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With the development of advanced nanofabrication techniques over the past decades, different nanostructure-based plasmonic fiber-optic sensors have been developed and have presented a low limit of detection for various biomolecules. However, owing to both the dependence on complex equipment and the trade-off between the fabrication cost and sensing performance, nanostructured plasmonic fiber-optic sensors are rarely used outside laboratories. To facilitate wider application of the plasmonic fiber-optic sensors, a parylene-mediated hybrid plasmonic-photonic cavity-based sensor was developed. Compared with a similar plasmonic sensor which only works in the plasmonic mode, the proposed hybrid sensor shows a higher reproducibility (CV < 2.5%) due to its resistance to fabrication variations. Meanwhile, a self-referenced detection mechanism and a novel miniaturized system were developed to adapt to the hybrid resonance sensor. The entire system only has a weight of 263 g, and a size of 12 cm × 10 cm × 8 cm, and is especially suitable for outdoor applications in a handheld manner. In experiments, a high refractive index sensitivity of 3.148 RIU-1 and real-time biomolecule monitoring at nanomolar concentrations were achieved by the proposed system, further confirming the potential of the miniaturized system as a candidate for point-of-care health diagnostics outside laboratories.
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Técnicas Biossensoriais , Tecnologia de Fibra Óptica , Tecnologia de Fibra Óptica/instrumentação , Técnicas Biossensoriais/instrumentação , Reprodutibilidade dos Testes , Ouro , Nanopartículas MetálicasRESUMO
This paper investigates the statistical inference of inverse power Lomax distribution parameters under progressive first-failure censored samples. The maximum likelihood estimates (MLEs) and the asymptotic confidence intervals are derived based on the iterative procedure and asymptotic normality theory of MLEs, respectively. Bayesian estimates of the parameters under squared error loss and generalized entropy loss function are obtained using independent gamma priors. For Bayesian computation, Tierney-Kadane's approximation method is used. In addition, the highest posterior credible intervals of the parameters are constructed based on the importance sampling procedure. A Monte Carlo simulation study is carried out to compare the behavior of various estimates developed in this paper. Finally, a real data set is analyzed for illustration purposes.
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Entropy measures the uncertainty associated with a random variable. It has important applications in cybernetics, probability theory, astrophysics, life sciences and other fields. Recently, many authors focused on the estimation of entropy with different life distributions. However, the estimation of entropy for the generalized Bilal (GB) distribution has not yet been involved. In this paper, we consider the estimation of the entropy and the parameters with GB distribution based on adaptive Type-II progressive hybrid censored data. Maximum likelihood estimation of the entropy and the parameters are obtained using the Newton-Raphson iteration method. Bayesian estimations under different loss functions are provided with the help of Lindley's approximation. The approximate confidence interval and the Bayesian credible interval of the parameters and entropy are obtained by using the delta and Markov chain Monte Carlo (MCMC) methods, respectively. Monte Carlo simulation studies are carried out to observe the performances of the different point and interval estimations. Finally, a real data set has been analyzed for illustrative purposes.
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In this paper, the evidential estimation method for the parameters of the mixed exponential distribution is considered when a sample is obtained from Type-II progressively censored data. Different from the traditional statistical inference methods for censored data from mixture models, here we consider a very general form where there is some uncertain information about the sub-class labels of units. The partially specified label information, as well as the censored data are represented in a united frame by mass functions within the theory of belief functions. Following that, the evidential likelihood function is derived based on the completely observed failures and the uncertain information included in the data. Then, the optimization method using the evidential expectation maximization algorithm (E2M) is introduced. A general form of the maximal likelihood estimates (MLEs) in the sense of the evidential likelihood, named maximal evidential likelihood estimates (MELEs), can be obtained. Finally, some Monte Carlo simulations are conducted. The results show that the proposed estimation method can incorporate more information than traditional EM algorithms, and this confirms the interest in using uncertain labels for the censored data from finite mixture models.
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Narcissus pseudonarcissus is an important bulbous plant with white or yellow perianths and light yellow to orange-red coronas, but little is known regarding the biochemical and molecular basis related to flower color polymorphisms. To investigate the mechanism of color formation, RNA-Seq of flower of two widely cultured cultivars ('Slim Whitman' and 'Pinza') with different flower color was performed. A total of 84,463 unigenes were generated from the perianths and coronas. By parallel metabolomic and transcriptomic analyses, we provide an overview of carotenoid biosynthesis, degradation, and accumulation in N. pseudonarcissus. The results showed that the content of carotenoids in the corona was higher than that in the perianth in both cultivars. Accordingly, phytoene synthase (PSY) transcripts have a higher abundance in the coronas than that in perianths. While the expression levels of carotenoid biosynthetic genes, like GGPPS, PSY, and LCY-e, were not significantly different between two cultivars. In contrast, the carotenoid degradation gene NpCCD4 was highly expressed in white-perianth cultivars, but was hardly detected in yellow-perianth cultivars. Silencing of NpCCD4 resulted in a significant increase in carotenoid accumulation, especially in all-trans-ß-carotene. Therefore, we presume that NpCCD4 is a crucial factor that causes the low carotenoid content and color fading phenomenon of 'Slim Whitman' by mediating carotenoid turnover. Our findings provide mass RNA-seq data and new insights into carotenoid metabolism in N. pseudonarcissus.
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Flores/genética , Narcissus/genética , Pigmentação/genética , Análise de Sequência de RNA , Transcriptoma/genética , Vias Biossintéticas/genética , Carotenoides/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Anotação de Sequência Molecular , Fenótipo , Transcrição GênicaRESUMO
Systemic delivery of mRNA-based therapeutics remains a challenging issue for preclinical and clinical studies. Here, we describe new lipid-like nanoparticles (TT-LLNs) developed through an orthogonal array design, which demonstrates improved delivery efficiency of mRNA encoding luciferase in vitro by over 350-fold with significantly reduced experimental workload. One optimized TT3 LLN, termed O-TT3 LLNs, was able to restore the human factor IX (hFIX) level to normal physiological values in FIX-knockout mice. Consequently, these mRNA based nanomaterials merit further development for therapeutic applications.
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Lipídeos/química , Nanopartículas , RNA Mensageiro/administração & dosagem , HumanosRESUMO
The evaluation of nanoparticles (NPs) cytotoxicity is crucial for advancing nanotechnology and assessing environmental pollution. However, existing methods for NPs cytotoxicity evaluation suffer from limited accuracy and inadequate information content. In the study, we developed a novel detection platform that enables the identification of cellular carbonyl metabolites at the organ level. The platform is integrated with a cell co-culture lung organ chip (LOC) and a micropillar concentrator. Notably, our work represents the successful measurement of the amounts of cellular metabolites on LOC system. The volatile carbonyl metabolites (VCMs) generated by cells exposure to various types of NPs with different concentrations were captured and detected by high-resolution mass spectrometry (MS). Compared with conventional cell viability and reactive oxygen species (ROS) analysis, our method discerns the toxicological impact of NPs at low concentrations by analyzed VCM at levels as low as ppb level. The LOC system based metabolic gas detection confirmed that low concentrations of NPs have a toxic effect on the cell model, which was not reflected in the fluorescence detection, and the effect of NP material is more significant than the size effect. Furthermore, this method can distinguish different NPs acting on cell models through cluster analysis of multiple VCMs.
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Dispositivos Lab-On-A-Chip , Pulmão , Nanopartículas , Compostos Orgânicos Voláteis , Humanos , Pulmão/citologia , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/metabolismo , Nanopartículas/química , Nanopartículas/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Células A549 , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/análise , Sistemas MicrofisiológicosRESUMO
Exosomes are of great significance in clinical diagnosis, due to their high homology with parental generation, which can reflect the pathophysiological status. However, the quantitative and classification detection of exosomes is still faced with the challenges of low sensitivity and complex operation. In this study, we develop an electrical and label-free method to directly detect exosomes with high sensitivity based on a Silicon nanowire field effect transistor biosensor (Si-NW Bio-FET). First, the impact of Debye length on Si-NW Bio-FET detection was investigated through simulation. The simulation results demonstrated that as the Debye length increased, the electrical response to Si-NW produced by charged particle at a certain distance from the surface of Si-NW was greater. A Si-NW Bio-FET modified with specific antibody CD81 on the nanowire was fabricated then used for detection of cell line-derived exosomes, which achieved a low limit of detection (LOD) of 1078 particles/mL in 0.01 × PBS. Furthermore, the Si-NW Bio-FETs modified with specific antibody CD9, CD81 and CD63 respectively, were employed to distinguish exosomes derived from human promyelocytic leukemia (HL-60) cell line in three different states (control group, lipopolysaccharide (LPS) inflammation group, and LPS + Romidepsin (FK228) drug treatment group), which was consistent with nano-flow cytometry. This study provides a highly sensitive method of directly quantifying exosomes without labeling, indicating its potential as a tool for disease surveillance and medication instruction.
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Técnicas Biossensoriais , Exossomos , Nanofios , Silício , Transistores Eletrônicos , Silício/química , Nanofios/química , Humanos , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Exossomos/química , Células HL-60 , Proteínas de Membrana/análise , Limite de DetecçãoRESUMO
BACKGROUND: Colitis caused by checkpoint inhibitors (CPI) is frequent and is treated with empiric steroids, but CPI colitis mechanisms in steroid-experienced or refractory disease are unclear. METHODS: Using colon biopsies and blood from predominantly steroid-experienced CPI colitis patients, we performed multiplexed single-cell transcriptomics and proteomics to nominate contributing populations. RESULTS: CPI colitis biopsies showed enrichment of CD4+resident memory (RM) T cells in addition to CD8+ RM and cytotoxic CD8+ T cells. Matching T cell receptor (TCR) clonotypes suggested that both RMs are progenitors that yield cytotoxic effectors. Activated, CD38+ HLA-DR+ CD4+ RM and cytotoxic CD8+ T cells were enriched in steroid-experienced and a validation data set of steroid-naïve CPI colitis, underscoring their pathogenic potential across steroid exposure. Distinct from ulcerative colitis, CPI colitis exhibited perturbed stromal metabolism (NAD+, tryptophan) impacting epithelial survival and inflammation. Endothelial cells in CPI colitis after anti-TNF and anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) upregulated the integrin α4ß7 ligand molecular vascular addressin cell adhesion molecule 1 (MAdCAM-1), which may preferentially respond to vedolizumab (anti-α4ß7). CONCLUSIONS: These findings nominate CD4+ RM and MAdCAM-1+ endothelial cells for targeting in specific subsets of CPI colitis patients.
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Linfócitos T CD8-Positivos , Colite , Humanos , Células Endoteliais , Inibidores do Fator de Necrose Tumoral , Colite/induzido quimicamente , Colite/tratamento farmacológico , Linfócitos T CD4-Positivos , Esteroides/farmacologia , Esteroides/uso terapêutico , Células EstromaisRESUMO
The aberrant expression of microRNAs (miRNAs) is associated with a variety of diseases, including cancer. In our study, we examined the miRNA expression profile of meningiomas, which is a common type of benign intracranial tumor derived from the protective meninges membranes that surround the brain and spinal cord. To define a typical human meningioma miRNA profile, the expression of 200 miRNAs in a training sample set were screened using quantitative reverse transcription polymerase chain reaction analysis, and then significantly altered miRNAs were validated in a secondary independent sample set. Kaplan-Meier and univariate/multivariate Cox proportional hazard regression analyses were performed to assess whether miRNA expression could predict the recurrence of meningioma after tumor resection. After a two-phase selection and validation process, 14 miRNAs were found to exhibit significantly different expression profiles in meningioma samples compared to normal adjacent tissue (NAT) samples. Unsupervised clustering analysis indicated that the 14-miRNA profile differed between tumor and NAT samples. Downregulation of miR-29c-3p and miR-219-5p were found to be associated with advanced clinical stages of meningioma. Kaplan-Meier analysis showed that high expression of miR-190a and low expression of miR-29c-3p and miR-219-5p correlated significantly with higher recurrence rates in meningioma patients. Cox proportional hazard regression analysis revealed that miR-190a expression level is an important prognostic predictor that is independent of other clinicopathological factors. Our results suggest that the use of miRNA profiling has significant potential as an effective diagnostic and prognostic marker in defining the expression signature of meningiomas and in predicting postsurgical outcomes.
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Neoplasias Meníngeas/genética , Meningioma/genética , Meningioma/patologia , MicroRNAs/biossíntese , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Adolescente , Adulto , Idoso , Criança , Análise por Conglomerados , Regulação para Baixo , Feminino , Seguimentos , Perfilação da Expressão Gênica/métodos , Humanos , Estimativa de Kaplan-Meier , Masculino , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/patologia , Meningioma/metabolismo , MicroRNAs/genética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , Adulto JovemRESUMO
The feasibility of allogeneic transplantation, without myeloablation or post-transplant immunosuppression, was tested using in vivo chemoselection of allogeneic hematopoietic stem cells (HSCs) after transduction with a novel tricistronic lentiviral vector (MGMT(P140K)-2A-GFP-IRES-TK (MAGIT)). This vector contains P140K-O(6)-methylguanine-methyltransferase (MGMT(P140K)), HSV-thymidine kinase (TK(HSV)), and enhanced green fluorescent protein (eGFP) enabling (i) in vivo chemoselection of HSC by conferring resistance to benzylguanine (BG), an inhibitor of endogenous MGMT, and to chloroethylating agents such as 1,3-bis(2-chloroethyl)nitrosourea (BCNU) and, (ii) depletion of proliferating cells such as malignant clones or transduced donor T cells mediating graft versus host disease (GVHD), by expression of the suicide gene TK(HSV) and Ganciclovir (GCV) administration. Non-myeloablative transplantation of transduced, syngeneic, lineage-depleted (Lin(-)) BM in neonates resulted in 0.67% GFP(+) mononuclear cells in peripheral blood. BG/BCNU chemoselection, 4 and 8 weeks post-transplant, produced 50-fold donor cell enrichment. Transplantation and chemoselection of major histocompatibility complex (MHC)-mismatched MAGIT-transduced Lin(-) BM also produced similar expansion for >40 weeks. The efficacy of this allotransplant approach was validated in Hbb(th3) heterozygous mice by correction of ß-thalassemia intermedia, without toxicity or GVHD. Negative selection, by administration of GCV resulted in donor cell depletion without graft ablation, as re-expansion of donor cells was achieved with BG/BCNU treatment. These studies show promise for developing non-ablative allotransplant approaches using in vivo positive/negative selection.
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Facilitação Imunológica de Enxerto , Rejeição de Enxerto/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Talassemia beta/terapia , Animais , Animais Recém-Nascidos , Antivirais/farmacologia , Carmustina/farmacologia , Proliferação de Células , Separação Celular , Forma Celular , Sobrevivência Celular/efeitos dos fármacos , Metilases de Modificação do DNA/antagonistas & inibidores , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/antagonistas & inibidores , Enzimas Reparadoras do DNA/genética , Inibidores Enzimáticos/farmacologia , Eritrócitos/patologia , Feminino , Citometria de Fluxo , Ganciclovir/farmacologia , Rejeição de Enxerto/imunologia , Proteínas de Fluorescência Verde/biossíntese , Proteínas de Fluorescência Verde/genética , Células HEK293 , Humanos , Lentivirus/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Timidina Quinase/genética , Transdução Genética , Transplante Homólogo , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/genética , Proteínas Virais/genéticaRESUMO
Objective: Deficiencies in klotho are implicated in various kidney dysfunctions including diabetic nephropathy (DN) related to inflammatory responses. Klotho is closely related to inflammatory responses and is a potential target for ameliorating kidney failure. Pyroptosis, an inflammatory form of programmed cell death, is reported to take part in DN pathogenesis recently. This study is aimed at exploring whether and how klotho inhibited podocyte pyroptosis and whether astragaloside IV (AS-IV) protect podocyte through the regulation of klotho. Materials and Methods: SD rat model of DN and conditionally immortalized mouse podocytes exposed to high glucose were treated with AS-IV. Biochemical assays and morphological examination, cell viability assay, cell transfection, phalloidin staining, ELISA, LDH release assay, SOD and MDA detection, MMP assay, ROS level detection, flow cytometry analysis, TUNEL staining assay, PI/Hoechst 33342 staining, immunofluorescence assay, and western blot were performed to elucidate podocyte pyroptosis and to observe the renal morphology. Results: The treatment of AS-IV can improve renal function and protect podocytes exposed to high glucose. Klotho was decreased, and AS-IV increased klotho levels in serum and kidney tissue of DN rats as well as podocytes exposed to high glucose. AS-IV can inhibit DN glomeruli pyroptosis in vivo. In vitro, overexpressed klotho and treatment with AS-IV inhibited pyroptosis of podocytes cultured in high glucose. Klotho knockdown promoted podocyte pyroptosis, and treatment with AS-IV reversed this effect. Furthermore, the overexpression of klotho and AS-IV reduces oxidative stress levels and inhibited NF-κB activation and NLRP3-mediated podocytes' pyroptosis which was abolished by klotho knockdown. In addition, both the ROS inhibitor NAC and the NF-κB pathway inhibitor PDTC can inhibit NLRP3 inflammasome activation. NLRP3 inhibitor MCC950 can inhibit pyroptosis of podocytes exposed to high glucose. Conclusion: Altogether, our results demonstrate that the protective effect of AS-IV in upregulating klotho expression in diabetes-induced podocyte injury is associated with the inhibition of NLRP3-mediated pyroptosis via the NF-κB signaling pathway.
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Diabetes Mellitus , Nefropatias Diabéticas , Podócitos , Ratos , Camundongos , Animais , NF-kappa B/metabolismo , Nefropatias Diabéticas/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ratos Sprague-Dawley , Glucose/farmacologia , Glucose/metabolismo , Podócitos/metabolismo , Inflamassomos/metabolismo , Diabetes Mellitus/metabolismoRESUMO
The bivariate or multivariate distribution can be used to account for the dependence structure between different failure modes. This paper considers two dependent competing failure modes from Gompertz distribution, and the dependence structure of these two failure modes is handled by the Marshall-Olkin bivariate distribution. We obtain the maximum likelihood estimates (MLEs) based on classical likelihood theory and the associated bootstrap confidence intervals (CIs). The posterior density function based on the conjugate prior and noninformative (Jeffreys and Reference) priors are studied; we obtain the Bayesian estimates in explicit forms and construct the associated highest posterior density (HPD) CIs. The performance of the proposed methods is assessed by numerical illustration.
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Modelos Estatísticos , Projetos de Pesquisa , Teorema de Bayes , Funções VerossimilhançaRESUMO
OBJECTIVE: We aimed to evaluate the efficacy of IVIG in the treatment with patients with recurrent spontaneous abortion (RSA). METHODS: PubMed, Embase, Web of science, Cochrane library were searched for randomized controlled (RCTs) about effect of IVIG on RSA from inception to August 20, 2021. Values of standardized mean differences (SMD) were determined for continuous outcomes. RESULTS: A total of 15 articles involving 902 patients were included in meta-analysis. Compared with the control group, IVIG can increase the live birth rate of recurrent spontaneous abortion patients [OR = 3.06, 95%CI (1.23, 7.64, P = .02]. However, recurrent abortion was divided into primary and secondary abortion for subgroup analysis, and there was no statistical difference. Besides, IVIG can also increase the expression in peripheral blood CD3+[OR = .4, 95%CI(-2.47, 3.15, P = .81],CD4+[OR = 1.16, 95%CI(-4.60, 6.93, P = .69], and a decrease in the expression of CD8+[OR = -1.78, 95%CI(-5.30, 1.75, P = .32], but there is no statistical significance. CONCLUSIONS: IVIG can significantly increase the live birth rate of recurrent spontaneous abortion. However, the evidence needs further verification and the curative effect is uncertain. It is necessary to further explore the pathogenesis of recurrent abortion and the mechanism of IVIG in the treatment of recurrent spontaneous abortion. Besides, more high-quality randomized controlled trials suitable for population, race, dosage and timing of IVIG in the treatment of recurrent abortion are needed to confirm its effectiveness, and effective systematic evaluation is also needed to evaluate its use benefit.
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Aborto Habitual , Aborto Espontâneo , Gravidez , Feminino , Humanos , Imunoglobulinas Intravenosas , Aborto Habitual/terapia , Coeficiente de NatalidadeRESUMO
Diabetic nephropathy (DN) is a microvascular complication of diabetes mellitus (DM) and the most common cause of death in diabetic patients. DN progression is associated with podocyte damage due to reduced autophagy caused by mTORC1 activation. Tangshenning (TSN) has been shown to reduce proteinuria, protect renal function, and reduce podocyte damage. Still, the effect of TSN on the autophagic activity of podocytes remains unclear. Herein, in vitro experiments using a high glucose-induced podocyte injury model were performed. Results showed that TSN treatment enhanced the weakened nephrin expression and autophagic activity of podocytes and inhibited the mTORC1 pathway (p-mTOR, mTOR, p-p70S6K, p70S6K, ULK1, and 4EBP1) under high glucose conditions. Furthermore, the mTORC1 activator (siRNA-TSC2) partially inhibited the above beneficial effects of TSN, suggesting that mTORC1 was the target of TSN to regulate autophagy. In summary, TSN reduces podocyte damage induced by high glucose via inhibiting mTORC1 pathway and downstream targets and restoring podocyte autophagy.
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Nefropatias Diabéticas , Podócitos , Autofagia , Nefropatias Diabéticas/metabolismo , Glucose/metabolismo , Glucose/toxicidade , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Podócitos/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
This tutorial review highlights the mechanism of a novel non-enzymatic fast repair of DNA damage, which refers exclusively to repair DNA radicals including DNA-OH* adducts, DNA radical cations and anions by various endogenous, natural and synthetic compounds. The repair rate constants are as high as 10(9) M(-1) s(-1). In cells, when the enzymatic repair system was inhibited or before the enzymatic repair mechanism was initiated, DNA oxidative damage was significantly reduced by natural polyphenols. This decrease of DNA damage is assigned to the fast repair. Fast repair takes place through an electron transfer process, and docking of polyphenol into the DNA minor groove could be the essential step.
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Adutos de DNA/química , Adutos de DNA/metabolismo , Reparo do DNA , Células/metabolismo , Transporte de Elétrons , Radicais Livres/química , Radicais Livres/metabolismo , Humanos , Fatores de TempoRESUMO
BACKGROUND: Podocyte injury plays an important role in diabetic nephropathy (DN). The aim of this study was to determine the potential therapeutic effects of the ginsenoside Rg1 on hyperlipidemia-stressed podocytes and elucidate the underlying mechanisms. METHODS: In vitro and in vivo models of DN were established as previously described, and the expression levels of relevant markers were analyzed by Western blotting, real-time Polymerase Chain Reaction (PCR), immunofluorescence, and immunohistochemistry. RESULTS: Ginsenoside Rg1 alleviated pyroptosis in podocytes cultured under hyperlipidemic conditions, as well as in the renal tissues of diabetic rats, and downregulated the mammalian target of rapamycin (mTOR)/NF-κB pathway. In addition, Rg1 also inhibited hyperlipidemia-induced NLRP3 inflammasome in the podocytes, which was abrogated by the mTOR activator L-leucine (LEU). The antipyroptotic effects of Rg1 manifested as improved renal function in the DN rats. CONCLUSION: Ginsenoside Rg1 protects podocytes from hyperlipidemia-induced damage by inhibiting pyroptosis through the mTOR/NF-κB/NLRP3 axis, indicating a potential therapeutic function in DN.
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BACKGROUND: Diabetic nephropathy (DN), a complication of diabetes, is the result of high glucose-induced pathological changes in podocytes, such as epithelial-mesenchymal transition (EMT). Autophagy is an important mechanism of podocyte repair. Ginsenoside Rg1, the active ingredient of ginseng extract, has antifibrotic and proautophagic effects. Therefore, we hypothesized that ginsenoside Rg1 can reverse podocyte EMT via autophagy and alleviate DN. AIM: This study aimed to investigate the effect of ginsenoside Rg1 on DN rats and high glucose-induced podocyte EMT by regulating the AKT/GSK3ß/ß/. METHODS: Diabetic rats induced by STZ injection were treated with 50 mg/kg ginsenoside Rg1 for 8 weeks, and the renal functional, metabolic, and histopathological indices were evaluated. DN was simulated in vitro by exposing podocytes to high glucose levels and treated with ginsenoside Rg1. The expression of EMT and autophagy-related markers was analyzed in vivo and in vitro by exposing podocytes to high glucose levels and treated with ginsenoside Rg1. The expression of EMT and autophagy-related markers was analyzed. RESULTS: Ginsenoside Rg1 significantly alleviated renal fibrosis and podocyte EMT in diabetic rats, and podocytes exposed to high glucose levels, which was abolished by the autophagy inhibitor 3-MA. Furthermore, ginsenoside Rg1 regulated the AKT/GSK3 ß/ß/. CONCLUSION: Ginsenoside Rg1 alleviated podocyte EMT by enhancing AKT/GSK3ß/ß-catenin pathway-mediated autophagy, indicating its therapeutic potential for DN and other glomerular diseases.ß/ß/.
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The non-enzymatic repair of DNA oxidative damage can occur in a purely chemical system, but data show that it might also occur in cells. Human hepatoma cells (SMMC-7721) and human hepatocyte cells (LO2) were treated with 200microM H(2)O(2) for 30min to induce oxidative DNA damage quantified by amount of 8-OHdG and degree of DNA strand breaks, without inducing enzymatic repair. The dynamics of enzymatic repair activity quantified by unscheduled DNA synthesis, within 30min after removal of H(2)O(2) enzymatic repair mechanism has not been initiated. However, pre-incubation with low micromolar level polyphenols, quercetin or rutin can significantly attenuate DNA damage in both cell lines, indicating that the polyphenols did not work through an enzymatic mechanism. Unscheduled DNA synthesis after removal of H(2)O(2) was also markedly decreased by quercetin and rutin. Combined with our previous studies of fast reaction chemistry, the inhibitory effect of polyphenols have to be assigned to non-enzymatic repair mechanism rather than to enzymatic repair mechanism or antioxidant mechanism.
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Dano ao DNA/efeitos dos fármacos , Reparo do DNA/fisiologia , Flavonoides/metabolismo , Fenóis/metabolismo , 8-Hidroxi-2'-Desoxiguanosina , Linhagem Celular , Ensaio Cometa , Reparo do DNA/efeitos dos fármacos , Desoxiguanosina/análogos & derivados , Desoxiguanosina/síntese química , Desoxiguanosina/metabolismo , Humanos , Peróxido de Hidrogênio/farmacologia , Polifenóis , Quercetina/metabolismo , Rutina/metabolismoRESUMO
Narcissus pseudonarcissus (daffodil) is a valuable plant for the cosmetic, pharmaceutical and therapeutical traits. The flower volatile compounds (FVCs) of ten Narcissus pseudonarcissus cultivars were analyzed by Headspace/Solid Phase Micro Extraction-Gas Chromatography Mass Spectrometry (HS/SPME- GC/MS). 69 and 73 FVCs were detected in perianth and corona of the ten cultivars. The compounds are largely comprised of monoterpenes, sesquiterpene, benzenoid compounds and other minor compounds classes. Monoterpenes were major component among the FVCs, with beta-ocimene and beta-myrcene as the two major compounds in most perianths and coronas. The composition and content of the FVCs of different cultivars are quite different from each other.