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1.
Cell ; 180(1): 50-63.e12, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31923399

RESUMO

Mucosal barrier immunity is essential for the maintenance of the commensal microflora and combating invasive bacterial infection. Although immune and epithelial cells are thought to be the canonical orchestrators of this complex equilibrium, here, we show that the enteric nervous system (ENS) plays an essential and non-redundant role in governing the antimicrobial protein (AMP) response. Using confocal microscopy and single-molecule fluorescence in situ mRNA hybridization (smFISH) studies, we observed that intestinal neurons produce the pleiotropic cytokine IL-18. Strikingly, deletion of IL-18 from the enteric neurons alone, but not immune or epithelial cells, rendered mice susceptible to invasive Salmonella typhimurium (S.t.) infection. Mechanistically, unbiased RNA sequencing and single-cell sequencing revealed that enteric neuronal IL-18 is specifically required for homeostatic goblet cell AMP production. Together, we show that neuron-derived IL-18 signaling controls tissue-wide intestinal immunity and has profound consequences on the mucosal barrier and invasive bacterial killing.

2.
Biosci Rep ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31912868

RESUMO

Microcystic adnexal carcinoma (MAC) is a rare, locally aggressive malignant neoplasm that derives from cutaneous eccrine/apocrine glands. MAC is classified as an eccrine/apocrine gland tumor and usually occurs in the skin. Here, we characterized and compared two cases of MAC. One is extremely rare in terms of its occurrence in the tongue. The other occurred in the lip, which is common. Histories of disease, diagnosis, and differentials were reviewed by attending physicians. Hematoxylin and eosin (HE) slides were evaluated by an experienced pathologist. Immunological markers for malignant eccrine/apocrine gland tumors were used to characterize the tumor's nature. The examined markers included EMA, CK5/6, CK8/18, CK7, CK20, p63, S-100, Calponin, CD10, MYB, Bcl-2, Her-2, CD34, SMA, p53, CD43, CD117, and Ki-67. Both patients were males, presenting with painless lumps in the lower lip and in the tongue, respectively. Both lumps were similar in terms of appearance, being whitish and infiltrative with irregular borders. Both tumors also had similar histological features with nests of bland keratinocytes, cords and ductal differentiation filled with Periodic Acid-Schiff (PAS) positive eosinophilic material. In both cases, circular or ovary tumor cells invaded into muscles and nerves. All tumor cells wereCK5/6, CK8/18, EMA, and CK7 positive. Particularly, keratinocytes were p63 positive, and paraductal cells were p63, S-100 and SMA positive. Therefore, the rare case of MAC in the tongue appears to derive from the salivary gland.

3.
Blood ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932841

RESUMO

Mutations in the epigenetic regulators DNMT3A and IDH1/2 co-occur in patients with acute myeloid leukemia and lymphoma. Here, we demonstrate that these two epigenetic mutations cooperate to induce leukemia. Leukemia-initiating cells from Dnmt3a-/- mice that express an IDH2 neomorphic mutant have a megakaryocyte-erythroid progenitor-like immunophenotype, activate a stem-cell-like gene signature, and repress differentiated-progenitor genes. We observe there is an epigenomic dysregulation with the gain of repressive H3K9 trimethylation and loss of H3K9 acetylation in diseased mouse bone marrow stem and progenitor cells (HSPC). Here we found that HDAC inhibitors rapidly reverse the H3K9 methylation/acetylation imbalance in diseased mouse HSPC while reducing the leukemia burden. Additionally, using targeted metabolomic profiling for the first time in mouse leukemia models, we also show that prostaglandin E2 is overproduced in double-mutant hematopoietic stem and progenitor cells (HSPCs), rendering them sensitive to prostaglandin synthesis inhibition. These data reveal that Dnmt3a and Idh2 mutations are synergistic events in leukemogenesis and that HSPCs carrying both mutations are sensitive to induced differentiation by the inhibition of both prostaglandin synthesis and HDAC, which may reveal new therapeutic opportunities for patients carrying IDH1/2 mutations.

4.
Pancreas ; 49(1): 46-52, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31856079

RESUMO

OBJECTIVES: This work aimed to study the early predictive value of extrapancreatic inflammation on magnetic resonance imaging (EPIM) for acute pancreatitis (AP) severity. METHODS: The EPIM score, magnetic resonance severity index, Acute Physiology and Chronic Health Evaluation (APACHE II) score, bedside index of severity in AP, and high-sensitivity C-reactive protein levels were evaluated for 337 AP patients. The extrapancreatic inflammation on computed tomography (EPIC) was also assessed for 86 patients undergoing computed tomography. The predictive values of these scores for severe AP and organ failure were evaluated using receiver operating characteristic curve analyses. RESULTS: Of the 337 AP patients, 55 (16.3%) had organ failure and 17 (5.0%) had severe AP. The EPIM showed a strong correlation with the EPIC (r = 0.794, P < 0.001) and had a higher correlation with the APACHE II and hospital stay compared with the EPIC. The accuracy of the EPIM in predicting severe AP and organ failure (areas under the curve, 0.844 and 0.817) was consistent with that of the APACHE II and bedside index of severity in AP, and higher than that of the magnetic resonance severity index. CONCLUSION: The EPIM is more helpful in assessing AP severity than the EPIC and can indicate the occurrence of severe AP and organ failure early.

5.
Exp Cell Res ; 386(1): 111708, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682811

RESUMO

Recent studies revealed that macrophages are polarized towards the M2 phenotype in an ovalbumin (OVA)-induced asthmatic model. Alveolar macrophages (AMs) are immune barriers in alveoli to various pathogens in the respiratory tract; AMs suppress Th2 cell proliferation, inhibit interleukin (IL)-4, IL-5, and IL-13 secretion, and protect against airway hyperresponsiveness in allergic asthma. However, the polarization status and effects of different types of AMs in the pathogenesis of asthma are not known. ATP/P2X7r, expressed mainly on macrophages and dendritic cells, is associated with acute and chronic asthmatic airway inflammation and Th2 immune responses in mice and humans and functions by activating the NLRP3 inflammasome complex and inducing proinflammatory cytokine release (IL-1ß and IL-18). Therefore, we evaluated the association between the ATP/P2X7r axis and different types of AMs in the pathology of allergic asthma. A murine AM-depleted asthma model was established by administration of clodronate-encapsulated liposomes, and M1-or M2-AMs were adoptively transferred to confirm the effects of different AMs in allergic asthma. Brilliant Blue G and BzATP were administered to OVA/HDM-induced mice in vivo. Lipopolysaccharide + OVA, ATP, Brilliant Blue G, and BzATP were used to stimulate AMs isolated from control and asthmatic mice. We found that selective depletion of AMs aggravated lung inflammation in asthmatic mice. Further, M2-type AMs may play a key role in mediating asthmatic inflammatory responses via the adoptive transfer of M2-type AMs to AM-depleted asthmatic mice, and the phenotype of AMs differentiated to M2 type in asthma. P2X7r expression in M2-type AMs was higher than that in M1-type AMs. Activating P2X7r induced polarization of M2-type AMs and inhibited polarization of M1-type AMs, while blockage of P2X7r had the opposite effect. The ATP/P2X7r axis may participate in the pathogenesis of asthma by mediating the M2-type AM polarization.

6.
Med Image Anal ; 59: 101561, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31671320

RESUMO

Diabetic Retinopathy (DR) is the most common cause of avoidable vision loss, predominantly affecting the working-age population across the globe. Screening for DR, coupled with timely consultation and treatment, is a globally trusted policy to avoid vision loss. However, implementation of DR screening programs is challenging due to the scarcity of medical professionals able to screen a growing global diabetic population at risk for DR. Computer-aided disease diagnosis in retinal image analysis could provide a sustainable approach for such large-scale screening effort. The recent scientific advances in computing capacity and machine learning approaches provide an avenue for biomedical scientists to reach this goal. Aiming to advance the state-of-the-art in automatic DR diagnosis, a grand challenge on "Diabetic Retinopathy - Segmentation and Grading" was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI - 2018). In this paper, we report the set-up and results of this challenge that is primarily based on Indian Diabetic Retinopathy Image Dataset (IDRiD). There were three principal sub-challenges: lesion segmentation, disease severity grading, and localization of retinal landmarks and segmentation. These multiple tasks in this challenge allow to test the generalizability of algorithms, and this is what makes it different from existing ones. It received a positive response from the scientific community with 148 submissions from 495 registrations effectively entered in this challenge. This paper outlines the challenge, its organization, the dataset used, evaluation methods and results of top-performing participating solutions. The top-performing approaches utilized a blend of clinical information, data augmentation, and an ensemble of models. These findings have the potential to enable new developments in retinal image analysis and image-based DR screening in particular.

7.
Front Pharmacol ; 10: 1098, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798443

RESUMO

Deoxynivalenol (DON) is a major fusarium toxin widely detected in cereal grains. The inadvertent exposure to this fungal secondary-metabolite gives rise to a myriad of adverse health effects including appetite loss, emesis, and suppression of the immune system. While most of the attention this mycotoxin has gained in the past four decades was related to its eukaryotic toxicity (monogastric animals and plants more precisely), recent studies have begun to reveal its negative influence on prokaryotes. Recently presented evidence indicates that DON can negatively affect many bacterial species, raising the possibility of DON-induced imbalances within the microbiota of the human and animal gut, in addition to other environmental niches. This in turn has led to a greater interest in understanding bacterial responses toward DON, and the involved mechanism(s) and metabolic pathways, in order to build a more comprehensive picture of DON-induced changes in both prokaryotes and eukaryotes alike. This study reveals the transcriptomic profiling of Devosia mutans strain 17-2-E-8 after the inclusion of DON within its growth medium. The results highlight three adaptive mechanisms involved in the response of D. mutans 17-2-E-8 to this mycotoxin, which include: (a) activation of adenosine 5'-triphosphate-binding cassette transporters; (b) engagement of a toxin-specific pyrroloquinoline quinone-dependent detoxification pathway; and finally (c) the upregulation of auxiliary coping proteins such as porins, glutathione S-transferases, and phosphotransferases. Some of the identified mechanisms are universal in nature and are shared with other bacterial genera and species.

8.
J Org Chem ; 2019 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-31814407

RESUMO

A novel visible-light photocatalytic difluoromethylselenolation of aryl amines via in situ generation of aryldiazonium salts was achieved using Se-(difluoromethyl) 4-methylbenzenesulfonoselenoate, which was synthesized for the first time. The reagent is readily accessible and shelf-stable. The metal-free reaction conditions and the broad substrate scope provide a green protocol for the efficient and rapid introduction of the difluoromethylselenylether group.

9.
Int Immunopharmacol ; 78: 106047, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31816576

RESUMO

Isosteroid alkaloids, natural products from Fritillariae Cirrhosae Bulbus, are well known for its antitussive, expectorant, anti-asthmatic and anti-inflammatory properties. However, the anti-inflammatory effect and its mechanism have not been fully explored. In this study, the anti-inflammatory activitives and the potential mechanisms of five isosteroid alkaloids from F. Cirrhosae Bulbus were investigated in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells. The pro-inflammatory mediators and cytokines were measured by Griess reagent, ELISA and qRT-PCR. The expression of MAPKs was investigated by western blotting. Treatment with the five isosteroid alkaloids in appropriate concentrations could reduce the production of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in supernatant, and suppressed the mRNA expressions of TNF-α and IL-6. Meanwhile, the five isosteroid alkaloids significantly inhibited the phosphorylated activation of mitogen activated protein kinase (MAPK) signaling pathways, including extracellular signal-regulated kinase (ERK1/2), p38 MAPK and c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK). These results demonstrated that isosteroid alkaloids from F. Cirrhosae Bulbus exert anti-inflammatory effects by down-regulating the level of inflammatory mediators via mediation of MAPK phosphorylation in LPS-induced RAW264.7 macrophages, thus could be candidates for the prevention and treatment of inflammatory diseases.

10.
BMC Plant Biol ; 19(1): 529, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783790

RESUMO

BACKGROUND: Trees of the genus Taxus are highly valuable medicinal plants with multiple pharmacological effects on various cancer treatments. Paclitaxel from Taxus trees is an efficient and widely used anticancer drug, however, the accumulation of taxoids and other active ingredients can vary greatly among Taxus species. In our study, the metabolomes of three Taxus species have been investigated. RESULTS: A total of 2246 metabolites assigned to various primary and secondary metabolic pathways were identified using an untargeted approach. Analysis of differentially accumulated metabolites identified 358 T. media-, 220 T. cuspidata-, and 169 T. mairei-specific accumulated metabolites, respectively. By searching the metabolite pool, 7 MEP pathway precursors, 11 intermediates, side chain products and derivatives of paclitaxel, and paclitaxel itself were detected. Most precursors, initiated intermediates were highly accumulated in T. mairei, and most intermediate products approaching the end point of taxol biosynthesis pathway were primarily accumulated in T. cuspidata and T. media. Our data suggested that there were higher-efficiency pathways to paclitaxel in T. cuspidata and T. media compared with in T. mairei. As an important class of active ingredients in Taxus trees, a majority of flavonoids were predominantly accumulated in T. mairei rather than T. media and T. cuspidata. The variations in several selected taxoids and flavonoids were confirmed using a targeted approach. CONCLUSIONS: Systematic correlativity analysis identifies a number of metabolites associated with paclitaxel biosynthesis, suggesting a potential negative correlation between flavonoid metabolism and taxoid accumulation. Investigation of the variations in taxoids and other active ingredients will provide us with a deeper understanding of the interspecific differential accumulation of taxoids and an opportunity to accelerate the highest-yielding species breeding and resource utilization.

11.
BMC Cancer ; 19(1): 1164, 2019 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783810

RESUMO

Following publication of the original article [1], the authors reported the following error is the article.

12.
Cancer Sci ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31834989

RESUMO

Detecting EBV DNA load in nasopharyngeal (NP) brushing samples for NPC's diagnosis has attracted great attentions. Further improvements without the need of clinical settings will greatly extend its application. A total of 250 participants were recruited to obtain the NP brushing samples. Brush sampling with and without the guide of endoscopy was both conducted in 38 NPC patients. EBV DNA load, EBV RNA transcript and EBV DNA C - promoter methylation status were respectively evaluated. Typical latency II transcripts were observed in brushing samples from NPC patients but not controls. Unlike in tissues, multiple lytic gene transcripts were observed not only in NPC patients but also in controls. Apart from EBV RNA transcript, samples from NPC patients also showed higher levels of EBV DNA load, and C - promoter methylated degree than their levels from controls. Qualitative analysis further showed EBV DNA C - promoter in NPC patients was 100% methylated type, while methylated type was only 18.4% in the control group. Combined analysis of EBV DNA methylated type and EBV DNA load increased the sensitivity to 100% in the detection of NPC. Using qualitative methylated type as the criteria, up to 89.5% of samples collected via blind brushing showed consistent results with samples collected via endoscopy - guided brushing from NPC patients. Detection of methylation status of EBV DNA C - promoter in NP brushing samples shows great potential in diagnosing NPC and may provide an appealing alternative for the non-invasive detection and screening of NPC without clinical settings.

13.
BMC Plant Biol ; 19(1): 574, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31864283

RESUMO

BACKGROUND: Phenotypic diversity of floral organs plays an important role in plant systematic taxonomy and genetic variation studies. Previous research have focused on the direction of variation but disregarded its degree. Phenotypic variation (including directions and degrees) of 17 floral traits from wild to cultivated crabapples were explored by comparing their distributions and deviations in three different dimensions: floral organ number, size, and the shape. RESULTS: Except for petal number, petal length / petal width, and sepal length / sepal width, the analyzed floral traits of cultivated crabapples all showed downward distributed box bodies in box plot analysis and left deviations of fitted curves in frequency distribution function analysis when compared to the wild, which revealed consistent variation directions of petaloid conversion (pistils or stamens → petals), size miniaturization (large → small), and shape narrowness (petal shape: circular → elliptic; sepal shape: triangular → lanceolate). However, only seven floral traits exhibited significant differences in box plot analysis, while all of the traits in frequency distribution function analysis were obviously offset. The variation degrees were quantitatively characterized by sizing traits > shaping traits > numbering traits and by horizontal dimensions > radial dimensions. CONCLUSIONS: Frequency distribution function analysis was more sensitive than the box plot analysis, which constructed a theoretical basis for Malus flower type breeding and would provide a new quantitative method for future evaluation of floral variation among different groups of angiosperms at large.

14.
Molecules ; 25(1)2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31878239

RESUMO

DJ-1 was recently reported to be involved in the cardioprotection of hypoxic preconditioning (HPC) against hypoxia/reoxygenation (H/R)-induced oxidative stress damage, by preserving mitochondrial complex I activity and, subsequently, inhibiting mitochondrial reactive oxygen species (ROS) generation. However, the molecular mechanism by which HPC enables mitochondrial translocation of DJ-1, which has no mitochondria-targeting sequence, to preserve mitochondrial complex I, is largely unknown. In this study, co-immunoprecipitation data showed that DJ-1 was associated with glucose-regulated protein 75 (Grp75), and this association was significantly enhanced after HPC. Immunofluorescence imaging and Western blot analysis showed that HPC substantially enhanced the translocation of DJ-1 from cytosol to mitochondria in H9c2 cells subjected to H/R, which was mimicked by DJ-1 overexpression induced by pFlag-DJ-1 transfection. Importantly, knockdown of Grp75 markedly reduced the mitochondrial translocation of DJ-1 induced by HPC and pFlag-DJ-1 transfection. Moreover, HPC promoted the association of DJ-1 with mitochondrial complex I subunits ND1 and NDUFA4, improved complex I activity, and inhibited mitochondria-derived ROS production and subsequent oxidative stress damage after H/R, which was also mimicked by pFlag-DJ-1 transfection. Intriguingly, these effects of HPC and pFlag-DJ-1 transfection were also prevented by Grp75 knockdown. In conclusion, these results indicated that HPC promotes the translocation of DJ-1 from cytosol to mitochondria in a Grp75-dependent manner and Grp75 is required for DJ-1-mediated protection of HPC on H/R-induced mitochondrial complex I defect and subsequent oxidative stress damage.

15.
Spectrochim Acta A Mol Biomol Spectrosc ; 229: 117943, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31855811

RESUMO

Conventional organic dye encoding is limited by photo-bleaching and spectral overlap, thus restricting the number of distinguishable codes that can be used in practice. The utility of a single dye for increasing additional encoding capacity has yet to be explored. To this end, we firstly report a facile, flexible and green sustainable method to maximize the time-resolved encoding capacity of the xanthene red dye, eosin. By simply adjusting the concentration, pH and viscosity of the eosin solution, eleven distinguishable populations of fluorescence lifetimes were obtained with a short lifetime range of 1.0-3.4 ns, which in turn could increase the difficulty of duplication and provide extra high-level security protection. The results provide a facile strategy to increase the temporal multiplexing capacity, and may result in the reuse of existing organic dyes as lifetime-coded polymer microspheres in the fields of information security.

16.
Org Lett ; 21(23): 9559-9563, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31710502

RESUMO

An unprecedented copper-catalyzed tandem cross-coupling/[2 + 2] cycloaddition of 1,6-allenynes with diazo compounds was reported, chemo- and regioselectively providing 3-azabicyclo[5.2.0] frameworks in moderate to excellent yields under mild reaction conditions. Moreover, the products readily convert to highly functionalized quinolines via oxidative radical rearrangement.

17.
Ann Transl Med ; 7(18): 439, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31700875

RESUMO

Background: With the improvement of survival for non-small cell lung cancer (NSCLC), research focused on second primary malignancy (SPM) in NSCLC survivors is becoming urgent. This study aimed to estimate the risk of SPM in NSCLC patients. Methods: We retrospectively analysed NSCLC patients diagnosed between 2004 and 2010 in SEER database. We firstly evaluated the crude and cumulative incidence of SPM. SPM incidence in NSCLC survivors compared to that in the reference population was calculated as standardized incidence ratio (SIR). A competing risk nomogram was also built, to predict the incidence of SPM. Results: The crude and 10-year cumulative incidences of SPM were 4.04% and 5.05%, respectively, while the SIR was 1.62. The nomogram was well calibrated and had good discriminative ability, with c-index of 0.80. It showed a significantly wide interval of SPM cumulative incidence between the first and tenth-decile according to the risk model (1.04% vs. 16.70%, P<0.05). The decision curve analysis indicated that the clinical net benefit of risk model was larger than that in other scenarios (all-screening or no-screening) in a range of threshold probabilities (1% to 20%). Conclusions: Our study firstly performed a systematic estimation of the incidence of SPM in NSCLC, which implied the necessity of a risk predicting model. We developed the first competing risk nomogram to predict the risk of SPM, which performed well in the evaluation and might be helpful for individualized SPM screening.

18.
Ann Transl Med ; 7(18): 452, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31700888

RESUMO

Background: Four multi-targeted tyrosine kinase inhibitors (TKIs) including apatinib, anlotinib, fruquintinib and lenvatinib are currently available as third-line regimen for advanced non-small cell lung cancer (NSCLC) patients who failed at least two lines of systemic therapy. Limited evidence was provided to demonstrate the general efficacy and safety profile of these drugs as third-line treatment approach for NSCLC. Methods: Eligible literature was searched from electronic database. Data of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), treatment related adverse event (TRAE), treatment related adverse event grade 3-5 (TRAE3-5), hypertension, proteinuria, hand-foot skin reaction (HFSR), elevated ALT/AST, nausea and vomiting, diarrhea were synthetically extracted. Multiple-treatments comparisons (MTCs) based on a Bayesian consistency model integrated the efficacy and toxicity outcomes. Rank probabilities of each regimen were assessed and clustered by the surface under the cumulative ranking curve. Results: Five phase II/III randomized trials involving 915 advanced NSCLC patients were enrolled. MTCs showed that four multi-targeted TKIs shared equivalent efficacy in terms of outcome measures, of which anlotinib stood out in ORR (OR =39.26; 95% CI: 2.36-2,748.06), DCR (OR =8.69; 95% CI: 1.70-50.18) and PFS (HR =0.27; 95% CI: 0.10-0.78) when compared with placebo plus BSC. No significantly differences were observed among these TKIs and placebo with respect to OS, TRAE and TRAE 3-5. Fruquintinib and lenvatinib may relate to high rate of HFSR while anlotinib may relate to hypertension. Conclusions: Multi-targeted TKIs (apatinib, anlotinib, fruquintinib and lenvatinib) with acceptable efficacy and safety profile were options for advanced NSCLC in third-line setting.

19.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(9): 769-775, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31750816

RESUMO

Objective To explore the functions and mechanisms of macrophages derived from PGRN gene knockout (PGRN-/- ) C57BL/6 mice in the invasion and migration of breast cancer cells. Methods Breast cancer cells were cultured in conditioned medium of macrophages derived from WT and PGRN-/- mice. TranswellTM assay and scratch assay were used to detect the invasion and migration ability of cancer cells. Western blot analysis was used to detect the expression of E-cadherin and N-cadherin in cancer cells. Cytokine array, real-time quantitative PCR and ELISA were performed to investigate the differences of cytokines secreted by macrophages derived from WT and PGRN-/- mice. Breast cancer cells were treated by the differentially expressed cytokine interleukin-6 (IL-6), and then the above methods were used to investigate its effect on cancer cells. Western blot analysis was used to verify the roles of NF-κB and JAK/STAT3 signaling pathways. Results The macrophages derived from PGRN-/- mice blocked NF-κB signaling pathway, reduced IL-6 secretion, and inhibited the invasion and migration of breast cancer cells. IL-6 activated JAK/STAT3 signaling pathway to promote the invasion and migration of breast cancer cells. Conclusion The macrophages derived from PGRN-/- mice can block the NF-κB and JAK/STAT3 signaling pathways, down-regulate IL-6 expression, and inhibit the invasion and migration of breast cancer cells.


Assuntos
Neoplasias da Mama/patologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Interleucina-6/imunologia , Macrófagos/imunologia , Transdução de Sinais , Animais , Neoplasias da Mama/imunologia , Caderinas , Movimento Celular , Meios de Cultivo Condicionados , Granulinas , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Invasividade Neoplásica , Fator de Transcrição STAT3/metabolismo , Células Tumorais Cultivadas
20.
Microbiome ; 7(1): 151, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779704

RESUMO

BACKGROUND: Ochratoxin A (OTA) is a widespread mycotoxin and induces liver inflammation to human and various species of animals. The intestinal microbiota has critical importance in liver inflammation; however, it remains to know whether intestinal microbiota mediates the liver inflammation induced by OTA. Here, we treated ducklings with oral gavage of OTA (235 µg/kg body weight) for 2 weeks. Then, the microbiota in the cecum and liver were analyzed with 16S rRNA sequencing, and the inflammation in the liver was analyzed. To explore the role of intestinal microbiota in OTA-induced liver inflammation, intestinal microbiota was cleared with antibiotics and fecal microbiota transplantation was conducted. RESULTS: Here, we find that OTA treatment in ducks altered the intestinal microbiota composition and structure [e.g., increasing the relative abundance of lipopolysaccharides (LPS)-producing Bacteroides], and induced the accumulation of LPS and inflammation in the liver. Intriguingly, in antibiotic-treated ducks, OTA failed to induce these alterations in the liver. Notably, with the fecal microbiota transplantation (FMT) program, in which ducks were colonized with intestinal microbiota from control or OTA-treated ducks, we elucidated the involvement of intestinal microbiota, especially Bacteroides, in liver inflammation induced by OTA. CONCLUSIONS: These results highlight the role of gut microbiota in OTA-induced liver inflammation and open a new window for novel preventative or therapeutic intervention for mycotoxicosis.

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