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1.
Cereb Cortex ; 34(6)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38937078

RESUMO

Table tennis players have adaptive visual and sensorimotor networks, which are the key brain regions to acquire environmental information and generate motor output. This study examined 20 table tennis players and 21 control subjects through ultrahigh field 7 Tesla magnetic resonance imaging. First, we measured percentage amplitude of fluctuation across five different frequency bands and found that table tennis players had significantly lower percentage amplitude of fluctuation values than control subjects in 18 brain regions, suggesting enhanced stability of spontaneous brain fluctuation amplitudes in visual and sensorimotor networks. Functional connectional analyses revealed increased static functional connectivity between two sensorimotor nodes and other frontal-parietal regions among table tennis players. Additionally, these players displayed enhanced dynamic functional connectivity coupled with reduced static connectivity between five nodes processing visual and sensory information input, and other large-scale cross-regional areas. These findings highlight that table tennis players undergo neural adaptability through a dual mechanism, characterized by global stability in spontaneous brain fluctuation amplitudes and heightened flexibility in visual sensory networks. Our study offers novel insights into the mechanisms of neural adaptability in athletes, providing a foundation for future efforts to enhance cognitive functions in diverse populations, such as athletes, older adults, and individuals with cognitive impairments.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Adulto Jovem , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Feminino , Adulto , Tênis/fisiologia , Atletas , Mapeamento Encefálico/métodos , Rede Nervosa/fisiologia , Rede Nervosa/diagnóstico por imagem , Vias Neurais/fisiologia , Adaptação Fisiológica/fisiologia , Adolescente
2.
Eur J Neurosci ; 59(8): 2118-2127, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38282277

RESUMO

Early diagnosis is crucial to slowing the progression of Alzheimer's disease (AD), so it is urgent to find an effective diagnostic method for AD. This study intended to investigate whether the transfer learning approach of deep Q-network (DQN) could effectively distinguish AD patients using local metrics of resting-state functional magnetic resonance imaging (rs-fMRI) as features. This study included 1310 subjects from the Consortium for Reliability and Reproducibility (CoRR) and 50 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) GO/2. The amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF) and percent amplitude of fluctuation (PerAF) were extracted as features using the Power 264 atlas. Based on gender bias in AD, we searched for transferable similar parts between the CoRR feature matrix and the ADNI feature matrix, resulting in the CoRR similar feature matrix served as the source domain and the ADNI similar feature matrix served as the target domain. A DQN classifier was pre-trained in the source domain and transferred to the target domain. Finally, the transferred DQN classifier was used to classify AD and healthy controls (HC). A permutation test was performed. The DQN transfer learning achieved a classification accuracy of 86.66% (p < 0.01), recall of 83.33% and precision of 83.33%. The findings suggested that the transfer learning approach using DQN could be an effective way to distinguish AD from HC. It also revealed the potential value of local brain activity in AD clinical diagnosis.


Assuntos
Doença de Alzheimer , Encéfalo , Humanos , Masculino , Feminino , Doença de Alzheimer/diagnóstico por imagem , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética/métodos , Sexismo , Aprendizado de Máquina
3.
Fish Shellfish Immunol ; 149: 109566, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38636735

RESUMO

Fish rely on innate immune system for immunity, and nucleotide-binding oligomerization domain-like receptors (NLRs) are a vital group of receptor for recognition. In the present study, NOD1 gene was cloned and characterized from golden pompano Trachinotus ovatus, a commercially important aquaculture fish species. The ORF of T. ovatus NOD1 was 2820 bp long, encoding 939 amino acid residues with a highly conserved domains containing CARD-NACHT-LRRs. Phylogenetic analysis revealed that the T. ovatus NOD1 clustered with those of fish and separated from those of birds and mammals. T. ovatus NOD1 has wide tissue distribution with the highest expression in gills. Bacterial challenges (Streptococcus agalactiae and Vibrio alginolyticus) significantly up-regulated the expression of NOD1 with different response time. The results of T. ovatus NOD1 ligand recognition and signaling pathway analysis revealed that T. ovatus NOD1 could recognize iE-DAP at the concentration of ≧ 100 ng/mL and able to activate NF-κB signaling pathway. This study confirmed that NOD1 play a crucial role in the innate immunity of T. ovatus. The findings of this study improve our understanding on the immune function of NOD1 in teleost, especially T. ovatus.


Assuntos
Sequência de Aminoácidos , Doenças dos Peixes , Proteínas de Peixes , Imunidade Inata , Proteína Adaptadora de Sinalização NOD1 , Filogenia , Alinhamento de Sequência , Vibrio alginolyticus , Animais , Proteína Adaptadora de Sinalização NOD1/genética , Proteína Adaptadora de Sinalização NOD1/imunologia , Proteína Adaptadora de Sinalização NOD1/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Proteínas de Peixes/química , Imunidade Inata/genética , Doenças dos Peixes/imunologia , Alinhamento de Sequência/veterinária , Vibrio alginolyticus/fisiologia , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/veterinária , Streptococcus agalactiae/fisiologia , Regulação da Expressão Gênica/imunologia , Perfilação da Expressão Gênica/veterinária , Vibrioses/imunologia , Vibrioses/veterinária , Ácido Diaminopimélico/química , Ácido Diaminopimélico/análogos & derivados , Perciformes/imunologia , Perciformes/genética , Peixes/imunologia , Peixes/genética
4.
Phys Chem Chem Phys ; 25(26): 17619-17626, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37365969

RESUMO

Here, spinodal decomposition is used as a strategy to enhance the mechanical properties of the 30Al2O3·70SiO2 glass. The melt-quenched 30Al2O3·70SiO2 glass exhibited a liquid-liquid phase separation with an interconnected snake-like nano-structure. Through further heat treatment at 850 °C for different durations of up to 40 hours, we observed a continuous increase of up to about 0.90 GPa in hardness (Hv) together with a drop in the slope for Hv rise at 4 hours. However, the crack resistance (CR) achieved a maximum value of 13.6 N when the heat treatment time was 2 hours. Detailed calorimetric, morphological and compositional analyses were conducted to elucidate the effect of tuning the thermal treatment time on hardness and crack resistance. These findings pave the way to utilize the spinodal phase-separated phenomena to enhance the mechanical properties of glasses.

5.
Curr Microbiol ; 80(12): 368, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37831112

RESUMO

A sedentary lifestyle affects the diversity and composition of the gut microbiota, but previous studies have mainly focused on bacteria instead of fungi. Here, we compared both the fecal bacterial and fungal microbiota compositions and functions in sedentary persons and controls. Subjects from the China Railway Corporation, including 99 inspectors and 88 officials, were enrolled in our study. Fecal microbiota communities were analyzed using 16S rRNA gene sequencing for bacteria and ITS sequencing for fungi. We found that the diversity of the gut microbiota of the sedentary group was significantly lower than that of the control group (P < 0.05). The sedentary group had a higher abundance of Firmicutes, a lower abundance of Actinobacteria and Proteobacteria and a higher abundance of Ascomycota, and a lower abundance of Basidiomycota. Furthermore, functional prediction analysis of the fungal microbiota revealed more L-tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde, more phospholipid remodeling (phosphatidylethanolamine, yeast), and more L-tyrosine degradation I, as well as less pentose phosphate pathway (non-oxidative branch), less adenosine nucleotide biosynthesis and less L-valine biosynthesis in the sedentary group (P < 0.05). Thus, a sedentary lifestyle changes the composition and function of the gut microbiota. It may change the pentose phosphate pathway (non-oxidative branch), nucleic acid and amino acid biosynthesis and phospholipid metabolism in fungi.


Assuntos
Microbioma Gastrointestinal , Micobioma , Humanos , Microbioma Gastrointestinal/genética , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Comportamento Sedentário , Bactérias , Fungos/genética , Fosfolipídeos/metabolismo
6.
Ultrason Imaging ; 45(1): 3-16, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36524755

RESUMO

Due to the advantages of non-radiation and real-time performance, ultrasound imaging is essential in medical imaging. Image quality is affected by the performance of the transducer in an ultrasound imaging system. For example, the bandwidth controls the pulse length, resulting in different axial resolutions. Therefore, a transducer with a large bandwidth helps to improve imaging quality. However, large bandwidths lead to increased system cost and sometimes a loss of sensitivity and lateral resolution in attenuating media. In this paper, a deconvolution recovery method combined with a frequency-domain filtering technique (DRF) is proposed to improve the imaging quality, especially for the axial resolution. In this method, the received low-bandwidth echo signals are converted into high-bandwidth signals, which is similar to the echo signals produced by a high-bandwidth transducer, and the imaging quality is improved. Simulation and experiment results show that, compared with Delay-and-sum (DAS) method, the DRF method improved axial resolution from 0.60 to 0.41 mm in simulation and from 0.62 to 0.47 mm in the tissue-mimicking phantom experiment. The contrast ratio performance is improved to some extent compared with the DAS in experimental and in-vivo images. Besides, the proposed method has the potential to further improve image quality by combining it with adaptive weightings, such as the minimum variance method.


Assuntos
Processamento de Imagem Assistida por Computador , Transdutores , Ultrassonografia/métodos , Simulação por Computador , Imagens de Fantasmas , Processamento de Imagem Assistida por Computador/métodos , Algoritmos
7.
Biomed Eng Online ; 21(1): 40, 2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35717330

RESUMO

BACKGROUND: The minimum variance (MV) beamformer can significantly improve the image resolution in ultrasound imaging, but it has limited performance in noise reduction. We recently proposed the covariance matrix-based statistical beamforming (CMSB) for medical ultrasound imaging to reduce sidelobes and incoherent clutter. METHODS: In this paper, we aim to improve the imaging performance of the MV beamformer by introducing a new pixel-based adaptive weighting approach based on CMSB, which is named as covariance matrix-based adaptive weighting (CMSAW). The proposed CMSAW estimates the mean-to-standard-deviation ratio (MSR) of a modified covariance matrix reconstructed by adaptive spatial smoothing, rotary averaging, and diagonal reducing. Moreover, adaptive diagonal reducing based on the aperture coherence is introduced in CMSAW to enhance the performance in speckle preservation. RESULTS: The proposed CMSAW-weighted MV (CMSAW-MV) was validated through simulation, phantom experiments, and in vivo studies. The phantom experimental results show that CMSAW-MV obtains resolution improvement of 21.3% and simultaneously achieves average improvements of 96.4% and 71.8% in average contrast and generalized contrast-to-noise ratio (gCNR) for anechoic cyst, respectively, compared with MV. in vivo studies indicate that CMSAW-MV improves the noise reduction performance of MV beamformer. CONCLUSION: Simulation, experimental, and in vivo results all show that CMSAW-MV can improve resolution and suppress sidelobes and incoherent clutter and noise. These results demonstrate the effectiveness of CMSAW in improving the imaging performance of MV beamformer. Moreover, the proposed CMSAW with a computational complexity of [Formula: see text] has the potential to be implemented in real time using the graphics processing unit.


Assuntos
Algoritmos , Processamento de Sinais Assistido por Computador , Simulação por Computador , Processamento de Imagem Assistida por Computador/métodos , Imagens de Fantasmas , Ultrassonografia/métodos
8.
Platelets ; 33(8): 1307-1311, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-35791514

RESUMO

MYH9-related disorder (MYH9-RD) is autosomal dominant thrombocytopenia caused by mutations in the MYH9 gene, which codes for the non-muscle myosin-IIA heavy chain. We present a case of a 24-year-old Chinese man with MYH9-RD who was initially misdiagnosed with immune thrombocytopenia. Whole-exome sequencing and Sanger sequencing revealed a novel missense mutation in the MYH9 gene at the position of c.4550 G > T (p.G1517V) in exon 32. The same phenotype was observed in the proband, his mother, and his brother, in addition to macrothrombocytopenia and Dohle-like bodies in neutrophil granulocytes without non-hematologic manifestations. Following failed treatment with eltrombopag, avatrombopag, which was not mentioned before in the MYH9-RD treatment, was administered to the patient, and thrombocytopenia improved. In this case report, we present a novel pathogenic mutation and show the potential of avatrombopag for temporarily increasing the platelet count in patients with MYH9-RD.


Assuntos
Perda Auditiva Neurossensorial , Trombocitopenia , Benzoatos , Perda Auditiva Neurossensorial/genética , Humanos , Hidrazinas , Masculino , Proteínas Motores Moleculares/genética , Mutação , Cadeias Pesadas de Miosina/genética , Pirazóis , Tiazóis , Tiofenos , Trombocitopenia/congênito , Trombocitopenia/diagnóstico , Trombocitopenia/tratamento farmacológico , Trombocitopenia/genética , Falha de Tratamento
9.
Molecules ; 27(16)2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-36014337

RESUMO

Tripterygium glycosides tablets (TGTs) are widely used in clinical practice to treat rheumatoid arthritis and other autoimmune diseases, with significant beneficial effects but also high toxicity, necessitating rigorous quality evaluation and control. In current study, a rapid resolution liquid chromatography tandem electrospray ionization triple quadrupole mass spectrometry (RRLC-ESI-MS/MS) method was developed and validated for the quantitative analysis of 14 components of ten batches of TGTs produced by different manufacturers, including four diterpenoids, three triterpenoids, and seven sesquiterpene alkaloids. Meanwhile, the NO inhibition effects of these TGTs were evaluated in LPS-induced RAW264.7 cells for their downstream anti-inflammatory activities, as well as their cytotoxicity. The results indicate that the TGTs from different manufacturers showed poor quality consistency, as evidenced by large variations in chemical profiles and biological effects, which may increase the risks associated with clinical use. To improve the quality status of TGTs, it is crucial to identify indicator components whose characterization can accurately reflect the efficacy and toxicity of TGTs from which they were derived. Our study reveals that triptolide, triptoquinone B, celastrol, and demethylzelaysteral considerably contributed to the anti-inflammatory activity and/or cytotoxicity of TGTs, implying that they should be further investigated as candidate indicator components for TGT quality control.


Assuntos
Medicamentos de Ervas Chinesas , Tripterygium , Bioensaio , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Glicosídeos/química , Comprimidos/química , Espectrometria de Massas em Tandem/métodos , Tripterygium/química
10.
Molecules ; 27(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36364101

RESUMO

Tripterygium wilfordii Hook. f. is a well-known traditional Chinese medicine used to treat autoimmune diseases. Sesquiterpene pyridine alkaloids (SPAs) are a major class of components found in this herb that have piqued the interest of researchers due to their complex and diverse structures as well as significant biological activities. In this study, ten new SPAs, wilfordatine A-J (1-10), were isolated from the roots of T. wilfordii, along with ten known analogues (11-20). Their structures were primarily elucidated by extensive 1D and 2D NMR spectroscopic analysis. To search for more immunosuppressive ingredients related to the clinical efficacy of T. wilfordii, the total alkaloids (TA) and compounds 4, 5, and 9-16 were tested for their inhibitory effects on nuclear factor-kappa B (NF-κB) pathway in Lipopolysaccharide (LPS) induced HEK293/NF-κB-Luc cells. Among them, TA, compounds 5, 11, and 16 showed potent immunosuppressive activity, with IC50 values of 7.25 µg/mL, 8.75 µM, 0.74 µM, and 15.66 µM, respectively, and no influence on the cell viability at a concentration of 100 µg/mL (TA) or 100 µM (5, 11, and 16). Accordingly, TA, 5, 11, and 16, especially 11, were identified as promising candidates for further investigation into their potential use as immunosuppressive agents.


Assuntos
Alcaloides , Medicamentos de Ervas Chinesas , Sesquiterpenos , Humanos , Tripterygium/química , NF-kappa B , Células HEK293 , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Alcaloides/farmacologia , Alcaloides/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Piridinas/farmacologia , Piridinas/química , Imunossupressores/farmacologia
11.
Zhongguo Zhong Yao Za Zhi ; 47(16): 4292-4304, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046855

RESUMO

Sesquiterpene pyridine alkaloids are important components in Tripterygium plants, possessing a wide range of pharmacological activities, such as anti-inflammation immunosuppression, anti-tumor, anti-virus, and deinsectization, and are of great research value. They are composed of highly oxidized dihydro-ß-furansquiterpene and pyridine dicarboxylic acid through ester bonds. According to the structural characteristics of pyridine dicarboxylic acid fragments, they can be divided into various structural subtypes. Up to now, more than 110 sesquiterpene pyridine alkaloids have been isolated and identified from Tripterygium plants. This study reviewed the structural features and spectral(i.e., UV, IR, MS, and NMR) characteristics of sesquiterpene pyridine alkaloids and summarized the structural elucidation process in detail to provide references for their further research and development.


Assuntos
Alcaloides , Medicamentos de Ervas Chinesas , Sesquiterpenos , Alcaloides/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Estrutura Molecular , Piridinas/química , Piridinas/farmacologia , Tripterygium/química
12.
Immunol Invest ; 50(8): 987-1006, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33390082

RESUMO

Objective: Inflammatory bowel disease (IBD) is a heterogeneous complex disease referring to two chronic disorders: Crohn's disease (CD) and ulcerative colitis (UC). To clarify the relationship between IL-12B gene polymorphisms and susceptibility to CD and UC, a meta-analysis was conducted.Methods: A comprehensive search of the PubMed, Web of Science, Embase and Cochrane databases was conducted up to Oct 2019. Studies evaluating the relationship between risk of IBD and variants of IL-12B (rs6887695, rs3212227 and rs10045431) were included. Odds ratio (OR) and 95% confidence interval (CI) were calculated. Trial sequential analysis (TSA) was implemented to estimate the required information size (RIS) and evaluate the credibility of the meta-analysis results.Results: Seventeen studies containing 9827 patients with CD, 7583 patients with UC and 16044 controls were included. The results showed significant association between rs6887695 polymorphism and susceptibility to CD (allele model: OR = 1.17, 95% CI: 1.12-1.22) and UC (allele model: OR = 1.16, 95% CI: 1.09-1.23), and "C" allele carriers had a higher risk, with TSA conclusive. For rs10045431, no significant association with CD susceptibility was identified, while a significantly increased risk in UC was found (allele mode: OR = 1.16, 95% CI: 1.07-1.25), both results were conclusive according to TSA. No significant association between rs3212227 and CD or UC susceptibility was found, and TSA research warranted further investigation to certify the results. No significant heterogeneity was found.Conclusion: IL-12B rs6887695 polymorphism was associated with increased risk of CD and UC, while IL-12B rs10045431 polymorphism might only be correlated with the risk of UC.Abbreviations: IBD: inflammatory bowel disease; CD: Crohn's disease; UC: ulcerative colitis; IL-12B: interleukin-12B; OR: odds ratio; CI: confidence interval; TSA: trial sequential analysis; RIS: required information size; DCs: dendritic cells; NK: nature killer; APCs: antigen-presenting cells; TNF: tumor necrosis factor; SNP: single nucleotide polymorphisms; HWE: Hardy-Weinberg equilibrium; NOS: Newcastle-Ottawa scale; RRR: relative risk reduction.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Colite Ulcerativa/genética , Predisposição Genética para Doença , Humanos , Doenças Inflamatórias Intestinais/genética , Subunidade p40 da Interleucina-12/genética , Polimorfismo de Nucleotídeo Único
13.
Clin Infect Dis ; 71(16): 2240-2242, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-32302000

RESUMO

COVID-19 has drawn global intensive attention. We analyzed the duration of viral shedding and the total time from illness onset to discharge in groups. This has important implications for making decisions for isolation of discharged patients and to provide guidance for the duration of hospitalization of patients with severe COVID-19.


Assuntos
COVID-19/diagnóstico , COVID-19/virologia , Faringe/virologia , Eliminação de Partículas Virais , Adolescente , Adulto , Idoso , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Fatores de Tempo , Adulto Jovem
14.
J Thromb Thrombolysis ; 50(1): 229-232, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32306290

RESUMO

The outbreak of 2019 novel coronavirus disease (COVID-19) began since early December 2019, and has been declared as a public health emergency by the World Health Organization. Due to the hypercoagulable state, blood stasis and endothelial injury, severe patients with COVID-19 are at high risk for thrombosis. We report a case of very severe COVID-19 complicated with venous thrombosis and arteriosclerosis obliterans of lower extremities. Risk stratification for deep vein thrombosis and peripheral arterial disease are of vital importance for the prognosis of COVID-19.


Assuntos
Arteriosclerose Obliterante/virologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Trombose Venosa/virologia , Idoso , COVID-19 , Humanos , Masculino , Pandemias
15.
Zhongguo Zhong Yao Za Zhi ; 45(2): 412-417, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237326

RESUMO

The bilirubin metabolism mediated by the phase Ⅱ metabolizing enzyme UGT1A1 in the liver was evaluated to study the potential hepatotoxicity risk based on investigation on the inhibitory effect of rhein and its metabolites on the UGT1A1 enzyme in Rhei Radix et Rhizoma. Firstly, in vitro liver microsomes incubation was used to initiate the phase Ⅱ metabolic reaction to investigate the inhibitory effect of rheinon UGT1A1 enzyme. Secondly, the phase Ⅰ and phase Ⅱ metabolic reactions were initiated to investigate the hepatotoxicity risk of rhein metabolites. It was found that the rhein and its phase Ⅱ metabolites had no significant inhibitory effect on UGT1A1 enzyme, but its phase Ⅰ metabolites significantly reduced UGT1A1 enzyme activity. Based on the metabolites analysis, it is speculated that the rhein phase Ⅰ metabolite rheinhydroxylate and its tautomers have certain hepatotoxicity risks, while the toxicity risk induced by the prototype and phase Ⅱ metabolites of rheinglucoside, rheinglucuronic acid and rhein sulfate is small.


Assuntos
Antraquinonas/toxicidade , Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas/toxicidade , Fígado/efeitos dos fármacos , Microssomos Hepáticos/efeitos dos fármacos , Glucuronosiltransferase/metabolismo , Humanos , Fígado/enzimologia , Rizoma
16.
Mol Cancer ; 18(1): 88, 2019 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-30979371

RESUMO

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) and cancer stem cells (CSCs) are two important cellular components in the tumor microenvironment, which may modify the cancer phenotype and affect patient survival. However, the crosstalk between MDSCs and multiple myeloma stem cells (MMSCs) are relatively poorly understood. METHODS: The frequencies of granulocytic-MDSCs (G-MDSCs) in MM patients were detected by flow cytometry and their association with the disease stage and patient survival were analyzed. RT-PCR, flow cytometry, western blot and sphere formation assays were performed to investigate the effects of G-MDSCs, piRNA-823 and DNA methylation on the maintenance of stemness in MM. Then a subcutaneous tumor mouse model was constructed to analyze tumor growth and angiogenesis after G-MDSCs induction and/or piRNA-823 knockdown in MM cells. RESULTS: Our clinical dataset validated the association between high G-MDSCs levels and poor overall survival in MM patients. In addition, for the first time we showed that G-MDSCs enhanced the side population, sphere formation and expression of CSCs core genes in MM cells. Moreover, the mechanism study showed that G-MDSCs triggered piRNA-823 expression, which then promoted DNA methylation and increased the tumorigenic potential of MM cells. Furthermore, silencing of piRNA-823 in MM cells reduced the stemness of MMSCs maintained by G-MDSCs, resulting in decreased tumor burden and angiogenesis in vivo. CONCLUSION: Altogether, these data established a cellular, molecular, and clinical network among G-MDSCs, piRNA-823, DNA methylation and CSCs core genes, suggesting a new anti-cancer strategy targeting both G-MDSCs and CSCs in MM microenvironment.


Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , Regulação Neoplásica da Expressão Gênica , Mieloma Múltiplo/genética , Células Supressoras Mieloides/metabolismo , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/metabolismo , RNA Interferente Pequeno/genética , Animais , Antagomirs/genética , Antagomirs/metabolismo , Comunicação Celular , Linhagem Celular Tumoral , DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA , Feminino , Granulócitos/metabolismo , Granulócitos/patologia , Humanos , Masculino , Camundongos , Camundongos Nus , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Células Supressoras Mieloides/patologia , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Células-Tronco Neoplásicas/patologia , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/mortalidade , Neovascularização Patológica/patologia , RNA Interferente Pequeno/antagonistas & inibidores , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Análise de Sobrevida , Microambiente Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto , DNA Metiltransferase 3B
17.
Biochem Biophys Res Commun ; 508(2): 339-347, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30473216

RESUMO

DNA mismatch repair-proficient colon cancer is the most common type of colon cancer, but its initiation and progression are still unknown. Our previous study has revealed that a long noncoding RNA (lncRNA) ENST00000455974 was significantly associated with TNM stage and distant metastasis in patients with DNA mismatch repair-proficient (pMMR) colon cancer (CC). Here, firstly, we observed that ENST00000455974 was gradual increased across colon normal-adenoma-carcinoma-metastasis sequence by quantitative real-time PCR. Secondly, ENST00000455974 showed a better sensitivity and specificity than CEA and CA19-9 in the diagnosis of pMMR CC by drawing the receiver operating characteristic (ROC) curve. Thirdly, a higher level of ENST00000455974 was associated with a poorer patient survival. Furthermore, Knockdown of ENST00000455974 led to reduced proliferation and migration of colon cancer cells. Mechanistically, ENST00000455974 was mainly located in the nucleus of colon cancer cells and it promoted the growth and metastasis of pMMR CC cells through up-regulating JAG2.


Assuntos
Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Reparo de Erro de Pareamento de DNA/genética , Proteína Jagged-2/genética , Proteína Jagged-2/metabolismo , RNA Longo não Codificante/genética , Adenoma/genética , Adenoma/metabolismo , Adenoma/patologia , Células CACO-2 , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias do Colo/patologia , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Oncogenes , Prognóstico , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/metabolismo , Regulação para Cima
18.
J Immunol ; 199(3): 941-954, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28652396

RESUMO

Innate regulation through TLR signaling has been shown to be important for promoting T cell subset development and function. However, limited information is known about whether differential TLR signaling can selectively inhibit Th17 and/or Th1 cells, which are important for controlling excessive inflammation and autoimmune responses. In this article, we demonstrate that activation of TLR7 signaling in T cells can inhibit Th17 cell differentiation from naive T cells and IL-17 production in established Th17 cells. We further report that downregulation of STAT3 signaling is responsible for TLR7-mediated inhibition of Th17 cells due to induction of suppressor of cytokine signaling 3 and 5. TLR7-mediated suppression of Th17 cells does not require dendritic cell involvement. In addition, we show that TLR7 signaling can suppress Th1 cell development and function through a mechanism different from Th17 cell suppression. Importantly, our complementary in vivo studies demonstrate that treatment with the TLR7 ligand imiquimod can inhibit Th1 and Th17 cells, resulting in the prevention of, and an immunotherapeutic reduction in, experimental autoimmune encephalomyelitis. These studies identify a new strategy to manipulate Th17/Th1 cells through TLR7 signaling, with important implications for successful immunotherapy against autoimmune and inflammatory diseases.


Assuntos
Autoimunidade/imunologia , Glicoproteínas de Membrana/metabolismo , Transdução de Sinais/imunologia , Células Th17/imunologia , Receptor 7 Toll-Like/metabolismo , Aminoquinolinas/administração & dosagem , Animais , Diferenciação Celular , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/fisiopatologia , Encefalomielite Autoimune Experimental/prevenção & controle , Encefalomielite Autoimune Experimental/terapia , Humanos , Imiquimode , Imunoterapia , Inflamação/terapia , Interleucina-17/biossíntese , Interleucina-17/imunologia , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/imunologia , Camundongos , Fator de Transcrição STAT3/metabolismo , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/imunologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th17/efeitos dos fármacos , Receptor 7 Toll-Like/genética , Receptor 7 Toll-Like/imunologia
19.
Rev Esp Enferm Dig ; 111(3): 209-213, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30449119

RESUMO

OBJECTIVE: to evaluate the medical economics and safety of two methods for the endoscopic removal of jujube pits, one with a transparent cap combined with a stone basket and the other with a transparent cap combined with foreign body forceps. METHODS: consecutive patients with a suspected jujube pit ingestion in the esophagus between January 2008 and December 2017 were enrolled into the study. Fifty-three patients who met the criteria were divided into two groups. Group A patients were treated by a transparent cap combined with a stone basket and group B patients were treated by a transparent cap combined with foreign body forceps. The following clinical data were collected: age, sex, location of jujube pits, complications, operation time, extraction success and average hospital costs. RESULTS: a total of 53 patients who met the criteria were enrolled into the study; 29 cases in group A and 24 cases in group B. Endoscopic removal was successful in 98.1% (52/53) of the patients and the remaining 1.9% (1/53) required surgery. Severe complications were less frequent in group A than in group B (p = 0.017). Surgery time was not significantly different between the two groups (p = 0.647). The extraction success in group A was higher than in group B (p = 0.001). The medical costs including the total cost, inspection, treatment, radiation and drug cost were not significantly different between the two groups (p > 0.05 in all cases). CONCLUSION: endoscopic baskets are suitable for cases of jujube pit ingestion and have a higher extraction success and a lower proportion of severe complications. Surgery time was not significantly extended and the medical costs did not increase.


Assuntos
Esofagoscopia/economia , Esôfago , Corpos Estranhos/cirurgia , Sementes , Ziziphus , Custos e Análise de Custo , Esofagoscopia/efeitos adversos , Esofagoscopia/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Instrumentos Cirúrgicos
20.
Zhongguo Zhong Yao Za Zhi ; 44(18): 4043-4047, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31872743

RESUMO

The purpose of this study was to investigate the effect of apigenin on UGT1 A1 enzyme activity and to predict the potential drug-drug interaction of apigenin in clinical use. First,on the basis of previous experiments,the binding targets and binding strength of apigenin to UGT1 A1 enzyme were predicted by computer molecular docking method. Then the inhibitory effect of apigenin on UGT1 A1 enzyme was evaluated by in vitro human liver microsomal incubation system. Molecular docking results showed that apigenin was docked into the active region of UGT1 A1 enzyme protein F,consistent with the active region of bilirubin docking,with moderate affinity. Apigenin flavone mother nucleus mainly interacted with amino acid residues ILE343 and VAL345 to form hydrophobic binding Pi-Alkyl. At the same time,the hydroxyl group on the mother nucleus and the amino acid residue LYS346 formed an additional hydrogen bond,which increased the binding of the molecule to the protein. These results suggested that the flavonoid mother nucleus structure had a special structure binding to the enzyme protein UGT1 A1,and the introduction of hydroxyl groups into the mother nucleus can increase the binding ability. In vitro inhibition experiments showed that apigenin had a moderate inhibitory effect on UGT1 A1 enzyme in a way of competitive inhibition,which was consistent with the results of molecular docking. The results of two experiments showed that apigenin was the substrate of UGT1 A1 enzyme,which could inhibit the activity of UGT1 A1 enzyme competitively,and there was a risk of drug interaction between apigenin and UGT1 A1 enzyme substrate in clinical use.


Assuntos
Apigenina/química , Bilirrubina/química , Interações Medicamentosas , Microssomos Hepáticos/efeitos dos fármacos , Simulação de Acoplamento Molecular , Glucuronosiltransferase/metabolismo , Humanos , Ligação de Hidrogênio
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