RESUMO
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of end-stage kidney disease (ESKD) worldwide. Guidelines for the diagnosis and management of ADPKD in Taiwan remains unavailable. In this consensus statement, we summarize updated information on clinical features of international and domestic patients with ADPKD, followed by suggestions for optimal diagnosis and care in Taiwan. Specifically, counselling for at-risk minors and reproductive issues can be important, including ethical dilemmas surrounding prenatal diagnosis and pre-implantation genetic diagnosis. Studies reveal that ADPKD typically remains asymptomatic until the fourth decade of life, with symptoms resulting from cystic expansion with visceral compression, or rupture. The diagnosis can be made based on a detailed family history, followed by imaging studies (ultrasound, computed tomography, or magnetic resonance imaging). Genetic testing is reserved for atypical cases mostly. Common tools for prognosis prediction include total kidney volume, Mayo classification and PROPKD/genetic score. Screening and management of complications such as hypertension, proteinuria, urological infections, intracranial aneurysms, are also crucial for improving outcome. We suggest that the optimal management strategies of patients with ADPKD include general medical care, dietary recommendations and ADPKD-specific treatments. Key points include rigorous blood pressure control, dietary sodium restriction and Tolvaptan use, whereas the evidence for somatostatin analogues and mammalian target of rapamycin (mTOR) inhibitors remains limited. In summary, we outline an individualized care plan emphasizing careful monitoring of disease progression and highlight the need for shared decision-making among these patients.
Assuntos
Falência Renal Crônica , Rim Policístico Autossômico Dominante , Humanos , Rim Policístico Autossômico Dominante/diagnóstico , Rim Policístico Autossômico Dominante/terapia , Rim Policístico Autossômico Dominante/complicações , Taiwan/epidemiologia , Tolvaptan , RimRESUMO
BACKGROUND: Interleukin (IL)-2 is a key cytokine capable of modulating the immune response by activating natural killer (NK) cells. This study was recruited to explore the therapeutic potential of IL-2-activated NK-92 cells in endometriosis in vitro. METHODS: Ectopic endometrial stromal cells (EESCs) were isolated and co-cultured with IL-2-activated NK-92 cells at varying effector-to-target (E:T) ratios (1:0 [Control], 1:1, 1:3, and 1:9). The viability, cytotoxicity, and cell surface antigen expression of IL-2-activated NK-92 cells were assessed. The viability, apoptosis, invasion, and migration ability of EESCs co-cultured with NK-92 cells at different ratios were evaluated. The apoptosis-related proteins, invasion and migration-related proteins as well as MEK/ERK pathway were examined via western blot. Each experiment was repeated three times. RESULTS: IL-2 activation enhanced NK-92 cytotoxicity in a concentration-dependent manner. Co-culturing EESCs with IL-2-activated NK-92 cells at E:T ratios of 1:1, 1:3, and 1:9 reduced EESC viability by 20%, 45%, and 70%, respectively, compared to the control group. Apoptosis rates in EESCs increased in correlation with the NK-92 cell proportion, with the highest rate observed at a 1:9 ratio. Moreover, EESC invasion and migration were significantly inhibited by IL-2-activated NK-92 cells, with a 60% reduction in invasion and a 50% decrease in migration at the 1:9 ratio. Besides, the MEK/ERK signalling pathway was down-regulated in EESCs by IL-2-activated NK-92 cells. CONCLUSION: IL-2-activated NK-92 cells exhibit potent cytotoxic effects against EESCs. They promote EESC apoptosis and inhibit viability, invasion, and migration through modulating the MEK/ERK signalling pathway.
Endometriosis is a common chronic systemic disease affecting approximately 190 million women worldwide. However, clinical treatments for endometriosis remain challenging due to the scarcity of high-quality scientific evidence and conflicting available guidelines. This research was designed to explore whether interleukin (IL)-2 affected the progression of endometriosis by modulating endometrial stromal cell apoptosis and natural killer (NK) cell-mediated cytotoxicity, thereby providing new therapeutic methods for endometriosis.
Assuntos
Apoptose , Técnicas de Cocultura , Endometriose , Interleucina-2 , Células Matadoras Naturais , Humanos , Endometriose/patologia , Endometriose/imunologia , Feminino , Interleucina-2/farmacologia , Interleucina-2/metabolismo , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Apoptose/efeitos dos fármacos , Adulto , Endométrio/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Células Estromais/efeitos dos fármacos , Progressão da Doença , Sobrevivência Celular/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células CultivadasRESUMO
Electrocatalytic water splitting is one of the most commercially valuable pathways of hydrogen production especially combined with renewable electricity; however, efficient and durable electrocatalysts are urgently needed to reduce electric energy consumption. Here, we reported a Ru and Fe co-doped Mo2 C on nitrogen doped carbon via a controllable two-step method, which can be used for efficient and enduring hydrogen evolution reaction. At 10, 100 and 200â mA cm-2 in acidic electrolyte, the resultant Ru-Fe/Mo2 C@NC delivered low overpotentials of 31, 78 and 103â mV, respectively, which are comparable to that of the commercial Pt/C (20â wt %). At an applied current density of 100â mA cm-2 , stable hydrogen production was conducted for 120â h without obvious degradation. In alkaline media, Ru-Fe/Mo2 C@NC can also deliver a current density of 100â mA cm-2 for more than 100â h. Furthermore, the Ru-Fe/Mo2 C@NC electrocatalyst was used as cathode in an anion exchange membrane water electrolyzer under industrial environments for robust hydrogen production. The characterization and electrochemical results prove the synergism effects between Ru, Fe dopants and Mo2 C for promoting hydrogen evolution activity. This work would pave a new avenue to fabricate low-cost, high-performance hydrogen evolution electrocatalysts for industrial water electrolyzers.
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Neutrophils are conspicuous components of gastric cancer (GC) tumors, increasing with tumor progression and poor patient survival. However, the phenotype, regulation and clinical relevance of neutrophils in human GC are presently unknown. Most intratumoral neutrophils showed an activated CD54+ phenotype and expressed high level B7-H3. Tumor tissue culture supernatants from GC patients induced the expression of CD54 and B7-H3 on neutrophils in time-dependent and dose-dependent manners. Locally enriched CD54+ neutrophils and B7-H3+ neutrophils positively correlated with increased granulocyte-macrophage colony stimulating factor (GM-CSF) detection ex vivo; and in vitro GM-CSF induced the expression of CD54 and B7-H3 on neutrophils in both time-dependent and dose-dependent manners. Furthermore, GC tumor-derived GM-CSF activated neutrophils and induced neutrophil B7-H3 expression via JAK-STAT3 signaling pathway activation. Finally, intratumoral B7-H3+ neutrophils increased with tumor progression and independently predicted reduced overall survival. Collectively, these results suggest B7-H3+ neutrophils to be potential biomarkers in GC.
Assuntos
Antígenos B7/metabolismo , Carcinoma/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Ativação de Neutrófilo , Neutrófilos/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Carcinoma/patologia , Progressão da Doença , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Técnicas In Vitro , Molécula 1 de Adesão Intercelular/metabolismo , Janus Quinases/efeitos dos fármacos , Janus Quinases/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Prognóstico , Fator de Transcrição STAT3/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Adulto JovemRESUMO
OBJECTIVE: Regulated in development and DNA damage responses-1 (REDD1) is a conserved and ubiquitous protein, which is induced in response to multiple stimuli. However, the regulation, function and clinical relevance of REDD1 in Helicobacter pylori-associated gastritis are presently unknown. APPROACH: Immunohistochemistry, real-time PCR and Western blot analyses were performed to examine the levels of REDD1 in gastric samples from H. pylori-infected patients and mice. Gastric tissues from Redd1-/- and wildtype (WT, control) mice were examined for inflammation. Gastric epithelial cells (GECs), monocytes and T cells were isolated, stimulated and/or cultured for REDD1 regulation and functional assays. RESULTS: REDD1 was increased in gastric mucosa of H. pylori-infected patients and mice. H. pylori induced GECs to express REDD1 via the phosphorylated cytotoxin associated gene A (cagA) that activated MAPKp38 pathway to mediate NF-κB directly binding to REDD1 promoter. Human gastric REDD1 increased with the severity of gastritis, and mouse REDD1 from non-marrow chimera-derived cells promoted gastric inflammation that was characterized by the influx of MHCII+ monocytes. Importantly, gastric inflammation, MHCII+ monocyte infiltration, IL-23 and IL-17A were attenuated in Redd1-/- mice. Mechanistically, REDD1 in GECs regulated CXCL1 production, which attracted MHCII+ monocytes migration by CXCL1-CXCR2 axis. Then H. pylori induced MHCII+ monocytes to secrete IL-23, which favored IL-17A-producing CD4+ cell (Th17 cell) polarization, thereby contributing to the development of H. pylori-associated gastritis. CONCLUSIONS: The present study identifies a novel regulatory network involving REDD1, which collectively exert a pro-inflammatory effect within gastric microenvironment. Efforts to inhibit this REDD1-dependent pathway may prove valuable strategies in treating of H. pylori-associated gastritis.
Assuntos
Citocinas/metabolismo , Mucosa Gástrica/microbiologia , Gastrite/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Células Th17/microbiologia , Fatores de Transcrição/metabolismo , Animais , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Técnicas de Cocultura , Modelos Animais de Doenças , Mucosa Gástrica/imunologia , Mucosa Gástrica/metabolismo , Gastrite/imunologia , Gastrite/metabolismo , Infecções por Helicobacter/complicações , Helicobacter pylori/imunologia , Helicobacter pylori/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Fenótipo , Fosforilação , Células Th17/imunologia , Células Th17/metabolismo , Fatores de Transcrição/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
BHLHE40, a member of the basic helix-loop-helix transcription factor family, has been reported to play an important role in inflammatory diseases. However, the regulation and function of BHLHE40 in Helicobacter pylori (H pylori)-associated gastritis is unknown. We observed that gastric BHLHE40 was significantly elevated in patients and mice with H pylori infection. Then, we demonstrate that H pylori-infected GECs express BHLHE40 via cagA-ERK pathway. BHLHE40 translocates to cell nucleus, and then binds to cagA protein-activated p-STAT3 (Tyr705). The complex increases chemotactic factor CXCL12 expression (production). Release of CXCL12 from GECs fosters CD4+ T cell infiltration in the gastric mucosa. Our results identify the cagA-BHLHE40-CXCL12 axis that contributes to inflammatory response in gastric mucosa during H pylori infection.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Quimiocina CXCL12/metabolismo , Células Epiteliais/metabolismo , Gastrite/microbiologia , Infecções por Helicobacter/metabolismo , Proteínas de Homeodomínio/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Linfócitos T CD4-Positivos/citologia , Núcleo Celular/metabolismo , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Gastrite/metabolismo , Regulação da Expressão Gênica , Helicobacter pylori , Humanos , Inflamação , Camundongos , Camundongos Endogâmicos C57BL , Estômago/microbiologia , Regulação para CimaRESUMO
A novel Gram-stain-positive, strictly anaerobic, elliptical, non-motile and non-flagellated bacterium, designed LZLJ-2T, was isolated from the mud in a fermentation cellar used for the production of Chinese Luzhou-flavour Baijiu. Growth occurred at 28-45 °C (optimum, 37 °C), at pH 6.0-7.0 (optimum, pH 6.0) and with concentrations of NaCl up to 2â% (w/v; optimum, 0â%). On the basis of 16S rRNA gene sequence similarity, strain LZLJ-2T belonged to the genus Thermophilibacter and was most closely related to Thermophilibacter mediterraneus Marseille-P3256T (similarity 96.9â%), Olsenella gallinarum ClaCZ62T (similarity 96.6â%) and Thermophilibacter provencensis Marseille-P2912T (similarity 96.4â%). In addition, strain LZLJ-2T had high similarity to the genus Olsenella, including Olsenella profusa DSM 13989T (similarity 94.9â%), Olsenella umbonata DSM 22620T (similarity 94.9â%), Olsenella uli ATCC 49627T (similarity 94.22â%), Tractidigestivibacter scatoligenes DSM 28304T (similarity 93.9â%) and Paratractidigestivibacter faecalis KCTC 15699T (similarity 93.25â%). Comparative genome analysis showed that orthoANI values between strain LZLJ-2T and Thermophilibacter mediterraneus Marseille-P3256T, Olsenella gallinarum ClaCZ62T, Thermophilibacter provencensis Marseille-P2912T, Olsenella profusa DSM 13989T, Olsenella umbonata DSM 22620T, Olsenella uli ATCC 49627T, Tractidigestivibacter scatoligenes DSM 28304T and Paratractidigestivibacter faecalis KCTC 15699T were 78.68, 78.99, 78.29, 73.40, 74.00, 74.30, 75.08 and 77.23â%, and the genome-to-genome distance values were respectively 22.3, 22.5, 22.4, 19.6, 20.5, 19.7, 20.5 and 21.5â%. The genomic DNA G+C content of strain LZLJ-2T was 65.21 mol%. The predominant cellular fatty acids (>10â%) of strain LZLJ-2T were C18â:â1 cis 9 (33.7â%), C14â:â0 (22.0â%) and C18â:â1 cis 9 DMA (13.5â%). d-Glucose, sucrose, mannose, maltose, lactose (weak), salicin, glycerol (weak), cellobiose and trehalose (weak) could be used by strain LZLJ-2T as sole carbon sources. Enzyme activity results showed positive reactions with valine arylamidase, leucine arylamidase, crystine arylamidase, acid phosphatase, alkaline phosphatase, esterase (C4) (weakly positive), naphthol-AS-BI-phosphohydrolase, α-glucosidase and ß-glucosidase. The major end products of glucose fermentation were lactic acid and acetic acid. It produced skatole from indole acetic acid, and produced p-cresol from modified peptone-yeast extract medium with glucose. Based on the 16S rRNA gene trees as well as the genome core gene tree, it is suggested that Olsenella gallinarum are transferred to genus Thermophilibacter as Thermophilibacter gallinarum comb. nov. Based on phenotypic, genotypic and phylogenetic data, strain LZLJ-2T is considered to represent a novel species of the genus Thermophilibacter, for which the name Thermophilibacter immobilis sp. nov. is proposed. The type strain is LZLJ-2T (=KCTC 25162T=JCM 34224T).
Assuntos
Actinobacteria/classificação , Ácidos Graxos , Fermentação , Filogenia , Microbiologia do Solo , Actinobacteria/isolamento & purificação , Bebidas Alcoólicas , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
Two new 1,3-benzodioxole derivatives, leucandioxoles A and B (1-2), together with two known related compounds (3-4), have been isolated from the South China Sea sponge Leucandra sp. The structures of all compounds were clearly elucidated on the basis of spectroscopic analyses and compared with the literatures. The cytotoxicity against A549, Hep G2, MDA-MB-231, and HeLa cell lines of 1-4 were evaluated. Only compound 1 exhibited moderate activity against MDA-MB-231 cells with the IC50 value of 7.98 ± 0.74 µM.
Assuntos
Antineoplásicos , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , China , Dioxóis , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Estrutura MolecularRESUMO
Cathepsin C (CtsC) functions as a central coordinator for activation of many serine proteases in immune cells. However, CtsC expression in gastric epithelial cells and its role in Helicobacter pylori infection remain unclear. Real-time PCR, Western blot, and immunohistochemistry analyses identified that CtsC was decreased in gastric mucosa of H. pylori-infected patients and mice. Isolated gastric epithelial cells and cell lines were stimulated with H. pylori and/or TGF-ß1 showed that down-regulation of CtsC in gastric epithelial cells largely depended on H. pylori cagA via Src/ERK and Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways, and the effect could be synergistically augmented by TGF-ß1 in an autocrine manner. In human gastric mucosa, CtsC expression was negatively correlated with bacteria colonization; accordingly, provision of exogenous active CtsC overwhelmed H. pylori persistence in gastric mucosa of mice. In the presence of active CtsC, isolated human neutrophils activated via NF-κB pathway with augmented bactericidal capacity in vitro. We also found that neutrophils activated and cleared bacteria in active CtsC-injected mice and that there was no bactericidal capacity in mice that were simultaneously neutrophil-depleted by Ly6G antibody. Our findings identified a mechanism that H. pylori abrogate CtsC to impair neutrophil activation and to ensure persistence in gastric mucosa. Efforts to enable and boost this neutrophil activation pathway by active CtsC may therefore become valuable strategies in treating H. pylori infection.-Liu, Y. G., Teng, Y. S., Cheng, P., Kong, H., Lv, Y. P., Mao, F. Y., Wu, X. L., Hao, C. J., Chen, W., Yang, S. M., Zhang, J. Y., Peng, L. S., Wang, T. T., Han, B., Ma, Q., Zou, Q. M., Zhuang, Y. Abrogation of cathepsin C by Helicobacter pylori impairs neutrophil activation to promote gastric infection.
Assuntos
Catepsina C/metabolismo , Mucosa Gástrica/microbiologia , Helicobacter pylori/patogenicidade , Ativação de Neutrófilo/fisiologia , Animais , Western Blotting , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Imunofluorescência , Infecções por Helicobacter/metabolismo , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Fagocitose/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Coal-based olefin (CTO) industry as a complement of traditional petrochemical industry plays vital role in China's national economic development. However, high CO2 emission in CTO industry is one of the fatal problems to hinder its development. In this work, the carbon emission and mitigation potentials by different reduction pathways are evaluated. The economic cost is analyzed and compared as well. According to the industry development plan, the carbon emissions from China's CTO industry will attain 189.43 million ton CO2 (MtCO2) and 314.11 MtCO2 in 2020 and 2030, respectively. With the advanced technology level, the maximal carbon mitigation potential could be attained to 15.3% and 21.9% in 2020 and 2030. If the other optional mitigation ways are combined together, the carbon emission could further reduce to some extent. In general, the order of mitigation potential is followed as: feedstock alteration by natural gas > CO2 hydrogenation with renewable electricity applied > CCS technology. The mitigation cost analysis indicates that on the basis of 2015 situation, the economic penalty for feedstock alteration is the lowest, ranged between 186 and 451 CNY/tCO2, and the cost from CCS technology is ranged between 404 and 562 CNY/tCO2, which is acceptable if the CO2 enhanced oil recovery and carbon tax are considered. However, for the CO2 hydrogenation technology, the cost is extremely high and there is almost no application possibility at present.
Assuntos
Alcenos/química , Dióxido de Carbono , Carbono , Carvão Mineral , Poluição Ambiental/prevenção & controle , Indústria Química , China , Poluição Ambiental/economiaRESUMO
In this work we investigate the role of soil texture in petroleum vapor intrusion (PVI) by performing numerical modeling, analytical calculations, and statistical analysis of the USEPA's PVI database. Numerical simulations were conducted for three kinds of soil (sand, sandy loam, and clay), and the results indicate that the maximum attenuations of vapor concentrations from source to indoor air were observed when the clay soil is below the building. In the anaerobic zone, the normalized soil gas concentration profiles were observed to be similar and independent of soil type, whereas in the aerobic zone, a more significant attenuation was observed in finer grained soils. Such a finding is consistent with the statistical results of the USEPA's PVI database, which indicate that in the near-source zone, the soil gas concentration in coarse-grained soil tends to be lower than that in fine-grained soil, possibly caused by a weaker source due to mass loss by volatilization, whereas at a distance away from the source, the measured soil gas concentrations in fine-grained soils become much lower because of aerobic biodegradation with a shorter diffusive reaction length. Thus, 3 and 5 m are proposed as soil-type-dependent vertical screening distances for fine and coarse-grained soils, respectively. It should be noted that the validity of these screening distances is examined only for relatively homogeneous soils, and they may not be applicable for cases involving layered soil systems, where the availability of O in the subfoundation should be evaluated with subslab or multidepth samples to confirm the presence of aerobic biodegradation.
Assuntos
Modelos Químicos , Petróleo/análise , Poluentes do Solo/química , Solo/química , VolatilizaçãoRESUMO
The phytochemical study on the leaves of Acanthopanax gracilistylus (Araliaceae) resulted in the discovery of a new lupane-triterpene compound, acangraciligenin S (1), and a new lupane-triterpene glycoside, acangraciliside S (2), as well as two known ones, 3α,11α-dihydroxy-lup-20(29)-en-23,28-dioic acid (3) and acankoreoside C (4). Their chemical structures were elucidated by mass, 1D- and 2D-nuclear magnetic resonance (NMR) spectroscopy. The chemical structures of the new compounds 1 and 2 were determined to be 1ß,3α-dihydroxy-lup-20(29)-en-23, 28-dioic acid and 1ß,3α-dihydroxy-lup-20(29)-en-23,28-dioic acid 28-O-[α-l-rhamnopyranosyl-(1â4)-ß-d-glucopyranosyl-(1â6)-ß-d-glucopyranosyl] ester, respectively. The anti-neuroinflammatory activity of the selective compounds, 1 and 3, were evaluated with lipopolysaccharide (LPS)-induced BV2 microglia. The tested compounds showed moderate inhibitory effect of nitric oxide (NO) production.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Eleutherococcus/química , Triterpenos/química , Triterpenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Avaliação Pré-Clínica de Medicamentos/métodos , Lipopolissacarídeos/farmacologia , Espectroscopia de Ressonância Magnética , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Estrutura Molecular , Óxido Nítrico/metabolismo , Folhas de Planta/químicaRESUMO
OBJECTIVE: Neutrophils are prominent components of solid tumours and exhibit distinct phenotypes in different tumour microenvironments. However, the nature, regulation, function and clinical relevance of neutrophils in human gastric cancer (GC) are presently unknown. DESIGN: Flow cytometry analyses were performed to examine levels and phenotype of neutrophils in samples from 105 patients with GC. Kaplan-Meier plots for overall survival were performed using the log-rank test. Neutrophils and T cells were isolated, stimulated and/or cultured for in vitro and in vivo regulation and function assays. RESULTS: Patients with GC showed a significantly higher neutrophil infiltration in tumours. These tumour-infiltrating neutrophils showed an activated CD54+ phenotype and expressed high level immunosuppressive molecule programmed death-ligand 1 (PD-L1). Neutrophils activated by tumours prolonged their lifespan and strongly expressed PD-L1 proteins with similar phenotype to their status in GC, and significant correlations were found between the levels of PD-L1 and CD54 on tumour-infiltrating neutrophils. Moreover, these PD-L1+ neutrophils in tumours were associated with disease progression and reduced GC patient survival. Tumour-derived GM-CSF activated neutrophils and induced neutrophil PD-L1 expression via Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) signalling pathway. The activated PD-L1+ neutrophils effectively suppressed normal T-cell immunity in vitro and contributed to the growth and progression of human GC in vivo; the effect could be reversed by blocking PD-L1 on these neutrophils. CONCLUSIONS: Our results illuminate a novel mechanism of PD-L1 expression on tumour-activated neutrophils in GC, and also provide functional evidence for these novel GM-CSF-PD-L1 pathways to prevent, and to treat this immune tolerance feature of GC.
Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Tolerância Imunológica , Ativação de Neutrófilo , Neutrófilos/metabolismo , Neoplasias Gástricas/imunologia , Animais , Estudos de Casos e Controles , Estudos de Coortes , Progressão da Doença , Feminino , Citometria de Fluxo , Humanos , Estimativa de Kaplan-Meier , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Infiltração de Neutrófilos , Neutrófilos/imunologia , Transdução de Sinais , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida , Linfócitos T/imunologiaRESUMO
Interleukin 6 (IL-6) was abundant in the tumor microenvironment and played potential roles in tumor progression. In our study, the expression of IL-6 in tumor tissues from 36 gastric cancer (GC) patients was significantly higher than in non-tumor tissues. Moreover, the number of CD163+CD206+ M2 macrophages that infiltrated in tumor tissues was significantly greater than those infiltrated in non-tumor tissues. The frequencies of M2 macrophages were positively correlated with the IL-6 expression in GC tumors. We also found that IL-6 could induce normal macrophages to differentiate into M2 macrophages with higher IL-10 and TGF-ß expression, and lower IL-12 expression, via activating STAT3 phosphorylation. Accordingly, knocking down STAT3 using small interfering RNA decreased the expression of M2 macrophages-related cytokines (IL-10 and TGF-ß). Furthermore, supernatants from IL-6-induced M2 macrophages promote GC cell proliferation and migration. Moreover, IL-6 production and CD163+CD206+ M2 macrophage infiltration in tumors were associated with disease progression and reduced GC patient survival. In conclusion, our data indicate that IL-6 induces M2 macrophage differentiation (IL-10highTGF-ßhighIL-12 p35low ) by activating STAT3 phosphorylation, and the IL-6-induced M2 macrophages exert a pro-tumor function by promoting GC cell proliferation and migration.
Assuntos
Interleucina-6/imunologia , Macrófagos/imunologia , Fator de Transcrição STAT3/imunologia , Neoplasias Gástricas/imunologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/imunologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Progressão da Doença , Humanos , Interleucina-6/biossíntese , Interleucina-6/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Proteínas Recombinantes/farmacologia , Transdução de Sinais , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , TransfecçãoRESUMO
Preferential pathways can be significant vapor intrusion (VI) contributors, causing potentially higher inhalation risk to residents of affected buildings than that arising through traditional intrusion pathways. To assess land drains as a preferential pathway, a three-dimensional model, validated using data from a 4-yr field study, was used to study the roles of subfoundation soil permeability on soil gas flow and indoor depressurization. Results indicated that it is almost impossible for an indirect preferential pathway like a land drain ending in subfoundation soils with a permeability <10 m to affect indoor air quality if the land drain connects to a source with the same vapor concentration as that of the groundwater source beneath the building. An equation was developed to estimate the threshold permeability. We also found that even after the preferential pathway was identified using indoor depressurization (also known as controlled pressure method [CPM]) and then turned off, the influence of the preferential pathway and indoor depressurization on indoor concentration might last for months, although it may not be significant (i.e., may not exceed one order of magnitude, in this study). In the absence of such a preferential VI pathway, CPM may actually reduce indoor air concentrations of contaminants below those present under natural indoor pressure conditions, due to the emission rate limit determined by the upward diffusion rate from the vapor source. Our study highlights the role of measuring subfoundation soil permeability to soil gas flow in site investigations and warns practitioners about the possible mischaracterization of indoor air concentration after applying CPM in the absence of a preferential pathway.
Assuntos
Poluição do Ar em Ambientes Fechados/análise , Gases/análise , Água Subterrânea , Solo/químicaRESUMO
OBJECTIVE: Helper T (Th) cell responses are critical for the pathogenesis of Helicobacter pylori-induced gastritis. Th22 cells represent a newly discovered Th cell subset, but their relevance to H. pylori-induced gastritis is unknown. DESIGN: Flow cytometry, real-time PCR and ELISA analyses were performed to examine cell, protein and transcript levels in gastric samples from patients and mice infected with H. pylori. Gastric tissues from interleukin (IL)-22-deficient and wild-type (control) mice were also examined. Tissue inflammation was determined for pro-inflammatory cell infiltration and pro-inflammatory protein production. Gastric epithelial cells and myeloid-derived suppressor cells (MDSC) were isolated, stimulated and/or cultured for Th22 cell function assays. RESULTS: Th22 cells accumulated in gastric mucosa of both patients and mice infected with H. pylori. Th22 cell polarisation was promoted via the production of IL-23 by dendritic cells (DC) during H. pylori infection, and resulted in increased inflammation within the gastric mucosa. This inflammation was characterised by the CXCR2-dependent influx of MDSCs, whose migration was induced via the IL-22-dependent production of CXCL2 by gastric epithelial cells. Under the influence of IL-22, MDSCs, in turn, produced pro-inflammatory proteins, such as S100A8 and S100A9, and suppressed Th1 cell responses, thereby contributing to the development of H. pylori-associated gastritis. CONCLUSIONS: This study, therefore, identifies a novel regulatory network involving H. pylori, DCs, Th22 cells, gastric epithelial cells and MDSCs, which collectively exert a pro-inflammatory effect within the gastric microenvironment. Efforts to inhibit this Th22-dependent pathway may therefore prove a valuable strategy in the therapy of H. pylori-associated gastritis.
Assuntos
Gastrite/microbiologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Mediadores da Inflamação/metabolismo , Interleucinas/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Biomarcadores/metabolismo , Células Cultivadas , Quimiocina CXCL2/imunologia , Quimiocina CXCL2/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Feminino , Gastrite/imunologia , Gastrite/fisiopatologia , Infecções por Helicobacter/fisiopatologia , Helicobacter pylori/patogenicidade , Humanos , Mediadores da Inflamação/imunologia , Interleucinas/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real , Papel (figurativo) , Sensibilidade e Especificidade , Linfócitos T Auxiliares-Indutores/metabolismo , Transfecção , Interleucina 22RESUMO
Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori-associated pathology are unknown. Here, we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA-dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a -/-, Angptl4 -/-, and Il17a -/- Angptl4 -/- mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K-AKT-NF-κB, resulting in increased gastric influx of regulatory CD4+ T cells (Tregs) via CCL5-CCR4-dependent migration. In turn, ANGPTL4 induced Treg proliferation by binding to ITGAV to activate PI3K-AKT-NF-κB, promoting H. pylori-associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection.
RESUMO
PURPOSE: This is a meta-analysis of randomized and non-randomized studies comparing the clinical and radiological efficacy of minimally invasive (MI) and conventional open transforaminal lumbar interbody fusion (open-TLIF) for degenerative lumbar diseases. METHODS: A literature search of the MEDLINE database identified 11 studies that met our inclusion criteria. A total of 785 patients were examined. Pooled estimates of clinical and radiological outcomes, and corresponding 95% confidence intervals were calculated. RESULTS: The pooled data revealed that MI-TLIF was associated with less blood loss, shorter hospital stay, and a trend of better functional outcomes when compared with open-TLIF. However, MI-TLIF significantly increased the intraoperative X-ray exposure. Both techniques had similar operative time, complication rate, and re-operation rate. CONCLUSIONS: Based on the available evidence, MI-TLIF for degenerative lumbar diseases might lead to better patient-based outcomes. MI-TLIF would be a promising procedure, but extra efforts are needed to reduce its intraoperative radiation exposure. More randomized controlled trials are needed to compare these two surgical options.
Assuntos
Degeneração do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Perda Sanguínea Cirúrgica , Feminino , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Tempo de Internação , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Avaliação de Resultados em Cuidados de Saúde , Radiografia , Resultado do TratamentoRESUMO
OBJECTIVE: To compare clinical efficacy between discectomy and discectomy plus Coflex fixation for lumbar disc herniation. METHODS: From December 2007 to August 2008, 50 patients (31 males and 19 females) were treated by surgery of discectomy and discectomy plus Coflex fixation. The average age was 52.5 years (range, 30 - 72 years). There were 24 cases in the group of discectomy plus Coflex fixation and 26 cases in the group of discectomy. Preoperative and postoperative visual analogue scales (VAS), Japanese Orthopadic Association (JOA) and Oswestry disability index (ODI) were recorded, as well as radiological index. And use a paired t-test and one-way analysis of variance (one-way ANOVA) statistical method to evaluate the Coflex dynamic stabilization system in value in the treatment of lumbar disc herniation. RESULTS: Both groups received significant improvement of JOA, ODI and VAS (t = -33.2 - 64.5, P < 0.01), but the group of discectomy was found with deterioration of ODI at last follow-up, 12 months after surgery 6.7 ± 1.5 to 10.2 ± 2.3 (t = -19.3, P < 0.05). The group of discectomy plus Coflex fixation was found with significant increase of height of dorsal intervertebral discs (HD), distance across the two adjacent spinous processes (DS), distance of intervertebral foramina (DIF) and spinal canal area(SA) (t = -34.4 - 4.5, P < 0.05). In contrast, the group of discectomy was found with significant decrease of HD, DS, DIF and SA (t = 3.4 - 52.8, P < 0.05). Coflex fixed group in HD, DIF, DS significant difference with simple discectomy group, with a statistically significant (F = 14.1 - 25.6, P < 0.05). CONCLUSIONS: Both discectomy and discectomy plus Coflex fixation are apparently effective when treating lumbar disc herniation. Coflex can significantly increase the HD and DIF when used for lumbar disc herniation, and it has positive influence for keeping height of lumbar vertebral space and treating the nerve root symptom of lumbar disc herniation. Discectomy plus Coflex is better than pure discectomy in preventing lumbar degeneration.
Assuntos
Fixadores Internos , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Husks are the main source of bran and furfural flavor in traditional Chinese light-aroma Baijiu, but they negatively affect its smell and taste. Here, bran husks were replaced with fresh bamboo to brew light-aroma Baijiu. Flavor components in Jiupei and Baijiu were detected through headspace solid-phase microextraction with gas chromatography-mass spectrometry, and physicochemical properties were assessed; flavor results were obtained from correlation, principal component, and cluster analyses. Starch and reducing sugar content in Jiupei negatively correlated with moisture, alcohol content, and acidity. Fresh bamboo reduced furfural from bran husks in Jiupei by 88.5% and increased alcohol distillation by 51%; it also improved starch efficiency (5%). Surprisingly, isovanillin was found to be present in Baijiu. Total Baijiu yield (57% ± 2.01%) was attained when crushed bamboo size was 1.5 cm × 0.3 cm × 0.3 cm. This study supports the use of fresh bamboo (an eco-friendly alternative for husks) in brewing light-aroma Baijiu. PRACTICAL APPLICATION: The use of fresh bamboo as a replacement for rice husks in brewing light-aroma Baijiu was investigated. It attenuated the chaff taste in light-aroma Baijiu and increased the liquor yield. Surprisingly, isovanillin was also present in the base Baijiu, and it added to the fragrance. This study not only supports the use of bamboo as an auxiliary material for brewing light-aroma Baijiu but also provides a reference for brewing light-aroma Baijiu with alternative auxiliary materials.