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N-acetyl glucosamine (NAG) is a natural amino sugar found in various human tissues with previously described anti-inflammatory effects. Various chemical modifications of NAG have been made to promote its biomedical applications. In this study, we synthesized two bi-deoxygenated NAG, BNAG1 and BNAG2 and investigated their anti-inflammatory properties, using an in vivo and in vitro inflammation mouse model induced by lipopolysaccharide (LPS). Among the parent molecule NAG, BNAG1 and BNAG2, BNAG1 showed the highest inhibition against serum levels of IL-6 and TNF α and the leukocyte migration to lungs and peritoneal cavity in LPS challenged mice, as well as IL-6 and TNF α production in LPS-stimulated primary peritoneal macrophages. BNAG2 displayed an anti-inflammatory effect which was comparable to NAG. These findings implied potential application of these novel NAG derivatives, especially BNAG1, in treatment of certain inflammation-related diseases.
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Acetilglucosamina , Anti-Inflamatórios , Lipopolissacarídeos , Macrófagos Peritoneais , Fator de Necrose Tumoral alfa , Animais , Acetilglucosamina/farmacologia , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/síntese química , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Interleucina-6/sangue , Inflamação/tratamento farmacológico , Masculino , Modelos Animais de DoençasRESUMO
AIMS: Formyl peptide receptor 1 (FPR1), from a G-protein coupled receptor family, was previously well-characterized in immune cells. But the function of FPR1 in osteogenesis and fracture healing was rarely reported. This study, using the FPR1 knockout (KO) mouse, is one of the first studies that try to investigate FPR1 function to osteogenic differentiation of bone marrow-derived stem cells (BMSCs) in vitro and bone fracture healing in vivo. MATERIALS AND METHODS: Primary BMSCs were isolated from both FPR1 KO and wild type (WT) mice. Cloned mouse BMSCs (D1 cells) were used to examine role of FoxO1 in FPR1 regulation of osteogenesis. A closed, transverse fracture at the femoral midshaft was created to compare bone healing between KO and WT mice. Biomechanical and structural properties of femur were compared between healthy WT and KO mice. KEY FINDINGS: FPR1 expression increased significantly during osteogenesis of both primary and cloned BMSCs. Compared to BMSCs from FPR1 KO mice, WT BMSCs displayed considerably higher levels of osteogenic markers as well as mineralization. Osteogenesis by D1 cells was inhibited by either an FPR1 antagonist cFLFLF or a specific inhibitor of FoxO1, AS1842856. In addition, the femur from WT mice had better biomechanical properties than FPR1 KO mice. Furthermore, bone healing in WT mice was remarkably improved compared to FPR1 KO mice analyzed by X-ray and micro-CT. SIGNIFICANCE: These findings indicated that FPR1 played a vital role in osteogenic differentiation and regenerative capacity of fractured bone, probably through the activation of FoxO1 related signaling pathways.
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Osteogênese , Receptores de Formil Peptídeo , Camundongos , Animais , Receptores de Formil Peptídeo/genética , Receptores de Formil Peptídeo/metabolismo , Camundongos Knockout , Consolidação da Fratura , Fêmur/metabolismo , Diferenciação Celular , Células da Medula ÓsseaRESUMO
Crohn's disease (CD) has been traditionally viewed as a chronic inflammatory disease that cause gut wall thickening and complications, including fistulas, by mechanisms not understood. By focusing on Parabacteroides distasonis (presumed modern succinate-producing commensal probiotic), recovered from intestinal microfistulous tracts (cavernous fistulous micropathologies CavFT proposed as intermediate between 'mucosal fissures' and 'fistulas') in two patients that required surgery to remove CD-damaged ilea, we demonstrate that such isolates exert pathogenic/pathobiont roles in mouse models of CD. Our isolates are clonally-related; potentially emerging as transmissible in the community and mice; proinflammatory and adapted to the ileum of germ-free mice prone to CD-like ileitis (SAMP1/YitFc) but not healthy mice (C57BL/6J), and cytotoxic/ATP-depleting to HoxB8-immortalized bone marrow derived myeloid cells from SAMP1/YitFc mice when concurrently exposed to succinate and extracts from CavFT-derived E. coli , but not to cells from healthy mice. With unique genomic features supporting recent genetic exchange with Bacteroides fragilis -BGF539, evidence of international presence in primarily human metagenome databases, these CavFT Pdis isolates could represent to a new opportunistic Parabacteroides species, or subspecies (' cavitamuralis' ) adapted to microfistulous niches in CD.
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Electric double-layer supercapacitors (EDLCs) have attracted much attention in the energy storage field due to their advantages such as high output power, long service life, safety and high efficiency. However, their low energy density limits their application. Aiming at the problem of the low energy density of EDLCs, improving quantum capacitance (CQ) of electrode materials is an effective strategy. In this paper, we systematically studied the effects of vacancy, doping, and metal atom adsorption on the CQ of borophene using first-principles calculations. The results show that S and N doping greatly enhance the charge accumulation of borophene at positive and negative potential, respectively. The maximum CQ values of S-doped and N-doped borophene are 157.3 µF cm-2 (0.38 V) and 187.8 µF cm-2 (-0.24 V), respectively. Both of them can serve as ideal candidates for the positive (S-doped one) and negative (N-doped one) electrodes of EDLCs. Besides, metal Al atom-adsorbed borophene can also effectively enhance the CQ, with a maximum value of 109.1 µF cm-2.
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In recent years, supercapacitors have been widely used in the fields of energy, transportation, and industry. Among them, electrical double-layer capacitors (EDLCs) have attracted attention because of their dramatically high power density. With the rapid development of computational methods, theoretical studies on the physical and chemical properties of electrode materials have provided important support for the preparation of EDLCs with higher performance. Besides the widely studied double-layer capacitance (CD), quantum capacitance (CQ), which has long been ignored, is another important factor to improve the total capacitance (CT) of an electrode. In this paper, we survey the recent theoretical progress on the CQ of two-dimensional (2D) electrode materials in EDLCs and classify the electrode materials mainly into graphene-like 2D main group elements and compounds, transition metal carbides/nitrides (MXenes), and transition metal dichalcogenides (TMDs). In addition, we summarize the influence of different modification routes (including doping, metal-adsorption, vacancy, and surface functionalization) on the CQ characteristics in the voltage range of ±0.6 V. Finally, we discuss the current difficulties in the theoretical study of supercapacitor electrode materials and provide our outlook on the future development of EDLCs in the field of energy storage.
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Background: Glucosamine and N-acetyl-glucosamine (NAG) are amino sugars found in human extracellular matrix with previously described anti-inflammatory effects. Despite mixed results from clinical studies, these molecules have been used extensively in supplements. Objective: We investigated the anti-inflammatory properties of two synthesized derivatives of N-acetyl-glucosamine (NAG), bi-deoxy-N-acetyl-glucosamine (BNAG) 1 and 2. Methods: Using mouse macrophage RAW 264.7 cells with lipopolysaccharide (LPS) to induce inflammation, the effects of NAG, BNAG 1, and BNAG 2 on the expression of IL-6, IL-1ß, inducible nitric oxide synthase (iNOS) and COX-2 were studied using ELISA, Western blot and quantitative RT-PCR. Cell toxicity and nitric oxide (NO) production were evaluated using WST-1 assay and the Griess reagent, respectively. Results: Among the three tested compounds, BNAG1 shows the highest inhibition of iNOS, IL-6, TNF α and IL-1ß expression and NO production. All three tested compounds show slight inhibition on cell proliferation of RAW 264.7 cells, except that BNAG1 displays a remarkable toxicity at the tested maximum dose of 5 mM. Conclusion: BNAG 1 and 2 exhibit notable anti-inflammatory effects compared to the parent NAG molecule.
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PURPOSE/AIM OF THE STUDY: The formyl peptide receptor (FPR) participates in the immune response, with roles in infection and inflammation. In this review article, we summarize the current literature on these roles before discussing the function of FPRs in the pathogenesis of musculoskeletal disorders including osteoarthritis (OA), degenerative disc disease (DDD), and rheumatoid arthritis (RA). Additionally, we discuss the potential diagnostic and therapeutic roles of FPRs in these domains. METHODS: PubMed and Ovid MEDLINE searches were performed from 1965 through March 2022. Keywords included "FPR, tissue expression, inflammation, infection, musculoskeletal disorder, bone, rheumatoid arthritis, osteoarthritis, degenerative disc disease, mitochondria." RESULTS: Sixty-nine studies were included in this review article. FPRs appear to be ubiquitous in the pathogenesis, diagnosis, and treatment of common musculoskeletal disorders. They can potentially be utilized for the earlier diagnosis of OA and DDD. They may be employed with mesenchymal stem cells (MSCs) to reverse OA and DDD pathologies. With anti-inflammatory, anti-osteolytic, and pro-angiogenic functions, they may broaden treatment options in RA. CONCLUSIONS: FPRs appear to be heavily involved in the pathogenesis of common musculoskeletal conditions, including arthritis, degenerative disc disease, and rheumatoid arthritis. Furthermore, they demonstrate much promise in the diagnosis and treatment of these conditions. Their roles should continue to be explored.
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Artrite Reumatoide , Degeneração do Disco Intervertebral , Doenças Musculoesqueléticas , Osteoartrite , Humanos , Receptores de Formil Peptídeo/metabolismo , Receptores de Formil Peptídeo/uso terapêutico , Inflamação/patologia , Artrite Reumatoide/patologiaRESUMO
ChaC glutathione-specific γ-glutamylcyclotransferase 1 (CHAC1) is involved in intracellular glutathione depletion, ferroptosis, and tumorigenesis. The functional role of CHAC1 expression in thyroid carcinoma has not yet been established. The present study aimed to investigate the impact and mechanisms of CHAC1 on ferroptosis and radiation sensitivity in thyroid carcinoma. CHAC1 expression was examined in tumor tissue specimens and microarrays and thyroid carcinoma cell lines. CHAC1 was silenced or overexpressed by lentivirus transfection in thyroid carcinoma cells. Cell viability and lipid ROS levels were evaluated by Cell Counting Kit-8 and flow cytometry, respectively. The effect of CHAC1 on tumor growth in vivo was also measured. Ferroptosis-related proteins were measured by western blotting. CHAC1 expression was decreased in patients with thyroid carcinoma, and overexpression of CHAC1 suppressed cell viability of BCPAP cells and tumor growth in xenografted nude mice. Exposure to Ferrostatin-1, a ferroptosis inhibitor, significantly attenuated the inhibitory effects of CHAC1 overexpression on cell viability. In CHAC1-overexpressing BCPAP cells, ferroptosis was induced as indicated by increased lipid ROS production and PTGS2 expression. Knocking down of CHAC1 in K1 cells significantly induced cell viability, reduced lipid ROS production and PTGS2 expression, and enhanced GPX4 expression. Such effects were attenuated by RSL3, a ferroptosis inducer. Furthermore, we showed that CHAC1 overexpression enhanced radiation sensitivity in BCPAP cells as indicated by decreased cell viability, while CHAC1 knockdown had reversed effects in K1 cells as indicated by increased cell viability. Taken together, CHAC1 overexpression promoted ferroptosis and enhanced radiation sensitivity in thyroid carcinoma.
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Ferroptose , Neoplasias da Glândula Tireoide , gama-Glutamilciclotransferase , Animais , Humanos , Camundongos , Ciclo-Oxigenase 2 , Ferroptose/genética , Glutationa , Lipídeos , Camundongos Nus , Espécies Reativas de Oxigênio , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/radioterapia , gama-Glutamilciclotransferase/genética , gama-Glutamilciclotransferase/metabolismoRESUMO
Although PYCR1 is a well-recognized oncogenic gene for malignant tumors, the causal relationship of its expression with malignant growth and cytotoxic chemotherapeutics remains unclear. Therefore, this study aimed to clarify the role of PYCR1 and its interaction with SLC25A10 in a chemotherapeutic agent 5-fluorouracil (5-FU)'s toxicity to colorectal cancer cells. PYCR1 and SLC25A10 expressions were detected in The Cancer Genome Atlas database and colon adenocarcinoma (COAD) clinical samples. PYCR1 upregulation was associated with SLC25A10 expression and poor prognosis, and its high expression indicated decreased survival rates in patients with COAD. PYCR1 overexpression inhibited lipid reactive oxygen species production and promoted SLC25A10 expression in colorectal cancer cells. PYCR1 silencing enhanced the antitumor effects of 5-FU. Ferroptosis inhibitor deferoxamine suppressed the antitumor effects of PYCR1 silencing, whereas ferroptosis inducer erastin inhibited the protumor effects of PYCR1 overexpression. SLC25A10 overexpression reversed the antitumor effects of PYCR1 silencing in vitro and inhibited the antitumor effects of erastin in vivo. Therefore, PYCR1 is an oncogenic gene that promotes colorectal tumor growth and desensitizes colorectal cancer cells to 5-FU cytotoxicity by preventing apoptosis and ferroptosis.
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Neoplasias do Colo , Neoplasias Colorretais , Transportadores de Ácidos Dicarboxílicos , Ferroptose , Pirrolina Carboxilato Redutases , Adenocarcinoma , Apoptose/genética , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Desferroxamina/farmacologia , Desferroxamina/uso terapêutico , Transportadores de Ácidos Dicarboxílicos/genética , Ferroptose/genética , Fluoruracila/farmacologia , Humanos , Lipídeos/farmacologia , Lipídeos/uso terapêutico , Pirrolina Carboxilato Redutases/genética , Espécies Reativas de Oxigênio/metabolismo , delta-1-Pirrolina-5-Carboxilato RedutaseRESUMO
Formyl peptide receptors (Fprs) play fundamental roles in multiple cell functions including promotion of osteogenesis and bone fracture healing. In this study, the role of Fpr1 gene in osteogenic and adipogenic differentiation of adipose derived stem cells (ADSCs) was investigated. Primary ADSCs (mADSCs) from either Fpr1 knockout (KO) or wild type (WT) mice and human ADSCs (hADSCs) were treated by osteogenic (OM) or adipogenic (AM) medium, with basal medium as control. Osteogenesis and adipogenesis were measured by histological and biochemical methods. In both hADSCs and mADSCs, Fpr1 gene expression, osteogenic gene expression, as well as mineralization were increased after osteogenic induction. The osteogenic capacity of KO ADSCs was remarkably reduced compared to WT ADSCs, with decreased levels of expression of osteogenic markers, alkaline phosphatase activity, and mineralization. In contrast, the adipogenesis of KO ADSCs was remarkably enhanced compared with WT ADSCs, forming more lipid droplets, and increasing expression of adipogenic markers PPARγ and aP2. Expression of the nuclear transcription factor Forkhead box protein O1 (FoxO1) was decreased in KO ADSCs, while OM and AM caused increase and decrease in FoxO1 expression, respectively. The current study revealed a correlation of Fpr1 gene expression with osteogenesis and adipogenesis of mADSCs, underlying a mechanism involving FoxO1. Our present research suggests that targeting Fpr1 might be a novel strategy to enhance osteogenesis of ADSCs.
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Adipócitos/metabolismo , Adipogenia/genética , Osteogênese/genética , Receptores de Formil Peptídeo/genética , Células-Tronco/metabolismo , Perfilação da Expressão Gênica , HumanosRESUMO
PURPOSE: Although inflammation has been recognized as a key process in the pathogenesis of osteoarthritis (OA), there remains no clinical noninvasive imaging modality that can specifically diagnose inflammatory activity of OA. In this study, a formyl peptide receptor 1 (Fpr1) targeting probe cFLFLF-PEG-HYNIC-99mTc and single-photon emission computed tomography (SPECT) imaging was used to detect inflammatory activity by targeting macrophages involved in the pathogenesis of OA. PROCEDURES: In vitro experiments were performed to evaluate Fpr1 expression during macrophage inflammatory response. In the in vivo studies, anterior cruciate ligament transection (ACLT) surgery was performed, and magnetic resonance imaging (MRI) and histological data were assessed to analyze the OA model in both mice and rats. The radioactive probe cFLFLF-PEG-HYNIC-99mTc and SPECT imaging were used to corroborate OA-related inflammation and compare ACLT vs sham knees. RESULTS: In vitro macrophage activation resulted in a remarkable increase in Fpr1 expression. In vivo experiments in mice and rats produced similar results. MRI and histological analysis demonstrated significant joint degeneration in the ACLT knee. The ACLT knee produced a much stronger signal from the probe when compared to the sham knee. It is important to note that the ratio of ACLT/sham knee signal intensity decreased with OA progression, indicating greater differences earlier in the progression of OA. CONCLUSION: The radioactive probe cFLFLF-PEG-HYNIC-99mTc and SPECT imaging are effective for detecting and monitoring inflammation during OA progression by targeting Fpr1 expression in the knee joint.
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Osteoartrite , Tomografia Computadorizada de Emissão de Fóton Único , Animais , Modelos Animais de Doenças , Inflamação/diagnóstico por imagem , Ativação de Macrófagos , Camundongos , Osteoartrite/diagnóstico por imagem , Peptídeos , Ratos , Tomografia Computadorizada de Emissão de Fóton Único/métodosRESUMO
Transformation of microplastics in aquatic environments and engineered systems (e.g., wastewater treatment plants) significantly affects their transport, fate and effects. Here, we present the counterintuitive finding that sulfide, a prevalent nucleophile and reductant, can result in oxidation of microplastics, in addition to sulfide addition. Treating four model microplastics (thermoplastic polyurethane, polystyrene, polyethylene terephthalate and polyethylene) with 0.1 mM sulfide in a Tris-buffer solution (pH 7.2, 25 °C) resulted in physical damages (embrittlement and cracking) and chemical transformation (increased O/C ratio and formation of C-S bonds) of the materials. Pre-aging of the microplastics with O3 or UV treatment had varied effects on their reactivities toward sulfide, depending on the specific structural and surface chemistry properties of the polymers. Electron paramagnetic resonance and radical trapping/quenching experiments showed that sulfide underwent spontaneous oxidation to form â¢OH radicals, which acted as the primary oxidant to attack the carbon atoms in the polymer chains, leading to surface oxidation and chain scission. Notably, sulfide addition, verified with X-ray photoelectron spectroscopy and 13C-nuclear magnetic resonance spectroscopy analyses, likely contributed to the physicochemical transformation of microplastics together with radical oxidation in a synergistic manner. The findings unravel an important transformation route (and a potential source) of microplastics in the environment.
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Poluentes Químicos da Água , Purificação da Água , Microplásticos , Oxirredução , Plásticos , Sulfetos , Poluentes Químicos da Água/análiseRESUMO
Corilagin, extracted from the Euphorbiaceae and Phyllanthus plants, inhibits the growth of a number of types of tumors. Compared with temozolomide, the traditional chemotherapy drug, corilagin has demonstrated stronger antitumor activity. However, the pharmaceutical mechanism of corilagin in glioma remains unclear. Nuclear factor erythroid 2 like 2 (NFE2L2 or NRF2) is positively associated with several types of tumor including glioma. In the present study, NRF2 expression was higher in glioma tissues compared with nonglioma specimens. Therefore, it was hypothesized that corilagin targets NRF2 regulation of U251 cell apoptosis. The present study used Hoechst 33258 staining to demonstrate that corilagin induced glioma cell apoptosis and observed that the expression of the apoptosisrelated gene Bcl2 was reduced. In addition, corilagin induced autophagy and promoted the conversion of light chain 3 (LC3) protein from LC3â to LC3II. NRF2 expression was downregulated by corilagin stimulation. Furthermore, the gene expression pattern following knockdown of NRF2 in U251 cells using siRNA was consistent with corilagin stimulation. Therefore, it was preliminarily concluded that corilagin induces apoptosis and autophagy by reducing NRF2 expression.
Assuntos
Autofagia/efeitos dos fármacos , Glioma/tratamento farmacológico , Glucosídeos/farmacologia , Taninos Hidrolisáveis/farmacologia , Fator 2 Relacionado a NF-E2/genética , Adulto , Idoso , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/genética , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/efeitos dos fármacos , Temozolomida/farmacologiaRESUMO
In recent years, the fabrication of well-organized proteinosomes has been a popular topic due to the potential applications of the structures in materials science and nanotechnology. A big challenge in the fabrication of proteinosomes is to maintain the structures and the functionalities of proteins on the proteinosomes. In this research, a new concept of polymerization-induced formation of proteinosomes is proposed. In thermal dispersion polymerization of N-isopropyl acrylamide (NIPAM) in the presence of bovine serum albumin (BSA), the growing PNIPAM chains experience phase transition from hydrated coils to dehydrated globules, and the dehydrated PNIPAM chains have hydrophobic interaction with BSA, leading to the formation of hollow proteinosomes. Kinetics studies indicate that there is a transition from the homogeneous polymerization of NIPAM in solution to the heterogeneous polymerization in the proteinosomes. Transmission electron microscopy, atomic force microscopy, confocal laser scanning microscopy and dynamic light scattering all demonstrate the formation of hollow structures. The results of circular dichroism spectroscopy indicate that the secondary structure of BSA remains unchanged in the polymerization process. The formation of proteinosomes is reversible. Upon cooling of the solution to a temperature below the phase transition temperature of PNIPAM, the proteinosomes are dissociated due to the absence of the hydrophobic interaction. The proteinosomes can be used in the encapsulation of hydrophilic compounds in aqueous solution. In this research, not only BSA but also ovalbumin (OVA) is used as a model protein for the fabrication of proteinosomes by the polymerization-induced approach.
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Polimerização , Proteínas/metabolismo , Propriedades de SuperfícieRESUMO
A poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel film was prepared by bulk polymerization. Then, it was surface modified by perfluorooctanoyl chloride to improve the anti-biofouling properties. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDXS), and atomic force microscopy (AFM) analyses demonstrated that the uniform dense fluorinated layer had been successfully grafted onto pHEMA. The water contact angle (WCA) of the modified pHEMA film increased to 135°, while the surface energy decreased to 13.32 mN/m. The protein and bacterial adhesion properties of the modified pHEMA were decreased significantly. The in vitro cytotoxicity showed that the modified pHEMA was noncytotoxic. Thus, the fluorinated modification on the material surface was a convenient and effective method to establish a hydrophobic and anti-biofouling surface.
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Incrustação Biológica/prevenção & controle , Hidrogéis/química , Poli-Hidroxietil Metacrilato/química , Adsorção , Aderência Bacteriana/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Halogenação , Humanos , Hidrogéis/farmacologia , Proteínas/química , Propriedades de Superfície , Água/química , MolhabilidadeRESUMO
OBJECTIVE: It has been reported that glutathione (GSH), the most abundant cellular antioxidant, can inhibit production of pro-inflammatory cytokines by activated macrophages. Bromosulfophthalein (BSP) has been recognized as an inhibitor of the efflux of reduced GSH from cells, leading to an increase in the intracellular GSH level. In this study, we evaluated, for the first time, whether BSP possessed anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated macrophages. MATERIALS AND METHODS: RAW 264.7 cells were treated with BSP and the levels of proinflammatory cytokines, GSH, and nitrite were assessed. Gene expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF α), interleukin-1beta (IL-1ß), and interleukin-6 (IL-6) was analyzed via quantitative RT-PCR. We also examined various inflammatory signaling pathways including Akt/forkhead box protein O1 (FoxO1)/toll-like receptor 4 (TLR4), mitogen-activated protein kinases (MAPKs), and Fas protein by Western blot and flow cytometry analysis. RESULTS: Our study demonstrated that BSP induced an increase in intracellular GSH level in LPS-stimulated macrophages. BSP inhibited production of nitric oxide and proinflammatory cytokines. BSP increased phosphorylation of Akt and nuclear exclusion of FoxO1 and suppressed TLR4 expression. Additionally, BSP decreased MAPKs activation and Fas expression. DISCUSSION AND CONCLUSION: Taken together, these data suggest that BSP can attenuate inflammation through multiple signaling pathways. These findings highlight the potential of BSP as a new anti-inflammatory agent.
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Anti-Inflamatórios/farmacologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Sulfobromoftaleína/farmacologia , Animais , Citocinas/genética , Citocinas/metabolismo , Proteína Forkhead Box O1/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células RAW 264.7 , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Receptor fas/metabolismoRESUMO
Poly(zwitterions) polymer brushes were fabricated by surface-initiated atom transfer radical polymerization (SI-ATRP) on PVA substrate. The results of XPS and FTIR proved the successful graft of CBMA and SBMA to PVA. The surface of the PVA films would be rougher after the functionalization. Its hydrophilicity increased dramatically and the water contact angle decreased from 45.2° to 7.2°. The visible light transmittance was above 88%. Mechanical properties decreased slightly after grafting, the tensile strength and tensile strain at break were in 1.23-1.85 MPa and 361.7-471.1%, respectively. The anti-protein adsorption performance of the modified PVA film was significantly enhanced and the lowest adsorption amount was up to 2.25 µg/cm2. The cytotoxicity grade of modified PVA film was 0-1, which indicated the modified film possessed no cytotoxicity. Additionally, the surface of zwitterion-grafted PVA film had strongly resistance to cell adhesion. All the results confirmed that the zwitterions modified PVA was a promising anti-fouling material for the further biomedical use.
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Incrustação Biológica , Polímeros , Adsorção , Incrustação Biológica/prevenção & controle , Polimerização , Propriedades de SuperfícieRESUMO
Along with the development of controlled delivery systems for targeted therapy, 'single-strategy' therapy often fails to achieve the desired performance in real body internal environments. In such a case, it is necessary to develop synergistic therapy strategies. Herein, for the first time, we designed and synthesized hyaluronic acid (HA) modified Ag@S-nitrosothiol core-shell nanoparticles for synergistic tumor cell targeted therapy based on photothermal therapy (PTT) and nitric oxide (NO) based chemotherapy. Triggered by near-infrared irradiation (NIR), the Ag core nanoparticle would convert the light to cytotoxic heat via a surface plasmon resonance mechanism for cancer cell apoptosis. Meanwhile, responding to NIR as well as the generated heat, the S-nitrosothiol polymeric shells would give off free NO at high concentration, inducing NO based chemotherapy. Tumor cell selective cytotoxicity assay in vitro as well as tumor bearing mouse experiments in vivo demonstrated the effective photothermal and NO based chemical synergistic tumor targeted therapy. This spatiotemporally controllable system could provide a new option and era for tumor targeted therapy in the future.
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Antineoplásicos/farmacologia , Nanopartículas/química , Terapia Fototérmica , S-Nitrosotióis/farmacologia , Prata/farmacologia , Enxofre/química , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Células Hep G2 , Humanos , Ácido Hialurônico/química , Raios Infravermelhos , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/patologia , Óxido Nítrico/análise , Tamanho da Partícula , S-Nitrosotióis/química , Prata/química , Ressonância de Plasmônio de Superfície , Propriedades de SuperfícieRESUMO
Design of artificial corneal scaffolds substitute is crucial for replacement of impaired cornea. In this paper, porous polyvinyl alcohol/silk fibroin/nano-hydroxyapatite (PVA/SF/n-HA) composite hydrogel was prepared via the genipin (GP) cross-linking, the pore diameter of the hydrogel ranged from 8.138 nm and 90.269 nm, and the physical and physiological function of hydrogel were investigated. The resulting hydrogel exhibited favourable physical properties. With the GP content increasing, the structural regularity of PVA/SF/n-HA composite hydrogel was enhanced and the thermal stability was improved. The moisture content was slightly decreased and generally maintained at approximately 70%. The tensile strength was heightened up to 0.64 MPa, while the breaking elongation was decreased slightly. Moreover, the biofunction was investigated. The in vitro degradation test demonstrated that with the addition of GP, the stability of the composite hydrogels in protease XIV solution was promoted and the three-dimensional porosity structure of composite hydrogels was maintained as ever. And the human corneal fibroblasts (HCFs) were employed to examine the cells cytotoxicity of the PVA/SF/n-HA composite hydrogels with different GP content by CCK-8 assay. Based on confocal laser scanning microscope (CLSM) and scanning electron microscope (SEM), HCFs had individually commendable adhesion and proliferation on PVA/n-HA/SF composite hydrogel. HCFs proliferated and grew into the pores of composite hydrogel. The results of biocompatibility experiments of composite hydrogel suggested that it was no acute toxicity, in vitro cytotoxicity was 0 or 1 grade. Overall, results from this paper, PVA/n-HA/SF composite hydrogel was a qualified medical material which conformed to the national standard, could be a promising alternative for artificial cornea scaffold material-a novel approach to corneal tissue engineering.
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Córnea/citologia , Durapatita/química , Fibroínas/química , Iridoides/química , Álcool de Polivinil/química , Alicerces Teciduais/química , Animais , Materiais Biocompatíveis/química , Bombyx/química , Linhagem Celular , Sobrevivência Celular , Reagentes de Ligações Cruzadas/química , Humanos , Hidrogéis/química , Engenharia TecidualRESUMO
PVA was dissolved in mixed solvent (DMSO and water) and followed by several freeze-thaw cycles in a mold to produce PVA membrane. Surface modification of PVA membranes by HA molecules was investigated to improve the hydrophilicity of the membrane surface thereby reducing adsorption of the proteins onto the membrane. The surface composition, water contact angle, optical and mechanical properties, surface morphology, cell compatibility and protein adhesion were systematically investigated. ATR-FTIR spectra, XPS, SEM and AFM indicated that PVA membranes were successfully modified by grafting of the HA. The modified membranes showed increased hydrophilicity and cytocompatibility, decreased surface roughness and mechanical properties, and suppressed cell and protein adhesion compared to the pristine membrane. In general, the achievement of the HA coating with anti-adhesive property can potentially be widely used on surface modification of artificial cornea and other biomedical implants.