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1.
J Mol Neurosci ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34478049

RESUMO

The activation of microglia is an important cause of central nervous system (CNS) inflammatory cell infiltration and inflammatory demyelination in experimental autoimmune encephalomyelitis (EAE). Furthermore, the proinflammatory response induced by the NLR family pyrin domain containing 3 (NLRP3) inflammasome can be amplified in microglia after NLRP3 inflammasome activation. Autophagy is closely related to the inflammatory response. Caffeine exerts anti-inflammatory and autophagy-stimulating effects, but the specific mechanism remains unclear. This study examined the mechanism underlying the anti-inflammatory effect of caffeine on EAE. In this study, C57BL/6 mice were immunized to induce EAE and treated with caffeine to observe its effect on prognosis. The effects of caffeine on autophagy and inflammation were also analysed in mouse primary microglia (PM) and the BV2 cell line. The data demonstrated that caffeine reduced the clinical score, the infiltration of inflammatory cells, the demyelination level, and the activation of microglia in EAE mice. Furthermore, caffeine increased the LC3-II/LC3-I levels and decreased the NLRP3 and P62 levels in EAE mice, whereas the autophagy inhibitor 3-methylamine (3-MA) blocked these effects. In vitro, caffeine promoted autophagy by suppressing the mechanistic target of rapamycin (mTOR) pathway and inhibited activation of the NLRP3 inflammasome. However, autophagy-related gene 5 (ATG5)-specific siRNA abolished the anti-inflammatory effect of caffeine treatment in PM and BV2 cells. Taken together, these data suggest that caffeine exerts a newly discovered effect on EAE by reducing NLRP3 inflammasome activation via the induction of autophagy in microglia.

2.
Thorac Cancer ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34523261

RESUMO

BACKGROUND: Drug resistance is a major clinical drawback behind the failure of chemotherapy in non-small cell lung cancer (NSCLC). In this study, we undertook to identify the precise role of circular RNA (circRNA) circ_0058357 in the functional properties of DDP-resistant NSCLC cells. METHODS: Circ_0058357, miR-361-3p and ATP-binding cassette (ABC) subfamily C member 1 (ABCC1) were quantified by qRT-PCR and western blot. Cell survival and viability were gauged by MTT assay. Cell proliferation, apoptosis, invasion and migration were measured by EdU, flow cytometry, transwell and wound-healing assays, respectively. The direct relationship between miR-361-3p and circ_0058357 or ABCC1 was validated by dual-luciferase reporter assay. RESULTS: Our data showed that circ_0058357 was highly expressed in DDP-resistant NSCLC tissues and cells. Inhibition of circ_0058357 repressed cell growth, invasion, migration, and promoted DDP sensitivity and cell apoptosis of H1299/DDP and A549/DDP cells in vitro. Moreover, inhibition of circ_0058357 diminished the growth of A549/DDP cells and sensitized them to the cytotoxic effect of DDP in vivo. Mechanistically, circ_0058357 contained a miR-361-3p binding site and miR-361-3p was identified as a molecular mediator of circ_0058357 regulation. MiR-361-3p suppressed ABCC1 expression by binding to ABCC1 3'UTR, and miR-361-3p-mediated inhibition of ABCC1 affected the growth, invasion, migration, apoptosis and DDP sensitivity of H1299/DDP and A549/DDP cells. Furthermore, circ_0058357 regulated ABCC1 expression by competitively binding to shared miR-361-3p. CONCLUSIONS: Our findings identified that inhibition of circ_0058357 suppresses the growth and metastasis of H1299/DDP and A549/DDP cells and sensitizes them to DDP therapy partially by targeting the miR-361-3p/ABCC1 axis.

3.
ACS Appl Mater Interfaces ; 13(33): 38979-38989, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433249

RESUMO

Chronic infections caused by Pseudomonas aeruginosa pose severe threats to human health. Traditional antibiotic therapy has lost its total supremacy in this battle. Here, nanoplatforms activated by the clinical microenvironment are developed to treat P. aeruginosa infection on the basis of dynamic borate ester bonds. In this design, the nanoplatforms expose targeted groups for bacterial capture after activation by an acidic infection microenvironment, resulting in directional transport delivery of the payload to bacteria. Subsequently, the production of hyperpyrexia and reactive oxygen species enhances antibacterial efficacy without systemic toxicity. Such a formulation with a diameter less than 200 nm can eliminate biofilm up to 75%, downregulate the level of cytokines, and finally promote lung repair. Collectively, the biomimetic design with phototherapy killing capability has the potential to be an alternative strategy against chronic infections caused by P. aeruginosa.


Assuntos
Antibacterianos/química , Verde de Indocianina/química , Nanocápsulas/química , Fármacos Fotossensibilizantes/química , Polímeros/química , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/radioterapia , Células A549 , Animais , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Composição de Medicamentos , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Humanos , Verde de Indocianina/farmacologia , Raios Infravermelhos , Masculino , Metacrilatos/química , Camundongos Endogâmicos BALB C , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Pseudomonas aeruginosa/efeitos dos fármacos
4.
Cancer Discov ; 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417225

RESUMO

Liver metastasis, the leading cause of colorectal cancer mortality, exhibits a highly heterogeneous and suppressive immune microenvironment. Here, we sequenced 97 matched samples by using single-cell RNA-seq and Spatial Transcriptomics. Strikingly, metastatic microenvironment underwent remarkable spatial reprogramming of immunosuppressive cells such as MRC1+ CCL18+ M2-like macrophages. We further developed scMetabolism, a computational pipeline for quantifying single-cell metabolism, and observed that those macrophages harbored enhanced metabolic activity. Interestingly, neoadjuvant chemotherapy could block this status and restore the antitumor immune balance in responsive patients, while the non-responsive patients deteriorated into a more suppressive one. Our work described the immune evolution of metastasis and uncovered the black box of how tumors respond to neoadjuvant chemotherapy.

5.
J Nanobiotechnology ; 19(1): 226, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34340698

RESUMO

BACKGROUND: Patients with diabetes have an increased risk of nonunion and delayed union of fractures. Macrophages have been shown as a key player in diabetic complications. However, it remains obscure how diabetic milieu affects macrophage-derived exosomes and its implications on osteogenic differentiation of BMSCs. In this study, we aim to define the impact of diabetic milieu on macrophage-derived exosomes, role of extracellular vesicles in intercellular communication with BMSCs, and subsequent effects on osteogenic differentiation and fracture repair. RESULTS: The osteogenic potential and the ability of fracture repair of exosomes derived from diabetic bone marrow-derived macrophages (dBMDM-exos) were revealed to be lower, as compared with non-diabetic bone marrow-derived macrophages (nBMDM-exos) in vitro and in vivo. Interestingly, miR-144-5p levels were sharply elevated in dBMDM-exos and it could be transferred into BMSCs to regulate bone regeneration by targeting Smad1. In addition, the adverse effects of dBMDM-exos on the osteogenic potential and the ability of fracture repair were reversed through the suppression of miR-144-5p inhibition in vitro and vivo. CONCLUSIONS: The results demonstrated an important role of exosomal miR-144-5p in bone regeneration, offering insight into developing new strategy for the improvement of fracture healing in patients with diabetes mellitus.

6.
Eur J Med Res ; 26(1): 100, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34454624

RESUMO

OBJECTIVE: This study aimed to present the case of a boy with acute distress syndrome (ARDS) treated with low-dose umbilical cord blood (UCB) therapy and explore the underlying possible mechanism. METHODS: A 7-year-old boy with severe Pneumocystis carinii pneumonia and severe ARDS was treated with allogeneic UCB as salvage therapy. RESULTS: The patient did not improve after being treated with lung protective ventilation, pulmonary surfactant replacement, and extracorporeal membrane oxygenation (ECMO) for 30 days. However, his disease reversed 5 days after allogeneic UCB infusion, and he weaned from ECMO after 7 days of infusion. Bioinformatics confirmed that his Toll-like receptor (TLR) was abnormal before UCB infusion. However, after the infusion, his immune system was activated and repaired, and the TLR4/MyD88/NF-κB signaling pathway was recovered. CONCLUSION: Allogenic UCB could treat ARDS by repairing the TLR4/MyD88/NF-κB signaling pathway, thereby achieving stability of the immune system.

7.
Plant Physiol Biochem ; 167: 296-308, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34391202

RESUMO

Plant respiratory burst oxidase homolog (Rboh) gene family encodes NADPH oxidases, and plays important roles in the production of reactive oxygen species (ROS), plant signaling, growth and stress responses. Cassava is an important starchy crops in tropical region. Environmental stresses, such as drought, pathogen, have caused great yield loss. The mechanisms of stress response are little known in MeRBOH family of cassava. Investigation of Rboh genes response to disease may provide a clue for clarification the disease resistance mechanisms. In this study, eight MeRboh genes were identified from the cassava genome. Comparisons of gene structure, protein motifs, and a phylogenetic tree showed conservation of Rboh gene families in cassava, Arabidopsis and rice. Transcript levels of most MeRboh genes increased following treatment with a pathogen, Xanthomonas axonopodis pv. manihotis, or with phytohormones salicylic acid or jasmonic acid. Analysis of cis-acting elements also indicated that MeRboh genes could response to light, hormone, abiotic and biotic stress. Prediction of miRNA target and post-translation modification sites of MeRboh suggested possible regulations of miRNA and protein phosphorylation; and transient expression of MeRboh in cassava protoplasts confirmed their localization on plasma membrane. Expression of MeRbohB, MeRbohF partially complemented PAMP responses in Arabidopsis rboh mutants, including the expression of PTI marker FRK1, ROS production, peroxide accumulation and callose deposition. It suggesting that MeRbohB and MeRbohF may participate in the PTI pathway and contributed to ROS production triggered by pathogens. Moreover, overexpression of MeRbohB and MeRbohF enhanced the resistance of Arabidopsis against Pseudomonas syringae pv. tomato DC3000. Together, these results suggest the evolutionary conservation of MeRboh gene family and their important role in the immune response and in regulating the plant disease resistance, providing a foundation for revealing molecular mechanisms of cassava disease resistance.


Assuntos
Arabidopsis , Manihot , Arabidopsis/genética , Resistência à Doença/genética , Regulação da Expressão Gênica de Plantas , Manihot/genética , Filogenia , Doenças das Plantas/genética
8.
Bioresour Technol ; 341: 125761, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34455252

RESUMO

A hollow-fiber membrane biofilm reactor was designed and constructed to achieve simultaneous nitrification-denitrification coupled to methane oxidation in low O2/CH4 ratio and high nitrogen removal rate. Three O2/CH4 ratio stages were operated. Ammonia removal rates reached 77.5 and 95 mg/(L·d) at the O2/CH4 ratio of 1.47 and 2.1, respectively. Microbial community analysis revealed that aeration through physical partition and O2/CH4 ratio stages achieved compartmentation of microbial community in structure and function. Combined functional genes analysis using qPCR, the aeration through gas distributer was proved to promote the enrichment of autotrophic ammonia oxidizers in the suspended liquid/mixed filler samples, and the aeration through hollow-fiber membrane favored the growth of methanotrophs and heterotrophic nitrification-aerobic denitrification bacteria. This study helps to develop effective regulatory strategies for high nitrogen removal based on the understanding of the community assembly process and the key driving factors.


Assuntos
Microbiota , Nitrificação , Biofilmes , Reatores Biológicos , Desnitrificação , Metano , Nitrogênio
9.
BMC Health Serv Res ; 21(1): 641, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34217292

RESUMO

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic has become a challenge for nursing homes in China. Nursing homes are particularly dangerous places in terms of the spread of COVID-19 given that they house vulnerable, high-risk populations. As such, several useful guidelines for coping with COVID-19 in nursing homes have been provided. However, the actual implementation rates of such guidelines are unknown. This study aims to document the adherence of nursing homes to the Ministry of Civil Affairs guidelines for COVID-19 prevention and control in nursing homes. METHODS: A cross-sectional study was conducted among 484 nursing homes in 136 cities of 28 provinces in China. A self-report questionnaire was created based on the Ministry of Civil Affairs guidelines for COVID-19 prevention and control in nursing homes (first edition). The questionnaire and the Transformational Leadership in the Public Sector Scale were sent to nursing home managers via the Wenjuanxing app online from February 7 to 29, 2020. Ultimately, 461 of 960 nursing homes participated, for a response rate of 48.0%. RESULTS: The average overall implementation rate of COVID-19 prevention and control measures was 80.0% (143.97/180). The average implementation rates for hygienic behaviour management and access management were lower, at 75.3 and 78.7%, respectively. Number of medical staff and transformational leadership score of nursing home's manager were associated with total implementation score (p < 0.05). A total of 69.8% (322/461) of the nursing home managers had serious resource problems, and inadequate protective supplies (72.0%) and staff shortages (47.7%) were the two primary problems. The nursing homes that located in urban, with large nursing home size, had hospital-nursing home cooperation and the transformational leadership score of manager> 60, had a lower risk of having serious resource problems. CONCLUSIONS: Overall, the implementation of prevention and control measures by nursing homes are insufficient during the epidemic in China. More medical staff, adequate resource, cooperation with hospitals, and higher transformational leadership of manager are required to improve the implementation rate. It is urgent for nursing homes to maintain the safety of residents and staff.


Assuntos
COVID-19 , China , Estudos Transversais , Humanos , Casas de Saúde , SARS-CoV-2
10.
Hum Cell ; 34(5): 1490-1503, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34228324

RESUMO

Circular RNAs (circRNAs) play a significant role in the progression of diverse malignancies. Here, we aimed to probe the function and mechanism of circ_0069244 in non-small cell lung cancer (NSCLC). In the present study, circ_0069244 was selected from the circRNA microarray datasets (GSE112214). Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to examine circ_0069244, miR-346 and XPC complex subunit, DNA damage recognition and repair factor (XPC) expression levels. Kaplan-Meier curve was employed to analyze the association between circ_0069244 expression and overall survival of NSCLC patients. Cell counting kit-8 (CCK-8) and 5-Bromo-2'-deoxyuridine (BrdU) experiments were utilized to examine the proliferation of NSCLC cells. Scratch healing and Transwell experiments were executed to examine the migration of NSCLC cells. Western blot was conducted to detect XPC expression at protein level in NSCLC cells. Bioinformatics analysis, dual-luciferase reporter gene and RNA immunoprecipitation (RIP) experiments predicted and validated the targeting relationships of circ_0069244 and miR-346, as well as miR-346 and 3'untranslated region (UTR) of XPC mRNA, respectively. We reported that circ_0069244 was remarkably down modulated in NSCLC and was linked to shorter survival and poor tumor histological grade in NSCLC patients. Functionally, circ_0069244 repressed NSCLC cell proliferation and migration. Furthermore, miR-346-5p was unveiled to be a downstream target of circ_0069244, and miR-346-5p specifically modulated XPC expression. Rescue experiments indicated that the inhibitory effect of circ_0069244 was abolished by co-expression of miR-346-5p mimics. Taken together, circ_0069244 restrained NSCLC progression by modulating the miR-346-5p/XPC axis.

11.
Biomacromolecules ; 22(7): 2834-2849, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34164980

RESUMO

Antibiotics are currently first-line therapy for bacterial infections. However, the curative effect of antibiotic remedies is limited due to increasingly prevalent bacterial resistance. The strategy to reverse intrinsic acquired drug resistance presents a promising option for reinvigorating antibiotic therapy. Here, we developed a ß-lactamase-inhibiting macromolecule composed of benzoxaborole and dextran for precise transport of ß-lactam antibiotics to strains overexpressing ß-lactamase. Benzoxaborole-derived nanotherapeutics enabled specific recognition and rapid internalization, and the nanotherapeutics with a high affinity toward bacteria distinctly inhibited the catalytic activity of bacterially secreted ß-lactamase by a reversible competitive mechanism. Thus, the system entrapping cefoxitin harbored a significantly enhanced ability to kill drug-resistant Escherichia coli compared to the ability of the drug by specifically overcoming the membrane barrier and acquired resistance mechanism of ß-lactamase overproduction. The reversible competitive nanotherapeutics exhibited a robust therapeutic efficacy in rat wounds infected with drug-resistant bacteria; the efficacy was due to efficient bacterial elimination and collateral benzoxaborole-dependent amelioration of the inflammatory response. The above results offered insights into the facile design of precise macromolecular adjuvants to exclusively reverse the acquired bacterial resistance mechanism and increase the utility of antibiotic therapies against antibiotic-resistant bacterial infections.


Assuntos
Antibacterianos , Bactérias Gram-Negativas , Animais , Antibacterianos/farmacologia , Escherichia coli , Testes de Sensibilidade Microbiana , Ratos , beta-Lactamases
12.
J Altern Complement Med ; 27(8): 657-668, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33979531

RESUMO

Objectives: This study describes the development and feasibility of Integrative Nutritional Counseling (INC), a Chinese medicine (CM)+biomedicine-based nutrition curriculum for Chinese Americans with type 2 diabetes. Although Chinese Americans often incorporate CM principles into their diet, scant research has explored how to integrate CM with biomedical nutrition standards in a culturally appropriate manner or if such a program could improve diabetes self-management. Design: This is a 1-month pre-post study design including three points of contact: baseline, in-person class, and 1-month follow-up. Subjects: Participants (n = 15) were Cantonese-speaking/reading Chinese Americans diagnosed with type 2 diabetes who had used some form of CM/medicinal foods in the last 12 months. Interventions and Outcome Measures: The INC program included baseline surveys and a CM intake interview conducted by a licensed acupuncturist. The acupuncturist generated a CM diagnosis, which was shared with the participant, and used this diagnosis to tailor brief nutrition education. To bolster this brief education, a bilingual registered dietitian provided a 2-h group education class in Cantonese to all participants, during which time participants also received a Chinese/English INC booklet. Participants completed surveys immediately after the class and at 1-month follow-up, with qualitative exit interviews. Results: Participants reported improved attitudes and dietary habits aligning directly with INC, and improvement in biomedically valued measures of type 2 diabetes, such as weight loss, and CM-valued measures of digestion/elimination and hot/cold feeling. Satisfaction with INC was high, but challenges included confusion with some INC information, structural barriers, and comorbidities. Conclusions: Chinese Americans with type 2 diabetes and interventionists found integrative nutrition approaches acceptable and feasible. Future research should examine INC with a larger population and explore optimal delivery of INC given reported challenges.

13.
J Hazard Mater ; 415: 125611, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-33725554

RESUMO

Arsenic (As) contamination is a worldwide problem and threatens human health. Here, we found that Rhizobium symbiosis can improve the tolerance to arsenate [As(V)], and a wild type R. meliloti Rm5038 symbiosis can significantly decrease the accumulation of As in Medicago truncatula shoots. The As content in plants could be decreased by nitrogen and the mutation of nitrate transporter NRT3.1. The expression of M. truncatula NRT3.1-like gene NRT3.1L1 could reverse the As(V)-tolerance phenotype of the Arabidopsis nrt3.1 mutant. Rm5038 symbiosis significantly increased the level of nitrogen in the shoot and reduced the expression of NRT3.1Ls in plants afflicted by As(V). The genetic analyses of aba2-1, pyr1/pyl1/2/4/5/8, and abi1-2/abi2-2/hab1-1/pp2ca-1 mutants revealed that abscisic acid (ABA) signaling regulates the tolerance of plants to As(V). ABA and linalool could promote the expression of NRT3.1Ls, however, their root biosynthesis was inhibited by ammonium, the first form of nitrogen fixed by Rhizobium symbiosis. Moreover, ABA and linalool may also control As and nitrate accumulation in Rhizobium symbionts via signaling pathways other than ammonia and NRT3.1Ls. Thus, Rhizobium symbiosis modulates the accumulation of As in plants via nitrogen and NRT3.1Ls regulated by ABA and linalool, which provides novel approaches to reduce As accumulation in legume crops.


Assuntos
Proteínas de Transporte de Ânions/genética , Arsênio , Medicago truncatula , Proteínas de Plantas/genética , Rhizobium/fisiologia , Monoterpenos Acíclicos , Regulação da Expressão Gênica de Plantas , Medicago truncatula/genética , Medicago truncatula/metabolismo , Nitrogênio , Fixação de Nitrogênio , Raízes de Plantas/microbiologia , Rhizobium/genética , Simbiose
14.
Sci Rep ; 11(1): 2820, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531576

RESUMO

Enlarged perivascular spaces (EPVS) are widely considered as a feature of cerebral small vessel diseases (SVD), but its underlying pathology is still under active investigation. The aim of this study was to explore the association between hemoglobin level and the severity of EPVS. Consecutive patients with acute ischemic stroke who underwent baseline MRI scan and hemoglobin testing were evaluated. EPVS in basal ganglia (BG) and central semiovale (CS) were rated with a validated 4-point semiquantitative scale (0 = none; 1 = 1-10; 2 = 11-20; 3 = 21-40; and 4 ≥ 40). Bivariate logistic regression models were used to identify the associations of hemoglobin with predefined high-degree (score > 1) CS-EPVS and BG-EPVS. Multinomial logistic regression models were used to analyze the associations between hemoglobin and CS-/BG-EPVS predominance patterns. A total of 401 patients were included in the final analysis, 94 patients (23.4%) had a high degree of CS-EPVS and 45 patients (11.2%) had a high degree of BG-EPVS. Compared with tertile 1 of hemoglobin, tertile 3 of hemoglobin was independently associated with high degree of CS-EPVS after adjusting for other features of SVD (odds ratio [OR] 2.399, 95% confidence interval [CI] 1.315-4.379, P = 0.004) and potential confounding factors (OR 2.611, 95% CI 1.346-5.066, P = 0.005). In multinomial logistic regression models, compared with tertile 1 of hemoglobin, tertile 2 (OR 2.463, 95% CI 1.195-5.075, P = 0.015) and tertile 3 (OR 2.625, 95% CI 1.102-6.251, P = 0.029) of hemoglobin were associated with higher odds of BG-EPVS = CS-EPVS pattern, and tertile 3 of hemoglobin (OR 2.576, 95% CI 1.004-6.608, P = 0.049) was associated with higher odds of BG-EPVS < CS-EPVS pattern. Elevated hemoglobin level was independently associated with high degree of CS-EPVS and higher odds of CS-EPVS predominance pattern, but not with BG-EPVS, which support that the topography of EPVS is characteristic. However, the pathogenesis linking hemoglobin and CS-EPVS is unclear and still needs further investigation.

15.
BMC Pulm Med ; 21(1): 45, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33509151

RESUMO

BACKGROUND: Cigarette smoke (CS) is a major risk factor for Chronic Obstructive Pulmonary Disease (COPD). Follistatin-like protein 1 (FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tried to investigate the role of FSTL1 in CS-induced autophagy dysregulation, airway inflammation and remodeling. METHODS: Serum and lung specimens were obtained from COPD patients and controls. Adult female wild-type (WT) mice, FSTL1± mice and FSTL1flox/+ mice were exposed to room air or chronic CS. Additionally, 3-methyladenine (3-MA), an inhibitor of autophagy, was applied in CS-exposed WT mice. The lung tissues and serum from patients and murine models were tested for FSTL1 and autophagy-associated protein expression by ELISA, western blotting and immunohistochemical. Autophagosome were observed using electron microscope technology. LTB4, IL-8 and TNF-α in bronchoalveolar lavage fluid of mice were examined using ELISA. Airway remodeling and lung function were also assessed. RESULTS: Both FSTL1 and autophagy biomarkers increased in COPD patients and CS-exposed WT mice. Autophagy activation was upregulated in CS-exposed mice accompanied by airway remodeling and airway inflammation. FSTL1± mice showed a lower level of CS-induced autophagy compared with the control mice. FSTL1± mice can also resist CS-induced inflammatory response, airway remodeling and impaired lung function. CS-exposed WT mice with 3-MA pretreatment have a similar manifestation with CS-exposed FSTL1± mice. CONCLUSIONS: FSTL1 promotes CS-induced COPD by modulating autophagy, therefore targeting FSTL1 and autophagy may shed light on treating cigarette smoke-induced COPD.


Assuntos
Remodelação das Vias Aéreas/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteínas Relacionadas à Folistatina/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Adenina/análogos & derivados , Adenina/farmacologia , Adulto , Animais , Biomarcadores/metabolismo , Líquido da Lavagem Broncoalveolar , Fumar Cigarros/efeitos adversos , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Proteínas Relacionadas à Folistatina/sangue , Proteínas Relacionadas à Folistatina/genética , Humanos , Inflamação/metabolismo , Pulmão/patologia , Pulmão/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia
16.
Pediatr Pulmonol ; 56(5): 1182-1188, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33289279

RESUMO

AIM: To examine the differences between oxygenation index (OI) and arterial partial pressure of oxygen to the fraction of inspired oxygen (PaO2 /FiO2 , [P/F]) in evaluating the severity of pediatric acute respiratory distress syndrome (PARDS). METHODS: The severity of PARDS was graded by using the OI score and P/F ratio, respectively. The data including clinical indexes and prognosis indicators were recorded and analyzed. RESULTS: During the 3-year study period, there were significant differences between OI and P/F scores in the severity grading of PARDS patients (p < .05). However, in severe diseases, both the scorings of OI and P/F were consistent (24.6% vs. 25.6%). The OI scores appeared more accurate when compared with P/F in the correlation between them and the pediatric critical illness score, multiple organ dysfunction syndromes (MODS), pressure indexes of ventilators and patients' prognosis. In the receiver operating characteristic curve, the critical values of OI and P/F were 8.42 and 144.71. Area under the curve of them were 0.839 and 0.853. The sensitivity values were both 0.854. The specificity values were 0.584 and 0.602. CONCLUSIONS: The OI and P/F were consistent in designating patients with severe PARDS. Among patients with mild to moderate diseases, the P/F could still be used for rapid determination given its simple calculation. Combined with the prognostic factors, the OI score was more accurate.

17.
Nano Lett ; 21(2): 891-898, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33079559

RESUMO

While many technologies rely on multilayer heterostructures, most of the studies on chemical functionalization have been limited to monolayer graphene. In order to use functionalization in multilayer systems, we must first understand the interlayer interactions between functionalized and nonfunctionalized (intact) layers and how to selectively functionalize one layer at a time. Here, we demonstrate a method to fabricate single- or double-sided fluorinated bilayer graphene (FBG) by tailoring substrate interactions. Both the top and bottom surfaces of bilayer graphene on the rough silicon dioxide (SiO2) are fluorinated; meanwhile, only the top surface of graphene on hexagonal boron nitride (hBN) is fluorinated. The functionalization type affects electronic properties; double-sided FBG on SiO2 is insulating, whereas single-sided FBG on hBN maintains conducting, showing that the intact bottom layer becomes electrically decoupled from the fluorinated top insulating layer. Our results define a straightforward method to selectively functionalize the top and bottom surfaces of bilayer graphene.

18.
J Pers Med ; 10(4)2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33050659

RESUMO

Analysis of circulating miRNAs (cmiRNAs) before surgical operation (BSO) and after the surgical operation (ASO) has been informative for lung adenocarcinoma (LUAD) diagnosis, progression, and outcomes of treatment. Thus, we performed a biological network analysis to identify the potential target genes (PTGs) of the overexpressed cmiRNA signatures from LUAD samples that had undergone surgical therapy. Differential expression (DE) analysis of microarray datasets, including cmiRNAs (GSE137140) and cmRNAs (GSE69732), was conducted using the Limma package. cmiR-1246 was predicted as a significantly upregulated cmiRNA of LUAD samples BSO and ASO. Then, 9802 miR-1246 target genes (TGs) were predicted using 12 TG prediction platforms (MiRWalk, miRDB, and TargetScan). Briefly, 425 highly expressed overlapping miRNA-1246 TGs were observed between the prediction platform and the cmiRNA dataset. ClueGO predicted cell projection morphogenesis, chemosensory behavior, and glycosaminoglycan binding, and the PI3K-Akt signaling pathways were enriched metabolic interactions regulating miRNA-1245 overlapping TGs in LUAD. Using 425 overlapping miR-1246 TGs, a protein-protein interaction network was constructed. Then, 12 PTGs of three different Walktrap modules were identified; among them, ubiquitin-conjugating enzyme E2C (UBE2C), troponin T1(TNNT1), T-cell receptor alpha locus interacting protein (TRAIP), and ubiquitin c-terminal hydrolase L1(UCHL1) were positively correlated with miR-1246, and the high expression of these genes was associated with better overall survival of LUAD. We conclude that PTGs of cmiRNA-1246 and key pathways, namely, ubiquitin-mediated proteolysis, glycosaminoglycan binding, the DNA metabolic process, and the PI3K-Akt-mTOR signaling pathway, the neurotrophin and cardiomyopathy signaling pathway, and the MAPK signaling pathway provide new insights on a noninvasive prognostic biomarker for LUAD.

19.
Cell Death Dis ; 11(7): 545, 2020 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-32683410

RESUMO

Skeletal muscle atrophy is one of the clinical symptoms of myotonic dystrophy type 1 (DM1). A decline in skeletal muscle regeneration is an important contributor to muscle atrophy. Skeletal muscle satellite cells (SSCs) drive skeletal muscle regeneration. Increased autophagy can reduce the proliferative capacity of SSCs, which plays an important role in the early regeneration of damaged skeletal muscle in DM1. Discovering new ways to restore SSC proliferation may aid in the identification of new therapeutic targets for the treatment of skeletal muscle atrophy in DM1. In the pathogenesis of DM1, muscleblind-like 1 (MBNL1) protein is generally considered to form nuclear RNA foci and disturb the RNA-splicing function. However, the role of MBNL1 in SSC proliferation in DM1 has not been reported. In this study, we obtained SSCs differentiated from normal DM1-04-induced pluripotent stem cells (iPSCs), DM1-03 iPSCs, and DM1-13-3 iPSCs edited by transcription activator-like (TAL) effector nucleases (TALENs) targeting CTG repeats, and primary SSCs to study the pathogenesis of DM1. DM1 SSC lines and primary SSCs showed decreased MBNL1 expression and elevated autophagy levels. However, DM1 SSCs edited by TALENs showed increased cytoplasmic distribution of MBNL1, reduced levels of autophagy, increased levels of phosphorylated mammalian target of rapamycin (mTOR), and improved proliferation rates. In addition, we confirmed that after MBNL1 overexpression, the proliferative capability of DM1 SSCs and the level of phosphorylated mTOR were enhanced, while the autophagy levels were decreased. Our data also demonstrated that the proliferative capability of DM1 SSCs was enhanced after autophagy was inhibited by overexpressing mTOR. Finally, treatment with rapamycin (an mTOR inhibitor) was shown to abolish the increased proliferation capability of DM1 SSCs due to MBNL1 overexpression. Taken together, these data suggest that MBNL1 reverses the proliferation defect of SSCs in DM1 by inhibiting autophagy via the mTOR pathway.


Assuntos
Autofagia/efeitos dos fármacos , Distrofia Miotônica/patologia , Proteínas de Ligação a RNA/metabolismo , Células Satélites de Músculo Esquelético/metabolismo , Células Satélites de Músculo Esquelético/patologia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Linhagem Celular , Núcleo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Feminino , Genoma , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação , Células Satélites de Músculo Esquelético/efeitos dos fármacos , Sirolimo/farmacologia , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição
20.
Life Sci ; 255: 117826, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32450163

RESUMO

MicroRNAs have been demonstrated to play critical role in the development of non-small cell lung cancer (NSCLC) and hypoxia is a common hallmark of NSCLC. MiRNA-130a-3p (miR-130a) is a well-known tumor suppressor, and we intended to explore the role and mechanism of miR-130a in NSCLC cells under hypoxia. We used real-time quantitative polymerase chain reaction method to measure miR-130a expression, and found that miR-130a was downregulated in human NSCLC tumors and cell lines (A549 and H1299), accompanied with upregulation of hypoxia-inducible factor 1 alpha (HIF1A), a marker of hypoxia. Besides, miR-130a low expression was associated with tumor burden and poor overall survival. Moreover, miR-130a expression was even downregulated in hypoxia-treated A549 and H1299 cells. Ectopic expression of miR-130a suppressed Warburg effect, migration and invasion in hypoxic A549 and H1299 cells, as evidenced by decreased glucose consumption, lactate production, hexokinase 2 expression, and numbers of migration cells and invasion cells analyzed by commercial glucose and lactate assay kits, western blotting and transwell assays. Furthermore, overexpression of miR-130a restrained xenograft tumor growth of A549 cells in mice. However, recovery of HIF1A could reverse the suppressive effect of miR-130a overexpression on cell migration, invasion and Warburg effect in hypoxic A549 and H1299 cells. Mechanically, dual-luciferase reporter assay, RNA immunoprecipitation and RNA pull-down assay confirmed a target relationship between miR-130a and HIF1A. Collectively, we demonstrated an anti-tumor role of miR-130a in NSCLC cells under hypoxia through targeting HIF1A, suggesting a potential target for the interfering of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Hipóxia Celular , Movimento Celular/genética , Regulação para Baixo , Feminino , Humanos , Neoplasias Pulmonares/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
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