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1.
Angew Chem Int Ed Engl ; : e202404454, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683297

RESUMO

Sustainable carbon dots comprising surficial oxime ester groups following homolytic bond cleavage exhibit potential as photoinitiators for traditional free radical photopolymerization. Carbon dots were made following a solvothermal procedure from sustainable furfural available from lignocellulose. Surficial aldehyde moieties reacted with hydroxylamine to the respective oxime while reaction with benzoyl chloride resulted in a biobased Type I photoinitiator comprising sustainable carbon dot (CD-PI). Photoinitiating ability was compared with the traditional photoinitiator (PI) ethyl (2,4,6-trimethyl benzoyl) phenyl phosphinate (TPO-L) by real-time FTIR with UV exposure at 365 nm. Photopolymer composition based on a mixture of urethane dimethacrylate (UDMA) and tripropylene glycol diethacrylate (TPGDA) resulted in a similar final conversion of about 70% using either CD-PI or TPO-L. Nevertheless, it appeared homogeneous in the case of compositions processed with CD-PI, while those made with TPO-L were heterogeneous as shown by two glass transition temperatures. Moreover, the migration rate of CD-PI in the cured samples was lower in comparison with those samples using TPO-L as PI.

2.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124342, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38676981

RESUMO

Two spirobifluene-based fluorescent probes SPF1 and SPF2, were designed and synthesized. The probes displayed "turn-on" fluorescence response for Cysteine. One of the challenges in developing a Cysteine probe is to secure high selectivity. SPF1/SPF2 can discriminate Cysteine from GSH as well as Hcy, and showed high substrate selectivity. The detection limit of SPF1 is 36 nM, which is excellent comparing with other optical sensors for Cysteine. The sensing mechanism of SPF1/SPF2 was verified by experimental data and theoretical calculations. There was a good linear relationship between the fluorescence intensity of SPF1/SPF2 and the concentration of Cysteine. The MTT tests indicated that SPF1/SPF2 had low cytotoxicity and good biocompatibility. Theoretical calculations demonstrated that SPF1, SPF2, and their related reaction products with Cysteine exhibited good two-photon absorption properties. Finally, SPF1/SPF2 had been successfully applied to the imaging of Cysteine in living cells under two-photon excitation.


Assuntos
Cisteína , Corantes Fluorescentes , Compostos de Espiro , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Cisteína/análise , Humanos , Compostos de Espiro/química , Células HeLa , Imagem Óptica/métodos , Limite de Detecção , Fótons , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Espectrometria de Fluorescência/métodos
3.
Nat Commun ; 15(1): 1590, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383517

RESUMO

Photocured room temperature phosphorescent (RTP) materials hold great potential for practical applications but are scarcely reported. Here, we develop photocured RTP materials (P-Lig) using a combination of lignosulfonate, acrylamide, and ionic liquid (1-ethyl-3-methylimidazolium bromide). With this design, lignosulfonate simultaneously serves as RTP chromophore and photoinitiator. Specifically, lignosulfonate in the ionic liquid generates radicals to polymerize the acrylamide upon UV irradiation. The resulting lignosulfonate is automatically confined in an as-formed crosslinked matrix to provide RTP. As such RTP with an emission lifetime of ~110 ms is observed from the confined lignosulfonate in P-Lig. Additionally, energy transfer occur between P-Lig and Rhodamine B (RhB), triggering red afterglow emission when P-Lig is in situ loaded with RhB (P-Lig/RhB). As a demonstration of potential applications, the P-Lig and P-Lig/RhB are used as photocured RTP coatings and RTP inks for fabricating 3D materials and for information encryption.

4.
Nat Rev Chem ; 7(11): 800-812, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37749285

RESUMO

Room-temperature phosphorescent (RTP) materials have enormous potential in many different areas. Additionally, the conversion of natural resources to RTP materials has attracted considerable attention. Owing to their inherent luminescent properties, natural materials can be efficiently converted into sustainable RTP materials. However, to date, only a few reviews have focused on this area of endeavour. Motivated by this lack of coverage, in this Review, we address this shortcoming and introduce the types of natural resource available for the preparation of RTP materials. We mainly focus on the inherent advantages of natural resources for RTP materials, strategies for activating and enhancing the RTP properties of the natural resources as well as the potential applications of these RTP materials. In addition, we discuss future challenges and opportunities in this area of research.

5.
Int Urol Nephrol ; 54(12): 3079-3086, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35987936

RESUMO

PURPOSE: In patients undergoing bone scanning, the positive rate of bone metastasis (BM) of prostate cancer (PCa) is quite low. The main purpose of this study was to explore the application of %p2PSA and prostate health index (phi) in predicting BM of PCa before bone scanning to reduce unnecessary bone scanning. METHODS: A total of 279 PCa patients were enrolled in our study. The area under the ROC curve was used to evaluate the prediction accuracy of the variables. Binary logistic regression analysis was performed to establish a prediction model. A multivariate regression model was established to evaluate the predictive value of the variables. The nomogram model was established by R software. The patients were stratified into an intermediate-risk subgroup (T2b-T2c, Gleason score = 6-7) and a high-risk subgroup (cT3-4, Gleason score = 8-10). In the overall cohort and subgroups, McNemar's test was used for comparison of different predictive variables. RESULTS: Of the 279 patients included in the study, 43 patients were identified as having BM by bone scanning. Univariate logistic regression analysis showed that age (p = 0.043), tPSA (p = 0.001), Ki-67 (p = 0.003), Gleason score (p = 0.001), clinical T stage (p < 0.001) and phi (p < 0.001) were significantly different in BM patients. In multivariate regression analysis, the model with phi showed significant diagnostic ability for predicting BM (AUC = 0.854). In the subgroup analysis, phi was significantly superior to tPSA in terms of the positive predictive value at sensitivities of 84.62% and 61.54% in the overall cohort (p < 0.001) and intermediate-risk subgroup (p < 0.001), respectively. Moreover, %p2PSA showed no significant advantage over tPSA (p > 0.05). CONCLUSION: The level of phi was significantly related to the positive rate of BM in initially diagnosed PCa. In PCa patients with clinical stage T2b-T2c and Gleason score = 6-7, phi can be used as a surrogate indicator of tPSA for screening BM.


Assuntos
Neoplasias Ósseas , Neoplasias da Próstata , Masculino , Humanos , Antígeno Prostático Específico , Próstata/patologia , Antígeno Ki-67 , Neoplasias da Próstata/patologia , Gradação de Tumores , Curva ROC , Neoplasias Ósseas/diagnóstico por imagem , Biópsia
6.
Dis Markers ; 2022: 9443407, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35299868

RESUMO

Background: Clear cell renal cell carcinoma (ccRCC) is a type of life-threatening malignant tumor of the urinary system. IL20RB, interleukin 20 receptor subunit beta, is a cytokine receptor subunit coding gene and was initially found to play a vital role in human cancers, while its role in ccRCC still remains unclear. Methods: In this work, we explored the prognostic value and therapeutic potential of IL20RB in ccRCC mainly by online tools. Firstly, we used UALCAN and GEPIA to explore the expression profile and prognostic value of IL20RB in various cancers; the expression profile in tumor cell lines was also analysed with CCLE and Expression Atlas. Then, we decided to focus on ccRCC for further analysis; we further demonstrated the significant correlation between expression and clinical features by GEPIA and UALCAN. In order to reveal the potential intrinsic mechanism responsible for the upregulation of IL20RB in ccRCC, we made genetic alternation analysis and methylation analysis. cBioPortal was used for genetic alternation analysis. UALCAN, MethSurv, and Xena were used for methylation analysis. To learn details of how IL20RB might function in ccRCC, we further conducted functional analysis and immune infiltration analysis. STRING and GSEA were used to do functional analysis. TIMER was used for immune infiltration analysis; KM plotter was used for survival analysis. Results: Results show that IL20RB is upregulated in ccRCC, and low methylation may be responsible for its upregulation. Both high expression and low methylation of IL20RB predict worse survival, and both have a strong positive correlation with clinical characteristics. In addition, results indicate that there exists a crosstalk between IL20RB and neutrophils. Furthermore, the immune microenvironment could influence the prognosis predicting ability of IL20RB. Conclusions: In conclusion, IL20RB plays an important role in ccRCC and is identified as a novel prognostic and potential therapeutic biomarker in ccRCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Prognóstico , Receptores de Interleucina , Transcriptoma , Linhagem Celular Tumoral , Biologia Computacional , Humanos , Análise de Sobrevida , Microambiente Tumoral , Regulação para Cima
7.
JAMA Netw Open ; 4(11): e2133596, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34751758

RESUMO

Importance: The labor migration of parents in China often leaves children behind, which may be adversely associated with children's health. However, few studies have assessed the association of parental migration with nonsuicidal self-injury (NSSI) or with suicidality among their offspring. Objective: To examine the associations of parental labor migration with NSSI and with suicidality as well as potential differential associations by sex among offspring left behind. Design, Setting, and Participants: This nationwide cross-sectional study was conducted from February to October 2015 among individuals aged 11 to 20 years from 45 public middle and high schools across 5 provinces of China. Data analysis was performed from November 1, 2020, to March 1, 2021. Exposures: Parental labor migration, including parental migration status (yes vs no), migration pattern (father, mother, or both), and the child's age at the initial parent-child separation. Main Outcomes and Measures: Less frequent (1-4 episodes) NSSI, more frequent (≥5 episodes) NSSI, suicidal ideation, and suicide attempt in the past year were measured using validated questionnaires. Multinomial or binomial logistic regression analyses were used separately to estimate adjusted odds ratios (aORs) and 95% CIs of the associations between parental migration and NSSI, suicidal ideation, or suicide attempt. Potential covariates (demographic, family-level, and psychological characteristics) were adjusted for in 3 sequential models. Results: A total of 15 312 participants (7904 male [51.6%] and 7408 female [48.4%]) aged 11 to 20 years (mean [SD] age, 15.1 [1.8] years) were included. Of those participants, 5963 (23.3%) experienced parental migration. The 12-month prevalence of less frequent NSSI was 17.2% (2635 of 15 312), the 12-month prevalence of more frequent NSSI was 11.6% (1783 of 15 312), the 12-month prevalence of suicidal ideation was 15.2% (2335 of 15 312), and the 12-month prevalence of suicide attempt was 3.5% (535 of 15 312). Parental migration was associated with less frequent NSSI (adjusted odds ratio [aOR], 1.13; 95% CI, 1.03-1.24); no significant association of parental migration with more frequent NSSI (aOR, 1.01; 95% CI, 0.90-1.13), suicidal ideation (aOR, 1.00; 95% CI, 0.90-1.10), or suicide attempt (aOR, 1.09; 95% CI, 0.90-1.33) was identified. Compared with children whose parents did not migrate, the aOR for less frequent NSSI for participants whose father migrated was 1.18 (95% CI, 1.06-1.31), and the aOR for less frequent NSSI for participants having both parents migrate was 1.12 (95% CI, 1.01-1.28). Compared with children whose parents did not migrate, participants who experienced initial separation from 1 or both parents at preschool age had an aOR for less frequent NSSI of 1.16 (95% CI, 1.03-1.31). No sex disparities were found in these associations except for participants who experienced initial separation from 1 or both migrant parents at preschool age, for which the aOR for more frequent NSSI was higher among male (aOR, 1.27; 95% CI, 1.04-1.55) than female (aOR, 0.96; 95% CI, 0.77-1.19) participants. Conclusions and Relevance: This cross-sectional study found that parental migration, mainly of the father or of both parents, or an initial separation of children at preschool age from 1 or both parents who migrated was associated with higher odds of experiencing 1 to 4 NSSI episodes in 1 year among offspring. Overall, the associations of parental migration with NSSI and suicidality were similar between male and female participants.


Assuntos
Filho de Pais com Deficiência/psicologia , Emigração e Imigração/estatística & dados numéricos , Comportamento Autodestrutivo/epidemiologia , Ideação Suicida , Criança , China , Estudos Transversais , Feminino , Humanos , Masculino , Relações Pais-Filho , Pais , Prevalência , Fatores de Risco , Comportamento Autodestrutivo/psicologia
8.
J Cancer ; 12(14): 4134-4147, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093816

RESUMO

Background: Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor of the urinary system. The ubiquitin proteasome system (UPS) plays an important role in the generation, metabolism and survival of tumor. We are aimed to make a comprehensive exploration of the UPS's role in ccRCC with bioinformatic tools, which may contribute to the understanding of UPS in ccRCC, and give insight for further research. Methods: The UPS-related genes (UPSs) were collected by an integrative approach. The expression and clinical data were downloaded from TCGA database. R soft was used to perform the differentially expressed UPSs analysis, functional enrichment analysis. We also estimated prognostic value of each UPS with the help of GEPIA database. Two predicting models were constructed with the differentially expressed UPSs and prognosis-related genes, respectively. The correlations of risk score with clinical characteristics were also evaluated. Data of GSE29609 cohort were obtained from GEO database to validate the prognostic models. Results: We finally identified 91 differentially expressed UPSs, 48 prognosis related genes among them, and constructed a prognostic model with 18 UPSs successfully, the AUC was 0.760. With the help of GEPIA, we found 391 prognosis-related UPSs, accounting for 57.84% of all UPSs. Another prognostic model was constructed with 28 prognosis-related genes of them, and with a better AUC of 0.825. Additionally, our models can also stratify patients into high and low risk groups accurately in GSE29609 cohort. Similar prognostic values of our models were observed in the validated GSE29609 cohort. Conclusions: UPS is dysregulated in ccRCC. UPS related genes have significant prognostic value in ccRCC. Models constructed with UPSs are effective and applicable. An abnormal ubiquitin proteasome system should play an important role in ccRCC and be worthy of further study.

9.
ACS Appl Mater Interfaces ; 13(6): 7443-7452, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33528998

RESUMO

Flexible electronics greatly facilitate human life due to their convenience and comfortable utilization. Liquid metals are an ideal candidate for flexible devices; however, the high surface tension and poor surface wettability restrict their application on diverse substrates. Herein, a printable and recyclable ink composed of poly(vinyl alcohol) and a liquid metal (PVA-LM) was developed to resolve these problems. The materials were designed considering the compatibility between PVA and the liquid metal, and the composite theory was applied to determine the component proportion. The developed composites improved the surface wettability of the liquid metal on diverse substrates, and three-dimensional (3D) printing technology was chosen to maximize the use of this material. Moreover, the PVA-LM ink showed excellent conductivity of about 1.3 × 105 S/m after being turned on, which favored the designing of alarm systems and object locators. The flexible sensors produced with this ink have broad application, high sensitivity, and superstable signal generation even after 200 cycles. When acting as strain sensors, the constructed composites had high sensitivity for monitoring the human movements. Furthermore, liquid metals in printed products can be recycled under alkaline conditions. This study opens a new direction for the next generation of environmentally friendly flexible devices.

10.
Talanta ; 218: 121210, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32797934

RESUMO

Two spirobifluorene-based two-photon fluorescent probes for the detection of hydrazine, namely SPF-MN and SPF- PA, have been designed and synthesized. Along with the addition of hydrazine to a solution of SPF-MN, both a colorimetric change from yellow to colorless and a fluorescence change from yellow to blue (Under 365 nm UV light) can be observed by ''naked-eye''. Probe SPF- PA displayed response toward hydrazine with fluorescence enhancement. The detection limits are 6.9 µM for SPF- PA and 0.29 µM for SPF-MN, respectively. Moreover, SPF-MN and SPF- PA can be used as two-photon fluorescent probes for hydrazine with large two-photon absorption cross-sections and used for the imaging of hydrazine in living cells. Specially, SPF-PA can located at the surface of the cells, and it is the first fluorescent probe which possesses the capability of sensing intercellular hydrazine. Besides, SPF-MN is the first colorimetric two-photon fluorescent probe for meeting the criteria of both hydrazine bioimaging and visual detection of hydrazine in solution.


Assuntos
Corantes Fluorescentes , Hidrazinas , Colorimetria , Humanos , Fótons , Espectrometria de Fluorescência
11.
Int J Med Sci ; 17(6): 762-772, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32218698

RESUMO

Tumor-infiltrating immune cells are closely related to the prognosis of bladder cancer. Analysis of tumor infiltrating immune cells is usually based on immunohistochemical analysis. Since many immune cell marker proteins are not specific for different immune cells, which may induce misleading or incomplete. CIBERSORT is an algorithm to estimate specific cell types in a mixed cell population using gene expression data. In this study, the CIBERSORT algorithm was used to identify the immune cell infiltration signatures. The gene expression profiles, mutation data, and clinical data were collected from The Cancer Genome Atlas (TCGA) database. Unsupervised consensus clustering was used to acquire the immune cell infiltration subtypes of bladder cancer based on the fractions of 22 immune cell types. Four immune cell clusters with different immune infiltrate and mutation characteristics were identified. In addition, this stratification has a prognostic relevance, with cluster 2 having the best outcome, cluster 1 the worst. These clusters showed distinct mRNA expression patterns. The characteristic genes in subtype cluster 1 were mainly involved in cell division, those in subtype cluster 2 were mainly related in antigen processing and presentation, those in subtype cluster 3 were mainly involved in epidermal cell differentiation, and those in subtype cluster 4 were mainly related in the humoral immune response. These differences may affect the development of the bladder cancer, the sensitivity to treatment as well as the prognosis. Through further validation, this study may contribute to the development of personalized therapy and precision medical treatments.


Assuntos
Linhagem da Célula/imunologia , Genômica , Proteínas de Neoplasias/genética , Neoplasias da Bexiga Urinária/genética , Linfócitos B/metabolismo , Linfócitos B/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Linhagem da Célula/genética , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/imunologia , Genoma Humano/genética , Humanos , Mutação/genética , Proteínas de Neoplasias/imunologia , Medicina de Precisão , Prognóstico , Linfócitos T/metabolismo , Linfócitos T/patologia , Neoplasias da Bexiga Urinária/classificação , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/patologia
12.
Neurourol Urodyn ; 39(2): 613-624, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31905258

RESUMO

AIMS: Cell death and inflammation are involved in the development of bladder dysfunction. Pyroptosis is programmed cell death, causing cytotoxic effects and local inflammation. As one of the biggest health threats in the world, smoking is also closely related to urinary system diseases. The aims of this study were to investigate the role of NLRP3 inflammasome-mediated pyroptosis in the bladder after cigarette smoke exposure. METHODS: The expression of NLRP3 inflammasome and the activity of caspase-1 in bladder tissue was investigated after cigarette smoke exposure. In vitro, bladder urothelial cells were stimulated by cigarette smoke extract and then the activity of caspase-1 and the expression of NLRP3 inflammasome were measured. The role of oxidative stress was also assessed. RESULTS: The activity of caspase-1 in bladder tissue increased by 50% after cigarette smoke exposure. Cigarette smoke caused oxidative stress injury and the activation of NLRP3 inflammasome. In addition, reactive oxygen species (ROS) inhibitor N-acetyl-cysteine alleviated the pyroptosis of urothelial cells. CONCLUSIONS: Cigarette smoke-induced pyroptosis of bladder tissue by activating ROS/NLRP3/caspase-1 signaling pathway. Inhibition of bladder urothelial cell pyroptosis may be a new approach to alleviate bladder damage caused by smoking.


Assuntos
Caspase 1/metabolismo , Células Epiteliais/metabolismo , Piroptose/fisiologia , Transdução de Sinais/fisiologia , Urotélio/metabolismo , Animais , Linhagem Celular , Células Epiteliais/citologia , Humanos , Inflamassomos/metabolismo , Masculino , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Fumaça , Urotélio/citologia
13.
Int J Med Sci ; 17(1): 89-96, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929742

RESUMO

Bladder cancer is one of the most commonly diagnosed tumors and is results from the accumulation of somatic mutations in the DNA. Tumor mutation burden (TMB) has been associated with cancer immunotherapeutic response. In this study, we attempted to explore the correlation between TMB and cancer prognosis. Identify the different expressed genes and immune cell infiltration signatures between low and high TMB group. Mutation data, gene expression profiles and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. Patients were divided into high and low TMB groups, allowing differentially expressed genes (DEGs) to be identified. Functional enrichment and protein-protein interaction (PPI) network analysis were used to identify the functions of the DEGs. And immune cell infiltration signatures were evaluated by CIBERSORT algorithm. These results shown that high TMB was significantly associated with prognosis. We obtained a list of TMB related genes which may influence the infiltrations of immune cells. We also found a higher proportion of CD8 T cells, CD4 T cells and NK cells in the high TMB group. Our data suggest that higher TMB tends to promote the infiltrations of T cells and NK cells and patients with higher TMB may achieve a more favorable prognosis in bladder cancer.


Assuntos
Biomarcadores Tumorais/genética , Quimiocina CXCL10/genética , Proteínas de Neoplasias/genética , Neoplasias da Bexiga Urinária/genética , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Prognóstico , Transdução de Sinais/genética , Transcriptoma/genética , Transcriptoma/imunologia , Carga Tumoral/genética , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/patologia
14.
Neurourol Urodyn ; 39(1): 158-169, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31729056

RESUMO

PURPOSE: Cannabinoids have been shown to exert analgesic and anti-inflammatory effects, and the effects of cannabinoids are mediated primarily by cannabinoid receptors 1 and 2 (CB1 and CB2). The objective of this study was to determine efficacy and mechanism of CB2 activation on cyclophosphamide (CYP)-induced cystitis in vivo. METHODS: Cystitis was induced by intraperitoneal (IP) injection of CYP in female C57BL/6J mice. Mice were pretreated with CB2 agonist JWH-133 (1 mg/kg, intraperitoneally), CB2 antagonist AM-630 (1 mg/kg, intraperitoneally) or autophagy inhibitor 3-methyladenine (3-MA) (50 mM, intraperitoneally) before IP injection of CYP. Peripheral nociception and spontaneous voiding were investigated in these mice. Bladders were collected, weighed, and processed for real-time polymerase chain reaction, immunoblotting analysis, histological and immunohistochemical analysis. RESULTS: Twenty-four hours after IP injection of CYP, the bladder of CYP-treated mice showed histological evidence of inflammation. The expression of CB2 in bladder was significantly increased in CYP-treated mice. Mechanical sensitivity was significantly increased in CYP-treated mice and CB2 agonist JWH-133 attenuated this effect (P < .05). The number of urine spots was significantly increased after CYP treatment and it was decreased in JWH-133 treated mice (P < .05). Activating CB2 with JWH-133 significantly alleviated bladder tissue inflammatory responses and oxidative stress induced by CYP. Activation of CB2 by JWH-133 increased the expression of LC3-II/LC3-I ratio, and decreased the expression of SQSTM1/p62 in the bladder of cystitis mice, whereas AM-630 induced inverse effects. Further study indicated that JWH-133 could promote autophagy and blocking autophagy by 3-MA dismissed the effort of CB2 in alleviating bladder tissue inflammatory responses and oxidative stress injury. Furthermore, treatment with 3-MA decreased the expression of p-AMPK and induced the phosphorylation of mTOR in the presence of JWH-133 stimulation in cystitis model. CONCLUSIONS: Activation of CB2 decreased severity of CYP-induced cystitis and ameliorated bladder inflammation. CB2 activation is protective in cystitis through the activation of autophagy and AMPK-mTOR pathway may be involved in the initiation of autophagy.


Assuntos
Autofagia/efeitos dos fármacos , Cistite/metabolismo , Receptor CB2 de Canabinoide/agonistas , Animais , Agonistas de Receptores de Canabinoides/farmacologia , Antagonistas de Receptores de Canabinoides/farmacologia , Canabinoides/farmacologia , Ciclofosfamida , Cistite/induzido quimicamente , Feminino , Indóis/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Receptor CB2 de Canabinoide/antagonistas & inibidores , Micção/efeitos dos fármacos
15.
Am J Physiol Cell Physiol ; 317(3): C544-C555, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31241987

RESUMO

The specific regulatory mechanism of bladder urothelial barrier dysfunction after infection with uropathogenic Escherichia coli (UPEC) is still unclear. The cross talk between bladder urothelial cells and mast cells may play an important role during UPEC infection. In this study, the pyroptosis of urothelial cells was investigated after UPEC infection both in vivo and in vitro. The levels of IL-1ß and IL-18 in exosomes derived from bladder urothelial cells after UPEC infection were detected. The role of these processes in the recruitment and activation of mast cells was measured. The mechanism of mast cell-induced disruption of bladder epithelial barrier function was also assessed. We found that UPEC infection induced pyroptosis of bladder urothelial cells and led to the release of IL-1ß and IL-18 in the form of exosomes, which promoted the migration of mast cells. Tryptase secreted by mast cells aggravated the damage to the barrier function of the bladder urothelium by acting on protease-activated receptor 2 (PAR2). Inhibition of pyroptosis or the tryptase-PAR2 axis reduced the disruption of bladder urothelial barrier function and decreased the bacterial burden. The present study supports a novel mechanism by which pyroptosis-dependent release of exosomes from bladder urothelial cells activates mast cells and regulates bladder urothelial barrier function during UPEC infection.


Assuntos
Infecções por Escherichia coli/metabolismo , Exossomos/metabolismo , Mastócitos/metabolismo , Piroptose/fisiologia , Infecções Urinárias/metabolismo , Urotélio/metabolismo , Animais , Linhagem Celular , Infecções por Escherichia coli/imunologia , Exossomos/imunologia , Feminino , Humanos , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Bexiga Urinária/imunologia , Bexiga Urinária/metabolismo , Bexiga Urinária/microbiologia , Infecções Urinárias/imunologia , Escherichia coli Uropatogênica , Urotélio/imunologia , Urotélio/microbiologia
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