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1.
J Hazard Mater ; 382: 121018, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31446354

RESUMO

The broad spectrum detection of veterinary drugs is very important for rapid and large-scale safe screen of animal-derived foods. Metal-organic frameworks (MOFs), as a kind of emerged functional porous materials are quite promising in the chemical sensing and molecular detection. In this work, we report the high-performance broad spectrum detection of 15 commonly-used veterinary drugs through the fluorescence quenching in a newly-designed chemically stable Al-based MOF, Al3(µ3-O)(OH)(H2O)2(PPTTA)3/2 (BUT-22). To the best of our knowledge, this is the first systematic investigation for the application of MOFs in the detection/sensing of veterinary drugs through fluorescence quenching method. The quenching efficiencies of the tested veterinary drugs on BUT-22 are all beyond 82%, and the limits of detection (LOD) are low at parts per billion (ppb) levels. Interestingly, BUT-22 also enables the selective detection of nicarbazin (NIC) through the clearly-observed red shift of its maximum fluorescence emission wavelength. Moreover, the fluorescence quenching mechanism was explored with the help of theoretical calculations. Our work indicates that MOFs are favorable materials for the detection of veterinary drugs, being potentially useful in monitoring drug residues of animal-derived foods.

2.
Arch Osteoporos ; 15(1): 1, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31802295

RESUMO

PURPOSE: This study aimed to evaluate the prevalence and risk factors of secondary osteoporosis (OP) in patients with systemic lupus erythematosus (SLE) and provide a theoretical basis for clinical prevention and treatment of SLE. METHODS: Take systematic review and meta-analysis of relevant studies. Data sources are CINAHL databases, PubMed, Embase, Wan Fang, Weipu, and CNKI databases. Eligibility criteria are cross-sectional or case-control studies which analyzed the prevalence and risk factors of OP in SLE. Two authors independently screened all studies; a third author verified and identify controversial studies. The quality of the included articles was evaluated. Stata 11 and Rev-Man 5.2 software were used for data processing. RESULTS: Thirty-one articles were included, with a total sample size of 3089 SLE, including 529 OP cases and 2560 non-OP cases. Meta-analysis showed that the prevalence of OP among SLE was 16% (95% CI (0.12, 0.19)). The risk of OP in SLE cases compared with controls was significantly greater with OR of 2.03 (95% CI 1.33-3.10, P = 0.001). Age, disease duration, cumulative glucocorticoid dose, duration of glucocorticoid therapy, SLICC, and menopause had significant differences between two groups. No statistical differences of daily glucocorticoid dose, SLEDAI, and BMI were found between OP and non-OP cases. CONCLUSIONS: Our study found a statistically significant increased risk of OP in SLE patients compared with controls. SLE patients should be actively screened for OP and its consequences. Larger longitudinal studies are needed to confirm this possible association. The prevalence of OP in SLE was 16%. Compared with controls, the risk of OP in SLE was 2.03. There were significant differences of age, disease duration, cumulative glucocorticoid dose, time of glucocorticoid, SLICC, and menopause, while daily glucocorticoid dose, SLEDAI, and BMI had no statistical differences between OP and non-OP cases.

3.
Adv Immunol ; 144: 121-153, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31699215

RESUMO

T helper 17 (Th17) cells, characterized by secretion of IL-17 and IL-17F, are a specialized CD4+ effector T cell lineage that not only facilitates host defense against pathogen infection and maintenance of mucosal barrier, but also potently induces tissue inflammation and autoimmune diseases. Since its discovery in 2005, the developmental program of Th17 cells has been characterized, which involves a number of key cytokines, transcription factors and multiple layers of epigenetic modifications. However, how these mechanisms integrate into the complex regulatory network in Th17 cells has not been well defined. Emerging evidences have revealed essential roles of cofactors in controlling chromosome accessibilities and activities of Th17-specific transcription factors. Moreover, cofactors also act as critical signaling integrators to coordinate multiple signaling pathways and transcriptional programs. Deficiency or dysregulation of these cofactors results in defects in Th17 responses and induction of associated autoimmune diseases. Our lab has recently reported several important cofactors in Th17 cells. Here we summarize our findings regarding this new scenario of developmental regulation of Th17 cells. These findings may benefit the development of innovative strategies to treat autoimmune diseases.

4.
Radiat Res ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714866

RESUMO

It is well known that mitochondria and the endoplasmic reticulum (ER) play important roles in radiation response, but their functions in radiation-induced bystander effect (RIBE) are largely unclear. In this study, we found that when a small portion of cells in a population of human lung fibroblast MRC-5 cells were precisely irradiated through either the nuclei or cytoplasm with counted microbeam protons, the yield of micronuclei (MN) and the levels of intracellular reactive oxygen species (ROS) in nonirradiated cells neighboring irradiated cells were significantly increased. Mito/ER-tracker staining demonstrated that the mitochondria were clearly activated after nuclear irradiation and ER mass approached a higher level after cytoplasmic irradiation. Moreover, the radiation-induced ROS was diminished by rotenone, an inhibitor of mitochondria activation, but it was not influenced by siRNA interference of BiP, an ER regulation protein. While for nuclear irradiation, rotenone-enhanced radiation-induced ER expression, and BiP siRNA eliminated radiation-induced activation of mitochondria, these phenomena were not observed for cytoplasmic irradiation. Bystander MN was reduced by rotenone but enhanced by BiP siRNA. When the cells were treated with both rotenone and BiP siRNA, the MN yield was reduced for nuclear irradiation but was enhanced for cytoplasmic irradiation. Our results suggest that the organelles of mitochondria and ER have different roles in RIBE with respect to nuclear and cytoplasmic irradiation, and the function of ER is a prerequisite for mitochondrial activation.

5.
Nanoscale ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31782464

RESUMO

This work reports a fundamental study on the relationship of the electronic structure, catalytic activity and surface reconstruction process of Fe doped NiS2 (FexNi1-xS2) for the oxygen evolution reaction (OER). A combined photoemission and X-ray absorption spectroscopic study reveals that Fe doping introduces more occupied Fe 3d6 states at the top of the valence band and thereby induces a metallic phase. Meanwhile, Fe doping also significantly increases the OER activity and results in much better stability with the optimum found for Fe0.1Ni0.9S2. More importantly, we performed detailed characterization to track the evolution of the structure and composition of the catalysts after different cycles of OER testing. Our results further confirmed that the catalysts gradually transform into amorphous (oxy)hydroxides which are the actual active species for the OER. However, a fast phase transformation in NiS2 is accompanied by a decrease of OER activity, because of the formation of a thick insulating NiOOH layer limiting electron transfer. On the other hand, Fe doping retards the process of transformation, because of a shorter Fe-S bond length (2.259 Å) than Ni-S (2.400 Å), explaining the better electrochemical stability of Fe0.1Ni0.9S2. These results suggest that the formation of a thin surface layer of NiFe (oxy)hydroxide as an active OER catalyst and the remaining Fe0.1Ni0.9S2 as a conductive core for fast electron transfer is the base for the high OER activity of FexNi1-xS2. Our work provides important insight and design principle for metal chalcogenides as highly active OER catalysts.

6.
ACS Appl Mater Interfaces ; 11(47): 44451-44457, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31689078

RESUMO

Lead sulfide nanoparticles (PbS NPs) are used in the short-wavelength infrared photodetectors because of their excellent photosensitivity, band gap tunability, and solution processability. It has been a challenge to synthesize high-quality PbS NPs with an absorption peak beyond 2000 nm. In this work, using PbS seed crystals with an absorption peak at 1960 nm, we report a successful synthesis of very large monodispersed PbS NPs having a diameter up to 16 nm by multiple injections. The resulting NPs have an absorption peak over 2500 nm with a small full width at half-maximum of 24 meV. To demonstrate the applications of such large quantum dots (QDs), broadband heterojunction photodetectors are fabricated with the large PbS QDs of an absorption peak at 2100 nm. The resulting devices have an external quantum efficiency (EQE) of 25% (over 50% internal quantum efficiency) at 2100 nm corresponding to a responsivity of 0.385 A/W and an EQE of ∼60% in the visible range.

7.
Immunity ; 51(5): 826-839.e5, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31732165

RESUMO

T follicular helper (Tfh) cells provide essential help to B cells in germinal center (GC) reactions. Bcl6 is the obligatory lineage transcription factor in Tfh cells. Here, we examined the molecular pathways that induce Bcl6 gene expression and underscore Bcl6-dependent function during Tfh cell commitment. Integration of genome-wide Bcl6 occupancy in Tfh cells and differential gene expression analyses suggested an important role for the transcription factor Tox2 in Tfh cell differentiation. Ectopic expression of Tox2 was sufficient to drive Bcl6 expression and Tfh development. In genome-wide ChIP-seq analyses, Tox2-bound loci associated with Tfh cell differentiation and function, including Bcl6. Tox2 binding was associated with increased chromatin accessibility at these sites, as measured by ATAC-seq. Tox2-/- mice exhibited defective Tfh differentiation, and inhibition of both Tox2 and the related transcription factor Tox abolished Tfh differentiation. Thus, a Tox2-Bcl6 axis establishes a transcriptional feed-forward loop that promotes the Tfh program.

9.
Inorg Chem ; 58(23): 15909-15916, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31725278

RESUMO

In recent years, more and more research on metal-organic frameworks (MOFs) has focused on exploring their practical applications, where the stability is crucial. Besides the metal-ligand coordination bond, the configuration of the ligand also plays an important role in determining the stability of resulting MOFs. In this work, we demonstrate that fixing flexible arms of core-shared ligands can enhance the stability of their Zr(IV)-MOFs. Two groups, four core-shared tetracarboxylate ligands, 3,3',3″,3‴-(pyrene-1,3,6,8-tetrayltetrakis(benzene-4,1-diyl))tetraacrylate (PTSA4-) and 6,6',6″,6‴-(pyrene-1,3,6,8-tetrayl)tetrakis(2-naphthoate) (PTNA4-) with the pyrene core and 3,3',3″,3‴-((9H-carbazole-1,3,6,8-tetrayl)tetrakis(benzene-4,1-diyl))-tetraacrylate (CTSA4-) and 6,6',6″,6‴-(9H-carbazole-1,3,6,8-tetrayl)tetrakis-(2-naphthoate) (CTNA4-) with the carbazole core are rationally designed. Two ligands in each group have different flexibilities due to the distinct side arms: the styrene arm is flexible, whereas the naphthalene is rigid. Constructed with Zr6 clusters, four 4,8-connected Zr(IV)-MOFs, Zr6O4(OH)8(H2O)4(PTSA)2 (BUT-72) and Zr6O4(OH)8(H2O)4(PTNA)2 (BUT-73) with a sqc-a topologic framework structure and Zr6O4(OH)8(H2O)4(CTSA)2 (BUT-74) and Zr6O4(OH)8(H2O)4(CTNA)2 (BUT-63) with a scu-a structure are obtained, respectively. It is found that the stability of BUT-73 and -63 with the rigid naphthoate-based ligands is significantly enhanced compared with that of BUT-72 and -74 with the flexible phenyl acrylate-based ones. Moreover, stable BUT-63 represents outstanding performance in the molecular recognition of most solvents commonly used in organic synthesis and industrial manufacture.

10.
Environ Int ; 134: 105288, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31765862

RESUMO

Despite the global abundance of studies on children's lead (Pb) exposure, the magnitude of Pb exposure among children across China remains unclear, especially for rural areas. In 2000, Pb was removed from petrol, marking a change in the sources of Pb exposure in China. To better understand children's Pb exposure and inform potential approaches to exposure reduction, we conducted a national blood Pb survey of 31,373 children (0-84 months old) from May 2013 to March 2015, using a multi-stage and multi-strata sampling method. Blood lead levels (BLLs) were tested using graphite furnace atomic absorption spectrometry with a detection limit of 1 µg/L. The results show that Chinese children had a contemporary geometric mean (GM) BLL of 26.7 µg/L, with 8.6% of BLLs exceeding 50 µg/L. Boys had higher BLLs (GM 27.2 µg/L) compared to girls (GM: 25.9 µg/L) (p < 0.001). Children at the age of 0-36 months had a lower PbB (GM 25.7 µg/L) level compared with those aged 36-84 months (GM 27.9 µg/L) (p < 0.001). When taking into account sociodemographic factors, a multivariate logistic regression analysis shows that the odds ratios (OR) of having a BLL of 27 µg/dL (i.e., median BLL of this study) or higher were 1.88 (95% CI: 1.76, 2.02) and 1.35 (95% CI: 1.22, 1.49) for homes using coal and biomass fuels, respectively, compared to those using gas or electricity. Meanwhile, children in homes close to roads were more likely to have BLLs exceeding 27 µg/dL (OR: 1.11, 95% CI: 1.03, 1.20). In China, rural children had higher BLLs compared to urban children. As a result of pediatric exposure to Pb, there were approximately 144 million and 36 million IQ points lost for rural children and urban children, respectively, revealing a disparity of Pb exposure between rural and urban areas in China. Cleaner domestic fuels and improved cooking/heating equipment will reduce contemporary Pb exposure in rural areas. In addition, the association between contemporary BLLs and distance away from roads further suggests that resuspension of legacy soil/dust Pb should not be neglected in future remediation programs and household interventions. As a large scale survey, this study provides evidence for revising the reference value of BLL, improving the guideline for clinical and public health management, and implementing interventions to prevent adverse health outcomes associated with low-level Pb exposure in children.

11.
Mucosal Immunol ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31780776

RESUMO

Maintenance of regulatory T (Treg) cells is crucial for the regulatory function of Treg cells in immune homeostasis and self-tolerance; however, the detailed underlying mechanisms remain elusive. In the current study, we found that the cytokine suppressor CIS (cytokine induced SH-2 protein) is required for maintenance of Treg cell identity. Mice with Treg-specific Cis-deficiency displayed aggravated experimental allergic asthma, and in adulthood, developed splenomegaly, lymphadenopathy and spontaneous eosinophilic airway inflammation, accompanied by accumulation of effector memory helper T (TH) cells. Cis-deficiency led to the loss of Foxp3 expression and the decrease in suppressive function of Treg cells. Cis-deficient Treg cells expressed TH2 cell signature genes, Gata3, Irf4 and Il4, and excessive interleukin-4-signal transducer and activator of transcription 6 (IL-4-STAT6) signals resulted in repressive chromatin modification in the Foxp3 locus and permissive modification in the Il4 loci. In vitro, blockade of IL-4 restored the expression of Foxp3 and the suppressive function of inducible Treg (iTreg) cells. Thus, we identified a novel feedback loop in stabilization of Treg cells and suppression of TH2-type inflammation in a Treg-intrinsic manner.

12.
Medicine (Baltimore) ; 98(39): e17305, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574858

RESUMO

Until now, the recognition of sodium taurocholate cotransporting polypeptide (NTCP) deficiency has been mainly based on sporadic case reports. It was previously believed to be mildly symptomatic and resulting in mild liver dysfunction. However, to our knowledge, there have been no reports about the histopathologic and ultrastructural pathologic characteristics of the disease. The aim of the study was to analyze the clinical, histopathologic and ultrastructural pathologic characteristics of NTCP deficiency in 13 pediatric patients.From August 2012 to October 2018, this retrospective study conducted in the Department of Pediatrics of Tongji Hospital, China analyzed the data of 13 NTCP deficient patients with an SLC10A1 gene mutation. Except for NTCP deficiency, no other liver diseases were present in the patients, which was determined by both a genetic testing panel for jaundice and by reviewing medical records. The laboratory results, imaging, histopathologic, and ultrastructural pathologic information were recorded for analysis.The serum level of total bile acid was high in all 13 patients. All patients had adequate growth and development. Eight of the patients (8/13) presented with visible jaundice and 12 (12/13) were found to have hyperbilirubinemia. A needle liver biopsy was performed in 11 cases, which revealed slightly chronic inflammation in all 11 patients. One of the patients (1/13) was found to be suffering from gallstones.The data showed that although NTCP deficiency was often asymptomatic, some of the patients showed obvious clinical expressions, such as jaundice. Among the 13 pediatric patients with NTCP deficiency, both the biochemical and histopathologic features were similar to those of mild hepatocellular jaundice. In addition, it was determined that the clinical features in the patient with gallstones may have been caused by NTCP deficiency.


Assuntos
Ácidos e Sais Biliares/sangue , Icterícia , Hepatopatias , Fígado , Transportadores de Ânions Orgânicos Dependentes de Sódio , Simportadores , Desenvolvimento Infantil , Pré-Escolar , China/epidemiologia , Testes Genéticos/métodos , Humanos , Biópsia Guiada por Imagem/métodos , Lactente , Icterícia/diagnóstico , Icterícia/etiologia , Fígado/metabolismo , Fígado/patologia , Hepatopatias/diagnóstico , Hepatopatias/genética , Hepatopatias/fisiopatologia , Hepatopatias/terapia , Testes de Função Hepática/métodos , Glicoproteínas de Membrana/metabolismo , Mutação , Transportadores de Ânions Orgânicos Dependentes de Sódio/deficiência , Transportadores de Ânions Orgânicos Dependentes de Sódio/genética , Pediatria/métodos , Estudos Retrospectivos , Simportadores/deficiência , Simportadores/genética
13.
Cell Mol Immunol ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31611650

RESUMO

Although PD-L1/PD-1 blockade therapy has been approved to treat many types of cancers, the majority of patients with solid tumors do not respond well, but the underlying reason remains unclear. Here, we studied ovarian cancer (OvCa), a tumor type generally resistant to current immunotherapies, to investigate PD-1-independent immunosuppression. We found that PD-L1 was not highly expressed in the tumor microenvironment (TME) of human OvCa. Instead, B7-H3, another checkpoint molecule, was highly expressed by both tumor cells and tumor-infiltrating antigen-presenting cells (APCs), which correlated with T-cell exhaustion in patients. Using ID8 OvCa mouse models, we found that B7-H3 expressed on tumor cells, but not host cells, had a dominant role in suppressing antitumor immunity. Therapeutically, B7-H3 blockade, but not PD-1 blockade, prolonged the survival of ID8 tumor-bearing mice. Collectively, our results demonstrate that tumor-expressed B7-H3 inhibits the function of CD8+ T cells and suggest that B7-H3 may be a target in patients who are not responsive to PD-L1/PD-1 inhibition, particularly OvCa patients.

14.
Nanoscale ; 11(40): 18881-18893, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31596295

RESUMO

Nanomaterials with high catalytic activity and good SERS properties can be used for sensitive and real-time in situ tracking of a catalytic process via SERS, which can be a powerful tool for investigating the products and mechanisms of the catalytic reaction. In the present work, Au@AgPt NPs with a {431}-faceted hexoctahedral Au core and an AgPt alloy shell exhibiting enhanced catalysis and good SERS activity were prepared by a facile silver-mediated temperature-controlled selective deposition of Pt. The complex hexoctahedral Au nanoparticles were synthesized first as nano-templates, followed by coating with a thin layer of Ag. Then, a temperature-controlled synthesis method for preferably depositing Pt on the hexoctahedral Au NPs was proposed to prepare Au@AgPt NPs. With the increase of the synthesis temperature, the Pt atoms were controlled to selectively deposit on the tips, edges or the entire surface of the nano-templates. By systematically investigating the effects of temperature, precursor consumption and synthesis time on the morphology, composition, optical properties, catalysis and SERS properties of the Au@AgPt NPs, the kinetic and thermodynamic mechanisms of the deposition of Pt on hexoctahedral Au nanoparticles were explored. The performance of the Au@AgPt NPs in SERS-based real-time in situ monitoring of the catalytic reaction was also investigated and verified. Besides, it is easy to regulate and control their SERS and catalytic performances through the selective deposition of Pt, according to the demand of the catalytic reaction and SERS monitoring. This work not only presents a new Au@AgPt nanostructure with good catalytic and SERS properties, but also develops a facile, universal and controllable method for selective deposition of Pt on Au nano-templates with a variety of morphologies.

15.
Exp Cell Res ; 385(1): 111645, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585117

RESUMO

The past decade has seen significant interest in the isolation of pluripotent stem cells corresponding to various stages of mammalian embryonic development. Two distinct and well-defined pluripotent states can be derived from mouse embryos: "naïve" pluripotent cells with properties of pre-implantation epiblast, and "primed" pluripotent cells, resembling post-implantation epiblast. Prompted by the successful interconversion between these two stem cell states in the mouse system, several groups have devised strategies for inducing a naïve state of pluripotency in human pluripotent stem cells. Here, we review recent insights into the naïve state of human pluripotency, focusing on two methods that confer defining transcriptomic and epigenomic signatures of the pre-implantation embryo. The isolation of naïve human pluripotent stem cells offers a window into early developmental mechanisms that cannot be adequately modeled in primed cells, such as X chromosome reactivation, metabolic reprogramming, and the regulation of hominid-specific transposable elements. We outline key unresolved questions regarding naïve human pluripotency, including its extrinsic and intrinsic control mechanisms, potential for embryonic and extraembryonic differentiation, and general utility as a model system for human development and disease.

16.
ACS Appl Mater Interfaces ; 11(46): 43789-43795, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31657202

RESUMO

Being a metallic transition-metal dichalcogenide, monolayer vanadium diselenide (VSe2) exhibits many novel properties, such as charge density waves and magnetism. Its interfaces with other materials can potentially be used in device applications as well as for manipulating its intrinsic properties. Here, we present a scanning tunneling microscopy and synchrotron-based X-ray photoemission spectroscopy study of the surface charge-transfer doping using efficient electron-withdrawing and electron-donating materials, that is, molybdenum trioxide (MoO3) and potassium (K), on the molecular beam epitaxy-grown monolayer VSe2 on highly oriented pyrolytic graphite (HOPG). We demonstrate that monolayer VSe2 is immune to MoO3- and K-doping effects. However, at the monolayer edges where the local chemical reactivity is higher because of Se deficiency, MoO3 is seen to react with VSe2 to form molybdenum dioxide (MoO2) and vanadium dioxide (VO2). Compared to the obvious charge-transfer doping effects of MoO3 and K on HOPG, the electronic structure of monolayer VSe2 is barely perturbed. This is attributed to the large density of states at the Fermi level of monolayer VSe2 carrying the metallic character. This work provides new insights into the chemical and electronic properties of monolayer VSe2, important for future VSe2-based electronic device design.

17.
Clin Rheumatol ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578648

RESUMO

OBJECTIVE: The main purpose of this study was to investigate the current situation of primary Sjögren's syndrome (pSS) patients with interstitial lung disease (ILD) in China. The relationships between social demography, disease activity, psychological status, clinical variables, and ILD were analyzed. Besides that, the quality of life (QoL) in pSS with ILD was also analyzed. METHODS: In the cross-sectional study, 101 pSS patients participated in this study. Under the guidance of the researchers, the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI), EULAR Sjögren's Syndrome Patient-Reported Index (ESSPRI), the Short-Form 36 health survey (SF-36), Hospital Anxiety and Depression Scale (HADS), Pittsburgh sleep quality index (PSQI), Summated Xerostomia Inventory (SXI), and other related questionnaires were completed. Independent sample t tests, Mann-Whitney U test, chi-square test, and correlational analysis were used. RESULTS: The data showed that 28 (30.1%) pSS people with ILD. The occurrence and development of ILD were associated with disease duration, fatigue, alanine aminotransferase (ALT), neutrophils, albumin, and use of hormone. The survey also found that the QoL of pSS-ILD was significantly lower than non-ILD, especially the score in the dimension of role physical function. CONCLUSIONS: ILD was very common in pSS. ILD had a significant negative impact on the QoL of patients. Therefore, it is of great significance to strengthen the early intervention and drug treatment of pSS patients to prevent ILD and improve their QoL. Key Points • This cross-sectional study finds that the incidence of ILD in patients with pSS is 30.1%. • The occurrence and development of ILD is associated with disease duration, fatigue, alanine aminotransferase (ALT), neutrophils, albumin, and use of hormone. •The study also finds that the QoL of pSS-ILD is significantly lower than in patients with non-ILD, especially the score in the dimension of role physical function.

18.
JCI Insight ; 4(19)2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31578305

RESUMO

B7-H4 is a negative regulatory B7 family member. We investigated the role of host and donor B7-H4 in regulating acute graft-versus-host disease (GVHD). Allogeneic donor T cells infused into B7-H4-/- versus WT recipients markedly accelerated GVHD-induced lethality. Chimera studies pointed toward B7-H4 expression on host hematopoietic cells as more critical than parenchymal cells in controlling GVHD. Rapid mortality in B7-H4-/- recipients was associated with increased donor T cell expansion, gut T cell homing and loss of intestinal epithelial integrity, increased T effector function (proliferation, proinflammatory cytokines, cytolytic molecules), and reduced apoptosis. Higher metabolic demands of rapidly proliferating donor T cells in B7-H4-/- versus WT recipients required multiple metabolic pathways, increased extracellular acidification rates (ECARs) and oxygen consumption rates (OCRs), and increased expression of fuel substrate transporters. During GVHD, B7-H4 expression was upregulated on allogeneic WT donor T cells. B7-H4-/- donor T cells given to WT recipients increased GVHD mortality and had function and biological properties similar to WT T cells from allogeneic B7-H4-/- recipients. Graft-versus-leukemia responses were intact regardless as to whether B7-H4-/- mice were used as hosts or donors. Taken together, these data provide new insights into the negative regulatory processes that control GVHD and provide support for developing therapeutic strategies directed toward the B7-H4 pathway.

19.
Eur J Pharmacol ; 863: 172664, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31539552

RESUMO

As a nuclear receptor, peroxisome-proliferator-activated receptor α (PPARα) plays a critical role in regulation of metabolism and cancer, while the effect of PPARα agonist on cancer cell glucose metabolism-linked tumor growth is still unclear. Here we found that PPARα agonist (Wy14,643) decreased Glut1 (Glucose transporter 1) gene and protein expressions of colorectal cancer cell lines in response to normoxia or hypoxia. Dual-luciferase analysis showed that Wy14,643 inhibited Glut1 transcription activity. Importantly, ChIP-qPCR analysis showed that Wy14,643 increased the binding of PPARα to Glut1 promoter region. Wy14,643 suppressed Glut1 transcription activity resulting in reduced influx of glucose in cancer cells in response to normoxia or hypoxia. Further analysis showed that Wy14,643-mediated inhibition of tumor growth and chemo-resistance was associated with inhibition of mTOR pathway. Taken together, PPARα agonist Wy14,643 suppressed Glut1 transcription activity, glucose uptake and mTOR pathway in colorectal cancer cells, which was involved in reduced tumor growth and chemo-resistance. These findings provided a novel therapy strategy for cancer progression.

20.
Pol J Pathol ; 70(2): 63-78, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31556556

RESUMO

The aim of this research was to investigate the clinical role and prognostic value of CD117 expression assessed immunohistochemically in lung carcinoma through a comprehensive meta-analysis in which 27 publications were acquired and 2645 patients were ultimately analysed. Statistical analysis and corresponding plots were performed using STATA version 12.0. Publication bias was assessed by Begg's funnel plots and Egger's test. Pooled HR and its 95% CI (HR = 1.53, 95% CI: 1.13-2.07, p = 0.007) for overall survival of patients indicated a poor prognostic value for CD117 expression in lung carcinoma, which was accompanied by heterogeneity and publication bias. In the subgroup analysis, there was strong evidence that could support an association between CD117 expression and poor prognosis in NSCLC patients (HR = 2.03, 95% CI: 1.41-2.90, p < 0.001; heterogeneity: I2 = 41.9%, c2 = 15.49, p = 0.078). Multivariate analysis also revealed consistent results in high-quality studies with reported HRs (HR = 2.16, 95% CI: 1.67-2.79, p < 0.001), and Asian patients (HR = 2.12, 95% CI: 1.45-3.10, p < 0.001). The correlations between CD117 expression and age, clinical stage, TNM stage, lymph node metastasis, or histology were not statistically significant. In conclusion, CD117 expression might be a potential marker for predicting poor prognosis, faster tumour growth, and early lymph node metastasis in NSCLC.


Assuntos
Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas c-kit/genética , Biomarcadores Tumorais/genética , Progressão da Doença , Humanos , Neoplasias Pulmonares/diagnóstico , Metástase Linfática , Prognóstico
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