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Owing to excellent catalytic activity, single-atom catalysts (SACs) have recently attracted considerable research interest in the electrochemiluminescence (ECL) field. However, the applications of SACs are mostly limited to conventional luminol ECL system. Hence, it is necessary to explore the application of SACs in more ECL systems. In this work, nickel single-atom catalysts (Ni SACs) were successfully applied in the graphitic carbon nitride (g-C3N4)-H2O2 ECL system to significantly enhance its cathodic emission. Notably, g-C3N4 acted not only as an ECL luminophore but also as a support to anchor Ni SACs. Ni SACs can significantly activate H2O2 to produce abundant OH⢠radicals for enhancing the cathodic ECL emission of g-C3N4. Ni SACs-anchored g-C3N4 (Ni SACs@g-C3N4) had a 10-fold enhanced ECL intensity as compared to g-C3N4. Finally, the Ni SACs@g-C3N4-H2O2 ECL system was developed to detect hepatitis B virus (HBV) DNA by incorporating an entropy-driven DNA walking machine-assisted CRISPR-Cas12a amplification strategy. The constructed biosensor exhibited excellent detection performance for HBV DNA with a limit of detection as low as 17 aM. This work puts forward a new idea for enhancing the cathodic ECL of g-C3N4-H2O2 and expands the application of SACs in the ECL system.
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Técnicas Biosensibles , ADN Viral , Níquel , Técnicas Electroquímicas , Peróxido de Hidrógeno , Mediciones Luminiscentes , Límite de DetecciónRESUMEN
In this study, the evidence map system was used to sort out the clinical research evidence on traditional Chinese medicine(TCM) treatment of vertigo and understand the evidence distribution in this field. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Web of Science were searched for the clinical randomized controlled trial(RCT) and systematic reviews/Meta-analysis on TCM treatment of vertigo in recent five years, and the evidence was analyzed and presented in the form of text and charts. The Cochrane handbook for systematic reviews of interventions was used to evaluate the quality of the clinical RCT, and the AMSTAR mea-surement tool was used to evaluate the quality of the systematic reviews/Meta-analysis. A total of 382 RCTs and eight systematic reviews/Meta-analysis were included. In recent five years, the number of published articles has been on the rise. There were many intervention measures and TCM therapies for vertigo. Outcome indicators mainly included clinical efficacy, TCM syndrome score, vertigo score, occurrence of adverse reactions, and effective rate. The overall quality of clinical RCT and systematic reviews/Meta-analysis was low. Most studies have proven the potential efficacy of TCM in treating vertigo, but there was still no clear clinical evidence of efficacy. The results show that TCM has advantages in the treatment of vertigo, but there are also problems. More high-quality studies are still lacking, suggesting that more large-sample and multi-center RCT should be conducted in the future, and the quality of relevant syste-matic reviews/Meta-analysis should be improved to fully explore the advantages of TCM in the treatment of vertigo, and provide strong support for the effectiveness and safety of TCM in the treatment of vertigo.
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Medicamentos Herbarios Chinos , Medicina Tradicional China , Humanos , Revisiones Sistemáticas como Asunto , Resultado del Tratamiento , Síndrome , Publicaciones , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
Wuzhuyu Decoction, the classical formula recorded in the Treatise on Febrile Diseases(Shang Han Lun), has been included in the Catalogue of Ancient Classic Prescriptions(the First Batch). Consisting of Euodiae Fructus, Ginseng Radix et Rhizoma, Zingiberis Rhizoma Recens, and Jujubae Fructus, it is effective in warming the middle, tonifying deficiency, dispelling cold, and descending adverse Qi, and is widely applied clinically with remarkable efficacies. For a classical formula, the chemical composition is the material basis and an important premise for quantity value transfer. This study aimed to establish a rapid identification method of chemical components in Wuzhuyu Decoction by high-resolution mass spectrometry(HR-MS) and molecular network. AQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) was used for sample separation, and acetonitrile-0.1% formic acid in water was used as mobile phases for gradient elution. Q-Exactive Orbitrap MS data were collected in positive and negative ion modes, and GNPS molecular network was plotted according to the similarity of MS/MS fragmentation modes. Cytoscape 3.6.1 was used to screen molecular clusters with similar structures. Finally, the chemical components of Wuzhuyu Decoction were rapidly identified according to the controls, as well as the information of retention time, accurate relative molecular weight of HR-MS, and MS/MS multistage fragments. A total of 105 chemical components were identified in Wuzhuyu Decoction. This study can provide data for the follow-up quality control, standard substance research, and pharmacodynamic material research on Wuzhuyu Decoction, as well as references for the rapid qualitative analysis of the chemical components of Chinese medicine.
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Medicamentos Herbarios Chinos , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Control de CalidadRESUMEN
To study the adverse reactions' factors to Danhong injection in the real world. A multi-center, large sample and prospective hospital centralized monitoring method was adopted, and 30 888 cases of Danhong injection from 37 national 3A hospitals were collected to carry out a nested case control design study. These cases were divided into adverse reaction group and non-adverse group. Single factor logistic regression and multiple factor logistic regression were used to analyze data, and investigate the correlation between adverse reaction and gender, allergy history, methods of administration, and combined drug use. One hundred and eight cases of adverse reactions in 30 888 patients were determined, with an incidence of 0.35%. The results showed that Danhong injection combined with other medication(potassium mendoxine magnesium, thymic peptide, celecoxib, fumarate bisoprolol) with history of adverse reactions including scephalosporin allergy and proprietary Chinese medicine allergies had more adverse reactions than the control group(P<0.05, estimated coefficient>0), indicating that these six factors were the risk factors for the adverse reaction of Danhong injection. The adverse reaction of Danhong injection combined with the aspirin was less than that in the control group(P<0.05, estimated coefficient<0), indicating that the aspirin was a non-risk factor for the adverse reaction of Danhong injection. All the above results indicate that the adverse factors to Danhong injection include scephalosporin allergy, patent Chinese medicine allergy, Danhong injection combined with medication(potassium mendoxine magnesium, thymic peptide, celecoxib, fumarate bisoprolol), suggesting special attention shall be paid in clinical application.
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Medicamentos Herbarios Chinos , Estudios de Casos y Controles , Humanos , Inyecciones , Estudios ProspectivosRESUMEN
OBJECTIVE: Inactivation of the Janus kinase 2 in treated NSCs. Furthermore, QNYZD may play a direct role in suppressing the formation of GFAP-positive cells and enhancing neuronal differentiation by inhibiting JAK2/STAT3 activation. Overall, these results provide insights into the possible mechanism underlying QNYZD-mediated neurogenesis. (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling axis plays a crucial role in determining the fate of neural stem cells (NSCs). Qingnaoyizhi decoction (QNYZD) has been used for the treatment of vascular dementia and has shown to improve synaptic remodeling. The aim of this study was to evaluate the effect of cerebrospinal fluid (CSF) containing QNYZD (CSF-QNYZD) on the differentiation of cultured NSCs and the involvement of the JAK2/STAT3 pathway. METHODS: The protein expression levels of glial fibrillary acidic protein (GFAP), tubulin, drosophila mothers against decapentaplegic protein (SMAD-1), STAT3, and phosphorylated-STAT3 were detected by western immunoblot analysis in the groups: control, CSF, JAK/STAT inhibitor (AG490), CSF-QNYZD, and CSF-XDZ (CSF-Xidezhen). The differentiation of NSCs was determined by immunofluorescence staining. The proliferation of NSCs was measured using the Cell Counting Kit-8 proliferation assay. RESULTS: Compared with the control group, CSF-QNYZD and AG490 significantly increased the number and expression of tubulin-positive cells, reduced the number and expression of GFAP-positive cells, and down-regulated the expression of p-STAT3. However, CSF-QNYZD also decreased the expression of SMAD-1 and STAT3. CONCLUSION: Enhanced neuronal differentiation may be associated with the down-regulation of glial differentiation instead of promoting proliferation in treated NSCs. Furthermore, QNYZD may play a direct role in suppressing the formation of GFAP-positive cells and enhancing neuronal differentiation by inhibiting JAK2/STAT3 activation. Overall, these results provide insights into the possible mechanism underlying QNYZD-mediated neurogenesis.
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Medicamentos Herbarios Chinos/farmacología , Proteína Ácida Fibrilar de la Glía/metabolismo , Janus Quinasa 2/metabolismo , Células-Madre Neurales/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Regulación hacia Abajo/efectos de los fármacos , Femenino , Proteína Ácida Fibrilar de la Glía/genética , Janus Quinasa 2/genética , Masculino , Ratones , Células-Madre Neurales/citología , Células-Madre Neurales/metabolismo , Conejos , Factor de Transcripción STAT3/genéticaRESUMEN
Existing traditional Chinese medicine (TCM)-related databases are still insufficient in data standardization, integrity and precision, and need to be updated urgently. Herein, an Encyclopedia of Traditional Chinese Medicine version 2.0 (ETCM v2.0, http://www.tcmip.cn/ETCM2/front/#/) was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books, 9872 Chinese patent drugs, 2079 Chinese medicinal materials and 38,298 ingredients. To facilitate the mechanistic research and new drug discovery, we improved the target identification method based on a two-dimensional ligand similarity search module, which provides the confirmed and/or potential targets of each ingredient, as well as their binding activities. Importantly, five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0, which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy, to summarize the rules of prescription use, and to find alternative drugs for endangered Chinese medicinal materials. Moreover, ETCM v2.0 provides an enhanced JavaScript-based network visualization tool for creating, modifying and exploring multi-scale biological networks. ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs, the TCM-derived drug discovery and repurposing, and the pharmacological mechanism investigation of TCMs against various human diseases.
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BACKGROUND: In Traditional Chinese Medicine (TCM) theory, functional dyspepsia (FD) can be divided into different syndromes according to different clinical symptoms and signs, and the most common one is spleen-deficiency and qi-stagnation syndrome that can be treated by Chinese traditional patent medicine--two kinds of Zhizhu pills, between which the primary difference in ingredients is that one contains immature orange fruit of Citrus aurantium L.(IFCA) and the other contains that of Citrus sinensis Osbeck (IFCS). The trial's objective was to compare the efficacy of two kinds of Zhizhu pills on symptom changes in patients with FD of spleen-deficiency and qi-stagnation syndrome. METHODS: A randomized, group sequential, double-blinded, multicenter trial was conducted in patients with FD of spleen-deficiency and qi-stagnation syndrome at 3 hospitals in Beijing between June 2003 and May 2005. Participants were randomly allocated into two groups (IFCA group and IFCS group) in a 1:1 ratio, and respectively took one of the two kinds of Zhizhu pills orally, 6 g each time, 3 times a day, for 4 weeks. Statistical analysis was performed with use of a group sequential method, the triangular test (TT). RESULTS: A total of 163 patients were randomized, and 3 patients were excluded from analysis because of early dropouts, leaving 160 patients (IFCA group: n = 82; IFCS group: n = 78) for statistical analysis. Three interim analyses were done after 62, 116, and 160 patients had completed their 4-week treatment, respectively. At the third interim analysis, the sample path crossed the upper boundary and the trial was stopped, the cure-markedly effective rates were 45% for IFCS group and 67% for IFCA group, respectively, the one-sided p-value was 0.0036, the median unbiased estimate of the odds ratio (OR) for the benefit of IFCA relative to IFCS was 2.91 with 95%CI: 1.40 to 6.06.No adverse events were observed in the two groups. CONCLUSIONS: Zhizhu pills containing IFCA was superior to Zhizhu pills containing IFCS in the treatment of FD of spleen-deficiency and qi-stagnation syndrome. The application of group sequential analysis in clinical trials of TCM may offer some financial and ethical benefits. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR): ChiCTR-TRC-00000485.
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Citrus sinensis , Citrus , Medicamentos Herbarios Chinos/uso terapéutico , Dispepsia/tratamiento farmacológico , Fitoterapia , Enfermedades del Bazo/tratamiento farmacológico , Adulto , Método Doble Ciego , Dispepsia/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Qi , Enfermedades del Bazo/patología , Síndrome , Comprimidos , Resultado del TratamientoRESUMEN
OBJECTIVE: To explore the network control mechanism of the calcium signaling pathway in cerebral ischemic injury after intervention by the main components of Qingkailing (see text), i.e. Baicalin, Jasminoidin and their combination. METHODS: Thirty mice were randomly divided into 5 groups, a baicalin group, a Jasminoidin group, a baicalin plus Jasminoidin group, a nimodipine group, and a model group (n = 6). The global cerebral ischemia-reperfusion mouse model was established. The mice were administrated respectively by injection of baicalin, Jasminoidin, mixture of baicalin and Jasminoidin, and nimodipine into the caudal vein, with the model group given no any drug. Three hours after operation, the brain was removed and sectioned. After calculation of cerebral ischemic area by 2,3,5-triphenyltetrazolium staining, the percentage of infarct volume was calculated. The total RNA of the mouse brain tissue was extracted to obtain the whole genome expression profile, and the differentially expressed genes related to the calcium signaling pathway was analyzed with Bayesian network structures. RESULTS: Compared with the model group, the ischemic area was significantly reduced in the baicalin group, the Jasminoidin group, the Baicalin plus Jasminoidin group (all P < 0.05). The ischemic area in the baicalin plus Jasminoidin group was smaller than the other three groups (all P < 0.01). In the gene regulatory network structures of calcium signaling pathway, the average length and equitability were the highest in the baicalin plus Jasminoidin group, followed by the nimodipine group. CONCLUSION: Compared with a single component, combination of Baicalin and Jasminoidin can more obviously intervene in the overall expression of calcium signaling pathway, and the mechanism is related with the aggregation characteristic of the gene expression network.
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Isquemia Encefálica/tratamiento farmacológico , Señalización del Calcio/efectos de los fármacos , Medicamentos Herbarios Chinos/uso terapéutico , Animales , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Flavonoides/uso terapéutico , Iridoides/uso terapéutico , Masculino , Ratones , Nimodipina/uso terapéuticoRESUMEN
Stomach adenocarcinoma (STAD) is one of the most malignant cancers that endanger human health. There is growing evidence that competitive endogenous RNA (ceRNA) regulatory networks play an important role in various human tumors. However, the complexity and behavioral characteristics of the ceRNA network in STAD are still unclear. In this study, we constructed a ceRNA regulatory network to identify the potential prognostic biomarkers associated with STAD. The expression profile of lncRNA, miRNA, and mRNA was downloaded from The Cancer Genome Atlas (TCGA). After performing bioinformatics analysis, the CCDC144NL-AS1/hsa-miR-145-5p/SERPINE1 ceRNA network associated to STAD prognosis of STAD was obtained. The CCDC144NL-AS1/SERPINE1 axis in the ceRNA network was identified by correlation analysis and considered as a clinical prognosis model by Cox regression analysis. In addition, methylation analysis indicated that the abnormal upregulation of CCDC144NL-AS1/SERPINE1 axis might be related to the aberrant methylation of some sites, and immune infiltration analysis suggested that CCDC144NL-AS1/SERPINE1 axis probably influences the alteration of tumor immune microenvironment and the occurrence and development of STAD. In particular, the CCDC144NL-AS1/SERPINE1 axis based on the ceRNA network constructed in the present study might be an important novel factor correlating with the diagnosis and prognosis of STAD.
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OBJECTIVE: To compare the different gene expression profiles among Qingkailing components of BA (baicalin), JA (jasminoidin), CA (cholic acid) and CM (concha margaritiferausta) in regulating hippocampus ischemia related genes of mice. METHOD: The hippocampus ischemia-reperfusion model mice were randomly divided into groups of BA, JA, CA, CM and M (model group), 15 mice for each group, and decapitated after 24 hours. Coronal brain slices were stained with TTC (2, 3, 5-Triphenylte trazolium Chloride) and the percentages of infarct volume were calculated. Meanwhile, total RNA were extracted from the hippocampus. We selected 374 genes which related to cerebral ischemia to find the different gene expression profiles among the Qingkailing components. Then T-tests was used to select different genes between BA and CM, JA and CM, CA and CM by Arraytrack software (P < 0. 05, Fold change > 1.5), and the pharmacodynamic characteristics were explored according to GO functional classification. RESULT: Compared with the model group BA, JA and CA could effectively reduce infarct size of hippocampus ischemic (P < 0.05). the numbers of significantly differentially expressed genes were 41 (24 up, 17 down) between BA and CM, 22 (13 up, 9 down) between JA and CM, and 11(8 up, 3 down) between CA and CM. All of BA, JA and CA could inhibit the expression of Myb gene. CONCLUSION: When exerting its pharmacological effects, BA, JA, CA not only have common gene targets but also have diversity in pharmacological character.
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Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/genética , Medicamentos Herbarios Chinos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Hipocampo/efectos de los fármacos , Animales , Isquemia Encefálica/metabolismo , Modelos Animales de Enfermedad , Hipocampo/irrigación sanguínea , Hipocampo/metabolismo , Humanos , Masculino , Ratones , Distribución AleatoriaRESUMEN
Background: As non-small cell lung cancer (NSCLC) seriously threatens human health, several clinical studies have reported that Chinese herbal injections (CHIs) combined with vinorelbine and cisplatin (NP) are beneficial. This multidimensional network meta-analysis was performed to explore the preferable options among different CHIs for treating NSCLC. Methods: A literature search was performed in several databases to identify randomized controlled trials (RCTs) of CHIs in the treatment of NSCLC from inception to January 31, 2019. Final included studies met the eligibility criteria and methodological quality recommendations. Data analysis was performed using Stata 13.0 and WinBUGS 14.0 software. Each outcome was presented as an odds ratio and the surface under the cumulative ranking curve value (SCURA). The "scatterplot3d" package in R 3.6.1 software was used to perform multidimensional cluster analysis. Results: Ultimately, 97 eligible RCTs involving 7,440 patients and 14 CHIs were included in this network meta-analysis. Combined with NP chemotherapy, Kanglaite injection plus NP exhibited a better impact on the clinical effectiveness rate (SCURA probability: 78.34%), and Javanica oil emulsion injection plus NP was better in the performance status (95.44%). Huachansu injection plus NP was dominant in reducing thrombocytopenia (92.67%) and gastrointestinal reactions (92.52%). As to multidimensional cluster analysis, Shenmai injection plus NP was superior considering improving the clinical effectiveness rate, performance status and relieving leukopenia. Conclusions: The combination of CHIs and NP has a better impact on patients with NSCLC than NP alone. Among them, Shenmai injection plus NP, Kanglaite injection plus NP and Javanica oil emulsion injection plus NP were notable. Nevertheless, more multicenter and better designed RCTs are needed to validate our findings.
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INTRODUCTION: Considering the limitations of pure paclitaxel plus cisplatin chemotherapy in the treatment of non-small-cell lung cancer and the extensive exploration of Chinese herbal injections, this study performed a multidimensional network meta-analysis to systematically evaluate the clinical efficacy and safety of 12 Chinese herbal injections in the treatment of non-small-cell lung cancer. METHODS: Randomized controlled trials were obtained from several databases according to the eligibility criteria, and the study quality was assessed by the Cochrane risk of bias tool. Data analysis was performed by Stata 13.1 software and WinBUGS 14.0 software. Multidimensional cluster analysis was performed with the "scatterplot3d" package in R 3.6.1 software (PROSPERO ID: CRD42020163503). RESULTS: A total of 58 eligible randomized controlled trials involving 4578 patients and 12 Chinese herbal injections were included. Combined with paclitaxel plus cisplatin chemotherapy, Xiaoaiping injection exhibited a better impact on the clinical effective rate than paclitaxel plus cisplatin alone. Shenqifuzheng injection was associated with a preferable response in performance status and reduced leukopenia and gastrointestinal reactions. Kangai injection was dominant in the comprehensive results of the cluster analysis. CONCLUSIONS: Chinese herbal injections combined with paclitaxel plus cisplatin chemotherapy have a certain adjuvant effect in treating non-small-cell lung cancer, but the results of this study need to be verified by more well-designed, large-sample, multicenter randomized controlled trials.
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OBJECTIVE: To assess the clinical efficacy and safety of ginkgo injections (GIs) combined with conventional treatment (CT) against angina pectoris (AP) due to coronary heart disease (CHD). METHODS: Randomized controlled trials (RCTs) that used GIs to treat AP were searched in SinoMed, PubMed, China National Knowledge Infrastructure Database, Chinese Scientific Journals Database, Wanfang Database, Embase and Cochrane Library until March 2017. The Cochrane"risk of bias"method was used to evaluate the methodological quality of RCTs. Data were analyzed using Stata v13.1 and WinBUGS v1.4.3. RESULTS: A total of 73 RCTs involving 7621 patients were included. A Bayesian network Meta-analysis of RCTs was undertaken, and the advantages of four types of GI-supplemented CT in AP treatment were determined. CONCLUSION: GI-assisted CT was more effective against AP than CT alone. However, based on the limitations of the study, additional high-quality RCTs are required to confirm our findings.
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Angina de Pecho/tratamiento farmacológico , Angina de Pecho/etiología , Enfermedad Coronaria/complicaciones , Ginkgo biloba/química , Extractos Vegetales/uso terapéutico , Animales , Humanos , Metaanálisis en Red , Extractos Vegetales/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
BACKGROUND: Compound Kushen Injection (CKI) is a Chinese patent drug that shows good efficacy in treating lung cancer (LC). However, its underlying mechanisms need to be further clarified. METHODS: In this study, we adopted a network pharmacology method to gather compounds, predict targets, construct networks, and analyze biological functions and pathways. Moreover, molecular docking simulation was employed to assess the binding potential of selected target-compound pairs. RESULTS: Four networks were established, including the compound-putative target network, protein-protein interaction (PPI) network of LC targets, compound-LC target network, and herb-compound-target-pathway network. Network analysis showed that 8 targets (CHRNA3, DRD2, PRKCA, CDK1, CDK2, CHRNA5, MMP1, and MMP9) may be the therapeutic targets of CKI in LC. In addition, molecular docking simulation indicated that CHRNA3, DRD2, PRKCA, CDK1, CDK2, MMP1, and MMP9 had good binding activity with the corresponding compounds. Furthermore, enrichment analysis indicated that CKI might exert a therapeutic role in LC by regulating some important pathways, namely, pathways in cancer, proteoglycans in cancer, PI3K-Akt signaling pathway, non-small-cell lung cancer, and small cell lung cancer. CONCLUSIONS: This study validated and predicted the mechanism of CKI in treating LC. Additionally, this study provides a good foundation for further experimental studies and promotes the reasonable application of CKI in the clinical treatment of LC.
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The mechanism of Chinese medications have some characteristic such as multi-pathway, multi-components, multi-targets and so on, which decide the direction of systems research. In the recent years, microarrays be concerned with the relative field of Chinese medications for its superiority of highthough, parallel and high-density. This paper mainly generalize the approach of these methods in the recent three years, such as finding effective target of Chinese medications, effective part of Chinese medications, checkup of Chinese medications, screening new drugs and so on. We suggest the concept of Pharmacogenomics of Chinese medications with the guidance of the theory of Chinese medications for further development of Chinese medications.
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Perfilación de la Expresión Génica , Genómica/métodos , Análisis de Secuencia por Matrices de Oligonucleótidos , Plantas Medicinales/genética , Animales , Evaluación Preclínica de Medicamentos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/metabolismo , Medicamentos Herbarios Chinos/farmacología , Humanos , Modelos Teóricos , Farmacogenética/métodos , Plantas Medicinales/química , Plantas Medicinales/metabolismoRESUMEN
BACKGROUND: Cerebral ischemia-reperfusion injury may simultaneously result in functional variation of multiple genes/pathways. However, most prior time-sequence studies on its pathomechanism only focused on a single gene or pathway. Our study aimed to systematically analyze the time-dependent variation in the expression of multiple pathways and networks within 24 h after cerebral ischemia-reperfusion injury. RESULTS: By uploading 374 ischemia-related genes into the MetaCore software, the variation in the expression of multiple pathways and networks in 3 h, 12 h, and 24 h after cerebral ischemia-reperfusion injury had been analyzed. The conserved TNFR1-signaling pathway, among the top 10 pathways, was consistently enriched in 3 h, 12 h, and 24 h groups. Three overlapping pathways were found between 3 h and 12 h groups; 2 between 12 h and 24 h groups; and 1 between 3 h and 24 h groups. Five, 4, and 6 non-overlapping pathways were observed in 3 h, 12 h, and 24 h groups, respectively. Apart from pathways reported by earlier studies, we identified a novel pathway related to the time-dependent development of cerebral ischemia pathogenesis. The process of apoptosis stimulation by external signals, among the top 10 processes, was consistently enriched in 3 h, 12 h, and 24 h groups; 2, 1, and 2 processes overlapped between 3 h and 12 h groups, 12 h and 24 h groups, and 3 h and 24 h groups, respectively. Four, 5, and 5 non-overlapping processes were found in 3 h, 12 h and 24 h groups, respectively. The presence of apoptotic processes was observed in all the 3 groups; while anti-apoptotic processes only existed in 3 h and 12 h groups. Additionally, according to node degree, network comparison identified 1, 8,and 5 important genes or proteins (e.g. Pyk2, PKC, E2F1, and VEGF-A) in 3 h, 12 h, and 24 h groups, respectively. The Jaccard similarity index revealed a higher level of similarity between 12 h and 24 h groups than that between 3 h and 12 h groups. CONCLUSION: Time-dependent treatment can be utilized to reduce apoptosis, which may activate anti-apoptotic pathways within 12 h after cerebral ischemia-reperfusion injury. Pathway and network analyses may help identify novel pathways and genes implicated in disease pathogenesis.
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Apoptosis , Isquemia Encefálica/complicaciones , Perfilación de la Expresión Génica , Daño por Reperfusión/complicaciones , Daño por Reperfusión/metabolismo , Transducción de Señal , Biología de Sistemas , Animales , Isquemia Encefálica/metabolismo , Masculino , Ratones , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Daño por Reperfusión/genética , Daño por Reperfusión/patología , Programas Informáticos , Factores de TiempoRESUMEN
OBJECTIVE: To reveal the cutoff point and influencing factors in the dynamic change in phenotypic group in patients with stable angina pectoris (SAP) after Xinxuekang capsule treatment. METHODS: Five hundred and seventy-six SAP patients were randomly assigned to receive Xinxuekang (XXK) capsules or Compound Danshen (CDS) tablets for 8 weeks. Global similarity degree analysis and nonlinear mixed effects modeling (NONMEM) were employed to reveal the cutoff points and influencing factors in dynamic changes in the SAP phenotypic group. The phenotypic group was defined as the six phenotypes in SAP, including angina, choking sensation in the chest, palpitations, dark purple lips, ecchymosis on the tongue, and fine-choppy pulse, which were quantitatively evaluated on Days 0, 14, 28, 42, and 56. RESULTS: Variation in the six individual phenotypes and distribution of the SAP phenotypic profile were similar between the two experimental groups, but cutoff points for changes in the SAP phenotypic group were 7.28 and 10.73 weeks in XXK and CDS groups, respectively. Degree of severity of SAP as well as study site significantly affected the tendency for change in the SAP Xueyu Zheng in both XXK and CDS treatment groups. Different Chinese patent drugs affected the tendency for change in phenotypic group in patients with SAP. XXK was superior to CDS in controlling a clinical phenotypic group. CONCLUSION: Based on global similarity degree analysis and NONMEM, the cutoff point and influencing factors in phenomic variation of SAP may be determined, to improve the development and modification of treatment regimens.
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Angina Estable/diagnóstico , Angina Estable/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China/métodos , Adulto , Anciano , Cápsulas , Interpretación Estadística de Datos , Método Doble Ciego , Medicamentos Herbarios Chinos/administración & dosificación , Humanos , Persona de Mediana Edad , Salvia miltiorrhiza , Resultado del TratamientoRESUMEN
INTRODUCTION: Cerebral ischemia is considered to be a highly complex disease resulting from the complicated interplay of multiple pathways. Disappointedly, most of the previous studies were limited to a single gene or a single pathway. The extent to which all involved pathways are translated into fusing mechanisms of a combination therapy is of fundamental importance. AIMS: We report an integrative strategy to reveal the additive mechanism that a combination (BJ) of compound baicalin (BA) and jasminoidin (JA) fights against cerebral ischemia based on variation of pathways and functional communities. RESULTS: We identified six pathways of BJ group that shared diverse additive index from 0.09 to 1, which assembled broad cross talks from seven pathways of BA and 16 pathways of JA both at horizontal and vertical levels. Besides a total of 60 overlapping functions as a robust integration background among the three groups based on significantly differential subnetworks, additive mechanism with strong confidence by networks altered functions. CONCLUSIONS: These results provide strong evidence that the additive mechanism is more complex than previously appreciated, and an integrative analysis of pathways may suggest an important paradigm for revealing pharmacological mechanisms underlying drug combinations.
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Antiinflamatorios no Esteroideos/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Flavonoides/uso terapéutico , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Iridoides/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Quimioterapia Combinada , Masculino , Ratones , Ratones Endogámicos , Análisis por Micromatrices , Datos de Secuencia Molecular , Análisis de Componente Principal , Transducción de Señal/efectos de los fármacosRESUMEN
Until now the overlapping and diverse pharmacological protective mechanisms of different compounds in the treatment of cerebral ischemia, both on the signaling pathway and network levels have not been revealed. In order to find differential pathway networks from gene expression profiles of hippocampus of ischemic mice treated with baicalin (BA), ursodeoxycholic acid (UA) and jasminoidin (JA), a microarray comprising 16,463 genes, FDA Arraytrack software and Ingenuity Pathway Analysis, was employed. A total of 5, 8, 11, 9 networks and 6, 7, 40, 16 pathways were found in vehicle (vs sham), BA, UA and JA (vs vehicle), respectively. Only 4 and 7 overlapping pathways were shared between BA and UA, UA and JA, accounting for 9.3% and 14.3% of the total number of all pathways, respectively. BA, UA and JA all acted on Ca(2+)-dependent signaling cascades in diverse links. BA intervened in arachidonic acid metabolism. UA affected eicosanoid, cyclin-dependent kinase 5, nuclear factor-kB, and T-helper 1 cell cytokine production. It was found that JA might decrease oxidative damage via nuclear factor erythroid 2-related factor 2-mediated antioxidant response. Compared to vehicle, no overlapping pathways were found among three groups. However, the total of 60 (71.4%) overlapping functions could be approximately divided into diseases and disorders, molecular and cellular functions, physiological system development and function as categories with ratio of 1:1:1. Analysis of network functions and known pathways may be two complementary paradigms for revealing potential pharmacological mechanisms based on the same phenotype variation.
Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Redes Reguladoras de Genes/fisiología , Transducción de Señal/fisiología , Transcriptoma/fisiología , Animales , Isquemia Encefálica/patología , Flavonoides/farmacología , Flavonoides/uso terapéutico , Redes Reguladoras de Genes/efectos de los fármacos , Iridoides/farmacología , Iridoides/uso terapéutico , Masculino , Ratones , Distribución Aleatoria , Transducción de Señal/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Ácido Ursodesoxicólico/farmacología , Ácido Ursodesoxicólico/uso terapéuticoRESUMEN
In order to elucidate the overlapping and diverse pharmacological protective mechanisms of different Chinese medicinal compounds, we investigated the alteration of gene expression and activation of signaling pathways in the mouse hippocampus after treatment of cerebral ischemia-reperfusion injury with various compounds. A microarray including 16,463 genes was used to identify differentially expressed genes among six treatment groups: baicalin (BA), jasminoidin (JA), cholic acid (CA), concha margaritiferausta (CM), sham, and vehicle. The US Food and Drug Administration (FDA) ArrayTrack system and Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used to screen significantly altered genes and pathways (P < 0.05, fold change >1.5). Vehicle treatment alone resulted in alteration of 726 genes (283 upregulated, 443 downregulated) compared to the sham treatment group. BA, JA, and CA treatments, but not CM treatment, were effective in reducing infarct volume compared with vehicle treatment (P < 0.05). Compared with the CM group, a total of 167 (73 upregulated, 94 downregulated), 379 (211 upregulated, 168 downregulated), and 181 (76 upregulated, 105 downregulated) altered genes were found in the BA, JA, and CA groups, respectively. The numbers of overlapping genes between the BA and JA, BA and CA, and JA and CA groups were 28 (16 upregulated, 12 downregulated), 14 (4 upregulated, 10 downregulated), and 31 (8 upregulated, 23 downregulated), respectively. Three overlapping genes were identified among the BA, JA, and CA treatment groups: Il1rap, Gnb5, and Wdr38. Based on KEGG pathway analysis, two, seven, and four pathways were significantly activated in the BA, JA, and CA groups, respectively, when compared to the CM group. The ATP-binding cassette (ABC) transporters general pathway was activated by BA and JA treatment, and the mitogen-activated protein kinase (MAPK) signaling pathway was activated by JA and CA treatment. Alteration of IL-1 and Hspa1a expression was found by real time reverse transcription polymerase chain reaction, confirming the results of the microarray analysis. Our data demonstrated that polytypic profiles of 167-379 altered genes exist in the mouse hippocampus treated with different compounds known to be therapeutically effective in cerebral ischemia-reperfusion injury, and we were able to identify overlapping genes and pathways among these groups. Therefore, these different compounds may function through both overlapping and distinct pharmacological mechanisms to exert their therapeutic action.