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1.
Brief Bioinform ; 25(3)2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38555472

RESUMEN

Predicting interactions between microbes and hosts plays critical roles in microbiome population genetics and microbial ecology and evolution. How to systematically characterize the sophisticated mechanisms and signal interplay between microbes and hosts is a significant challenge for global health risks. Identifying microbe-host interactions (MHIs) can not only provide helpful insights into their fundamental regulatory mechanisms, but also facilitate the development of targeted therapies for microbial infections. In recent years, computational methods have become an appealing alternative due to the high risk and cost of wet-lab experiments. Therefore, in this study, we utilized rich microbial metagenomic information to construct a novel heterogeneous microbial network (HMN)-based model named KGVHI to predict candidate microbes for target hosts. Specifically, KGVHI first built a HMN by integrating human proteins, viruses and pathogenic bacteria with their biological attributes. Then KGVHI adopted a knowledge graph embedding strategy to capture the global topological structure information of the whole network. A natural language processing algorithm is used to extract the local biological attribute information from the nodes in HMN. Finally, we combined the local and global information and fed it into a blended deep neural network (DNN) for training and prediction. Compared to state-of-the-art methods, the comprehensive experimental results show that our model can obtain excellent results on the corresponding three MHI datasets. Furthermore, we also conducted two pathogenic bacteria case studies to further indicate that KGVHI has excellent predictive capabilities for potential MHI pairs.


Asunto(s)
Aprendizaje Profundo , Humanos , Reconocimiento de Normas Patrones Automatizadas , Redes Neurales de la Computación , Algoritmos , Bacterias
2.
Brief Bioinform ; 24(6)2023 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-37742053

RESUMEN

Identifying the potential bacteriophages (phage) candidate to treat bacterial infections plays an essential role in the research of human pathogens. Computational approaches are recognized as a valid way to predict bacteria and target phages. However, most of the current methods only utilize lower-order biological information without considering the higher-order connectivity patterns, which helps to improve the predictive accuracy. Therefore, we developed a novel microbial heterogeneous interaction network (MHIN)-based model called PTBGRP to predict new phages for bacterial hosts. Specifically, PTBGRP first constructs an MHIN by integrating phage-bacteria interaction (PBI) and six bacteria-bacteria interaction networks with their biological attributes. Then, different representation learning methods are deployed to extract higher-level biological features and lower-level topological features from MHIN. Finally, PTBGRP employs a deep neural network as the classifier to predict unknown PBI pairs based on the fused biological information. Experiment results demonstrated that PTBGRP achieves the best performance on the corresponding ESKAPE pathogens and PBI dataset when compared with state-of-art methods. In addition, case studies of Klebsiella pneumoniae and Staphylococcus aureus further indicate that the consideration of rich heterogeneous information enables PTBGRP to accurately predict PBI from a more comprehensive perspective. The webserver of the PTBGRP predictor is freely available at http://120.77.11.78/PTBGRP/.


Asunto(s)
Bacteriófagos , Infecciones Estafilocócicas , Humanos , Aprendizaje , Bacterias , Redes Neurales de la Computación
3.
Molecules ; 26(6)2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33808667

RESUMEN

Novel α-aminoamide derivatives containing different benzoheterocyclics moiety were synthesized and evaluated as voltage-gated sodium ion channels blocks the treatment of pain. Compounds 6a, 6e, and 6f containing the benzofuran group displayed more potent in vivo analgesic activity than ralfinamide in both the formalin test and the writhing assay. Interestingly, they also exhibited potent in vitro anti-Nav1.7 and anti-Nav1.8 activity in the patch-clamp electrophysiology assay. Therefore, compounds 6a, 6e, and 6f, which have inhibitory potency for two pain-related Nav targets, could serve as new leads for the development of analgesic medicines.


Asunto(s)
Amidas , Analgésicos , Dolor/tratamiento farmacológico , Bloqueadores de los Canales de Sodio , Amidas/síntesis química , Amidas/química , Amidas/farmacología , Analgésicos/síntesis química , Analgésicos/química , Analgésicos/farmacología , Animales , Evaluación de Medicamentos , Masculino , Ratones , Canal de Sodio Activado por Voltaje NAV1.7/metabolismo , Canal de Sodio Activado por Voltaje NAV1.8/metabolismo , Dolor/inducido químicamente , Dolor/metabolismo , Bloqueadores de los Canales de Sodio/síntesis química , Bloqueadores de los Canales de Sodio/química , Bloqueadores de los Canales de Sodio/farmacología
4.
Cell Physiol Biochem ; 38(6): 2247-60, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27188168

RESUMEN

BACKGROUND/AIMS: Due to its antitumor and gastroprotective properties, cochinchina momordica seed (CMS), has been widely used to treat cancer patients in Asia. Our previous reports have shown that CMS is able to induce the differentiation of B16-F1 melanoma cells. However, its functional component and mechanism remain unclear and are addressed in this study. METHODS AND RESULTS: CMSP (p-hydroxycinnamaldehyde isolated from CMS) inhibited the proliferation, migration and invasiveness of B16-F1 cells both in vivo and in vitro. CMSP also induced the differentiation of B16-F1 cells, as characterized by dendrite-like outgrowth, increased melanogenesis and enhanced tyrosinase activity. Furthermore, CMSP treatment reduced the level of malignant markers of melanoma, specifically S-100B and melanoma-derived growth regulatory protein precursor (MIA), in a concentration-dependent manner. According to a western blot analysis, B16-F1 cells treated with CMSP exhibited a sustained increase in p-P38 and decreased activities of ERK and JNK. Our data further indicated that the downregulation of GTP-RhoA, which was mediated by increased cAMP release, was involved in CMSP-induced changes in MAPK, while LPA (Lysophosphatidic acid) partially reversed CMSP-induced B16 cell differentiation. CONCLUSION: These results demonstrated that CMSP-induced differentiation of B16F1 cells may occur through the RhoA-MAPK axis, which suggests a new potential strategy for melanoma treatment.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Diferenciación Celular/efectos de los fármacos , Cinamatos/farmacología , Melanoma Experimental/tratamiento farmacológico , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Transducción de Señal/efectos de los fármacos , Proteína de Unión al GTP rhoA/metabolismo , Animales , Antineoplásicos Fitogénicos/química , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Cinamatos/química , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Ratones , Momordica/química , Monofenol Monooxigenasa/metabolismo , Semillas/química
5.
Mol Med Rep ; 11(2): 871-80, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25373392

RESUMEN

Forsythia suspensa root is used in the treatment of fever and jaundice in Traditional Chinese Medicine. In the present study, the anti-tumor activity of the ethanolic extract of Forsythia suspensa root (FSREE) against esophageal carcinoma cells was investigated in vitro and in vivo and its anti-cancer mechanism was examined. The results revealed that FSREE, rather than Forsythia suspensa ethanolic extracts from the leaf (FSLEE) and fruit (FSFEE) exhibited marked anti-tumor activity towards human esophageal cancer cells. FSREE induced cancer cell apoptosis and growth arrest by downregulating B­cell lymphoma (Bcl)­2, Bcl­extra large and myeloid cell leukemia 1, while upregulating Bcl­2­associated X protein, Bcl­2 antagonist of cell death and phorbol­12­myristate­13­acetate­induced protein 1. This led to the activation of poly(ADP ribose) polymerase, caspase­3 and caspase­9, but not caspase­8. Furthermore, the anti-cancer activity of FSREE was associated with a decreased level of phosphorylated Janus kinase/signal transducer and activator of transcription 3 and extracellular­signal­regulated kinase signaling activity. It was also observed that the levels of cytochrome c were elevated in the cytoplasm, accounting for the loss of mitochondrial membrane potential in the TE­13 cells upon treatment with FSEER. In addition, FSEER inhibited the growth of esophageal cancer cells in xenograft models and no detectable toxicity was present in the lung or liver tissues. These observations provided further evidence of the anti-tumor effect of FSEER and may be of importance to further examine the potential role of Forsythia suspensa root as a therapeutic agent in esophageal carcinoma therapy.


Asunto(s)
Apoptosis/efectos de los fármacos , Forsythia/química , Mitocondrias/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Carcinoma/tratamiento farmacológico , Carcinoma/metabolismo , Carcinoma/patología , Caspasas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Forsythia/metabolismo , Humanos , Ratones , Ratones Desnudos , Mitocondrias/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Fosforilación/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Raíces de Plantas/química , Raíces de Plantas/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Transducción de Señal/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismo
6.
Asian Pac J Cancer Prev ; 13(8): 3795-802, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23098473

RESUMEN

Cochinchina momordica seeds (CMS) have been widely used due to antitumor activity by Mongolian tribes of China. However, the details of the underlying mechanisms remain unknown. In the present study, we found that an EtOAc (ethyl ester) extract of CMS (CMSEE) induced differentiation and caused growth inhibition of melanoma B16 F1 cells. CMSEE at the concentration of 5-200 µg/ml exhibited strongest anti-proliferative effects on B16 F1 cells among other CMS fractions (water or petroleum ether). Moreover, CMSEE induced melanoma B16 F1 cell differentiation, characterized by dendrite-like outgrowth, increasing melanogenesis production, as well as enhancing tyrosinase activity. Western blot analysis showed that sustained phosphorylation of p38 MAP accompanied by decrease in ERK1/2 and JNK dephosphorylation were involved in CMSEE-induced B16 F1 cell differentiation. Notably, 6 compounds that were isolated and identified may be responsible for inducing differentiation of CMSEE. These results indicated that CMSEE contributes to the differentiation of B16 F1 cells through modulating MAPKs activity, which may throw some light on the development of potentially therapeutic strategies for melanoma treatment.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , MAP Quinasa Quinasa 4/metabolismo , Melanoma Experimental/patología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Momordica/química , Fitoterapia , Semillas/química , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Proliferación Celular/efectos de los fármacos , Ésteres/química , Citometría de Flujo , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/metabolismo , Ratones , Estructura Molecular , Monofenol Monooxigenasa/metabolismo , Fosforilación/efectos de los fármacos , Extractos Vegetales/farmacología , Transducción de Señal , Células Tumorales Cultivadas
7.
Yao Xue Xue Bao ; 47(2): 206-9, 2012 Feb.
Artículo en Chino | MEDLINE | ID: mdl-22512032

RESUMEN

To study the coumarins of Anemone raddeana Regel, the compounds were separated by silica gel column chromatography and HPLC. Their structures were identified by their physicochemical property and spectral analysis. Two new compounds were isolated and identified as 4, 7-dimethoxyl-5-methyl-6-hydroxy coumarin (1) and 4, 7-dimethoxyl-5-formyl-6-hydroxycoumarin (2). The bioassays indicated that compounds 1 and 2 could significantly inhibit the proliferation of cancer cell, and showed the agonist effect on the transactivity of retinoic acid receptor-alpha (RARalpha). In addition, the two compounds had inhibitory effect against human leukocyte elastase (HLE).


Asunto(s)
Anemone/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Cumarinas/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cumarinas/química , Cumarinas/farmacología , Humanos , Concentración 50 Inhibidora , Elastasa de Leucocito/metabolismo , Estructura Molecular , Plantas Medicinales/química , Receptores de Ácido Retinoico/genética , Receptores de Ácido Retinoico/metabolismo , Receptor alfa de Ácido Retinoico , Rizoma/química , Activación Transcripcional
8.
Antiviral Res ; 90(1): 54-63, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21352856

RESUMEN

gp41 is a major component of the envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) responsible for fusion of the viral envelope with the target cellular membrane. The formation of the trimer-of-hairpins core structure of gp41, via the interaction between its N-terminal heptad repeat (NHR) and its C-terminal heptad repeat (CHR) plays a key role in the membrane fusion process. Hence, inhibitors of trimer-of-hairpins formation have become a promising new class of HIV therapeutics. In the present study, based on the mammalian two-hybrid system, we developed a cell-based assay for detecting small-molecular HIV-1 fusion inhibitors targeting gp41. The optimized assay can be adapted to high-throughput screening in 96- and 384-well microplates with high signal-to-background ratios and acceptable Z' factors. The known small-molecular gp41 inhibitors, ADS-J1, XTT formazan and tannin acid, tested positive in this assay, with half-maximal inhibitory concentration (IC50) values of 4.9 µM, 5.6 µM and 0.8 µM, respectively. These data suggested that this novel assay is robust, sensitive and specific for identifying small-molecular HIV-1 gp41 inhibitors.


Asunto(s)
Fármacos Anti-VIH/farmacología , Inhibidores de Fusión de VIH/farmacología , VIH-1/efectos de los fármacos , Técnicas del Sistema de Dos Híbridos , Fármacos Anti-VIH/aislamiento & purificación , Evaluación Preclínica de Medicamentos/métodos , Proteína gp41 de Envoltorio del VIH , Inhibidores de Fusión de VIH/aislamiento & purificación , Ensayos Analíticos de Alto Rendimiento/métodos , Humanos , Pruebas de Sensibilidad Microbiana/métodos , Sensibilidad y Especificidad
9.
Oncol Rep ; 24(2): 375-83, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20596624

RESUMEN

Cancer of the colon and rectum is the third most commonly diagnosed cancer and accounts for approximately 10% of all cancer-related deaths. Although surgical resection or radiotherapy are potentially curative for localized disease, advanced colon cancer is currently associated with poor prognosis. Therefore, the development of a new and effective chemotherapeutic agent is required to target critical pathways to induce responsiveness of colon cancer cells to death signals. Dysregulation of the beta-catenin/TCF pathway plays a central role in early activities of colorectal carcinogenesis. In this study, human colon cancer SW480 cells were used to investigate the effect of CPP (periplocin from Cortex periplocae) on the modulation of the beta-catenin/TCF signaling pathway. Our research results showed that CPP caused a dose- and time-dependent inhibition of cell growth as assessed by MTT assay and an induction in apoptosis as measured by flow cytometry and transmission electron microscopy. Furthermore, the CPP- treated cells were characterized by a decreased expression of beta-catenin protein in the total cell lysates and cytosolic and nuclear extracts. This expression alleviates the binding activity of T-cell factor (Tcf) complexes to its specific DNA-binding sites. Thus, the protein expression of the downstream elements survivin and c-myc was down-regulated. To determine the precise inhibitory mechanisms involved, further in-depth in vivo studies of CPP are warranted. In conclusion, our data suggest that CPP wields a multi-prong strategy to target the beta-catenin/Tcf signaling pathway, leading to the induction of apoptosis and inhibition of growth of colon cancer cells in vitro and in vivo. Therefore, CPP may become a potential agent against colon cancer.


Asunto(s)
Carcinoma/patología , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/patología , Genes myc/efectos de los fármacos , Proteínas Asociadas a Microtúbulos/genética , Saponinas/farmacología , Factores de Transcripción TCF/fisiología , beta Catenina/fisiología , Antineoplásicos Fitogénicos/farmacología , Carcinoma/genética , Neoplasias del Colon/genética , Regulación hacia Abajo/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Proteínas Inhibidoras de la Apoptosis , Proteínas Asociadas a Microtúbulos/metabolismo , Modelos Biológicos , Periploca/química , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Survivin , Factores de Transcripción TCF/genética , Factores de Transcripción TCF/metabolismo , Células Tumorales Cultivadas , beta Catenina/genética , beta Catenina/metabolismo
10.
Yao Xue Xue Bao ; 44(7): 764-7, 2009 Jul.
Artículo en Chino | MEDLINE | ID: mdl-19806917

RESUMEN

To study chemical constituents of Polygonatum odoratum (Mill.) Druce, the compounds were separated with column chromatography and HPLC. On the basis of physicochemical properties and spectral data, their structures were confirmed. Nine compounds were isolated and identified as 5,7-dihydroxy-6-methoxyl-8-methyl-3-(2',4'-dihydroxybenzyl)chroman-4-one (1), 5,7-dihydroxy-6-methyl-3-(2',4'-dihydroxybenzyl)chroman-4-one (2), 5,7-dihydroxy-6-methoxyl-8-methyl-3-(4'-methoxybenzyl)chroman-4-one (3), disporopsin (4), chrysoeriol (5), 5,4'-dihydroxy-7-methoxy-6-methylflavone (6), N-trans-feruloyltyramine (7), N-trans-feruloyloctopamine (8), and (+)-syringaresinol (9). Compounds 1-3 are new homoisoflavanones. Compounds 4-9 are isolated from this plant for the first time.


Asunto(s)
Isoflavonas/aislamiento & purificación , Polygonatum/química , Estructura Molecular
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