RESUMO
Hybrid waveguides consisting of two-dimensional layered materials pad on the surface of optical waveguides suffer from a nonuniform and loose contact between the two-dimensional material and the waveguide, which can reduce the efficiency of the pulsed laser. Here, we present high-performance passively Q-switched pulsed lasers in three distinct structures of monolayer graphene-Nd:YAG hybrid waveguides irradiated by energetic ions. The ion irradiation enables the monolayer graphene a tight contact and strong coupling with the waveguide. As a result, Q-switched pulsed lasers with narrow pulse width and high repetition rate are obtained in three designed hybrid waveguides. The narrowest pulse width is 43.6â ns, provided by the ion-irradiated Y-branch hybrid waveguide. This study paves the way toward developing on-chip laser sources based on hybrid waveguides by using ion irradiation.
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This study investigated the effects of infliximab (INF) on oxidative stress and inflammation in H9c2 cardiomyocytes, aiming to address the damage caused by myocardial infarction (MI). H9c2 cells were divided into three groups: control, H2O2 treatment, and H2O2+INF. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. Protein expression of SOD1, SOD2, TNF-α, and IL-1ß was examined through Western blot, while mRNA expression was analyzed via polymerase chain reaction (PCR). Reactive oxygen species (ROS) levels were measured, and IL-1ß immunofluorescence was utilized to observe inflammation. The expression of IκB-α and IκKα was evaluated to investigate the mechanism of action. INF significantly improved H9c2 cell viability and reduced LDH and MDA levels in the supernatant. Moreover, INF enhanced the expression of SOD1 and SOD2, reducing ROS production. In comparison to the H2O2 group, TNF-α and IL-1ß expression markedly decreased in the H2O2+INF group. Additionally, the fluorescence intensity of IL-1ß immunofluorescence was higher in the H2O2+INF group. INF treatment decreased TNF-α and IL-1ß expression and reduced IL-1ß fluorescence intensity. Furthermore, INF increased IκB-α expression and decreased IκKα expression, suggesting inhibition of the nuclear factor-κB (NF-κB) pathway. In summary, INF effectively suppressed H2O2-induced oxidative stress and inflammation in H9c2 cells by targeting the NF-κB pathway.
Assuntos
Peróxido de Hidrogênio , NF-kappa B , Humanos , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Infliximab/farmacologia , Infliximab/metabolismo , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Superóxido Dismutase-1/metabolismo , Superóxido Dismutase-1/farmacologia , Estresse Oxidativo , Miócitos Cardíacos/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismoRESUMO
Platycodonis Radix (PR), a widely consumed herbal food, and its bioactive constituents, platycodins, have therapeutic potential for lung inflammation. Transient Receptor Potential Ankyrin 1 (TRPA1), which is essential for the control of inflammation, may be involved in the development of inflammation in the lungs. The aim of this study was to determine the TRPA1-targeted effects of PR against pulmonary inflammation and to investigate the affinity of PR constituents for TRPA1 and their potential mechanisms of action. Using a C57BL/6J mouse lipopolysaccharides (LPS) intratracheal instillation pneumonia model and advanced analytical techniques (UPLC-Q-TOF-MS/MS, molecular docking, immuno-fluorescence), five platycodins were isolated from PR, and the interaction between these platycodins and hTRPA1 was verified. Additionally, we analyzed the impact of platycodins on LPS-induced TRPA1 expression and calcium influx in BEAS-2B cells. The results indicated that PR treatment significantly reduced the severity of LPS-triggered inflammation in the mouse model. Interestingly, there was a mild increase in the expression of TRPA1 caused by PR in healthy mice. Among five isolated platycodins identified in the PR extract, Platycodin D3 (PD3) showed the highest affinity for hTRPA1. The interaction between platycodins and TRPA1 was verified through molecular docking methods, highlighting the significance of the S5-S6 pore-forming loop in TRPA1 and the unique structural attributes of platycodins. Furthermore, PD3 significantly reduced LPS-induced TRPA1 expression and calcium ion influx in BEAS-2B cells, substantiating its own role as an effective TRPA1 modulator. In conclusion, PR and platycodins, especially PD3, show promise as potential lung inflammation therapeutics. Further research should explore the precise mechanisms by which platycodins modulate TRPA1 and their broader therapeutic potential.
Assuntos
Pneumonia , Canais de Potencial de Receptor Transitório , Camundongos , Animais , Canais de Potencial de Receptor Transitório/metabolismo , Lipopolissacarídeos/toxicidade , Canal de Cátion TRPA1/metabolismo , Espectrometria de Massas em Tandem , Cálcio/metabolismo , Simulação de Acoplamento Molecular , Camundongos Endogâmicos C57BL , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológicoRESUMO
BACKGROUND: Coinfection with human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type 1 (HTLV-1) diminishes the value of the CD4+ T-cell count in diagnosing AIDS, and increases the rate of HTLV-1-associated myelopathy. It remains elusive how HIV-1/HTLV-1 coinfection is related to such characteristics. We investigated the mutual effect of HIV-1/HTLV-1 coinfection on their integration sites (ISs) and clonal expansion. METHODS: We extracted DNA from longitudinal peripheral blood samples from 7 HIV-1/HTLV-1 coinfected, and 12 HIV-1 and 13 HTLV-1 monoinfected individuals. Proviral loads (PVL) were quantified using real-time polymerase chain reaction (PCR). Viral ISs and clonality were quantified by ligation-mediated PCR followed by high-throughput sequencing. RESULTS: PVL of both HIV-1 and HTLV-1 in coinfected individuals was significantly higher than that of the respective virus in monoinfected individuals. The degree of oligoclonality of both HIV-1- and HTLV-1-infected cells in coinfected individuals was also greater than in monoinfected subjects. ISs of HIV-1 in cases of coinfection were more frequently located in intergenic regions and transcriptionally silent regions, compared with HIV-1 monoinfected individuals. CONCLUSIONS: HIV-1/HTLV-1 coinfection makes an impact on the distribution of viral ISs and clonality of virus-infected cells and thus may alter the risks of both HTLV-1- and HIV-1-associated disease.
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Coinfecção , Infecções por HIV/complicações , HIV-1 , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical/epidemiologia , Contagem de Linfócito CD4 , Infecções por HIV/epidemiologia , HIV-1/genética , HIV-1/isolamento & purificação , Infecções por HTLV-I/epidemiologia , Sequenciamento de Nucleotídeos em Larga Escala , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Paraparesia Espástica Tropical/diagnóstico , Provírus/genética , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Segmental infantile hemangiomas affecting the upper body are associated with PHACE(S) (Posterior fossa anomalies, Hemangioma, Arterial anomalies, Cardiac anomalies, Eye anomalies, and Sternal defects) syndrome, whereas segmental infantile hemangiomas affecting the lower body are the cutaneous hallmark of LUMBAR (Lower body hemangioma and other skin defects, Urogenital anomalies and Ulceration, Myelopathy, Bony deformities, Anorectal malformations and Arterial anomalies, and Renal anomalies) syndrome. We present two individuals with concurrent features of both PHACE and LUMBAR syndromes demonstrating an overlap phenotype. The overlapping features seen in our patients suggest that these syndromes occur on the same phenotypic spectrum and derive from a common embryonic pathophysiology.
Assuntos
Anormalidades Múltiplas , Coartação Aórtica , Anormalidades do Olho , Hemangioma , Síndromes Neurocutâneas , Anormalidades Múltiplas/diagnóstico , Anormalidades do Olho/diagnóstico , Hemangioma/diagnóstico , Humanos , Síndromes Neurocutâneas/diagnóstico , SíndromeRESUMO
Addition of citrus leaf extract (CLE) into frying oil was found to be renoprotective in rats that consumed heated palm oil diet. This study examined the effects of dietary CLE supplementation on renal vasoactive substances in rats given heated palm oil diet. Forty-two male Sprague-Dawley rats were randomly split and fed with (i) control, (ii) fresh palm oil (FPO), (iii) FPO + CLE, (iv) five-time-heated palm oil (5HPO), (v) 5HPO+CLE, (vii) ten-time-heated palm oil (10HPO) and (vii) 10HPO+CLE diets for 16 weeks. CLE was added into diet at 0.15% (w/w). CLE decreased renal angiotensin-converting enzyme, inducible nitric oxide synthase and angiotensin II expressions in rats given heated oil diets, but only decreased renal NADPH oxidase activity in the 5HPO group. Supplementation of citrus leaf extract has shown beneficial effects in regulating renal vasoactive substances in rats consumed heated palm oil diet.
Assuntos
Citrus , Rim , Óleo de Palmeira , Extratos Vegetais , Animais , Pressão Sanguínea , Citrus/química , Dieta , Suplementos Nutricionais , Masculino , Óleo de Palmeira/administração & dosagem , Extratos Vegetais/farmacologia , Óleos de Plantas/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Rapid and sensitive detection technology is the key to preventing food-borne disease outbreaks. In this study, a low-field nuclear magnetic resonance (NMR) biosensor based on polyamidoamine dendrimers was prepared for the rapid detection of Salmonella in milk. The polyamidoamine dendrimer was biotinylated by amide reaction and chelated to diethylene triamine pentacetate acid and gadolinium to form magnetic complexes. The antibody and magnetic complexes were combined through a streptavidin-biotin system using streptavidin as an intermediate bridge to obtain the immunoprobe. Salmonella was captured by the immunoprobe via antigen-antibody interaction and then separated from the mixture by membrane filtration. Finally, the longitudinal relaxation signal of the filtrate was obtained by NMR. The biosensor had excellent anti-interference capability and could detect Salmonella within 1.5 h at a sensitivity of 103 cfu mL-1. This method based on NMR can realize detection in complex samples and has the potential to be a quick and nondestructive method for detecting target bacteria.
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Técnicas Biossensoriais , Doenças Transmitidas por Alimentos/microbiologia , Gadolínio/química , Leite/microbiologia , Poliaminas/química , Salmonella/isolamento & purificação , Animais , Reações Antígeno-Anticorpo , Biotina/química , Dendrímeros/química , Feminino , Filtração , Doenças Transmitidas por Alimentos/prevenção & controle , Espectroscopia de Ressonância Magnética , Sensibilidade e Especificidade , Espectroscopia de Infravermelho com Transformada de Fourier , Estreptavidina/química , Fatores de TempoRESUMO
Rapid and sensitive detection of foodborne pathogens is of great importance for food safety. Here, a set of nuclear magnetic resonance (NMR) biosensors based on a O-carboxymethyl chitosan target gadolinium (Gd) probe was developed to quickly detect Salmonella in milk by combining NMR technology and bioimmunotechnology with membrane filtration technology. First, O-carboxymethyl chitosan (O-CMC) was biotinylated to prepare biotinylated O-carboxymethyl chitosan (biotin-O-CMC) through amide reaction, and biotinylated magnetic complexes (biotin-O-CMC-Gd) were obtained by using O-CMC, which has strong chelating adsorption on Gd. The target probe was obtained by combining biotin-O-CMC-Gd with the biotinylated antibody (biotin-antibody) via streptavidin (SA) by introducing the SA-biotin system. Then, Salmonella was captured by the target probe through antigen-antibody interaction. Finally, NMR was used to measure the longitudinal relaxation time (T1) of the filtrate collected by membrane filtration. This NMR biosensor with good specificity and high efficiency can detect Salmonella with the sensitivity of 1.8 × 103 cfu/mL within 2 h; in addition, it can realize the detection of complex samples because of its strong anti-interference capability and may open up a new method for rapid detection of Salmonella, which has a great application potential.
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Técnicas Biossensoriais , Biotina , Animais , Técnicas Biossensoriais/veterinária , Quitosana/análogos & derivados , Gadolínio , Espectroscopia de Ressonância Magnética , Leite , Salmonella , EstreptavidinaRESUMO
RHOA is a member of the Rho family of GTPases that are involved in fundamental cellular processes including cell adhesion, migration, and proliferation. RHOA can stimulate the formation of stress fibers and focal adhesions and is a key regulator of actomyosin dynamics in various tissues. In a Genematcher-facilitated collaboration, we were able to identify four unrelated individuals with a specific phenotype characterized by hypopigmented areas of the skin, dental anomalies, body asymmetry, and limb length discrepancy due to hemihypotrophy of one half of the body, as well as brain magnetic resonance imaging (MRI) anomalies. Using whole-exome and ultra-deep amplicon sequencing and comparing genomic data of affected and unaffected areas of the skin, we discovered that all four individuals carried the identical RHOA missense variant, c.139G>A; p.Glu47Lys, in a postzygotic state. Molecular modeling and in silico analysis of the affected p.Glu47Lys residue in RHOA indicated that this exchange is predicted to specifically alter the interaction of RHOA with its downstream effectors containing a PKN-type binding domain and thereby disrupts its ability to activate signaling. Our findings indicate that the recurrent postzygotic RHOA missense variant p.Glu47Lys causes a specific mosaic disorder in humans.
Assuntos
Alelos , Códon , Estudos de Associação Genética , Variação Genética , Placa Neural/metabolismo , Fenótipo , Proteína rhoA de Ligação ao GTP/genética , Adolescente , Adulto , Encéfalo/anormalidades , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância Magnética , Modelos Moleculares , Placa Neural/anormalidades , Placa Neural/embriologia , Conformação Proteica , Relação Estrutura-Atividade , Adulto Jovem , Proteína rhoA de Ligação ao GTP/químicaRESUMO
BACKGROUND: Coccidiosis is a prevalent problem in chicken production. Dietary addition of coccidiostats and vaccination are two approaches used to suppress coccidia in the practical production. Methionine (Met) is usually the first limiting amino acid that plays important roles in protein metabolism and immune functions in chickens. The present study is aimed to investigate whether increasing dietary Met levels will improve the anticoccidial effects in broilers medicated or vaccinated against coccidia under Eimeria (E.) tenella-challenged condition. Two thousand male Partridge Shank broiler chicks were obtained from a hatchery. After hatch, birds were weighed, color-marked and allocated equally into two anticoccidial treatments, namely medicated and vaccinated groups. Chicks were either fed, from 1 d of age, diets containing coccidiostat (narasin) or diets without the coccidiostat but were inoculated with an anticoccidial vaccine at 3 d of age. At 22 d of age, 1080 chicks among them were randomly allocated evenly into 6 groups under a 2 × 3 treatment with 2 anticoccidial programs and 3 dietary methionine (Met) levels. Chicks medicated or vaccinated against coccidia were fed diets containing 0.45%, 0.56% or 0.68% of Met from 22 to 42 d of age. All chicks were orally introduced with an amount of 5 × 104 sporulated oocysts of E. tenella at 24 d of age. The growth performance, serum anti-oxidative indexes, intestinal morphology, cecal lesion scores, fecal oocyst counts and immune parameters were measured. RESULTS: The results showed increasing dietary Met level from 0.45% to 0.56% and 0.68% improved weight gain and feed conversion of broilers medicated against coccidia. In contrast, higher dietary levels of Met did not improve growth performance of the vaccinated chickens. Higher Met levels helped the medicated chickens resist E. tenella infection, as indicated by improved intestinal morphology and immune functions as well as decreased cecal lesion and fecal oocyst counts. CONCLUSIONS: Anticoccidial vaccination is a better strategy for controlling coccidiosis than feeding narasin, due to not only greater growth performance, but also the lower Met supplementation. Furthermore, higher dietary Met levels improved growth performance of chickens medicated rather than vaccinated against coccidia under E. tenella-challenged condition.
Assuntos
Coccidiose/veterinária , Eimeria tenella , Metionina/farmacologia , Doenças das Aves Domésticas/parasitologia , Vacinas Protozoárias/uso terapêutico , Animais , Galinhas , Coccidiose/parasitologia , Coccidiose/prevenção & controle , Dieta/veterinária , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática/veterinária , Citometria de Fluxo/veterinária , Metionina/administração & dosagem , Contagem de Ovos de Parasitas/veterinária , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/prevenção & controle , Reação em Cadeia da Polimerase em Tempo Real/veterináriaRESUMO
Resistance of hepatocellular carcinoma (HCC) to systemic chemotherapy is partially due to presence of drug-resistant cancer stem cells. Bmi1 protein is essential for survival and proliferation of HCC cancer stem cells (CSCs). Here, we report that Bmi1 siRNA (Bmi1siR) loaded in cationic nanocapsules of cisplatin (NPC) eliminated stem cells in situ HCC in mice. NPC/Bmi1siR was fabricated via electrostatic complexation of Bmi1 siRNA to NPCs, which had cores composed of cisplatin and were coated with cationic lipids. In vivo, NPC/Bmi1siR showed higher anti-tumor activity in HCC bearing mice compared with cisplatin or NPC. Critically, both flow cytometry (FACS) analysis in vitro and histological examination in vivo revealed that side population or CD133+ HCC cells were dramatically decreased by NPC/Bmi1siR treatment, suggesting that HCC CSCs were eliminated. Altogether, our results suggest that drug resistance of HCC can be overcome by co-delivering Bmi1 siRNA with cisplatin in cationic nanocapsules.
Assuntos
Carcinoma Hepatocelular/terapia , Cisplatino/administração & dosagem , Neoplasias Hepáticas/terapia , Nanocápsulas/administração & dosagem , Células-Tronco Neoplásicas/efeitos dos fármacos , Complexo Repressor Polycomb 1/antagonistas & inibidores , RNA Interferente Pequeno/genética , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Apoptose , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Cátions , Ciclo Celular , Proliferação de Células , Cisplatino/farmacologia , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanocápsulas/química , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Complexo Repressor Polycomb 1/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
As an insulin sensitizer and modulator of inflammatory responses, adiponectin has become a therapeutic target for insulin resistance, diabetes, and diabetes-related complications. Wogonin possesses anti-oxidative, anti-inflammatory, and anti-diabetic abilities. However, its effect on generation and secretion of adiponectin is ill-defined in adipocytes. Here, we demonstrated that wogonin administration augmented intracellular adiponectin levels and attenuated adiponectin release in a dose- and time-dependent manner in mature 3T3-L1 adipocytes, along with a suppression of PKCδ phosphorylation. Wogonin treatment also prevented PKCδ overexpression-induced reduction of intracellular adiponectin levels and enhancement of adiponectin release. In addition, wogonin supplementation dramatically increased AMPK phosphorylation and SirT1 expression. Inhibition of either AMPK or SirT1 mitigated wogonin action on adiponectin production and release. Furthermore, inhibition of AMPK by its specific inhibitor markedly reduced wogonin-enhanced mRNA and protein expressions of SirT1. These results suggested that wogonin regulated expression and secretion of adiponectin via PKCδ/AMPK/SirT1 signaling pathway in mature 3T3-L1 adipocytes.
Assuntos
Adipócitos/efeitos dos fármacos , Adiponectina/genética , Adiponectina/metabolismo , Flavanonas/farmacologia , Células 3T3-L1 , Adenilato Quinase/metabolismo , Adipócitos/metabolismo , Animais , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Camundongos , Proteína Quinase C-delta/metabolismo , Via Secretória/efeitos dos fármacosRESUMO
Hepatocellular carcinoma (HCC) is a prevalent and lethal disease that is characterized by drug resistance. Doxorubicin (DOX) is a widely used chemotherapeutic drug and miR-375 has been shown to be a tumor suppressor in HCC. Here, we reported that miR-375 and DOX co-loaded into lipid-coated calcium carbonate nanoparticles (LCC-DOX/miR-375 NPs), enhanced the anti-tumor effects through combination therapy, and were highly effective in reversing drug resistance in HCC. LCC-DOX/miR-375 NPs were prepared by a reverse microemulsions method. In vitro, LCC-DOX/miR-375 NPs exhibited enhanced intracellular accumulation, pH-sensitive DOX release and potent cytotoxicity. In vivo, LCC-DOX/miR-375 NPs showed efficient antitumor effect both in xenograft and primary HCC murine models. Our results showed that the LCC-DOX/miR-375 nanoparticles provide a novel strategy to overcome the drug resistance and promote addictive effect between miR-375 and DOX in HCC.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Carbonato de Cálcio/química , Carcinoma Hepatocelular/terapia , Doxorrubicina/administração & dosagem , Lipídeos/química , Neoplasias Hepáticas/terapia , MicroRNAs/administração & dosagem , Nanopartículas/química , Animais , Antibióticos Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Nus , MicroRNAs/uso terapêuticoRESUMO
Bmi1 is a member of the polycomb group family of proteins, and it drives the carcinogenesis of various cancers and governs the self-renewal of multiple types of stem cells. Our previous studies have revealed that Bmi1 acts as an oncogene in hepatic carcinogenesis in an INK4a/ARF locus independent manner. However, whether Bmi1 can be used as a potential target for hepatocellular carcinoma treatment has not been fully confirmed yet. Here, we show that perturbation of Bmi1 expression by using short hairpin RNA can inhibit the tumorigenicity and tumor growth of hepatocellular carcinoma cells both in vitro and in vivo. Importantly, Bmi1 knockdown can block the tumor growth, both in the initiating stages and the fast growing stages. Cellular biology analysis revealed that Bmi1 knockdown induces cell cycle arrest and apoptosis. Our findings verify Bmi1 as a qualified treatment target for hepatocellular carcinoma (HCC) and support Bmi1 targeting treatment with chemotherapeutic agents.
Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Complexo Repressor Polycomb 1/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , RNA Interferente Pequeno/metabolismo , Animais , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Complexo Repressor Polycomb 1/genética , Complexo Repressor Polycomb 1/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Interferência de RNA , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/uso terapêutico , Transplante HeterólogoRESUMO
It is a key task to estimate the atmospheric parameters from the observed stellar spectra in exploring the nature of stars and universe. With our Large Sky Area Multi-Object Fiber Spectroscopy Telescope (LAMOST) which begun its formal Sky Survey in September 2012, we are obtaining a mass of stellar spectra in an unprecedented speed. It has brought a new opportunity and a challenge for the research of galaxies. Due to the complexity of the observing system, the noise in the spectrum is relatively large. At the same time, the preprocessing procedures of spectrum are also not ideal, such as the wavelength calibration and the flow calibration. Therefore, there is a slight distortion of the spectrum. They result in the high difficulty of estimating the atmospheric parameters for the measured stellar spectra. It is one of the important issues to estimate the atmospheric parameters for the massive stellar spectra of LAMOST. The key of this study is how to eliminate noise and improve the accuracy and robustness of estimating the atmospheric parameters for the measured stellar spectra. We propose a regression model for estimating the atmospheric parameters of LAMOST stellar(SVM(lasso)). The basic idea of this model is: First, we use the Haar wavelet to filter spectrum, suppress the adverse effects of the spectral noise and retain the most discrimination information of spectrum. Secondly, We use the lasso algorithm for feature selection and extract the features of strongly correlating with the atmospheric parameters. Finally, the features are input to the support vector regression model for estimating the parameters. Because the model has better tolerance to the slight distortion and the noise of the spectrum, the accuracy of the measurement is improved. To evaluate the feasibility of the above scheme, we conduct experiments extensively on the 33 963 pilot surveys spectrums by LAMOST. The accuracy of three atmospheric parameters is log Teff: 0.006 8 dex, log g: 0.155 1 dex, [Fe/H]: 0.104 0 dex.
RESUMO
The authors propose a novel method of feature extraction for stellar spectra parameterization. The basic procedures are: First, stellar spectra are decomposed by multi-scale Harr wavelet and the coefficients with high-frequency are rejected. Secondly, the optimal features are detected by the lasso algorithm. Finally, we input the optimal feature vector to non-parametric regression model to estimate the atmospheric parameters. Haar wavelet can remove the high-frequency noise from the stellar spectrum. Lasso algorithm can further compress data by analyzing their significance on parameterization and removing redundancy. Experiments show that the proposed Haar+lasso method improves the accuracy and efficiency of the estimation. The authors used this scheme to estimate the atmospheric parameters from a subsample of some 40,000 stellar spectra from SDSS. The accuracies of our predictions (mean absolute errors) for each parameter are 0.0071 dex for log Teff, 0.2252 dex for log g, and 0.1996 dex for [Fe/H]. Compared with the results of the existing literature, this scheme can derive more accurate atmospheric parameters.
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As a bioactive saponin derived from the seeds of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chow, jujuboside B (JuB) shows great potential in anti-anxiety, anti-depression and improving learning and memory function. However, its oral bioavailability is very poor. In this study, a novel drug-loading nanoparticles system was prepared with polyethylene glycol and polylactic-co-glycolic acid copolymer (PEG-PLGA), and further modified with L-carnitine (LC) to target intestinal organic cation/carnitine transporter 2 (OCTN2) to improve the oral absorption of JuB. Under the optimized preparation conditions, the particle sizes of obtained JuB-PEG-PLGA nanoparticles (B-NPs) and LC modified B-NPs (LC-B-NPs) were 110.67 ± 11.37 nm and 134.00 ± 2.00 nm with the entrapment efficiency (EE%) 73.46 ± 1.26 % and 76.01 ± 2.10 %, respectively. The pharmacokinetics in SD rats showed that B-NPs and LC-B-NPs increased the bioavailability of JuB to 134.33 % and 159.04 % respectively. In Caco-2 cell model, the prepared nanoparticles significantly increased cell uptake of JuB, which verified the pharmacokinetic results. The absorption of LC-B-NPs mainly depended on OCTN2 transporter, and Na+ played an important role. Caveolin and clathrin were involved in the endocytosis of the two nanoparticles. In conclusion, both B-NPs and LC-B-NPs can improve the oral absorption of JuB, and the modification of LC can effectively target the OCTN2 transporter.
Assuntos
Nanopartículas , Poliésteres , Polietilenoglicóis , Saponinas , Humanos , Ratos , Animais , Carnitina/farmacocinética , Células CACO-2 , Ratos Sprague-Dawley , Tamanho da PartículaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Platycodonis Radix (PR) is a traditional herbal remedy used to prevent and treat lung inflammation, and platycodins are speculated to be the major active constituents. However, concrete experimental verification for this assertion remains absent thus far. AIM OF THE STUDY: This study aims to compare the pulmonary distribution dynamics of five platycodins and analyze their effects on cytokines. Through the grey relational analysis (GRA) between pulmonary active components and cytokines, the study ascertains platycodins as the potential effective component against lung inflammation. MATERIALS AND METHODS: A rat lung inflammation model was created using lipopolysaccharides (LPS). Pulmonary distribution dynamics were analyzed via LC-MS/MS. Cytokine changes and distribution patterns in lung tissues were studied by multi-factor reagent kit. GRA was applied to determine correlations between pulmonary components and cytokines. Finally, the anti-inflammatory properties of platycodins were further studied using LPS-induced BEAS-2B cells in vitro. RESULTS: The results showed that five platycodins (Platycodin D, Platycodin D3, Deapio Platycodin D, 3-O-ß-D-Glucopyranosyl Platycodigenin, and Platycodigenin) featured fast absorption rate, short time to peak, and slow metabolism rate. The pulmonary distribution dynamics were significantly affected within 2 h after LPS modeling. At the same time, PR altered the relationships among different cytokines induced by LPS stimulation, particularly inflammatory cytokines IL-6 and IFN-γ. The GRA results indicated good correlation between the pulmonary distribution dynamics of the five platycodins components and the changing patterns of cytokine levels, with Platycodin D3 contributing the most. Additionally, Platycodin D3 exhibited a protective role against LPS-induced inflammation by reducing the production of pro-inflammatory mediators such as IL-1ß, IL-8, and ROS, as well as increasing the expression of the anti-inflammatory mediator IL-10. CONCLUSIONS: Platycodins are the main anti-inflammatory agents in PR and there is a good correlation with cytokines. This contributes to the anti-pneumonia effect of PR.
Assuntos
Citocinas , Pneumonia , Saponinas , Triterpenos , Ratos , Animais , Citocinas/metabolismo , Cromatografia Líquida , Lipopolissacarídeos/farmacologia , Espectrometria de Massas em Tandem , Pulmão , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico , Pneumonia/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismoRESUMO
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