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1.
J Transl Med ; 22(1): 98, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263117

RESUMO

BACKGROUND: Interindividual variation characterizes the relief experienced by constipation-predominant irritable bowel syndrome (IBS-C) patients following linaclotide treatment. Complex bidirectional interactions occur between the gut microbiota and various clinical drugs. To date, no established evidence has elucidated the interactions between the gut microbiota and linaclotide. We aimed to explore the impact of linaclotide on the gut microbiota and identify critical bacterial genera that might participate in linaclotide efficacy. METHODS: IBS-C patients were administered a daily linaclotide dose of 290 µg over six weeks, and their symptoms were then recorded during a four-week posttreatment observational period. Pre- and posttreatment fecal samples were collected for 16S rRNA sequencing to assess alterations in the gut microbiota composition. Additionally, targeted metabolomics analysis was performed for the measurement of short-chain fatty acid (SCFA) concentrations. RESULTS: Approximately 43.3% of patients met the FDA responder endpoint after taking linaclotide for 6 weeks, and 85% of patients reported some relief from abdominal pain and constipation. Linaclotide considerably modified the gut microbiome and SCFA metabolism. Notably, the higher efficacy of linaclotide was associated with enrichment of the Blautia genus, and the abundance of Blautia after linaclotide treatment was higher than that in healthy volunteers. Intriguingly, a positive correlation was found for the Blautia abundance and SCFA concentrations with improvements in clinical symptoms among IBS-C patients. CONCLUSION: The gut microbiota, especially the genus Blautia, may serve as a significant predictive microbe for symptom relief in IBS-C patients receiving linaclotide treatment. TRIAL REGISTRATION: This trial was registered with the Chinese Clinical Trial Registry (Chictr.org.cn, ChiCTR1900027934).


Assuntos
Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Peptídeos , Humanos , Estudos Prospectivos , RNA Ribossômico 16S , Constipação Intestinal
2.
Dig Dis Sci ; 68(2): 521-528, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36383269

RESUMO

BACKGROUND: Functional dyspepsia (FD) is characterized with multiple symptoms of indigestion and often accompanied with anxiety. However, there is currently an absence of effective treatment. Tandospirone is commonly used to treat generalized anxiety disorders. Whether tandospirone can improve the clinical symptoms of FD remain unknown. AIMS: The present study was designed to explore the pharmacological effect of tandospirone on FD patient with anxiety, and the potential mechanisms were also elucidated. METHODS: FD patients with anxiety were randomly divided into placebo and tandospirone treatment groups. Healthy volunteers were simultaneously recruited as control group. The gastrointestinal symptom score (GIS) and Hamilton anxiety scale (HAM-A) were performed before and after treatments with placebo or tandospirone. The serum levels of brain-derived neurotrophic factor (BDNF) and multiple inflammatory cytokines including tumor necrosis factor-α (TNF-α), and interleukin (IL)-6, IL-4, IL-1ß, and IL-10 were determined. Regression analyses relating BDNF levels and gastrointestinal symptoms were performed. RESULTS: Tandospirone significantly alleviated the gastrointestinal and anxiety symptoms of FD patient, as evidenced by reductions of GIS index and HAM-A scores. Compared with the healthy volunteers, FD patients had lower BDNF and IL-10 levels, but higher levels of IL-6 and TNF-α. Importantly, tandospirone increased serum BDNF and IL-10 and decreased IL-6 levels in FD patients. Relative analysis revealed that BDNF level was negatively associated with gastrointestinal symptoms in FD patients. CONCLUSION: Tandospirone effectively improved both anxiety and gastrointestinal symptoms of patients with FD, and these therapeutic effects may be associated with the modulation of BDNF and inflammatory cytokines.


Assuntos
Dispepsia , Humanos , Dispepsia/diagnóstico , Interleucina-10 , Fator Neurotrófico Derivado do Encéfalo/uso terapêutico , Interleucina-6 , Fator de Necrose Tumoral alfa , Ansiedade , Resultado do Tratamento , Transtornos de Ansiedade/complicações , Citocinas
3.
Environ Toxicol ; 38(11): 2595-2607, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37466184

RESUMO

BACKGROUND: Exosomes are applied as biomarkers in several diseases according to their disease-specific profiles. However, the exosomes effects in functional dyspepsia (FD) are still fragmentary. Here we examined the role of Eosinophil and mast cell derived-exosomes in FD progression. METHODS: Fifty FD subjects and age- and sex-matched healthy controls were included in this retrospective cohort study. Duodenal mucosa and gastric juice were collected to analyze molecular difference. Eosinophil and mast cell were evaluated by immunofluorescence and microarray was subjected to examine the expression levels of NEAT1, miR-211-5p, and glial cell line-derived neurotrophic factor (GDNF), which were subsequently were tested by quantitative reverse transcription PCR (RT-qPCR) validation cohorts. CCK-8 assays, and wound healing assays were used to evaluate integrity of intestinal mucosal barrier in vitro. Rats' weights and gastric emptying rates were used as evaluation of FD severity in vivo. RESULTS: Eosinophil and mast cell were enriched and secreted more exosomes in duodenal mucosa of FD patients. We identified differential lncRNAs that were consistently and significantly up regulated in FD cases. Of these, NEAT1 was further validated by RT-qPCR and had closely relationship with GDNF. MiR-211-5p level was found to be reduced in FD and negatively related with NEAT1 and GDNF. Furthermore, NEAT1and GDNF relived FD while miR-211-5p made symptoms worse. The NEAT1/miR-211-5p/GDNF axis had a good predictive ability for FD. CONCLUSIONS: The NEAT1/miR-211-5p/GDNF could be a potential FD biomarker.


Assuntos
Exossomos , MicroRNAs , RNA Longo não Codificante , Humanos , Ratos , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Estudos Retrospectivos , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Eosinófilos , Mastócitos/metabolismo , Exossomos/genética , Duodeno/metabolismo , Mucosa Intestinal/metabolismo , RNA Longo não Codificante/metabolismo
4.
Angew Chem Int Ed Engl ; 56(29): 8459-8463, 2017 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-28471042

RESUMO

There is a strong desire to design and synthesize catalysts that assemble at the oil-water interface to improve the efficiency of biphasic reactions. Anisotropic dumbbell-shaped bi-component mesoporous carbon-organosilica Janus particles with asymmetric wettability are synthesized through a one-step compartmentalized growth of a mesoporous organosilica sphere attached to a mesoporous resorcinol-formaldehyde (RF) sphere. A library was prepared of tunable Janus particles possessing diverse hollow structures with various functionalities. As a proof of concept, the Janus particle-derived catalyst can assemble at the oil-water interface to stabilize Pickering emulsions. Owing to the increased reaction interface area, the Janus catalyst exhibits a more than three-fold increase in catalytic efficiency compared to the Pt loaded carbon sphere catalyst in aqueous hydrogenation reactions.

5.
Langmuir ; 32(38): 9826-35, 2016 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-27592513

RESUMO

Monodispersed microcapsules for gas capture and sensing were developed consisting of elastic semipermeable polymer shells of tunable size and thickness and pH-sensitive, gas selective liquid cores. The microcapsules were produced using glass capillary microfluidics and continuous on-the-fly photopolymerization. The inner fluid was 5-30 wt % K2CO3 solution with m-cresol purple, the middle fluid was a UV-curable liquid silicon rubber containing 0-2 wt % Dow Corning 749 fluid, and the outer fluid was aqueous solution containing 60-70 wt % glycerol and 0.5-2 wt % stabilizer (poly(vinyl alcohol), Tween 20, or Pluronic F-127). An analytical model was developed and validated for prediction of the morphology of the capsules under osmotic stress based on the shell properties and the osmolarity of the storage and core solutions. The minimum energy density and UV light irradiance needed to achieve complete shell polymerization were 2 J·cm(-2) and 13.8 mW·cm(-2), respectively. After UV exposure, the curing time for capsules containing 0.5 wt % Dow Corning 749 fluid in the middle phase was 30-40 min. The CO2 capture capacity of 30 wt % K2CO3 capsules was 1.6-2 mmol/g depending on the capsule size and shell thickness. A cavitation bubble was observed in the core when the internal water was abruptly removed by capillary suction, whereas a gradual evaporation of internal water led to buckling of the shell. The shell was characterized using TGA, DSC, and FTIR. The shell degradation temperature was 450-460 °C.

6.
J Med Biochem ; 43(2): 250-256, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38699694

RESUMO

Background: To investigate the expression levels and diagnostic value of glial cell line-derived neurotrophic factor (GDNF), carcinoembryonic antigen (CEA) and carbohydrate antigen199 (CA199) in patients with colorectal carcinoma (CRC). Methods: 50 CRC patients at our hospital from Feb. 2020 to Feb. 2021 were chosen as the malignant group, another 50 patients with benign colonic diseases were chosen as the benign group, and 50 healthy people who came to our hospital for physical examination during the same period were considered as the control group. Fasting peripheral venous blood was taken from all research subjects in the morning and tested by a fully-automated electrochemiluminometer to determine the GDNF, CEA and CA199 levels. The sensitivity and specificity of the combined detection of the three indexes for CRC were analyzed, and the receiver operating characteristic (ROC) curve was plotted to record the area under the curve (AUC). Results: The malignant group had remarkably higher CEA and CA199 levels (P<0.001) and a lower GDNF level (P<0.001) when compared with the benign and control groups. The sensitivity, specificity, positive predictive value and negative predictive value of the combined detection were 96.0%, 94.0%, 88.9% and 97.9%, respectively. Under combined detection, AUC (95% CI) = 0.950 (0.909-0.991), standard error = 0.021, and P<0.001. Conclusions: The combined diagnosis of serum GDNF, CEA and CA199 is a reliable method to improve the diagnostic accuracy of CRC, and this strategy can effectively reduce the missed diagnosis rate and has high application value in clinic.

7.
Biomimetics (Basel) ; 8(1)2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36975342

RESUMO

The quadruped robot has a strong motion performance and broad application prospects in practical applications. However, during the movement of the quadruped robot, it is easy to be affected by external disturbance and environmental changes, which makes it unable to achieve the ideal effect movement. Therefore, it is very important for the quadruped robot to adjust actively according to its own state detection. This paper proposes an active state adjustment control method based on its own state, which can realize disturbance recovery and active environment adaptation. Firstly, the controller is designed according to the physical model of the quadruped robot, and the foot forces are optimized using the quadratic program (QP) method. Then, the disturbance compensation method based on dynamic analysis is studied and combined with the controller itself. At the same time, according to the law of biological movement, the movement process of the quadruped robot is actively adjusted according to the different movement environment, so that it can adapt to various complex environments. Finally, it is verified in a simulation environment and quadruped robot prototype. The results show that the quadruped robot has a strong active disturbance recovery ability and active environment adaptability.

8.
Can J Gastroenterol Hepatol ; 2022: 9394381, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36569394

RESUMO

Background: Overexpression of miRNA-211 suppresses the differentiation of bone marrow stem cells into intestinal ganglion cells via downregulation of GDNF, a regulator of intestine barrier function. The study aimed to investigate the interaction between miR-211 and GDNF on intestinal epithelial cells. Methods: The expression levels of miR-211 and GDNF in duodenal biopsy specimens from FD patients and healthy controls were compared. Enteric glia cell (EGCs) cell line transfected with miR-211 mimics and inhibitors were used to clarify the expression levels of GDNF were analyzed by qRT-PCR and ELISA. Intestine epithelial cell (IECs) cell line cultured in medium from ECGs in different transfection conditions were used in wound healing assay, cell proliferation assay, and western blotting for evaluation of p38 MAPK phosphorylation level. Results: MiR-211 expression was significantly upregulated in the duodenal tissue of patients with FD compared to healthy subjects, whereas GDNF expression was significantly downregulated (both p < 0.05). Transfection with miR-211 mimics significantly decreased GDNF mRNA expression and protein secretion (p < 0.001). An inhibited intestinal epithelial cell wound healing (p < 0.05) and increased expression levels of phosphorylated p38 MAPK (p < 0.05) were found in IECs cultured with medium from EGCs transfected with miR-211 mimics. Conclusions: MiR-211 may downregulates GDNF mRNA and protein expression via activation of the pp38 MAPK signaling pathway. Targeting miR-211 or the MAPK pathway may be a potential intervention for FD.


Assuntos
Dispepsia , MicroRNAs , Humanos , Regulação para Baixo , Dispepsia/genética , Dispepsia/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Fosforilação
9.
J Imaging ; 8(7)2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35877643

RESUMO

Cell migration is essential for physiological, pathological and biomedical processes such as, in embryogenesis, wound healing, immune response, cancer metastasis, tumour invasion and inflammation. In light of this, quantifying mechanical properties during the process of cell migration is of great interest in experimental sciences, yet few theoretical approaches in this direction have been studied. In this work, we propose a theoretical and computational approach based on the optimal control of geometric partial differential equations to estimate cell membrane forces associated with cell polarisation during migration. Specifically, cell membrane forces are inferred or estimated by fitting a mathematical model to a sequence of images, allowing us to capture dynamics of the cell migration. Our approach offers a robust and accurate framework to compute geometric mechanical membrane forces associated with cell polarisation during migration and also yields geometric information of independent interest, we illustrate one such example that involves quantifying cell proliferation levels which are associated with cell division, cell fusion or cell death.

10.
ACS Biomater Sci Eng ; 8(10): 4092-4109, 2022 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-34494831

RESUMO

Porous inorganic materials play an important role in adsorbing targeted analytes and supporting efficient reactions in analytical science. The detection performance relies on the structural properties of porous materials, considering the tunable pore size, shape, connectivity, etc. Herein, we first clarify the enhancement mechanisms of porous materials for bioanalysis, concerning the detection sensitivity and selectivity. The diagnostic applications of porous material-assisted platforms by coupling with various analytical techniques, including electrochemical sensing, optical spectrometry, and mass spectrometry, etc., are then reviewed. We foresee that advanced porous materials will bring far-reaching implications in bioanalysis toward real-case applications, especially as diagnostic assays in clinical settings.


Assuntos
Porosidade , Ensaios Enzimáticos , Técnicas Eletroquímicas
11.
Cyborg Bionic Syst ; 2022: 9816495, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36285308

RESUMO

In this paper, a parallel quadrupedal robot was designed that is capable of versatile dynamic locomotion and perception-less terrain adaptation. Firstly, a quadrupedal robot with a symmetric legs and a powerful actuator was implemented for highly dynamic movement. Then, a fast and reliable method based on generalized least square was proposed for estimating the terrain parameters by fusing the body, leg, and contact information. On the basis of virtual model control (VMC) with the quadratic program (QP) method, the optimal foot force for terrain adaptation was achieved. Finally, the results obtained by simulation and indoor and outdoor experiments demonstrate that the robot can achieve a robust and versatile dynamic locomotion on uneven terrain, and the rejection of disturbances is reliable, which proves the effectiveness and robustness of this proposed method.

12.
BJPsych Open ; 8(4): e138, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35880308

RESUMO

BACKGROUND: Early COVID-19 research suggests a detrimental impact of the initial lockdown on young people's mental health. AIMS: We investigated mental health among university students and young adults after the first UK lockdown and changes in symptoms over 6 months. METHOD: In total, 895 university students and 547 young adults not in higher education completed an online survey at T1 (July-September 2020). A subset of 201 university students also completed a 6 month follow-up survey at T2 (January-March 2021). Anxiety, depression, insomnia, substance misuse and suicide risk were assessed. RESULTS: At T1, approximately 40%, 25% and 33% of the participants reported moderate to severe anxiety and depression and substance misuse risk, clinically significant insomnia and suicidal risk. In participants reassessed at T2, reductions were observed in anxiety and depression but not in insomnia, substance misuse or suicidality. Student and non-student participants reported similar levels of mental health symptoms. Student status was not a significant marker of mental health symptoms, except for lower substance misuse risk.Cross-sectionally, greater symptoms across measures were consistently associated with younger age, pre-existing mental health conditions, being a carer, worse financial status, increased sleep irregularity and difficulty since lockdown. Longitudinally, T2 symptoms were consistently associated with worse financial status and increased difficulty sleeping at T1. However, these associations were attenuated when baseline mental health symptoms were adjusted for in the models. CONCLUSIONS: Mental health symptoms were prevalent in a large proportion of young people after the first UK lockdown. Risk factors identified may help characterise high-risk groups for enhanced support and inform interventions.

13.
Medicine (Baltimore) ; 100(20): e26045, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011117

RESUMO

OBJECTIVE: The effect of Helicobacter pylori (H pylori) eradication therapy in functional dyspepsia (FD) patients was inconsistent in previously published randomized controlled trials. Therefore, we performed a comprehensive protocol for systematic review and meta-analysis in order to assess whether H pylori eradication therapy benefits patients with FD. METHODS: In this systematic review and meta-analysis, we will search Web of Science, Embase, PubMed, Wanfang Data, Medline, Science Direct, Cochrane Library through April, 2021. The protocol was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. Data extraction was performed independently and only randomized clinical trials were included in this study. The risk of bias assessment was performed using the tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions. All calculations were carried out with Stata 11.0 (The Cochrane Collaboration, Oxford, United Kingdom). RESULTS: We hypothesized that H pylori eradication therapy compared to no eradication therapy has a statistically significant benefit for symptom relief and can also reduce the development of peptic ulcer disease. CONCLUSION: This study expects to provide credible and scientific evidence for the efficacy of H pylori eradication therapy for patients with FD. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/4EHRB.


Assuntos
Dispepsia/prevenção & controle , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Dispepsia/microbiologia , Infecções por Helicobacter/complicações , Humanos , Metanálise como Assunto
14.
Bioresour Technol ; 319: 124238, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33254461

RESUMO

Lignin is the renewable and abundant source of aromatics on earth, and the depolymerization of lignin provides significant potential for producing valuable monophenols. In this work, catalytic hydrogenolysis of organosolv poplar lignin (OPL) in ethanol/isopropanol solvent over monometallic and bimetallic nonprecious catalysts was investigated. Ni/C and a series of NiCu/C catalyst with different Cu loadings were prepared and applied for depolymerization of OPL. The highest yield of phenolic monomers was 63.4 wt% achieved over the Ni10Cu5/C catalyst at 270 °C without external H2. The introduction of Cu in catalysts further promoted the hydrogen donor process of ethanol/isopropanol solvent and facilitated the cleavage of lignin linkages, resulting in the decreased molecular weight of bio-oil. The possible lignin dimer type structures, such as diphenylethane (ß-1) type, phenylcoumaran (ß-5) type, and pinoresinol (ß-ß) type structures, were proposed and identified by MALDI-TOF MS, giving a better understanding of the NiCu/C catalyzed lignin depolymerization.


Assuntos
2-Propanol , Níquel , Catálise , Carvão Vegetal , Cobre , Etanol , Lignina
15.
J Mater Chem B ; 9(6): 1521-1535, 2021 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-33474559

RESUMO

The locoregional recurrence of breast cancer after tumor resection represents several clinical challenges, and conventional post-surgical adjuvant therapeutics always bring about significant systemic side effects. Thus, the local therapy strategy has received considerable interest in breast cancer treatment, and hydrogels can function as ideal platforms due to their remarkable properties such as good biocompatibility, biodegradability, flexibility, and multifunctionality. The nano-hydrogel composites can further incorporate the advantages of nanomaterials into the hydrogel system, to fabricate hierarchical structures for stimulating controlled multi-stage release of different therapeutic agents and improving the synergistic effects of combination therapy. In this review, the problems of clinical treatments of breast cancer and properties of hydrogels in current biomedical applications are briefly overviewed. The focus is on recent advances in local therapy based on nano-hydrogel composites for both monotherapy (chemotherapy, photothermal and photodynamic therapy) and combination therapy (dual chemotherapy, photothermal chemotherapy, photothermal immunotherapy, radio-chemotherapy). Moreover, the challenges and perspectives in the development of advanced nano-hydrogel systems are also discussed.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Hidrogéis/química , Nanocompostos/química , Animais , Feminino , Humanos , Tamanho da Partícula , Propriedades de Superfície
16.
ACS Omega ; 5(38): 24684-24692, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33015485

RESUMO

Gas explosions are destructive disasters in coal mines. Coal mine gas is a multi-component gas mixture, with methane (CH4) being the dominant constituent. Understanding the process and mechanism of mine gas explosions is of critical importance to the safety of mining operations. In this work, three flammable gases (CO, C2H6, and H2) which are commonly present in coal mines were selected to explore how they affect a methane explosion. The explosion characteristics of the flammable gases were investigated in a 20 L spherical closed vessel. Experiments on binary- (CH4/CO, CH4/C2H6, and CH4/H2) and multicomponent (CH4/CO/C2H6/H2) mixtures indicated that the explosion of such mixtures is more dangerous and destructive than that of methane alone in air, as measured by the explosion pressure. Furthermore, a self-promoting microcirculation reaction network is proposed to help analyze the chemical reactions involved in the multicomponent (CH4/CO/C2H6/H2) gas explosion. This work will contribute to a better understanding of the explosion mechanism of gas mixtures in coal mines and provide a useful reference for determining the safety limits in practice.

17.
ACS Biomater Sci Eng ; 6(7): 3994-4004, 2020 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-33463342

RESUMO

The extracellular matrix (ECM) stiffening is an important sign of local microenvironment change, which is considered as a hallmark of many diseases including hepatocellular carcinoma (HCC). The fates of both cancer cells and immune cells can be regulated by mechanical feedbacks acquired from ECM, but there is a lack of a precise study of mechanical feedback modes in different cell phenotypes following with the progressively increasing ECM stiffness. Herein, we used a biopolymeric film without further modification of adhesive molecules, as a natural local niche to mimic a gradually stiffening manner from HCC onset in liver cirrhosis to its metastasis in the spinal cord. Three distinct manners of mechanical feedbacks were found: the gradual manner in HCC cell spreading, migration and early apoptosis to oxaliplatin, the stepwise manner in HCC cell adhesion, proliferation, focal adhesion (FA) formation, drug resistance, and macrophage M1 polarization; the specific manner in the stages of the progression of epithelial-mesenchymal transition at different stiffness ranges. Further investigation of molecular mechanisms confirmed those mechanical feedback manners by signaling activation of FA kinase, phosphatidylinositol 3-kinase, and expression of pro-/antiapoptotic and pro-/anti-inflammatory genes. Our results pave a novel avenue to know about mechanical feedbacks from ECM, which could be used for future cancer studies and in vitro drug screening applications.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomimética , Carcinoma Hepatocelular/genética , Retroalimentação , Humanos , Neoplasias Hepáticas/genética , Macrófagos , Fenótipo , Microambiente Tumoral
18.
ACS Appl Mater Interfaces ; 11(16): 14660-14671, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30973698

RESUMO

Cancer progression is regulated by multiple factors of extracellular matrix (ECM). Understanding how cancer cells integrate multiple signaling pathways to achieve specific behaviors remains a challenge because of the lack of appropriate models to copresent and modulate ECM properties. Here we proposed a strategy to build a thin biomaterial matrix by poly(l-lysine) and hyaluronan as an artificial stiffness-tunable ECM. Transforming growth factor-beta 1 (TGF-ß1) was used as a biochemical cue to present in an immobilized and spatially controlled manner, with a high loading efficiency of 90%. Either soft matrix with immobilized TGF-ß1 (i-TGF) or bare stiff matrix could only promote HCC cells to form the epithelial phenotype, whereas stiff matrix with i-TGF was the only condition to induce the mesenchymal phenotype. Further investigation revealed that i-TGF increased the specific TGF-ß1 receptor (TßRI) expression to activate PI3K pathway. i-TGF-TßRI interactions also promoted HCC cell adhesion to enlarge contact area for stiffness sensing, resulting in the raising expression of the mechano-sensor (ß1 integrin). Mechanotransduction would then be enhanced by the ß1 integrin/vinculin/p-FAK pathway, leading to a noble PI3K activation. Using our model, a novel mechanism was discovered to elucidate regulation of cell fates by coupling mechanotransduction and biochemical signaling.


Assuntos
Carcinoma Hepatocelular , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Matriz Extracelular/química , Neoplasias Hepáticas , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1 , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Proteínas de Neoplasias/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fator de Crescimento Transformador beta1/química , Fator de Crescimento Transformador beta1/farmacologia
19.
Bioresour Technol ; 255: 39-49, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29414171

RESUMO

A novel framework, integrating dynamic simulation (DS), life cycle assessment (LCA) and techno-economic assessment (TEA) of a bioelectrochemical system (BES), has been developed to study for the first time wastewater treatment by removal of chemical oxygen demand (COD) by oxidation in anode and thereby harvesting electron and proton for carbon dioxide reduction reaction or reuse to produce products in cathode. Increases in initial COD and applied potential increase COD removal and production (in this case formic acid) rates. DS correlations are used in LCA and TEA for holistic performance analyses. The cost of production of HCOOH is €0.015-0.005 g-1 for its production rate of 0.094-0.26 kg yr-1 and a COD removal rate of 0.038-0.106 kg yr-1. The life cycle (LC) benefits by avoiding fossil-based formic acid production (93%) and electricity for wastewater treatment (12%) outweigh LC costs of operation and assemblage of BES (-5%), giving a net 61MJkg-1 HCOOH saving.


Assuntos
Análise da Demanda Biológica de Oxigênio , Formiatos , Águas Residuárias , Fontes de Energia Bioelétrica , Eletricidade , Eletrodos
20.
Zhonghua Gan Zang Bing Za Zhi ; 15(3): 204-8, 2007 Mar.
Artigo em Zh | MEDLINE | ID: mdl-17407712

RESUMO

OBJECTIVE: To study the preventive effects of Lycium barbarum polysaccharide (LBP) on the development of alcoholic fatty liver (AFL) in rats and its possible mechanisms. METHODS: One hundred twenty-five Wistar rats were randomly divided into 4 groups: a blank control group, with distilled water intragastric infusion (GI); an alcohol group, with alcohol GI; a 5% LBP plus alcohol GI group; and a 10% LBP plus alcohol GI group. Liver pathologic changes were studied together with the activity of serum ALT, AST, GGT, the activity of liver SOD, GSH-PX and the content of liver MDA, GSH, H2O2; CYP2E1 gene and protein expressions were also detected. RESULTS: At the end of ten weeks, the activity of serum AST [(132.3+/-25.7) U/L, (127.5+/-29.1)U/L] and GGT [(1.9+/-0.5)U/L, (1.8+/-0.7)U/L] of the two LBP groups were all significantly lower than those of the alcohol group [serum AST (245.7+/-32.1) and GGT (4.4+/-0.6)]. At the end of ten weeks, the content of liver MDA [(5.1+/-0.3) nmol/mg, (5.1+/-0.4) nmol/mg] and H2O2 [(135.4+/-23.5) mmol/g, (132.6+/-31.8) mmol/g] of the two LBP groups were significantly lower than those of the alcohol group [MDA (14.5+/-3.2) nmol/mgprot) and H2O2 (328.5+/-45.6)]. The activity of SOD [(206.7+/-13.2)U/L, (203.2+/-18.8)U/L], GSH-PX [(13.5+/-1.4)U/mg/min, (13.6+/-1.5)U/mg/min] and the content of GSH [(65.1+/-11.0)mg/g, (66.6+/-11.1) mg/g] of the two LBP groups were all significantly higher than those of the alcohol group [SOD (116.5+/-13.6)U/mg/min, GSH-PX (7.2+/-1.6)U/mg/min and the content of GSH (30.5+/-10.7)mg/g] (P less than 0.01). At the end of five weeks, levels of CYP2E1 gene and protein expression of the two LBP groups were 0.39+/-0.04, 0.40+/-0.06 and 3.49+/-0.36, 3.29+/-0.30 respectively. At the end of ten weeks, levels of CYP2E1 gene and protein expression of the two LBP groups were 0.41+/-0.05, 0.42+/-0.08 and 3.58+/-0.30, 3.36+/-0.37 respectively. They were all significantly lower than those of the alcohol group [the gene expression (5 week: 0.74+/-0.05, 10 week: 1.02+/-0.08) and the protein expression (5 week: 5.63+/-0.44, 10 week: 7.90+/-0.26)]. There were no typical alcoholic fatty liver pathologic changes observed in the two LBP groups. CONCLUSION: LBP can effectively prevent AFL. This may be due to its effects in inhibiting the hepatocyte CYP2E1 expression and prevention of lipid peroxidation.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Fígado Gorduroso Alcoólico/tratamento farmacológico , Fitoterapia , Animais , Citocromo P-450 CYP2E1/metabolismo , Fígado Gorduroso Alcoólico/metabolismo , Fígado Gorduroso Alcoólico/prevenção & controle , Peróxido de Hidrogênio , Peroxidação de Lipídeos , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar
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