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1.
COPD ; 19(1): 118-124, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35385369

RESUMO

OBJECTIVE: We aimed to establish an easy-to-use screening questionnaire with risk factors and suspected symptoms of COPD for primary health care settings. METHODS: Based on a nationwide epidemiological study of pulmonary health among adults in mainland China (China Pulmonary Health, CPH study) between 2012 and 2015, participants ≥40 years who completed the questionnaire and spirometry tests were recruited and randomly divided into development set and validation set by the ratio of 2:1. Parameters including sex, age, BMI, residence, education, smoking status, smoking pack-years, biomass exposure, parental history of respiratory diseases and daily respiratory symptoms were initially selected for the development of scoring system. Receiver operating characteristic (ROC) curve, area under curve (AUC), positive and negative predictive values were calculated in development set and validation set. RESULTS: After random split by 2:1 ratio, 22443 individuals were assigned to development set and 11221 to validation set. Ten variables were significantly associated with COPD independently in development set after a stepwise selection by multivariable logistic model and used to develop scoring system. The scoring system yielded good discrimination, as measured by AUC of 0.7737, and in the validation set, the AUC was 0.7711. When applying a cutoff point of ≥16, the sensitivity in development set was 0.69 (0.67 - 0.71); specificity 0.72 (0.71 - 0.73), PPV 0.25 (0.24 - 0.26) and NPV 0.94 (0.94 - 0.95). CONCLUSION: We developed and validated a comprehensive screening questionnaire, COPD-CPHS, with good discrimination. The score system still needs to be validated by large cohort in the future.Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2042504 .


Assuntos
Doença Pulmonar Obstrutiva Crônica , Adulto , Área Sob a Curva , China/epidemiologia , Estudos Epidemiológicos , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Curva ROC , Espirometria , Inquéritos e Questionários
2.
Front Immunol ; 13: 824188, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35444652

RESUMO

Exosomes are small extracellular vesicles that are secreted by almost all types of cells and exist in almost all extracellular spaces. As an important mediator of intercellular communication, exosomes encapsulate the miRNA, lncRNA, cirRNA, mRNA, cytokine, enzyme, lipid, and other components from the cytoplasm into its closed single membrane structure and transfer them to recipient units in an autocrine, paracrine, or endocrine manner. Hypoxia is a state of low oxygen tension and is involved in many pathological processes. Hypoxia influences the size, quantity, and expression of exosome cargos. Exosomes derived from hypoxic tumor cells transfer genetics, proteins, and lipids to the recipient units to exert pleiotropic effects. Different donor cells produce different cargo contents, target different recipient units and lead to different biological effects. Hypoxic exosomes derived from tumor cells uptaken by normoxic tumor cells lead to promoted proliferation, migration, and invasion; uptaken by extracellular space or liver lead to promoted metastasis; uptaken by endothelial cells lead to promoted angiogenesis; uptaken by immune cells lead to promoted macrophage polarization and changed tumor immune microenvironment. In addition to various types of tumors, hypoxic exosomes also participate in the development of diseases in the cardiovascular system, neuron system, respiratory system, hematology system, endocrine system, urinary system, reproduction system, and skeletomuscular system. Understanding the special characteristics of hypoxic exosomes provide new insight into elaborating the pathogenesis of hypoxia related disease. This review summarizes hypoxia induced cargo changes and the biological effects of hypoxic exosomes in tumors and non-malignant diseases in different systems.


Assuntos
Exossomos , Neoplasias , Comunicação Celular , Células Endoteliais/metabolismo , Exossomos/metabolismo , Humanos , Hipóxia/metabolismo , Neoplasias/metabolismo , Microambiente Tumoral
3.
ACS Appl Mater Interfaces ; 14(12): 14520-14531, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35306804

RESUMO

Constructing multifunctional electromagnetic interference (EMI) shielding films with superior mechanical strength has sparked a lot of interest in the fields of wearable electronics. In this work, the conductive silver nanowires (AgNWs) were synthesized and impregnated into the highly aligned cellulose scaffold (CS) fabricated by wood delignification followed by hot-pressing and polydimethylsiloxane (PDMS) dipping processes to obtain the outstanding EMI shielding cellulosic film (d-AgNWs@CS-PDMS). The consecutively conductive pathway of AgNWs was constructed in the microchannels of the CS as a result of the hydrogen bonding between AgNWs and cellulose fibers, which is conducive to the reflection of incident EM waves. The higher degree of nanofiber alignment and the compact conductive network were improved by densification upon hot pressing, which endows the composite film with striking mechanical properties (maximum tensile strength of 511.8 MPa) and superb EMI shielding performance (shielding effectiveness value of 46 dB with a filler content of 21.6 wt %) at the X band (8.2-12.4 GHz). Moreover, the existence of an intensive AgNWs network and the introduction of the PDMS layer improve the hydrophobicity and antibacterial activity of the composite film, avoiding serious health concerns in the long-term wearing. These results demonstrate that the obtained d-AgNWs@CS-PDMS composite film has high potential as an EMI shielding material used for wearable devices.


Assuntos
Nanofios , Prata , Antibacterianos/farmacologia , Celulose , Condutividade Elétrica
4.
Environ Res ; 209: 112877, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35131324

RESUMO

BACKGROUND: Studies on the association of greenness with respiratory health are scarce in developing countries, and previous studies in China have focused on only one or two indicators of lung function. OBJECTIVE: The study aims to evaluate the associations of residential greenness with full-spectrum lung function indicators and prevalence of chronic obstructive pulmonary disease (COPD). METHODS: This nationwide cross-sectional survey included 50,991 participants from the China Pulmonary Health study. Lung function indicators included four categories: indicators of obstructive ventilatory dysfunction (FEV1, FVC and FEV1/FVC); an indicator of large-airway dysfunction (PEF); indicators of small-airway dysfunction (FEF25-75% and FEV3/FEV6); and other indicators. Residential greenness was assessed by the Normalized Difference Vegetation Index (NDVI). Multivariable linear regression models and logistic regression models were used to analyze associations of greenness with lung function and COPD prevalence. RESULTS: Within the 500 m buffer, an interquartile range (IQR) increase in NDVI was associated with higher FEV1 (24.76 mL), FVC (16.52 mL), FEV1/FVC (0.38), FEF50% (56.34 mL/s), FEF75% (33.43 mL/s), FEF25-75% (60.73 mL/s), FEV3 (18.59 mL), and FEV6 (21.85 mL). However, NDVI was associated with lower PEF. In addition, NDVI was significantly associated with 10% lower odds of COPD. The stratified analyses found that the associations were only significant in middle-young people, females, and nonsmokers. The associations were influenced by geographic regions. CONCLUSIONS: Residential greenness was associated with better lung function and lower odds of COPD in China. These findings provide a scientific basis for healthy community planning.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Adolescente , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Pulmão , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Testes de Função Respiratória
5.
BMC Health Serv Res ; 22(1): 252, 2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35209891

RESUMO

BACKGROUND: As a common female pelvic tumor, uterine fibroids remain the leading cause for hysterectomy in China. Hysterectomy provides a good surgical treatment of uterine fibroids, and it guarantees the removal of all uterine fibroids without lower risk of recurrence. This study compares the cost effectiveness of total laparoscopic hysterectomy (TLH) versus total abdominal hysterectomy (TAH) for women with uterine fibroids from a societal perspective. METHODS: An economic analysis was conducted in 392 patients (TLH n = 75; TAH n = 317), including all relevant costs over a 12-month time horizon. Primary outcome was major surgical complications; secondary outcomes were postoperative discomfort symptoms and time of return to normal activities. Clinical, outcomes and costs data were collected from medical records, telephone survey and financial information system. Generalized linear models were used to assess costs and outcomes differences between the two groups. Incremental cost effectiveness ratio (ICER) was used to estimate the cost effectiveness. RESULTS: Mean direct costs were $2,925.71 for TLH, $2,436.24 for TAH, respectively. Mean indirect costs were $1,133.22 for TLH, $1,394.85 for TAH, respectively. Incremental societal costs were $256.86 (95%CI: 249.03-264.69). Mean differences in outcome were: 4.53% (95%CI: 4.35-4.71) for major surgical complications; 6.75% (95%CI: 6.45-7.05) for postoperative discomfort symptoms; 1.27 (95%CI: 1.23-1.30) weeks for time to return to normal activities. ICER of TLH was $5,669.16 (95%CI: 5,384.76-5,955.56) per complication averted, $3,801.54 (95%CI: 3,634.81-3,968.28) per postoperative discomfort symptoms averted and $202.96 (95%CI: 194.97-210.95) per week saved to return to normal activities. CONCLUSIONS: TLH is cost effective compared with TAH in preventing additional complications based on our estimated conservative threshold in China. The findings provide useful information for researchers to conduct further cost effectiveness analysis based on prospective study which can provide stronger and more evidence, in China. In addition, the data may be useful for Chinese health care policy-makers and medical insurance payers to make related health care decisions.


Assuntos
Laparoscopia , Leiomioma , Análise Custo-Benefício , Feminino , Humanos , Histerectomia , Leiomioma/cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos
6.
Int J Mol Med ; 49(3)2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35059734

RESUMO

Spliced X­box binding protein 1 (XBP1s) has been reported to participate in the pathogenesis of numerous types of cancer; however, whether XBP1s plays a role in lung cancer remains to be elucidated. In the present study, bioinformatics analysis was performed to determine the mRNA expression level of XBP1 in lung cancer and adjacent normal tissues. Gene Ontology terms, pathway enrichment and Pearson's correlation analysis were performed to investigate the possible mechanism involved. Western blot and reverse transcription­quantitative PCR were performed to quantify the protein and mRNA expression level of target proteins, respectively. Small interfering RNA or overexpression plasmid were used to knockdown or overexpress the expression level of XBP1s. EdU staining, colony formation, Cell Counting Kit­8, Transwell and wound healing assays, and flow cytometry were performed to detect the proliferation, colony forming ability, cell viability, migration and invasion ability, and the apoptosis rate. The results showed that the mRNA and protein expression level of XBP1 was higher in tumor tissues compared with that in adjacent normal tissues using data from the TIMER2.0, ONCOMINE and UALCAN online databases. In addition, the mRNA expression level of XBP1 was also associated with clinical features, including age, smoking habit, individual cancer stage and nodal metastasis status. In the in vitro experiments, the mRNA and protein expression level of XBP1s was increased in the A549 cell line compared with that in the human bronchial epithelial (HBE), H1299, PC9 and H460 cell lines. Hypoxia further increased the protein expression level of XBP1s in the A549 cell line. Knockdown of XBP1s expression in the A549 cell line resulted in decreased proliferation, colony formation, cell viability, migration and invasion, and increased apoptosis. By contrast, overexpressing XBP1s in the HBE cell line led to the opposite results. To investigate the mechanism involved, proteins associated with XBP1 were analyzed using the LinkedOmics database. Pathway enrichment revealed the MAPK pathway to be the possible XBP1 downstream target. Furthermore, Pearson's correlation and western blot analyses verified that phosphorylated (p)­JNK rather than p­ERK or p­p38 was the downstream effector of XBP1s. Phosphorylation of JNK was decreased when XBP1s expression was knocked down in the A549 cell line under normoxic and hypoxic conditions. Inhibiting p­JNK with SP600125 reversed the increased prosurvival effects caused by XBP1s overexpression. The results from the present study suggest that XBP1s/p­JNK function as a prosurvival factors in the A549 cell line and could be a potential target for the treatment of lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Proteína 1 de Ligação a X-Box , Adenocarcinoma de Pulmão/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Sistema de Sinalização das MAP Quinases , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo
7.
Eur Respir J ; 2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35086828

RESUMO

Although DNA methylation has been recognized in the pathogenesis of idiopathic pulmonary fibrosis (IPF), the exact mechanisms, however, are yet to be fully addressed. Herein, we demonstrated that lungs originated from IPF patients and mice after bleomycin (BLM)-induced pulmonary fibrosis are characterized by the altered DNA methylation along with overexpression of methyl-CpG-binding domain 2 (MBD2) in myofibroblasts, a reader responsible for interpreting DNA methylome-encoded information. Specifically, depletion of Mbd2 in fibroblasts or myofibroblasts protected mice from BLM-induced pulmonary fibrosis coupled with a significant reduction of fibroblast differentiation. Mechanistically, TGF-ß1 induced a positive feedback regulatory loop between transforming growth factor-ß receptor I (TßRI), Smad3 and Mbd2, and erythroid differentiation regulator 1 (Erdr1). TGF-ß1 induced fibroblasts to undergo a global DNA hypermethylation along with Mbd2 overexpression in a TßRI/Smad3 dependent manner, and Mbd2 selectively bound to the methylated CpG DNA within the Erdr1 promoter to repress its expression, through which it enhances TGF-ß/Smads signaling to promote fibroblast differentiating into myofibroblast and exacerbate pulmonary fibrosis. Therefore, enhancing Erdr1 expression strikingly reversed established pulmonary fibrosis. Collectively, our data support that strategies aimed at silencing Mbd2 or increasing Erdr1 could be viable therapeutic approaches for prevention and treatment of pulmonary fibrosis in clinical settings.

8.
Nat Commun ; 13(1): 114, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013220

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with limited therapeutic options. Tartrate-resistant acid phosphatase 5 (ACP5) performs a variety of functions. However, its role in IPF remains unclear. Here, we demonstrate that the levels of ACP5 are increased in IPF patient samples and mice with bleomycin (BLM)-induced pulmonary fibrosis. In particular, higher levels of ACP5 are present in the sera of IPF patients with a diffusing capacity of the lungs for carbonmonoxide (DLCO) less than 40% of the predicted value. Additionally, Acp5 deficiency protects mice from BLM-induced lung injury and fibrosis coupled with a significant reduction of fibroblast differentiation and proliferation. Mechanistic studies reveal that Acp5 is upregulated by transforming growth factor-ß1 (TGF-ß1) in a TGF-ß receptor 1 (TGFßR1)/Smad family member 3 (Smad3)-dependent manner, after which Acp5 dephosphorylates p-ß-catenin at serine 33 and threonine 41, inhibiting the degradation of ß-catenin and subsequently enhancing ß-catenin signaling in the nucleus, which promotes the differentiation, proliferation and migration of fibroblast. More importantly, the treatment of mice with Acp5 siRNA-loaded liposomes or Acp5 inhibitor reverses established lung fibrosis. In conclusions, Acp5 is involved in the initiation and progression of pulmonary fibrosis and strategies aimed at silencing or suppressing Acp5 could be considered as potential therapeutic approaches against pulmonary fibrosis.


Assuntos
Fibroblastos/metabolismo , Fibrose Pulmonar/genética , Proteína Smad3/genética , Fosfatase Ácida Resistente a Tartarato/genética , Fator de Crescimento Transformador beta1/genética , Animais , Bleomicina/administração & dosagem , Monóxido de Carbono/metabolismo , Diferenciação Celular , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Fibroblastos/patologia , Regulação da Expressão Gênica , Humanos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Fosforilação , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Fibrose Pulmonar/prevenção & controle , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Testes de Função Respiratória , Transdução de Sinais , Proteína Smad3/metabolismo , Fosfatase Ácida Resistente a Tartarato/antagonistas & inibidores , Fosfatase Ácida Resistente a Tartarato/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
9.
Respir Res ; 23(1): 6, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35016680

RESUMO

BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a chronic progressive advanced disorder pathologically characterized by pulmonary vascular remodeling. Notch4 as a cell surface receptor is critical for vascular development. However, little is known about the role and mechanism of Notch4 in the development of hypoxic vascular remodeling. METHODS: Lung tissue samples were collected to detect the expression of Notch4 from patients with HPH and matched controls. Human pulmonary artery smooth muscle cells (HPASMCs) were cultured in hypoxic and normoxic conditions. Real-time quantitative PCR and western blotting were used to examine the mRNA and protein levels of Notch4. HPASMCs were transfected with small interference RNA (siRNA) against Notch4 or Notch4 overexpression plasmid, respectively. Cell viability, cell proliferation, apoptosis, and migration were assessed using Cell Counting Kit-8, Edu, Annexin-V/PI, and Transwell assay. The interaction between Notch4 and ERK, JNK, P38 MAPK were analyzed by co-immunoprecipitation. Adeno-associated virus 1-mediated siRNA against Notch4 (AAV1-si-Notch4) was injected into the airways of hypoxic rats. Right ventricular systolic pressure (RVSP), right ventricular hypertrophy and pulmonary vascular remodeling were evaluated. RESULTS: In this study, we demonstrate that Notch4 is highly expressed in the media of pulmonary vascular and is upregulated in lung tissues from patients with HPH and HPH rats compared with control groups. In vitro, hypoxia induces the high expression of Delta-4 and Notch4 in HPASMCs. The increased expression of Notch4 promotes HPASMCs proliferation and migration and inhibits cells apoptosis via ERK, JNK, P38 signaling pathways. Furthermore, co-immunoprecipitation result elucidates the interaction between Notch4 and ERK/JNK/P38. In vivo, silencing Notch4 partly abolished the increase in RVSP and pulmonary vascular remodeling caused by hypoxia in HPH rats. CONCLUSIONS: These findings reveal an important role of the Notch4-ERK/JNK/P38 MAPK axis in hypoxic pulmonary remodeling and provide a potential therapeutic target for patients with HPH.


Assuntos
Regulação da Expressão Gênica , Hipertensão Pulmonar/genética , Hipóxia/complicações , Miócitos de Músculo Liso/metabolismo , Receptor Notch4/genética , Remodelação Vascular/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Animais , Apoptose , Proliferação de Células , Células Cultivadas , Modelos Animais de Doenças , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/patologia , Hipóxia/genética , Hipóxia/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Miócitos de Músculo Liso/patologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Ratos , Ratos Sprague-Dawley , Receptor Notch4/biossíntese , Transdução de Sinais , Regulação para Cima , Proteínas Quinases p38 Ativadas por Mitógeno/biossíntese
10.
Am J Respir Crit Care Med ; 205(4): 450-458, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34813411

RESUMO

Rationale: It remains unknown whether long-term ozone exposure can impair lung function. Objectives: To investigate the associations between long-term ozone exposure and adult lung function in China. Methods: Lung function results and diagnosis of small airway dysfunction (SAD) were collected from a cross-sectional study, the China Pulmonary Health Study (N = 50,991). We used multivariable linear and logistic regression models to examine the associations of long-term ozone exposure with lung function parameters and SAD, respectively, adjusting for demographic characteristics, individual risk factors, and longitudinal trends. We then performed a stratification analysis by chronic obstructive pulmonary disease (COPD). Measurements and Main Results: We observed that each 1 SD (4.9 ppb) increase in warm-season ozone concentrations was associated with a 14.2 ml/s (95% confidence interval [CI], 8.8-19.6 ml/s] decrease in forced expiratory flow at the 75th percentile of vital capacity and a 29.5 ml/s (95% CI, 19.6-39.5 ml/s) decrease in mean forced expiratory flow between the 25th and 75th percentile of vital capacity. The odds ratio of SAD was 1.09 (95% CI, 1.06-1.11) for a 1 SD increase in warm-season ozone concentrations. Meanwhile, we observed a significant association with decreased FEV1/FVC but not with FEV1 or FVC. The association estimates were greater in the COPD group than in the non-COPD group. Conclusions: We found independent associations of long-term ozone exposure with impaired small airway function and higher SAD risks, while the associations with airflow obstruction were weak. Patients with COPD appear to be more vulnerable.


Assuntos
Poluentes Atmosféricos/toxicidade , Exposição Ambiental/efeitos adversos , Pulmão/fisiopatologia , Ozônio/toxicidade , Adulto , Idoso , China , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testes de Função Respiratória
11.
J Cell Physiol ; 237(3): 1948-1963, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34964131

RESUMO

Hypoxic pulmonary hypertension (HPH) is characterized by elevated pulmonary artery resistance and vascular remodeling. Endoplasmic reticulum stress (ERS) is reported to be involved in HPH, but the underlying mechanisms remain uncertain. We found that Xbp1s, a potent transcription factor during ERS, was elevated in hypoxic-cultured rat PASMCs and lung tissues from HPH rats. Our in vitro experiments demonstrated that overexpressing Xbp1s can promote proliferation, cell viability, and migration and inhibit the apoptosis of PASMCs, while silencing Xbp1s led to the opposite. Through data-independent acquisition (DIA) mass spectrometry, we identified extensive proteomic alterations regulated by hypoxia and Xbp1s. Further validation revealed that p-JNK, rather than p-ERK or p-p38, was the downstream effector of Xbp1s. p-JNK inhibition reversed the biological effects of Xbp1s overexpression in vitro. In the animal HPH model, rats were randomly assigned to five groups: normoxia, hypoxia, hypoxia+AAV-CTL (control), hypoxia+AAV-Xbp1s (prevention), and hypoxia+AAV-Xbp1s (therapy). Adeno-associated virus (AAV) serotype 1-mediated Xbp1s knockdown in the prevention and therapy groups significantly reduced right ventricular systolic pressure, total pulmonary resistance, right ventricular hypertrophy, and the medial wall thickness of muscularized distal pulmonary arterioles; AAV-Xbp1s also decreased proliferating cell nuclear antigen expression and increased apoptosis in pulmonary arterioles. Collectively, our findings demonstrated that the Xbp1s-p-JNK pathway is important in hypoxic vascular remodeling and that targeting this pathway could be an effective strategy to prevent and alleviate HPH development.


Assuntos
Hipertensão Pulmonar , Sistema de Sinalização das MAP Quinases , Proteína 1 de Ligação a X-Box , Animais , Proliferação de Células/genética , Modelos Animais de Doenças , Hipertensão Pulmonar/metabolismo , Hipóxia/metabolismo , Miócitos de Músculo Liso/metabolismo , Proteômica , Artéria Pulmonar/metabolismo , Ratos , Ratos Sprague-Dawley , Remodelação Vascular , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo
12.
Healthcare (Basel) ; 9(12)2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34946491

RESUMO

Elderly individuals with chronic diseases (CDs) have a much higher risk of mental disorders, especially depression. This study aimed to identify the multidomain social determinants of occurrence and degree of depressive symptoms for the Chinese elderly with CDs. Data of 3438 elderly individuals (aged over 60 years) with CDs were drawn from the fourth wave of the China Health and Retirement Longitudinal Study implemented in 2018. Logistic regression was used to describe associations with the occurrence of depressive symptoms within and across multidomain social determinants (demographic, economic, neighborhood, environmental, and social and cultural). The Shapley value decomposition method was used to measure the relative importance of variables of the five domains. A quantile regression model was used to test how the effects of social factors vary across different points of depression score distributions. Approximately 40.1% of Chinese elderly individuals with CDs reported depressive symptoms. Respondents who were female, had a low income, experienced a disability, lived in rural areas, and were not engaged in work had a higher probability of suffering from depressive symptoms. Conversely, increased age, being covered by social security and being well-educated had a protective effect. Data also showed that the effects of these associated factors varied across different points of depression score distributions. The fact that socially disadvantaged people are more vulnerable to severe depressive symptoms implies that psychological health services and intervention strategies should target this population.

13.
Respir Res ; 22(1): 312, 2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34906150

RESUMO

BACKGROUND: Hypoxic pulmonary hypertension (PH) is a refractory pulmonary vascular remodeling disease, and the efficiency of current PH treatment strategies is unsatisfactory. Tribbles homolog 3 (TRB3), a member of the pseudokinase family, is upregulated in diverse types of cellular stresses and functions as either a pro-proliferative or pro-apoptotic factor depending on the specific microenvironment. The regulatory mechanisms of TRB3 in hypoxic PH are poorly understood. METHODS: We performed studies using TRB3-specific silencing and overexpressing lentiviral vectors to investigate the potential roles of TRB3 on hypoxic pulmonary artery smooth muscle cells (PASMCs). Adeno-associated virus type 1(AVV1) vectors encoding short-hairpin RNAs against rat TRB3 were used to assess the role of TRB3 on hypoxic PH. TRB3 protein expression in PH patients was explored in clinical samples by western blot analysis. RESULTS: The results of whole-rat genome oligo microarrays showed that the expression of TRB3 and endoplasmic reticulum stress (ERS)-related genes was upregulated in hypoxic PASMCs. TRB3 protein expression was significantly upregulated by hypoxia and thapsigargin. In addition, 4-PBA and 4µ8C, both inhibitors of ERS, decreased the expression of TRB3. TRB3 knockdown promoted apoptosis and damaged the proliferative and migratory abilities of hypoxic PASMCs as well as inhibited activation of the MAPK signaling pathway. TRB3 overexpression stimulated the proliferation and migration of PASMCs but decreased the apoptosis of PASMCs, which was partly reversed by specific inhibitors of ERK, JNK and p38 MAPK. The Co-IP results revealed that TRB3 directly interacts with ERK, JNK, and p38 MAPK. Knockdown of TRB3 in rat lung tissue reduced the right ventricular systolic pressure and decreased pulmonary medial wall thickness in hypoxic PH model rats. Further, the expression of TRB3 in lung tissues was higher in patients with PH compared with those who have normal pulmonary artery pressure. CONCLUSIONS: TRB3 was upregulated in hypoxic PASMCs and was affected by ERS. TRB3 plays a key role in the pathogenesis of hypoxia-induced PH by binding and activating the ERK, JNK, and p38 MAPK pathways. Thus, TRB3 might be a promising target for the treatment of hypoxic PH.


Assuntos
Estresse do Retículo Endoplasmático/genética , Regulação da Expressão Gênica , Hipertensão Pulmonar/genética , Hipóxia/complicações , Sistema de Sinalização das MAP Quinases/genética , Remodelação Vascular/genética , Animais , Apoptose , Comunicação Celular , Modelos Animais de Doenças , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/metabolismo , Hipóxia/genética , Hipóxia/metabolismo , Masculino , /genética , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Regulação para Cima
14.
Clin Sci (Lond) ; 135(21): 2467-2481, 2021 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-34676402

RESUMO

Pulmonary hypertension (PH) is a life-threatening disease characterized by vascular remodeling. Exploring new therapy target is urgent. The purpose of the present study is to investigate whether and how spliced x-box binding protein 1 (xbp1s), a key component of endoplasmic reticulum stress (ERS), contributes to the pathogenesis of PH. Forty male SD rats were randomly assigned to four groups: Control, Monocrotaline (MCT), MCT+AAV-CTL (control), and MCT+AAV-xbp1s. The xbp1s protein levels were found to be elevated in lung tissues of the MCT group. Intratracheal injection of adeno-associated virus serotype 1 carrying xbp1s shRNA (AAV-xbp1s) to knock down the expression of xbp1s effectively ameliorated the MCT-induced elevation of right ventricular systolic pressure (RVSP), total pulmonary resistance (TPR), right ventricular hypertrophy and medial wall thickness of muscularized distal pulmonary arterioles. The abnormally increased positive staining rates of proliferating cell nuclear antigen (PCNA) and Ki67 and decreased positive staining rates of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) in pulmonary arterioles were also reversed in the MCT+AAV-xbp1s group. For mechanistic exploration, bioinformatics prediction of the protein network was performed on the STRING database, and further verification was performed by qRT-PCR, Western blots and co-immunoprecipitation (Co-IP). DNA damage-inducible transcript 3 (Ddit3) was identified as a downstream protein that interacted with xbp1s. Overexpression of Ddit3 restored the decreased proliferation, migration and cell viability caused by silencing of xbp1s. The protein level of Ddit3 was also highly consistent with xbp1s in the animal model. Taken together, our study demonstrated that xbp1s-Ddit3 may be a potential target to interfere with vascular remodeling in PH.


Assuntos
Pressão Arterial , Hipertensão Pulmonar/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Fator de Transcrição CHOP/metabolismo , Remodelação Vascular , Proteína 1 de Ligação a X-Box/metabolismo , Animais , Apoptose , Movimento Celular , Proliferação de Células , Células Cultivadas , Modelos Animais de Doenças , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Direita/induzido quimicamente , Hipertrofia Ventricular Direita/metabolismo , Hipertrofia Ventricular Direita/fisiopatologia , Masculino , Monocrotalina , Músculo Liso Vascular/fisiopatologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/fisiopatologia , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Transcrição CHOP/genética , Disfunção Ventricular Direita/induzido quimicamente , Disfunção Ventricular Direita/metabolismo , Disfunção Ventricular Direita/fisiopatologia , Função Ventricular Direita , Proteína 1 de Ligação a X-Box/genética
15.
Carbohydr Polym ; 270: 118385, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34364627

RESUMO

Cellulose, as the most abundant natural polysaccharide, is an excellent material for developing green humidity sensors, especially due to its humidity responsiveness as a result of its rich hydrophilic groups. In combination with other components including carbon materials and polymers, cellulose and its derivatives can be used to design high-performance humidity sensors that meet various application requirements. This review summarizes the recent advances in the field of various cellulose-derived humidity sensors, with particular attention paid to different sensing mechanisms including resistance, capacitance, colorimetry and gravity, and so on. Furthermore, the roles of cellulose and its derivatives are highlighted. This work may promote the development of cellulose-derived humidity sensors, as well as other cellulose-based intelligent materials.


Assuntos
Celulose/química , Desenho de Equipamento/métodos , Umidade , Carbono/química , Colorimetria/métodos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Nanoestruturas/química , Polímeros/química , Temperatura , Água/química
16.
Theranostics ; 11(14): 7110-7125, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093874

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fatal interstitial lung disease characterized by abnormal transition and proliferation of fibroblasts. The uncontrolled transition of fibroblasts, commonly known as myofibroblasts, are the principal source of the enormous extracellular matrix (ECM) depositing in lung parenchyma, leading to gradual failure of gas exchange and mortality of the patients. However, up to now, rare effective therapeutic strategies have been developed to blockade fibroblast-to-myofibroblast transition (FMT) in IPF. Method: We illustrated that the lungs originated from IPF patients and mice with pulmonary fibrosis are characterized by the overexpression of sushi-repeat-containing protein, X-linked 2 (SRPX2). Further functionality studies identified the pivotal role of SRPX2 in FMT. Mechanistically, SRPX2 was involved in a TGFßR1/SMAD3/SRPX2/AP1/SMAD7 positive feedback loop. Specifically, SRPX2 was upregulated by TGF-ß1 in a TGFßR1/SMAD3-dependent manner, after which SRPX2 in turn repressed the expression of AP1, subsequently minimized SMAD7 expression, through which it reduced the formation of inhibitory complex with TGFßR1 and enhanced SMAD signaling pathway to promote FMT and exacerbate pulmonary fibrosis. Notably, intratracheal administration of siRNA-loaded liposomes could effectively suppress the expression of Srpx2 in the lung and remarkably protect mice against BLM-induced pulmonary fibrosis, concomitant with a significant reduction of FMT. Results: Accordingly, these data indicate that Srpx2 plays an essential role in the pathogenesis of pulmonary fibrosis and suggests the strategy aiming at silencing Srpx2 could be a promising therapeutic approach against pulmonary fibrosis in clinical settings.


Assuntos
Proliferação de Células/genética , Fibroblastos/metabolismo , Terapia Genética/métodos , Lipossomos/administração & dosagem , Proteínas de Membrana/metabolismo , Mioblastos/metabolismo , Proteínas de Neoplasias/metabolismo , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/terapia , Idoso , Animais , Movimento Celular/genética , Retroalimentação Fisiológica , Feminino , Fibroblastos/patologia , Inativação Gênica , Humanos , Lipossomos/metabolismo , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Mioblastos/patologia , Proteínas de Neoplasias/genética , Fibrose Pulmonar/genética , RNA Interferente Pequeno , RNA-Seq , Proteína Smad3/metabolismo , Proteína Smad7/metabolismo , Fator de Transcrição AP-1/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Regulação para Cima
17.
Environ Int ; 156: 106707, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34182192

RESUMO

The associations of long-term exposure to various constituents of fine particulate matter (≤2.5 µm in aerodynamic diameter, PM2.5) air pollution with lung function were not clearly elucidated in developing countries. The aim was to evaluate the associations of long-term exposure to main constituents of PM2.5 with lung function in China. This is a nationwide, cross-sectional analysis among 50,991 study participants from the China Pulmonary Health study. Multivariable linear regression models were used to obtain differences of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF), and forced expiratory flow at 25-75% of exhaled FVC (FEF25-75%) associated with an interquartile range (IQR) change of PM2.5 or its constituents. Residential annual PM2.5 levels varied from 26 µg/m3 to 92 µg/m3 (average: 53 µg/m3). An IQR increase of PM2.5 concentrations was associated with lower FEV1 (19.82 mL, 95% CI: 11.30-28.33), FVC (17.45 mL, 95% CI: 7.16-27.74), PEF (86.64 mL/s, 95% CI: 59.77-113.52), and FEF25-75% (31.93 mL/s, 95% CI: 16.64-47.22). Black carbon, organic matter, ammonium, sulfate, and nitrate were negatively associated with most lung function indicators, with organic matter and nitrate showing consistently larger magnitude of associations than PM2.5 mass. This large-scale study provides first-hand epidemiological evidence that long-term exposure to ambient PM2.5 and some constituents, especially organic matter and nitrate, were associated with lower large- and small- airway function.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China , Estudos Transversais , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Volume Expiratório Forçado , Humanos , Pulmão , Material Particulado/análise
18.
Thorac Cancer ; 12(15): 2214-2216, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34145962

RESUMO

With the increased use of immune checkpoint inhibitors (ICIs) in lung cancer, which are of great benefit to patients, more and more immune-related adverse events (irAEs) are being reported. Checkpoint inhibitor pneumonitis (CIP) is one of the most challenging adverse events, which pose a huge challenge to clinical diagnosis and treatment, and its incidence in the real world is greatly underestimated. Currently, the treatment of CIP mainly depends on the use of glucocorticoids. As for steroid-resistant CIP, there is no unified standardized treatment strategy. Herein, we report a case of steroid-resistant CIP induced by pembrolizumab in a patient with advanced non-small cell lung cancer (NSCLC), in which their symptoms were successfully controlled with pirfenidone.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico , Piridonas/administração & dosagem , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Humanos , Masculino
19.
Biomed Pharmacother ; 139: 111500, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33901873

RESUMO

Idiopathic pulmonary fibrosis (IPF) is the most common fatal interstitial lung disease, with limited therapeutic options. The abnormal and uncontrolled differentiation and proliferation of fibroblasts have been confirmed to play a crucial role in driving the pathogenesis of IPF. Therefore, effective and well-tolerated antifibrotic agents that interfere with fibroblasts would be an ideal treatment, but no such treatments are available. Remarkably, we found that dopamine (DA) receptor D1 (D1R) and DA receptor D2 (D2R) were both upregulated in myofibroblasts in lungs of IPF patients and a bleomycin (BLM)-induced mouse model. Then, we explored the safety and efficacy of DA, fenoldopam (FNP, a selective D1R agonist) and sumanirole (SMR, a selective D2R agonist) in reversing BLM-induced pulmonary fibrosis. Further data showed that DA receptor agonists exerted potent antifibrotic effects in BLM-induced pulmonary fibrosis by attenuating the differentiation and proliferation of fibroblasts. Detailed pathway analysis revealed that DA receptor agonists decreased the phosphorylation of Smad2 induced by TGF-ß1 in primary human lung fibroblasts (PHLFs) and IMR-90 cells. Overall, DA receptor agonists protected mice from BLM-induced pulmonary fibrosis and may be therapeutically beneficial for IPF patients in a clinical setting.


Assuntos
Antibióticos Antineoplásicos , Bleomicina , Agonistas de Dopamina/uso terapêutico , Fibroblastos/efeitos dos fármacos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Animais , Benzimidazóis/farmacologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Agonistas de Dopamina/farmacologia , Fenoldopam/farmacologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Receptores de Dopamina D1/efeitos dos fármacos , Receptores de Dopamina D2/efeitos dos fármacos , Proteína Smad2/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima/efeitos dos fármacos
20.
Animals (Basel) ; 11(2)2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33567555

RESUMO

Testicular expression of taste receptor type 1 subunit 3 (T1R3), a sweet/umami taste receptor, has been implicated in spermatogenesis and steroidogenesis in mice. We explored the role of testicular T1R3 in porcine postnatal development using the Congjiang Xiang pig, a rare Chinese miniature pig breed. Based on testicular weights, morphology, and testosterone levels, four key developmental stages were identified in the pig at postnatal days 15-180 (prepuberty: 30 day; early puberty: 60 day; late puberty: 90 day; sexual maturity: 120 day). During development, testicular T1R3 exhibited stage-dependent and cell-specific expression patterns. In particular, T1R3 levels increased significantly from prepuberty to puberty (p < 0.05), and expression remained high until sexual maturity (p < 0.05), similar to results for phospholipase Cß2 (PLCß2). The strong expressions of T1R3/PLCß2 were observed at the cytoplasm of elongating/elongated spermatids and Leydig cells. In the eight-stage cycle of the seminiferous epithelium in pigs, T1R3/PLCß2 levels were higher in the spermatogenic epithelium at stages II-VI than at the other stages, and the strong expressions were detected in elongating/elongated spermatids and residual bodies. The message RNA (mRNA) levels of taste receptor type 1 subunit 1 (T1R1) in the testis showed a similar trend to levels of T1R3. These data indicate a possible role of T1R3 in the regulation of spermatid differentiation and Leydig cell function.

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