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1.
Toxicol Res (Camb) ; 10(5): 1013-1021, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34733486

RESUMO

Circular RNAs (circRNAs), is a novel type of endogenous non-coding RNAs (ncRNAs) participated in the pathogenesis of many diseases. Beryllium is one of the carcinogenesis elements. However, the mechanism and function of circRNAs in human bronchial epithelial cells (16HBE) induced by beryllium sulfate (BeSO4) was rarely reported. Therefore, the high-throughput RNA sequencing analysis was performed to detect the circRNA profiles between control groups and BeSO4-induced groups. Furthermore, circRNA-miRNA-mRNA network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and PPI network analysis were used for bioinformatics analysis. CircRNA sequencing analysis revealed that 36 circRNAs were up-regulated and 35 circRNAs were down-regulated in the BeSO4-exposed groups. The selected circRNAs were verified by real-time fluorescent quantitative PCR (qRT-PCR). Hsa_circ_0004214 and hsa_circ_0003586 were validated to be up-regulated, hsa_circ_0047958, hsa_circ_0001944, and hsa_circ_0008982 were down-regulated. The circRNA-miRNA-mRNA network annotated the key signaling pathway including cellular senescence, TNF signaling pathway, NF-kappa B signaling pathway, HIF-1 signaling pathway, and Hippo signaling pathway. The PPI network indicated the most circRNAs might participate in the BeSO4 toxicity by acting as a sponge for the miR-663b through JAK-STAT signaling pathway. In summary, our study suggests that circRNAs may play roles in the mechanism of beryllium toxicity.

2.
Ecotoxicol Environ Saf ; 228: 112963, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34781126

RESUMO

Epidemiological studies suggest that ambient particulate matter exposure may be a new risk factor of glaucoma, but it lacks solid experimental evidence to establish a causal relationship. In this study, young mice (4 weeks old) were exposed concentrated ambient PM2.5 (CAP) for 9 months, which is throughout most of the life span of a mouse under heavy pollution. CAP was introduced using a versatile aerosol concentration enrichment system which mimics natural PM2.5 exposure. CAP exposure caused a gradual elevation of intraocular pressure (IOP) and an increase in aqueous humor outflow resistance. In the conventional outflow tissues that regulates IOP, inducible nitric oxide synthase (iNOS) was up-regulated and 3-nitrotyrosine (3-NT) formation increased. At the cellular level, PM2.5 exposure increased the transendothelial electrical resistance of cells that control IOP (AAP cells). This is accompanied by increased reactive oxygen species (ROS), iNOS and 3-NT levels. Peroxynitrite scavenger MnTMPyP successfully treated the IOP elevation and restored it to normal levels by reducing 3-NT formation in outflow tissues. This study provides the novel evidence that in young mice, lifetime whole-body PM2.5 exposure has a direct toxic effect on intraocular tissues, which imposes a significant risk of IOP elevation and may initiate the development of ocular hypertension and glaucoma. This occurs as a result of protein nitration of conventional aqueous humor outflow tissues.

4.
Ecotoxicol Environ Saf ; 227: 112866, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34634599

RESUMO

OBJECTIVES: To investigate how PM2.5 exposure affects the microstructure, metabolites or functions of the visual system. METHODS: C57BL/6J mice were randomly assigned to groups exposed to the filtered air (the control group) or the concentrated ambient PM2.5 (the PM2.5 group). Visual evoked potentials (VEP), electroretinograms (ERG), diffusion tensor imaging (DTI), proton magnetic resonance spectroscopy (1H-MRS) and resting-state functional MRI (rsfMRI) were performed. Parameters were obtained and compared between the two groups, including latencies and amplitudes of the P1 wave, N1 wave and P2 wave from VEP, latencies and amplitudes of the a wave and b wave from ERG, fractional anisotropy (FA), mean diffusion (MD), axial diffusivity (AD) and radial diffusivity (RD) from DTI, visual cortex (VC) metabolites from 1H-MRS, and regional homogeneity (ReHo) from rsfMRI. RESULTS: Compared with the values of the control group, the PM2.5 group showed a prolonged N1 latency (43.11 ±â€¯7.94 ms vs. 38.75 ±â€¯4.60 ms) and lowered P1 amplitude (5.62 ±â€¯4.38 µV vs. 8.56 ±â€¯5.92 µV) on VEP (all p < 0.05). On ERG, the amplitude of the a wave was lowered (- 91.39 ±â€¯56.29 µV vs. - 138.68 ±â€¯89.05 µV), the amplitude of the b wave was lowered (194.38 ±â€¯126.27 µV vs. 284.72 ±â€¯170.99 µV), and the latency of the b wave was prolonged (37.78 ±â€¯10.72 ms vs. 33.01 ±â€¯4.34 ms) than the values of the control group (all p < 0.05). DTI indicated FA increase in the bilateral piriform cortex (Pir), FA decrease in the bilateral somatosensory cortex (S) and the bilateral striatum (Stri), AD decrease in the bilateral VC, the right S and the bilateral Pir, MD decrease in the bilateral Pir, and RD decrease in the bilateral Pir in the PM2.5 mice (all p < 0.05, Alphasim corrected). 1H-MRS showed Glutamate (Glu) increase and Phosphocholine (PCh) increase in the VC of the PM2.5 group than those of the control group (PCh 1.63 ±â€¯0.25 vs. 1.50 ±â€¯0.25; PCh/total creatine(tCr) 0.19 ±â€¯0.03 vs. 0.18 ±â€¯0.03; Glu 10.46 ±â€¯1.50 vs. 9.60 ±â€¯1.19; Glu/tcr 1.23 ±â€¯0.11 vs. 1.12 ±â€¯0.11) (all p < 0.05). rsfMRI showed higher ReHo in the PM2.5 mice in the left superior colliculus, the left motor cortex, the hippocampus, the periaqueductal gray and the right mesencephalic reticular formation (all p < 0.01, AlphaSim corrected). CONCLUSIONS: This study revealed that PM2.5 exposure triggered visual dysfunction, and altered microstructure, metabolite and function in the retina and visual brain areas along the visual system.


Assuntos
Imagem de Tensor de Difusão , Potenciais Evocados Visuais , Animais , Imageamento por Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Material Particulado/toxicidade
6.
Biomaterials ; 277: 121074, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34482086

RESUMO

High intraocular pressure (IOP) has been regarded as a predominant risk factor for glaucoma. Nitric oxide (NO) is shown to lower IOP, but the magnitude and duration of IOP reduction are not satisfying due to the poor cornea penetration of NO drugs and limited NO generation in the trabecular meshwork (TM)/Schlemm's canal (SC) area. Herein, we introduce deep cornea penetrating biodegradable hollow mesoporous organosilica (HOS) nanocapsules for the efficient co-delivery of hydrophobic JS-K (JR) and hydrophilic l-Arginine (LO). The resulting HOS-JRLO can be reduced and oxidized by the ascorbic acid (AA) and catalysis of endothelial nitric oxide synthase (eNOS) in the TM/SC microenvironment to release NO for inducing appreciable IOP reduction in various glaucoma mouse models. In addition to developing an endogenous stimuli-responsive NO nanotherapeutic, this study is also expected to establish a versatile, non-invasive, and efficacious treatment paradigm for precision glaucoma therapy.


Assuntos
Glaucoma , Pressão Intraocular , Animais , Humor Aquoso , Córnea , Glaucoma/tratamento farmacológico , Camundongos , Óxido Nítrico , Malha Trabecular
7.
Qual Life Res ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34532834

RESUMO

PURPOSE: Dietary intake and patients' quality of life (QoL) are important supportive care issues in breast cancer survivorship. This study aimed to identify dietary pattern before and after breast cancer diagnosis. In addition, the association between dietary patterns and QoL were cross-sectionally and longitudinally investigated. METHODS: A breast cancer cohort which included 1462 Chinese women were longitudinally interviewed at four time-points, namely baseline, 18-, 36-, and 60 months after diagnosis. At each follow-up, validated food frequency questionnaires (FFQ) were used to assess patients' dietary intake, and factor analysis was used to derive dietary patterns. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) were used to measure QoL at each follow-up. This study included 1368, 1226, 1079 and 1095 patients with invasive disease who completed assessment at baseline, 18-, 36- and 60-month follow-up and had detailed data of dietary intake and QoL. RESULTS: Based on data obtained at 18-month follow-up, two major dietary patterns were identified: "grain and animal food pattern" and "vegetables and fruits pattern". Similar dietary patterns were obtained at baseline, 36- and 60- month follow-up. Generalized Estimating Equations (GEE) were used to analyze the longitudinal associations between dietary patterns and QoL over the four follow-ups. High intake of grain and animal food was inversely associated with scores for role functioning (B = - 0.744; 95%CI - 0.147 to - 0.017), dyspnea (B = - 0.092; 95%CI - 0.092 to - 0.092) and constipation (B = - 1.355; 95%CI - 2.174 to - 0.536). Vegetables and fruits intake were positively associated with scores for global health status/QoL (B = 1.282; 95%CI 0.545-2.019), physical functioning (B = 0.545; 95%CI: 0.037-1.053), emotional functioning (B = 1.426; 95%CI 0.653-2.200) and cognitive functioning (B = 0.822; 95%CI 0.007-1.637), while inversely associated with scores for nausea and vomiting (B = - 0.382; 95%CI - 0.694 to - 0.071), dyspnea (B = - 0.570; 95%CI - 0.570 to - 0.570), insomnia (B = - 1.412; 95%CI - 2.647 to - 0.177), loss of appetite (B = - 0.722; 95%CI - 1.311 to - 0.132), constipation (B = - 2.028; 95%CI - 2.775 to - 1.281) and diarrhea (B = - 0.929; 95%CI - 1.481 to - 0.377). CONCLUSION: This study suggested that high adherence to "grain and animal food pattern" or "vegetables and fruits pattern" was significantly associated with several aspects of QoL. For instance, vegetables and fruits pattern appears to have beneficial effect on global health status/QoL among Chinese breast cancer patients. Prospective follow-up data could further confirm whether a specific dietary pattern has impact on cancer outcomes.

8.
Mol Ther Oncolytics ; 22: 380-387, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34553026

RESUMO

The immune infiltration in the tumor microenvironment has been demonstrated to be relevant to radiotherapy response. Here, we sought to understand the immune infiltration in head and neck cancer (HNC) and evaluate its significance in predicting prognosis and radiotherapy response. Using RNA sequencing data of 522 retrospective head and neck squamous cell carcinomas (HNSCCs), we constructed an immune content score based on genes related to 6 prognostic infiltrating cell types. Unsupervised hallmark pathway clustering demonstrated an immune-related tumor cluster containing the immune content score. Patients with high immune content scores exhibited favorable overall survival and disease-free survival (DFS). Moreover, the immune content score was an independent prognostic factor for DFS in HNSCC. Interestingly, the immune content score was strongly associated with radiation response pathways. These results were also extended to nasopharyngeal carcinoma. Furthermore, patients in the low immune content score group significantly gained overall survival benefits from postoperative radiotherapy (PORT), whereas patients in the high immune content score group did not. Therefore, this study identifies the immune content score as a prognostic tool, which might have a potential association with PORT response, thereby facilitating outcome prediction and treatment decision in HNC.

9.
BMC Cancer ; 21(1): 839, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284751

RESUMO

BACKGROUND: Body weight management was an important component in breast cancer survivorship care. The present study described the change patterns of body weight and waist-to-hip ratio (WHR) during the first 5 years of survival, and investigated potential factors associated with very substantial changes. PATIENTS AND METHODS: Based on a longitudinal cohort with 1462 Chinese women with breast cancer, anthropometric measurements including body weight, height, waist and hip circumferences were measured by trained interviewers following standard protocol at four time-points: baseline at study entry, 18-, 36- and 60-months follow up assessments (termed as T0, T1, T2 and T3, respectively). Body height was measured at baseline and body weight at cancer diagnosis were retrieved from medical record. RESULTS: Compared to weight at breast cancer diagnosis, the median weight change was - 0.5 kg, 0 kg, + 0.5 kg, and + 1 kg at T0, T1, T2 and T3, respectively. During the first 5 years of survival, the proportion of women who were obese have slightly increased. At 60-months after diagnosis, only 14.3% of women had weight gain by > 5 kg; and the percentage of women who had weight gain by > 10% was 10.7%. Nearly half of patients had abdominal obesity at study entry, and this proportion were gradually increased to nearly 70% at 60-months follow-up. Multivariate analysis indicated that older age, and frequent sports participation during the first 5 years of survival were related to lower risk of very substantial weight gain (> 10%) at 60-month follow-up; patients aged 40-49 years, having ≥2 comorbidities and ER negative were associated with less likelihood of very substantial WHR substantial increase (> 10%) at 60-month follow-up. CONCLUSION: Weight gain was modest in Chinese breast cancer survivors during the first 5 years of survival, while central adiposity has become a contemporary public health issue. The incorporation of healthy weight and abdominal circumference patient education and management has a potential to improve cancer survivorship.


Assuntos
Índice de Massa Corporal , Manutenção do Peso Corporal/fisiologia , Neoplasias da Mama/complicações , Relação Cintura-Quadril/métodos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Análise de Sobrevida , Fatores de Tempo
10.
J Appl Toxicol ; 2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34091916

RESUMO

Beryllium and its compounds are systemic toxicants that are widely applied in many industries. Hydrogen sulfide has been found to protect cells. The present study aimed to determine the protective mechanisms involved in hydrogen sulfide treatment of 16HBE cells following beryllium sulfate-induced injury. 16HBE cells were treated with beryllium sulfate doses ranging between 0 and 300 µM BeSO4 . Additionally, 16HBE cells were subjected to pretreatment with either a 300 µM dose of sodium hydrosulfide (a hydrogen sulfide donor) or 10 mM DL-propargylglycine (a cystathionine-γ-lyase inhibitor) for 6 hr before then being treated with 150 µM beryllium sulfate for 48 hr. This study illustrates that beryllium sulfate induces a reduction in cell viability, increases lactate dehydrogenase (LDH) release, and increases cellular apoptosis and autophagy in 16HBE cells. Interestingly, pretreating 16HBE cells with sodium hydrosulfide significantly reduced the beryllium sulfate-induced apoptosis and autophagy. Moreover, it increased the mitochondrial membrane potential and alleviated the G2/M-phase cell cycle arrest. However, pretreatment with 10 mM DL-propargylglycine promoted the opposite effects. PI3K/Akt/mTOR and Nrf2/ARE signaling pathways are also activated following pretreatment with sodium hydrosulfide. These results indicate the protection provided by hydrogen sulfide in 16HBE cells against beryllium sulfate-induced injury is associated with the inhibition of apoptosis and autophagy through the activation of the PI3K/Akt/mTOR and Nrf2/ARE signaling pathways. Therefore, hydrogen sulfide has the potential to be a promising candidate in the treatment against beryllium disease.

11.
Expert Opin Drug Saf ; 20(10): 1163-1175, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33951990

RESUMO

Introduction: For young premenopausal breast cancer (BC) patients, adjuvant chemotherapy and other anti-cancer treatments can increase the risk of menopausal symptoms and may cause chemotherapy-related amenorrhea (CRA), infertility and premature ovarian insufficiency (POI).Areas covered: In this report, menopausal symptoms related to anti-cancer treatment are described. Menstrual disturbances associated with the use of adjuvant chemotherapy, endocrine therapy, and targeted therapy against human epidermal growth factor receptor 2 (HER2) in premenopausal women withBC are discussed. To prevent menopausal symptoms, CRA and POI, data on the efficacy of temporary ovarian suppression with gonadotropin-releasing hormone analogues (GnRHa) during chemotherapy are highlighted. Pooled analyses have confirmed that concurrent administration of GnRHa during chemotherapy could significantly reduce the risk of developing chemotherapy-induced POI in premenopausal women with early-stageBC. In addition, reports have suggested that embryo/oocyte cryopreservation may increase the chance of pregnancy after the diagnosis ofBC, although such data remain limited.Expert opinion: Commonly experienced by pre-menopausal women withBC, anti-cancer treatment could cause severe menopausal symptoms. Temporary ovarian suppression with GnRHa during chemotherapy provided asafe and efficient strategy to reduce the likelihood of chemotherapy-induced POI in premenopausal patients with early-stageBC undergoing (neo)-adjuvant chemotherapy.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Menopausa/efeitos dos fármacos , Antineoplásicos/administração & dosagem , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/análogos & derivados , Humanos , Estadiamento de Neoplasias , Pré-Menopausa , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/prevenção & controle
12.
J Mater Chem B ; 9(15): 3335-3345, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33881417

RESUMO

The elevation of intraocular pressure (IOP) is an important risk factor in the development of primary open angle glaucoma (POAG), which is the main cause of irreversible vision loss. miRNAs are promising new anti-glaucoma therapeutic agents. However, the low stability and cellular transfection of miRNA in vivo hinder its further application. This study aims to investigate the use of polydopamine-polyethylenimine nanoparticles (PDA/PEI NPs) as miRNA carriers in the treatment of ocular hypertension and glaucoma. The in vitro study proves that the carrier preserves the activity of nucleic acid for a long period. Besides, it has comparable transfection efficiency with commercially available vehicles, while having lower cytotoxicity. It has been demonstrated in the animal model that PDA/PEI NPs successfully reach the target tissues without an obvious inflammatory response. PDA/PEI NPs/miR-21-5p increases the permeability of porcine angular aqueous plexus cells, thereby reducing IOP by facilitating the conventional outflow pathway at least partially through the pathway involving endothelial nitric oxide synthase. Our results indicate that PDA/PEI NPs/miR-21-5p is a promising anti-glaucoma drug for treating POAG. And the delivery strategy may be extended to other gene therapy in treating intraocular diseases.


Assuntos
Sistemas de Liberação de Medicamentos , Glaucoma/terapia , Indóis/química , Pressão Intraocular , MicroRNAs/metabolismo , Nanopartículas/química , Polímeros/química , Animais , Sobrevivência Celular , Portadores de Fármacos/química , Glaucoma/metabolismo , Glaucoma/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Estrutura Molecular , Polietilenoimina/química
13.
J Mater Chem B ; 9(16): 3595, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33909747

RESUMO

Correction for 'A miRNA stabilizing polydopamine nano-platform for intraocular delivery of miR-21-5p in glaucoma therapy' by Chen Tan et al., J. Mater. Chem. B, 2021, DOI: 10.1039/d0tb02881a.

14.
Mol Med Rep ; 23(6)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33786614

RESUMO

Cervical cancer is a common public health issue with high morbidity worldwide. Paeonol (Pae) has been recognized as a traditional Chinese medicine used for the treatment of various cancer types. However, whether Pae could exert a protective effect on cervical cancer remains to be investigated. The aim of the present study was to explore the role of Pae in cervical cancer cells and identify the potential mechanism. Cell Counting Kit­8 and colony­formation assays were conducted to test the proliferation of HeLa cells. Additionally, wound healing and transwell assays were used to detect the migratory and invasive abilities of cells. The plasmid that overexpressed 5­lipoxygenase (5­LO) or control vector was constructed and transfected into the cells. Subsequently, flow cytometry was used to monitor the apoptotic rate of cells. The expression levels of apoptosis­associated proteins and 5­LO were detected using western blot analysis. Reverse transcription­quantitative PCR analysis detected the expression of 5­LO. Pae inhibited the proliferation, invasion and migration of HeLa cells, promoted cell apoptosis and downregulated the expression of 5­LO. Overexpression of 5­LO, however, attenuated these effects. Thus, Pae could inhibit the proliferation, migration and invasion, as well as promote apoptosis of HeLa cells by regulating the expression of 5­LO.


Assuntos
Acetofenonas/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Araquidonato 5-Lipoxigenase/metabolismo , Movimento Celular/efeitos dos fármacos , Araquidonato 5-Lipoxigenase/genética , Proliferação de Células/efeitos dos fármacos , Células HeLa , Humanos
15.
Part Fibre Toxicol ; 18(1): 10, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33663554

RESUMO

BACKGROUND: Particulate matter (PM) is strongly linked to human health and has detrimental effects on the eye. Studies have, however, focused on the ocular surface, with limited research on the impact of PM2.5 on intraocular pressure (IOP). METHODS: To investigate the impact of PM2.5 on IOP and the associated mechanism, C57BL/6 mouse eyes were topically exposed to a PM2.5 suspension for 3 months, and human trabecular meshwork (HTM) cells were subjected to various PM2.5 concentrations in vitro. Cell viability, NLRP3/caspase-1, IL-1ß, and GSDMD expression, reactive oxygen species (ROS) production and cell contractility were measured by western blot, ELISA, cell counting kit-8, ROS assay kit or a cell contractility assay. ROS scavenger N-acetyl-L-cysteine (NAC) and caspase-1 inhibitor VX-765 were used to intervene in PM2.5-induced damages. RESULTS: The results revealed that the IOP increased gradually after PM2.5 exposure, and upregulations of the NLRP3 inflammasome, caspase-1, IL-1ß, and GSDMD protein levels were observed in outflow tissues. PM2.5 exposure decreased HTM cell viability and affected contraction. Furthermore, elevated ROS levels were observed as well as an activation of the NLRP3 inflammasome and downstream inflammatory factors caspase-1 and IL-1ß. NAC improved HTM cell viability, inhibited the activation of the NLRP3 inflammasome axis, and HTM cell contraction by scavenging ROS. VX-765 showed similar protection against the PM2.5 induced adverse effects. CONCLUSION: This study provides novel evidence that PM2.5 has a direct toxic effect on intraocular tissues and may contribute to the initiation and development of ocular hypertension and glaucoma. This occurs as a result of increased oxidative stress and the subsequent induction of NLRP3 inflammasome mediated pyroptosis in trabecular meshwork cells.


Assuntos
Glaucoma , Hipertensão Ocular , Material Particulado/toxicidade , Animais , Inflamassomos , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Espécies Reativas de Oxigênio , Transdução de Sinais
16.
Ther Adv Chronic Dis ; 12: 2040622320986721, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717426

RESUMO

Aims: CD4+ T cells play crucial roles as both mediators and regulators of the pathogenesis of rheumatoid arthritis (RA). However, the characteristics of CD4+ T cell subpopulations in the earliest stage of RA development remain unclear. Hence, we determined the proportions and absolute counts of circulating CD4+ T cell subsets in patients with seropositive undifferentiated arthritis (SUA), the early and preclinical stage of RA. Methods: Peripheral blood samples and clinical information were collected from 177 patients with SUA, 104 patients with RA, and 120 healthy controls. All patients were newly diagnosed and untreated. Proportions and absolute counts of CD4+ T cell subpopulations were determined by flow cytometric analysis. Results: In patients with SUA, percentages and absolute counts of circulating regulatory T (Treg) cells were decreased significantly and Th17/Treg cell ratios were abnormally increased, whereas Th17 cell numbers were similar to those in healthy controls. In addition, sex-based differences in circulating Treg cells were observed, with female SUA patients having lower proportions and absolute counts of Treg cells than those in males. Moreover, female patients with SUA had higher erythrocyte sedimentation rates and 28-joint Disease Activity Scores than those in males. Conclusion: Immune tolerance deficiency resulting from an abnormal reduction in circulating Treg cells might be the most crucial immunological event in the earliest stage of RA. The sex-specific disparity in Treg cells should also be considered for immunoregulatory and preventive strategies targeting early RA.

17.
Qual Life Res ; 30(6): 1583-1594, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33447955

RESUMO

PURPOSE: This study aimed to investigate changes of QoL during the first 5 years of survival among disease-free Chinese breast cancer survivors. METHODS: A prospective cohort study enrolled 1462 Chinese women with early-stage breast cancer, and longitudinally visited those patients at four time-points, namely baseline (T0), 18- (T1), 36- (T2), and 60-month (T3) after diagnosis. This study included 992 patients who were disease-free during the first 5 years of survival and who had completed QoL assessments at all four time-points. RESULTS: The score of global health status/QoL improved gradually (T1, T2, T3 > T0; P < 0.001 for overall comparisons). Social functioning score significantly improved when compared to that of T0 (T1, T2, T3 > T0; P < 0.001 for overall comparisons). In contrast, cognitive functioning score decreased (T0 > T1, T2, T3; P < 0.001 for overall comparisons). Scores of physical functioning, role functioning and emotional functioning showed a fluctuated picture, with the highest score achieved at T1. In symptoms profile, most of them scored lowest at T1 (best QoL). Multivariate analysis showed that several characteristics significantly correlated to changes in QoL from T0 to T3. For instance, patients with higher education had better recovery of physical functioning, role functioning, and social functioning. CONCLUSION: During the first 5 years of survival, patients' global health status/QoL improved over time, social functioning consistently improved, but cognitive functioning steadily deteriorated. Most of functioning domains and symptoms improved at 18-month follow-up, but such improvements were not maintained and even deteriorated at 36- and 60-month post-diagnosis. This study suggested that some interventions should be investigated during such period.


Assuntos
Neoplasias da Mama/psicologia , Sobreviventes de Câncer/psicologia , Nível de Saúde , Qualidade de Vida/psicologia , Adulto , China , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Ajustamento Social
18.
Mol Cancer ; 20(1): 14, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33430876

RESUMO

Currently, there is no strong evidence of the well-established biomarkers for immune checkpoint inhibitors (ICIs) in nasopharyngeal carcinoma (NPC). Here, we aimed to reveal the heterogeneity of tumour microenvironment (TME) through virtual microdissection of gene expression profiles. An immune-enriched subtype was identified in 38% (43/113) of patients, which was characterized by significant enrichment of immune cells or immune responses. The remaining patients were therefore classified as a non-Immune Subtype (non-IS), which exhibited highly proliferative features. Then we identified a tumour immune evasion state within the immune-enriched subtype (18/43, 42%), in which high expression of exclusion- and dysfunction-related signatures was observed. These subgroups were designated the Evaded and Active Immune Subtype (E-IS and A-IS), respectively. We further demonstrated that A-IS predicted favourable survival and improved ICI response as compared to E-IS and non-IS. In summary, this study introduces the novel immune subtypes and demonstrates their feasibility in tailoring immunotherapeutic strategies.


Assuntos
Heterogeneidade Genética , Imunoterapia , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/terapia , Microambiente Tumoral , Estudos de Coortes , Genoma Humano , Humanos , Carcinoma Nasofaríngeo/genética , Prognóstico , Reprodutibilidade dos Testes , Microambiente Tumoral/genética
19.
Exp Eye Res ; 202: 108280, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33069697

RESUMO

Nitric oxide (NO) donors are promising therapeutic candidates for treating intraocular hypertension (IOP) and glaucoma. This study aims to investigate the effect of prolonged use of NO donor sodium nitroprusside (SNP) on IOP. Since SNP has a short biological half-life, a nanoparticle drug delivery system (mesoporous silica nanoparticles) has been used to deliver SNP to the target tissues (trabecular meshwork and Schlemm's canal). We find that the sustained use of NO donor initially reduced IOP followed, surprisingly, by IOP elevation, which could not recover by drug withdraw but could be reversed by the antioxidant MnTMPyP application. The IOP elevation and normalization coincide with increased and reduced protein nitration in the mouse conventional outflow tissue. These findings suggest that the prolonged use of NO donor SNP may be problematic as it can cause outflow tissue damage by protein nitration. MnTMPyP is protective of the nitrative damage which could be considered to be co-applied with NO donors.


Assuntos
Pressão Intraocular/efeitos dos fármacos , Doadores de Óxido Nítrico/toxicidade , Nitroprussiato/toxicidade , Hipertensão Ocular/induzido quimicamente , Administração Oftálmica , Animais , Western Blotting , Caveolina 1/genética , Portadores de Fármacos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nanopartículas , Doadores de Óxido Nítrico/administração & dosagem , Nitroprussiato/administração & dosagem , Hipertensão Ocular/diagnóstico , Hipertensão Ocular/metabolismo , Soluções Oftálmicas , Ácido Peroxinitroso/metabolismo , Tonometria Ocular , Malha Trabecular/metabolismo
20.
J Natl Cancer Inst ; 113(4): 471-480, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33094348

RESUMO

BACKGROUND: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma. However, some patients obtain little benefit and experience unnecessary toxicities from IC. We intended to develop a gene-expression signature that can identify beneficiaries of IC. METHODS: We screened chemosensitivity-related genes by comparing gene-expression profiles of patients with short-term tumor response or nonresponse to IC (n = 95) using microarray analysis. Chemosensitivity-related genes were quantified by digital expression profiling in a training cohort (n = 342) to obtain a gene signature. We then validated this gene signature in the clinical trial cohort (n = 187) and an external independent cohort (n = 240). Tests of statistical significance are 2-sided. RESULTS: We identified 43 chemosensitivity-related genes associated with the short-term tumor response to IC. In the training cohort, a 6-gene signature was developed that was highly accurate at predicting the short-term tumor response to IC (area under the curve [AUC] = 0.87, sensitivity = 87.5%, specificity = 75.6%). We further found that IC conferred failure-free survival benefits only in patients in the benefit group (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.34 to 0.87; P = .01) and not on those in the no-benefit group (HR = 1.25, 95% CI = 0.62 to 2.51; P = .53). In the clinical trial cohort, the 6-gene signature was also highly accurate at predicting the tumor response (AUC = 0.82, sensitivity = 87.5%, specificity = 71.8%) and indicated failure-free survival benefits. In the external independent cohort, similar results were observed. CONCLUSIONS: The 6-gene signature can help select beneficiaries of IC and lay a foundation for a more individualized therapeutic strategy for locoregionally advanced nasopharyngeal carcinoma patients.


Assuntos
Expressão Gênica , Quimioterapia de Indução , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Adulto , Idoso , Área Sob a Curva , Estudos de Coortes , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Sensibilidade e Especificidade , Resultado do Tratamento
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