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1.
Nature ; 535(7610): 148-52, 2016 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-27362227

RESUMO

The non-receptor protein tyrosine phosphatase SHP2, encoded by PTPN11, has an important role in signal transduction downstream of growth factor receptor signalling and was the first reported oncogenic tyrosine phosphatase. Activating mutations of SHP2 have been associated with developmental pathologies such as Noonan syndrome and are found in multiple cancer types, including leukaemia, lung and breast cancer and neuroblastoma. SHP2 is ubiquitously expressed and regulates cell survival and proliferation primarily through activation of the RAS­ERK signalling pathway. It is also a key mediator of the programmed cell death 1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) immune checkpoint pathways. Reduction of SHP2 activity suppresses tumour cell growth and is a potential target of cancer therapy. Here we report the discovery of a highly potent (IC50 = 0.071 µM), selective and orally bioavailable small-molecule SHP2 inhibitor, SHP099, that stabilizes SHP2 in an auto-inhibited conformation. SHP099 concurrently binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thus inhibiting SHP2 activity through an allosteric mechanism. SHP099 suppresses RAS­ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells in vitro and is efficacious in mouse tumour xenograft models. Together, these data demonstrate that pharmacological inhibition of SHP2 is a valid therapeutic approach for the treatment of cancers.


Assuntos
Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Piperidinas/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/antagonistas & inibidores , Pirimidinas/farmacologia , Receptores Proteína Tirosina Quinases/metabolismo , Regulação Alostérica/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Concentração Inibidora 50 , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Camundongos Nus , Modelos Moleculares , Neoplasias/patologia , Proteína Oncogênica p21(ras)/metabolismo , Piperidinas/química , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Estabilidade Proteica/efeitos dos fármacos , Estrutura Terciária de Proteína/efeitos dos fármacos , Proteína Tirosina Fosfatase não Receptora Tipo 11/química , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Pirimidinas/química , Pirimidinas/uso terapêutico , Reprodutibilidade dos Testes , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Crit Rev Eukaryot Gene Expr ; 31(1): 1-9, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33639050

RESUMO

We investigated expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and endoglin (CD105) in renal cell carcinoma (RCC), and its potential role in predicting tumor growth and progression. A total of 47 RCC specimens and 15 adjacent normal kidney tissues were obtained. Expression of CEACAM1 and CD105 was assessed by immunohistochemistry. Microvessel density (MVD) was counted under the microscope by labeling the endothelial cells with biomarker CD34. The positivity of CEACAM1 expression in RCC (42.6%) was significantly lower than that in the normal kidney (73.%, P = 0.038). In contrast, the positivity of CD105 expression was significantly higher in RCC (78.7%) compared to that in the normal kidney (46.7%, P = 0.017). The expression level of CD105 in 47 RCC patients was significantly associated with the clinical stages of RCC (P < 0.05) but not with gender, age, tumor size, or histologic grade. Average MVD in RCC (78.05 ± 16.57) was significantly higher than that in normal tissue (43.62 ± 12.37, P < 0.05), and was significantly higher in RCC patients with advanced histologic grades (P < 0.05) or clinical stages (P < 0.01). In addition, MVD was significantly correlated with CD105 but negatively correlated with CEACAM1. Our findings suggest that down-regulation of CEACAM1 may promote angiogenesis in RCC, and that up-regulation of CD105 may promote RCC progress. MVD may be an indicator of RCC malignancy.


Assuntos
Antígenos CD/metabolismo , Carcinoma de Células Renais/metabolismo , Moléculas de Adesão Celular/metabolismo , Endoglina/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/metabolismo , Densidade Microvascular , Antígenos CD34/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/patologia , Progressão da Doença , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Humanos , Imuno-Histoquímica/métodos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Neovascularização Patológica/metabolismo , Prognóstico
3.
Nat Chem Biol ; 15(2): 179-188, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30643281

RESUMO

The identification of activating mutations in NOTCH1 in 50% of T cell acute lymphoblastic leukemia has generated interest in elucidating how these mutations contribute to oncogenic transformation and in targeting the pathway. A phenotypic screen identified compounds that interfere with trafficking of Notch and induce apoptosis via an endoplasmic reticulum (ER) stress mechanism. Target identification approaches revealed a role for SLC39A7 (ZIP7), a zinc transport family member, in governing Notch trafficking and signaling. Generation and sequencing of a compound-resistant cell line identified a V430E mutation in ZIP7 that confers transferable resistance to the compound NVS-ZP7-4. NVS-ZP7-4 altered zinc in the ER, and an analog of the compound photoaffinity labeled ZIP7 in cells, suggesting a direct interaction between the compound and ZIP7. NVS-ZP7-4 is the first reported chemical tool to probe the impact of modulating ER zinc levels and investigate ZIP7 as a novel druggable node in the Notch pathway.


Assuntos
Proteínas de Transporte de Cátions/genética , Estresse do Retículo Endoplasmático/fisiologia , Receptor Notch1/genética , Animais , Apoptose , Proteínas de Transporte/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Proteínas de Transporte de Cátions/fisiologia , Linhagem Celular , Transformação Celular Neoplásica , Retículo Endoplasmático/fisiologia , Humanos , Mutação , Transporte Proteico , Receptor Notch1/fisiologia , Transdução de Sinais , Zinco/metabolismo
4.
Hum Psychopharmacol ; 36(5): e2790, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33856697

RESUMO

BACKGROUND: Patients with schizophrenia have an increased prevalence of type 2 diabetes mellitus that has shown a significant association with the rs7754840 polymorphism in the gene encoding the cyclin-dependent kinase 5 (CDK5) regulatory subunit-associated protein 1-like 1 (CDKAL1). OBJECTIVE: To examine whether this polymorphism was involved in the susceptibility in first-episode drug-naive schizophrenic patients (FDSP), and further influenced their clinical symptoms. METHODS: This polymorphism was genotyped in 239 FDSP and 368 healthy controls. The clinical symptoms in FDSP were assessed using the Positive and Negative Syndrome Scale (PANSS) five-factor models. RESULTS: There was no significant difference in the allelic and genotypic frequencies of this polymorphism between two groups (both p > 0.05) after adjusting for covariates. However, the PANSS depressive score significantly differed by genotype in FDSP after adjusting for covariates (F = 5.25, p = 0.006). This significant difference also persisted after Bonferroni correction (p < 0.05). FDSP with C/C genotype had significantly higher PANSS depressive score than those with C/G genotype (p = 0.007) and those with G/G genotype (p = 0.005). Moreover, further stepwise multivariate regression analysis showed the significant association between the rs7754840 polymorphism and PANSS depressive score in FDSP (ß = -1.07, t = -2.75, p = 0.007). CONCLUSIONS: Our findings demonstrated that although the CDKAL1 rs7754840 polymorphism did not contribute to the susceptibility to FDSP, it might be implicated in depressive symptoms in this patient group.


Assuntos
Depressão , Diabetes Mellitus Tipo 2 , Esquizofrenia , Depressão/complicações , Depressão/genética , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único/genética , Esquizofrenia/complicações , Esquizofrenia/genética , tRNA Metiltransferases/genética
5.
Knowl Based Syst ; 2332021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36059387

RESUMO

We introduce a new classifier for small-sample image data based on a two-dimensional discriminative regression approach. For a test example, our method estimates a discriminative representation from training examples, which accounts for discriminativeness between classes and enables accurate derivation of categorical information. Unlike existing methods that vectored image data, the learning of the representation in our method is performed with the two-dimensional features of the data, and thus inherent spatial information of the data is fully exploited. This new type of two-dimensional discriminative regression, different from existing regression models, allows for building a highly effective and robust classifier for image data through explicitly incorporating discriminative information and inherent spatial information. We compare our method with several state-of-the-art classifiers of small-sample images and experimental results show superior performance of the proposed method in classification accuracy as well as robustness to noise corruption.

6.
EMBO Rep ; 19(9)2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30126924

RESUMO

Autophagy maintains cellular homeostasis by targeting damaged organelles, pathogens, or misfolded protein aggregates for lysosomal degradation. The autophagic process is initiated by the formation of autophagosomes, which can selectively enclose cargo via autophagy cargo receptors. A machinery of well-characterized autophagy-related proteins orchestrates the biogenesis of autophagosomes; however, the origin of the required membranes is incompletely understood. Here, we have applied sensitized pooled CRISPR screens and identify the uncharacterized transmembrane protein TMEM41B as a novel regulator of autophagy. In the absence of TMEM41B, autophagosome biogenesis is stalled, LC3 accumulates at WIPI2- and DFCP1-positive isolation membranes, and lysosomal flux of autophagy cargo receptors and intracellular bacteria is impaired. In addition to defective autophagy, TMEM41B knockout cells display significantly enlarged lipid droplets and reduced mobilization and ß-oxidation of fatty acids. Immunostaining and interaction proteomics data suggest that TMEM41B localizes to the endoplasmic reticulum (ER). Taken together, we propose that TMEM41B is a novel ER-localized regulator of autophagosome biogenesis and lipid mobilization.


Assuntos
Autofagia/fisiologia , Mobilização Lipídica/fisiologia , Proteínas de Membrana/genética , Proteínas de Membrana/fisiologia , Autofagossomos/metabolismo , Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Proteína 9 Associada à CRISPR/metabolismo , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/fisiologia , Retículo Endoplasmático/metabolismo , Ácidos Graxos/metabolismo , Técnicas de Inativação de Genes , Células HeLa , Homeostase , Humanos , Lentivirus , Gotículas Lipídicas/metabolismo , Mobilização Lipídica/genética , Lisossomos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo
7.
Eur Arch Otorhinolaryngol ; 276(11): 3131-3138, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31456038

RESUMO

OBJECTIVE: We investigated the correlation between the expression of IL-17A in nasopharyngeal carcinoma tissues and cells and the occurrence and development of NPC was also investigated. METHODS: Forty-five NPC biopsy specimens from January 2014 to January 2016 were selected. Forty-five NPC tissue specimens and 45 chronic nasopharyngitis tissue samples were detected by immunohistochemistry. Statistical methods were used to analyze the correlation between IL-17A expression and the clinicopathological variables of NPC. The NPC patients were followed up. The levels of IL-17A mRNA in 40 NPC tissue specimens and 45 chronic nasopharyngitis tissue samples were detected by real-time PCR. IL-17A expression in 15 NPC tissue specimens and chronic nasopharyngitis tissue samples was further detected by Western blotting assays. RESULTS: IL-17A expression in NPC tissues was significantly higher than that of chronic nasopharyngitis tissues (P < 0.05). IL-17A was expressed in the nucleus and cytoplasm of both NPC tissues and chronic nasopharyngitis tissues. Stage III + IV NPC, tumor volume ≥ 50 mm, and hepatic envelope invasion and cervical lymph node metastasis were associated with significantly higher IL-17A levels versus stage I + II NPC, tumor size < 50 mm, no membrane invasion and lack of cervical lymph node metastasis (P < 0.05). IL-17A was statistically associated with tissue differentiation, serum EBV-lgA levels, and EBV infection. IL-17A-positive patients had significantly longer median survival versus IL-17A-negative patients (21.0 vs. 13.0 months, log-rank test: P < 0.05). Furthermore, 65% (26/40) of NPC tissue samples had significantly higher IL-17A mRNA levels than chronic nasopharyngitis (P < 0.05). IL-17A expression was significantly higher in NPC ≥ 50 mm, stage III + IV NPC and NPC with cervical lymph node invasion than its corresponding chronic nasopharyngitis tissue. CONCLUSION: IL-17A may be involved in the regulation of various malignant biological behaviors of NPC, which is closely related to the occurrence and development of NPC.


Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Interleucina-17/metabolismo , Linfonodos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Adulto , Correlação de Dados , Feminino , Humanos , Imuno-Histoquímica , Linfonodos/imunologia , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/patologia , Nasofaringite/imunologia , Estadiamento de Neoplasias
8.
Foodborne Pathog Dis ; 16(5): 339-345, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31013442

RESUMO

Salmonella is one of the most important foodborne pathogens associated with animal and human diseases. In this study, 672 samples of fresh meat (pork, 347; chicken, 196; and duck, 129) were collected from retail markets in different provinces of China from 2010 to 2014. We identified 10 different serotypes among 80 Salmonella isolates, whereas 12 isolates were nonmotile precluding conventional identification of complete serotype. Among these 92 isolates, Salmonella enterica serovar Derby (n = 21) was the most prevalent serotype, followed by Salmonella Enteritidis (n = 17), Salmonella Typhimurium (n = 15), Salmonella Indiana (n = 9), Salmonella Agona (n = 7), and Salmonella Assinie (n = 5). Antimicrobial resistance testing for 18 antimicrobial agents revealed that all 92 isolates were resistant to at least 1 antimicrobial agent, and 39 different resistance profiles were identified. The highest resistance was to trimethoprim-sulfamethoxazole (n = 87), followed by tetracycline (n = 51), carbenicillin (n = 38), amoxicillin/A.clav (n = 30), and piperacillin (n = 24). Our results demonstrated that meats presented a potential public health risk, thereby underlining the necessity for local regulatory enforcement agencies in China to monitor salmonellosis.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Contaminação de Alimentos , Salmonella/isolamento & purificação , Animais , Galinhas , China/epidemiologia , Patos , Microbiologia de Alimentos , Humanos , Produtos da Carne/microbiologia , Testes de Sensibilidade Microbiana , Prevalência , Salmonella/classificação , Intoxicação Alimentar por Salmonella/epidemiologia , Infecções por Salmonella/microbiologia , Sorotipagem , Suínos
9.
Cell Physiol Biochem ; 46(6): 2232-2238, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29734196

RESUMO

BACKGROUND/AIMS: The objective of this study was to investigate the potential role of IL-17 in the development of nasopharyngeal carcinoma (NPC) and to screen microRNAs (miRNAs) that potentially target IL-17 in NPC cells. METHODS: Blood was collected from NPC patients and normal subjects, and plasma IL-17 concentration was quantified by enzyme-linked immunosorbent assay. An immortalized normal human nasopharyngeal epithelial cell line, NP69, was treated with or without human IL-17 (15 ng/mL) for various times, and expression of IL-1ß, IL-6, IL-12, and TNF-α mRNA was assessed by real-time reverse transcription PCR. The candidate miRNAs that potentially target IL-17 were predicted by a bioinformatics strategy. The selected miR-135a mimic was transfected into primary NPC cells, and cell proliferation was assessed by MTT assay. RESULTS: The concentration of plasma IL-17 was significantly higher in the NPC patients (92.5 ± 7.3 pg/mL) than in the control subjects (56.8 ± 2.9 pg/mL). In response to IL-17 treatment, the mRNA expression of IL-1ß and IL-6 was significantly upregulated and reached a peak at 12 h, followed by a slight decrease at 24 h, while the mRNA expression of IL-12 and TNF-α was significantly upregulated at 12 h and remained high even at 48 h after exposure to IL-17. Moreover, miR-135a specifically targets IL-17 and was dramatically downregulated in NPC cells compared with NP69 cells. Transfection of exogenous miR-135a mimic resulted in significant suppression of IL-17 secretion and subsequent inhibition of NPC cell proliferation. CONCLUSIONS: Blood IL-17 was significantly higher in NPC patients compared with normal subjects. Expression of miR-135a in the cancer cells isolated from nasopharyngeal tumors was significantly lower than that in NP69 cells, and suppression of IL-17 by miR-135a mimic resulted in significant inhibition of NPC cell proliferation. These findings suggested that downregulation of miR-135a may contribute to the development of NPC via the mechanism of IL-17 stimulation of proinflammatory cytokine expression.


Assuntos
Carcinoma/genética , Regulação Neoplásica da Expressão Gênica , Interleucina-17/genética , MicroRNAs/genética , Neoplasias Nasofaríngeas/genética , Carcinoma/sangue , Proliferação de Células , Regulação para Baixo , Feminino , Humanos , Interleucina-17/sangue , Masculino , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/sangue , Células Tumorais Cultivadas
10.
Bioorg Med Chem Lett ; 25(7): 1647-52, 2015 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-25716904

RESUMO

Mutated epidermal growth factor receptor (EGFR) is an important biomarker for cancer diagnosis and molecular target for many anticancer drugs. Localizing EGFR and evaluating EGFR mutational status can help to identify patients who are potentially the most suitable ones for targeted treatments. Hence, we developed a novel EGFR tyrosine kinase inhibitor labeled with (99m)Tc ((99m)Tc-HYNIC-MPG) and evaluated its EGFR binding capacity in vitro and in vivo. This molecular probe was synthesized by one-step method that is simple and highly efficient. Importantly, the uptake rate for (99m)Tc-HYNIC-MPG in the liver was as low as 28.44 ± 0.15% (mean ± SD, n=3). This finding presents for the first time that (99m)Tc-HYNIC-MPG can bind to mutated EGFR efficiently and thus provides a novel molecular tool to detect mutated EGFR and suppress tumorigenesis.


Assuntos
Receptores ErbB/antagonistas & inibidores , Sondas Moleculares/farmacologia , Compostos de Organotecnécio/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Compostos Radiofarmacêuticos/farmacologia , Tomografia Computadorizada de Emissão de Fóton Único , Animais , Linhagem Celular , Receptores ErbB/genética , Feminino , Humanos , Camundongos , Camundongos Endogâmicos , Imagem Molecular , Sondas Moleculares/síntese química , Sondas Moleculares/química , Mutação , Compostos de Organotecnécio/síntese química , Compostos de Organotecnécio/química , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Quinazolinas/síntese química , Quinazolinas/química , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Relação Estrutura-Atividade
11.
Zhonghua Nan Ke Xue ; 21(10): 921-4, 2015 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-26665683

RESUMO

OBJECTIVE: To investigate the clinical value of Paroxetine combined with mid-frequency electrical pulse acupoint stimulation (EPAS) in the treatment of premature ejaculation (PE). METHODS: Totally 69 PE patients were equally assigned to receive oral Paroxetine 20 mg/d, mid-frequency EPAS, or oral Paroxetine 10 mg/d combined with mid-frequency EPAS (P + EPAS) , all for 8 weeks. We obtained the intravaginal ejaculation latency time (IELT) and Chinese Index of Premature Ejaculation (CIPE-5) scores of the patients before and after treatment, and compared adverse reactions among the three groups of patients. RESULTS: One patient of the Paroxetine group gave up treatment because of abdominal pain and nausea. Compared with the baseline, the patients in the Paroxetine, EPAS, and P + EPAS groups all showed markedly increased IELT ([0.92 ± 0.11] vs [4.07 ± 0.11] min, P < 0.01; [0.92 ± 0.12] VS [2.78 ± 0.17] min P < 0.05; [0.91 ± 0.09] vs [5.31 ± 0.13], P < 0.01) and decreased CIPE-5 scores (12.5 ± 3.0 vs 22.0 ± 2.1, P < 0.01; 12.8 ± 2.9 vs 19.5 ± 1.9, P > 0.05; 13.1 ± 2.8 vs 25.2 ± 2.1, P 0.01), with statistically significant differences between the P + EPAS group and the other two (P < 0.05). The total effectiveness rate was 95.7% in the P + EPAS group, remarkably higher than in the Paroxetine (72.7%, P < 0.05) and the EPAS group (47.8, P < 0.01). CONCLUSION: Oral Paroxetine combined with mid-frequency EPAS has a higher safety and efficacy than either Paroxetine or EPAS alone in the treatment of PE.


Assuntos
Pontos de Acupuntura , Eletroacupuntura/métodos , Paroxetina/uso terapêutico , Ejaculação Precoce/terapia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Idoso , Terapia Combinada/métodos , Ejaculação , Humanos , Masculino , Resultado do Tratamento
12.
IEEE Trans Image Process ; 33: 3145-3160, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38656843

RESUMO

Multi-view subspace clustering (MVSC) has drawn significant attention in recent study. In this paper, we propose a novel approach to MVSC. First, the new method is capable of preserving high-order neighbor information of the data, which provides essential and complicated underlying relationships of the data that is not straightforwardly preserved by the first-order neighbors. Second, we design log-based nonconvex approximations to both tensor rank and tensor sparsity, which are effective and more accurate than the convex approximations. For the associated shrinkage problems, we provide elegant theoretical results for the closed-form solutions, for which the convergence is guaranteed by theoretical analysis. Moreover, the new approximations have some interesting properties of shrinkage effects, which are guaranteed by elegant theoretical results. Extensive experimental results confirm the effectiveness of the proposed method.

13.
J Chromatogr Sci ; 62(5): 465-470, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38213303

RESUMO

Although Vibrio parahaemolyticus (V. parahaemolyticus) is a pathogen frequently found in seafood, there is a possibility of its presence in other foods, such as dairy products. The main virulence factors of V. parahaemolyticus are thermostable direct hemolysins (TDHs) which are lethal toxins, so it is necessary to establish qualitative and quantitative methods for determining TDHs. HPLC-ESI-TOF was employed to establish a method for identifying TDHs. The identification and quantification ions of TDHs were confirmed by HPLC-ESI-TOF. The method was developed for detecting TDHs in milk powder using HPLC-ESI-TOF in this paper, and limits of detection (were between 0.20 and 0.40 mg/kg, limits of quantitation were between 0.5 and 1.0 mg/kg and recoveries of all TDHs were between from 78% to 94% with relative standard deviation lower than 10%. This research will provide a reference for developing methods of HPLC-MS/MS to detect TDHs in food samples, which can provide a tool for the government to monitor TDHs contamination in foods.


Assuntos
Proteínas Hemolisinas , Limite de Detecção , Leite , Espectrometria de Massas por Ionização por Electrospray , Cromatografia Líquida de Alta Pressão/métodos , Leite/química , Leite/microbiologia , Animais , Espectrometria de Massas por Ionização por Electrospray/métodos , Proteínas Hemolisinas/análise , Proteínas Hemolisinas/química , Toxinas Bacterianas/análise , Toxinas Bacterianas/química , Reprodutibilidade dos Testes , Modelos Lineares , Espectrometria de Massas em Tandem/métodos , Pós/química , Contaminação de Alimentos/análise , Vibrio parahaemolyticus/química , Vibrio parahaemolyticus/isolamento & purificação
14.
Heliyon ; 10(10): e31197, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38807876

RESUMO

Electroacupuncture (EA) is an effective alternative for the treatment of functional dyspepsia (FD). It reduces low-grade duodenal inflammation and improves the symptoms of FD by downregulating the expression of NF-κB p65 and NLRP3, but its mechanism needs to be elucidated. To examine the regulatory effect of electroacupuncture (EA) on intestinal flora and NF-κB p65/NLRP3 pyroptosis pathway in FD rats. The FD rat model was established via multi-factor stress intervention for two weeks. The rats were randomly divided into the NC group, model group, NF-kB inhibitor group (NF-κB inhibitor BAY 11-7082 was administered), EA group, and EA + NF-kB inhibitor group. After 14 days of treatment, the rats were sacrificed, and the protein and mRNA levels of NF-κB p65, IκB, and NLRP3 in the duodenum were evaluated by Western blotting assays and real-time fluorescent quantitative PCR. The Illumina MiSeq sequencing platform was used to analyze the V4 region of the 16S rRNA gene of intestinal flora and predict functional genes. The concentration of short-chain fatty acids (SCFAs) in feces was assessed by metabolomics. EA can decrease low-grade duodenal inflammation and promote gastrointestinal motility in FD rats. This effect is mediated by inhibition of the NF-κB p65/NLRP3 pyroptosis pathway, an increase in the alpha and beta diversity of gut microbiota in the duodenum, an increase in the abundance of beneficial bacteria at the phylum and genus levels, and an increase in the content of SCFAs. The protective effect of EA against FD might involve multiple hierarchy and pathways. EA may remodel intestinal flora by inhibiting the NF-κB p65/NLRP3 pyroptosis pathway, thereby improving low-grade duodenal inflammation in FD rats.

15.
Sci Total Environ ; 860: 160362, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36427736

RESUMO

Molybdenum disulfide (MoS2) nanosheets have been used extensively in a variety of fields including medical and industrial. However, little is known about their toxicity effects, especially to edible plants. In this greenhouse study, maize (Zea mays) seedlings were exposed for 4 weeks, through the soil route, to 10 and 100 mg/kg of 2H MoS2 nanosheets. Plant growth, physiological parameters (chlorophyll, antioxidants, and MDA), along with Mo and nutrient element contents were determined in plant tissues. Results showed that at both doses, the nanosheets decreased plant growth. Inductively coupled plasma-mass spectrometry data also showed that both 2H MoS2 concentrations allowed Mo absorption and translocation by maize plants. Additionally, at 100 mg/kg the nanosheets significantly reduced Ca, Mg, Mn, and Zn in leaves, and Na in roots. Gene sequencing data of 16S rRNA showed, that MoS2 nanosheets changed the soil microbial community structure, compared with the untreated control. In addition, nitrogen-fixing microorganisms such as Burkholderiales, Rhizobiales and Xanthobacteraceae were enriched. Overall, the data suggest that, even at low dose (10 mg/kg), the 2H MoS2 nanosheets perturbed both the nutrient uptake by maize plants and the soil microbial communities.


Assuntos
Poluentes do Solo , Solo , Solo/química , Zea mays , Molibdênio/toxicidade , Molibdênio/análise , RNA Ribossômico 16S/análise , Clorofila/análise , Raízes de Plantas/química , Plantas , Poluentes do Solo/análise
16.
Mol Med Rep ; 27(2)2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36579659

RESUMO

The mechanism underlying bladder cancer metastasis is associated with tumor angiogenesis. The present study aimed to evaluate the predictive role and value of an angiogenesis­associated long non­coding (lnc)RNA signature in patients with bladder cancer and the role of long intergenic non­coding RNA (LINC)02321 in the progression of this malignancy. Angiogenesis­related lncRNAs were screened using Pearson correlation analysis and the signaturewas constructed using Cox regression analysis and evaluated using the receiver operating characteristic curve. LINC02321, which expressed the largest difference in bladder cancer, was screened using reverse transcription­quantitative PCR. The role of LINC02321 in the malignant progression of bladder cancer was evaluated using Transwell, wound healing and Cell Counting Kit 8 assays. A total of six angiogenesis­associated lncRNAs (USP30­AS1, LINC02321, PSMB8­AS1, KRT7­AS, LINC01767 and OCIAD1­AS1) were identified as candidates for the prognostic signature using Cox regression analysis. The overall survival of patients in the low­risk group was significantly longer compared with that in the high­risk group, with the highest area under the curve value being 0.807. A nomogram was constructed based on the traditional clinical indicators (age, sex, grade, American Joint Committee on Cancer stage) and risk score of patients. Compared with the traditional clinical indicators, the risk score demonstrated better clinical prediction capacity for predicting the prognosis of patients with bladder cancer. The Cancer Genome Atlas prediction and RT­qPCR experimental results demonstrated that only LINC02321 was highly expressed in bladder cancer tissue and promoted the proliferation, invasion, migration and cisplatin resistance of the malignancy. Gene set enrichment, Pearson's correlation analysis and experimental results demonstrated that the VEGFA signalling pathway may be involved in the LINC02321­regulated progression of bladder cancer. In conclusion, the six angiogenesis­associated lncRNA signatures reported in the present study may be used to predict the prognosis of patients with bladder cancer, and LINC02321 promoted malignant progression of bladder cancer via the VEGFA signalling pathway.


Assuntos
RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Prognóstico , Neoplasias da Bexiga Urinária/genética , Fatores de Risco , Transdução de Sinais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Tioléster Hidrolases/genética , Tioléster Hidrolases/metabolismo , Proteínas Mitocondriais/metabolismo
17.
Environ Sci Pollut Res Int ; 30(50): 108694-108705, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37751004

RESUMO

Staphylococcal enterotoxins (SEs) secreted by Staphylococcus aureus (S. aureus) can cause foodborne disease, nausea, vomiting and diarrhea, and even death. Regulation of SE expression is related to accessory gene regulators (Agr). It is important to reveal which environmental factors influence regulation of SE expression to prevent SE food poisoning outbreak. Hence, natural environmental factors which may have an impact on SE expression were selected, such as temperature, food types, strains, and competing strains. Seven strains of S. aureus carrying different SE genes were collected from the Chinese Academy of Inspection and Quarantine (CAIQ) strain bank for study. Strains were cultured with different conditions. Temperature was 8 °C, 22 °C, and 30 °C. Food type was milk powder and nutrient broth. Competing strains were Vibrio parahaemolyticus (V. parahaemolyticus), Escherichia coli (E. coli), and Bacillus cereus (B. cereus). The expression culture solution was pretreated by centrifugation, then determined by using SDS-PAGE, and distinguished SEs apart from each other by HPLC-ESI-TOF. There are 168 samples collected from SE expression culture; the result of SDS-PAGE suggests 23 samples were positive for SEs, and the other 145 samples were negative for SEs. The result of HPLC-ESI-TOF suggests that SEs with similar molecular weight can be distinguished in terms of m/z. The most important factor contributing to regulate expression of SEs was estimated by logistic regressive analysis. The result shows that McFadden R2 is 0.213; p value is 0.000 (p < 0.05); this result illustrates that the model is valid and meaningful. Strains, food types, temperature, and competing strands can explain the 21% change in SE expression. Temperature (z = 3.029, p = 0.002 < 0.01), strains (z = - 3.132, p = 0.002 < 0.01), and food types (z = - 2.415, p = 0.016 < 0.05) have significant impact on SE expression, and the competing strains (z = 1.230, p = 0.219 > 0.05) have no impact on the SE expression. More important impact on SE expression was estimated by OR value; the result shows that strength of temperature influencing on SE expression is bigger than strains and food types in terms of values of OR, temperature (OR = 2.862), strains (OR = 0.641), and food types (OR = 0.561); consequently, temperature is a key factor for stimulating SE expression and had high expression at 30 °C. Therefore, food easily contaminated with S. aureus should be monitored intensively at early and late summer, when proper temperature for expressing SEs may result in S. aureus food poisoning prevalence.


Assuntos
Intoxicação Alimentar Estafilocócica , Infecções Estafilocócicas , Humanos , Enterotoxinas/análise , Staphylococcus aureus/genética , Escherichia coli , Intoxicação Alimentar Estafilocócica/epidemiologia , Microbiologia de Alimentos
18.
Poult Sci ; 102(8): 102830, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37343345

RESUMO

Poultry is one of the most commonly farmed species and the most widespread meat industries. However, numerous poultry flocks have been long threatened by pathogenic bacterial infections, especially antimicrobial resistant pathogens. Here the prevalence and the antimicrobial resistance (AMR) profiles of bacterial pathogens isolated from poultry in Jiangxi Province, China were investigated. From 2020 to 2022, 283 tissue and liquid samples were collected from clinically diseased poultry, including duck, chicken, and goose, with an overall positive isolation rate of 62.90%. Among all the 219 bacterial isolates, 29 strains were gram-positive and 190 strains were gram-negative. Major bacteria species involved were avian pathogenic Escherichia coli (APEC; 57.53%; 126/219), followed by Salmonella spp. (11.87%, 26/219), Pasteurella multocida (6.39%, 14/219), and Staphylococcus spp. (1.22%, 11/219). Antimicrobial susceptibility testing showed the APEC isolates displayed considerably higher levels of AMR than the Salmonella and P. multocida isolates. The APEC isolates showed high resistance rate to amoxicillin (89.68%), ampicillin (89.68%), and florfenicol (83.33%), followed by streptomycin (75.40%), cefradine (65.87%), and enrofloxacin (64.29%). Multidrug-resistant isolates were observed in APEC (99.21%), Salmonella spp. (96.16%), and P. multocida (85.71%), and nearly 3 quarters of the APEC strains were resistant to 7 or more categories of antimicrobial drugs. Moreover, blaNDM genes associated with carbapenemase resistance and mcr-1 associated with colisitin resistance were detected in the APEC isolates. Our findings could provide evidence-based guidance for veterinarians to prevent and control bacterial diseases, and be helpful for monitoring the emerging and development of AMR in poultry bacterial pathogens.


Assuntos
Infecções por Escherichia coli , Pasteurella multocida , Doenças das Aves Domésticas , Animais , Aves Domésticas , Antibacterianos/farmacologia , Galinhas , Farmacorresistência Bacteriana , Prevalência , Escherichia coli , Infecções por Escherichia coli/veterinária , Salmonella , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/microbiologia
19.
IEEE Trans Cybern ; 52(9): 8976-8986, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33729977

RESUMO

Graph-based subspace clustering methods have exhibited promising performance. However, they still suffer some of these drawbacks: they encounter the expensive time overhead, they fail to explore the explicit clusters, and cannot generalize to unseen data points. In this work, we propose a scalable graph learning framework, seeking to address the above three challenges simultaneously. Specifically, it is based on the ideas of anchor points and bipartite graph. Rather than building an n×n graph, where n is the number of samples, we construct a bipartite graph to depict the relationship between samples and anchor points. Meanwhile, a connectivity constraint is employed to ensure that the connected components indicate clusters directly. We further establish the connection between our method and the K -means clustering. Moreover, a model to process multiview data is also proposed, which is linearly scaled with respect to n . Extensive experiments demonstrate the efficiency and effectiveness of our approach with respect to many state-of-the-art clustering methods.

20.
Artigo em Inglês | MEDLINE | ID: mdl-35576414

RESUMO

Graph convolutional network (GCN) outputs powerful representation by considering the structure information of the data to conduct representation learning, but its robustness is sensitive to the quality of both the feature matrix and the initial graph. In this article, we propose a novel multigraph fusion method to produce a high-quality graph and a low-dimensional space of original high-dimensional data for the GCN model. Specifically, the proposed method first extracts the common information and the complementary information among multiple local graphs to obtain a unified local graph, which is then fused with the global graph of the data to obtain the initial graph for the GCN model. As a result, the proposed method conducts the graph fusion process twice to simultaneously learn the low-dimensional space and the intrinsic graph structure of the data in a unified framework. Experimental results on real datasets demonstrated that our method outperformed the comparison methods in terms of classification tasks.

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