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1.
J Psychiatr Res ; 170: 174-186, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38150769

RESUMEN

Based on existing evidence of the effects of the most commonly used non-invasive brain stimulation (NIBS), which includes transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), we conducted a meta-analysis to investigate the cognitive improvement and safety of NIBS on schizophrenia-related cognitive impairment. PubMed, EMBASE, Cochrane Library, and Web of Science were searched. The Cochrane Risk of Bias tool was used to assess the risk of bias of the included RCTs; Review Manager, version 5.4.1, was used to perform the statistical analysis. Twenty double-blind, randomized, sham-controlled trials involving 997 patients were included. As a result, no significant improvement in cognitive function was observed after NIBS treatment. However, the overall treatment effect of the two main NIBS modes (i.e., rTMS and tDCS) was associated with significantly larger improvements in negative symptoms and good tolerability in patients with schizophrenia compared to sham-controls (SMD = -0.56, 95% CI [-1.03, -0.08], p = 0.02, I2 = 88%). NIBS model and stimulus parameters influenced the effect of NIBS. More favorable effects were observed in patients who received rTMS stimulation (SMD = 0.25, 95% CI [0.01, 0.49], p = 0.04, I2 = 0%) in the left dorsolateral prefrontal cortex with a stimulation intensity of 20 Hz (p = 0.004) for a period longer than 1 month (p < 0.05). Yet, due to the limited number of included studies and heterogeneity in both study design and target population, the results of this analysis need to be interpreted with caution.


Asunto(s)
Disfunción Cognitiva , Esquizofrenia , Estimulación Transcraneal de Corriente Directa , Humanos , Estimulación Transcraneal de Corriente Directa/efectos adversos , Estimulación Transcraneal de Corriente Directa/métodos , Esquizofrenia/complicaciones , Esquizofrenia/terapia , Estimulación Magnética Transcraneal/efectos adversos , Estimulación Magnética Transcraneal/métodos , Cognición , Disfunción Cognitiva/etiología , Disfunción Cognitiva/terapia , Encéfalo/fisiología , Ensayos Clínicos Controlados Aleatorios como Asunto
2.
Am J Cancer Res ; 13(8): 3659-3667, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37693126

RESUMEN

Ferroptosis results from metabolic dysregulation and is closely linked to liver cancer. Although a ferroptosis-related gene signature in liver cancer has been established, the precise regulatory mechanism is still unclear. To identify shared pathogenic genes linked to ferroptosis across liver cancer patients from diverse racial backgrounds, we evaluated various ferroptosis-related genes, constructing a signature for both Asian and White patients using The Cancer Genome Atlas (TCGA) database. Based on the differential expression and functionality of ferroptosis-associated genes, we selected Farnesyl diphosphate farnesyl transferase 1 (FDFT1), Acyl-CoA synthetase long-chain 4 (ACSL4) and Endoplasmic reticulum membrane protein complex 2 (EMC2) for further study in liver cancer cells. FDFT1, ACSL4 and EMC2 induced ferroptosis of liver cancer cells though upregulation of reactive oxygen species (ROS) levels and downregulation of glutathione peroxidase (GPX4). Current data indicate no notable influence of racial differences on the functionality of ferroptosis-related genes. Our data suggests potential novel therapeutic avenues for liver cancer treatment.

3.
Free Radic Biol Med ; 206: 125-133, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37406742

RESUMEN

Excessive drinking is one of the main causes of liver cancer. In the process of alcohol metabolism, aldehyde dehydrogenase 2 (ALDH2) is the key enzyme of acetaldehyde metabolism. ALDH2 gene deficiency is positively associated with the risk of hepatocellular carcinoma (HCC). However, no studies have shown a connection between ALDH2 and another metabolic regulatory gene, SLC3A2. In this study, we analyzed the expression levels of ALDH2 and SLC3A2 in liver cancer tissues based on the TCGA database. Subsequently, we constructed ALDH2 knockout and SLC3A2 knock-in transgenic mice to check the roles of ALDH2 and SLC3A2 in tumorigenesis in vivo. In addition, we examined the mechanisms of ALDH2 and SLC3A2 in HCC cells using small RNA interference technology. Consistent with previous studies, we also confirmed the functions of ALDH2 in inhibiting hepatocarcinogenesis, while SLC3A2 had the opposite effect. The main finding of this study is that ALDH2 inhibited BSG expression through the TGF-ß1 pathway, which indirectly inhibited SLC3A2 expression; subsequently, the sphingolipid metabolism pathway was also inhibited in HCC cells. Therefore, SLC3A2 is a novel target for HCC treatment.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratones , Animales , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/patología , Aldehído Deshidrogenasa Mitocondrial/genética , Aldehído Deshidrogenasa Mitocondrial/metabolismo , Etanol/metabolismo , Ratones Transgénicos , Esfingolípidos , Aldehído Deshidrogenasa/genética , Aldehído Deshidrogenasa/metabolismo , Acetaldehído/metabolismo
4.
BMC Neurol ; 23(1): 210, 2023 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-37259037

RESUMEN

BACKGROUND: Depressive symptoms are the most common neuropsychiatric symptoms in patients with Alzheimer's disease (AD). However, despite being common, no definite consensus recommendations exist for the management of depression in AD. OBJECTIVE: To assess the effects of selective serotonin reuptake inhibitors (SSRIs) on the alleviation of depressive symptoms in patients with AD. MATERIAL AND METHODS: Medline, Scopus, Web of Science, Google Scholar, and PsychINFO were electronically searched from inception until October 2022. Response to therapy and mean depression scores between the treatment (or before) and placebo (or after) groups were the primary outcomes. For depression scores, the standard mean deviation and accompanying 95% confidence interval were determined. The risk of bias was determined using the funnel plot, trim and fill, Egger's and Begg's analyses. RESULTS: SSRIs attenuated depressive symptoms in patients with AD (0.905 SMD, 95%CI, 0.689 to 1.121, p < 0.000). At individual SSRI level, escitalopram, paroxetine, and sertraline significantly alleviated depressive symptoms in AD patients (0.813 SMD, 95%CI, 0.207 to 1.419, p = 0.009, 1.244 SMD, 95%CI, 0.939 to 1.548, p < 0.000, and 0.818 SMD, 95%CI, 0.274 to 1.362, p < 0.000). The funnel plot, trim and fill, Begg's test (p = 0.052), and Egger's test (p = 0.148), showed no significant risk of publication bias. CONCLUSION: Our meta-analysis supports the use of SSRIs for the alleviation of depression in patients with AD. However, we recommend larger randomized clinical trials that would compare the efficacy of different SSRIs in AD patients with depression.


Asunto(s)
Enfermedad de Alzheimer , Inhibidores Selectivos de la Recaptación de Serotonina , Humanos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Depresión/tratamiento farmacológico , Depresión/etiología , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/tratamiento farmacológico , Sertralina/uso terapéutico , Escitalopram
5.
Am J Cancer Res ; 13(3): 802-817, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37034207

RESUMEN

Cancer stem cells (CSCs) are a subset of cancer cells with stem cell characteristics. The discovery of CSCs has opened a new era for cancer research. CSCs not only play a critical role in tumorigenesis, but also are responsible for the failure of cancer treatments. Here, we performed weighted gene co-expression network analysis (WGCNA) to identify key stemness genes and prognostic signatures using the data of an Asian liver cancer patient cohort and a White liver cancer patient cohort in The Cancer Genome Atlas (TCGA) database. To compare the difference in tumorigenesis between the Asian patients and the White patients, the prognostic value of the key genes from the Asian patients was evaluated in the White patient cohort and vice versa. We found that some key genes could predict the survival of the patients regardless of race. In addition, the key genes, NUCB2 and KLF4A, were selected from Asian patients and White patients, respectively, for further experimental validation. Knocking down NUCB2 could inhibit the activity of the AKT/mTOR signaling pathway and reverse the epithelial-mesenchymal transition (EMT) in liver cancer cells. We also confirmed that the knockdown of KLF4A suppressed ABCG2 activity and reduced the side population (SP) in liver cancer cells for the first time. Our results suggest that the stemness index is a useful method to identify key genes in tumorigenesis. Compared to the analysis for all patients, applying this index to the analysis of the patients of different races will provide more potential therapeutic targets for cancer treatment.

6.
Int J Med Sci ; 19(14): 2087-2092, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36483594

RESUMEN

In this review, we discussed an interesting case infected with "COVID-19" (Corona Virus Disease 2019). The patients with Hodgkin's lymphoma recovered after infection with COVID-19. It may be that COVID-19 activates the patient's immune system, or it may be a coincidence. COVID-19 spike protein can interact with CD147 and use it as an entry to invade host cells. CD147 is a partner of SLC3A2, which is the chaperone subunit of cystine/glutamate reverse transporter (system XC). The catalytic subunit of system XC is SLC7A11. SLC7A11 mediated cysteine uptake plays a key role in ferroptosis. Through literature review and data analysis, we suggest that CD147, as a new potential COVID-19 infection entry, may also lead to ferroptosis of host cells. Our hypothesis is that spike protein of COVID-19 induced ferroptosis in host cells via CD147/SLC3A2/SLC7A11 complex. This is another explanation for the cancer patient recovered after COVID-19 infection.


Asunto(s)
COVID-19 , Neoplasias , Humanos , Glicoproteína de la Espiga del Coronavirus , Análisis de Datos , Neoplasias/complicaciones
7.
Biomed Res Int ; 2022: 2146236, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35299894

RESUMEN

This paper addresses the mixture symptom mention problem which appears in the structuring of Traditional Chinese Medicine (TCM). We accomplished this by disassembling mixture symptom mentions with entity relation extraction. Over 2,200 clinical notes were annotated to construct the training set. Then, an end-to-end joint learning model was established to extract the entity relations. A joint model leveraging a multihead mechanism was proposed to deal with the problem of relation overlapping. A pretrained transformer encoder was adopted to capture context information. Compared with the entity extraction pipeline, the constructed joint learning model was superior in recall, precision, and F1 measures, at 0.822, 0.825, and 0.818, respectively, 14% higher than the baseline model. The joint learning model could automatically extract features without any extra natural language processing tools. This is efficient in the disassembling of mixture symptom mentions. Furthermore, this superior performance at identifying overlapping relations could benefit the reassembling of separated symptom entities downstream.


Asunto(s)
Aprendizaje Automático , Registros Médicos , Medicina Tradicional China , Evaluación de Síntomas/métodos , Humanos
8.
Biomed Res Int ; 2021: 9758328, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34869774

RESUMEN

[This corrects the article DOI: 10.1155/2021/1738932.].

9.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 38(6): 1134-1143, 2021 Dec 25.
Artículo en Chino | MEDLINE | ID: mdl-34970897

RESUMEN

In the study of embryo development process, the morphological features at different stages are essential to evaluate developmental competence of the embryo, which can be used to optimize and improve the system for in-vitro embryo culture. In this paper, an online monitoring system was designed for long-term culture of embryos, based on a monitoring strategy of low-magnification search and high-magnification observation. Three optical modules of 4× phase contrast, 10× and 20× Hoffman modulation phase contrast were configured in this system to meet the requirements of different fields of view, especially when the size of the embryo increases during the culture. Using an optomechanical system matching design, an error control and alignment test, the resolution of optical imaging was guaranteed, and a relief stereoscopic imaging with high contrast of embryos was obtained. Through low-magnification field of view to identify and locate embryos and high-magnification field of view to capture the details, the system realized online tracking and monitoring of embryos. In addition, we developed and verified an embryo identifying and locating algorithm based on image contour area and definition evaluation. The online monitoring system of in-vitro embryo culture proposed in this paper can track and record the morphological features of embryos without affecting the embryo development, providing a basis for the assessment of embryo development and the optimization of in-vitro culture system.


Asunto(s)
Blastocisto , Técnicas de Cultivo de Embriones , Desarrollo Embrionario , Fertilización In Vitro
10.
Front Pharmacol ; 12: 707442, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34658854

RESUMEN

Objective: For patients with chronic diseases requiring long-term use of medications who are quarantined at home, the management of medication therapy during the COVID-19 pandemic is a problem that pharmacists urgently need to discuss and solve. The study aims to establish and launch a telepharmacy framework to implement pharmaceutical care during the COVID-19 pandemic. Methods: To establish a remote pharmacy service model based on a medication consultation service platform under the official account of the "Beijing Pharmacists Association" on the social software WeChat app, obtain the medication consultation records from February 28 to April 27, 2020, during the worst period of the epidemic in China, and to perform a statistical analysis of the information about the patients seeking consultation, consultation process, content and follow-up results. Results: The medication consultation service system and telepharmacy service model based on social software were established in February 2020. The "Cloud Pharmacy Care" platform had 1,432 views and 66 followers and completed 39 counseling cases in 2 months. Counseling was available for patients of all ages. Of the 39 cases, 82.05% of patients were young and middle-aged. During the COVID-19 pandemic, the long-term medication usage problems of patients with chronic disease were effectively addressed using "Cloud Pharmacy Care". In the consultation, 35 cases (89.7%) were related to the use of medicines or health products, and 4 cases (10.3%) involved disease state management and the use of supplements. The top five drug-related issues included the selection of medications, the dosage and usage of drugs, medications for special populations, medication therapy management of chronic diseases, and adverse drug reactions. All consultations were completed within 4 h, with a positive review rate of 97.4%. Conclusion: During the COVID-19 pandemic, a remote pharmacy service "Cloud Pharmacy Care" based on the social software WeChat app was quickly constructed and applied to solve the medication-related problems of patients and the public during home quarantining. The significance of the study lies in the timely and interactive consultation model helps to carry out medication therapy management for chronically ill patients and improves patients' medication compliance, improves medical quality, and plays a positive role in promoting the popularization of safe medication knowledge.

11.
Biomed Res Int ; 2021: 1738932, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34337000

RESUMEN

BACKGROUND: Over the past decades, lots of advance have occurred in the prevention, diagnosis, and treatment of head and neck cancer (HNC). However, the contemporaneous incidence and survival trends, on the basis of population-based registry, have not been reported. METHODS: The HNC cancer cases were accessed from the Surveillance, Epidemiology, and End Results (SEER) database. The incidence trend was analyzed by joinpoint analysis, with the survival trend being analyzed by period analysis of relative survival rate (RSR) and Kaplan-Meier analyses. Cox regression analysis was performed to identify the prognostic factors for overall survival. RESULTS: The general incidence trend of HNC increases slightly, with an average annual percentage change of 0.6%, along with five fluctuating segments. The improvement of net survival over the past decades was showed by increasing 60-month RSR, from 54.1% to 56.0% to 60.9% to 66.8%, which was further confirmed by Kaplan-Meier analyses. Moreover, disparities in incidence and survival patterns can be observed in different subgroups. CONCLUSION: A fluctuating incidence pattern and an ever-improving survival were observed in HNC over time.


Asunto(s)
Neoplasias de Cabeza y Cuello/epidemiología , Adolescente , Adulto , Distribución por Edad , Factores de Edad , Niño , Preescolar , Femenino , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Incidencia , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Grupos Raciales , Sistema de Registros , Programa de VERF , Tasa de Supervivencia , Estados Unidos/epidemiología , Adulto Joven
12.
Sci Rep ; 8(1): 6141, 2018 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-29643394

RESUMEN

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

13.
Mol Cell Probes ; 37: 39-47, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29179987

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is a common cancer with high morbidity and mortality. However, its molecular mechanism is not clear, nor the genes related to CRC stages. METHODS: Gene expression data in CRC and healthy colorectal tissues were obtained from gene expression omnibus. Limma package was used to identify the differentially expressed genes (DEGs) between control and CRC (stage I, II, III, and IV), obtaining 4 DEG sets. VennPlex was utilized to find all DEGs and intersection DEGs. Functional interactions between all DEGs and protein-protein interactions (PPIs) between intersection DEGs were analyzed using ReactomeFIViz and STRING, respectively, and networks were visualized. Known CRC-related genes were down-loaded from Comparative Toxicogenomics Database and mapped to PPI network. RESULTS: Totally, 851, 760, 729, and 878 DEGs were found between control and CRC stage I, II, III, and IV, respectively. Taken together, 1235 DEGs were found, as well as 128 up-regulated intersection DEGs, 365 down-regulated intersection DEGs, and 0 contra-regulated DEG. A functional interaction network of all DEGs and a PPI network of intersection DEGs were constructed, in which CDC20, PTTG1, and MAD2L1 interacted with BUB1B; UGT2B17 interacted with ADH1B; MCM7 interacted with MCM2. BUB1B, ADH1B, and MCM2 were known CRC-related genes. Gradually upregulated expressions of CDC20, PTTG1, MAD2L1, UGT2B17, and MCM7 in stage I, II, III, and IV CRC were confirmed by using quantitative PCR. Besides, up-regulated intersection DEGs enriched in pathways about Cell cycle, DNA replication, and p53 signaling. CONCLUSION: CDC20, PTTG1, MAD2L1, UGT2B17, and MCM7 might be CRC stage-related genes.


Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Perfilación de la Expresión Génica , Proteínas Adaptadoras Transductoras de Señales/análisis , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Cdc20/análisis , Proteínas Cdc20/genética , Proteínas Cdc20/metabolismo , Proteínas de Ciclo Celular/análisis , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Bases de Datos Genéticas , Regulación Neoplásica de la Expresión Génica , Glucuronosiltransferasa/análisis , Glucuronosiltransferasa/genética , Glucuronosiltransferasa/metabolismo , Humanos , Componente 7 del Complejo de Mantenimiento de Minicromosoma/análisis , Componente 7 del Complejo de Mantenimiento de Minicromosoma/genética , Componente 7 del Complejo de Mantenimiento de Minicromosoma/metabolismo , Antígenos de Histocompatibilidad Menor/análisis , Antígenos de Histocompatibilidad Menor/genética , Antígenos de Histocompatibilidad Menor/metabolismo , Estadificación de Neoplasias , Proteínas Nucleares/análisis , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Mapas de Interacción de Proteínas , Securina/análisis , Securina/genética , Securina/metabolismo
14.
Exp Ther Med ; 14(2): 1212-1218, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28810580

RESUMEN

Colorectal cancer has a relatively low sensitivity to paclitaxel. The purpose of this study was to investigate the role of connexin 43 (Cx43), which is a structural component of gap junctional communication (GJC), in paclitaxel cytotoxicity in colorectal cancer cells. Three colorectal cancer cell lines (HCT106, HCT116 and LoVo) were transfected with Cx43 and used to examine paclitaxel cytotoxicity. A western blot assay was used to confirm Cx43 expression in transfected cell lines as well as the expression of several proteins that are associated with paclitaxel cytotoxicity. A parachute dye-coupling assay was used to measure GJC function. An MTT assay was used to analyze the viability of paclitaxel-treated cells. Cx43 expression level and GJC function were significantly upregulated by the transfection (P<0.05). The viability of transfected cells was significantly inhibited compared with that of untransfected cells when treated with paclitaxel (20 or 80 nM) at high culture density but not at low culture density (P<0.05). Cx43 transfection significantly increased the mitotic arrest, tubulin polymerization and apoptosis effects of paclitaxel (P<0.05). It was also found that paclitaxel had an inhibitory effect on GJC function after 12 h of treatment in LoVo cells (P<0.05). These results indicate that Cx43 may serve as a target of paclitaxel chemotherapy for colorectal cancer.

15.
Molecules ; 22(6)2017 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-28621744

RESUMEN

Mangiferin (MGF), the predominant constituent of extracts of the mango plant Mangifera Indica L., has been investigated extensively because of its remarkable pharmacological effects. In vitro recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was used to investigate the inhibition of mangiferin and aglycone norathyriol towards various isoforms of UGTs in our study, which evaluated the inhibitory capacity of MGF and its aglycone norathyriol (NTR) towards UDP-glucuronosyltransferase (UGT) isoforms. Initial screening experiment showed that deglycosylation of MGF into NTR strongly increased the inhibitory effects towards almost all the tested UGT isoforms at a concentration of 100 µM. Kinetic experiments were performed to further characterize the inhibition of UGT1A3, UGT1A7 and UGT1A9 by NTR. NTR competitively inhibited UGT1A3, UGT1A7 and UGT1A9, with an IC50 value of 8.2, 4.4, and 12.3 µM, and a Ki value of 1.6, 2.0, and 2.8 µM, respectively. In silico docking showed that only NTR could dock into the activity cavity of UGT1A3, UGT1A7 and UGT1A9. The binding free energy of NTR to UGT1A3, 1A7, 1A9 were -7.4, -7.9 and -4.0 kcal/mol, respectively. Based on the inhibition evaluation standard ([I]/Ki < 0.1, low possibility; 0.1 < [I]/Ki < 1, medium possibility; [I]/Ki > 1, high possibility), an in vivo herb-drug interaction between MGF/NTR and drugs mainly undergoing UGT1A3-, UGT1A7- or UGT1A9-catalyzed metabolism might occur when the plasma concentration of NTR is above 1.6, 2.0 and 2.8 µM, respectively.


Asunto(s)
Glucuronosiltransferasa/metabolismo , Isoenzimas/metabolismo , Xantonas/química , Glucuronosiltransferasa/antagonistas & inhibidores , Interacciones de Hierba-Droga , Isoenzimas/antagonistas & inhibidores , Xantenos/química
16.
J Stroke Cerebrovasc Dis ; 26(7): 1622-1634, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28438516

RESUMEN

OBJECTIVE: This study aims to investigate the molecular mechanism of injury development in the cortex and the striatum after cerebral ischemia/reperfusion (I/R). METHODS: Gene expression data (GSE23160) in the cortex and the striatum of an intraluminal middle cerebral artery occlusion-I/R mouse model (N = 12) and sham controls (N = 4) were downloaded from the Gene Expression Omnibus. Limma package was used to identify the differentially expressed genes (DEGs) between the I/R (2, 8, and 24 hours) and control groups. Correlation analysis was then performed to identify the highly correlated differentially expressed genes (HCDEGs). STRING and Cytoscape software were used to construct a protein-protein interaction (PPI) network of HCDEGs. Furthermore, Venny 2.0 was used to identify common overlapped DEGs whose transcription factors (TFs) were predicted using iRegulon in Cytoscape. RESULTS: For the cortex and the striatum, 2295 and 2282 DEGs were respectively identified between the I/R group and the controls, and were classified into 3 and 2 correlation modules. For each module, a PPI network was constructed, and Toll-like receptor 2 (Tlr2, degree = 25), interleukin 1ß (Il1b, degree = 21), and heme oxygenase-1 (Hmox1, degree = 17) had high connective degrees. Furthermore, 29 common overlapped DEGs were found across time and tissue, which might be targeted by 13 TFs. Especially, Tlr2, Il1b, and Hmox1 were targeted by myeloblastosis protein (Myb, target count = 16) and FBJ osteosarcoma protein (Fos, target count = 15). Moreover, plasminogen activator urokinase receptor (Plaur) was targeted by Fos, and it was an HCDEG in correlation modules of both cortex and striatum. Upregulation of Tlr2, Il1b, Hmox1, and Plaur in I/R injury was confirmed using quantitative polymerase chain reaction and immunohistochemical staining. CONCLUSION: Tlr2, Il1b, Hmox1, and Plaur regulated by Myb and Fos might participate in cortex and striatum injury after cerebral I/R.


Asunto(s)
Ganglios Basales/metabolismo , Corteza Cerebral/metabolismo , Perfilación de la Expresión Génica/métodos , Infarto de la Arteria Cerebral Media/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Daño por Reperfusión/genética , Transcriptoma , Animales , Ganglios Basales/patología , Corteza Cerebral/patología , Biología Computacional , Bases de Datos Genéticas , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Mapas de Interacción de Proteínas , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-fos/metabolismo , Proteínas Proto-Oncogénicas c-myb/genética , Proteínas Proto-Oncogénicas c-myb/metabolismo , Receptores del Activador de Plasminógeno Tipo Uroquinasa/genética , Receptores del Activador de Plasminógeno Tipo Uroquinasa/metabolismo , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Transducción de Señal , Factores de Tiempo , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/metabolismo
17.
Sci Rep ; 7(1): 1280, 2017 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-28455529

RESUMEN

Taxol, a first-line anti-tumour drug, has low effectiveness against colorectal cancer. Combination with other agents is an effective strategy to enhance Taxol cytotoxicity. Kanglaite injection is an extract from Coix lacryma-jobi seed and is usually combined with other agents to treat cancer. The aim of this study was to investigate the treatment effect of Taxol combined with Kanglaite on colorectal cancer cell lines. Kanglaite pretreatment followed by Taxol treatment was found to show the best synergism among all combination strategies. This combination also resulted in the smallest tumour volume in a Balb/c mice model. Kanglaite inhibited the expression of nuclear factor (NF)-κΒ and upregulated that of connexin 43, both of which sensitized cancer cells to Taxol. Moreover, Kanglaite increased many cellular variations caused by Taxol, including tubulin polymerization, caspase-3 cleavage, and upregulated expression of survivin and cyclin B1. These results suggest that Kanglaite pretreatment may increase the effect of Taxol on colorectal cancer.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Conexina 43/biosíntesis , Sinergismo Farmacológico , Medicamentos Herbarios Chinos/farmacología , FN-kappa B/antagonistas & inhibidores , Paclitaxel/farmacología , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/administración & dosificación , Ratones Endogámicos BALB C , Paclitaxel/administración & dosificación , Resultado del Tratamiento , Regulación hacia Arriba
18.
Pathol Res Pract ; 213(5): 548-557, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28318762

RESUMEN

AIMS: Dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) can cause heart failure, and this study aims to identify genes and transcription factors (TFs) associated with DCM and ICM. METHODS: Gene expression dataset GSE42955 was generated from GEO database, and it contained 12 DCM, 12 ICM, and 5 control samples. Differentially expressed genes (DEGs) were identified between DCM (or ICM) and controls. Gene functions were investigated, and their associations were analyzed using Enrichmentmap plugin in Cytoscape. Protein-protein interactions (PPIs) between DEGs were determined, and DEGs with high degree were defined as key DEGs. Potential TFs of key DEGs were predicted using iRegulon plugin. Common DEGs were found, and their functional interactions were investigated using GeneMANIA. RESULTS: A total of 362 and 300 DEGs were respectively identified for DCM and ICM in comparison with controls, and these DEGs mainly participated in similar functions about extracellular region, membrane, immune process, and defense response. PPI networks were respectively constructed for DCM and ICM, and 26 key DEGs (e.g. CXCL10, IL6, TLR3, and VCAM1) were found, which might be targeted by 35 TFs (e.g. IRF1). Besides, 47 common up-regulated DEGs were found, which participated in 14 pathways like Apoptosis, Collagen formation, as well as 127 common down-regulated DEGs that involved in 20 pathways like Adaptive immune system, Interferon γ signaling (e.g. IRF1, VCAM1), and Toll-like receptor signaling pathway (e.g. CXCL10, IL6, TLR3). CONCLUSION: DCM and ICM may share similar mechanism, and TFs (e.g. IRF1) play crucial roles in their development via regulating gene expression.


Asunto(s)
Cardiomiopatía Dilatada/genética , Isquemia Miocárdica/genética , Factores de Transcripción/genética , Biología Computacional , Bases de Datos Genéticas , Regulación hacia Abajo , Perfilación de la Expresión Génica , Humanos , Transducción de Señal , Regulación hacia Arriba
19.
Xenobiotica ; 47(5): 376-381, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27359323

RESUMEN

1. The exposed level of vitamin A in plasma might be exceeded due to the both inadvertent and clinical utilization. The adverse effects of vitamin A have been frequently reported, however, the mechanism remains unclear. The inhibition of vitamin A on the activity of UDP-glucuronosyltransferases (UGTs) was determined using in vitro incubation system to explain the adverse effects of vitamin A from a new perspective. 2. UGT supersomes catalyzed glucuronidation of 4-methylumbelliferone (4-MU), trifluoperazine (TFP), and cotinine was used as the probe reaction to evaluate the inhibition of vitamin A toward UGT isoforms, and 100 µM of vitamin A significantly inhibited the activity of all the tested UGT isoforms. Vitamin A exerted competitive inhibition on the activity of UGT1A1, 2B4, 2B7, and 2B15, and the inhibition kinetic parameters (Ki) were calculated to be 31.1, 16.8, 2.2, and 11.6 µM for UGT1A1, 2B4, 2B7, and 2B15. In silico docking method was used to try to elucidate the inhibition mechanism of vitamin A toward UGT2B7. The results showed the significant contribution of hydrogen bonds and hydrophobic interaction on the UGT2B7 inhibition by vitamin A. 3. The present study provides a new perspective for the adverse effects of vitamin A through reporting the inhibition of vitamin A on the activity of important phase II drug-metabolizing enzymes UGTs, which benefits our deep understanding of mechanism of vitamin A's adverse effects when high exposure of vitamin A occurs.


Asunto(s)
Inhibidores Enzimáticos/farmacología , Glucuronosiltransferasa/metabolismo , Vitamina A/farmacología , Inhibidores Enzimáticos/metabolismo , Himecromona , Cinética , Vitamina A/metabolismo
20.
Molecules ; 21(12)2016 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-27916843

RESUMEN

As one of the main active ingredients from Radix Astragali (RA), orally dosed astragaloside IV (AST) is easily transformed to sapogenin-cycloastragenol (CAG) by deglycosylation in the gastrointestinal tract. Because the potential adverse effects of AST and CAG remain unclear, the present study in this article was carried out to investigate the inhibition effects of AST and CAG on UDP-glucuronosyltransferases (UGTs) to explore potential clinical toxicity. An in vitro UGTs incubation mixture was employed to study the inhibition of AST and CAG towards UGT isoforms. Concentrations of 100 µM for each compound were used to initially screen the inhibitory efficiency. Deglycosylation of AST to CAG could strongly increase the inhibitory effects towards almost all of the tested UGT isoforms, with an IC50 of 0.84 µM and 11.28 µM for UGT1A8 and UGT2B7, respectively. Ulteriorly, the inhibition type and kinetics of CAG towards UGT1A8 and UGT2B7 were evaluated depending on the initial screening results. Data fitting using Dixon and Lineweaver-Burk plots demonstrated that CAG competitively inhibited UGT1A8 and noncompetitively inhibited UGT2B7. From the second plot drawn with the slopes from the Lineweaver-Burk plot versus the concentrations of CAG, the inhibition constant (Ki) was calculated to be 0.034 µM and 20.98 µM for the inhibition of UGT1A8 and UGT2B7, respectively. Based on the [I]/Ki standard ([I]/Ki < 0.1, low possibility; 1 > [I]/Ki > 0.1, medium possibility; [I]/Ki > 1, high possibility), it was successfully predicted here that an in vivo herb-drug interaction between AST/CAG and drugs mainly undergoing UGT1A8- or UGT2B7-catalyzed metabolism might occur when the plasma concentration of CAG is above 0.034 µM and 20.98 µM, respectively.


Asunto(s)
Glucuronosiltransferasa/antagonistas & inhibidores , Sapogeninas/farmacología , Sapogeninas/farmacocinética , Saponinas/farmacología , Saponinas/farmacocinética , Triterpenos/farmacología , Triterpenos/farmacocinética , Medicamentos Herbarios Chinos , Interacciones de Hierba-Droga , Isoformas de Proteínas/antagonistas & inhibidores
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