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1.
Shanghai Kou Qiang Yi Xue ; 33(1): 36-39, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38583022

RESUMO

PURPOSE: To study the effect of different cleaning methods on the shear bond strength of self-adhesive resin cement to saliva-contaminated high translucency zirconia and surface wettability. METHODS: Eighty zirconia specimens were randomly divided into 5 groups (n=16), i.e., control group(not contaminated), 75% ethanol group,cleaning paste group,airborne-particle abrasion group, and atmospheric pressure cold plasma group. The contact angles was measured, shear bond strength were examined, and fracture types were determined. SPSS 26.0 software package was used for statistical analysis of the data. RESULTS: The atmospheric pressure cold plasma group produced the lowest contact angle(P<0.05). The shear bond strength of the airborne-particle abrasion group, the cleaning paste group and the atmospheric pressure cold plasma group respectively were similar to the control group without significant difference(P>0.05), while those were significantly higher than 75% ethanol group(P<0.05). The mixed fracture mode of the atmospheric pressure cold plasma group evidently increased. CONCLUSIONS: Airborne-particle abrasion, cleaning paste and atmospheric pressure cold plasma overcome the effects of saliva contamination, producing the shear bond strength to zirconia similar to the control group. The atmospheric pressure cold plasma improves hydrophilicity of high translucency zirconia significantly.


Assuntos
Colagem Dentária , Gases em Plasma , Molhabilidade , Propriedades de Superfície , Cimentos de Resina , Zircônio/química , Etanol , Teste de Materiais , Resistência ao Cisalhamento , Análise do Estresse Dentário
2.
Sci Immunol ; 9(94): eadh2334, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669316

RESUMO

T cells are often absent from human cancer tissues during both spontaneously induced immunity and therapeutic immunotherapy, even in the presence of a functional T cell-recruiting chemokine system, suggesting the existence of T cell exclusion mechanisms that impair infiltration. Using a genome-wide in vitro screening platform, we identified a role for phospholipase A2 group 10 (PLA2G10) protein in T cell exclusion. PLA2G10 up-regulation is widespread in human cancers and is associated with poor T cell infiltration in tumor tissues. PLA2G10 overexpression in immunogenic mouse tumors excluded T cells from infiltration, resulting in resistance to anti-PD-1 immunotherapy. PLA2G10 can hydrolyze phospholipids into small lipid metabolites, thus inhibiting chemokine-mediated T cell mobility. Ablation of PLA2G10's enzymatic activity enhanced T cell infiltration and sensitized PLA2G10-overexpressing tumors to immunotherapies. Our study implicates a role for PLA2G10 in T cell exclusion from tumors and suggests a potential target for cancer immunotherapy.


Assuntos
Neoplasias , Linfócitos T , Regulação para Cima , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Imunoterapia/métodos , Linfócitos do Interstício Tumoral/imunologia , Camundongos Endogâmicos C57BL , Neoplasias/imunologia , Fosfolipases A/imunologia , Fosfolipases A/genética , Fosfolipases A2/imunologia , Linfócitos T/imunologia , Regulação para Cima/imunologia
3.
J Integr Neurosci ; 23(1): 12, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38287842

RESUMO

BACKGROUND: The acute changes that occur in the small-world topology of the brain in concussion patients remain unclear. Here, we investigated acute changes in the small-world organization of brain networks in concussion patients and their influence on persistent post-concussion symptoms. METHODS: Eighteen concussion patients and eighteen age-matched controls were enrolled in this study. All participants underwent computed tomography, magnetic resonance imaging (MRI), susceptibility weighted imaging, and blood oxygen level-dependent functional MRI. A complex network analysis method based on graph theory was used to calculate the parameters of small-world networks under different degrees of network sparsity. All subjects were evaluated using the Glasgow Coma Scale and Rivermead Postconcussion Symptom Questionnaire. RESULTS: Compared with the controls, the normalized cluster coefficient (γ) of whole brain networks in patients and the "small-world" index (σ) was slightly enhanced, whereas the standardized minimum path (λ) was slightly shorter. Whole brain effect (Eglobal) and local effect (Elocal) changes were not pronounced. Under the condition of minimum network sparsity (Dmin = 0.13), the numbers of nodes in the "right intraorbital superior frontal gyrus" (Anatomical Automatic Labeling, AAL26), right globus pallidus (AAL76), and bilateral temporal transverse gyrus (AAL79,80) in brain concussion patients were significantly lower. The numbers of nodes in the left subcapital lobe (AAL61) and left occipital gyrus (AAL51) were significantly higher, and the normalized cluster coefficients of the right intraorbital supraphalus (AAL26) and left posterior cingulate gyrus (AAL35) were significantly increased. The normalized clustering coefficients of the right triangular subfrontal gyrus (AAL55) (based on the normalized clustering coefficients of nodes in AAL14) and left sub-parietal lobes (AAL61) were significantly reduced. The mean local effects of nodes in the right intraorbital upper frontal gyrus (AAL26), left posterior cingulate gyrus (AAL35), and bilateral auxiliary motor cortex (AAL19, 20) were enhanced, whereas the mean local effects of the bilateral triangular inferior frontal gyrus (AAL13,14) and left insular cap (AAL11) were reduced (p < 0.05). CONCLUSIONS: The overall trend of network topology abnormalities in patients was random, and generalized and local functional abnormalities were seen. Changes in the function and affective circuitry of the resting default network were particularly pronounced in these patients, which we speculate may be one of the main drivers of the cognitive dysfunction and mood changes seen in concussion patients.


Assuntos
Concussão Encefálica , Humanos , Concussão Encefálica/diagnóstico por imagem , Concussão Encefálica/patologia , Encéfalo , Mapeamento Encefálico/métodos , Lobo Parietal , Lobo Frontal , Imageamento por Ressonância Magnética/métodos
4.
Nat Commun ; 15(1): 891, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291026

RESUMO

Procaspase 9 is the initiator caspase for apoptosis, but how its levels and activities are maintained remains unclear. The gigantic Inhibitor-of-Apoptosis Protein BIRC6/BRUCE/Apollon inhibits both apoptosis and autophagy by promoting ubiquitylation of proapoptotic factors and the key autophagic protein LC3, respectively. Here we show that BIRC6 forms an anti-parallel U-shaped dimer with multiple previously unannotated domains, including a ubiquitin-like domain, and the proapoptotic factor Smac/DIABLO binds BIRC6 in the central cavity. Notably, Smac outcompetes the effector caspase 3 and the pro-apoptotic protease HtrA2, but not procaspase 9, for binding BIRC6 in cells. BIRC6 also binds LC3 through its LC3-interacting region, probably following dimer disruption of this BIRC6 region. Mutation at LC3 ubiquitylation site promotes autophagy and autophagic degradation of BIRC6. Moreover, induction of autophagy promotes autophagic degradation of BIRC6 and caspase 9, but not of other effector caspases. These results are important to understand how the balance between apoptosis and autophagy is regulated under pathophysiological conditions.


Assuntos
Apoptose , Proteínas Inibidoras de Apoptose , Apoptose/genética , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Caspases/metabolismo , Autofagia/genética , Ubiquitinação , Proteínas Mitocondriais/metabolismo
5.
Discov Oncol ; 14(1): 184, 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37847433

RESUMO

Previous clinic models for patients with hepatocellular carcinoma (HCC) receiving transarterial chemoembolization (TACE) mainly focused on the overall survival, whereas a simple-to-use tool for predicting the response to the first TACE and the management of risk classification before TACE are lacking. Our aim was to develop a scoring system calculated manually for these patients. A total of 437 patients with hepatocellular carcinoma (HCC) who underwent TACE treatment were carefully selected for analysis. They were then randomly divided into two groups: a training group comprising 350 patients and a validation group comprising 77 patients. Furthermore, 45 HCC patients who had recently undergone TACE treatment been included in the study to validate the model's efficacy and applicability. The factors selected for the predictive model were comprehensively based on the results of the LASSO, univariate and multivariate logistic regression analyses. The discrimination, calibration ability and clinic utility of models were evaluated in both the training and validation groups. A prediction model incorporated 3 objective imaging characteristics and 2 indicators of liver function. The model showed good discrimination, with AUROCs of 0.735, 0.706 and 0.884 and in the training group and validation groups, and good calibration. The model classified the patients into three groups based on the calculated score, including low risk, median risk and high-risk groups, with rates of no response to TACE of 26.3%, 40.2% and 76.8%, respectively. We derived and validated a model for predicting the response of patients with HCC before receiving the first TACE that had adequate performance and utility. This model may be a useful and layered management tool for patients with HCC undergoing TACE.

6.
Ying Yong Sheng Tai Xue Bao ; 34(7): 1817-1824, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37694465

RESUMO

To screen environment-friendly seedling cultivation substrates which could replace peat and with less cost, we compared the effects of different agricultural and forestry residue mixed substrates on cutting propagation of Thuja sutchuenensis, in an experiment following randomized block design. There were five types of mixed substrates, including peat + vermiculite + perlite (T1), edible mushroom residue (EMR) + vermiculite + perlite (T2), carbo-nized rice husk (CRH) + vermiculite + perlite (T3), EMR + slag + sawdust (T4) and CRH + EMR + slag (T5). The results showed that the bulk density of T3 was the lowest, followed by T2, which significantly differed from other mixed substrates. The non-capillary porosity of T2 was significantly greater than that of T1, while the capillary porosity and the total porosity of T2 was lower than T1 and T3, respectively. T2 had the highest contents of total nitrogen, total phosphorus, total potassium, alkali-hydrolyzed nitrogen, available phosphorus, substrate moisture and the highest pH, which differed significantly from other mixed substrates in most chemical indicators. The membership function values of rooting rate and growth indicators of cuttings with different mixed substrates were in order of T2 > T3 > T1> T5 > T4. Most indicators with larger grey relation values were physical indicators. The top five indicators were capillary water capacity, total potassium, field water capacity, maximum water capacity, and total porosity, with both capillary water capacity and total potassium content ranking first. In general, the physicochemical properties, rooting rate, and growth characteristics of cuttings under T2 were better than those of other mixed substrates. The capillary water capacity and total potassium were the main factors affecting rooting and growth of cuttings. At the early stage of cutting, the physical properties of mixed substrate had greater effect on rooting rate and growth of cuttings than the chemical properties. Overall, our results suggested that T2 should be preferred in the cutting propagation of T. sutchuenensis.


Assuntos
Agaricales , Oryza , Thuja , Agricultura Florestal , Plântula , Solo , Carvão Vegetal , Nitrogênio , Fósforo , Potássio
7.
J Cancer Res Clin Oncol ; 149(12): 10161-10168, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37268850

RESUMO

BACKGROUND: The pre-operative non-invasive differential diagnosis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) mainly depends on imaging. However, the accuracy of conventional imaging and radiomics methods in differentiating between the two carcinomas is unsatisfactory. In this study, we aimed to establish a novel deep learning model based on computed tomography (CT) images to provide an effective and non-invasive pre-operative differential diagnosis method for HCC and ICC. MATERIALS AND METHODS: We retrospectively investigated the CT images of 395 HCC patients and 99 ICC patients who were diagnosed based on pathological analysis. To differentiate between HCC and ICC we developed a deep learning model called CSAM-Net based on channel and spatial attention mechanisms. We compared the proposed CSAM-Net with conventional radiomic models such as conventional logistic regression, least absolute shrinkage and selection operator regression, support vector machine, and random forest models. RESULTS: With respect to differentiating between HCC and ICC, the CSAM-Net model showed area under the receiver operating characteristic curve (AUC) values of 0.987 (accuracy = 0.939), 0.969 (accuracy = 0.914), and 0.959 (accuracy = 0.912) for the training, validation, and test sets, respectively, which were significantly higher than those of the conventional radiomics models (0.736-0.913 [accuracy = 0.735-0.912], 0.602-0.828 [accuracy = 0.647-0.818], and 0.638-0.845 [accuracy = 0.618-0.849], respectively. The decision curve analysis showed a high net benefit of the CSAM-Net model, which suggests potential efficacy in differentiating between HCC and ICC in the diagnosis of liver cancers. CONCLUSIONS: The proposed CSAM-Net model based on channel and spatial attention mechanisms provides an effective and non-invasive tool for the differential diagnosis of HCC and ICC on CT images, and has potential applications in diagnosis of liver cancers.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Diagnóstico Diferencial , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/patologia , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos
8.
Front Immunol ; 14: 1266667, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38283340

RESUMO

Intestinal tuft cells (TCs) are defined as chemosensory cells that can "taste" danger and induce immune responses. They play a critical role in gastrointestinal parasite invasion, inflammatory bowel diseases and high-fat diet-induced obesity. Intestinal IL-25, the unique product of TCs, is a key activator of type 2 immunity, especially to promote group 2 innate lymphoid cells (ILC2s) to secret IL-13. Then the IL-13 mainly promotes intestinal stem cell (ISCs) proliferation into TCs and goblet cells. This pathway formulates the circuit in the intestine. This paper focuses on the potential role of the intestinal TC, ILC2 and their circuit in obesity-induced intestinal damage, and discussion on further study and the potential therapeutic target in obesity.


Assuntos
Imunidade Inata , Interleucina-13 , Humanos , Interleucina-13/metabolismo , Células em Tufo , Linfócitos , Intestinos , Obesidade/metabolismo
9.
Science ; 376(6596): 996-1001, 2022 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-35617401

RESUMO

T cell quiescence is essential for maintaining a broad repertoire against a large pool of diverse antigens from microbes and tumors, but the underlying molecular mechanisms remain largely unknown. We show here that CD8α is critical for the maintenance of CD8+ T cells in a physiologically quiescent state in peripheral lymphoid organs. Upon inducible deletion of CD8α, both naïve and memory CD8+ T cells spontaneously acquired activation phenotypes and subsequently died without exposure to specific antigens. PILRα was identified as a ligand for CD8α in both mice and humans, and disruption of this interaction was able to break CD8+ T cell quiescence. Thus, peripheral T cell pool size is actively maintained by the CD8α-PILRα interaction in the absence of antigen exposure.


Assuntos
Antígenos CD8 , Linfócitos T CD8-Positivos , Ativação Linfocitária , Glicoproteínas de Membrana , Receptores Imunológicos , Animais , Antígenos , Antígenos CD8/genética , Antígenos CD8/metabolismo , Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Deleção de Genes , Glicoproteínas de Membrana/metabolismo , Camundongos , Receptores Imunológicos/metabolismo
10.
J Clin Neurol ; 18(1): 41-47, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35021275

RESUMO

BACKGROUND AND PURPOSE: Mutations in the FIG4 gene have been linked to amyotrophic lateral sclerosis (ALS) type 11 in Caucasian populations. The purpose of this study was to identify FIG4 variants in a cohort of 15 familial ALS (FALS) indexes and 275 sporadic ALS (SALS) patients of Han Chinese origin. METHODS: All 23 exons of FIG4 were sequenced using targeted next-generation sequencing. An extensive literature review was performed to detect genotype-phenotype associations of FIG4 mutations. RESULTS: No FIG4 variants were identified in the FALS patients. One novel heterozygous missense variant (c.352G>T [p.D118Y]) and one novel heterozygous nonsense variant (c.2158G>T [p.E720X]) in FIG4 were identified in two SALS patients. The p.E720X variant is interpreted as likely pathogenic while the p.D118Y variant is a variant of uncertain significance. The patient carrying the p.E720X mutation developed lower-limb-onset slowly progressive ALS, and survived for 11.5 years. The patient harboring the FIG4 p.D118Y variant also presented with progressive ALS, with the score on the ALS Functional Rating Scale-Revised (ALSFRS-R) decreasing by 0.4 per month. The rate of decrease in the ALSFRS-R scores from symptom onset to diagnosis seemed to be lower in the patients carrying FIG4 variants than the no-FIG4-mutation ALS patients in this study. CONCLUSIONS: Our findings suggest that ALS patients carrying FIG4 mutations are not common in the Chinese population and are more likely to exhibit slow progression.

11.
Cancer Discov ; 11(7): 1700-1715, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33658301

RESUMO

Specific mechanisms by which tumor-infiltrating lymphocytes (TIL) become dysfunctional remain poorly understood. Here, we employed a two-pronged approach using single-cell mass cytometry and tissue imaging technologies to dissect TILs from 25 patients with resectable and 35 patients with advanced non-small cell lung cancer (NSCLC). We identified a burned-out CD8+ TIL subset (Ebo) that specifically accumulated within the tumor microenvironment (TME) but not in adjacent nontumoral tissues. Ebo showed the highest expression of proliferation and activation markers but produced the lowest amount of IFNγ and were the most apoptotic CD8+ TIL subset. Using a humanized patient-derived tumor xenograft model, we demonstrated that Ebo expansion occurred within the TME in a PD-1/B7-H1 pathway-dependent manner. Ebo abundance in baseline tumor tissues was associated with resistance to anti-PD therapy in patients with NSCLC. Our study identifies a dysfunctional TIL subset, with distinct features from previously described exhausted T cells, and implies strategies to overcome immunotherapy resistance. SIGNIFICANCE: We identified a highly proliferative, overactivated, and apoptotic dysfunctional CD8+ tumor-infiltrating subpopulation that is functionally distinct from previously described exhausted T cells. This population is expanded in lung cancer tissues in a PD-1/B7-H1-dependent manner, and its abundance is associated with resistance to cancer immunotherapy, thus becoming a potential tissue biomarker.This article is highlighted in the In This Issue feature, p. 1601.


Assuntos
Linfócitos T CD8-Positivos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Microambiente Tumoral , Idoso , Animais , Carcinoma Pulmonar de Células não Pequenas/terapia , Feminino , Humanos , Imunoterapia , Neoplasias Pulmonares/terapia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Estudos Prospectivos
12.
Front Neurol ; 12: 604052, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33633666

RESUMO

Myasthenia gravis (MG) is an autoimmune disease in which antibodies bind to acetylcholine receptors (AChR) or other functional molecules in the postsynaptic membrane at the neuromuscular junction. Vitamin D (VD) has a number of pluripotent effects, which include immune-regulation and bone metabolism. The immunomodulatory actions of 1,25(OH)2D3 are mediated by its binding to a vitamin D receptor (VDR). In the study, we undertook a case-control study to explore the association between VDR gene polymorphism and the susceptibility and severity of MG patients. Four hundred and eighty MG patients and 487 healthy controls were included and gene polymorphisms of VDR were determined with improved multiplex ligation detection reaction technique and SNPscanTM technique. MG patients were classified into subgroups by essential clinical features and by a comprehensive classification. The frequencies of alleles and genotypes were compared between the MG group and the control group, between each MG subgroup and the control group, and between each pair of MG subgroups. There were no significant differences in frequencies of alleles and genotypes between MG patients and healthy controls, between MG subgroups and healthy controls, or between each pair of MG subgroups in the analysis of subgroups classified by essential clinical features (onset age, gender, thymoma, AChRAb positivity, onset involvement) and the maximal severity (modified Oosterhuis score). In the analysis of subgroups with a comprehensive classification, the frequencies of alleles and genotypes in rs731236 showed significant differences between adult non-thymoma AChRAb negative MG subgroup and the control group, as well as the adult non-thymoma AChRAb positive MG group. In the Chinese Han population, rs731236 was found to be possibly associated with adult non-thymoma AChRAb negative MG patients, although this needs further confirmation.

13.
Diabetes Metab Res Rev ; 35(5): e3142, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30767421

RESUMO

OBJECTIVES: Pancreas steatosis is the description of fat accumulation in the pancreatic gland. The prevalence and development mechanisms of pancreatic steatosis in patients with metabolic disorders still remain unclear. The aim of this study is to systematically review the association between pancreatic steatosis and metabolic co-morbidities. METHODS: We performed a systematic search strategy using three electronic databases (MEDLINE, Scopus, and Embase) for relevant studies concerning the associations of pancreatic steatosis with metabolic syndrome (MetS) and its clinical relevance from inception until 30 September 2018. RESULTS: One thousand three hundred fifty one references were identified in the initial search, and a total of 13 studies involving 49 329 subjects were included. This analyses elucidated the presence of non-alcoholic fatty pancreas disease (NAFPD) and was associated with a significant increased risk of metabolic syndrome (RR = 2.25; 95% CI, 2.00-2.53; P < 0.0001; I2  = 42.8%; eight studies included), hypertension (RR = 1.43; 95% CI, 1.08-1.90; P = 0.013; I2  = 94.7%; nine studies included), non-alcoholic fatty liver disease (NAFLD) (RR = 2.49; 95% CI, 2.06-3.02; P < 0.0001; I2  = 96.9%; nine studies included), diabetes mellitus (RR = 1.99; 95% CI, 1.18-3.35; P = 0.01; I2  = 97.6%; 10 studies included), and central obesity (RR = 1.91; 95% CI, 1.67-2.19; P < 0.0001; I2  = 95.9%; six studies included). The association between NAFPD and hyperlipidaemia was not statistically significant (RR = 1.33; 95% CI, 0.82-2.17; P = 0.249; I2  = 97%; five studies included). CONCLUSIONS: The existing evidence indicates that NAFPD is significantly associated with an increased risk of metabolic syndrome and its components. Well-designed prospective cohort studies between pancreatic steatosis and MetS are needed to elaborate the causality in the future.


Assuntos
Transtornos do Metabolismo dos Lipídeos/epidemiologia , Síndrome Metabólica/epidemiologia , Pancreatopatias/epidemiologia , Complicações do Diabetes/epidemiologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/metabolismo , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/epidemiologia , Transtornos do Metabolismo dos Lipídeos/complicações , Síndrome Metabólica/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade Abdominal/complicações , Obesidade Abdominal/epidemiologia , Pancreatopatias/complicações , Prevalência , Fatores de Risco
14.
Cell ; 176(1-2): 334-347.e12, 2019 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-30580966

RESUMO

Lymphocyte-activation gene 3 (LAG-3) is an immune inhibitory receptor, with major histocompatibility complex class II (MHC-II) as a canonical ligand. However, it remains controversial whether MHC-II is solely responsible for the inhibitory function of LAG-3. Here, we demonstrate that fibrinogen-like protein 1 (FGL1), a liver-secreted protein, is a major LAG-3 functional ligand independent from MHC-II. FGL1 inhibits antigen-specific T cell activation, and ablation of FGL1 in mice promotes T cell immunity. Blockade of the FGL1-LAG-3 interaction by monoclonal antibodies stimulates tumor immunity and is therapeutic against established mouse tumors in a receptor-ligand inter-dependent manner. FGL1 is highly produced by human cancer cells, and elevated FGL1 in the plasma of cancer patients is associated with a poor prognosis and resistance to anti-PD-1/B7-H1 therapy. Our findings reveal an immune evasion mechanism and have implications for the design of cancer immunotherapy.


Assuntos
Antígenos CD/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/fisiologia , Animais , Antígenos CD/imunologia , Linhagem Celular , Fibrinogênio/imunologia , Fibrinogênio/metabolismo , Genes MHC da Classe II/genética , Genes MHC da Classe II/imunologia , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Imunoterapia , Ligantes , Fígado/metabolismo , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas de Neoplasias/genética , Neoplasias/imunologia , Linfócitos T Citotóxicos/imunologia , Proteína do Gene 3 de Ativação de Linfócitos
15.
Int J Rheum Dis ; 21(2): 573-578, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26224252

RESUMO

Weber-Christian disease (WCD) is a chronic recurrent organ disease characterized by the formation of painful dense nodes in subcutaneous fat tissues, free from suppuration and accompanied by episodic temperature changes, chills and muscular pain. Sometimes it can involve the visceral organs. WCD often relapses during irregular intervals. It is a rare autoimmune inflammatory disorder of subcutaneous adipose tissue. However, lung involvement in WCD is rare. Here we report a man presenting with lung nodules. He was diagnosed as having WCD and successfully treated by corticosteroid and immonosuppressive agents. A 53-year-old male presented with a 2.5-year history of painful subcutaneous nodules on his trunk and limbs, accompanied by fever, night sweats, fatigue and malaise. A skin biopsy showed fat degeneration with foamy cells and infiltration of mononuclear cells. He was diagnosed as panniculitis and effectively treated by corticosteroid therapy at first. However, symptoms relapsed when the dosage of corticosteroid was tapered, and multiple lung nodules were found with the symptom of dyspnea in chest computed tomography scan during the follow-up period. Histological examination of the biopsy specimens from the lung was compatible with panniculitis change in the subcutanous nodule. Combination therapy of corticosteroid with cyclophosphamide was effective during the following 27 months.


Assuntos
Corticosteroides/uso terapêutico , Metilprednisolona/uso terapêutico , Nódulos Pulmonares Múltiplos/tratamento farmacológico , Paniculite Nodular não Supurativa/tratamento farmacológico , Biópsia , Ciclofosfamida/uso terapêutico , Quimioterapia Combinada , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos/diagnóstico , Nódulos Pulmonares Múltiplos/etiologia , Paniculite Nodular não Supurativa/complicações , Paniculite Nodular não Supurativa/diagnóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Resultado do Tratamento
16.
Nat Prod Res ; 32(6): 668-675, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28602105

RESUMO

Chemical investigation of the ethanolic extracts of the dried leaves of Bergenia purpurascens led to the isolation and identification of a new aromatic glycoside, 1-O-ß-D-glucopyranosyl-2-methoxy-3-hydroxyl-phenylethene (1), along with other 19 known compounds (2-20). The structure of compound 1 was determined by a detailed analysis using various analytical techniques, including 1D and 2D NMR. In vitro anti-proliferative activities of compound 1 on five human cancer cell lines were evaluated. The results showed that compound 1 possessed the most potent effects with the IC50 values of 14.36 ± 1.04 µM against T24 cells. The further bioactivity analysis showed that compound 1 induced apoptosis of T24 cells, and altered anti- and pro-apoptotic proteins, leading to mitochondrial dysfunction and activation of caspase-3 for causing cell apoptosis. The present investigation illustrated compound 1 might be used as a potential antitumour chemotherapy candidate.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Saxifragaceae/química , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular , Estrutura Molecular , Extratos Vegetais/química , Folhas de Planta/química , Plantas Medicinais/química , Proteínas Proto-Oncogênicas c-bcl-2/química , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
17.
Nat Prod Commun ; 11(2): 177-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27032194

RESUMO

Chemical constituents of the dried aerial parts of Euphorbia nematocypha were investigated. A new oleanane triterpenoid, trans, trans-2',4'- hexadienedioicacid-1'-ß-amyrin ester (1), together with, ß-amyrin (2), ß-amyrin acetate (3), betulinic acid (4), ellagic acid (5), oleanolic acid (6), ß-sitosterol (7), kaempferol (8), quercetin (9), lupeol (10) and pseudo-taraxasterol (11) were isolated from the methylene chloride extract. Their structures were elucidated on the basis of extensive spectroscopic (1D- & 2D-NMR) and ESI-MS analysis and comparison with data reported in the literature. The new isolated triterpenoid showed moderate cytotoxic activities against HeLa and MCF-7cell lines.


Assuntos
Euphorbia/química , Componentes Aéreos da Planta/química , Triterpenos/química , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Estrutura Molecular , Ácido Oleanólico/análogos & derivados
18.
PLoS One ; 11(1): e0142687, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26727517

RESUMO

The kidney displays specialized regions devoted to filtration, selective reabsorption, and electrolyte and metabolite trafficking. The polarized membrane pumps, channels, and transporters responsible for these functions have been exhaustively studied. Less examined are the contributions of spectrin and its adapter ankyrin to this exquisite functional topography, despite their established contributions in other tissues to cellular organization. We have examined in the rodent kidney the expression and distribution of all spectrins and ankyrins by qPCR, Western blotting, immunofluorescent and immuno electron microscopy. Four of the seven spectrins (αΙΙ, ßΙ, ßΙΙ, and ßΙΙΙ) are expressed in the kidney, as are two of the three ankyrins (G and B). The levels and distribution of these proteins vary widely over the nephron. αΙΙ/ßΙΙ is the most abundant spectrin, found in glomerular endothelial cells; on the basolateral membrane and cytoplasmic vesicles in proximal tubule cells and in the thick ascending loop of Henle; and less so in the distal nephron. ßΙΙΙ spectrin largely replaces ßΙΙ spectrin in podocytes, Bowman's capsule, and throughout the distal tubule and collecting ducts. ßΙ spectrin is only marginally expressed; its low abundance hinders a reliable determination of its distribution. Ankyrin G is the most abundant ankyrin, found in capillary endothelial cells and all tubular segments. Ankyrin B populates Bowman's capsule, podocytes, the ascending thick loop of Henle, and the distal convoluted tubule. Comparison to the distribution of renal protein 4.1 isoforms and various membrane proteins indicates a complex relationship between the spectrin scaffold, its adapters, and various membrane proteins. While some proteins (e.g. ankyrin B, ßΙΙΙ spectrin, and aquaporin 2) tend to share a similar distribution, there is no simple mapping of different spectrins or ankyrins to most membrane proteins. The implications of this data are discussed.


Assuntos
Anquirinas/análise , Rim/química , Espectrina/análise , Animais , Anquirinas/genética , Western Blotting , Citoesqueleto/ultraestrutura , Éxons/genética , Rim/fisiologia , Rim/ultraestrutura , Proteínas de Membrana/análise , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Microscopia Imunoeletrônica , Reação em Cadeia da Polimerase , Isoformas de Proteínas/análise , Isoformas de Proteínas/genética , RNA Mensageiro/análise , RNA Mensageiro/genética , Organismos Livres de Patógenos Específicos , Espectrina/genética
19.
Bull Environ Contam Toxicol ; 95(6): 815-21, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26508427

RESUMO

This study evaluated the level of PAH pollution in typical contaminated coking sites in Shenyang. Sixty surface soil samples were collected from an area of 1.3 × 10(5) m(2) polluted by PAHs. The concentrations, sources and possible health risks of 16 PAHs in the area were analyzed. The average content of Σ16 PAHs was 6.1 × 10(3) mg/kg. In oral intake, benzo(a)pyrene (BaP) presented the largest exposure risk (hazard quotient HQ = 1.17 × 10(-5)), followed by dibenz(a,h)anthracene (DbA) (HQ = 1.14 × 10(-5)). The non-carcinogenic hazard indices and carcinogenic risks of the PAHs were arranged in the order of BaP > DbA > benzo(b)fluoranthene (BbF) > benz(a)anthracene (BaA) > indeno(1,2,3-cd)pyrene (InP) > benzo(k)fluoranthene (BkF) > chrysene (Chr). Bap and DbA were the principal pollution sources, followed by BbF, BaA, InP, BkF and Nap successively. Oral intake was the main route of PAH entry into the human body.


Assuntos
Carcinógenos/análise , Coque , Hidrocarbonetos Policíclicos Aromáticos/análise , Solo/química , Carcinógenos/toxicidade , China , Cidades , Humanos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Pirenos , Medição de Risco
20.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 34(10): 1207-11, 2014 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-25509263

RESUMO

OBJECTIVE: To study the effect of electro-acupuncture (EA) at points along Foot Yangming Channel on metabolite of ulcerative colitis (UC) rats' cerebral cortex and to identify key metabolites by referring to Pi/Wei-brain related theory in Chinese medicine (CM). METHODS: The UC rat model was set up by dextran sulfate sodium (DSS) method. Male SD rats were randomly divided into the model group and the EA group, 13 in each group. Another 13 rats were recruited as the blank control group. Rats in the blank control group and the model group received no EA. EA was performed at Zusanli (ST36), Shangjuxu (ST37), and Tianshu (ST25) for 5 days by using disperse-dense wave. Then all rats were sacrificed. Their recto-colon and the ileocecal junction were pathomorphologically observed by light microscope and transmission electron microscope (TEM). Cerebral cortexes were extracted. Water-soluble and lipid-soluble brain tissue metabolites were respectively extracted for metabolic research using 1H nuclear magnetic resonance (1H-NMR). RESULTS: EA could obviously improve the general condition of UC model rats, decrease the value of DAI, reduce the infiltration of inflammatory cells in the intestinal tract, stabilize structures such as mitochondria, endoplasmic reticulum and so on (P <0.05). 1HNMR analysis showed that in the model group, contents of glutamic acid, cholesterol, very low density lipoproein (VLDL) in the pallium obviously decreased, while alanine and low density lipoprotein (LDL) significantly increased. After EA, levels of lactic acid, glutamic acid, total cholesterol (TC), and VLDL all increased, and levels of alanine and LDL decreased. All indices were approximate to those of the blank control group. CONCLUSION: EA at Foot Yangming channel was found to have some effect on metabolites in the brain tissue of UC model rats, which had specific metabonomic material basis and mechanism based on the Pi/Wei-brain related theory.


Assuntos
Córtex Cerebral/metabolismo , Colite Ulcerativa , Eletroacupuntura , Pontos de Acupuntura , Animais , Lipídeos , Masculino , Ratos Sprague-Dawley
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