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1.
BMC Geriatr ; 19(1): 214, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31390985

RESUMO

BACKGROUND: Hearing loss is one of the most common modifiable factors associated with cognitive and functional decline in geriatric populations. An accurate, easy-to-apply, and inexpensive hearing screening method is needed to detect hearing loss in community-dwelling elderly people, intervene early and reduce the negative consequences and burden of untreated hearing loss on individuals, families and society. However, available hearing screening tools do not adequately meet the need for large-scale geriatric hearing detection due to several barriers, including time, personnel training and equipment costs. This study aimed to propose an efficient method that could potentially satisfy this need. METHODS: In total, 1793 participants (≥60 years) were recruited to undertake a standard audiometric air conduction pure tone test at 4 frequencies (0.5-4 kHz). Audiometric data from one community were used to train the decision tree model and generate a pure tone screening rule to classify people with or without moderate or more serious hearing impairment. Audiometric data from another community were used to validate the tree model. RESULTS: In the decision tree analysis, 2 kHz and 0.5 kHz were found to be the most important frequencies for hearing severity classification. The tree model suggested a simple two-step screening procedure in which a 42 dB HL tone at 2 kHz is presented first, followed by a 47 dB HL tone at 0.5 kHz, depending on the individual's response to the first tone. This approach achieved an accuracy of 91.20% (91.92%), a sensitivity of 95.35% (93.50%) and a specificity of 86.85% (90.56%) in the training dataset (testing dataset). CONCLUSIONS: A simple two-step screening procedure using the two tones (2 kHz and 0.5 kHz) selected by the decision tree analysis can be applied to screen moderate-to-profound hearing loss in a community-based geriatric population in Shanghai. The decision tree analysis is useful in determining the optimal hearing screening criteria for local elderly populations. Implanting the pair of tones into a well-calibrated sound generator may create a simple, practical and time-efficient screening tool with high accuracy that is readily available at healthcare centers of all levels, thereby facilitating the initiation of extensive nationwide hearing screening in older adults.

2.
Biomed Pharmacother ; 114: 108856, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30981109

RESUMO

Patient survival time generally reflects the tumor progression and represents a key clinical parameter. In this study, we aimed to comprehensively characterize the prognosis-associated molecular alterations in hepatocellular carcinoma (HCC). In this study, copy-number changes, gene mutations, mRNA expression, and reverse phase protein arrays data in HCC samples profiled by The Cancer Genome Atlas (TCGA) were obtained. Tumors were then stratified into two groups based on the clinical outcome and identified genomic, transcriptomic, and proteomic traits associated to HCC prognosis. We found that several copy number amplifications and deletions can discriminate HCC patients with poor prognosis from those with better prognosis. Mutated DNAH8 showed a worse prognosis-specific pattern and correlated with a reduced disease-free survival in HCC. By integrating RNA sequencing data, we found that HCC samples with poor prognosis are consistently associated with the up-regulation of cell cycle process, such as chromosome separation, DNA replication, cytokinesis, and etc. At the proteomic level, seven proteins were significantly enriched in samples with poor prognosis, including acetylated α-Tubulin, p62-LCK-ligand, ARID1 A, MSH6, B-Raf, Cyclin B1, and PEA15. Acetylated α-Tubulin was frequently expressed in HCC tissues and acted as a promising prognostic factor for HCC. These alterations lay a foundation for developing relevant therapeutic strategies and improve our knowledge of the pathogenesis of HCC.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/genética , Transcriptoma/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Ciclo Celular/genética , Progressão da Doença , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Genômica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteômica/métodos
3.
J Cell Biochem ; 120(6): 10205-10214, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30592329

RESUMO

Solute carrier 34 A2 (SLC34A2) is a member of SLC34 family that is a group of phosphate transporters. SLC34A2 has been reported to play critical roles in tumorigenesis and progression. However, the researches about the biological roles of SLC34A2 in glioma have not yet been reported. In this study, we analyzed the expression patterns of SLC34A2 in clinical glioma tumor tissues and cell lines. The results demonstrated that SLC34A2 was generally overexpressed in both glioma tissues and cell lines. To further investigate the roles of SLC34A2 in glioma, lentivirus containing specific SLC34A2 short hairpin RNA (sh-SLC34A2) was used to infect glioma cell lines U251 and U87 for the knockdown of SLC34A2. The following studies proved that SLC34A2 knockdown exhibited suppressive effects on cell proliferation and migration/invasion. SLC34A2 knockdown also inhibited epithelial-mesenchymal transition (EMT) phenotype, as evidenced by the increased E-cadherin expression, and the decreased N-cadherin and fibronectin expressions. Besides, knockdown of SLC34A2 enhanced the temozolomide (TMZ) sensitivity of U251 and U87 cells. In vivo tumorigenicity assay demonstrated that SLC34A2 knockdown inhibited tumor growth. Moreover, SLC34A2 knockdown suppressed the activation of epidermal growth factor receptor (EGFR)/PI3K/AKT signaling pathway in U87 cells. GW2974 (EGFR inhibitor) increased SLC34A2 knockdown-inhibited cell proliferation, migration/invasion, as well as enhanced SLC34A2 knockdown-increased the TMZ sensitivity of glioma cells. These findings suggested that SLC34A2 might be a new potential therapeutic target for the therapy of glioma patients.

4.
EBioMedicine ; 39: 472-483, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30527625

RESUMO

BACKGROUND: Accumulating evidence has revealed the pivotal role of epigenetic regulation in the pathogenesis of liver disease. However, the epigenetic mechanism that accounts for hepatic stellate cells (HSCs) activation in liver fibrosis remains largely unknown. METHODS: Primary HSCs were used to screen the differentially expressed histone H3 lysine methyltransferases and demethylases during HSC activation. Loss-of-function experiments were applied to determine the cellular functions of KDM4D in HSCs. Transcriptome analysis was applied to explore the downstream targets of KDM4D. Real-time qPCR, western blotting, immunohistochemical staining, and chromatin immunoprecipitation were performed to uncover the underlying mechanism concerning KDM4D during liver fibrogenesis. FINDINGS: KDM4D was identified as a remarkable up-regulated histone H3 demethylase during HSC activation. The overexpression profile of KDM4D was confirmed in three fibrosis animal models and human fibrotic liver tissues. In vitro Kdm4d knockdown impaired the collagen gel contraction and migration capacity of primary HSCs. In established CCl4-induced mice model, Kdm4d knockdown inhibited fibrosis progression, and promoted fibrosis reversal, with enhanced thinning and splitting of fibrotic septa, as well as a dramatic decrease in collagen area. Whole gene transcriptome analysis showed the regulatory role of KDM4D in Toll-Like Receptor (TLR) signaling pathway. Mechanistically, KDM4D catalyzed histone 3 on lysine 9 (H3K9) di-, and tri-demethylation, which promoted TLR4 expression, and subsequently prompted liver fibrogenesis by activating NF-κB signaling pathways. INTERPRETATION: KDM4D facilitates TLR4 transcription through demethylation of H3K9, thus activating TLR4/NF-κB signaling pathways in HSCs, contributing to HSC activation and collagen crosslinking, further, hepatic fibrosis progression. FUND: Shanghai New Hundred Talents Program, Shanghai Municipal Commission of Health and Family Planning, Key Developing Disciplines Program, Shanghai Key disciplines program of Health and Family Planning and Shanghai Sailing Program.


Assuntos
Tetracloreto de Carbono/efeitos adversos , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Cirrose Hepática/patologia , Tioacetamida/efeitos adversos , Receptor 4 Toll-Like/genética , Animais , Linhagem Celular , Epigênese Genética , Redes Reguladoras de Genes , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Histonas/metabolismo , Humanos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Masculino , Camundongos , Ratos , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Transcrição Genética , Regulação para Cima
5.
Mikrochim Acta ; 185(11): 507, 2018 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-30338341

RESUMO

This paper describes the synthesis of fluorescent copper nanoclusters (CuNC) with a fluorescence quantum yield as high as 2.3% after modification with cysteamine. The modified CuNC are shown to be viable probes for the determination of picric acid (PA). Fluorescence drops with increasing concentration of PA which can be detected fluorometrically with a 0.14 µM limit of detection. This is much lower than required by the People's Republic of China Surface Water Environmental Quality Standard (2.2 µM). The probe was successfully applied to the determination of PA in spiked tap water, lake water and river water. Graphical abstract Copper nanoclusters (CuNC) have weak fluorescence but after the modification with cysteamine, the fluorescence of CuNC is strongly enhanced. The fluorescence of such cysteamine-coated copper nanoclusters (CuNC-CA) is reduced upon the addition of picric acid (PA) through an inner filter effect (IFE).

6.
Mikrochim Acta ; 185(11): 511, 2018 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-30343449

RESUMO

A ratiometric probe is described for the fluorometric determination of Cu(II) ions based on their quenching effect on the luminescence of dually-emitting quantum dots (QDs). ZnS QDs were doped with Mn(II) and subsequently modified with mercaptopropionic acid to give the QD probe which consists of a  sole fluorophore but has two emission peaks (at 430 and 590 nm under 310 nm excitation, respectively). On addition of Cu(II) ions, the 590 nm band is quenched while the 430 nm band exhibits a little change. The changes in the intensity ratios of the yellow and the purple bands increases linearly in the 0 to 3.0 µM Cu(II) concentration range, and the detection limit reached 14 nM. The QD probe was validated and successfully applied to the determination of Cu(II) in spiked real water samples. Graphical abstract Mn-doped ZnS (ZnS:Mn(II)) quantum dots were synthesized with yellow fluorescence. After the modification of 3-mercaptopropionic acid (MPA), ZnS:Mn(II) was transferred to aqueous phase and became MPA modified Mn-doped ZnS (MPA- ZnS:Mn(II)). The fluorescence was changed to purple upon the addition of copper ions because the yellow band was largely quenched while the purple band only changed a little.

7.
ACS Omega ; 3(3): 2855-2864, 2018 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30221223

RESUMO

Herein, we developed a natural surface-enhanced Raman scattering (SERS) substrate based on size-tunable Au@Ag nanoparticle-coated mussel shell to form large-scale three-dimensional (3D) supercrystals (up to 10 cm2) that exhibit surface-laminated structures and crossed nanoplates and nanochannels. The high content of CaCO3 in the mussel shell results in superior hydrophobicity for analyte enrichment, and the crossed nanoplates and nanochannels provided rich SERS hot spots, which together lead to high sensitivity. Finite-difference time-domain simulations showed that nanoparticles in the channels exhibit apparently a higher electromagnetic field enhancement than nanoparticles on the platelets. Thus, under optimized conditions (using Au@AgNPs with 5 nm shell thickness), highly sensitive SERS detection with a detection limit as low as 10-9 M for rhodamine 6G was obtained. Moreover, the maximum electromagnetic field enhancement of different types of 3D supercrystals shows no apparent difference, and Au@AgNPs were uniformly distributed such that reproducible SERS measurements with a 6.5% variation (613 cm-1 peak) over 20 spectra were achieved. More importantly, the as-prepared SERS substrates can be utilized for the fast discrimination of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa by discriminant analysis. This novel Au@Ag self-assembled mussel shell template holds considerable promise as low-cost, durable, sensitive, and reproducible substrates for future SERS-based biosensors.

8.
Gut Pathog ; 10: 37, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30214488

RESUMO

Background: Culture-based diagnostic methods cannot achieve rapid and precise diagnoses for the identification of multiple diarrhoeal pathogens (DPs). A high-throughput multiplex genetic detection system (HMGS) was adapted and evaluated for the simultaneous identification and differentiation of infectious DPs and a broad analysis of DP infection aetiology. Results: DP-HMGS was highly sensitive and specific for DP detection compared with culture-based techniques and was similar to singleplex real-time PCR. The uniform level of sensitivity of DP-HMGS for all DPs allowed us to remap the aetiology of acute diarrhoeal infections in Shanghai, correcting incidences of massively underdiagnosed DP species with accuracy approaching that of sequencing-based methods. The most frequent DPs were enteropathogenic Escherichia coli, rotavirus and Campylobacter jejuni. DP-HMGS detected two additional causes of infectious diarrhoea that were previously missed by routine culture-based methods: enterohemorrhagic E. coli and Yersinia enterocolitica. We demonstrated the age dependence of specific DP distributions, especially the distributions of rotavirus, intestinal adenovirus and Clostridium difficile in paediatric patients as well as those of dominant bacterial infections in adults, with a distinct "top 3" pattern for each age group. Finally, the multiplexing capability and high sensitivity of DP-HMGS allowed the detection of infections co-induced by multiple pathogens (approximately 1/3 of the cases), with some DPs preferentially co-occurring as infectious agents. Conclusions: DP-HMGS has been shown to be a rapid, specific, sensitive and appropriate method for the simultaneous screening/detection of polymicrobial DP infections in faecal specimens. Widespread use of DP-HMGS is likely to advance routine diagnostic and clinical studies on the aetiology of acute diarrhoea.

10.
PeerJ ; 6: e5145, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29967757

RESUMO

Objective: This study was undertaken to detect if free fatty acids (FFA) induce hepatocyte senescence in L-02 cells and if huperzine A has an anti-aging effect in fatty liver cells. Methods: L-02 cells were treated with a FFA mixture (oleate/palmitate, at 3:0, 2:1, 1:1, 1:2 and 0:3 ratios) at different concentrations. Cell viability and fat accumulation rate were assessed by a Cell Counting Kit 8 and Nile Red staining, respectively. The mixture with the highest cell viability and fat accumulation rate was selected to continue with the following experiment. The L-02 cells were divided into five groups, including the control group, FFA group, FFA + 0.1 µmol/L huperzine A (LH) group, FFA + 1.0 µmol/L huperzine A (MH) group and FFA + 10 µmol/L huperzine A (HH) group, and were cultured for 24 h. The expression of senescence-associated ß-galactosidase (SA-ß-gal) was detected by an SA-ß-gal staining kit. The expression levels of aging genes were measured by qRT-PCR. The expression levels of apoptosis proteins were detected by a Western blot. ELISA kits were used to detect inflammatory factors and oxidative stress products. The expression of nuclear factor (NF-κB) and IκBα were detected by immunofluorescence. Results: The FFA mixture (oleate/palmitate, at a 2:1 ratio) of 0.5 mmol/L had the highest cell viability and fat accumulation rate, which was preferable for establishing an in vitro fatty liver model. The expression of inflammatory factors (TNF-α and IL-6) and oxidants Malonaldehyde (MDA), 4-hydroxynonenal (HNE) and reactive oxygen species (ROS) also increased in the L-02 fatty liver cells. The expression levels of aging markers and aging genes, such as SA-ß-gal, p16, p21, p53 and pRb, increased more in the L-02 fatty liver cells than in the L-02 cells. The total levels of the apoptosis-associated proteins Bcl2, Bax, Bax/Bcl-2, CyCt and cleaved caspase 9 were also upregulated in the L-02 fatty liver cells. All of the above genes and proteins were downregulated in the huperzine A and FFA co-treatment group. In the L-02 fatty liver cells, the expression of IκBα decreased, while the expression of NF-κB increased. After the huperzine A and FFA co-treatment, the expression of IκBα increased, while the expression of NF-κB decreased. Conclusion: Fatty liver cells showed an obvious senescence and apoptosis phenomenon. Huperzine A suppressed hepatocyte senescence, and it might exert its anti-aging effect via the NF-κB pathway.

11.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 34(1): 9-15, 2018 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-29595451

RESUMO

Objective To investigate the expression of leucine rich repeats and immunoglobulin like domains 1 (LRIG1) in the tumor tissues of human pituitary tumor, and the effects of LRIG1 over-expression on the proliferation and apoptosis of human pituitary tumor cells induced by cisplatin (DDP). Methods The expression of LRIG1 in the tumor tissues and adjacent tissues of 45 cases with pituitary tumor was detected by immunohistochemistry, and the correlations between the positive expression of LRIG1 and the clinicopathological data of the patients were analyzed. In addition, the isolated human pituitary tumor cells were selected. The LRIG1 gene over-expression plasmid pEGFP-N1-LRIG1 was transfected into the cells by liposome-mediated gene transfection. The cells transfected with LRIG1 were screened, and meanwhile, the cells transfected with empty plasmid pEGFP-N1 were selected as a control group. The cells of the two groups were induced by 20 g/mL DDP, and 48 hours later, the cell apoptosis was detected by flow cytometry; the proliferation capacity was tested by plate cloning experiment; and the relative expressions of apoptosis-related proteins Bax, caspase-3 and Bcl2 in the cells were examined by Western blot analysis. Results LRIG1 in the tumor tissues of pituitary tumor was obviously lower than that of the adjacent tissues, and LRIG1 was significantly reduced in the invasive tumor tissues. Compared with the control group, after LRIG1 was over-expressed, the cell apoptosis rate significantly increased, the cell proliferation significantly decreased, and the levels of Bax and caspase-3 increased as well, while the level of Bcl2 decreased remarkably. Conclusion Over-expression of LRIG1 increases the apoptosis and inhibits the proliferation of human pituitary tumor cells induced by DDP.


Assuntos
Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , Glicoproteínas de Membrana/fisiologia , Neoplasias Hipofisárias/tratamento farmacológico , Humanos , Neoplasias Hipofisárias/patologia , Proteínas Proto-Oncogênicas c-bcl-2/análise
12.
Cancer Lett ; 420: 26-37, 2018 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-29409972

RESUMO

Obesity is a major risk factor for hepatocellular carcinoma (HCC) and is typically accompanied by higher levels of serum dipeptidyl peptidase 4 (DPP4). However, the role of DPP4 in obesity-promoted HCC is unclear. Here, we found that consumption of a high-fat diet (HFD) promoted HCC cell proliferation and metastasis and led to poor survival in a carcinogen-induced model of HCC in rats. Notably, genetic ablation of DPP4 or treatment with a DPP4 inhibitor (vildagliptin) prevented HFD-induced HCC. Moreover, HFD-induced DPP4 activity facilitated angiogenesis and cancer cell metastasis in vitro and in vivo, and vildagliptin prevented tumor progression by mediating the pro-angiogenic role of chemokine ligand 2 (CCL2). Loss of DPP4 effectively reversed HFD-induced CCL2 production and angiogenesis, indicating that the DPP4/CCL2/angiogenesis cascade had key roles in HFD-associated HCC progression. Furthermore, concomitant changes in serum DPP4 and CCL2 were observed in 210 patients with HCC, and high serum DPP4 activity was associated with poor clinical prognosis. These results revealed a link between obesity-related high serum DPP4 activity and HCC progression. Inhibition of DPP4 may represent a novel therapeutic intervention for patients with HCC.

13.
PLoS One ; 13(1): e0191485, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29352300

RESUMO

Obesity is associated with a series of metabolic complications, including dyslipidemia and insulin resistance (IR) that lack effective therapies. In recent years, intestinal inflammation has been suggested to contribute to obesity related metabolic syndrome and targeting gut inflammation with 5-ASA improves diet induced IR, however, its role in dyslipidemia is unknown and has never been explored. In the present study, we reported for the first time that administration of 5-ASA for 12 weeks significantly improved lipid profile by repressing plasma triglycerides and free cholesterol levels in mice fed high-fat cholesterol diet (HFC). In addition, liver lipids were significantly reduced by 5-ASA treatment in HFC-fed mice. Mechanistically, anti-inflammatory genes peroxisome proliferator-activated receptor-γ (Pparγ) and M2 marker, such as Mrc1 and Ym1, were remarkably upregulated, while pro-inflammation gene monocyte chemoattractant protein-1 (Mcp-1) were downregulated in small intestine of mice treated by 5-ASA. Further, 5-ASA improved gastrointestinal barrier by increasing the expression of the tight junction marker ZO-1. 5-ASA also enhanced cholesterol translocation by elevating genes expression of Npc1l1 and Abcg5/8. Moreover, mice fed HFC 5-ASA expressed increased Pparα in small intestinal and its target genes function in lipid oxidation and hydrolysis were remarkable elevated. Taken together, we reported a novel role of 5-ASA which may serve as a therapy target intestinal inflammation induced dyslipidemia.


Assuntos
Colesterol na Dieta/administração & dosagem , Dieta Hiperlipídica/efeitos adversos , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Mesalamina/farmacologia , PPAR alfa/metabolismo , PPAR gama/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Dislipidemias/tratamento farmacológico , Dislipidemias/genética , Dislipidemias/metabolismo , Ácidos Graxos/metabolismo , Hipolipemiantes/farmacologia , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/metabolismo , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , PPAR gama/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
14.
Oncol Lett ; 13(5): 3379-3386, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28521443

RESUMO

Previous studies have investigated the mechanisms of immune evasion of tumor cells in numerous types of advanced solid malignant tumor, and several types of immune preparations have been administered as antitumor adjuvant therapies. However, in the majority of studies, the efficacy of therapies has been revealed to be limited. The present study aimed to investigate the immune evasion mechanisms employed by early colorectal cancer cells and the expression of the molecules associated with immune evasion during the malignant transformation process of normal colorectal epithelial cells to measure the effects of immune intervention for early colorectal cancer, and to improve the efficacy of immunotherapy. A total of 60 colorectal tissues, including 15 normal mucosa, 15 adenoma, 15 early cancer and 15 advanced cancer tissues, from patients undergoing endoscopic procedures in Huadong Hospital Affiliated to Fudan University (Shanghai, China) were collected. A comparison of baseline characteristics among these four groups was performed. The expression levels of human leukocyte antigen-A (HLA-A), apoptosis antigen 1 (Fas), c-c chemokine receptor type 5 (CCR5), Fas ligand (FasL) and HLA-E in each group were detected by immunohistochemical analysis. Furthermore, 15 patients with advanced colorectal cancer were enrolled into the present study. Advanced cancer and paracancer tissues (normal mucosal tissues 3 cm away from the margin of cancer tissues) were collected from each patient by colonoscopic biopsy. The expression levels of HLA-A, Fas, CCR5, FasL and HLA-E in each group were detected by western blot analysis. During the malignant transformation process of normal colorectal epithelial cells, the expression levels of CCR5, FasL and HLA-E increased significantly (P<0.001), whilst the expression levels of Fas reduced significantly (P=0.0271). In the early cancer group, the expression levels of Fas reduced significantly (P=0.0239), whilst the expression levels of HLA-E increased significantly (P<0.001) compared with adenoma group. In conclusion, a loss of Fas expression and high expression levels of HLA-E may promote the immune evasion of early colorectal cancer cells.

15.
Biomed Pharmacother ; 88: 102-108, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28095354

RESUMO

The heliangin is a natural agent mainly isolated from Helianthus tuberosus L. (Asteraceae). In order to investigate the anti-inflammatory effect of heliangin, several typical models in vivo and in vitro were performed. The RAW264.7 mouse macrophages cells were employed in vitro and dexamethasone were conducted as positive. The cytotoxicity results of heliangin on RAW 264.7 cells provided the safety in vitro for further study. The mRNA of TNF-α, IL-6, iNOS and COX-2 were degraded under heliangin exposure in LPS-stimulated RAW 264.7 cells. The protein expression of iNOS, COX-2 were decreased via heliangin exposure in a dose-dependent manner. Heliangin inhibited TNF-α, NO, IL-6 and PGE2 expression levels in macrophage cells lysate. The immunocytochemistry assay showed the fluorescence image of heliangin treatment intercepted the p65 translocation process from outside to inside of nuclei triggered by LPS. Moreover, we founded that MAPK and NF-κB signaling pathway play important roles in heliangin's activity on RAW264.7 cells. Secondly, the acute toxic study results of heliangin manifested the safety in vivo. Heliangin exerted anti-inflammation effect in a xylene-induced ear swelling in BALB/C mice and carrageenan-induced paw edema model in SD rats. The cytokines levels (TNF-α, IL-6 and PGE2) were decreased. The paw tissue immunochemistry assay demonstrated the IL-6 protein level changes in carrageenan-induced paw edema model under heliangin administration.


Assuntos
Inflamação/tratamento farmacológico , Lactonas/uso terapêutico , Macrófagos/metabolismo , Macrófagos/patologia , NF-kappa B/metabolismo , Sesquiterpenos/uso terapêutico , Transdução de Sinais , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Morte Celular/efeitos dos fármacos , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Dinoprostona/metabolismo , Edema/sangue , Edema/tratamento farmacológico , Edema/patologia , Imuno-Histoquímica , Inflamação/sangue , Inflamação/patologia , Lactonas/química , Lactonas/farmacologia , Lipopolissacarídeos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Células RAW 264.7 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Testes de Toxicidade
16.
Dig Dis Sci ; 62(2): 441-447, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28044230

RESUMO

BACKGROUND: Intestinal Behcet's disease (BD) is a specific subtype of BD. Effective drug therapy for intestinal BD remains elusive. AIMS: To investigate long-term outcomes and identify predictors of sustained response in intestinal BD patients receiving infliximab (IFX) treatment. METHODS: The medical records were reviewed of patients received IFX from September 2012 to March 2016. The cumulative probabilities of sustained response were calculated using the Kaplan-Meier. Predictor factors for sustained response were accessed by receiver operating characteristic curve. RESULTS: Totally, 27 active intestinal BD patients were enrolled. Sustained responses were observed in 17 patients, after a median follow-up duration 24 months (interquartile range 9-37). The proportion of clinical remission at week 14, 30, and 52 had occurred in 84.6, 70, and 70%, respectively, with the proportion of clinical remission of 69.2, 40, and 55%. The mucosal healing (MH) rate at week 14 was 72%. Kaplan-Meier estimated patients with achievement of clinical and biological responses at week 14 or MH was likely to remain sustained clinical response. ROC curve analysis revealed CRP level (of 6.85 mg/L) at week 14 is a potential predictor for discriminating patients with sustained response from relapse, with an area under the curve values of 0.837. CONCLUSIONS: IFX is effective and safe for induction and maintenance therapy in Chinese patients with moderate-to-severe active intestinal BD. Early achievement of clinical response and mucosal healing might associate long-term response. A lower CRP level seems to be associated with a more benign clinical course.


Assuntos
Síndrome de Behçet/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Infliximab/uso terapêutico , Enteropatias/tratamento farmacológico , Corticosteroides/uso terapêutico , Adulto , Síndrome de Behçet/complicações , Síndrome de Behçet/metabolismo , Proteína C-Reativa/metabolismo , China , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/uso terapêutico , Enteropatias/etiologia , Enteropatias/metabolismo , Estimativa de Kaplan-Meier , Quimioterapia de Manutenção , Masculino , Prognóstico , Curva ROC , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
17.
Sci Rep ; 6: 36783, 2016 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-27830836

RESUMO

Nonalcoholic fatty liver disease (NAFLD), a metabolic disorder related to insulin resistance and metabolic syndrome, has become a public health concern. Currently, the principal therapeutic modalities targeting NAFLD are lifestyle interventions. However, the efficacy of long-term lifestyle interventions in managing NAFLD remains largely unexplored. This study aimed to evaluate the efficacy of long-term lifestyle interventions in middle-aged and elderly men with NAFLD. All 280 eligible patients were randomized to the control or test group. Patients in the test group received counseling on diet and exercise from 2 physicians every 3 months via a phone call. Patients in the control group received only counseling in annual checkups without regular intervention. After the 2-year periodic intervention, body weight, abdominal circumference, ALT, TCH, LDL-C and HDL-C decreased in the test group. Specifically, the fatty liver index (FLI) and NAFLD-fibrosis score (NAFLD-FS) reduced markedly in the test group. However, in the control group, there was only a significant decrease in LDL-C, HDL-C and NAFLD-FS (P < 0.001). The liver steatosis grade of the test group decreased significantly, while it increased in the control group. In NAFLD, long-term lifestyle interventions exert an anti-obesity effect and attenuate liver dysfunction and steatosis.


Assuntos
Hepatopatia Gordurosa não Alcoólica/terapia , Comportamentos Relacionados com a Saúde , Humanos , Estilo de Vida , Fígado/diagnóstico por imagem , Fígado/metabolismo , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Resultado do Tratamento
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(5): 1611-1614, 2016 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-27784403

RESUMO

Multiple myeloma (MM), the second common malignant tumor in the blood system, is a kind of B cell malignancy and its prognosis is poor. The diagnosis of MM is mainly based on the number of abnormal plasma cells and the presence of monoclonal protein in the blood or urine, but there are limitations for diagnosis of MM. Multi-parameter flow cytometry analysis is increasingly used in the in the diagnosis of MM. Therefore, this review focuses on characteristics of immunophenotypes of malignant plasma cells and myeloma progenitor cells.


Assuntos
Citometria de Fluxo , Mieloma Múltiplo , Linfócitos B , Contagem de Células , Humanos , Imunofenotipagem , Proteínas do Mieloma , Plasmócitos , Prognóstico
20.
Future Microbiol ; 11: 1521-1534, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27599152

RESUMO

AIM: We evaluated the direct high-throughput multiple genetic detection system (dHMGS) for Helicobacter pylori in gastric biopsies. MATERIALS & METHODS: One hundred and thirty-three specimens were concurrently analyzed by dHMGS, rapid urease test, culture and sequencing. RESULTS: dHMGS was highly sensitive and specific for H. pylori identification compared with culture and rapid urease test. The correlation coefficient of the quantitative standard curve was R2 = 0.983. A significant difference in the relative H. pylori DNA abundance was found in different gastroduodenal diseases. Concordance rates between dHMGS and sequencing for resistance mutations were 97.1, 100.0, 85.3 and 97.1%, respectively. Finally, dHMGS could efficiently distinguish mixed infection in biopsy specimens. CONCLUSION: The dHMGS could efficiently diagnose and quantify H. pylori burden in biopsies, simultaneously screening for virulence, antibiotic resistance and presence of the multistrain infections.


Assuntos
Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biópsia , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Feminino , Infecções por Helicobacter/patologia , Helicobacter pylori/classificação , Helicobacter pylori/genética , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade , Urease/genética , Urease/metabolismo , Adulto Jovem
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