RESUMO
The development of novel method for drug-resistant bacteria detection is imperative. A simultaneous dual-gene Test of methicillin-resistant Staphylococcus aureus (MRSA) is developed using an Argonaute-centered portable biosensor (STAR). This is the first report concerning Argonaute-based pathogenic bacteria detection. Simply, the species-specific mecA and nuc gene are isothermally amplified using loop-mediated isothermal amplification (LAMP) technique, followed by Argonaute-based detection enabled by its programmable, guided, sequence-specific recognition and cleavage. With the strategy, the targeted nucleic acid signals gene are dexterously converted into fluorescent signals. STAR is capable of detecting the nuc gene and mecA gene simultaneously in a single reaction. The limit of detection is 10 CFU/mL with a dynamic range from 10 to 107 CFU/mL. The sample-to-result time is <65 min. This method is successfully adapted to detect clinical samples, contaminated foods, and MRSA-infected animals. This work broadens the reach of Argonaute-based biosensing and presents a novel bacterial point-of-need (PON) detection platform.
Assuntos
Técnicas Biossensoriais , Staphylococcus aureus Resistente à Meticilina , Técnicas de Amplificação de Ácido Nucleico , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Técnicas Biossensoriais/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Proteínas Argonautas/metabolismo , Proteínas Argonautas/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Ligação às Penicilinas/genética , Animais , Nuclease do Micrococo/metabolismo , Nuclease do Micrococo/genéticaRESUMO
BACKGROUND: The Psychosocial Assessment Tool (PAT2.0) is widely used to assess psychosocial risk in families of children with cancer. Our study aims to apply PAT2.0 to Chinese patients and assess the reliability, content validity, and construct validity of the Chinese version. METHODS: A total of 161 participants completed the study, each with only one child diagnosed with cancer. Psychometric evaluations, including internal consistency, score distribution, test-retest reliability, and construct validity, were conducted. RESULTS: Cronbach's alpha values ranged from 0.732 to 0.843, indicating good internal consistency. Additionally, intraclass correlation coefficient values ranged from 0.869 to 0.984, indicating excellent test-retest reliability. The Simplified Chinese version of PAT2.0 demonstrated high construct validity in factor analyses and correlations with the General Functioning Subscale of the Family Assessment Device. CONCLUSION: The translation process of the Chinese version of PAT2.0 was successful, proving its applicability for psychosocial evaluation and interventions in families of children with cancer in China.
Assuntos
Neoplasias , Criança , Humanos , Reprodutibilidade dos Testes , Inquéritos e Questionários , Psicometria , Neoplasias/diagnóstico , Neoplasias/psicologia , ChinaRESUMO
A novel cyclooxygenase-2 (COX-2) targeted H2S-activated cancer-specific fluorescent probe, namely, COX2-H2S, was designed and synthesized, with naphthalimide as the fluorophore and indomethacin as the targeting group. This H2S-sensing probe was developed to differentiate tumor cells from normal cells and was tested in living cells, Caenorhabditis elegans (C. elegans), and zebrafish. The probe could successfully be used for imaging endogenous and exogenous H2S in living cells, demonstrating high sensitivity and specificity and strong anti-interference. COX2-H2S had the ability to not only discern cancer cells from normal cells but also specifically recognize 9L/lacZ cells from other glioblastoma cells (U87-MG and LN229). It could also be successfully applied for the fluorescent live imaging of H2S in both C. elegans and zebrafish.
Assuntos
Sulfeto de Hidrogênio , Neoplasias , Animais , Humanos , Caenorhabditis elegans , Ciclo-Oxigenase 2 , Corantes Fluorescentes , Sulfeto de Hidrogênio/análise , Neoplasias/diagnóstico por imagem , Imagem Óptica/métodos , Peixe-Zebra , Linhagem Celular TumoralRESUMO
A novel three-component Pd/norbornene cooperative catalysis cascade decarboxylative [2+2+2]/[2+2+3]cyclization of 4-iodoisoquinolin-1(2H)-ones and o-bromobenzoic acids or 8-bromo-1-naphthoic acid has been developed. The method affords a range of fused phenanthridinones and hepta[1,2-c]isoquinolinones and displays unique regioselectivity and broad substrate scope. Palladium/norbornene (Pd/NBE)-catalyzed C-H activation and subsequent decarboxylative coupling reactions were involved, and NBE acts as a building block for the construction of rigid nonplanar molecular architectures.
Assuntos
Norbornanos , Paládio , Paládio/química , Ciclização , Norbornanos/química , CatáliseRESUMO
We previously found that the levels of metabolite N-acetylglutamine were significantly increased in urine samples of patients with heart failure (HF) and in coronary artery ligation (CAL)-induced HF mice, whereas the expression of its specific metabolic-degrading enzyme aminoacylase-1 (ACY1) was markedly decreased. In the current study, we investigated the role of ACY1 in the pathogenesis of HF and the therapeutic effects of 20(S)-ginsenoside Rg3 in HF experimental models in vivo and in vitro. HF was induced in mice by CAL. The mice were administered Rg3 (7.5, 15, 30 mg · kg-1· d-1, i.g.), or positive drug metoprolol (Met, 5.14 mg · kg-1· d-1, i.g.), or ACY1 inhibitor mono-tert-butyl malonate (MTBM, 5 mg · kg-1 · d-1, i.p.) for 14 days. We showed that administration of MTBM significantly exacerbated CAL-induced myocardial injury, aggravated cardiac dysfunction, and pathological damages, and promoted myocardial fibrosis in CAL mice. In Ang II-induced mouse cardiac fibroblasts (MCFs) model, overexpression of ACY1 suppressed the expression of COL3A1 and COL1A via inhibiting TGF-ß1/Smad3 pathway, whereas ACY1-siRNA promoted the cardiac fibrosis responses. We showed that a high dose of Rg3 (30 mg · kg-1· d-1) significantly decreased the content of N-acetylglutamine, increased the expression of ACY1, and inhibited TGF-ß1/Smad3 pathway in CAL mice; Rg3 (25 µM) exerted similar effects in Ang II-treated MCFs. Meanwhile, Rg3 treatment ameliorated cardiac function and pathological features, and it also attenuated myocardial fibrosis in vivo and in vitro. In Ang II-treated MCFs, the effects of Rg3 on collagen deposition and TGF-ß1/Smad3 pathway were slightly enhanced by overexpression of ACY1, whereas ACY1 siRNA partially weakened the beneficial effects of Rg3, suggesting that Rg3 might suppress myocardial fibrosis through ACY1. Our study demonstrates that N-acetylglutamine may be a potential biomarker of HF and its specific metabolic-degrading enzyme ACY1 could be a potential therapeutic target for the prevention and treatment of myocardial fibrosis during the development of HF. Rg3 attenuates myocardial fibrosis to ameliorate HF through increasing ACY1 expression and inhibiting TGF-ß1/Smad3 pathway, which provides some references for further development of anti-fibrotic drugs for HF.
Assuntos
Amidoidrolases , Ginsenosídeos , Insuficiência Cardíaca , Amidoidrolases/metabolismo , Animais , Modelos Animais de Doenças , Fibrose , Ginsenosídeos/uso terapêutico , Insuficiência Cardíaca/metabolismo , Camundongos , Miocárdio/patologia , RNA Interferente Pequeno/farmacologia , Transdução de Sinais , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
The inhalation of particulate matter (PM) is closely related to respiratory damage, including acute lung injury (ALI), characterized by inflammatory fluid edema and disturbed alveolar-capillary permeability. Ruscogenin (RUS), the main active ingredient in the traditional Chinese medicine Ophiopogonis japonicus, has been found to exhibit anti-inflammatory activity and rescue LPS-induced ALI. In this study, we investigated whether and how RUS exerted therapeutic effects on PM-induced ALI. RUS (0.1, 0.3, 1 mg·kg-1·d-1) was orally administered to mice prior to or after intratracheal instillation of PM suspension (50 mg/kg). We showed that RUS administration either prior to or after PM challenge significantly attenuated PM-induced pathological injury, lung edema, vascular leakage and VE-cadherin expression in lung tissue. RUS administration significantly decreased the levels of cytokines IL-6 and IL-1ß, as well as the levels of NO and MPO in both bronchoalveolar lavage fluid (BALF) and serum. RUS administration dose-dependently suppressed the phosphorylation of NF-κB p65 and the expression of TLR4 and MyD88 in lung tissue. Furthermore, TLR4 knockout partly diminished PM-induced lung injury, and abolished the protective effects of RUS in PM-instilled mice. In conclusion, RUS effectively alleviates PM-induced ALI probably by inhibition of vascular leakage and TLR4/MyD88 signaling. TLR4 might be crucial for PM to initiate pulmonary lesion and for RUS to exert efficacy against PM-induced lung injury.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Endotélio/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Espirostanos/uso terapêutico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/complicações , Lesão Pulmonar Aguda/patologia , Animais , Técnicas de Inativação de Genes , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/patologia , Pulmão/patologia , Masculino , Camundongos Endogâmicos ICR , Fator 88 de Diferenciação Mieloide/metabolismo , Material Particulado , Substâncias Protetoras/uso terapêutico , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismoRESUMO
Chronic heart failure is a common and fatal disease triggered by loss of normal cardiac function. Yiqi Fumai Lyophilized Injection is widely used in the treatment of cardiovascular diseases, especially chronic heart failure. In this study, a model of chronic heart failure in mice was established with permanent coronary artery ligation followed by Yiqi Fumai Lyophilized Injection intervention for 14 days. Then, the endogenous metabolites of mice plasma and urine samples were screened through nontargeted metabolomics techniques. The results indicated that Yiqi Fumai Lyophilized Injection treatment changed the metabolic pattern of chronic heart failure and regulated valine, leucine, and isoleucine biosynthesis, taurine and hypotaurine metabolism, histidine metabolism and arginine biosynthesis, etc. Finally, the cardioprotective mechanism of Yiqi Fumai Lyophilized Injection was further verified in the mouse model of chronic heart failure and angiotensin II-induced cardiac fibroblasts based on metabolomics. The results showed that Yiqi Fumai Lyophilized Injection could inhibit myocardial fibrosis to improve chronic heart failure. This study firstly elucidated the metabolic network and pathways regulated by Yiqi Fumai Lyophilized Injection, which might facilitate the realization of the clinically accurate application of Yiqi Fumai Lyophilized Injection in the treatment of chronic heart failure.
Assuntos
Medicamentos de Ervas Chinesas , Insuficiência Cardíaca/tratamento farmacológico , Injeções , Metabolômica , Animais , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Coração/efeitos dos fármacos , Insuficiência Cardíaca/fisiopatologia , Masculino , Espectrometria de Massas , Metabolômica/métodos , Camundongos , Miocárdio/patologiaRESUMO
Schizandrol A (SA) is an bioactive component isolated from the Schisandra chinensis (Turcz.) Baill., which has been used as a remedy to prevent oxidative injury. However, whether the cardioprotective effect of SA is associated with regulating endogenous metabolites remains unclear, thus we performed comprehensive metabolomics profiling in acute myocardial ischemia (AMI) mice following SA treatment. AMI was induced in ICR mice by coronary artery ligation, then SA (6 mg·kg-1·d-1, ip) was administered. SA treatment significantly decreased the infarct size, preserved the cardiac function, and improved the biochemical indicators and cardiac pathological alterations. Moreover, SA (10, 100 M) significantly decreased the apoptotic index in OGD-treated H8c2 cardiomycytes in vitro. By using HPLC-Q-TOF/MS, we conducted metabonomics analysis to screen the significantly changed endogenous metabolites and construct the network in both serum and urine. The results revealed that SA regulated the pathways of glycine, serine and threonine metabolism, lysine biosynthesis, pyrimidine metabolism, arginine and proline metabolism, cysteine and methionine metabolism, valine, leucine and isoleucine biosynthesis under the pathological conditions of AMI. Furthermore, we selected the regulatory enzymes related to heart disease, including ecto-5'-nucleotidase (NT5E), guanidinoacetate N-methyltransferase (GAMT), platelet-derived endothelial cell growth factor (PD-ECGF) and methionine synthase (MTR), for validation. In addition, SA was found to facilitate PI3K/Akt activation and inhibit the expression of NOX2 in AMI mice and OGD-treated H9c2 cells. In conclusion, we have elucidated SA-regulated endogenous metabolic pathways and constructed a regulatory metabolic network map. Furthermore, we have validated the new potential therapeutic targets and underlying molecular mechanisms of SA against AMI, which might provide a reference for its future application in cardiovascular diseases.
Assuntos
Cardiotônicos/uso terapêutico , Ciclo-Octanos/uso terapêutico , Lignanas/uso terapêutico , Isquemia Miocárdica/tratamento farmacológico , Compostos Policíclicos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Enzimas/metabolismo , Masculino , Metabolômica , Camundongos Endogâmicos ICR , Isquemia Miocárdica/patologia , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Mapas de Interação de Proteínas , Ratos , Transdução de Sinais/efeitos dos fármacosRESUMO
Chronic heart failure(CHF), a serious and end stage of various heart diseases, is a common chronic cardiovascular disease in the 21 st century. Literature data show that the 5-year mortality rate of hospitalized patients with heart failure is as high as 50%. Nowadays, the development of drugs treating heart failure has become a hot spot, meanwhile, traditional Chinese medicine(TCM) has shown the advantages in the treatment of chronic heart failure. In this article, four stages to develop traditional Chinese medicine for chronic heart failure were proposed. Firstly, discuss and screen ideas and methods with regard to the development of TCM and its prescriptions based on clinical needs. Secondly, study the preparation process and quality control method by referring to the existing clinical background of TCM prescriptions and analyzing the chemical compositions and pharmacological action characteristics of each herb in the prescription. Then, design non-clinical evaluation programs and carry out researches on pharmacodynamics and toxicology by combining the experience of clinical use of TCM prescriptions and future clinical positioning, and gradually adjust and improve the programs during implementation. Finally, conduct clinical trial application(IND) by submitting registration application data which are base on the clinical drug experience, preclinical research pharmacy, main pharmacodynamics, safety test results of the prescription, clinical positioning, and reasonable clinical trial plan designed by the theory of TCM. After passing the IND technical review, the clinical trial study shall be officially launched to achieve the desired results and obtain effective Chinese patent medicines for heart failure treatment.
Assuntos
Medicamentos de Ervas Chinesas , Insuficiência Cardíaca , Doença Crônica , Humanos , Medicina Tradicional Chinesa , Controle de QualidadeRESUMO
BACKGROUND/AIMS: Traditional Chinese medicine (TCM) has been used in clinical practice for thousands of years and has accumulated considerable knowledge concerning the in vivo efficacy of targeting complicated diseases. TCM formulae are a mixture of hundreds of chemical components with multiple potential targets, essentially acting as a combination therapy of multi-component drugs. However, the obscure substances and the unclear molecular mechanisms are obstacles to their further development and internationalization. Therefore, it is necessary to develop new modern drugs based on the combination of effective components in TCM with exact clinical efficacy. In present study, we aimed to detect optimal ratio of the combination of effective components based on Sheng-Mai-San for myocardial ischemia. METHODS: On the basis of preliminary studies and references of relevant literature about Sheng-Mai-San for myocardial ischemia, we chose three representative components (ginsenoside Rb1 (G), ruscogenin (R) and schisandrin (S)) for the optimization design studies. First, the proper proportion of the combination was explored in different myocardial ischemia mice induced by isoproterenol and pituitrin based on orthogonal design. Then, the different proportion combinations were further optimized through uniform design in a multi-model and multi-index mode. Finally, the protective effect of combination was verified in three models of myocardial ischemia injured by ischemia/reperfusion, chronic intermittent hypoxia and acute infarction. RESULTS: The optimized combination GRS (G: 6 mg/kg, R: 0.75 mg/kg, S: 6 mg/kg) obtained by experimental screening exhibited a significant protective effect on myocardial ischemia injury, as evidenced by decreased myocardium infarct size, ameliorated histological features, decreased myocardial myeloperoxidase (MPO) and malondiadehyde (MDA), calcium overload, and decreased serum lactate dehydrogenase (LDH), creatine kinase MB isoenzyme (CK-MB), cardiac troponin I (cTn-I) activity. In addition, the interactions of three components in combination GRS were also investigated. The combination, compared to G, R and S, could significantly reduce the concentration of serum CK-MB and cTn-I, and decrease myocardial infarct size, which demonstrated the advantages of this combination for myocardial ischemia. CONCLUSION: Our results demonstrated that the optimized combination GRS could exert significant cardioprotection against myocardial ischemia injury with similar effect compared to Sheng Mai preparations, which might provide some pharmacological evidences for further development of new modern Chinese drug for cardiovascular diseases basing on traditional Chinese formula with affirmative therapeutic effect.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Isquemia Miocárdica/tratamento farmacológico , Animais , Creatina Quinase Forma MB/sangue , Ciclo-Octanos/uso terapêutico , Modelos Animais de Doenças , Combinação de Medicamentos , Ginsenosídeos/uso terapêutico , Coração/efeitos dos fármacos , Isoproterenol/toxicidade , L-Lactato Desidrogenase/sangue , Lignanas/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Infarto do Miocárdio/patologia , Isquemia Miocárdica/induzido quimicamente , Isquemia Miocárdica/mortalidade , Isquemia Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Hormônios Neuro-Hipofisários/toxicidade , Compostos Policíclicos/uso terapêutico , Espirostanos/uso terapêutico , Troponina I/sangueRESUMO
Herbivore-induced terpenes have been reported to function as ecological signals in plant-insect interactions. Here, we showed that insect-induced cotton volatile blends contained 16 terpenoid compounds with a relatively high level of linalool. The high diversity of terpene production is derived from a large terpene synthase (TPS) gene family. The TPS gene family of Gossypium hirsutum and Gossypium raimondii consist of 46 and 41 members, respectively. Twelve TPS genes (GhTPS4-15) could be isolated, and protein expression in Escherichia coli revealed catalytic activity for eight GhTPS. The upregulation of the majority of these eight genes additionally supports the function of these genes in herbivore-induced volatile biosynthesis. Furthermore, transgenic Nicotiana tabacum plants overexpressing GhTPS12 were generated, which produced relatively large amounts of (3S)-linalool. In choice tests, female adults of Helicoverpa armigera laid fewer eggs on transgenic plants compared with non-transformed controls. Meanwhile, Myzus persicae preferred feeding on wild-type leaves over leaves of transgenic plants. Our findings demonstrate that transcript accumulation of multiple TPS genes is mainly responsible for the production and diversity of herbivore-induced volatile terpenes in cotton. Also, these genes might play roles in plant defence, in particular, direct defence responses against herbivores.
Assuntos
Alquil e Aril Transferases/genética , Gossypium/genética , Gossypium/imunologia , Herbivoria/fisiologia , Hidroliases/metabolismo , Família Multigênica , Proteínas de Plantas/metabolismo , Monoterpenos Acíclicos , Alquil e Aril Transferases/metabolismo , Animais , Afídeos , Cromatografia Gasosa-Espectrometria de Massas , Regulação da Expressão Gênica de Plantas , Gossypium/enzimologia , Gossypium/parasitologia , Larva , Monoterpenos/metabolismo , Mariposas/fisiologia , Filogenia , Plantas Geneticamente Modificadas , Nicotiana/genética , Compostos Orgânicos Voláteis/metabolismoRESUMO
This study was performed to investigate if the microRNA-related single-nucleotide polymorphisms (miR-SNPs) of XPO5 gene predicted the prognosis and pathological features of advanced non-small-cell lung cancer patients receiving chemotherapy. A total of 131 advanced non-small-cell lung cancer (NSCLC) patients were recruited. MicroRNA (miRNA) binding site prediction software was adopted for the prediction and screening of SNPs in XPO5 and miRNA binding regions. Polymerase chain reaction (PCR) amplification was further performed. Time-dependent survival-free curves were constructed using the Kaplan-Meier technique. Univariate and the multivariate survival analyses were conducted for confirmation of prognostic factor for advanced NSCLC patients receiving chemotherapy. There were no significant differences of SNP distribution frequencies between groups, without statistical significance (P > 0.05). Included clinical pathological features and chemotherapy regimens showed no apparent statistical significance in influencing the curative effect of chemotherapy in advanced NSCLC patients (all P > 0.05). While the objective response rate (ORR) in patients who carried AA and AC genotype was 35.48 and 51.22 %, respectively, with statistically significant difference (P < 0.05). Univariate survival analysis indicated that patients who carried AA genotype showed a significantly lower 5-year survival rate to those who carried AC genotype (P < 0.05). And, considering pathological features, statistical significance was found in patients with different pathological types, lymph node metastasis, differentiation degree, T staging, and pathological staging (all P < 0.05). Multivariate analysis results indicated that the SNP sites of rs11077 might be an independent prognostic factor of advanced NSCLC patients receiving chemotherapy (risk ratio [RR] = 0.346; 95 % confidence interval [95 % CI] = 0.174-0.685, P = 0.002). Other clinical features were all considered to have no apparent effect in influencing the prognostic outcomes of advanced NSCLC patients receiving chemotherapy except lymph node metastasis (P < 0.05). miR-SNP rs11077 of XPO5 may be independently connected with the prognosis and chemotherapy response of advanced NSCLC patients, and patients with AC genotype have relatively improved prognostic outcomes and better curative effect of chemotherapy than those with AA allele of XPO5. Further, lymph node metastasis may be also involved in influencing the prognosis of advanced NSCLC patients.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carioferinas/genética , Neoplasias Pulmonares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
YiQiFuMai Powder Injection (YQFM) is a re-developed preparation based on the well-known traditional Chinese medicine formula Sheng-mai-san. It has been widely used for the treatment of cardiovascular disease with definite clinical efficacy in China, but its bioactive molecules remain obscure. In this study, an effective method has been employed as a tool for screening active components in YQFM, using human umbilical vein endothelial cells (HUVECs) extraction and liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (Q-TOF MS/MS). Nine compounds, which could interact with HUVECs, were identified as ginsenosides Rb1, Rc, Rb2, Rd, 20(S)-Rg3, 20(R)-Rg3, Rk1/Rg5 and schisandrin by comparing with reference substances or literature. In vitro assays showed that schisandrin at concentrations of 10-100 µM protected HUVECs from hypoxia/reoxygenation (H/R) injury, increased cell viability, nitric oxide (NO) content and decreased lactate dehydrogenase (LDH) leakage, malonaldehyde (MDA) content and ROS generation. Moreover, schisandrin pretreatment inhibited cell apoptosis, as evidenced by inhibiting activation of caspase-3 and increasing the Bcl-2/Bax ratio. These data indicate that HUVECs biospecific extraction coupled with HPLC-ESI-Q-TOF-MS/MS analysis is a reliable method for screening potential bioactive components from traditional Chinese medicines. Meanwhile, the vascular endothelium protective property of schisandrin might be beneficial for the treatment of cardiovascular disease.
Assuntos
Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão/métodos , Ciclo-Octanos/isolamento & purificação , Ciclo-Octanos/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Medicamentos de Ervas Chinesas/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Lignanas/isolamento & purificação , Lignanas/farmacologia , Compostos Policíclicos/isolamento & purificação , Compostos Policíclicos/farmacologia , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Apoptose/efeitos dos fármacos , Fármacos Cardiovasculares , Hipóxia Celular/efeitos dos fármacos , Ciclo-Octanos/uso terapêutico , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Ginsenosídeos/isolamento & purificação , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , L-Lactato Desidrogenase/metabolismo , Lignanas/uso terapêutico , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Compostos Policíclicos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismoRESUMO
AIM: SMXZF (a combination of ginsenoside Rb1, ginsenoside Rg1, schizandrin and DT-13) derived from Chinese traditional medicine formula ShengMai preparations) is capable of alleviating cerebral ischemia-reperfusion injury in mice. In this study we used network pharmacology approach to explore the mechanisms of SMXZF in the treatment of cardio-cerebral ischemic diseases. METHODS: Based upon the chemical predictors, such as chemical structure, pharmacological information and systems biology functional data analysis, a target-pathway interaction network was constructed to identify potential pathways and targets of SMXZF in the treatment of cardio-cerebral ischemia. Furthermore, the most related pathways were verified in TNF-α-treated human vascular endothelial EA.hy926 cells and H2O2-treated rat PC12 cells. RESULTS: Three signaling pathways including the NF-κB pathway, oxidative stress pathway and cytokine network pathway were demonstrated to be the main signaling pathways. The results from the gene ontology analysis were in accordance with these signaling pathways. The target proteins were found to be associated with other diseases such as vision, renal and metabolic diseases, although they exerted therapeutic actions on cardio-cerebral ischemic diseases. Furthermore, SMXZF not only dose-dependently inhibited the phosphorylation of NF-κB, p50, p65 and IKKα/ß in TNF-α-treated EA.hy926 cells, but also regulated the Nrf2/HO-1 pathway in H2O2-treated PC12 cells. CONCLUSION: NF-κB signaling pathway, oxidative stress pathway and cytokine network pathway are mainly responsible for the therapeutic actions of SMXZF against cardio-cerebral ischemic diseases.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Ciclo-Octanos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Ginsenosídeos/farmacologia , Lignanas/farmacologia , Isquemia Miocárdica/tratamento farmacológico , Compostos Policíclicos/farmacologia , Saponinas/farmacologia , Animais , Isquemia Encefálica/imunologia , Isquemia Encefálica/metabolismo , Linhagem Celular , Combinação de Medicamentos , Humanos , Isquemia Miocárdica/imunologia , Isquemia Miocárdica/metabolismo , NF-kappa B/imunologia , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Mapas de Interação de Proteínas/efeitos dos fármacos , Ratos , Transdução de Sinais/efeitos dos fármacos , Biologia de Sistemas , Fator de Necrose Tumoral alfa/imunologiaRESUMO
The study aims to develop a unified method to determine seven phenolic acids (neochlorogenic acid, chlorogenic acid, 4-caffeoylquinic acid, caffeic acid, isochlorogenic acid B, isochlorogenic acid A and isochlorogenic acid C) contained in honeysuckle flower that is the monarch drug of all the eight Yinqiao Jiedu serial preparations using quantitative analysis of multi-components by single-marker (QAMS). Firstly, chlorogenic acid was used as a reference to get the average relative correction factors (RCFs) of the other phenolic acids in ratios to the reference; columns and instruments from different companies were used to validate the durability of the achieved RCFs in different levels of standard solutions; and honeysuckle flower extract was used as the reference substance to fix the positions of chromatographic peaks. Secondly, the contents of seven phenolic acids in eight different Yinqiao Jiedu serial preparations samples were calculated based on the RCFs durability. Finally, the quantitative results were compared between QAMS and the external standard (ES) method. The results have showed that the durability of the achieved RCFs is good (RSD during 0.80% - 2.56%), and there are no differences between the quantitative results of QAMS and ES (the relative average deviation < 0.93%). So it can be successfully used to the quantitative control of honeysuckle flower principally prescribed in Yinqiao Jiedu serial preparations.
Assuntos
Medicamentos de Ervas Chinesas/análise , Hidroxibenzoatos/análise , Ácidos Cafeicos/análise , Ácido Clorogênico/análogos & derivados , Ácido Clorogênico/análise , Cromatografia Líquida de Alta Pressão , Flores/química , Lonicera/química , Ácido Quínico/análogos & derivados , Ácido Quínico/análiseRESUMO
Here a reliable fabrication process enabling the integration of multiple functions in a single rod with one optical nano/microfiber (ONM) was proposed, which represents a further step in the "lab-on-a-rod" technology roadmap. With a unique 3D geometry, the all-fiber in-line devices based on lab-on-a-rod techniques have more freedom and potential for compactness and functionality than conventional fiber devices. With the hybrid polymer-metal-dielectric nanostructure, the coupling between the plasmonic and waveguide modes leads to hybridization of the fundamental mode and polarization-dependent loss. By functionalizing the rod surface with a nanoscale silver film and tuning the coil geometry, a broadband polarizer and single-polarization resonator, respectively, were demonstrated. The polarizer has an extinction ratio of more than 20 dB over a spectral range of 450 nm. The resonator has a Q factor of more than 78,000 with excellent suppression of polarization noise. This type of miniature single-polarization resonator is impossible to realize by conventional fabrication processes and has wide applications in fiber communication, lasing, and especially sensing.
RESUMO
Carboxylic acid amide (CAA) fungicides are an important class of agricultural fungicide with oomycete activity and low toxicity toward mammalian cells. To find CAA analogues with high activity against resistant pathogens, a series of substituted N-benzhydryl valinamide carbamate derivatives were designed and synthesized by introducing substituted aromatic rings into valinamide carbamate leads. Bioassays showed that some title compounds exhibited very good in vitro fungicidal activity against Phytophthora capsici and in vivo fungicidal activities against Pseudoperonospora cubensis. Topomer CoMFA was performed to explore the structure-activity relationship on the basis of the in vitro data. The dimethoxy substituted aromatic analogue 9e was found to display higher in vitro fungicidal activity against Phytophthora capsici than iprovalicarb but lower activity than mandipropamid, and higher in vivo fungicidal activity against Pseudoperonospora cubensis than dimethomorph at a dosage of 6.25 µg mL(-1).
Assuntos
Amidas/síntese química , Carbamatos/síntese química , Carbamatos/farmacologia , Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/farmacologia , Desenho de Fármacos , Fungicidas Industriais/síntese química , Amidas/química , Amidas/farmacologia , Carbamatos/química , Ácidos Carboxílicos/química , Fungos/efeitos dos fármacos , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Testes de Sensibilidade Microbiana , Modelos MolecularesRESUMO
In the title complex, [Co(C15H6ClO4)2(H2O)4]·2H2O, the Co(II) ion is bound by two carboxylate O atoms of two 5-chloro-9,10-anthra-quinone-1-carboxyl-ate anions and four water O atoms in a trans conformation, forming an irregular octa-hedral coordination geometry. This arrangement is stabilized by intra-molecular O-Hâ¯O hydrogen bonds between water and carboxyl-ate. Further O-Hâ¯O hydrogen bonds between coordinating and non-coordinating water and carboxyl-ate produce layers of mol-ecules that extend parallel to (001). The organic ligands project above and below the plane. Those ligands of adjacent planes are inter-digitated and there are π-π inter-actions between them with centroid-centroid distances of 3.552â (2) and 3.767â (2)â Å that generate a three-dimensional supra-molecular structure.
RESUMO
In the title compound, C9H9NO3·H2O, the plane of the acetamide group is oriented at 20.52â (8)° with respect to the benzene ring, whereas the plane of the carb-oxy-lic acid group is essentially coplanar with the benzene ring [maximum deviation = 0.033â (1)â Å]. In the crystal, classical O-Hâ¯O and N-Hâ¯O hydrogen bonds and weak C-Hâ¯O hydrogen bonds link the organic mol-ecules and water mol-ecules of crystallization into a three-dimensional supra-molecular architecture.
RESUMO
China, being a densely populated nation, faces a substantial economic burden due to a high incidence of lupus nephritis (LN) cases. The concealed onset of LN has resulted in many individuals have missed the optimal timing for treatment. The aim of the research is to study the serum metabolomics of Chinese LN patients using gas chromatography (GC)/mass spectrometry (MS) and liquid chromatography (LC)/MS to identify potential diagnostic markers. Fifty LN patients and fifty normal controls, matched for Body Mass Index (BMI) and age, were selected. Serum analysis was conducted using GC/MS and LC/MS, followed by multivariate statistical analysis. Various multidimensional analyses, including principal component analysis, partial least squares discrimination analysis, and orthogonal partial least squares discrimination analysis, along with one-dimensional analyses such as t-tests, were performed. Metabolites with variable importance in projection value > 1 and a p-value < 0.05 were considered critical biomarkers for LN. Furthermore, identified biomarkers delineated relevant metabolic pathways, and a metabolic pathway map was obtained from the database. Forty-one metabolites were identified as potential LN biomarkers, primarily associated with immune regulation, energy metabolism, intestinal microbial metabolism, renal damage, and oxidative stress. The potential for diagnosing LN and other diseases through metabolomics is demonstrated. Future research should explore larger sample sizes, metabolomic comparisons across different diseases and health states, and integration of metabolomics with clinical diagnostics. Such studies will enhance the understanding of metabolomics in medical diagnosis and provide robust support for its practical application.