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1.
J Hazard Mater ; : 127628, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34740506

RESUMO

Herein, we proposed a protocol to track realistic nanoplastics (NPs) by labeling them with an iridium-containing organic molecular agent (denoted as Ir) followed by inductively coupled plasma mass spectroscopy detection, as exemplified by polyethylene terephthalate (PET) NPs prepared from water bottles. The Ir showed satisfactory labeling stability in typical environmental and biological matrices. After 3d's incubation, the leaching ratios were less than 3% in water, phosphate buffered saline, sea water, cell culture medium, artificial gastric juice, artificial intestinal fluid, sediment resuspension, and around 5% in fetal bovine serum. On this basis, in vivo distribution of PET NPs in mice was analyzed. The intravenously injected NPs widely distributed in liver, spleen, lung and kidney. Comparatively, NPs could hardly be detected in these organs after intragastric administration, suggesting that they could not penetrate the intestinal barriers. The temporal and spatial distribution of the NPs in an intertidal zone sediment resuspension model was also investigated. The NPs mostly deposited at the overlying deposit, implying the absorption-driven sinking behavior of NPs with natural organic matters. This work provided an effective way to quantitatively track realistic NPs, which could promote the understanding of the fate and effect of NPs in natural environments and organisms.

2.
Int J Gen Med ; 14: 6477-6485, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675615

RESUMO

Purpose: The aim of this research was to investigate the clinical significance of the expression of flap structure-specific endonuclease 1 (FEN1) in primary osteosarcoma. Methods: The expression of FEN1 was detected by immunohistochemistry analysis. The association of the expression of FEN1 in osteosarcoma with clinicopathological parameters was analyzed by using χ 2 test or Fisher's exact test. Survival analyses were performed by Kaplan-Meier method and Cox proportional hazards regression model. Results: Of the 40 osteosarcoma patients, 19 (47.5%) patients presented with FEN1 high expression, while in the non-neoplastic bone specimens, the FEN1 high expression was observed in 10% (3/30), the positive expression rate in osteosarcoma patients was significantly higher than that of non-neoplastic bone specimens (P< 0.01). Univariate analysis indicated that the progression-free survival (PFS) and overall survival (OS) were correlated with the expression level of FEN1 (PFS, P < 0.001; OS, P = 0.002), Enneking staging (PFS, P = 0.026; OS, P = 0.044) and chemotherapy response (PFS, P = 0.019; OS, P = 0.031). Multivariate analysis demonstrated that FEN1 expression was an independent prognostic factor for the PFS (HR = 4.73, P = 0.002) and OS (HR = 4.01, P = 0.038) of osteosarcoma patients. Conclusion: This study showed that FEN1 was overexpressed in osteosarcoma patients and positively associated with poor prognosis of osteosarcoma patients. Further studies should focus on the relative mechanisms and the targeted FEN1 therapies for osteosarcoma.

3.
Zhongguo Yi Liao Qi Xie Za Zhi ; 45(5): 559-562, 2021 Sep 30.
Artigo em Chinês | MEDLINE | ID: mdl-34628773

RESUMO

This article introduces the safety risks of the novel light-based home-use hair removal device, and analyzes the differences in regulation among China, the United States and the European Union. In China, household intense pulsed light hair removal devices will also be supervised in accordance with medical device regulations. Therefore, the safety standards adopted in the absence of specific regulations are no longer applicable to the new regulatory requirements. It is imperative to adopt the new standards available to home photoepilators, so as to ensure the safety and effectiveness of the approved devices.


Assuntos
Remoção de Cabelo , China , União Europeia , Padrões de Referência , Estados Unidos
4.
Artigo em Inglês | MEDLINE | ID: mdl-34693451

RESUMO

Osteosarcoma (OS), the most common malignant bone tumor with high metastatic potential, frequently affects children and adolescents. Epidermal growth factor receptor (EGFR)-targeted tyrosine kinase inhibitors exhibit encouraging anti-tumor activity for patients with solid tumors, whereas their effects on OS remain controversial. In the present study, we aimed to elucidate the anti-tumor activity of gefitinib for OS, as well as to explore the underlying mechanisms. Gefitinib inhibits cell viability, tumor growth, cell migration, and invasion and promotes cell apoptosis and G1 cycle arrest in OS at a relatively high concentration via suppressing the PI3K/Akt and ERK pathways. However, gefitinib treatment results in the feedback activation of signal transducer and activator of transcription 3 (STAT3) induced by interleukin 6 (IL-6) secretion. Combined treatment with gefitinib and stattic, an inhibitor for STAT3 phosphorylation, engenders more evident inhibitory effects on cell proliferation, migration, and invasion and promotive effects on cell apoptosis and G1 phase arrest in OS, compared with the single exposure to gefitinib or stattic. Western blot analysis demonstrates that stattic treatment in gefitinib-treated OS abrogates the IL-6-induced STAT3 activation and subsequently further restrains the activities of EGFR, Akt, and ERK pathways in tumor cells. This study confirms that the EGFR inhibitor of gefitinib has moderate anti-tumor effects on OS through IL-6 secretion-mediated STAT3 activation. Additional administration of stattic in EGFR-targeted therapies may contribute to improve the efficacy for OS.

5.
J Hazard Mater ; 424(Pt B): 127425, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34634705

RESUMO

Hydrogen peroxide (H2O2) is an important active oxygen species that plays a major role in redox balance and in physiological and pathological processes of various diseases of biological systems. As H2O2 is an endogenous active molecule, fluctuations in H2O2 content are not only affected by the state of biological system itself but also easily affected by Bisphenol A (BPA, a typical estrogenic environmental pollutant) in the external environment. Here, the near-infrared fluorescent probe Cy-NOH2 (λem = 750 nm) as a tool was synthesized to detect fluctuations in H2O2 content in cells and organisms induced by BPA. High sensitivity and excellent selectivity were found when the probe Cy-NOH2 was used to monitor endogenous H2O2 in vitro. In addition, the expression of H2O2 induced by different concentrations of BPA was able to be detected by the probe. Zebrafish and mice models were induced with different concentrations of BPA, and the H2O2 content showed significant increasing trends in zebrafish and livers of mice with increasing BPA concentrations. This study reveals that the probe Cy-NOH2 can be used as an effective tool to monitor the redox state in vivo under the influence of BPA, which provides a basis for clarifying the mechanisms of BPA in a variety of physiological and pathological processes.

7.
Front Pharmacol ; 12: 724923, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34393801

RESUMO

Despite the development of diagnostic and treatment strategies, the survival outcome of patients with osteosarcoma remains poor. Nod-like receptor protein 3 (NLRP3) plays a crucial role in the inflammasome pathway, which is related to the progression of various tumors. However, the effect of NLRP3 on osteosarcoma has not yet been well explored. Our study aimed to investigate the role of NLRP3 in the malignant biological behavior of osteosarcoma as well as its therapeutic value. Immunohistochemistry was applied to investigate the NLRP3 expression in osteosarcoma and osteochondroma specimens. Cell Counting Kit-8, colony formation, wound healing, transwell, and flow cytometry assays were used to explore the contribution of NLRP3 to the proliferation, migration, invasion, apoptosis and cell cycle distribution of osteosarcoma cells in vitro. Western blot was performed to evaluate the expression of NLRP3 and the related proteins in osteosarcoma cell lines after the blockade of NLRP3 using CY-09 and lentivirus intervention. Furthermore, tumor formation assay was used to analyze the effect of NLRP3 on the growth of osteosarcoma in vivo. The results showed that the NLRP3 protein was overexpressed in osteosarcoma, which was independently correlated with the poor prognosis of patients. Moreover, NLRP3 suppression by the inhibitor of CY-09 or lentivirus-induced gene knockdown inhibited the cell proliferation, migration, invasion and promoted the cell apoptosis and G1 cell cycle arrest in osteosarcoma via targeting the inflammasome pathway. Our in vivo results confirmed that the inhibition of NLRP3 suppressed the tumor formation of osteosarcoma. In conclusion, NLRP3 may be regarded as an independent prognostic biomarker and a potential therapeutic target for osteosarcoma.

8.
Free Radic Biol Med ; 172: 578-589, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34242792

RESUMO

Acetaminophen (APAP) is the leading cause of acute liver failure (ALF), which is characterized by GSH depletion, oxidative stress and mitochondrial dysfunction. However, the specific mechanism of APAP-induced ALF remains to be clarified. In this study, we demonstrated that indoleamine 2,3-dioxygenase 1 (IDO1) aggravated APAP-induced ALF associated with excess lipid peroxidation, which was reversed by lipid peroxidation inhibitor (ferrostatin-1). Meanwhile, IDO1 deficiency effectively decreased the accumulation of reactive nitrogen species. Additionally, IDO1 deficiency prevented against APAP-induced liver injury through suppressing the activation of macrophages, thereby reduced their iron uptake and export, eventually reduced iron accumulation in hepatocytes through transferrin and transferrin receptor axis. In summary, our study confirmed that APAP-induced IDO1 aggravated ALF by triggering excess oxidative and nitrative stress and iron accumulation in liver. These results offer new insights for the clinical treatment of ALF or iron-dysregulated liver diseases in the future.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Dioxigenases , Falência Hepática Aguda , Acetaminofen/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Dioxigenases/metabolismo , Hepatócitos , Ferro/metabolismo , Fígado/metabolismo , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo
9.
Analyst ; 146(11): 3500-3509, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-33885074

RESUMO

For periprosthetic joint infection (PJI) patients, an early and rapid detection of methicillin-resistant Staphylococcus aureus (MRSA) in joint synovial fluid is of great significance for receiving timely treatment and avoiding side effects. In clinical practice, the methods for detecting MRSA include the culture-based method and the PCR-based mecA gene detection method with fluorescent readout. However, the culture-based method requires up to 3-7 days for incubation and elaborative screening. The PCR-based molecular diagnosis, due to its high sensitivity, improves the detection time but sacrifices cost and gives false-positive results. Herein, a ligation chain reaction (LCR)-based electrochemical biosensor was developed to detect the mecA of MRSA with the advantages of rapidity, accuracy and low cost. In this system, an integrated dsDNA labeled with thiol and biotin at both terminals is generated only in the presence of the target DNA after LCR, followed by immobilization of the integrated dsDNAs on the bovine serum albumin (BSA)-coated gold electrode, and then the streptavidin horseradish peroxidase (SA-HRPs) is specifically bound to the biotin labels via biotin-streptavidin interaction, generating the catalytic amperometric readout. Impressively, the developed method achieved the detection of rare mecA in the joint synovial fluid of PJI patients (417-666 copies as quantified by qPCR). The proposed electrochemistry-based method is highly convenient for the point-of-care testing and was comparable with PCR in sensitivity, but superior in selectivity (single-base differentiation) and cost (nanomolar DNA probe consumption and simple device), demonstrating its huge potential in clinical applications for MRSA diagnosis.


Assuntos
Técnicas Biossensoriais , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Proteínas de Bactérias/genética , DNA , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Proteínas de Ligação às Penicilinas/genética , Reação em Cadeia da Polimerase em Tempo Real , Infecções Estafilocócicas/diagnóstico , Líquido Sinovial
10.
Sci Rep ; 11(1): 5562, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33692448

RESUMO

Galectin-9 (Gal-9) is a multifunctional immunomodulatory factor highly expressed in RA. This study aimed to investigate the expression of Gal-9 and its correlation with disease activity and therapeutic response in RA patients. Active RA patients were enrolled and treated with tacrolimus (TAC) alone or in combination therapy for 12 weeks in a prospective cohort study. Clinical and immunological parameters were recorded at baseline and week 12. We measured Gal-9 expression in different T cell subsets and in plasma. The disease activity of RA patients decreased after treatment. At baseline, the Gal-9 expression percentage was higher in the group with severe disease than in mild or moderate groups. After treatment, the Gal-9 expression in CD3+, CD4+, CD8+ and CD4-CD8- cell subsets decreased, as well as Gal-9 mean fluorescence intensity in CD3+, CD4+ and CD8+ T cells. Similarly, plasma Gal-9 levels were lower at week 12 than at baseline. Good responders showed significantly lower Gal-9 expression on CD3+ and CD4+ T cell subsets and lower plasma Gal-9 levels than poor responders. Gal-9 expression positively correlates with disease activity in RA patients. Gal-9 can be regarded as a new biomarker for evaluating RA activity and therapeutic effect, including TAC.

11.
Adv Sci (Weinh) ; 8(6): 2003611, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33747742

RESUMO

The Cas13a system has great potential in RNA interference and molecular diagnostic fields. However, lacking guidelines for crRNA design hinders practical applications of the Cas13a system in RNA editing and single nucleotide polymorphism identification. This study posits that crRNAs with hairpin spacers improve the specificity of CRISPR/Cas13a system (termed hs-CRISPR). Gibbs free energy analysis suggests that the hairpin-spacer crRNAs (hs-crRNAs) suppress Cas13a's affinity to off-target RNA. A hepatitis B virus DNA genotyping platform is established to further validate the high-specificity of hs-CRISPR/Cas13a system. Compared to ordinary crRNA, hs-crRNAs increase the specificity by threefold without sacrificing the sensitivity of the CRISPR/Cas13a system. Furthermore, the mechanism of the Cas13a/hs-crRNA/target RNA composition is elucidated with theoretical simulations. This work builds on the fundamental understanding of Cas13a activation and offers significant improvements for the rational design of crRNA for the CRISPR/Cas13a system.

12.
J Mol Histol ; 52(2): 279-288, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33532936

RESUMO

MicroRNA-27a (miR-27a) modulates osteogenic differentiation (OD); however, the mechanism by which it influences osteoclastic activity in the glucocorticoid (GC)-elicited osteoporotic bone is still unclear. Bone marrow was obtained from the proximal femur of patients (n = 3) with a femoral neck fracture and those (n = 3) with steroid-related osteonecrosis of the femoral head (ONFH). GC was applied to an established ONFH cell model from human bone marrow mesenchymal stem cells (hBMSCs). The miR-27a expression profiles were found to be downregulated in ONFH samples and GC-induced hBMSCs using microarray analysis and real-time quantitative polymerase chain reaction, whereas the OD capacity of hBMSCs was significantly reduced in the GC group compared with the control group. Subsequent transfection of an miR-27a mimic in hBMSCs revealed that the OD capacity of cells was remarkably strengthened in the GC group compared with the miR-control group. Bioinformatics software (TargetScan) predicted that phosphoinositide 3-kinase (PI3K) might be a potential miR-27a target, which was indicated by dual-luciferase reporter assay. Compared with the control group, the GC group exhibited a significantly downregulated protein expression level of PI3K and its downstream protein kinase B (Akt) and mammalian target of rapamycin (mTOR) expression. Furthermore, administration of 10 µM 740 Y-P, a cell-permeable phosphopeptide activator of PI3K, to hBMSCs increased the expression of Akt and mTOR. Treatment with 740 Y-P reversed the effect of miR-27a on OD in hBMSCs. In conclusion, miR-27a is thought to relieve ONFH and the OD repression in GC-induced hBMSCs by targeting the PI3K/Akt/mTOR pathway.

13.
Nanoscale ; 13(2): 1016-1028, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33393578

RESUMO

Benzo[a]pyrene (Bap) is one of the main organic pollutants in the atmospheric haze that is rich in fine water drops and particulate matters. The understanding of the Bap's form in water is of great importance to unveil its real biological effects toward the respiratory system. To date, various reports have documented its toxicological effects in the molecular form. Herein, we found that Bap existed as self-aggregated nanoclusters of tunable sizes rather than as dissolved molecules in water and different sized nanoclusters illustrated varied cytotoxicity. These findings indicated that the size, which has been ignored in previous studies, is also a dominant parameter similar to the molecular concentration for determining Bap's cytotoxicity. Polystyrene (PS) nanoparticles, as a model for nanoplastics, could adsorb Bap nanoclusters and serve as carriers that enter the cells. The combination effect interestingly altered the cytotoxicity distinction of Bap of different sizes. The intracellular fate of the nanoparticles and subcellular organelle damages were studied to unveil the mechanisms of cytotoxic distinction. Small Bap nanoclusters entered cells faster than their large counterparts. The Bap of the PS@Bap complex was stably adsorbed on PS at the early stages of endocytosis until it was detached during the lysosomal transport and maturation process. The dissociated Bap may bypass the lysosome pathway and be released into the cytosol with a nanocluster structure or relocate into the endoplasmic reticulum. On the other hand, the detached PS preferred to bind to the mitochondria or be excreted out of the cell via the lysosomal pathway. Moreover, the PS@Bap complex resulted in a significant loss of the mitochondrial membrane potential and induced apoptosis through the mitochondria-involved apoptosis pathway. This study provides a new perspective towards the toxicological mechanism of insoluble hydrophobic organic compounds and reveals the environmental significance of nanoplastics for regulating the biological effects of conventional pollutants.


Assuntos
Benzo(a)pireno , Poluentes Ambientais , Adsorção , Benzo(a)pireno/análise , Benzo(a)pireno/toxicidade , Disponibilidade Biológica , Microplásticos
14.
J Hazard Mater ; 406: 124306, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33109409

RESUMO

Nanoplastics have recently become a worldwide concern as newly emerging airborne pollutants, which can associate with polycyclic aromatic hydrocarbons (PAHs) and form combined contaminant nanoparticles (CCNPs). After being inhaled in the respiratory system, the CCNPs would first encounter the mucous gel layer being rich in mucin. Herein, polystyrene-benzopyrene (PS@Bap) NPs were prepared as CCNPs model and their interaction with mucin and the resultant biological responses were studied. It was observed that mucin corona stably attached to the CCNPs surface, which significantly altered the fate of the CCNPs in lung epithelial cells (A 549 cell line). The mucin corona would 1) stably adsorbed on PS@Bap at the early stages of endocytosis until degraded during the lysosomal transport and maturation process, 2) delay intracellular trafficking of PS@Bap and the progress of Bap detached from PS, 3) enhance uptake of PS@Bap but reduce the cytotoxicity elicited by PS@Bap, as indicated by cell viability, generation of reactive oxygen species, impairment on mitochondrial function, and further cell apoptosis. In addition, in vivo study also verified the enhanced effect of PS on the development of an acute lung inflammatory response induced by Bap. This study highlights the significance of incorporating the effects of mucin for precisely assessing the respiratory system toxicity of nanoplastics based CCNPs in atmospheric environments.


Assuntos
Nanopartículas , Hidrocarbonetos Policíclicos Aromáticos , Benzopirenos , Microplásticos , Mucinas , Nanopartículas/toxicidade , Poliestirenos
15.
Biosens Bioelectron ; 174: 112825, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33243696

RESUMO

It is still challenging to sensitively detect protein biomarkers via surface-enhanced Raman scattering (SERS) technique owing to their low Raman activity. SERS tag-based immunoassay is usually applied; however, it is laborious and needs specific antibodies. Herein, an ultrasensitive and universal "Raman indicator" sensing strategy is proposed for protein biomarkers, with the aid of a glass capillary-based molecularly imprinted SERS sensor. The sensor consists of an inner SERS substrate layer for signal enhancement and an outer mussel-inspired polydopamine imprinted layer as a recognition element. Imprinted cavities have two missions: first, selectively capturing the target protein, and second, the only passageway of Raman indicator to access SERS substrate. Specific protein recognition means filling imprinted cavities and blocking Raman indicator flow. Thus, the quantity of captured protein can be reflected by the signal decrease of ultra-Raman active indicator molecule. The capillary sensor exhibited specific and reproducible detection at the level down to 4.1 × 10-3 µg L-1, for trypsin enzyme in as-received biological samples without sample preparation. The generality of the mechanism is confirmed by using three different protein models. This platform provides a facile, fast and general route for sensitive SERS detection of Raman inactive biomacromolecules, which offers great promising utility for in situ and fast point-of-care practical bioassay.


Assuntos
Técnicas Biossensoriais , Impressão Molecular , Biomarcadores , Imunoensaio , Análise Espectral Raman
16.
Anal Chem ; 92(21): 14814-14821, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33045167

RESUMO

Surface-enhanced Raman resonant scattering (SERRS) tags encoded with near-infrared (NIR) Raman reporters showed great potential for in vivo detection owing to their ultrasensitivity. However, in vivo signal stability of such tags is a remaining problem due to the lack of suitable silica coating method because the weakly adsorbed NIR reporters tend to detach from traditional gold nanosubstrates in the ethanol-rich and high pH conditions, which are commonly used for silica coating. Herein, we propose a silica coating method for NIR SERRS tags by using waxberry-like gold nanoparticles (NPs) as substrates. The lipid bilayer of the NPs played a crucial role in the coating, which can encapsulate the NIR Raman reporter via hydrophobic interactions and prevent the interference from a harsh medium. Thus, the silica-coated tags well preserved ultrasensitivity of bare tags and simultaneously gained satisfactory signal stability in vivo. Moreover, the coating method is compatible for the encapsulation of a variety of thiol group-free NIR reporters (as exemplified by DTTC, Cy7, IR792, and DIR), relying on which a tag-pair with distinguishable peaks can be screened (labeling with DTTC and Cy7, respectively). In vivo duplexing detection revealed that the tag-pair-labeled liposome was cleared faster in the liver than polydopamine NPs within one mouse. The developed method paves an easy way for gaining high-quality SERRS tags and will promote their in vivo multiplex analysis and diagnostics applications.


Assuntos
Materiais Biomiméticos/química , Corantes/química , Raios Infravermelhos , Magnoliopsida , Dióxido de Silício/química , Análise Espectral Raman/métodos , Animais , Ouro/química , Concentração de Íons de Hidrogênio , Nanopartículas Metálicas/química , Camundongos , Compostos de Sulfidrila/química , Propriedades de Superfície
17.
Curr Res Food Sci ; 3: 178-188, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32914133

RESUMO

The aim of this study was to investigate the fate of curcumin (CUR)-loaded Pickering emulsions with complex interfaces during in vitro gastrointestinal transit and test the efficacy of such emulsions on improving the bioaccessibility and cellular uptake of CUR. CUR-loaded Pickering emulsions tested were whey protein nanogel particle-stabilized Pickering emulsions (CUR-EWPN) and emulsions displaying complex interfaces included 1) layer-by-layer dextran sulphate-coated nanogel-stabilized Pickering emulsions (CUR-DxS+EWPN) and 2) protein+dextran-conjugated microgel-stabilized Pickering emulsions (CUR-EWPDxM). The hypothesis was that the presence of complex interfacial material at the droplet surface would provide better protection to the droplets against physiological degradation, particularly under gastric conditions and thus, improve the delivery of CUR to Caco-2 intestinal cells. The emulsions were characterized using droplet sizing, apparent viscosity, confocal and cryo-scanning electron microscopy, zeta-potential, lipid digestion kinetics, bioaccessibility of CUR as well as cell viability and uptake by Caco-2 cells. Emulsion droplets with modified to complex interfacial composition (i.e. CUR-DxS+EWPN and CUR-EWPDxM) provided enhanced kinetic stability to the Pickering emulsion droplets against coalescence in the gastric regime as compared to droplets having unmodified interface (i.e. CUR-EWPN), whereas droplet coalescence occurred in intestinal conditions irrespective of the initial interfacial materials. A similar rate and extent of free fatty acid release occurred in all the emulsions during intestinal digestion (p > 0.05), which correlated with the bioaccessibility of CUR. Striking, CUR-DxS+EWPN and CUR-EWPDxM significantly improved cellular CUR uptake as compared to CUR-EWPN (p < 0.05). These results highlight a promising new strategy of designing gastric-stable Pickering emulsions with complex interfaces to improve the delivery of lipophilic bioactive compounds to the cells for the future design of functional foods.

18.
Histochem Cell Biol ; 154(6): 629-638, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32997263

RESUMO

Proliferative vitreoretinopathy (PVR) is the most common cause of surgical failure in the rhegmatogenous retinal detachment (RD) treatment. Retinal pigment epithelial (RPE) cell proliferation, migration, and the synthesis of extracellular matrix (ECM) are intrinsic to the formation of a PVR membrane. High level of interleukin-6 (IL-6) has been found in the vitreous of PVR patients, while the role of IL-6 in RPE cells remaining further characterized. In the present study, we evaluated the potential regulatory effects of IL-6 on cell migration, ECM components, and transforming growth factor ß2 (TGF-ß2) expression in RPE cells. Furthermore, cell counting kit-8 (CCK­8) assay was used to investigate cell proliferation activity. We found that IL-6 promoted fibronectin (Fn) and type I collagen (COL-1), TGF-ß2 expression in RPE cells, also stimulate RPE cell migration effectively. Moreover, the induction of IL-6 activated the Janus kinase/signal transducers and activators of transcription (JAK/STAT3) and the nuclear factor kappa-B (NF-κB) signaling pathways significantly. Simultaneously, both JAK/STAT3 and NF-κB pathways inhibitors, WP1066 and BAY11-7082, alleviated IL-6-induced biological effects, respectively. However, it was noted that IL-6 had little effect on α-smooth muscle actin (α-SMA) expression. Collectively, our results reveal that IL-6 promotes RPE cell migration and ECM synthesis via activating JAK/STAT3 and NF-κB signaling pathways, which may play a crucial role in PVR formation.


Assuntos
Matriz Extracelular/metabolismo , Interleucina-6/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Movimento Celular , Células Cultivadas , Humanos , Epitélio Pigmentado da Retina/citologia
19.
Cell Biol Int ; 44(12): 2532-2540, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32869899

RESUMO

Osteogenic differentiation (OD) of bone marrow mesenchymal stem cells (BMSCs) is critically important for mitigation of osteoporosis. Glucocorticoids (GCs) are extensively used for treating chronic inflammation, although long-term exposure to GCs is capable of triggering osteoporosis. microRNAs (miRNAs) have been reported to play a critical role in bone diseases. In the present study, we treated BMSCs with dexamethasone (DEX) during OD to stimulate GC-mediated osteoporosis. Microarray and quantitative polymerase chain reaction (Q-PCR) assays demonstrated that miR-199a was upregulated during OD of BMSCs, while DEX treatment caused a significant reduction in miR-199a. Alkaline phosphatase (ALP) activity, Alizarin red (AR) staining, and Q-PCR were applied to assess the role of miRNA-199a overexpression in DEX-triggered OD inhibition. miR-199a was able to rescue OD and ALP activity, which were inhibited by DEX. Additionally, we observed that ALP, BMP2, COL1A1, and Runx2 were increased after transfection of miRNA-199a mimics. Furthermore, we confirmed that miRNA-199a facilitates OD of BMSCs through direct inhibition of Klotho protein and messenger RNA expression affecting the downstream fibroblast growth factor receptor 1/extracellular-signal-regulated kinase and Janus kinase 1/signal transducer and activator of transcription 1 pathways. This study indicates that miR-199a plays a critical role in preventing GC-mediated osteoblast differentiation and may function as a promising miRNA biomarker for osteoporosis.


Assuntos
Glucuronidase/metabolismo , MicroRNAs/genética , Osteogênese/genética , Animais , Células da Medula Óssea/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Dexametasona/efeitos adversos , Dexametasona/farmacologia , Feminino , Glucocorticoides/metabolismo , Glucocorticoides/farmacologia , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Osteoblastos/metabolismo , Osteogênese/efeitos dos fármacos , Osteoporose/metabolismo , Ratos , Ratos Sprague-Dawley
20.
J Hazard Mater ; 396: 122673, 2020 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-32361129

RESUMO

Hydrogen polysulfides (H2Sn, n>1) as important intracellular reactive sulfur species (RSS) are believe to be responsible for cellular redox regulation. Lots of researches about H2Sn focusing on their formation, detection and bio-function in signalling regulation are spring up but with poor understanding, especially for biosynthesis and bio-function remain complicated and confusing. Recent studies reveal that thionitrous acid (HSNO) as potential intermediate linked signalling molecules of nitrogenous and sulphureous during biotic redox regulation. However, there are limited evidences for supporting the interrelation and bioeffect between HSNO and H2Sn. Herein, we have successfully designed a near-infrared (NIR) fluorescent probe ((2-fluoro-5-nitrobenzoyl)oxy)-Benzo[e]cyanine (BCy-FN) for detection H2Sn and for the first time observing HSNO-mediated H2Sn generation in cells and in vivo. The probe is harvested from fluorophore BCy-Keto and 2-fluoro-5-nitrobenzoic acid in one step, featuring mitochondria localization. The unique Enol-Keto tautomerization of fluorophore enables the probe becomes more sensitive and has powerful application. Hypoxia model has been constructed and powerfully interpreted the pretreatment of HSNO for zebrafish hypoxia process effectively improves H2Sn levels and defends the hypoxia induced brain damage. We believe the present studies will help environmentalist and biologist for better understanding of biosynthesis and bio-function in HSNO-mediated H2Sn formation process under hypoxia stress.


Assuntos
Corantes Fluorescentes , Peixe-Zebra , Animais , Humanos , Hidrogênio , Hipóxia , Sulfetos
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