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Proteínas Repressoras/química , Proteínas Repressoras/genética , Sulfoglicoesfingolipídeos/farmacologia , Transcrição Genética/efeitos dos fármacos
6.
Front Oncol ; 9: 1448, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31921693

RESUMO

IL12 is an immune-stimulatory cytokine for key immune cells including T cells and NK cells. However, systemic administration of IL12 has serious side effects that limit its clinical application in patients. Recently, synthetic Notch (synNotch) receptors have been developed that induce transcriptional activation and deliver therapeutic payloads in response to the reorganization of specific antigens. NK92 cell is a human natural killer (NK) cell line which has been developed as tools for adjuvant immunotherapy of cancer. Here, we explored the possibility of using synNotch receptor-engineered NK92 cells to selectively secrete IL12 at the tumor site and increase the antitumor activities of chimeric antigen receptor (CAR)-modified T cells. Compared with the nuclear factor of activated T-cells (NFATs) responsive promoter, which is another regulatory element, the synNotch receptor was better at controlling the expression of cytokines. NK92 cells transduced with the GPC3-specific synNotch receptor could produce the proinflammatory cytokine IL12 (GPC3-Syn-IL12-NK92) in response to GPC3 antigen expressed in cancer cells. In vivo GPC3-Syn-IL12-NK92 cells controlling IL12 production could enhance the antitumor ability of GPC3-redirected CAR T cells and increase the infiltration of T cells without inducing toxicity. Taken together, our results demonstrated that IL12 supplementation by synNotch-engineered NK92 cells could secrete IL12 in a target-dependent manner, and promote the antitumor efficiency of CAR-T cells. Local expression of IL12 by synNotch-engineered NK92 cells might be a safe approach to enhance the clinical outcome of CAR-T cell therapy.

7.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(11): 904-910, 2018 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-30477620

RESUMO

OBJECTIVE: To find out the prevalence of respiratory syncytial virus (RSV) genotypes in southern Zhejiang Province, China, and to study the genetic characteristics of G protein from subtype A of RSV. METHODS: The lower respiratory tract secretions of children under 5 years of age who were hospitalized for pneumonia and bronchiolitis in three hospitals in southern Zhejiang Province from July 2009 to June 2014 were collected. Direct immunofluorescence assay was used to detect RSV antigens from the collected secretions. A total of 200 samples were randomly selected from RSV-positive specimens in each prevailing year (from July of a specific year to June of the next year). RT-PCR was used to determine RSV subtypes, and the near-full length gene sequence of G protein from subtype A was amplified and sequenced to identify the genotype. RESULTS: A total of 25 449 samples of lower respiratory tract secretions were collected from 2009 to 2014, among which 6 416 (25.21%) samples were RSV-positive. Among the 1 000 RSV-positive specimens randomly sampled, 462 strains (46.2%) were subtype A, and 538 strains (53.8%) were subtype B. Subtype A accounted for 22.5%, 74.5%, 84.5%, 19.0%, and 30.5% of the total strains in each year from 2009 to 2014. A total of 25 RSV subtype A strains were randomly sampled and sent out for bidirectional sequencing in each year, which confirmed 52 positive subtype A strains. Four genotypes of subtype A strains were obtained from the above strains, including NA1 (39 strains), NA4 (1 strain), ON1 (10 strains), and GA2 (2 strains). NA1 was the dominant genotype between 2009 and 2012, and ON1 was the only genotype of subtype A during 2013-2014. The nucleotide homology and amino acid homology between the G protein of subtype A and the prototype strain A2 were 80.7%-89.3% and 74.4%-82.6%, respectively. The nucleotide homology and amino acid homology between the isolates of subtype A were 81.5%-100% and 80.2%-100%, respectively. CONCLUSIONS: In southern Zhejiang Province from 2009 to 2014, there was a co-circulation of RSV subtypes A and B, as well as a co-circulation of several different genotypes of RSV subtype A, which had highly variable G protein genes.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Pré-Escolar , China , Estudos Epidemiológicos , Genótipo , Humanos , Lactente , Recém-Nascido , Filogenia , Infecções por Vírus Respiratório Sincicial/epidemiologia
8.
Oncotarget ; 8(33): 55478-55488, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28903435

RESUMO

BACKGROUND AND AIM: Recent epidemiological studies indicated that metformin might improve the survival of various cancers. However, its benefit on pancreatic cancer was controversial. METHODS: We performed this meta-analysis to investigate the benefit of metformin on pancreatic cancer. A comprehensive literature search was performed through PubMed, Cochrane Library and Embase. Relative risk (RR) and hazard ratio (HR) with 95% confidence interval (CI) were pooled. RESULTS: The meta-analysis of 2 randomized controlled trials including181 pancreatic patients, revealed that metformin use was not associated with an improved overall survival at 6 months (RR=0.90, 95% CI=0.67-1.21), overall survival (HR=1.19, 95% CI=0.86-1.63) and progression-free survival (HR=1.39, 95% CI=0.97-1.99). But the meta-analysis of 8 cohorts, involving 2805 pancreatic patients with diabetes, demonstrated a favorable result with improved overall survival (HR=0.78, 95% CI=0.66-0.92). CONCLUSIONS: Observations in the cohort studies supported a favorable role of metformin while the data from randomized controlled trials did not support that. Therefore, more high-quality RCTs are warranted.

9.
Onco Targets Ther ; 9: 3127-34, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27307753

RESUMO

BACKGROUND: Inflammatory responses play decisive roles in tumor development, immune surveillance, and responses to therapy. High neutrophil-to-lymphocyte ratio (NLR), as an inflammation index, has been reported to be a predictor for poor prognosis of various cancers. The purpose of this meta-analysis was to evaluate the prognostic value of NLR in patients with rectal cancer. METHODS: A comprehensive search of the literature was conducted through PubMed and EMBASE. Pooled hazard ratio (HR) with 95% confidence interval (CI) was used to evaluate the association between NLR and three outcomes: overall survival, disease-free survival, and recurrence-free survival. RESULTS: Seven cohorts involving 959 patients were included in this meta-analysis. Our pooled results demonstrated that elevated NLR was associated with poor overall survival (HR: 13.41, 95% CI: 4.90-36.72), disease-free survival (HR: 4.37, 95% CI: 2.33-8.19), and recurrence-free survival (HR: 3.64, 95% CI: 1.88-7.05). CONCLUSION: An elevated NLR is a valuable and easily available prognostic marker for rectal cancer. It is associated with unfavorable overall survival, disease-free survival, and recurrence-free survival. NLR could be a useful candidate factor for making treatment decisions for individual patients with rectal cancer.

10.
PLoS One ; 11(6): e0157259, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27295210

RESUMO

BACKGROUND: Fecal microbiota transplantation (FMT) has been recognized as a novel treatment for ulcerative colitis (UC). However, its efficacy and safety remain unclear. OBJECTIVE: We conducted this systematic review to assess the efficacy and safety of FMT in UC. DATA SOURCES: PubMed, EMBASE, Cochrane Central, Web of Science Core Collection, and three other Chinese databases were searched for reports of FMT in UC with clear outcomes. DATA EXTRACTION AND SYNTHESIS: We estimated pooled rates [with 95% confidence interval (CI)] of clinical remission among 15 cohort studies and clinical response among 16 cohort studies. RESULTS: Twenty five studies (2 randomized controlled trials, 15 cohort studies, and 8 case studies) with 234 UC patients were included. Overall, 41.58% (84/202) patients achieved clinical remission (CR) and 65.28% (126/193) achieved clinical response. Among the cohort studies, the pooled estimate of patients who achieved CR and clinical response were 40.5% (95% CI 24.7%-58.7%), and 66.1% (95% CI 43.7%-83.0%). Most adverse events were slight and self-resolving. The analyses of gut microbiota in 7 studies showed that FMT could increase microbiota diversity and richness, similarity, and certain change of bacterial composition. CONCLUSION: FMT provides a promising effect for UC with few adverse events. Successful FMT may be associated with an increase in microbiota diversity and richness, similarity, and certain change of bacterial composition.


Assuntos
Colite Ulcerativa/microbiologia , Colite Ulcerativa/terapia , Transplante de Microbiota Fecal/efeitos adversos , Transplante de Microbiota Fecal/métodos , Microbioma Gastrointestinal , Fezes/microbiologia , Humanos , Indução de Remissão , Resultado do Tratamento
11.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(12): 3416-21, 2015 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-26964221

RESUMO

At field scale, surface soil had special characteristics of volumetric moisture content (VMC) with a relatively little difference and spatial heterogeneity induced by physical and chemical properties, roughness, straw residues, etc. It has been a great challenge for near infrared diffuse reflectance spectroscopy (NIR-DRS) measurement of surface soil moisture in situ. In this study, exonential decay models based on seven water-related wavelengths (1200, 1400, 1450, 1820, 1940, 2000 and 2250 nm), linear models of normalized difference soil moisture index (NSMI) and relative absorption depth (RAD) based on wave-length combinations, linear or quadratic model of width of the inflection (σ), center amplitude of the function (Rd) and area under the Gaussian curve (A) from soil moisture Gaussian model (SMGM), and partial least square (PLS) regression models based on bands were used to quantify VMC. The results indicated that (1) of all the single wavelengths, 2 000 nm showed the best validation result, indicated by the lowest RMSEp (2.463) and the highest RPD value (1.060). (2) Comparing with RAD, the validation of NSMI was satisfactory with higher R² (0.312), lower RMSEp (2.133) and higher RPD value (1.224). (3) In the validation results of SMGM parameters and PLS fitting, Rd was found to produce the best fitting quality identified by the highest R² (0.253), the lowest RMSEp (2.222), and the highest RPD value (1.175). (4) Comprehensively, a linear model based on NSMI showed the highest validation accuracy of all the methods. What is more, its calculation process is simple and easy to operate, and therefore become the preferred method to quantify surface soil moisture content in situ.

12.
Guang Pu Xue Yu Guang Pu Fen Xi ; 29(8): 2075-8, 2009 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-19839311

RESUMO

In the present work, 111 soil samples from 11 different Chinese apple plant areas were used to take the diffuse reflection spectra from 12 500 to 4 000 cm(-1) by FT-NIR. The models of organic substance and pH value of soil samples were built by using partial least square regression (PLSR). The calibration model gave the correlation coefficients of 0.818 and 0.836 for the two values respectively, with the root mean square error of prediction (RMSEP) of 0.377 (%) and 0.251, respectively. In order to improve the robustness and performance of calibration, several spectra preprocessing methods were employed, including standard normalized variate (SNV), multiplicative scatter correction (MSC) and direct orthogonal signal correction (DOSC). Finally, the performance of DOSC was found to be the best for organic substance and pH value with RMSEP of 0.258 (%) an 0.248, respectively. The results showed that the technology of NIR spectroscopy was useful to nondestructive determination of the organic substance and pH value of soil. These research findings provide theoretic base for fertilization and pomiculture by means of NIR diffuse reflection.


Assuntos
Agricultura/métodos , Solo/química , Espectroscopia de Luz Próxima ao Infravermelho , Calibragem , Concentração de Íons de Hidrogênio , Análise dos Mínimos Quadrados , Malus
13.
Guang Pu Xue Yu Guang Pu Fen Xi ; 29(11): 2934-8, 2009 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-20101957

RESUMO

In the present study, 22 certified milk samples without melamine were collected, then 50 adulterated milk samples with added different content of melamine (0.1-1 500 mg x kg(-1)) were prepared. The near-infrared (NIR) spectra of these milk samples were measured. The possibility of using NIR spectra to detect melamine in milk was studied. Partial least square regression (PLSR) was applied to construct the calibration model between NIR spectra and the content of melamine. The results showed that NIR spectroscopy can not accurately predict the content of melamine because of its poor detection limit. However, the combination of NIR spectra and partial least square-discriminate analysis (PLS-DA) was applied to differentiate the certified milk samples and the adulterated milk sample. The classification accuracy was 100%. Therefore, NIR spectra could be used to preliminarily detect whether the milk was adulterated with melamine. As a complementary detecting method to the high performance liquid chromatography (HPLC), NIR spectra could improve the detecting efficiency of milk


Assuntos
Contaminação de Alimentos/análise , Leite , Espectroscopia de Luz Próxima ao Infravermelho , Triazinas/análise , Animais , Análise dos Mínimos Quadrados
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