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1.
Phytomedicine ; 80: 153398, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33130474

RESUMO

BACKGROUND: Celastrol, a pentacyclic triterpenoid quinonemethide isolated from several spp. of Celastraceae family, exhibits anti-inflammatory activities in a variety of diseases including arthritis. PURPOSE: This study aims to investigate whether the inhibition of NLRP3 inflammasome is engaged in the anti-inflammatory activities of celastrol and delineate the underlying mechanism. METHODS: The influence of celastrol on NLRP3 inflammasome activation was firstly studied in lipopolysaccharide (LPS)-primed mouse bone marrow-derived macrophages (BMDMs) and phorbol 12-myristate 13-acetate (PMA)-primed THP-1 cells treated with nigericin. Reconstituted inflammasome was also established by co-transfecting NLRP3, ASC, pro-caspase-1 and pro-IL-1ß in HEK293T cells. The changes of inflammasome components including NLRP3, ASC, pro-caspase-1/caspase-1 and pro-IL-1ß/IL-1ß were examined by enzyme-linked immunosorbent assay (ELISA), western blotting and immunofluorescence. Furthermore, Propionibacterium acnes (P. acnes)/LPS-induced liver injury and monosodium urate (MSU)-induced gouty arthritis in mice were employed in vivo to validate the inhibitory effect of celastrol on NLRP3 inflammasome. RESULTS: Celastrol significantly suppressed the cleavage of pro-caspase-1 and pro-IL-1ß, while not affecting the protein expressions of NLRP3, ASC, pro-caspase-1 and pro-IL-1ß in THP-1 cells, BMDMs and HEK293T cells. Celastrol suppressed NLRP3 inflammasome activation and alleviated P. acnes/LPS-induced liver damage and MSU-induced gouty arthritis. Mechanism study revealed that celastrol could interdict K63 deubiquitination of NLRP3, which may concern interaction of celastrol and BRCA1/BRCA2-containing complex subunit 3 (BRCC3), and thereby prohibited the formation of NLRP3, ASC and pro-caspase-1 complex to block the generation of mature IL-1ß. CONCLUSION: Celastrol suppresses NLRP3 inflammasome activation in P. acnes/LPS-induced liver damage and MSU-induced gouty arthritis via inhibiting K63 deubiquitination of NLRP3, which presents a novel insight into inhibition of celastrol on NLRP3 inflammasome and provides more evidences for its application in the therapy of inflammation-related diseases.

2.
J Hazard Mater ; 401: 123266, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-32763673

RESUMO

Thousands of hazardous compounds that contaminate foods and feeds pose potential risks for human and animal health. However, it remains a challenge to perform a fast monitoring for safety surveillance. Herein we report a novel approach, integrated data-dependent and data-independent acquisition (DDIA) method, to efficiently screen for hundreds of chemicals in a single run using ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap). This method was successfully applied to analyze 180 veterinary drugs in milk, 220 pesticides in tomato and 50 mycotoxins in maize, respectively. Compared with the widely used approaches of data-dependent acquisition (DDA) or data-independent acquisition (DIA), the obtained results indicate that DDIA-based method combines the advantages of both DDA and DIA, since it achieves higher reproducibility of identification, lower false results for targeted compounds. Notably, the advantage of DDIA approach is that it enables better date retroactivity for untargeted compounds, such as metabolites and decomposition products. With the improvement in high-resolution mass spectrometry (HRMS) as well as data-mining techniques, we believe that DDIA data acquisition approach based on LC-HRMS will be widely applied in various fields in the near future, especially in compound screening and omics field, such as metabolomics and proteomics.

3.
Spectrochim Acta A Mol Biomol Spectrosc ; 245: 118886, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32920442

RESUMO

Hydrogen sulfide (H2S) is a very important third endogenously generated gaseous signaling molecule and plays a key role in physiological and pathological regulation processes of living biosystems. Although a lot of H2S fluorescent probes have been reported, the relationship between the physiology and pathology of H2S in inflamed tissues remains unclear. Herein, by adopting a donor-π-acceptor (D-π-A)-structured naphthalimide derivative as the two-photon (TP) fluorophore and a 4-dinitrobenzene-ether (DNB) with a strong intramolecular charge transfer (ICT) effect as the recognition moiety, we reported a novel TP bioimaging probe NP-H2S for H2S with improved sensitivity. The NP-H2S exhibits very low background fluorescence in the absence of H2S, and a significant 258-fold fluorescence intensity enhancement was observed in the presence of H2S, resulting in a high sensitivity and selectivity to H2S in aqueous solutions with a detection limit of 18.8 nM observed. The probe also shows a wide linear response concentration range (0-10.0 µM) to H2S with high selectivity. All these features are favorable for direct monitoring of H2S in complex biological samples. It was then applied for direct TP imaging of H2S in tissues of inflammation model with satisfactory sensitivity, indicating it has the latent capability in further biological applications for investigation of the interaction H2S with inflammation.

4.
J Ethnopharmacol ; 265: 113302, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32860893

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Laminaria japonica, a brown seaweed, has been used in Traditional Chinese Medicine (TCM) to treat a variety of diseases including lung cancer. AIM OF THE STUDY: To demonstrate the effects of Fucoxanthin (FX), a major active component extracted from Laminaria japonica on metastasis and Gefitinib (Gef) sensitivity in human lung cancer cells both in vitro and in vivo. MATERIALS AND METHODS: Invasion and migration of lung cancer cells were detected using the wound healing assay and transwell assay. Epithelial-to-mesenchymal transition (EMT) factors and PI3K/AKT/NF-κB pathways were analyzed by western blotting. RNA interference (RNAi) technology was used to silence TIMP-2 gene expression in A549 cells. The anti-metastatic effect of FX was evaluated in vivo in an experimental lung metastatic tumor model. On the other hand, cell counting kit-8 assay was used to study the cell viability of human lung cancer PC9 cells and Gef resistant PC9 cells (PC9/G) after Gef, FX or FX combined with Gef treatment. PC9 xenograft model was established to explore the anti-tumor effect of FX or combined with Gef. Immunohistochemistry staining assay and immunofluorescence staining assay were used to reveal the effects of FX on lung cancer cell proliferation and apoptosis. RESULTS: FX was able to significantly inhibit lung cancer cells migration and invasion in vitro. FX suppressed the expressions of Snail, Twist, Fibronectin, N-cadherin, MMP-2, PI3K, p-AKT and NF-κB, and increased the expression of TIMP-2. Furthermore, knockdown of TIMP-2 attenuated FX-mediated invasion inhibition. Additionally, we demonstrated that FX inhibited lung cancer cells metastasis in vivo. The anti-metastatic effects of FX on lung cancer cells might be attributed to inhibition of EMT and PI3K/AKT/NF-κB pathway. We further demonstrated that the anti-tumor activity of FX was not only limited to the drug sensitive cell lines, but also prominent on lung cancer cells with Gef resistant phenotype. Furthermore, in vivo xenograft assay confirmed that FX inhibited tumor growth and enhanced the sensitivity of lung cancer cells to Gef and this effect may be due to inhibition of tumor cell proliferation and activation of apoptosis. CONCLUSION: Collectively, our findings suggested that FX suppresses metastasis of lung cancer cells and overcomes EGFR TKIs resistance. Thus, FX is worthy of further investigation as a drug candidate for the treatment of lung cancer.

5.
J Formos Med Assoc ; 120(1 Pt 1): 78-82, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32682701

RESUMO

Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection with SARS-CoV may cause coronary plaque instability and lead to acute coronary syndrome (ACS). Management of ACS in patients with COVID-19 needs more consideration of the balance between clinical benefit and transmission risk of virus. This review provides recommendations of management strategies for ACS in patients with suspected or confirmed COVID-19 in Taiwan.

6.
IEEE Trans Image Process ; 30: 264-276, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32870793

RESUMO

Rectilinear face recognition models suffer from severe performance degradation when applied to fisheye images captured by 360° back-to-back dual fisheye cameras. We propose a novel face rectification method to combat the effect of fisheye image distortion on face recognition. The method consists of a classification network and a restoration network specifically designed to handle the non-linear property of fisheye projection. The classification network classifies an input fisheye image according to its distortion level. The restoration network takes a distorted image as input and restores the rectilinear geometric structure of the face. The performance of the proposed method is tested on an end-to-end face recognition system constructed by integrating the proposed rectification method with a conventional rectilinear face recognition system. The face verification accuracy of the integrated system is 99.18% when tested on images in the synthetic Labeled Faces in the Wild (LFW) dataset and 95.70% for images in a real image dataset, resulting in an average accuracy improvement of 6.57% over the conventional face recognition system. For face identification, the average improvement over the conventional face recognition system is 4.51%.

7.
Food Chem ; 337: 127767, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32799162

RESUMO

Egg yolks are a good source of folates. However, the method for analyzing the naturally occurring folates in egg yolks is complicated and time-consuming. In this study, a simplified pre-treatment method followed by validated HPLC-MS/MS was developed to determine native folates in eggs from laying hens treated with different amounts of folic acid. The modified enhanced matrix removal -lipid method to purify samples showed good performance in lipid elimination, reduction of steps and time savings. According to experimental analysis, yolks contained total folate amounts ranging from 147 to 760 µg/100 g when laying hens' diet was supplemented with folic acid from 0 to 10 mg/kg. Four folate vitamers were detected in egg yolks: 5-methyltetrahydrofolate accounted for 91-98% of total folates, whereas folic acid, 5-formyltetrahydrofolate and 10-formylfolic acid together accounted for 2-9%. Therefore, laying hens efficiently converted folic acid in feed into 5-methyltetrahydrofolate in eggs with little folic acid deposition.


Assuntos
Cromatografia Líquida de Alta Pressão , Gema de Ovo/química , Ácido Fólico/análise , Lipídeos/química , Espectrometria de Massas em Tandem , Animais , Galinhas , Suplementos Nutricionais , Feminino , Ácido Fólico/isolamento & purificação , Extração em Fase Sólida , Tetra-Hidrofolatos/análise
8.
J Colloid Interface Sci ; 582(Pt B): 598-609, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32911408

RESUMO

A convenient and efficient method to fabricate isolated Fe single-atom catalysts deposited on Myriophyllum aquaticum-based biochar (ISA-Fe/MC) is reported for peroxymonosulfate-based organics degradation. Firstly, the Fe nanoparticles anchored on the hierarchical porous biochar (nano-Fe/MC) can be obtained by utilizing K2FeO4 as a synchronous activation and graphitization agent. Subsequently, ISA-Fe/MC was achieved by HCl etching of nano-Fe/MC to remove the excess Fe nanoparticles. Compared with nano-Fe/MC, ISA-Fe/MC demonstrated outperformed catalytic capacity towards PMS activation for phenol degradation. The combination of super high surface area, hierarchical porous structure, graphitization structure and atomically dispersed Fe species should be responsible for prominent catalytic oxidation ability and outstanding resistance to common anions and humic acid. Based on the chemical scavengers, EPR experiments and electrochemistry tests, the SO4•- dominated radical degradation pathway for nano-Fe/MC and electron transfer reigned non-radical degradation pathway for ISA-Fe/MC was revealed. In contrast to nano-Fe/MC, density functional theory calculations demonstrated the enhanced density of states around Fermi level in ISA-Fe/MC meaning the increased catalytic performance and more electron transfer between single-atom Fe to adjacent graphitic C and N which could serve as electron transfer channel for PMS activation.

9.
J Environ Manage ; 277: 111382, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33069143

RESUMO

The efficiency, accuracy and universality of ecological assessment methods comprise an important foundation for comprehensive assessment and restoration of large river ecological health at the watershed scale. New evaluation metrics and methods are urgently needed to be developed to adapt the characteristics of large rivers, including geographical differences in surface runoff, regional ecological complexity, and seasonal changes. In this study, a bacteria-weighted index of biotic integrity was developed to assess the ecological health of large rivers (lrBW-IBI) based on compositional and functional characteristics of sediment bacterial communities from 33 sections of the lower mainstream of Yangtze River. Five key metrics were determined by range, responsiveness, and redundancy tests. Principal component analysis (PCA), entropy method, criteria importance through intercriteria correlation and random forest were applied to calculate weighted coefficients of key metrics. The optimal lrBW-IBI was observed through the sum of PCA weighted-metrics: the relative abundance of Latescibacteria (0.234), Gemmatimonadaceae (0.149), Nitrospira spp. (0.234), Rhizobiales (0.228), and nitrogenase NifH (0.156). According to PCA based lrBW-IBI, 12.12%, 24.24%, 39.39%, and 24.24% of river sections were labeled excellent, good, moderate, and relatively poor, respectively. The ecological status of the lower mainstream of the Yangtze River did not change significantly across seasons but declined gradually from upstream to downstream. This study provides a new assessment tool for the ecological health of large rivers and highlights the importance of microbial ecological index in river ecology.


Assuntos
Monitoramento Ambiental , Rios , Bactérias , China , Ecossistema , Análise de Componente Principal , Estações do Ano
10.
BMC Pharmacol Toxicol ; 21(1): 74, 2020 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-33129351

RESUMO

BACKGROUND: Cigarette smoking is a critical risk factor for the destruction of lung parenchyma or the development of emphysema, which is characteristic of COPD. Disruption of epithelial layer integrity may contribute to lung injury following cigarette smoke extract (CSE) exposure. Tiotropium/olodaterol acts as a bronchodilator for COPD treatment; however, the effect of dual bronchodilators on epithelial cell injury and its underlying mechanism remain unclear. In this study, we evaluated the effect of tiotropium/olodaterol on CSE-mediated cell death and the underlying mechanisms. METHODS: Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis, necrosis, and autophagy were evaluated using flow cytometry. Autophagy-related protein, phosphorylated ERK, expression was determined using Western blotting. RESULTS: Tiotropium/olodaterol significantly inhibited CSE-induced cell death, mitochondria dysfunction, and autophagy, which had no significant effect on apoptosis or necrosis in BEAS-2B human bronchial epithelial cells. Moreover, tiotropium/olodaterol attenuated CSE-induced upregulation of JNK. CONCLUSIONS: CSE induced cell death and caused consistent patterns of autophagy and JNK activation in BEAS-2B human bronchial epithelial cells. Tiotropium/olodaterol treatment protected bronchial epithelial cells from CSE-induced injury and inhibited activation of autophagy and upregulation of JNK phosphorylation. These results indicate that tiotropium/olodaterol may protect epithelial cells from the deleterious effects of CSE exposure, which is associated with the regulation of autophagy and JNK activation.

11.
Environ Res ; : 110371, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33130168

RESUMO

Once in aquatic ecosystems, plastics can be easily colonized by diverse microbes, and these microbial communities on plastics-the 'plastisphere'-often differ from the communities in the surrounding water and other substrates. However, our knowledge of plastic-associated bacterial and fungal communities on diverse plastics in freshwater is poor, especially for fungal communities. Furthermore, intraspecies interactions among bacterial and fungal communities colonized on diverse plastics are poorly known. Here, we characterized the taxonomic composition and diversity of bacteria and fungi on three types of plastics in a lab-scale incubator with freshwater from an urban river. High-throughput sequencing revealed that the alpha diversity of bacterial communities was higher on polyethylene microplastics (MPs) than on polyethylene (PE) and polypropylene (PP) sheets. The structure of bacterial communities on MPs differed from those on plastic sheets. In contrast, no striking differences in alpha diversity and taxonomic composition were observed for fungal communities on different types of plastics. Members of Ascomycota, Basidiomycota, Blastocladiomycota and Mucoromycota dominated fungal assemblages on plastics. Co-occurrence network analysis revealed that the biotic interactions between bacteria and fungi on MPs were less complex than those on PE and PP sheets. The three types of plastics shared no keystone taxa. The functional profiles (KEGG) predicted by Tax4Fun showed that the pathways of alanine, aspartate, glutamate and biotin metabolism were enriched in biofilms on MPs. Nonetheless, the higher complexity of plastic sheet-associated biofilms might make them more resistant to environmental perturbation and facilitate the maintenance of microbial activities.

12.
Sci China Life Sci ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33141302

RESUMO

Interferon regulatory factors (IRFs) play pivotal and critical roles in innate and adaptive immune responses; thus, precise and stringent regulation of the stability and activation of IRFs in physiological processes is necessary. The stability and activities of IRFs are directly or indirectly targeted by endogenous and exogenous proteins in an ubiquitin-dependent manner. However, few reviews have summarized how host E3 ligases/DUBs or viral proteins regulate IRF stability and activity. Additionally, with recent technological developments, details about the ubiquitination of IRFs have been continuously revealed. As knowledge of how these proteins function and interact with IRFs may facilitate a better understanding of the regulation of IRFs in immune responses or other biological processes, we summarized current studies on the direct ubiquitination of IRFs, with an emphasis on how these proteins interact with IRFs and affect their activities, which may provide exciting targets for drug development by regulating the functions of specific E3 ligases.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33165800

RESUMO

Various retroviral and lentiviral vectors have been used for up-the-teat intraductal injection to deliver markers, oncogenes, and other genes into mammary epithelial cells in mice. These methods along with the large number of genetically engineered mouse lines have greatly helped us learn normal breast development and tumorigenesis. Rats are also valuable models for studying human breast development and cancer. However, genetically engineered rats are still uncommon, and previous reports of intraductal injection of retroviral vectors into rats appear to be inefficient in generating mammary tumors. Here, we report, and describe the method for, stably introducing marker genes and oncogenes into mammary glands in rats using intraductal injection of commonly used lentiviral vectors. This method can infect mammary epithelial cells efficiently, and the infected cells can initiate tumorigenesis, including estrogen receptor-positive and hormone-dependent tumors, which are the most common subtype of human breast cancer but are yet still difficult to model in mice. This technique provides another tool for studying formation, prevention, and treatment of breast cancer, especially estrogen receptor-positive breast cancer.

14.
Dig Dis Sci ; 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33159272

RESUMO

BACKGROUND: Duodenal Crohn's disease (CD) is rare and may present with obstructive symptoms, and few reports have focused on endoscopic balloon dilation (EBD) for duodenal CD-associated strictures. AIMS: To evaluate the efficacy and safety of EBD for duodenal CD-associated strictures. METHODS: Patients with duodenal CD-associated strictures who underwent EBD were recruited. The clinical date, stricture characteristics, number of EBDs, dilation diameter, complications, surgical interventions, and follow-up periods were recorded. Patients were also divided into a serial dilation group and a nonserial dilation group to analyze the efficacy and safety of serial EBD for duodenal strictures. RESULTS: A total of 54 patients with duodenal CD-associated strictures underwent a total of 153 dilations. Technical success was achieved in 98.69% (151/153) of cases. The short-term efficacy at 1 month and 2 months was 100%. At a median follow-up period of 223 days (range 30-866), 11 patients underwent surgery, and the total clinical efficacy was 79.63% (43/54). No difference in the safety or efficacy was noted between the serial dilation group and the nonserial dilation group. The median surgery-free survival of 507 days (range 170-857) and the median recurrence-free survival of 215 days (range 30-866) in the serial dilation group were significantly longer than those in the nonserial dilation group (185.5 days (range 73-275) and 124 days (range 30-699), respectively). CONCLUSIONS: EBD is a safe and effective treatment for duodenal CD-associated strictures. Serial dilations could delay recurrence and surgical intervention but did not change the long-term outcome or prevent surgery.

15.
Ann Thorac Surg ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33159863

RESUMO

Angiomatoid fibrous histiocytoma is a peculiar borderline neoplasm with indolent behavior, predominantly arising in the superficial area of extremities. We recently encountered a unique case of asymptomatic angiomatoid fibrous histiocytoma presenting on the chest wall and being adjacent to the parietal pleura, which has not yet been reported previously to our knowledge, expanding the spectrum of anatomical sites in which angiomatoid fibrous histiocytoma would occur.

16.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(5): 573-577, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33131509

RESUMO

Objective To investigate the expression levels of miRNA132 in patients with the first-episode major depressive disorder(MDD) and in chronic unpredictable mild stress(CUMS)rats.Methods Forty-one first-episode MDD patients(MDD group)were recruited from the outpatient departments of Hangzhou Seventh People's Hospital between March 2017 and May 2018,and 31 healthy volunteers(control group)were recruited.The patients' severity of symptoms was assessed with HAMD17.In addition,24 male SD rats were equally assigned into control group and CUMS group.The depression-like behaviors of rats was detected by sucrose preference test and forced swimming test.Plasma corticosterone levels of rats were assayed by ELISA.The expression levels of miRNA132 in the blood or prefrontal cortex were detected by quantitative real-time PCR.Results The expression level of miRNA132 in peripheral blood was significantly higher in MDD group(2.37±0.36)than in control group(1.34±0.16)(t=2.355,P=0.0213),and there was a positive correlation between miRNA132 levels and the HAMD17 score in MDD group(P=0.0004,rs=0.5303,n=41).The immobility time of CUMS group [(72.67±2.95)s] was significantly longer than that of control group [(40.00±5.49)s] in forced swim test(t=2.366,P=0.0395).The sucrose intake of CUMS group [(55.67±6.42)%] was significantly lower than that of control group [(98.21±1.28)%] in sucrose preference test(t=6.502,P<0.0001).The plasma corticosterone level in CUMS group [(1396.0±254.9)nmol/L] was significantly higher than that of control group [(557.3±158.4)nmol/L](t=2.795,P=0.0190).The miRNA132 levels in blood(2.32±0.88)and prefrontal cortex(2.80±0.76)of CUMS rats were significantly higher than those [1.18±0.36(t=2.273,P=0.0463)and 0.99±0.23(t=2.553,P=0.0287),respectively] of control group.Conclusions The expression trend of miRNA132 in peripheral blood is consistent between MDD patients and CUMS rats.In CUMS rats,the expression of miRNA132 in blood is also consistent with that in prefrontal cortex.The expression of miRNA132 in blood may reflect the change trend of miRNA132 expression in prefrontal cortex.

17.
Biochem Pharmacol ; : 114313, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33137324

RESUMO

Variability in P-glycoprotein (P-gp) efflux transporting activity was supposed to be involved in altered intestinal absorption and bioavailability of clopidogrel in patients; however, reliable evidence is still lacking. In this study, we sought to determine whether P-gp could play an important role in the metabolic activation of and platelet response to clopidogrel in mice. Abcb1a/1b knock-out (KO) and wild-type (WT) mice were used to evaluate differences in the intracellular accumulation of clopidogrel in the intestine, liver, and brain tissues and in systemic exposure of clopidogrel and its main metabolites as well as the mechanisms involved. Results indicated that, compared with WT mice, KO mice exhibited an 84% increase in systemic exposure of clopidogrel active thiol metabolite H4 and a 14.5% rise of suppression of ADP-induced platelet integrin αIIbß3 activation, paralleled by a 41% decrease in systemic exposure of clopidogrel due to enhanced systemic clearance. Furthermore, KO mice displayed a 45% increase in Cyp3a11 but a 23% decrease in Ces1 at their protein levels compared with WT mice. Concurrently, intracellular clopidogrel concentrations in the tissues examined did not differ significantly between KO and WT mice. We conclude that although P-gp does not transport clopidogrel and its major metabolites in mice, P-gp-deficient mice exhibit elevated formation of the active metabolite H4 and enhanced antiplatelet effect of clopidogrel through up-regulation of Cyp3a11 and down-regulation of Ces1, suggesting that P-gp activity may correlate inversely with the formation of H4 and antiplatelet efficacy of clopidogrel in clinical settings due to P-gp and CYP3A4 interplay.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33138695

RESUMO

The urgent demand for transplanted organs has motivated the development of regenerative medicine to biomimetically reconstruct the structure and function of natural tissues or organs. The prerequisites for constructing multicellular organs include specific cell sources, suitable scaffolding material, and interconnective bio-functional interfaces. As some of the most complex systems in nature, human organs, tissues, and cellular units have unique "bio-matrix" physicochemical interfaces. Human tissues support a large number of cells with distinct bio-functional interfaces for compartmentalization related to metabolism, material exchange, and physical barriers. These naturally shaped bio-functional interfaces support critical metabolic functions that drive adaptive human behavior. In contrast, mutations and disorders during organogenesis can disrupt these interfaces as a consequence of disease and trauma. To replicate the appropriate structure and physiological function of tissues and organs, the biomaterials used in these approaches should have properties that mimic those of natural bio-functional interfaces. In this review, the focus is on the biomimetic design of functional interfaces and hierarchical structures for four regenerative organs, liver, kidney, lung, heart and the immune system. Research on these organs provides understanding of cell-matrix interactions for hierarchically-bioinspired materials engineering, and guidance for the design of bioartificial organs. Finally, we provide perspectives on future challenges in bio-functional interface designs and discuss the obstacles that remain toward the generation of functional bioartificial organs.

19.
Nat Commun ; 11(1): 5519, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33139738

RESUMO

Lithium garnets have been widely studied as promising electrolytes that could enable the next-generation all-solid-state lithium batteries. However, upon exposure to atmospheric moisture and carbon dioxide, insulating lithium carbonate forms on the surface and deteriorates the interfaces within electrodes. Here, we report a scalable solid sintering method, defined by lithium donor reaction that allows for complete decarbonation of Li6.4La3Zr1.4Ta0.6O12 (LLZTO) and yields an active LiCoO2 layer for each garnet particle. The obtained LiCoO2 coated garnets composite is stable against air without any Li2CO3. Once working in a solid-state lithium battery, the LiCoO2-LLZTO@LiCoO2 composite cathode maintains 81% of the initial capacity after 180 cycles at 0.1 C. Eliminating CO2 evolution above 4.0 V is confirmed experimentally after transforming Li2CO3 into LiCoO2. These results indicate that Li2CO3 is no longer an obstacle, but a trigger of the intimate solid-solid interface. This strategy has been extended to develop a series of LLZTO@active layer materials.

20.
Br J Pharmacol ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33140842

RESUMO

BACKGROUND AND PURPOSE: Pulmonary veno-occlusive disease (PVOD) is a rare disease characterized by the obstruction of small pulmonary veins leading to pulmonary hypertension. However, the mechanisms underlying pulmonary vessel occlusion remain largely unclear. EXPERIMENTAL APPROACH: A mitomycin C (MMC)-induced PVOD rat model was used as in vivo animal model; and primarily cultured rat pulmonary microvascular endothelial cells (PMVECs) were used as in vitro cell model. RESULTS: Our data suggested an endothelial-to-mesenchymal transition (EndoMT) may be present in the pulmonary microvessels isolated from either PVOD patients or MMC-induced PVOD rats. In compare to the control vessels, vessels from both PVOD patients and PVOD rats represented co-localized staining of specific endothelial marker von Willebrand factor (vWF) and mesenchymal marker α-smooth muscle actin (α-SMA), suggesting the presence of cells that co-express endothelial and mesenchymal markers. Then, in both the lung tissues of MMC-induced PVOD rats and MMC-treated rat PMVECs, decreased levels of endothelial markers (e.g. VE-cadherin, CD31) and increased mesenchymal markers (e.g. Vimentin, Fibronectin, α-SMA) were detected, also indicating EndoMT. Moreover, MMC induced activation of the TGFß/Smad3/Snail axis, while blockage of this pathway with either specific Smad3 inhibitor (SIS3) or small interfering RNA (siRNA) against Smad3, both dramatically abolished the MMC-induced EndoMT. Notably, treatment with SIS3 remarkably prevented the pathogenesis of MMC-induced PVOD in rats. CONCLUSIONS: Our data indicated that targeted inhibition of Smad3 leads to a potential, novel strategy for PVOD therapy, likely by inhibiting the EndoMT in pulmonary microvasculature.

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