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The beneficial effect of a beta-lactam antibiotic, Ceftriaxone (CEF), to improve depressive-like symptoms has been documented previously, attributed to its modulation of glutamate neurotransmission. Here, we aimed to determine whether CEF could improve LPS-altered glutamatergic signaling associated with neuroinflammation-allied depression. To assess our goals, we established a neuroinflammation-allied depression mice model by injecting lipopolysaccharides (LPS), followed by behavioral and biochemical analysis. LPS-treated mice displayed depressive symptoms, neuroinflammation, dysregulated glutamate and its transporter (GLT-1) expression, altered expression of astrocyte reactive markers (GFAP, cxcl10, steap4, GBP2, and SRGN), and dysregulated BDNF/TrkB signaling. However, these changes were rescued by CEF treatment, as we found decreased neuroinflammation, relief of depression symptoms, and improved GLT-1 and BDNF/TrkB signaling upon CEF treatment. Moreover, GLT-1 and BDNF/TrkB regulation role of CEF was validated by K252a and DHK treatment. In summary, the anti-depressive effects of glutamate modulators, like CEF, are closely related to their anti-inflammatory role.
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Fator Neurotrófico Derivado do Encéfalo , Ceftriaxona , Camundongos , Animais , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Lipopolissacarídeos , Doenças Neuroinflamatórias , Ácido Glutâmico/metabolismo , Transportador 2 de Aminoácido Excitatório/metabolismoRESUMO
Amorphous silica particles (ASPs) have low biotoxicity and are used in foodstuffs; however, the adsorption states of proteins on their surfaces have not yet been clarified. If the adsorption states can be clarified and controlled, then a wide range of biological and medical applications can be expected. The conventional amorphous silica particles have the problem of protein adsorption due to the strong interaction with their dense silanol groups and denaturation. In this study, the surfaces of amorphous silica particles with a lower silanol group density were modified with a small amount of chlorine during the synthesis process to form a specific surface layer by adsorbing water molecules and ions in the biological fluid, thereby controlling the protein adsorption state. Specifically, the hydration state on the surface of the amorphous silica particles containing trace amounts of chlorine was evaluated, and the surface layer (especially the hydration state) for the adsorption of antibody proteins while maintaining their steric structures was evaluated and discussed. The results showed that the inclusion of trace amounts of chlorine increased the silanol groups and Si-Cl bonds in the topmost surface layer of the particles, thereby inducing the adsorption of ions and water molecules in the biological fluid. Then, it was found that a novel surface layer was formed by the effective adsorption of Na and phosphate ions, which would change the proportion of the components in the hydration layer. In particular, the proportion of the free water component increased by 21% with the doping of chlorine. Antibody proteins were effectively adsorbed on the particles doped with trace amounts of chlorine, and their steric adsorption states were evaluated. It was found that the proteins were clearly adsorbed and maintained the steric state of their secondary structure. In the immunoreactivity tests using streptavidin and biotin, biotin bound to the chlorine-doped particles showed efficient reactivity. In conclusion, this study is the first to discover the surface layer of the amorphous silica particles to maintain the steric structures of adsorbed proteins, which is expected to be used as a carrier particle for antibody test kits and immunochromatography.
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Cloro , Dióxido de Silício , Propriedades de Superfície , Dióxido de Silício/química , Cloro/química , Adsorção , Tamanho da Partícula , Anticorpos/químicaRESUMO
Major depression disorder is a severe mental illness often linked with metabolic disorders. Adiponectin is an adipocyte-secreted circulatory hormone with antidiabetic and glucose/lipid modulation capacities. Studies have demonstrated the pathophysiological roles of adiponectin involved in various neurological disorders, including depression. However, the underlying mechanisms are poorly understood. Here we showed that adiponectin deprivation enhanced antidepressive-like behaviors in the LPS-induced model of depression. APN KO mice displayed increased cytokines (both pro and anti-inflammatory), accompanied by an impaired expression of adiponectin receptors (mRNA/protein level) and decreasing IBA-1 level in the cortex and primary microglia of LPS treated APN KO mice. Further, LPS-treatment significantly reduced p-NFκB expression in the microglia of APN KO mice. However, the Bay11-7082 treatment recovered p-NFκB expression in the cortex of APN KO mice in the presence of LPS. Interestingly, the antidepressant potentials of APN KO mice were abolished by TrkB antagonist K252a, IKK inhibitor Bay11-7082, and AdipoRon suggesting crosstalk between TrkB/BDNF signaling and NFκB in depression. Furthermore, the effects of Bay11-7082 were abolished by a TrkB/BDNF activator (7,8-DHF), indicating a critical role of TrkB/BDNF signaling. Taken together, these findings showed that dysregulated neuroinflammatory status and BDNF signaling might underlie the antidepressive-like behaviors of APN KO mice. NFκB elicited BDNF changes may be accountable for the pathogenesis of LPS induced depression, where APN might present an alternative therapeutic target for depressive disorders.
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Adiponectina , Fator Neurotrófico Derivado do Encéfalo , Adiponectina/farmacologia , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Transdução de SinaisRESUMO
A quartz crystal microbalance with dissipation (QCM-D) analysis was used to investigate fetal bovine serum (FBS) protein preadsorption on a hydroxyapatite (HAp) surface and the subsequent adhesion process of fibroblasts as compared with the case of oxidized poly(styrene) (PSox). The results showed that the preadsorption of FBS proteins on HAp promoted the subsequent initial cell adhesion ability. Moreover, the measured frequency (Δf) and dissipation shift (ΔD) curves, ΔD-Δf plots and viscoelastic analysis were used to study the initial cell adhesion process in real time. It was suggested that FBS-HAp showed sensitive changes in mass and viscoelasticity as compared with FBS-PSox, which realized the in situ reflection of the cell adhesion state, and the interfacial reactions between the cells and FBS-HAp surfaces such as dehydration and binding occurred to promote the initial cell adhesion and spreading. The viscoelastic analysis of the interface layer showed that the adhered cells on FBS-HAp could secrete some viscous substances such as extracellular matrix (ECM) proteins at the interfaces to provide good adhesion behaviors, and the Voigt-based viscoelastic model could clearly reveal the cellular interfacial viscoelasticity depending on the substrate surface. In addition, the morphology of cells was observed by confocal laser scanning microscopy (CLSM) and atomic force microscopy (AFM), and it was found that the pseudopodia were more uniformly stretched on FBS-HAp than on FBS-PSox. Furthermore, the state of the interfacial protein layer was analyzed by localized Fourier-transform infrared (FT-IR) spectroscopy and fluorescence microscopy (FLM), and it was indicated that the type of substrate affects the formation state of ECM proteins, resulting in changes in cell adhesion properties and morphology. The abundant formation of connective proteins (i.e., collagen type I) on FBS-HAp promoted subsequent pseudopodia formation and cell spreading. Therefore, the initial adhesion properties of fibroblasts on the FBS-HAp surface were systematically studied, which is of great importance for understanding the interfacial interaction between biomaterials and cells, and has great application value in biomedical fields.
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Durapatita , Nanopartículas , Durapatita/química , Espectroscopia de Infravermelho com Transformada de Fourier , Proteínas , Adesão Celular , FibroblastosRESUMO
BACKGROUND: A wide spectrum of changes occurs in the brain with age, from molecular to morphological aspects, and inflammation accompanied by mitochondria dysfunction is one of the significant factors associated with age. Adiponectin (APN), an essential adipokine in glucose and lipid metabolism, is involved in the aging; however, its role in brain aging has not been adequately explored. Here, we aimed to explore the relationship between APN deficiency and brain aging using multiple biochemical and pharmacological methods to probe APN in humans, KO mice, primary microglia, and BV2 cells. RESULTS: We found that declining APN levels in aged human subjects correlated with dysregulated cytokine levels, while APN KO mice exhibited accelerated aging accompanied by learning and memory deficits, anxiety-like behaviors, neuroinflammation, and immunosenescence. APN-deficient mice displayed aggravated mitochondrial dysfunction and HDAC1 upregulation. In BV2 cells, the APN receptor agonist AdipoRon alleviated the mitochondrial deficits and aging markers induced by rotenone or antimycin A. HDAC1 antagonism by Compound 60 (Cpd 60) improved mitochondrial dysfunction and age-related inflammation, as validated in D-galactose-treated APN KO mice. CONCLUSION: These findings indicate that APN is a critical regulator of brain aging by preventing neuroinflammation associated with mitochondrial impairment via HDAC1 signaling.
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BACKGROUND: Selective serotonin reuptaker inhibitors, including fluoxetine, are widely studied and prescribed antidepressants, while their exact molecular and cellular mechanism are yet to be defined. We investigated the involvement of HDAC1 and eEF2 in the antidepressant mechanisms of fluoxetine using a lipopolysaccharide (LPS)-induced depression-like behavior model. METHODS: For in vivo analysis, mice were treated with LPS (2 mg/kg BW), fluoxetine (20 mg/kg BW), HDAC1 activator (Exifone: 54 mg/kg BW) and NH125 (1 mg/kg BW). Depressive-like behaviors were confirmed via behavior tests including OFT, FST, SPT, and TST. Cytokines were measured by ELISA while Iba-1 and GFAP expression were determined by immunofluorescence. Further, the desired gene expression was measured by immunoblotting. For in vitro analysis, BV2 cell lines were cultured; treated with LPS, exifone, and fluoxetine; collected; and analyzed. RESULTS: Mice treated with LPS displayed depression-like behaviors, pronounced neuroinflammation, increased HDAC1 expression, and reduced eEF2 activity, as accompanied by altered synaptogenic factors including BDNF, SNAP25, and PSD95. Fluoxetine treatment exhibited antidepressant effects and ameliorated the molecular changes induced by LPS. Exifone, a selective HDAC1 activator, reversed the antidepressant and anti-inflammatory effects of fluoxetine both in vivo and in vitro, supporting a causing role of HDAC1 in neuroinflammation allied depression. Further molecular mechanisms underlying HDAC1 were explored with NH125, an eEF2K inhibitor, whose treatment reduced immobility time, altered pro-inflammatory cytokines, and NLRP3 expression. Moreover, NH125 treatment enhanced eEF2 and GSK3ß activities, BDNF, SNAP25, and PSD95 expression, but had no effects on HDAC1. CONCLUSIONS: Our results showed that the antidepressant effects of fluoxetine may involve HDAC1-eEF2 related neuroinflammation and synaptogenesis.
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Antidepressivos de Segunda Geração/uso terapêutico , Depressão/metabolismo , Quinase do Fator 2 de Elongação/biossíntese , Fluoxetina/uso terapêutico , Histona Desacetilase 1/biossíntese , Lipopolissacarídeos/toxicidade , Animais , Antidepressivos de Segunda Geração/farmacologia , Linhagem Celular , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Modelos Animais de Doenças , Quinase do Fator 2 de Elongação/antagonistas & inibidores , Fluoxetina/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fosforilação/efeitos dos fármacos , Fosforilação/fisiologiaRESUMO
Previous studies have demonstrated a close association between an altered immune system and major depressive disorders, and inhibition of neuroinflammation may represent an alternative mechanism to treat depression. Recently, the anti-inflammatory activity of ibrutinib has been reported. However, the effect of ibrutinib on neuroinflammation-induced depression and its underlying mechanism has not been comprehensively studied. Therefore, we aimed to elucidate the potential anti-depressive role and mechanism of ibrutinib against neuroinflammation-induced depression and synaptic defects. Our results showed that ibrutinib treatment significantly reduced lipopolysaccharide (LPS)-induced depressive-like behaviors and neuroinflammation via inhibiting NF-kB activation, decreasing proinflammatory cytokine levels, and normalizing redox signaling and its downstream components, including Nrf2, HO-1, and SOD2, as well as glial cell activation markers, such as Iba-1 and GFAP. Further, ibrutinib treatment inhibited LPS-activated inflammasome activation by targeting NLRP3/P38/Caspase-1 signaling. Interestingly, LPS reduced the number of dendritic spines and expression of BDNF, and synaptic-related markers, including PSD95, snap25, and synaptophysin, were improved by ibrutinib treatment in the hippocampal area of the mouse brain. In conclusion, our findings suggest that ibrutinib can alleviate neuroinflammation and synaptic defects, suggesting it has antidepressant potential against LPS-induced neuroinflammation and depression.
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Transtorno Depressivo Maior , Lipopolissacarídeos , Adenina/análogos & derivados , Animais , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Inflamassomos , Camundongos , PiperidinasRESUMO
Major depressive disorder (MDD) is a life-threatening illness characterized by mood changes and high rates of suicide. Although the role of neuroinflammation in MMD has been studied, the mechanistic interplay between antidepressants, neuroinflammation, and autophagy is yet to be investigated. The present study investigated the effect of melatonin on LPS-induced neuroinflammation, depression, and autophagy impairment. Our results showed that in mice, lipopolysaccharide (LPS) treatment induced depressive-like behaviors and caused autophagy impairment by dysregulating ATG genes. Moreover, LPS treatment significantly increased the levels of cytokines (TNFα, IL-1ß, IL-6), enhanced NF-á´B phosphorylation, caused glial (astrocytes and microglia) cell activation, dysregulated FOXO3a expression, increased the levels of redox signaling molecules such as ROS/TBARs, and altered expression of Nrf2, SOD2, and HO-1. Melatonin treatment significantly abolished the effects of LPS, as demonstrated by improved depressive-like behaviors, normalized autophagy-related gene expression, and reduced levels of cytokines. Further, we investigated the role of autophagy in LPS-induced depressive-like behavior and neuroinflammation using autophagy inhibitors 3-MA and Ly294002. Interestingly, inhibitor treatment significantly abolished and reversed the anti-depressive, pro-autophagy, and anti-inflammatory effects of melatonin. The present study concludes that the anti-depressive effects of melatonin in LPS-induced depression might be mediated via autophagy modulation through FOXO3a signaling.
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Astrócitos/metabolismo , Transtorno Depressivo Maior , Proteína Forkhead Box O3/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Melatonina/farmacologia , Microglia/metabolismo , Proteínas do Tecido Nervoso/biossíntese , Animais , Astrócitos/patologia , Autofagia/efeitos dos fármacos , Transtorno Depressivo Maior/induzido quimicamente , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/patologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Lipopolissacarídeos/toxicidade , Masculino , CamundongosRESUMO
BACKGROUND: It is known that Fas ligand (FasL) is involved in the development of intervertebral disc degeneration (IDD). A recent study reported that lncRNA MAGI2-AS3 up-regulated the expression of FasL to promote breast cancer. Therefore, we investigated the roles that lncRNA MAGI2-AS3 might play in IDD. METHODS: A total of 66 IDD patients (IDD group) and 58 healthy volunteers (Control group) were recruited in this study. Quantitative real-time PCR (qRT-PCR) and western blot were used to investigate gene expression levels. Cell transfections were carried out to analyze gene interactions. The diagnostic value of lncRNA MAGI2-AS3 for IDD was assessed by ROC curve analysis. RESULTS: The expression levels of plasma lncRNA MAGI2-AS3 were lower in IDD patients compared to that in the control group. Down-regulation of lncRNA MAGI2-AS3 effectively distinguished IDD patients from the control group. The expression levels of plasma lncRNA MAGI2-AS3 were significantly increased after the treatments. Over-expression of lncRNA MAGI2-AS3 inhibited the expression of FasL, while the silencing of lncRNA MAGI2-AS3 promoted the expression of FasL in nucleus pulposus (NP) cells. CONCLUSIONS: Therefore, lncRNA MAGI2-AS3 is down-regulated in IDD and participates in the regulation of FasL expression in nucleus pulposus (NP) cells.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Regulação para Baixo/genética , Proteína Ligante Fas/genética , Guanilato Quinases/genética , Degeneração do Disco Intervertebral/genética , Núcleo Pulposo/metabolismo , RNA Longo não Codificante/genética , Proteínas Adaptadoras de Transdução de Sinal/sangue , Adulto , Idoso , Células Cultivadas , Proteína Ligante Fas/metabolismo , Feminino , Inativação Gênica , Guanilato Quinases/sangue , Humanos , Degeneração do Disco Intervertebral/sangue , Masculino , Pessoa de Meia-Idade , Núcleo Pulposo/patologia , RNA Longo não Codificante/sangue , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/genética , TransfecçãoRESUMO
Hypoxia-induced inhibition of apoptosis in pulmonary artery endothelial cells (PAECs) has an important role in pulmonary arterial remodeling leading to aggravated hypoxic pulmonary arterial hypertension. However, the mechanisms involved in the hypoxia-induced inhibition of PAEC apoptosis have not been elucidated. e-selectin and biliverdin reductase (BVR) have been reported to contribute to the cascade of apoptosis in several cell lines but not in PAECs. In the present study, we show that the expression of e-selectin and BVR was both up-regulated by hypoxia in PAECs. Moreover, hypoxia attenuated the decreased cell survival and apoptotic protein expression, and increased DNA fragmentation induced by serum deprivation in the PAECs, which was mediated by the e-selectin/BVR pathway. In addition, by examining the mitochondrial membrane potential and mitochondrial membrane proteins (Bcl-2 and BAX), we show that the mitochondrial-dependent apoptosis pathway was necessary for the e-selectin/BVR pathway inducing the anti-apoptotic effect of hypoxia in PAECs. Taken all together, our data show that the e-selectin/BVR pathway participates in the inhibitory process of hypoxia in PAEC apoptosis which is mediated by the mitochondrial-dependent apoptosis pathway.
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Apoptose , Selectina E/metabolismo , Células Endoteliais/enzimologia , Hipóxia/enzimologia , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo , Artéria Pulmonar/enzimologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Bovinos , Células Cultivadas , Modelos Animais de Doenças , Selectina E/genética , Células Endoteliais/patologia , Hipóxia/patologia , Masculino , Potencial da Membrana Mitocondrial , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Artéria Pulmonar/patologia , Interferência de RNA , Ratos Wistar , Transdução de Sinais , Fatores de Tempo , Transfecção , Regulação para CimaRESUMO
As a classical herb pair in clinics of traditional Chinese medicine, Curcumae Rhizoma-Sparganii Rhizoma (HP CR-SR) is used for activating blood circulation to remove blood stasis. The essential components in HP CR-SR and its single herbs were comparatively analyzed using gas chromatography-mass spectrometry data. 66, 22, and 54 components in volatile oils of Curcumae Rhizoma, Sparganii Rhizoma, and HP CR-SR were identified, and total contents accounted for 75.416%, 91.857%, and 79.553% respectively. The thirty-eight components were found in HP CR-SR, and not detected in single herbs Curcumae Rhizoma and Sparganii Rhizoma. The highest radical trapping action was seen by an essential oil of HP CR-SR (IC50 = 0.59 ± 0.04 mg/mL). Furthermore, the HP CR-SR essential oil showed more remarkable cytotoxicity on tumor cell lines than that of the single herbs Curcumae Rhizoma and Sparganii Rhizoma in a dose-dependent manner: IC50 values showing 32.32 ± 5.31 µg/mL (HeLa), 34.76 ± 1.82 µg/mL (BGC823), 74.84 ± 1.66 µg/mL (MCF-7), 66.12 ± 11.23 µg/mL (SKOV3), and 708.24 ± 943.91 µg/mL (A549), respectively. In summary, the essential oil of HP CR-SR is different from any one of Curcumae Rhizoma and Sparganii Rhizoma, nor simply their superposition, and HP CR-SR oil presented more remarkable anticancer and antioxidant activities compared with Curcumae Rhizoma and Sparganii Rhizoma oils.
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Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Curcuma/química , Óleos Voláteis/química , Antineoplásicos Fitogênicos/química , Antioxidantes/química , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Óleos Voláteis/farmacologia , Rizoma/químicaRESUMO
Dianbaizhu, a folk medicine from Gaultheria leucocarpa BLUME var. yunnanensis (FRANCH.) T. Z. HSU & R. C. FANG (Ericaceae) used as an antirheumatic, has multiple plant origins and officinal parts. A rapid high-performance liquid chromatography with diode array detector (HPLC-DAD) method was established for the simultaneous determination of the characteristic ingredient methyl benzoate-2-O-ß-D-glucopyranosyl(1 â 2) [O-ß-D-xylopyranosyl(1 â 6)]-O-ß-D-glucopyranoside and seven bioactive constituents in eight Gaultheria species. This chromatographic method is precise, accurate, and stable. Kruskal-Wallis analysis, hierarchical cluster analysis, and factor analysis were used to analyze the content of reference compounds in different Gaultheria species and officinal parts. The analyses showed significant differences (p<0.05) in Gaultheria species but few differences (p>0.05) in their medicinal parts. G. leucocarpa var. yunnanensis appeared to the best among the Gaultheria species tested for the treatment of rheumatic diseases. Taken together, the results show that this simultaneous quantiï¬cation of multiple active constituents using HPLC-DAD combined with chemometrics can be reliably applied to evaluate the quality of Dianbaizhu.
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Antirreumáticos/isolamento & purificação , Benzoatos/isolamento & purificação , Gaultheria/química , Glucosídeos/isolamento & purificação , Medicina Tradicional , Extratos Vegetais/química , Antirreumáticos/análise , Benzoatos/análise , Cromatografia Líquida de Alta Pressão/métodos , Análise por Conglomerados , Glucosídeos/análiseRESUMO
Component fingerprints are a recognized method used worldwide to evaluate the quality of traditional Chinese medicines (TCMs). To foster the strengths and circumvent the weaknesses of the fingerprint technique in TCM, spectrum-effect relationships would complementarily clarify the nature of pharmacodynamic effects in the practice of TCM. The application of the spectrum-effect relationship method is crucial for understanding and interpreting TCM development, especially in the view of the trends towards TCM modernization and standardization. The basic requirement for using this method is in-depth knowledge of the active material basis and mechanisms of action. It is a novel and effective approach to study TCMs and great progress has been made, but to make it more accurate for TCM research purposes, more efforts are needed. In this review, the authors summarize the current knowledge about the spectrum-effect relationship method, including the fingerprint methods, pharmacodynamics studies and the methods of establishing relationships between the fingerprints and pharmacodynamics. Some speculation regarding future perspectives for spectrum-effect relationship approaches in TCM modernization and standardization are also proposed.
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Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa/métodos , Animais , Padrões de Referência , PesquisaRESUMO
This review completely covers the various aspects of hydroxyapatite (HAp) nanoparticles and their role in different biological situations, and provides the surface and interface contents on (i) hydroxyapatite nanoparticles and their hybridization with organic molecules, (ii) surface designing of hydroxyapatite nanoparticles to provide their biocompatibility and photofunction, and (iii) coating technology of hydroxyapatite nanoparticles. In particular, we summarized how the HAp nanoparticles interact with the different ions and molecules and highlighted the potential for hybridization between HAp nanoparticles and organic molecules, which is driven by the interactions of the HAp nanoparticle surface ions with several functional groups of biological molecules. In addition, we highlighted the studies focusing on the interfacial interactions between the HAp nanoparticles and proteins for exploring the enhanced biocompatibility. Such studies focus on how these interactions affect the hydration layers and protein adsorption. However, the hydration layer state involves diverse molecular interactions that can alter the shape of the adsorbed proteins, thereby affecting cell adhesion and spreading on the surfaces. We also summarized the relationship between the surface properties of the HAp nanoparticles and the hydration layer. Furthermore, we spotlighted the cytocompatible photoluminescent probes that can be developed by designing HAp/organic nanohybrid structures. We then emphasized the importance of photofunctionalization in theranostics, which involves the integration of diagnostics and therapy based on the surface design of the HAp nanoparticles. Furthermore, the coating techniques using HAp nanoparticles and HAp nanoparticle/polymer composites were outlined for fusing base biomaterials with biological tissues. The advantages of HAp/biocompatible polymer composite coatings include the ability to effectively cover porous or irregularly shaped surfaces while controlling the thickness of the coating layer, and the addition of HAp nanoparticles to the polymer matrix improves the mechanical properties, increases the roughness, and forms the morphologies that mimic bone nanostructures. Therefore, the fundamental design of hydroxyapatite nanoparticles and their surfaces was suggested from various aspects for biomedical applications.
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Durapatita , Nanopartículas , Propriedades de Superfície , Durapatita/química , Nanopartículas/química , Humanos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/síntese química , AnimaisRESUMO
In the biomedical fields of bone regenerative therapy, the immobilization of proteins on the bioceramic particles to maintain their highly ordered structures is significantly important. In this review, we comprehensively discussed the importance of the specific surface layer, which can be called "non-apatitic layer", affecting the immobilization of proteins on particles such as hydroxyapatite and amorphous silica. It was suggested that the water molecules and ions contained in the non-apatitic layer can determine and control the protein immobilization states. In amorphous silica particles, the direct interactions between proteins and silanol groups make it difficult to immobilize the proteins and maintain their highly ordered structures. Thus, the importance of the formation of a surface layer consisting of water molecules and ions (i.e., a non-apatitic layer) on the particle surfaces for immobilizing proteins and maintaining their highly ordered structures was suggested and described. In particular, chlorine-containing amorphous silica particles were also described, which can effectively form the surface layer of protein immobilization carriers. The design of the bio-interactive and bio-compatible surfaces for protein immobilization while maintaining the highly ordered structures will improve cell adhesion and tissue formation, thereby contributing to the construction of social infrastructures to support super-aged society.
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Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease. Exosomes were involved in different inflammatory diseases, but their roles in CRSwNP were poorly explored. Method: We collected serum samples from 8 CRSwNP patients and 8 healthy controls (HC) and isolated their exosomes. MiRNA sequencing was performed for the exosome samples and differentially expressed miRNAs were identified. The top 3 differentially expressed exosomal miRNAs were confirmed in 2 validation cohorts, and their diagnostic values, predictive values for eosinophilic endotype, and recurrence were evaluated. Results: Distinctive serum exosomal miRNA profiles were observed between CRSwNP and HC groups. Reverse transcription-polymerase chain reaction results in the first validation cohort revealed that serum exosomal miR-141-3p levels were increased, and miR-18a-5p and miR-3679-5p levels were decreased in the CRSwNP group compared to the HC group. These 3 miRNAs were further validated in the second validation cohort, and the results showed that miR-141-3p levels were elevated and miR-3679-5p levels were reduced in the serum exosomes in the eosinophilic CRSwNP group in comparison with the non-eosinophilic CRSwNP group. Receiver operating characteristic (ROC) curves highlighted that exosomal miR-141-3p and miR-3679-5p exhibited promising values for predicting the eosinophilic endotype. The patients in the second cohort were followed up for 2 years, and categorized into recurrence and non-recurrence groups. The serum exosomal miR-141-3p levels were increased and miR-3679-5p levels were reduced in the recurrence group in comparison with the non-recurrence group. ROC curves and Kaplan-Meier survival analysis revealed significant associations between the levels of exosomal miR-141-3p and miR-3679-5p and the risk of postoperative recurrence. Conclusions: This study identified unique miRNA expression patterns in serum exosomes of CRSwNP patients. Circulating exosomal miR-141-3p and miR-3679-5p emerged as novel biomarkers for diagnosing CRSwNP, predicting the eosinophilic endotype, and forecasting postoperative recurrence.
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Stress response is a fundamental mechanism for cell survival, providing protection under unfavorable conditions. Mitochondrial stress, in particular, can trigger mitophagy, a process that restores cellular health. Exhaustive exercise (EE) is a form of acute mitochondrial stress. The objective of this current study is to investigate the impact of EE on tau pathology in pR5 mice, as well as the potential underlying mechanisms. To evaluate this, we examined the levels of total and phosphorylated tau in the hippocampus of pR5 mice, both with and without EE treatment. Furthermore, the application of weighted correlation network analysis (WGCNA) was employed to identify protein modules associated with the phenotype following the proteomic experiment. The findings of our study demonstrated a significant decrease in tau phosphorylation levels upon EE treatment, in comparison to the pR5 group. Moreover, the proteomic analysis provided additional insights, revealing that the mitigation of tau pathology was primarily attributed to the modulation of various pathways, such as translation factors and oxidative phosphorylation. Additionally, the analysis of heatmaps revealed a significant impact of EE treatment on the translation process and electron transport chain in pR5 mice. Furthermore, biochemical analysis provided further confirmation that EE treatment effectively modulated the ATP level in pR5 mice. In conclusion, our study suggests that the observed decrease in tau phosphorylation resulting from EE treatment may primarily be attributed to its regulation of the translation process and enhancement of mitochondrial function.
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Doença de Alzheimer , Fenômenos Biológicos , Camundongos , Animais , Camundongos Transgênicos , Fosforilação , Proteínas tau/genética , Proteínas tau/metabolismo , Transporte de Elétrons , Proteômica , Fosforilação Oxidativa , Processamento de Proteína Pós-Traducional , Doença de Alzheimer/genéticaRESUMO
The link between neuroinflammation and depression is a subject of growing interest in neuroscience and psychiatry; meanwhile, the precise mechanisms are still being unrevealed. However, glial cell activation, together with cytokine level elevation, suggests a connection between neuroinflammation and the development or exacerbation of depression. Glial cells (astrocytes) communicate with neurons via their extracellular neurotransmitter receptors, including glutamate receptors NMDARs. However, these receptor roles are controversial and enigmatic in neurological disorders, including depression. Therefore, we hypothesized whether NMDAR subnit NR2C deletion in the astrocytes exhibited anti-depressive effects concurrent with neuroinflammation prevention. To assess, we prepared astrocytic-NR2C knockout mice (G-2C: GFAPCre+Grin2Cflox/flox), followed by LPS administration, behavior tests, and biochemical analysis. Stimulatingly, astrocytic-NR2C knockout mice (G-2C) did not display depressive-like behaviors, neuroinflammation, and synaptic deficits upon LPS treatment. PI3K was impaired upon LPS administration in control mice (Grin2Cflox/flox); however, they were intact in the hippocampus of LPS-treated G-2C mice. Further, PI3K activation (via PTEN inhibition by BPV) restored neuroinflammation and depressive-like behavior, accompanied by altered synaptic protein and spine numbers in G-2C mice in the presence of LPS. In addition, NF-κB and JNK inhibitor (BAY, SP600125) treatments reversed the effects of BPV. Moreover, these results were further validated with an NR2C antagonist DQP-1105. Collectively, these observations support the astrocytic-NR2C contribution to LPS-induced neuroinflammation, depression, and synaptic deficits.
Assuntos
Astrócitos , Depressão , Hipocampo , Lipopolissacarídeos , Camundongos Knockout , Doenças Neuroinflamatórias , Receptores de N-Metil-D-Aspartato , Animais , Astrócitos/metabolismo , Astrócitos/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de N-Metil-D-Aspartato/genética , Depressão/imunologia , Camundongos , Doenças Neuroinflamatórias/imunologia , Doenças Neuroinflamatórias/tratamento farmacológico , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismoRESUMO
The genus Gaultheria, comprised of approximately 134 species, is mostly used in ethnic drugs to cure rheumatism and relieve pain. Phytochemical investigations of the genus Gaultheria have revealed the presence of methyl salicylate derivatives, C6-C3 constituents, organic acids, terpenoids, steroids, and other compounds. Methyl salicylate glycoside is considered as a characteristic ingredient in this genus, whose anti-rheumatic effects may have a new mechanism of action. In this review, comprehensive information on the phytochemistry, volatile components and the pharmacology of the genus Gaultheria is provided to explore its potential and advance research.