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1.
Materials (Basel) ; 17(12)2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38930186

RESUMO

Ultra-thin 304 stainless steel can be used to flexibly display substrates after they have been subjected to chemical mechanical polishing (CMP). The thickness of the chemical oxide layer directly affects the polishing efficiency and surface quality of 304 stainless steel. In the study presented in the following paper, the thickness variation of the chemical oxide layer of 304 stainless steel was analyzed following electrochemical corrosion under different oxidant concentration conditions. Furthermore, the impact of the oxidant concentration on the grooves, chips, and scratch depth-displacement-load curves was investigated during a nano-scratching experiment. Through this process, we were able to reveal the chemical reaction mechanism between 304 stainless steel materials and oxidizers. The corrosion rate was found to be faster at 8% oxidant content. The maximum values of the scratch depth and elastic-plastic critical load were determined to be 2153 nm and 58.47 mN, respectively.

2.
Lancet Reg Health West Pac ; 43: 100938, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38456093

RESUMO

The WHO Western Pacific region bears disproportionate deaths from non-communicable diseases (NCDs), with increased overall NCD proportional mortality over the past two decades. The disease burden of mental health increased, resulting from rapid ageing, enhanced stress, and the COVID-19 pandemic, but it was largely neglected. The highly diverse cultures, religions, political systems, socioeconomic contexts, lifestyles, and environmental factors probably have led to massive disparities across countries in NCD mortality, risk factors, and NCD management. Geographically, East Asia had the lowest NCD mortality whilst Pacific islands had the highest. Economic booms, ageing, nutrition transition, social stress, prevalent tobacco use, and fast-increasing obesity and hyperglycaemia are important drivers of NCDs. Men tended to have more adverse behavioural and metabolic risk factors. Rural residents are catching up with their urban counterparts in metabolic risk factors and conditions. Sustainable strategies tailored to NCD patterns are needed to fight the NCD epidemic and related disparities.

3.
Front Bioeng Biotechnol ; 12: 1353333, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38419723

RESUMO

Sonoporation is a popular membrane disruption technique widely applicable in various fields, including cell therapy, drug delivery, and biomanufacturing. In recent years, there has been significant progress in achieving controlled, high-viability, and high-efficiency cell sonoporation in microfluidics. If the microchannels are too small, especially when scaled down to the cellular level, it still remains a challenge to overcome microchannel clogging, and low throughput. Here, we presented a microfluidic device capable of modulating membrane permeability through oscillating three-dimensional array of microbubbles. Simulations were performed to analyze the effective range of action of the oscillating microbubbles to obtain the optimal microchannel size. Utilizing a high-precision light curing 3D printer to fabricate uniformly sized microstructures in a one-step on both the side walls and the top surface for the generation of microbubbles. These microbubbles oscillated with nearly identical amplitudes and frequencies, ensuring efficient and stable sonoporation within the system. Cells were captured and trapped on the bubble surface by the acoustic streaming and secondary acoustic radiation forces induced by the oscillating microbubbles. At a driving voltage of 30 Vpp, the sonoporation efficiency of cells reached 93.9% ± 2.4%.

4.
Int Urol Nephrol ; 56(4): 1497-1508, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37878200

RESUMO

PURPOSE: To explore the incidence of postoperative acute kidney injury (AKI) after coronary artery bypass grafting (CABG) in elderly Chinese patients (≥ 75 years old) and its impacts on the short- and long-term prognosis. METHODS: A total of 493 patients aged 75-88 years old who underwent CABG from two medical centers between January 2006 and October 2021 were involved. Perioperative (preoperative and 7 days after operation) serum creatinine (Scr) levels were measured in all the enrolled patients. Univariate and multivariate logistic regression analyses were conducted to explore the independent risk factors of postoperative in-hospital mortality. Kaplan-Meier curves and COX model were used to test the risk factors of all-cause death during follow-up. Propensity score matching was used to balance differences between AKI and control groups. The primary outcome event was in-hospital death, and the secondary outcome was all-cause death during follow-up. RESULTS: The 198 patients were diagnosed with postoperative AKI. Intra-aortic balloon pump (IABP), cardiopulmonary bypass, and postoperative AKI were independent risk factors of in-hospital death. Gender, New York Heart Association Classification, preoperative eGFR, last eGFR within 7 days after operation, postoperative AKI, and postoperative renal function all impacted long-term prognosis. After 1:1 matching, 190 patients were included in the AKI and control groups. Use of IABP, use of cardiopulmonary bypass, and occurrence of postoperative AKI were still independent risk factors of in-hospital death. Preoperative eGFR, last eGFR within 7 days after operation, postoperative AKI and postoperative renal function all impacted long-term prognosis. CONCLUSION: The incidence of postoperative AKI in elderly patients undergoing CABG is high, and postoperative AKI is an independent risk factor of both short- and long-term postoperative prognosis.


Assuntos
Injúria Renal Aguda , Ponte de Artéria Coronária , Idoso , Humanos , Idoso de 80 Anos ou mais , Mortalidade Hospitalar , Estudos Retrospectivos , Ponte de Artéria Coronária/efeitos adversos , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/diagnóstico , Prognóstico , Complicações Pós-Operatórias/etiologia , Fatores de Risco
5.
Methods Mol Biol ; 2695: 351-365, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37450131

RESUMO

Atrial fibrillation (AF) is a common arrhythmia disease with high morbidity in clinical practice and leads to stroke, heart failure, peripheral embolism, and other severe complications. With aging of the society, AF has become one of the biggest public health challenges. Effective treatments including antiarrhythmic drugs, electrical cardioversion, and ablation (with or without catheters) can alleviate the symptoms of AF. Ablation is the most effective method for the treatment of persistent AF, but cannot cure all patients. Recurrence of AF is a realistic and unavoidable problem. For early predicting and warning of AF and its recurrence, liquid biopsy for accurate molecular analysis of biofluids is a new strategy with potential value and easy sampling and can detect genetic and epigenetic polymorphisms, especially microRNAs. In this review, liquid biopsy is constructed as a new powerful way for diagnosing AF and predicting its recurrence, contributing to the treatment of AF.


Assuntos
Fibrilação Atrial , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/genética , Fibrilação Atrial/cirurgia , Antiarrítmicos/uso terapêutico , Resultado do Tratamento , Biópsia Líquida
6.
Adv Healthc Mater ; 11(23): e2201655, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36153843

RESUMO

The blood-brain barrier (BBB) is a major limiting factor that prevents the treatment of Parkinson's disease (PD). In the present study, MgOp@PPLP nanoparticles are explored by using MgO nanoparticles as a substrate, polydopamine as a shell, wrapping anti-SNCA plasmid inside, and modifying polyethylene glycol, lactoferrin, and puerarin on the surface to improve the hydrophilicity, brain targeting and antioxidant properties of the particles, respectively. MgOp@PPLP exhibits superior near-infrared radiation (NIR) response. Under the guidance of photothermal effect, these MgOp@PPLP particles are capable of penetrating the BBB and be taken up by neuronal cells to exert gene therapy and antioxidant therapy. In both in vivo and in vitro models of PD, MgOp@PPLP exhibits good neuroprotective effects. Therefore, combined with noninvasive NIR radiation, MgOp@PPLP nanoplatform with good biocompatibility becomes an ideal material to combat neurodegenerative diseases.


Assuntos
Barreira Hematoencefálica , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico
7.
Nat Genet ; 54(7): 996-1012, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35817971

RESUMO

Defects in pathways governing genomic fidelity have been linked to improved response to immune checkpoint blockade therapy (ICB). Pathogenic POLE/POLD1 mutations can cause hypermutation, yet how diverse mutations in POLE/POLD1 influence antitumor immunity following ICB is unclear. Here, we comprehensively determined the effect of POLE/POLD1 mutations in ICB and elucidated the mechanistic impact of these mutations on tumor immunity. Murine syngeneic tumors harboring Pole/Pold1 functional mutations displayed enhanced antitumor immunity and were sensitive to ICB. Patients with POLE/POLD1 mutated tumors harboring telltale mutational signatures respond better to ICB than patients harboring wild-type or signature-negative tumors. A mutant POLE/D1 function-associated signature-based model outperformed several traditional approaches for identifying POLE/POLD1 mutated patients that benefit from ICB. Strikingly, the spectrum of mutational signatures correlates with the biochemical features of neoantigens. Alterations that cause POLE/POLD1 function-associated signatures generate T cell receptor (TCR)-contact residues with increased hydrophobicity, potentially facilitating T cell recognition. Altogether, the functional landscapes of POLE/POLD1 mutations shape immunotherapy efficacy.


Assuntos
DNA Polimerase II/genética , Neoplasias , Proteínas de Ligação a Poli-ADP-Ribose/genética , Animais , DNA Polimerase III/genética , Humanos , Imunoterapia , Camundongos , Mutação , Neoplasias/genética
8.
Cancer Res ; 82(12): 2298-2312, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35472075

RESUMO

Identifying colorectal cancer patient populations responsive to chemotherapy or chemoradiation therapy before surgery remains a challenge. Recently validated mouse protocols for organoid irradiation employ the single hit multi-target (SHMT) algorithm, which yields a single value, the D0, as a measure of inherent tissue radiosensitivity. Here, we translate these protocols to human tissue to evaluate radioresponsiveness of patient-derived organoids (PDO) generated from normal human intestines and rectal tumors of patients undergoing neoadjuvant therapy. While PDOs from adenomas with a logarithmically expanded Lgr5+ intestinal stem cell population retain the radioresistant phenotype of normal colorectal PDOs, malignant transformation yields PDOs from a large patient subpopulation displaying marked radiosensitivity due to reduced homologous recombination-mediated DNA repair. A proof-of-principle pilot clinical trial demonstrated that rectal cancer patient responses to neoadjuvant chemoradiation, including complete response, correlate closely with their PDO D0 values. Overall, upon transformation to colorectal adenocarcinoma, broad radiation sensitivity occurs in a large subset of patients that can be identified using SHMT analysis of PDO radiation responses. SIGNIFICANCE: Analysis of inherent tissue radiosensitivity of patient-derived organoids may provide a readout predictive of neoadjuvant therapy response to radiation in rectal cancer, potentially allowing pretreatment stratification of patients likely to benefit from this approach.


Assuntos
Neoplasias Colorretais , Neoplasias Retais , Animais , Transformação Celular Neoplásica , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/radioterapia , Humanos , Camundongos , Organoides/patologia , Tolerância a Radiação , Neoplasias Retais/patologia , Reto/patologia
9.
Mar Drugs ; 20(3)2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35323500

RESUMO

Hematopoietic damage is a serious side effect of cytotoxic drugs, and agents promoting hematopoiesis are quite important for decreasing the death rate in cancer patients. In our previous work, we prepared the simulated digestive product of fucoidan from Sargassum fusiforme, DSFF, and found that DSFF could activate macrophages. However, more investigations are needed to further evaluate whether DSFF could promote hematopoiesis in the chemotherapy process. In this study, the protective effect of DSFF (1.8-7.2 mg/kg, i.p.) on cyclophosphamide-induced hematopoietic damage in mice and the underlying mechanisms were investigated. Our results show that DSFF could restore the numbers of white blood cells, neutrophils, and platelets in the peripheral blood, and could also retard bone marrow cell decrease in mice with cyclophosphamide-induced hematopoietic damage. UPLC/Q-Extraction Orbitrap/MS/MS-based lipidomics results reveal 16 potential lipid biomarkers in a serum that responded to hematopoietic damage in mice. Among them, PC (20:1/14:0) and SM (18:0/22:0) were the key lipid molecules through which DSFF exerted protective actions. In a validation experiment, DSFF (6.25-100 µg/mL) could also promote K562 cell proliferation and differentiation in vitro. The current findings indicated that DSFF could affect the blood cells and bone marrow cells in vivo and thus showed good potential and application value in alleviating the hematopoietic damage caused by cyclophosphamide.


Assuntos
Ciclofosfamida/toxicidade , Hematopoese/efeitos dos fármacos , Agonistas Mieloablativos/toxicidade , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Sargassum , Animais , Biomarcadores/sangue , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Proliferação de Células/efeitos dos fármacos , DNA/metabolismo , Humanos , Células K562 , Contagem de Leucócitos , Lipidômica , Camundongos , Neutrófilos/efeitos dos fármacos , Contagem de Plaquetas
10.
Int J Gen Med ; 14: 8509-8519, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34824547

RESUMO

OBJECTIVE: To evaluate the powers of European Heart Surgery Risk Assessment System II (EuroSCORE II) and the Society of Thoracic Surgeons (STS) score in predicting in-hospital and medium-term mortality of patients undergoing coronary artery bypass grafting (CABG). METHODS: Totally 1628 Chinese patients were included between January 2000 and January 2018. Their perioperative clinical data were collected and the patients were closely followed up. According to the length of follow-up time, the total cohort was divided into 1-year, 2-year, 3-year, 4-year and 5-year groups. The in-hospital and medium-term risk prediction of EuroSCORE II and STS score were comparatively assessed by calibration, discrimination, decision curve analysis (DCA), net reclassification index (NRI), integrated discrimination improvement (IDI) and Bland-Altman analysis. RESULTS: About 36 (2.21%) patients died during hospitalization. Both EuroSCORE II and STS score performed extremely well in predicting in-hospital mortality (area under curve = 0.900 and 0.879, respectively). However, calibration and discrimination analyses showed gradual decrease when these two risk evaluation systems were used to predict mortality during the follow-up period. At the same time, the predictive ability of EuroSCORE II was better than STS score. DCA curves showed that the performances of the two evaluation systems were roughly equal between the threshold probability of 0% to 20%. The percentage of correct reclassification of EuroSCORE II was 21.64% higher than that of STS score in predicting 2-year postoperative mortality. The IDI index showed that the predictive capabilities of these two systems were roughly equivalent. Bland-Altman analysis showed no significant difference between the values of the two systems. CONCLUSION: EuroSCORE II and STS score have excellent predictive powers in predicting in-hospital mortality of patients undergoing CABG. In particular, EuroSCORE II is superior in calibration and discrimination. The prediction efficiency of the two risk evaluation systems is still acceptable for two-year postoperative mortality, but decreases year by year.

11.
Int J Gen Med ; 14: 2541-2551, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34163222

RESUMO

BACKGROUND: Cardiac troponin T (cTnT) is currently one of the important indicators for clinical diagnosis of myocardial injury, which is inevitable in cardiac surgery, especially coronary artery bypass grafting (CABG). Describing the release profile of cTnT and finding out the risk factors of postoperative myocardial injury (PMI) are of great significance. The purposes of this study are to explore the release profile of cTnT in patients undergoing CABG and to search for independent risk factors of PMI. METHODS: In this retrospective study, clinical data of CABG patients were collected. The cTnT was measured at 24 hours before and 6, 12, 24, 48, 72, 96 and 120 hours after operation separately. The release profiles and peak time of cTnT in total cohort and sub-cohorts were observed. Independent risk factors of PMI were explored via univariate and multivariate logistic regression analyses. RESULTS: In total, 2084 patients were enrolled, including 998 patients in a cTnT group and 1086 patients in a high-sensitive cTnT (hs-cTnT) group. PMI was recognized in 797 patients. In both groups, cTnT showed a trend of rising first and then falling within 120 hours after operation. The peak cTnT appeared within 12-24 hours after operation, while the peak hs-cTnT occurred mostly within 24-48 hours after operation. Univariate logistic analysis showed that body mass index (BMI), New York Heart Association (NYHA) classification, coronary artery disease (CAD) classification, cerebrovascular disease, left ventricular ejection fraction, number of diseased vessels, valvular disease, intra-aortic balloon pump (IABP) implantation, chronic obstructive pulmonary disease, pulmonary hypertension, previous percutaneous coronary intervention (PCI), BMI, bypass graft number, cardiopulmonary bypass, and preoperative cTnT were related risk factors. Multivariate logistic regression analysis showed that NYHA classification, CAD classification, valvular disease, IABP implantation, pulmonary hypertension, previous PCI, bypass graft number, cardiopulmonary bypass, and preoperative cTnT were independent risk factors of PMI. CONCLUSION: NYHA classification, CAD classification, valvular disease, IABP implantation, pulmonary hypertension, previous PCI, bypass graft number, cardiopulmonary bypass, and preoperative cTnT are independent risk factors of PMI in patients undergoing CABG.

12.
Mar Drugs ; 19(4)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805423

RESUMO

Plant volatile organic compounds (VOCs) represent a relatively wide class of secondary metabolites. The VOC profiles of seven seaweeds (Grateloupia filicina, Polysiphonia senticulosa, Callithamnion corymbosum, Sargassum thunbergii, Dictyota dichotoma, Enteromorpha prolifera and Ulva lactuca) from the Yellow Sea of China were investigated using multifiber headspace solid phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME/GC-MS), among them, the VOCs of three red algae Grateloupia filicina, Polysiphonia senticulosa, and Callithamnion corymbosum were first reported. Principal component analysis (PCA) was used to disclose characteristic categories and molecules of VOCs and network pharmacology was performed to predict potential biomedical utilization of candidate seaweeds. Aldehyde was found to be the most abundant VOC category in the present study and (E)-ß-ionone was the only compound found to exist in all seven seaweeds. The chemical diversity of aldehydes in E. prolifera suggest its potential application in chemotaxonomy and hinted that divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) fiber is more suitable for aldehyde extraction. VOCs in D. dichotoma were characterized as sesquiterpenes and diterpenes and the most relevant pharmacological pathway was the neuroactive ligand-receptor interaction pathway, which suggests that D. dichotoma may have certain preventive and therapeutic values in cancer, especially in lung cancer, in addition to neuropsychiatric diseases.


Assuntos
Aldeídos/isolamento & purificação , Diterpenos/farmacologia , Rodófitas/metabolismo , Alga Marinha/metabolismo , Compostos Orgânicos Voláteis/isolamento & purificação , Aldeídos/farmacologia , Animais , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Fármacos do Sistema Nervoso Central/isolamento & purificação , Fármacos do Sistema Nervoso Central/farmacologia , Diterpenos/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Metabolismo Secundário , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Microextração em Fase Sólida , Compostos Orgânicos Voláteis/farmacologia , Volatilização
13.
Clin Cancer Res ; 26(13): 3239-3247, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32444418

RESUMO

PURPOSE: Genomic methods can identify homologous recombination deficiency (HRD). Rigorous evaluation of their outcome association to DNA damage response-targeted therapies like platinum in pancreatic ductal adenocarcinoma (PDAC) is essential in maximizing therapeutic outcome. EXPERIMENTAL DESIGN: We evaluated progression-free survival (PFS) and overall survival (OS) of patients with advanced-stage PDAC, who had both germline- and somatic-targeted gene sequencing. Homologous recombination gene mutations (HRm) were evaluated: BRCA1, BRCA2, PALB2, ATM, BAP1, BARD1, BLM, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, RAD50, RAD51, RAD51C, and RTEL1 HRm status was grouped as: (i) germline versus somatic; (ii) core (BRCAs and PALB2) versus non-core (other HRm); and (iii) monoallelic versus biallelic. Genomic instability was compared using large-scale state transition, signature 3, and tumor mutation burden. RESULTS: Among 262 patients, 50 (19%) had HRD (15% germline and 4% somatic). Both groups were analyzed together due to lack of difference in their genomic instability and outcome. Median [95% confidence interval (CI)] follow-up was 21.9 (1.4-57.0) months. Median OS and PFS were 15.5 (14.6-19) and 7 (6.1-8.1) months, respectively. Patients with HRD had improved PFS compared with no HRD when treated with first-line (1L) platinum [HR, 0.44 (95% CI: 0.29-0.67); P < 0.01], but not with 1L-non-platinum. Multivariate analysis showed HRD patients had improved OS regardless of their first-line treatment, but most had platinum exposure during their course. Biallelic HRm (11%) and core HRm (12%) had higher genomic instability, which translated to improved PFS on first-line platinum (1L-platinum) versus 1L-non-platinum. CONCLUSIONS: Pathogenic HRm identifies HRD in patients with PDAC with the best outcome when treated with 1L-platinum. Biallelic HRm and core HRm further enriched benefit from 1L-platinum from HRD.


Assuntos
Biomarcadores Tumorais , Genômica , Recombinação Homóloga , Neoplasias Pancreáticas/genética , Idoso , Gerenciamento Clínico , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genômica/métodos , Mutação em Linhagem Germinativa , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Prognóstico , Neoplasias Pancreáticas
14.
Int J Mol Sci ; 20(20)2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31618976

RESUMO

Non-alcoholic fatty liver disease (NAFLD) can progress from steatosis to non-alcoholic steatohepatitis (NASH) characterized by liver inflammation, possibly leading to cirrhosis and hepatocellular carcinoma (HCC). Mice with impaired macrophage activation, when fed a high-fat diet, develop severe NASH. Evidence is mounting that Kupffer cells are implicated. However, it is unknown whether the resident CD68+ or bone marrow-derived CD11b+ Kupffer cells are involved. Characterization of the FSP1cre-Pparb/d-/- mouse liver revealed that FSP1 is expressed in CD11b+ Kupffer cells. Although these cells only constitute a minute fraction of the liver cell population, Pparb/d deletion in these cells led to remarkable hepatic phenotypic changes. We report that a higher lipid content was present in postnatal day 2 (P2) FSP1cre-Pparb/d-/- livers, which diminished after weaning. Quantification of total lipids and triglycerides revealed that P2 and week 4 of age FSP1cre-Pparb/d-/- livers have higher levels of both. qPCR analysis also showed upregulation of genes involved in fatty acid ß-oxidation, and fatty acid and triglyceride synthesis pathways. This result is further supported by western blot analysis of proteins in these pathways. Hence, we propose that FSP1cre-Pparb/d-/- mice, which accumulate lipids in their liver in early life, may represent a useful animal model to study juvenile NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , PPAR beta/genética , Proteína A4 de Ligação a Cálcio da Família S100/genética , Animais , Biomarcadores , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Hepatócitos/metabolismo , Espaço Intracelular/metabolismo , Células de Kupffer/metabolismo , Metabolismo dos Lipídeos , Camundongos , Camundongos Transgênicos , Modelos Biológicos , Oxirredução , PPAR beta/metabolismo , Proteína A4 de Ligação a Cálcio da Família S100/metabolismo
15.
Ann Hepatol ; 18(6): 825-832, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31548167

RESUMO

INTRODUCTION AND OBJECTIVES: Liver fibrosis is a major characteristic of most chronic liver diseases which leads to accumulation of extracellular matrix (ECM) proteins. Hedgehog (Hh) pathway activated by Gli genes participated in the pathogenesis of liver fibrosis. However, the regulatory role of miR-125b in liver fibrosis via targeting Gli genes remains unknown. MATERIALS AND METHODS: RT-qPCR and western blot were employed to the expression levels of mRNA and protein, respectively. The fibrosis level of liver tissue was determined by Masson's trichrome staining. The interaction between miR-125b and Gli3 was tested by luciferase reporter assay. In addition, LX2 cells were activated and CCl4-induced rat model was used in this study. RESULTS: miR-125b was significantly declined in serum samples of the clinical liver fibrosis patient, activated LX2 cells and the liver tissues of the CCl4-induced rat model. Furthermore, in cellular level, the alpha-smooth muscle actin (α-SMA) and Albumin expressions were ascending and descending in LX2 cells, respectively, with the decline of miR-125b. However, when transfecting with miR-125b mimic, the expressions of α-SMA and Albumin was reversed and Gli3 expression was notably repressed in LX2 cells. The target interaction between miR-125b and Gli3 was determined by dual-luciferase assays. It was further discovered that the changes of α-SMA, Albumin, and Gli3 were similar to the expression trend in LX2 cells with miR-125b mimic transfection. CONCLUSION: These results suggested that miR-125b might be protective against liver fibrosis via regulating Gli3 and it might be a promising target in the development of novel therapies to treat pathological fibrotic disorders.


Assuntos
Cirrose Hepática Experimental/genética , Cirrose Hepática/genética , MicroRNAs/genética , Proteínas do Tecido Nervoso/genética , Proteína Gli3 com Dedos de Zinco/genética , Actinas/genética , Actinas/metabolismo , Albuminas/metabolismo , Animais , Tetracloreto de Carbono/toxicidade , Estudos de Casos e Controles , Células HEK293 , Humanos , Técnicas In Vitro , Cirrose Hepática/metabolismo , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/metabolismo , Cirrose Hepática Experimental/patologia , Masculino , MicroRNAs/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células THP-1 , Proteína Gli3 com Dedos de Zinco/metabolismo
16.
Int J Mol Sci ; 19(7)2018 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-29954129

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a major health issue in developed countries. Although usually associated with obesity, NAFLD is also diagnosed in individuals with low body mass index (BMI) values, especially in Asia. NAFLD can progress from steatosis to non-alcoholic steatohepatitis (NASH), which is characterized by liver damage and inflammation, leading to cirrhosis and hepatocellular carcinoma (HCC). NAFLD development can be induced by lipid metabolism alterations; imbalances of pro- and anti-inflammatory molecules; and changes in various other factors, such as gut nutrient-derived signals and adipokines. Obesity-related metabolic disorders may be improved by activation of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)ß/δ, which is involved in metabolic processes and other functions. This review is focused on research findings related to PPARß/δ-mediated regulation of hepatic lipid and glucose metabolism and NAFLD development. It also discusses the potential use of pharmacological PPARß/δ activation for NAFLD treatment.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , PPAR delta/metabolismo , PPAR beta/metabolismo , Animais , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , PPAR delta/uso terapêutico , PPAR beta/uso terapêutico
17.
Oncogene ; 37(15): 2067-2078, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29367760

RESUMO

Tumor stroma has an active role in the initiation, growth, and propagation of many tumor types by secreting growth factors and modulating redox status of the microenvironment. Although PPARß/δ in fibroblasts was shown to modulate oxidative stress in the wound microenvironment, there has been no evidence of a similar effect in the tumor stroma. Here, we present evidence of oxidative stress modulation by intestinal stromal PPARß/δ, using a FSPCre-Pparb/d-/- mouse model and validated it with immortalized cell lines. The FSPCre-Pparb/d-/- mice developed fewer intestinal polyps and survived longer when compared with Pparb/dfl/fl mice. The pre-treatment of FSPCre-Pparb/d-/- and Pparb/dfl/fl with antioxidant N-acetyl-cysteine prior DSS-induced tumorigenesis resulted in lower tumor load. Gene expression analyses implicated an altered oxidative stress processes. Indeed, the FSPCre-Pparb/d-/- intestinal tumors have reduced oxidative stress than Pparb/dfl/fl tumors. Similarly, the colorectal cancer cells and human colon epithelial cells also experienced lower oxidative stress when co-cultured with fibroblasts depleted of PPARß/δ expression. Therefore, our results establish a role for fibroblast PPARß/δ in epithelial-mesenchymal communication for ROS homeostasis.


Assuntos
Antioxidantes/metabolismo , Fibroblastos/metabolismo , PPAR delta/genética , PPAR beta/genética , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/farmacologia , Carga Tumoral/efeitos dos fármacos , Animais , Células Cultivadas , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Técnicas de Silenciamento de Genes , Células HCT116 , Células HT29 , Humanos , Camundongos , Camundongos Knockout , Carga Tumoral/genética
18.
Sci Rep ; 6: 36937, 2016 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-27853235

RESUMO

Nuclear receptor PPARγ has been proven to affect metabolism in multiple tissues, and has received considerable attention for its involvement in colon cancer and inflammatory disease. However, its role in intestinal metabolism has been largely ignored. To investigate this potential aspect of PPARγ function, we submitted intestinal epithelium-specific PPARγ knockout mice (iePPARγKO) to a two-week period of 25% caloric restriction (CR), following which iePPARγKO mice retained more fat than their wild type littermates. In attempting to explain this discrepancy, we analysed the liver, skeletal muscle, intestinal lipid trafficking, and the microbiome, none of which appeared to contribute to the adiposity phenotype. Interestingly, under conditions of CR, iePPARγKO mice failed to activate their sympathetic nervous system (SNS) and increase CR-specific locomotor activity. These KO mice also manifested a defective control of their body temperature, which was overly reduced. Furthermore, the white adipose tissue of iePPARγKO CR mice showed lower levels of both hormone-sensitive lipase, and its phosphorylated form. This would result from impaired SNS signalling and possibly cause reduced lipolysis. We conclude that intestinal epithelium PPARγ plays an essential role in increasing SNS activity under CR conditions, thereby contributing to energy mobilization during metabolically stressful episodes.


Assuntos
PPAR gama/metabolismo , Sistema Nervoso Simpático/metabolismo , Tecido Adiposo Branco/metabolismo , Adiposidade/fisiologia , Animais , Restrição Calórica/métodos , Mucosa Intestinal/metabolismo , Lipólise/fisiologia , Fígado/metabolismo , Locomoção/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Esquelético/metabolismo
19.
Pediatrics ; 125(4): e899-905, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20211946

RESUMO

OBJECTIVE: The goal was to determine whether the components of low lung function in adulthood were associated with low birth weight in a Chinese population. METHODS: A retrospective cohort study was conducted from December 1995 to August 1996. A total of 627 men and women who were born between 1948 and 1954 were recruited; lung function indices were tested and respiratory diseases were examined in the Peking Union Medical College Hospital. Information on variables was recorded, and multivariate analysis of variance was performed to evaluate associations. RESULTS: Significant associations were observed between birth weight and forced expiratory volume in 1 second (FEV(1)), forced vital capacity (FVC), and peak expiratory flow (PEF) in adulthood, after adjustment for maternal age, gestational week, offspring's gender, birth height, history of dyspnea and asthma, lung diseases before 16 years of age, lung diseases after measles and pneumonia before 16 years of age, cough with sputum within 2 years, current asthma, taking medicine for asthma, adult BMI, male alcohol consumption, and male smoking (P < .001). Linear trends between birth weight and FEV(1), FVC, and PEF were noted (P < .001, 1-way analysis of variance); FEV(1), FVC, and PEF values increased with increasing birth weight. Low birth weight was associated with the FEV(1)/FVC predictive value (P < .05), but there was no linear trend (P > .05). CONCLUSIONS: Low birth weight may increase the prevalence of and risk for low lung function in adulthood in the Chinese population. The development of lung function may be affected by hypogenesis in utero.


Assuntos
Recém-Nascido de Baixo Peso/fisiologia , Pneumopatias/epidemiologia , Pneumopatias/fisiopatologia , Pulmão/fisiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adulto , China/epidemiologia , Estudos de Coortes , Feminino , Seguimentos , Volume Expiratório Forçado/fisiologia , Humanos , Recém-Nascido , Pneumopatias/etiologia , Masculino , Pessoa de Meia-Idade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Testes de Função Respiratória/tendências , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
20.
Biomed Environ Sci ; 22(4): 340-4, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19950530

RESUMO

OBJECTIVE: To study the prevalence of different types of neural tube defects (NTDs) in Luliang Prefecture, Shanxi province, where the prevalence of NTDs is unusually high and the correlation between NTDs prevalence and patterns. METHODS: A surveillance population-based birth defects was performed in Luliang Prefecture, Shanxi province. RESULTS: The results of our study showed that the prevalence of NTDs was 2-fold higher in Luliang Prefecture than in other areas of Shanxi province. Unusual patterns of NTDs were found, however, multiple NTDs were relatively common in Luliang Prefecture, accounting for over 13% of all NTDs cases in China. CONCLUSION: The prevalence of NTDs is associated with its patterns.


Assuntos
Defeitos do Tubo Neural/epidemiologia , Pré-Escolar , China/epidemiologia , Humanos , Lactente , Recém-Nascido , Defeitos do Tubo Neural/classificação , Fatores de Risco
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