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1.
Heliyon ; 10(5): e26711, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38444491

RESUMO

Diabetes serves as a severe chronic disease that severely affects the normal life of human beings. Diabetes causes the complication of diabetic wound dysfunction, which is characterized by sustained inflammation, altered angiogenesis, delayed epithelialization and abnormal secretion of protease. Dang-Gui-Bu-Xue decoction (DBD) is a Chinese traditional medicine that comprises Radix Astragali and Radix Angelicae sinensis and is widely applied in treatment of multiple diseases owing to its functions against inflammation, lipid peroxidation and oxidative stress. Nevertheless, the impact of DBD on diabetic wound healing remains elusive. In this study, we aimed to explore the function of DBD in the regulation of wound healing. We observed that the gavage administration of DBD reduced the wound area, inflammatory infiltration, inflammatory factor levesl, and enhanced granulation tissue formation, wound extracellular matrix (ECM) production, and CD31 accumulation in the diabetic rat wound model, and the co-treatment of gavage administration and the external administration of gauze containing DBD further improved the wound healing effect, while the combination of Notch signaling inhibitor DAPT ((N- [N- (3, 5-difluorophenacetyl)-l-alanyl]-s-phenylglycinet-butyl ester)) could attenuate the improvement. Regarding to the mechanism, the expression levels of Notch1, Delta-like canonical Notch ligand 4 (Dll4), Jagged1, and Hairy Enhancer of Split-1 (Hes1) were increased by DBD, while the treatment of DAPT impaired the effect in the rats. Furthermore, we found that the high glucose (HG)-inhibited viability and tube formation were induced by DBD in human umbilical vein endothelial cells (HUVECs), in which DAPT could reverse this effect. Therefore, we concluded that DBD contributed to wound healing by the activation of Notch signaling. Our finding provides new insight into the potential role of DBD in promoting diabetic wound healing.

2.
Environ Sci Pollut Res Int ; 29(42): 63640-63654, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35460477

RESUMO

The purpose of this research is to seek a better inversion algorithm. And on this basis, it explores the feasibility of using hyperspectral monitoring technology instead of laboratory physical and chemical index test and evaluates the prediction effect of inversion model on water quality change. So as to be more convenient, more economical and extensive monitoring methods for water quality monitoring of urban internal river are provided. This paper takes the water samples collected in Fuyang River in downtown Handan as the research object and obtains original spectral data of the samples by the ASD FieldSpec 4 field hyperspectral spectrometer. After the smoothing filter pretreatment by the Savitzky-Golay (SG) method and specified mathematical transformations, the modeling spectral indicators of various water quality parameters are selected and determined by calculating the maximum mean of absolute values for correlation coefficients of various spectral indicators and measured values in the wavelength range from 400 to 950 nm. By introducing partial least squares (PLS), random forest (RF), and Lasso (least absolute shrinkage and selection operator), six water quality parameter fitting models were constructed including turbidity (Turb), suspended substance (SS), chemical oxygen demand (COD), NH4-N, total nitrogen (TN), and total phosphorus (TP), which are also testified and evaluated through hyperspectral data. The results show that different spectral transformation methods highlight different information inversion effects. The first derivative of reciprocal logarithm of spectral data after SG smoothing has a good modeling effect on four water quality parameters including Turb, COD, NH4-N, and TP; and the first derivative of smoothed spectral data has a good modeling effect on both water quality parameters of SS and TN. Among the three models, the PLS model has a good prediction effect, with the [Formula: see text] for COD, TN, and TP ranging from 0.74 to 0.80, while that for Turb and SS shows relatively poorer prediction effect, followed by even worse effect on HN4-H. Both machine learning algorithms of RF and Lasso have respectively obtained the best prediction models for different water quality parameters. The Lasso model has a [Formula: see text] value above 0.8 for water body organic pollutants COD, TN, and TP, and the decrease value for [Formula: see text] and [Formula: see text] is below 0.1, which indicates that the model has high prediction accuracy and strong generalization ability, but the results of SS and NH4-N do not meet the expected accuracy. In the inversion model of RF for COD, [Formula: see text] is higher than [Formula: see text], which shows excellent performance, and has certain prediction ability for SS and NH4-N. The RF model and Lasso model complement each other effectively in applicability and prediction accuracy. Compared with the traditional regression model PLS, machine learning has obvious overall advantages, making it more suitable for classified inversion prediction of urban river water quality parameters.


Assuntos
Poluentes da Água , Qualidade da Água , Monitoramento Ambiental/métodos , Imageamento Hiperespectral , Nitrogênio/análise , Fósforo , Rios/química , Tecnologia
3.
Hum Brain Mapp ; 43(8): 2478-2494, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35122347

RESUMO

The visual attentional blink can be substantially reduced by delivering a task-irrelevant sound synchronously with the second visual target (T2), and this effect is further modulated by the semantic congruency between the sound and T2. However, whether the cross-modal benefit originates from audiovisual interactions or sound-induced alertness remains controversial, and whether the semantic congruency effect is contingent on audiovisual temporal synchrony needs further investigation. The current study investigated these questions by recording event-related potentials (ERPs) in a visual attentional blink task wherein a sound could either synchronize with T2, precede T2 by 200 ms, be delayed by 100 ms, or be absent, and could be either semantically congruent or incongruent with T2 when delivered. The behavioral data showed that both the cross-modal boost of T2 discrimination and the further semantic modulation were the largest when the sound synchronized with T2. In parallel, the ERP data yielded that both the early occipital cross-modal P195 component (192-228 ms after T2 onset) and late parietal cross-modal N440 component (424-448 ms) were prominent only when the sound synchronized with T2, with the former being elicited solely when the sound was further semantically congruent whereas the latter occurring only when that sound was incongruent. These findings demonstrate not only that the cross-modal boost of T2 discrimination during the attentional blink stems from early audiovisual interactions and the semantic congruency effect depends on audiovisual temporal synchrony, but also that the semantic modulation can unfold at the early stage of visual discrimination processing.


Assuntos
Intermitência na Atenção Visual , Estimulação Acústica , Percepção Auditiva , Eletroencefalografia , Potenciais Evocados , Humanos , Estimulação Luminosa , Semântica , Percepção Visual
4.
Mol Cancer ; 20(1): 156, 2021 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-34856993

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of human lung cancers, which has diverse pathological features. Although many signaling pathways and therapeutic targets have been defined to play important roles in NSCLC, limiting efficacies have been achieved. METHODS: Bioinformatics methods were used to identify differential long non-coding RNA expression in NSCLC. Real-time RT-PCR experiments were used to examine the expression pattern of lncRNA PKMYT1AR, miR-485-5p. Both in vitro and in vivo functional assays were performed to investigate the functional role of PKMYT1AR/miR-485-5p/PKMYT1 axis on regulating cell proliferation, migration and tumor growth. Dual luciferase reporter assay, fluorescent in situ hybridization (FISH), immunoblot, co-immunoprecipitation experiments were used to verify the molecular mechanism. RESULT: Here, we identify a human-specific long non-coding RNA (lncRNA, ENST00000595422), termed PKMYT1AR (PKMYT1 associated lncRNA), that is induced in NSCLC by Yin Yang 1 (YY1) factor, especially in cancerous cell lines (H358, H1975, H1299, H1650, A549 and SPC-A1) compared to that in normal human bronchial epithelium cell line (BEAS-2B). We show that PKMYT1AR high expression correlates with worse clinical outcome, and knockdown of PKMYT1AR inhibits tumor cell proliferation, migration and xenograft tumor formation abilities. Bioinformatic analysis and a luciferase assay demonstrate that PKMYT1AR directly interacts with miR-485-5p to attenuate the inhibitory role on its downstream oncogenic factor PKMYT1 (the protein kinase, membrane-associated tyrosine/threonine 1) in NSCLC. Furthermore, we uncover that miR-485-5p is downregulated in both cancerous cell lines and peripheral blood serum isolated from NSCLC patients compared to reciprocal control groups. Consistently, forced expression of miR-485-5p inhibits the proliferation and migration abilities of tumor cells. Moreover, we provide evidence showing that PKMYT1AR targeting antisense oligonucleotide (ASO) dramatically inhibit tumor growth in vivo. Mechanistic study shows that PKMYT1AR/ miR-485-5p /PKMYT1 axis promotes cancer stem cells (CSCs) maintenance in NSCLC via inhibiting ß-TrCP1 mediated ubiquitin degradation of ß-catenin proteins, which in turn causes enhanced tumorigenesis. CONCLUSIONS: Our findings reveal the critical role of PKMYT1AR/miR-485-5p /PKMYT1 axis during NSCLC progression, which could be used as novel therapeutic targets in the future.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/etiologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/metabolismo , Proteínas de Membrana/genética , Células-Tronco Neoplásicas/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Tirosina Quinases/genética , RNA Longo não Codificante/genética , Via de Sinalização Wnt , Regiões 3' não Traduzidas , Animais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Proteínas de Membrana/antagonistas & inibidores , Camundongos , MicroRNAs , Terapia de Alvo Molecular , Oligonucleotídeos Antissenso , Prognóstico , Ligação Proteica , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Estabilidade Proteica , Proteínas Tirosina Quinases/antagonistas & inibidores , Interferência de RNA
5.
World J Gastroenterol ; 27(40): 6888-6907, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34790013

RESUMO

BACKGROUND: Fuzi (Radix aconiti lateralis)-Gancao (Radix glycyrrhizae) is one of the most classical drug pairs of traditional Chinese medicine. In clinical practice, decoctions containing Fuzi-Gancao (F-G) are often used in the treatment of liver diseases such as hepatitis and liver failure. AIM: To investigate the metabolomics of F-G in CCl4 induced acute liver injury in rats and its regulatory effect on the bile acid profile. METHODS: The pharmacodynamic effect of F-G on CCl4 induced acute liver injury in rats was evaluated, and an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of 92 metabolites from multiple pathways was established to explore the protective metabolic mechanism of F-G in serum on the liver. RESULTS: Twenty-four differential metabolites were identified in serum samples. The primary bile acid biosynthetic metabolic pathway was the major common pathway in the model group and F-G group. Subsequently, a UPLC-MS/MS method for simultaneous determination of 11 bile acids, including cholic acid, ursodeoxycholic acid, glycochenodeoxycholic acid, glycochenodeoxycholic acid, taurocholic acid, glycocholic acid, chenodeoxycholic acid, deoxycholic acid, taurochenodeoxycholic acid, taurocholic acid, and glycinic acid, was established to analyze the regulatory mechanism of F-G in serum. F-G decreased the contents of these 11 bile acids in serum in a dose-dependent manner compared with those in the model control group. CONCLUSION: F-G could protect hepatocytes by promoting the binding of free bile acids to glycine and taurine, and reducing the accumulation of free bile acids in the liver. F-G could also regulate the compensatory degree of taurine, decreasing the content of taurine-conjugated bile acids to protect hepatocytes.


Assuntos
Ácidos e Sais Biliares , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida , Diterpenos , Medicamentos de Ervas Chinesas , Glycyrrhiza , Fígado , Metabolômica , Ratos
6.
Ann Transl Med ; 9(14): 1146, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34430587

RESUMO

BACKGROUND: The current National Comprehensive Cancer Network guidelines recommend surgical treatment for patients with stages I-IIA small cell lung cancer (SCLC), but it still cannot deny the effect of surgical treatment on other limited-stage SCLC. Although more advanced diagnostic methods are now used for the diagnosis and classification of SCLC, the selection of surgical candidates is still arbitrary. METHODS: Data were collected from patients with SCLC who underwent surgery at the First Affiliated Hospital of Zhengzhou University from January 2011 to January 2021. Kaplan-Meier method was used to calculate cumulative survival curves, and log-rank test was used to evaluate differences among different subgroups. The Cox proportional hazard regression model was used to assess the predictive power of the variables for prognosis and survival. RESULTS: Smoking index, surgical resection method, TNM stage of postoperative pathology, and postoperative chemotherapy were significantly correlated with postoperative survival (P<0.05), which were independent predictors for postoperative survival. Patients with a smoking index >800 had a higher risk of death after surgery [hazard ratio (HR): 7.050, 95% confidence interval (CI): 3.079-16.143, P<0.001]. Compared with patients who underwent pulmonary lobectomy, those who underwent other pneumoresections (e.g., wedge resection, segmental resection, sleeve resection) had an increased risk of death (HR: 2.822, 95% CI: 1.030-7.734, P=0.044). Compared with stage I patients, stage II and stage III patients had an increased risk of death, with HRs of 6.039 and 3.145, respectively. Compared with those who received ≤4 courses of postoperative chemotherapy, those who received >4 courses of postoperative chemotherapy had reduced postoperative mortality risk (HR: 0.211, 95% CI: 0.097-0.459, P<0.001). CONCLUSIONS: A high smoking index suggests worse prognosis; therefore, patients who smoke should be advised to quit smoking. Compared with stage II and stage III patients, surgical treatment is recommended for stage I SCLC patients. TNM staging, especially N staging, should be evaluated prior to surgery. Pulmonary lobectomy with mediastinal lymph node dissection should be the preferred surgical treatment for patients with SCLC. Patients should receive at least 5 courses of adjuvant chemotherapy after surgery.

7.
Cereb Cortex ; 31(4): 2291-2304, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33279971

RESUMO

The present study recorded event-related potentials (ERPs) in a visual object-recognition task under the attentional blink paradigm to explore the temporal dynamics of the cross-modal boost on attentional blink and whether this auditory benefit would be modulated by semantic congruency between T2 and the simultaneous sound. Behaviorally, the present study showed that not only a semantically congruent but also a semantically incongruent sound improved T2 discrimination during the attentional blink interval, whereas the enhancement was larger for the congruent sound. The ERP results revealed that the behavioral improvements induced by both the semantically congruent and incongruent sounds were closely associated with an early cross-modal interaction on the occipital N195 (192-228 ms). In contrast, the lower T2 accuracy for the incongruent than congruent condition was accompanied by a larger late occurring cento-parietal N440 (424-448 ms). These findings suggest that the cross-modal boost on attentional blink is hierarchical: the task-irrelevant but simultaneous sound, irrespective of its semantic relevance, firstly enables T2 to escape the attentional blink via cross-modally strengthening the early stage of visual object-recognition processing, whereas the semantic conflict of the sound begins to interfere with visual awareness only at a later stage when the representation of visual object is extracted.


Assuntos
Estimulação Acústica/métodos , Intermitência na Atenção Visual/fisiologia , Eletroencefalografia/métodos , Estimulação Luminosa/métodos , Semântica , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
8.
Zhongguo Zhen Jiu ; 40(6): 648-51, 2020 Jun 12.
Artigo em Chinês | MEDLINE | ID: mdl-32538018

RESUMO

On the base of the relevant theories on disease identification of western medicine and traditional Chinese medicine, professor FANG Jian-qiao has made the differentiation of cranial tinnitus and proposes the intervention measures. The location of disease is identified firstly. Secondly, the deficiency is distinguished from the excess, and the involved zangfu organs are determined as well. In view of the holistic idea and in combination of meridian differentiation of acupuncture-moxibustion, the principle of treatment is proposed, named "regulating qi, harmonizing blood circulation, clearing office and tranquilizing the mind". In treatment, the disease is treated individually. According to the involved location of onset and the related meridian running course, acupuncture-moxibustion therapy is exerted, in which, the local acupoints are combined with the distal ones. Additionally, electroacupuncture is used flexibly. The appropriate electric wave and frequency are selected in consideration of the syndromes/patterns of disease so as to optimize the regimen of acupuncture-moxibustion therapy. All of the approaches aforementioned provide the reference to clinical treatment of traditional Chinese medicine.


Assuntos
Terapia por Acupuntura , Meridianos , Moxibustão , Zumbido/terapia , Pontos de Acupuntura , Humanos , Medicina Tradicional Chinesa
9.
Mol Med Rep ; 18(4): 3760-3768, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30132527

RESUMO

Endoplasmic reticulum (ER) stress­induced apoptosis serves a crucial role in the development of myocardial ischemia/reperfusion (I/R) injury. Salidroside is a phenylpropanoid glycoside isolated from Rhodiola rosea L., which is a plant often used in traditional Chinese medicine. It possesses multiple pharmacological actions and protects against myocardial I/R injury in vitro and in vivo. However, it is not yet clear whether ER stress or ER stress­induced apoptosis contributes to the cardioprotective effects of salidroside against myocardial I/R injury. Hence, hypoxia/reoxygenation (H/R)­treated H9c2 cardiomyocytes were used in the current study to mimic myocardium I/R injury in vivo. It was hypothesized that salidroside alleviates ER stress and ER stress­induced apoptosis, thereby reducing H/R injury in H9c2 cells. The results demonstrated that salidroside attenuated H/R­induced H9c2 cardiomyocyte injury, as cell viability was increased, lactate dehydrogenase release was decreased, morphological changes in apoptotic cells were ameliorated and the apoptosis ratio was reduced compared with the H/R group. ER stress was reversed, indicated by the downregulation of glucose regulated protein 78 and C/EBP homologous protein following pretreatment with salidroside. In addition, salidroside attenuated ER stress­induced apoptosis, as the expression of cleaved caspase­12 and pro­apoptotic protein Bcl­2 associated X protein and activity of caspase­3 was decreased, while the expression of anti­apoptotic protein Bcl­2 was increased following pretreatment with salidroside. Furthermore, the results indicated that salidroside decreases the activation of the ER stress­associated signaling pathway, as the expression of phosphorylated protein kinase RNA (PKR)­like ER kinase (p­PERK) and phosphorylated inositol­requiring enzyme­1α (p­IRE1α) proteins were decreased following pretreatment with salidroside. These results demonstrate that salidroside protects against H/R injury via regulation of the PERK and IRE1α pathways, resulting in alleviation of ER stress or ER stress­induced apoptosis in H9c2 cardiomyocytes.


Assuntos
Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Glucosídeos/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Fenóis/farmacologia , Animais , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular , Hipóxia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos , Transdução de Sinais/efeitos dos fármacos
10.
Neuroimage ; 174: 208-218, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29567502

RESUMO

Two identical visual disks moving towards one another on a two-dimensional display can be perceived as either "streaming through" or "bouncing off" each other after their coincidence/overlapping. A brief sound presented at the moment of the coincidence of the disks could strikingly bias the percept towards bouncing, which was termed the audiovisual bounce-inducing effect (ABE). Although the ABE has been studied intensively since its discovery, the debate about its origin is still unresolved so far. The present study used event-related potential (ERP) recordings to investigate whether or not early neural activities associated with cross-modal interactions play a role on the ABE. The results showed that the fronto-central P2 component ∼200 ms before the coincidence of the disks was predictive of subsequent streaming or bouncing percept in the unimodal visual display but not in auditory-visual display. More importantly, the cross-modal interactions revealed by the fronto-central positivity PD170 (125-175 ms after sound onset), as well as the occipital positivity PD190 (180-200 ms), were substantially enhanced on bouncing trials compared to streaming trials in the auditory-visual display. These findings provide direct electrophysiological evidence that early cross-modal interactions contribute to the origin of ABE phenomenon at the perceptual stage of processing.


Assuntos
Percepção Auditiva/fisiologia , Encéfalo/fisiologia , Percepção de Movimento/fisiologia , Estimulação Acústica , Adulto , Eletroencefalografia , Potenciais Evocados Auditivos , Potenciais Evocados Visuais , Feminino , Humanos , Masculino , Estimulação Luminosa , Adulto Jovem
11.
Zhongguo Zhong Yao Za Zhi ; 42(6): 1194-1201, 2017 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-29027438

RESUMO

Erigeron breviscapus injection(DZXI) and Breviscapus injection(DZSI) are two popular injections in treatment of acute ischemic stroke in China. Both of them are manufactured from a same herbal medicine, E. breviscapus, but DZXI is an herbal extract(mixture) preparation and DZSI is a pure compound injection. This article was aimed to systemically evaluate and compare their efficacy and safety in treatment of acute ischemic stroke. The randomized controlled trials(RCTs) were collected for comparing DZXI and DZSI with Salvia miltiorrhiza injection(FDI) as the medium, and they were compared with indirect Meta-analysis(ITC). Thirty-nine RCTs with 4 180 patients were included. Meta-analysis results showed that both DZXI and DZSI had better efficacy than FDI in acute ischemic stroke. In the indirect comparison, DZSI had a higher total efficacy than DZXI, with significantly statistical differences[OR=0.634, 95%CI = (0.432,0.928), P<0.000 01], but there was no significant difference in improvement of neurological deficit [MD=-1.19, 95%CI=(-3.57,1.19), P=0.953]. On the safety aspect, adverse reaction rate of DZXI was 1.14%, mainly including head swelling, fever and chills while DZSI had no significant adverse reactions. The limited evidences in this study showed that Breviscapine injection had higher total efficiency and safety than E. breviscapine injection, but due to the low quality of the included RCTs, these two medicines should be comprehensively compared in further high-quality clinical trials.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Erigeron/química , Acidente Vascular Cerebral/tratamento farmacológico , China , Humanos , Fitoterapia , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
J Med Chem ; 59(7): 2942-61, 2016 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-27003636

RESUMO

By use of the 6-hydroxypyridazinone framework, a new series of potent σ1 receptor ligands associated with pharmacological antineuropathic pain activity was synthesized and is described in this article. In vitro receptor binding studies revealed high σ1 receptor affinity (Ki σ1 = 1.4 nM) and excellent selectivity over not only σ2 receptor (1366-fold) but also other CNS targets (adrenergic, µ-opioid, sertonerigic receptors, etc.) for 2-(3,4-dichlorophenyl)-6-(3-(piperidin-1-yl)propoxy)pyridazin-3(2H)-one (compound 54). Compound 54 exhibited dose-dependent antiallodynic properties in mouse formalin model and rats chronic constriction injury (CCI) model of neuropathic pain. In addition, functional activity of compound 54 was evaluated using phenytoin and indicated that the compound was a σ1 receptor antagonist. Moreover, no motor impairments were found in rotarod tests at antiallodynic doses and no sedative side effect was evident in locomotor activity tests. Last but not least, good safety and favorable pharmacokinetic properties were also noted. These profiles suggest that compound 54 may be a member of a novel class of candidate drugs for treatment of neuropathic pain.


Assuntos
Neuralgia/tratamento farmacológico , Piridazinas/farmacologia , Receptores Opioides delta/metabolismo , Analgésicos não Narcóticos/síntese química , Analgésicos não Narcóticos/química , Analgésicos não Narcóticos/farmacocinética , Analgésicos não Narcóticos/farmacologia , Animais , Técnicas de Química Sintética , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Canal de Potássio ERG1 , Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Formaldeído/toxicidade , Cobaias , Ligantes , Camundongos , Medição da Dor/métodos , Piridazinas/síntese química , Piridazinas/química , Ratos Sprague-Dawley , Teste de Desempenho do Rota-Rod , Relação Estrutura-Atividade
13.
Exp Mol Pathol ; 100(2): 294-302, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26896649

RESUMO

While investigating the inhibitory effect of S-allylmercaptocysteine (SAMC), a garlic derivative, on ovarian cancer, we subjected three ovarian cancer cell lines, HO8910, HO8910PM, and SKOV3, to SAMC treatment. In vivo and in vitro experiments showed that only HO8910 and SKOV3 cells were highly sensitive to SAMC, whereas HO8910PM cells were resistant to SAMC. Subsequently, we examined the apoptosis-related genes in the three cell lines. We found that survivin gene was highly expressed in HO8910PM cells. Down regulation of survivin gene in HO8910PM cells with small interference RNA (siRNA), resulted in increased sensitivity to SAMC together with a decrease in invasiveness of tumor cells. We therefore concluded that the S-allylmercaptocysteine suppresses both the proliferation and distant metastasis of epithelial ovarian cancer cells, insensitivity of HO8910PM cells to SAMC was closely related to the high level of survivin expression and that combination of SAMC treatment together with survivin knockdown might be a potential strategy for treatment of certain variants of ovarian cancers.


Assuntos
Cisteína/análogos & derivados , Regulação Neoplásica da Expressão Gênica , Proteínas Inibidoras de Apoptose/genética , Neoplasias Ovarianas/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Western Blotting , Caderinas/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Cisteína/farmacologia , Feminino , Alho/química , Humanos , Integrina beta1/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Survivina , Ensaio Tumoral de Célula-Tronco , Ensaios Antitumorais Modelo de Xenoenxerto
14.
PLoS One ; 9(1): e86578, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24497955

RESUMO

BACKGROUND: Schistosomiasis japonica remains a major public-health concern in China. Praziquantel-based chemotherapy effectively reduces both infections and intensity; however, it can not prevent re-infection. Furthermore, there is an increasing concern about praziquantel resistance following long-term repeated use of the drug in endemic areas. Therefore, development of a schistosomiasis vaccine, as a strategy to prevent and control schistosomiasis japonica, has been given high priority. The present study was conducted to develop PAMAM dendrimers as a novel vaccine delivery vector for a schistosomiasis japonica DNA vaccine and evaluate its ability to enhance protective effects against Schistosoma japonicum infection. METHODOLOGY/PRINCIPAL FINDINGS: Lysine was used to modify 4.0G PAMAM, and the modified product PAMAM-Lys was synthesized. PAMAM-Lys showed both high transfection and low cytotocity for gene delivery in vitro. DNA vaccines combined with PAMAM-Lys produced higher level of protection compare with naked DNA vaccines against S. japonicum infection in a mouse model. Futhermore,antibodies from mice immunized with PAMAM-Lys combined DNA vaccines were significantly higher than those of mice immunized with the naked DNA vaccines. The PAMAM-Lys vector elicited a predominantly IgG2a antibody response and a tremendously increase in the production of IL-2 and IFN-γ. CONCLUSION/SIGNIFICANCE: Lysine-modified PAMAM-Lys is an excellent vector. PAMAM-Lys may enhance the immunoreactivity of DNA vaccine and increase the protective effect of the SjC23 DNA vaccine against S. japonicum infection.


Assuntos
Adjuvantes Imunológicos/química , Dendrímeros/química , Lisina/análogos & derivados , Schistosoma japonicum/imunologia , Vacinas de DNA/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Anticorpos Anti-Helmínticos/sangue , Dendrímeros/farmacologia , Feminino , Células HEK293 , Humanos , Imunidade Humoral , Fígado/parasitologia , Lisina/química , Lisina/farmacologia , Camundongos Endogâmicos BALB C , Plasmídeos , Esquistossomose Japônica/imunologia , Esquistossomose Japônica/parasitologia , Esquistossomose Japônica/prevenção & controle , Caramujos/parasitologia , Vacinas de DNA/genética
15.
Chin Med J (Engl) ; 126(24): 4720-3, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24342318

RESUMO

BACKGROUND: The extract of Ginkgo biloba leaves tablets, ginaton, is widely used in treating ischemic cerebrovascular disease in the clinic. This study aimed to investigate the expression of aquaporin-1 (AQP-1) in rat lung with ischemia/reperfusion injury after pretreatment with ginaton, and whether the pretreatment with ginaton reduces the acute lung injury caused by ischemia/reperfusion injury. METHODS: Adult Wistar rats were divided into two groups. Some rats were used as donors (n = 20), the others as recipients (n = 20). Left lungs of donor rats were used for the isolated lung reperfusion model, which perfused only with low potassium dextran (LPD) solution as group A (n = 10); the others were pretreated with ginaton before reperfusion as group C (n = 10). Right lung of donor rat without any treatment was used as a control group (group B and group D, n = 10 for each group). After the model was established, the expression of AQP-1 in the lung tissues was examined by immunohistochemistry, Western blotting, and reverse transcriptase-polymerase chain reaction. RESULTS: Immunohistochemical examination revealed that AQP-1 was expressed in endothelia. Immunoblotting demonstrated that the relative gray values of AQP-1 protein in groups A and C were 0.65±0.06, 0.88±0.11, respectively. The relative gray values of the mRNA expression in groups A and C were 0.30±0.08, 0.49±0.11, respectively. The expression of AQP-1 protein and mRNA in group C was significantly higher than in group A (P < 0. 05). CONCLUSION: The pretreatment with ginaton can reduce the acute lung injury caused by ischemia/reperfusion.


Assuntos
Aquaporina 1/metabolismo , Ginkgo biloba/química , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Folhas de Planta/química , Traumatismo por Reperfusão/metabolismo , Animais , Aquaporina 1/genética , Imuno-Histoquímica , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Traumatismo por Reperfusão/tratamento farmacológico , Comprimidos
16.
Zhonghua Yi Xue Za Zhi ; 87(12): 851-4, 2007 Mar 27.
Artigo em Chinês | MEDLINE | ID: mdl-17565873

RESUMO

OBJECTIVE: To explore the effect of Astragalus polysaccharides (APS) and Cordyceps sinensis (CP) mycelium mixture on the chronic rejection of artery transplantation. METHODS: The abdominal arteries of 180 Wistar rats were isolated and transplanted to 180 SD rats whose with their abdominal arteries resected. The 180 recipient SD rats were randomly divided into blank control group (n = 20), APS group (n = 40, receiving gastric perfusion of APS 1 mg/kg bid), APS + low-dose CP group (n = 40, receiving APS and CP mycelium powder 1.25 g/d), APS + medium-dose CP group (n = 40, receiving APS and CP mycelium powder 2.5 g/d), and APS + high-dose CP group (n = 40, receiving APS and CP mycelium powder 5 g/d). Thirty days later the SD rats were killed with the transplanted abdominal arteries taken out to undergo microscopy. The expression of transforming growth factor (TGF)-beta(1) in the transplanted artery was examined by immunohistochemistry. RESULTS: In the control group, overexpression of TGF-beta(1) was observed in the intimal smooth muscle cells, monocytes, arterial endothelial cells, and arteriole, venule, and blood capillary endothelial cells in extima. However, the expression levels of TGF-beta(1) in the APS group and the 3 mixture administration groups were all significantly lower, especially in the medium- and high-dose groups (all P < 0.01). Severe edema of arterial endothelial cells and proliferation of monocytes were observed microscopically in the control group. Under electron microscope, rough endoplasmic reticulum and Golgi body were abundant in the control group. While in the mixture administration groups these changes were either weakened or absent. CONCLUSION: Astragalus polysaccharides and Cordyceps sinensis mycelium polysaccharides mixture can decrease the expression of TGF-beta(1) and inhibit the synthesis of collagen in the transplanted arteries.


Assuntos
Artérias/transplante , Rejeição de Enxerto/tratamento farmacológico , Medicina Tradicional Chinesa , Fator de Crescimento Transformador beta1/biossíntese , Animais , Artérias/ultraestrutura , Astrágalo/química , Doença Crônica , Colágeno/biossíntese , Cordyceps/química , Modelos Animais de Doenças , Combinação de Medicamentos , Feminino , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/patologia , Imuno-Histoquímica , Masculino , Microscopia Eletrônica de Transmissão , Micélio/química , Polissacarídeos/uso terapêutico , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Transplante Homólogo
17.
Artigo em Inglês | WPRIM | ID: wpr-314153

RESUMO

<p><b>OBJECTIVE</b>To study the targeted point and mechanism of the function of the blood-activating and stasis-removing Chinese drugs, Paeoniae Radix 801(PR801) in its cardiovascular protective effects and its specific binding with endothelin 1 (ET-1) as well as the dynamics of the two's interactive function by means of using affinity biosensors: IAsys Plus and quartz crystal microbalance (IAQCM).</p><p><b>METHODS</b>ET-1 was immobilized on the surfaces of IAQCM by using the new surface modification methods. The PR801 in the solution was detected by modified substrates and the specific binding between PR801 and ET-1 was studied.</p><p><b>RESULTS</b>The curves went up or down after adding PR801. There is specific binding between PR801 and ET-1. The bound mass were 0.458 ng/mm(2) and 133.54 ng/cm(2), respectively. There exists relatively good stability with these two methods.</p><p><b>CONCLUSION</b>The affinity biosensors: IAQCM can be used to study the interaction mechanism between PR801 and ET-1, providing a new way to study the interaction mechanism of TCM. PR801 can bind ET-1 specifically in the experiments. Therefore, ET-1 is another target that PR801 can bind specifically besides thromboxane A(2).</p>


Assuntos
Humanos , Técnicas Biossensoriais , Padrões de Referência , Circulação Sanguínea , Medicamentos de Ervas Chinesas , Metabolismo , Usos Terapêuticos , Endotelina-1 , Metabolismo , Quartzo
18.
Yao Xue Xue Bao ; 37(6): 437-9, 2002 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-12579800

RESUMO

AIM: To study the chemical constituents of Lycianthes biflora. METHODS: Column chromatography was used to separate the chemical constituents. IR, MS, 1HNMR, 13CNMR and 2D-NMR technique were used to determine the structures of the isolated constituents. RESULTS: Five compounds were isolated from this plant. Their structures were identified to be bifloride A (1), N-trans-cinnamoyltyramine (2), liquiritigenin (3), N-trans-p-coumaroyloctopamine (4), 1-O-beta-D-glucopyranosyl-2-N-2'-hydroxypalmitoyl-sphinga-4- trans-8-trans-dienine (5). CONCLUSION: Compounds 1 and 2 are new compounds, the others were isolated from this plant for the first time. Compound 2 showed inhibitory effects on P-388.


Assuntos
4-Butirolactona/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Cinamatos/isolamento & purificação , Plantas Medicinais/química , Solanaceae/química , Tiramina/isolamento & purificação , 4-Butirolactona/análogos & derivados , 4-Butirolactona/química , Animais , Antineoplásicos Fitogênicos/química , Cinamatos/química , Leucemia P388/patologia , Camundongos , Estrutura Molecular , Células Tumorais Cultivadas , Tiramina/análogos & derivados , Tiramina/química
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