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Objective:To observe the effects of transcranial direct current stimulation (tDCS) on functional connectivity (FC) in language-related brain regions of patients with picture-naming dysfunction after cerebral infarction by using resting state functional magnetic resonance imaging(rs-fMRI).Methods:Twenty-eight patients with post-infarction picture-naming dysfunction were divided into an acute stage group( n=16) and a recovery stage group( n=12) according to the course of the disease, and 18 middle-aged and elderly volunteers were recruited as the normal control group.The anodic tDCS was applied on the posterior perisylvian region(PPR) of the left sylvian of the patients, 5 days a week for 2 weeks.Before and after the 2 weeks′ treatment, the rs-fMRI and Psycholinguistic Assessment of Chinese Aphasia (PACA)-picture-naming subscale were performed, and FC changes in language-related brain areas were observed. Results:After treatment, the PACA scores of patients in both acute and recovery stage groups were significantly improved after treatment( P<0.05). Compared with normal subjects, FC in multiple brain regions and particularly the Wernicke area was reduced in both cerebral hemispheres among the patient group. It was more severe in the dominant hemisphere.After the tDCS treatment, FC in both frontotemporal lobes and in the Wernicke area was significantly enhanced in both the acute and recovery groups. Further comparison showed that in the acute group FC in both temporo-occipital lobes was significantly enhanced after treatment. In the recovery group, the enhanced FC in the left temporal lobe before the treatment was significantly reduced after treatment. Conclusion:The fMRI technique can evaluate changes in brain connectivity in aphasia patients with picture-naming dysfunction after cerebral infarction accurately and non-invasively.tDCS may improve picture-naming function of stroke patients by enhancing the FC in bilateral language-related brain areas(concentrated in frontotemporal lobes) and Wernicke area.
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Obiective Alzheimer’s disease (AD) is a degenerative disease of the central nervous system (CNS) caused by a variety of risk factors. There are various pathological changes, but apoptosis of the neurological meridian cells is one of the most important pathological bases. Hyperlipidemia is a high-risk factor for the development of AD, which can lead to increased levels of oxidized low-density lipoprotein (ox-LDL) in brain tissues. PCSK9 is a protease closely related to lipid metabolism, but studies have shown that it may be related to the development of AD. LRP1 is abundantly expressed in neuronal cells, and it is an important transporter for the clearance of Aβ. There is now a large amount of literature confirming that PCSK9 can induce the degradation of LRP1. PI3K/AKT is an important signaling pathway in vivo, which plays an important role in apoptosis, and there is now a large amount of literature confirming that LRP1 activates the PI3K/AKT pathway, which has an anti-apoptotic effect. So can PCSK9 affect the PI3K/AKT pathway through LRP1 and thus regulate neuronal apoptosis? This deserves further investigation.The aim of this study was to explore the role of PCSK9 in mediating ox-LDL pro-apoptotic neuronal cell death and its mechanism, and then further elaborate the mechanism of hyperlipidemia leading to neurodegenerative diseases such as AD. MethodsFirstly, PC12 cells were treated with different concentrations of ox-LDL (0, 25, 50, 75 and 100 mg/L) for 24 h. Oil red O staining was used to detect lipid accumulation in PC12 cells, Hoechst33258 staining and flow cytometry to detect apoptosis in PC12 cells, ELISA to detect the content of Aβ secreted by PC12, Western blot to detect expression of SREBP2, PCSK9 and LRP1. Then PC12 cells were treated with 75 mg/L ox-LDL for different times (0, 6, 12, 24, 48 h), and Western blot were performed to detect the expression of SREBP2, PCSK9 and LRP1. Finally, after transfecting 100 nmol/L PCSK9 siRNA into PC12 cells for 48 h, PC12 cells were treated with 75 mg/L ox-LDL for 24 h, Hoechst33258 staining and flow cytometry to detect apoptosis rate of PC12 cells, and Western blot to detect PCSK9, LRP1, PI3K, AKT, P-PI3K , P-AKT, NF-κB, Bcl-2, Bax, Caspase-9 and Caspase-3 expression, and ELISA detected Aβ content secreted by PC12 cells. Resultsox-LDL increased lipid accumulation and promoted apoptosis and Aβ secretion in PC12 cells, as well as increasing the expression of SREBP2 and PCSK9 and decreasing the expression of LRP1 in PC12 cells. pCsk9 siRNA could be inhibited through the PI3K/AKT pathway and the NF-κB-Bcl-2/Bax-Caspase-9/3 pathway to inhibit ox-LDL-induced apoptosis in PC12 cells while increasing Aβ secretion in PC12 cells. Conclusionox-LDL plays a bidirectional regulatory role in ox-LDL-induced apoptosis of PC12 cells by inducing an increase in PCSK9 expression and a decrease in LRP1 expression in PC12 cells, which in turn affects different signaling pathways downstream.
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OBJECTIVE@#To assess the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on clinical outcomes of patients receiving anti-PD-1 immunotherapy for hepatocellular carcinoma.@*METHODS@#We conducted a retrospective study among 215 patients with primary liver cancer receiving immunotherapy between June, 2018 and October, 2020. The patients with balanced baseline characteristics were selected based on propensity matching scores, and among them 33 patients who used NSAIDs were matched at the ratio of 1∶3 with 78 patients who did not use NSAIDs. We compared the overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) between the two groups.@*RESULTS@#There was no significant difference in OS between the patients using NSAIDs (29.7%) and those who did not use NSAIDs (70.2%). Univariate and multivariate analyses did not show an a correlation of NSAIDs use with DCR (univariate analysis: OR=0.602, 95% CI: 0.299-1.213, P=0.156; multivariate analysis: OR=0.693, 95% CI: 0.330-1.458, P=0.334), PFS (univariate analysis: HR=1.230, 95% CI: 0.789-1.916, P=0.361; multivariate analysis: HR=1.151, 95% CI: 0.732-1.810, P=9.544), or OS (univariate analysis: HR=0.552, 95% CI: 0.208-1.463, P=0.232; multivariate analysis: HR=1.085, 95% CI: 0.685-1.717, P=0.729).@*CONCLUSION@#Our results show no favorable effect of NSAIDs on the efficacy of immunotherapy in patients with advanced primary liver cancer, but this finding still needs to be verified by future prospective studies of large cohorts.
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Humanos , Antiinflamatorios no Esteroideos/uso terapéutico , Inmunoterapia/métodos , Neoplasias Hepáticas/tratamiento farmacológico , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Objective:To compare the prediction of Ischemic Stroke Predictive Risk Score (iScore), Preadmission Comorbidities, Level of Consciousness, Age, and Neurologic Deficit (PLAN), Acute Stroke Registry and Analysis of Lausanne (ASTRAL) and Totaled Health Risks in Vascular Events (THRIVE) for short- and long-term death for patients with acute ischemic stroke (AIS). Methods:From August, 2015 to June, 2018, 323 AIS patients in emergency ward were included, and followed up 30 days, three months and a year after including. Receiver operating characteristic (ROC) curve was used to analyze the predictive effects of iScore, PLAN, ASTRAL and THRIVE. Results:The all-cause mortality 30 days, three months and a year after including was 12.4% (40/323), 17.3% (56/323) and 25.7% (83/323), respectively. The area under curve (AUC) from more to less arranged as iScore, PLAN, ASTRAL and THRIVES. There was significant difference of AUC between iScore and THRIVE (Z > 1.990, P < 0.05), but not among the others (Z < 1.943, P > 0.05). Conclusion:iScore, PLAN, ASTRAL and THRIVE may predict short- and long-term death of AIS patients in the emergency well, and iScore is the best. However, the procedure of iScore is complex, it is recommended to use PLAN and ASTRAL for emergency.
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Objective:To explore the change of serum 25-hydroxyvitamin D [25(OH)D] and prediction for outcome of acute ischemic stroke in emergency. Methods:From October, 2017 to September, 2019, 224 patients with acute ischemic stroke in emergency and 240 healthy controls were detected serum 25(OH)D within 24 hours after enrollment. The patients were assessed with National Institute of Health Stroke Scale (NIHSS) and Nutritional Risk Screening 2002 (NRS2002), and measured biochemics within 24 hours after admission. They were assessed with modified Rankin Scale (mRS) 180 days after stroke, and divided into favourable group (mRS ≤ 2, n = 106) and unfavourable group (mRS > 2, n = 118). The factors related with the outcome were analyzed with Logistic regression, and the prediction of 25(OH)D for the outcome were analyzed with receiver operator characteristic (ROC) curve. Results:Serum 25(OH)D was less in the patients than in the controls (Z = 4.296, P < 0.001), and less in the unfavourable group than in the favourable group (Z = 5.876, P < 0.001). Serum 25(OH)D (OR = 0.925, P < 0.05) was related with the outcome even controlling the impacts of age, sex, nutritional risk, infarct volume, scores of NIHSS, etc. The area under curve for serum 25(OH)D predicting outcome was 0.795 (P < 0.001). The cut-off point of prediction was 13.17 ng/ml, with the Yoden index of 0.548, which yielded a sensitivity of 0.746 and a specificity of 0.802. Conclusion:Serum 25-hydroxyvitamin D may predict the outcome 180 days after acute ischemic stroke, which may help for risk stratification in emergency.
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Objective:To explore the characteristics of nosocomial infection in patients with spinal cord injury, and analyze the risk factors. Methods:From January, 2015 to June, 2017, 526 patients with spinal cord injury in our hospital were reviewed. The distribution of pathogens and the characteristics of drug resistance of strains were summarized, and the risk factors of nosocomial infection were analyzed. Results:There were 159 person-times with nosocomial infection, and most of the infections were found in urinary tract (60.4%) and lower in respiratory tract (28.9%). The main pathogenic germs were Escherichia coli (39.0%), Pseudomonas aeruginosa (15.7%), Klebsiella pneumoniae (11.3%) and Proteus mirabilis (9.4%). The main pathogens were resistant to second or third generation of cephalosporins and quinolones moderately or severely, but sensitive to compound preparations containing beta-lactamase inhibitors, carbapenems and aminoglycosides. The risk factors for the nosocomial infections in the spinal cord injury patients included the hospitalization time, severity of spinal cord injury, invasive operation history, nutritional risk and use of antibiotics (P < 0.05). Conclusion:Most of the nosocomial infections in patients with spinal cord injury are in urinary tract and respiratory tract. Gram-negative bacilli are the main pathogenic bacteria, which often show multiple drug resistance. It is necessary to take targeted interventions according to the risk factors of nosocomial infections in order to improve the quality of life of patients.
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Drug resistance is a key factor for poor clinical efficacy of chemotherapy. One of the important reasons for drug resistance is the abnormal expression of drug metabolizing enzymes and drug transporters, which results in the decrease of drug concentration in cancer cells. In this paper, the mechanism of abnormal uptake transporter expression in tumors is analyzed from aspects of drug metabolism enzymes and transporters and tumor drug resistance, drug epigenetics and drug resistance, and potential targets of renal cancer drug resistance, such as OCT2. It is proposed that the regulation of uptake drug transporter expression in tumors by epigenetic mechanism is a new way to reverse drug resistance in tumors.
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This paper summarizes research progresses of Chinese scholars in the field of drug metabolism and pharmacokinetics (DMPK) in 2018. Chinese scholars focused on drug metabolizing enzymes and transporters, and carried out studies on the mechanisms of drug metabolism and transport of active molecules. Topics of research included regulatory mechanisms of drug metabolizing enzymes or transporters, and their implications in drug development and disease etiology or progression. Here, we summarized studies on drug toxicity based on drug metabolism or transport, rational drug use in the clinic, drug metabolism mediated by intestinal flora, metabolism of traditional Chinese medicines, and new technologies or models in DMPK. In recent years, the research focus of drug metabolism in China has transformed from serving for new drug discovery and rational use, to innovation driven and mechanism oriented research. The domestic research topics and technology utilization are gradually aligning with the international conventions.
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Pharmacological activities and adverse side effects of ginkgolic acids (GAs), major components in extracts from the leaves and seed coats of Ginkgo biloba L, have been intensively studied. However, there are few reports on their hepatotoxicity. In the present study, the metabolism and hepatotoxicity of GA (17 : 1), one of the most abundant components of GAs, were investigated. Kinetic analysis indicated that human and rat liver microsomes shared similar metabolic characteristics of GA (17 : 1) in phase I and II metabolisms. The drug-metabolizing enzymes involved in GA (17 : 1) metabolism were human CYP1A2, CYP3A4, UGT1A6, UGT1A9, and UGT2B15, which were confirmed with an inhibition study of human liver microsomes and recombinant enzymes. The MTT assays indicated that the cytotoxicity of GA (17 : 1) in HepG2 cells occurred in a time- and dose-dependent manner. Further investigation showed that GA (17 : 1) had less cytotoxicity in primary rat hepatocytes than in HepG2 cells and that the toxicity was enhanced through CYP1A- and CYP3A-mediated metabolism.
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Animales , Humanos , Ratas , Células Cultivadas , Citocromo P-450 CYP1A2 , Metabolismo , Citocromo P-450 CYP3A , Metabolismo , Ginkgo biloba , Química , Glucuronosiltransferasa , Metabolismo , Hepatocitos , Química , Metabolismo , Cinética , Hígado , Química , Metabolismo , Microsomas Hepáticos , Química , Metabolismo , Extractos Vegetales , Química , Metabolismo , Toxicidad , Ratas Sprague-Dawley , Salicilatos , Química , Metabolismo , ToxicidadRESUMEN
<p><b>BACKGROUND</b>Acupuncture can not only be used for well-known diseases, but also for so-called modern lifestyle-related diseases. Using innovative methods like e.g. new analyses of heart rate variability (HRV), it is also possible to investigate diseases like burnout syndrome, ie., qi deficiency in Chinese medicine (CM).</p><p><b>OBJECTIVE</b>The main object of this research protocol is to perform research on the relationship of burnout syndrome and heart rate (HR) and HRV.</p><p><b>METHODS</b>A total of 175 patients with burnout syndrome (qi deficiency syndrome) in five groups and 35 healthy volunteers will be investigated. Based on random numbers generated by computer and concealed in opaque envelops, the patients will be assigned to four acupuncture groups using Zusanli (ST 36) acupuncture stimulation, Guanyuan (CV4) acupuncture stimulation, both points, and both points with Streitberger device respectively, and a moxibustion group using both points mentioned above, with 35 cases in each group. Altogether four different experiments are planned. Experiment 1 includes 70 subjects and is a comparison between a burnout group and a control group (healthy volunteers). The evaluation parameters are different scores and indices of HR and HRV. Experiment 2 includes 140 subjects and compares the efficacy of different acupuncture points. In experiment 3 (105 subjects), acupuncture and moxibustion should be compared to healthy volunteers. Experiment 4 (70 subjects) investigates the long-term therapeutic effects of acupuncture and moxibustion on the scores of qi deficiency and HR/HRV in qi deficiency patients. In both the acupuncture and moxibustion groups, a total of 10 treatments will be performed.</p><p><b>CONCLUSIONS</b>The joint research aims at the scientific evaluation of CM, mainly in the field of HRV. This parameter could be a very good indicator of the state of health and can be inflfluenced by different acupuncture methods, as shown in the past.</p>
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Adulto , Femenino , Humanos , Terapia por Acupuntura , Austria , Agotamiento Profesional , Terapéutica , China , Frecuencia Cardíaca , Fisiología , Estilo de Vida , Moxibustión , Proyectos de InvestigaciónRESUMEN
@#Objective To compare the performance of Prestroke Independence, Sex, Age, National Institutes of Health Stroke Scale (ISAN) score, Age, Atrial fibrillation, Dysphagia, Sex, Stroke Severity (A2DS2) score, acute ischemic stroke-as-sociated pneumonia score (AIS-APS), and Preventive ANtibacterial THERapy in Acute Ischemic Stroke (PAN-THERIS) score in predicting the risk of stroke-associated pneumonia (SAP). Methods The baseline characteristics and laboratory data of 338 patients with ischemic stroke in emergency ward from April, 2014 to December, 2017 were retrospectively analyzed. Patients were allocated into SAP group (n=125) and non-SAP group (n=213). Receiver operating characteristic curve (ROC) was used to evaluate the predictive effect of four different scoring systems for ischemic SAP. Results Totally, 125 (37.0%) patients developed SAP. There were significant differences in age, complications (atrial fi-brillation, coronary heart disease and history of stroke), Glasgow Coma Scale (GCS) score, National Institute of Health Stroke Scale (NIHSS) score, ISAN score, A2DS2 score, AIS-APS score and PANTHERIS score between two groups (P<0.05). The A value of PANTHERIS score was 0.818, which was the lowest among four scoring systems (P<0.05). No significant difference was found in the A value between A2DS2 score and ISAN score (P>0.05). Conclusion ISAN, A2DS2 and AIS-APS scoring systems all present good discrimination and calibration in predicting the risk of ischemic SAP. The AIS-APS score calculation is relatively complex, so it is suggested that ISAN and A2DS2 scoring systems be used in emergency.
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Pharmacological activities and adverse side effects of ginkgolic acids (GAs), major components in extracts from the leaves and seed coats of Ginkgo biloba L, have been intensively studied. However, there are few reports on their hepatotoxicity. In the present study, the metabolism and hepatotoxicity of GA (17 : 1), one of the most abundant components of GAs, were investigated. Kinetic analysis indicated that human and rat liver microsomes shared similar metabolic characteristics of GA (17 : 1) in phase I and II metabolisms. The drug-metabolizing enzymes involved in GA (17 : 1) metabolism were human CYP1A2, CYP3A4, UGT1A6, UGT1A9, and UGT2B15, which were confirmed with an inhibition study of human liver microsomes and recombinant enzymes. The MTT assays indicated that the cytotoxicity of GA (17 : 1) in HepG2 cells occurred in a time- and dose-dependent manner. Further investigation showed that GA (17 : 1) had less cytotoxicity in primary rat hepatocytes than in HepG2 cells and that the toxicity was enhanced through CYP1A- and CYP3A-mediated metabolism.
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Animales , Humanos , Ratas , Células Cultivadas , Citocromo P-450 CYP1A2 , Metabolismo , Citocromo P-450 CYP3A , Metabolismo , Ginkgo biloba , Química , Glucuronosiltransferasa , Metabolismo , Hepatocitos , Química , Metabolismo , Cinética , Hígado , Química , Metabolismo , Microsomas Hepáticos , Química , Metabolismo , Extractos Vegetales , Química , Metabolismo , Toxicidad , Ratas Sprague-Dawley , Salicilatos , Química , Metabolismo , ToxicidadRESUMEN
<p><b>OBJECTIVE</b>To compare the effect between nebulized and intravenous administration of Shenmai Injection () on pulmonary gas exchange function of patients following tourniquet-induced lower limb ischemia-reperfusion.</p><p><b>METHODS</b>Thirty-eight patients scheduled for lower extremity surgery were randomized into three groups using the closed envelop method: Shenmai Injection was administered 30 min before tourniquet inflflation by nebulization [0.6 mL/kg in 10 mL normal saline (NS)] in the nebulization group or by intravenous drip (0.6 mL/kg dissolved in 250 mL of 10% glucose) in the intravenous drip group, and equal volume of NS was given intravenously in the NS group; 15 in each group. Arterial blood gases were analyzed, serum levels of malonaldehyde (MDA) and interleukine-6 (IL-6) and interleukine-8 (IL-8) were determined using the method of thiobarbituric acid reaction and enzyme-linked immuno sorbent assay respectively just before tourniquet inflflation (T0), and at 0.5 h (T1), 2 h (T2), 6 h (T3) after tourniquet deflflation.</p><p><b>RESULTS</b>Compared with baselines at T0, MDA levels signifificantly increased at T2, T3 in the NS group and at T3 in the nebulization group, and IL-6 and IL-8 levels were signifificantly increased at T2, T3 in NS, the intravenous drip and the nebulization groups (P <0.05). Arterial pressure of oxygen (PaO) at T3 was decreased, while alveolararterial oxygen tension showed difference (PA-aDO) at T3 in the NS group; RI at T3 in both intravenous drip and the nebulization groups were enhanced (P <0.05). Compared with the NS group, MDA and IL-8 levels at T2, T3, IL-6 at T3 in the intravenous drip group, and IL-8 at T3 in the nebulization group were all remarkably increased (P <0.05). Additionally, MDA level at T3 in the nebulization group was higher than that in the intravenous drip group (P <0.05).</p><p><b>CONCLUSIONS</b>Intravenous administration of Shenmai Injection provided a better protective effect than nebulization in mitigating pulmonary gas exchange dysfunction in patients following tourniquet-induced limb ischemia-reperfusion.</p>
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Adulto , Femenino , Humanos , Masculino , Análisis de los Gases de la Sangre , Vías de Administración de Medicamentos , Combinación de Medicamentos , Medicamentos Herbarios Chinos , Farmacología , Usos Terapéuticos , Inyecciones , Interleucina-6 , Sangre , Interleucina-8 , Sangre , Malondialdehído , Sangre , Intercambio Gaseoso Pulmonar , Daño por Reperfusión , Sangre , Quimioterapia , TorniquetesRESUMEN
Ginkgolic acids (GAs), primarily found in the leaves, nuts, and testa of ginkgo biloba, have been identified with suspected allergenic, genotoxic and cytotoxic properties. However, little information is available about GAs toxicity in kidneys and the underlying mechanism has not been thoroughly elucidated so far. Instead of GAs extract, the renal cytotoxicity of GA (15 : 1), which was isolated from the testa of Ginkgo biloba, was assessed in vitro by using MDCK cells. The action of GA (15 : 1) on cell viability was evaluated by the MTT and neutral red uptake assays. Compared with the control, the cytotoxicity of GA (15 : 1) on MDCK cells displayed a time- and dose-dependent manner, suggesting the cells mitochondria and lysosomes were damaged. It was confirmed that GA (15 : 1) resulted in the loss of cells mitochondrial trans-membrane potential (ΔΨm). In propidium iodide (PI) staining analysis, GA (15 : 1) induced cell cycle arrest at the G0/G1 and G2/M phases, influencing on the DNA synthesis and cell mitosis. Characteristics of necrotic cell death were observed in MDCK cells at the experimental conditions, as a result of DNA agarose gel electrophoresis and morphological observation of MDCK cells. In conclusion, these findings might provide useful information for a better understanding of the GA (15 : 1) induced renal toxicity.
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Animales , Perros , Apoptosis , Puntos de Control del Ciclo Celular , Supervivencia Celular , Ginkgo biloba , Química , Toxicidad , Lisosomas , Metabolismo , Células de Riñón Canino Madin Darby , Mitocondrias , Metabolismo , Necrosis , Quimioterapia , Metabolismo , Extractos Vegetales , Toxicidad , Salicilatos , Química , ToxicidadRESUMEN
Pharmacogenomics is defined as research into the relationship between inherited genetic variations in drug metabolizing enzymes, transporters and targets and individual variations in person's response to drugs (fate of drug in human body, safety and efficacy). Personalized dosing is pharmacogenomics-based therapeutic regimen tailored to other individual characteristics. This article summarizes the progress in clinical application of personalized dosing from the perspective of pharmacogenomics of drug metabolizing enzymes and transporters, and proposes to draw attention to key scientific issues (e.g., the effect of multi-genes and non-genetic factors on drug effects, the integration of therapeutic drug monitoring and pharmacogenomics); meanwhile, bottle necks in the clinical application and corresponding strategies are proposed.
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In our preliminary studies, we observed zolmitriptan (ZOL) treatment led to induction of CYP3A2 in male not female rats. To figure out the reason is of great significance for drug-drug interactions and personalized administration. Since growth hormone (GH) is known as the major mechanistic determinant of sexually-dimorphic gene expression like CYP3A2 in rat liver, the impacts of ZOL on both plasma GH levels in non monosodium glutamate (MSG)-treated rats and CYP3A2 expression in GH depleted MSG-treated rats were studied. ZOL was shown to partially suppress GH levels in both genders. Furthermore, CYP3A2 protein and mRNA level declined in male not female MSG-treated rats. In order to study the possible molecular events involved in the depression of GH and gender-selective induction on rat CYP3A2 by ZOL, the mRNA and protein level (whole protein and nuclear protein) of hepatocyte nuclear factor 4α (HNF4α) was investigated. Nuclear accumulation of HNF4α was observed in the normal male not female rat liver tissue following ZOL treatment. However, this kind of nuclear translocation did not occur in rat hepatocytes and MSG-treated rats. These findings demonstrated CYP3A2 inducibility by ZOL was gender-selective. GH and HNF4α may play an important role in CYP3A2 induction.
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<p><b>OBJECTIVE</b>To investigate the expression of microRNA-107 (miR-107) and its functional role in hepatocellular carcinoma(HCC).</p><p><b>METHODS</b>The gene chip data of HCC obtained from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database were used to analyze the expression levels of miR-107 in liver cancer. Twenty-two pairs of fresh surgical specimens of HCC and adjacent tissues and 53 paraffin-embedded specimens of HCC were examined for miR-107 expression by qRT-PCR. The correlation of the expression levels of miR-107 with the clinicopathologic characteristics of the patients were analyzed. The role of miR-107 in regulating the proliferation of hepatocellular carcinoma cells were determined by MTT assay in Huh7 cells transfected with a miR-107 mimic or inhibitor.</p><p><b>RESULTS</b>The expression levels of miR-107 were significantly up-regulated in HCC tissues as compared to the adjacent tissues (P<0.05) in positive correlation with the tumor size (P<0.032). Transfection with miR-107 mimics significantly promoted the cell proliferation (P<0.0001) while miR-107 inhibitor inhibited the cell proliferation (P<0.0001).</p><p><b>CONCLUSION</b>The expression of miR-107 is up- regulated in HCC tissues and its expression levels are correlated with HCC cell proliferation, suggesting its role as a potential oncogene in liver cancer.</p>
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Humanos , Carcinoma Hepatocelular , Genética , Proliferación Celular , Neoplasias Hepáticas , Genética , MicroARNs , Genética , Activación Transcripcional , Regulación hacia ArribaRESUMEN
NTCP is specifically expressed on the basolateral membrane of hepatocytes, participating in the enterohepatic circulation of bile salts, especially conjugated bile salts, to maintain bile salts homeostasis. In addition, recent studies have found that NTCP is a functional receptor of HBV and HDV. Therefore, it is important to study the interaction between drugs and NTCP and identify the inhibitors/substrates of NTCP. In the present study, a LLC-PK1 cell model stably expressing human NTCP was established, which was simple and suitable for high throughput screening, and utilized to screen and verify the potential inhibitors of NTCP from 102 herbal medicinal ingredients. The results showed that ginkgolic acid (GA) (13 : 0), GA (15 : 1), GA (17 : 1), erythrosine B, silibinin, and emodin have inhibitory effects on NTCP uptake of TCNa in a concentration-dependent manner. Among them, GA (13 : 0) and GA (15 : 1) exhibited the stronger inhibitory effects, with IC50 values being less than 8.3 and 13.5 μmol·L(-1), respectively, than the classical inhibitor, cyclosporin A (CsA) (IC50 = 20.33 μmol·L(-1)). Further research demonstrated that GA (13 : 0), GA (15 : 1), GA (17 : 1), silibinin, and emodin were not substrates of NTCP. These findings might contribute to a better understanding of the disposition of the herbal ingredients in vivo, especially in biliary excretion.
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Animales , Humanos , Evaluación Preclínica de Medicamentos , Cinética , Células LLC-PK1 , Modelos Biológicos , Transportadores de Anión Orgánico Sodio-Dependiente , Química , Metabolismo , Extractos Vegetales , Química , Farmacología , Plantas Medicinales , Química , Relación Estructura-Actividad , Porcinos , Simportadores , Química , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To compare the bidirectional effect of rhubarb total anthraquinone (TA) and total tannins (TT) on rats' liver.</p><p><b>METHODS</b>One hundred rats were randomly divided into 10 groups, i.e., the blank group, the model group, the blank + high dose TA group, the blank +low dose TA group, the blank + high dose TT group, the blank + low dose TT group, the model + high dose TA group, the model + low dose TA group, the model +high dose TT group, and the model + low dose TT group, 10 in each group. The carbon tetrachloride (CCI4) was used to prepare the acute liver injury rat model. TA and TT of rhubarb (at 5.40 g crude drugs/kg and 14.69 g crude drugs/kg) were intragastrically administrated to rats in all groups except the blank group and the model group, once daily for 6 successive days.The general state of rats, biochemical indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), laminin (LN), hyaluronic acid (HA), transforming growth factor beta1 (TGF-beta1), as well pathological results of rat liver tissues. Finally the protection laws of TA and TT for rats' liver were analyzed using factor analysis.</p><p><b>RESULTS</b>Compared with the blank control group, all biochemical indices increased in the blank group (P < 0.05, P < 0.01). HA also increased in the blank + high dose TA group; AST, ALT, and HA also increased in the blank +high dose TT group (P < 0.05). Compared with the model group, AST, ALT, ALP, HA, and TGF-beta1 significantly decreased in the model + low dose TA group, the model + high dose TA group, the model + low dose TT group (P < 0.05, P < 0.01). Serum AST, ALT, and ALP also decreased in the model + high dose TT group (P < 0.05, P < 0.01). Pathological results showed that mild swollen liver cells in the model + high dose TA group. Fatty degeneration and fragmental necrosis around the central veins occurred in the blank + high dose TA group. The pathological injury was inproved in the model +low dose TA group. Two common factors, liver fibrosis and liver cell injury, were extracted by using factor analysis. TA showed stronger improvement of the two common factors than TT.</p><p><b>CONCLUSIONS</b>Rhubarb TA and TT showed protective and harmful effects on rats' liver. At an equivalent dosage, TA had better liver protection than TT. High dose TT played a role in liver injury to some extent.</p>