RESUMEN
OBJECTIVE: To detect the expression of miR-124 in colorectal carcinoma (CRC) cells and tissue specimens and analyze its association with the radiosensitivity of the cells. METHODS: The expression of miR-124 in CRC cell lines and tissues were detected using qRT-PCR. The effect of miR-124 in modulating cell radiosensitivity was assessed in CRC cells with miRNA-124 overexpression and miRNA-124 knockdown, and bioinformatics prediction and dual luciferase reporter system were employed to identify the direct target of miR-124. RESULTS: s miR-124 expression was down-regulated in CRC cell lines and tissues. CRC cells over-expressing miR-124 showed an obviously enhanced radiosensitivity, whereas miR-124 knockdown resulted in a reduced radiosensitivity of the cells. Bioinformatics prediction and dual luciferase reporter system verified PRRX1 as a direct target of miR-124, which regulated the radiosensitivity of CRC cells by directly inhibiting PRRX1. CONCLUSION: miR-124 can enhance the radiosensitivity of CRC cells by directly targeting PRRX1, which provides a target for improving the therapeutic effect of radiotherapy of CRC.
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Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/metabolismo , MicroARNs/metabolismo , Tolerancia a Radiación , Línea Celular Tumoral , Neoplasias Colorrectales/radioterapia , Regulación hacia Abajo , Proteínas de Homeodominio/genética , Humanos , Luciferasas , MicroARNs/genéticaRESUMEN
BACKGROUND AND AIMS: It is suggested that regulatory immune cells play a critical role in cancer cell growth by facilitating cancer cells to escape from the immune surveillance. The generation of the immune regulatory cells in cancer has not been fully understood yet. This study aims to investigate the role of the hepatoma-derived growth factor (HDGF) in the generation of regulatory T cells (Treg). METHODS: CCL-9.1 cells (A mouse hepatoma cell line), were cultured. The expression of HDGF in CCL-9.1 cells was assessed by quantitative RT-PCR and Western blotting. The generation of Foxp3(+) T cells was assessed by cell culture and flow cytometry. The immune suppressor function of the Foxp3(+) T cells on CD8(+) T cell activities was assessed by the carboxyfluorescein succinimidyl ester (CFSE)-dilution assay and enzyme-linked immunosorbent assay. RESULTS: The results showed that exposure to PolyIC markedly increased the expression of HDGF in CCL-9.1 cells. Coculture of CCL-9.1 cells and CD4(+) CD25(-) T cells in the presence of PolyIC generated the Forkhead box protein (Foxp)3(+) T cells. The exposure to HDGF increased the expression of Foxp3 and decreased the expression of GATA3 in CD4(+) T cells. After activation, the Foxp3(+) T cells suppressed the CD8(+) T cell proliferation and the release of the cytotoxic cytokines. CONCLUSIONS: Liver cancer cell-derived HDGF can induce Foxp3(+) T cells; the latter has the immune suppressor functions on CD8(+) T cell activities.
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Carcinoma Hepatocelular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/fisiología , Linfocitos T Citotóxicos/inmunología , Linfocitos T Reguladores/inmunología , Animales , Western Blotting , Línea Celular Tumoral , Técnicas de Cocultivo , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Factores de Transcripción Forkhead/metabolismo , Péptidos y Proteínas de Señalización Intercelular/aislamiento & purificación , Neoplasias Hepáticas/metabolismo , Activación de Linfocitos , Ratones , Ratones Endogámicos BALB C , Poli I-C/farmacología , Reacción en Cadena en Tiempo Real de la Polimerasa , Linfocitos T Reguladores/fisiologíaRESUMEN
BACKGROUND: Alzheimer disease (AD) is a chronic neurodegenerative disease that is characterized by its gradual progression. At present, the cause and mechanism of AD are yet unclear, and there is no effective therapy for treating it. With development of global aging, the prevalence rate of AD is increasing. The life quality of elderly people is affected severely by AD that is ultimately life-threatening. Recently, study on treating AD with traditional Chinese medicine (TCM) has deepened. OBJECTIVE: To explore the therapeutic effects of a syndrome differentiation-based TCM regime in treating patients with mild to moderate AD for improving cognition, and to evaluate the changes in brain function of AD patients observed by resting-state functional magnetic resonance imaging (fMRI) technique. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Adopting the internationally recognized criteria developed by National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association, the clinical trial was conducted on 131 patients with mild to moderate AD from 5 communities and 7 social welfare institutions. Participants were accepted after informed consent was received, and laboratory tests and a head imaging study were conducted. The patients were randomly divided into Chinese medicine group (CMG) (66 cases) or Western medicine group (WMG) (65 cases). Patients in the CMG were treated monthly with Chinese medicine according to syndrome differentiation. Patients in the WMG were treated with donepezil at a dose of 5 mg once daily. The therapeutic course lasted 48 weeks. MAIN OUTCOME MEASURES: The scores of Mini-Mental State Examination (MMSE), Fuld Object-Memory Evaluation (FOM), Block Design (BD) and Digit Span (DS) were used to evaluate the cognitive function; resting-state fMRI was used for observing brain function. The questionnaires and fMRI were performed before and after treatments. RESULTS: The cognitive functions of the patients in the CMG and WMG were improved after treatment. MMSE score was improved significantly in both groups (P<0.05 or P<0.001). After 48 weeks of treatment, 70.91% patients in the CMG had an improved MMSE score and 20% got worse, however, 55.77% patients in the WMG were improved in MMSE score and 34.62% got worse. Scores of FOM denominator and BD increased significantly in both groups; scores of FOM numerator and DS were also increased in the CMG (P<0.05 or P<0.01). The results of fMRI suggested that both Chinese medicine and donepezil treatment improved the connectivity between posterior cingulated gyrus and specific areas in the brain. The influence range of Chinese medicine primarily impacted on the left parietal lobe, being less than the influence range of donepezil, which primarily affected both sides of frontal lobes. CONCLUSION: TCM treatment based on syndrome differentiation is effective in improving cognitive function of patients with mild to moderate AD and increasing the brain function by increasing connectivity between posterior cingulated gyrus and specific areas in the brain.
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Enfermedad de Alzheimer/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Cognición/efectos de los fármacos , Donepezilo , Humanos , Indanos/uso terapéutico , Nootrópicos/uso terapéutico , Piperidinas/uso terapéuticoRESUMEN
OBJECTIVE: To observe the therapeutic effect of Shenyin Oral Liquid (SOL) in relieving mild cognitive impairment (MCI) and decreasing the Alzheimer's disease (AD) transformation rate. METHODS: One hundred and seventeen MCI patients were randomly assigned to the Chinese medicine group (42 cases), the vitamin E group (38 cases) and the placebo group (37 cases). The treatment course was 12 months and a 6-month follow-up was conducted after ending the treatment course. RESULTS: After treatment, the scores of clock drawing test (CDT), nonsensical figure recognition and mini-mental state examination (MMSE) raised significantly in the Chinese medicine group (P < 0.05 or P < 0.01), the activity of acetylcholine esterase in erythrocytic membrane was lower in the Chinese medicine group than that in the placebo group and the Vitamin E group (P < 0.05 or P < 0.01). Six months after the treatment, there were 2 and 5 cases in the placebo group and the vitamin E group which were diagnosed as AD, respectively, and none in the Chinese medicine group. CONCLUSION: SOL has an effect similar to cholinesterase inhibitor, it could improve cognitive function in MCI patients and reduce the AD transformation rate in them.
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Enfermedad de Alzheimer/prevención & control , Trastornos del Conocimiento/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Fitoterapia , Anciano , Femenino , Humanos , Masculino , Memoria/efectos de los fármacos , Escala del Estado Mental , Persona de Mediana Edad , Nootrópicos/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVE: To research the mechanism of TX0201 abstracted from heart-regulating formula in the treatment of rat with Alzheimer's disease (AD). METHOD: The rat models of AD were induced by A beta(1-40) injected into the bilateral amygdale. All rats were divided into five groups at random, namely control group, model group, heart-regulating formula group, TX0201 group and aricept group. The rats were intragastrically treated with different solution respectively for 20 days. The effect of TX0201 on spatial learning and memory ability of these rat models was investigated with the method of Morris water maze. By using the method of RT-PCR, the expression of apoptosis associated genes (such as Bcl-2 and Bax) in cerebral cortex and hippocampus of rats were examined. RESULT: Heart-regulating formula, TX0201 and aricept could significantly improve the spatial learning and memory ability of rats. Heart-regulating formula could comprehensively redress the abnormal expression of Bax mRNA and Bcl-2 mRNA in cerebral cortex and hippocampus. TX0201 could rectify the abnormal expression of Bax mRNA in cerebral cortex and hippocampus. Aricept could regulate the abnormal expression of Bax mRNA in cerebral cortex. CONCLUSION: TX0201 could ameliorate the learning and memory ability of these model rats by alleviating neuron apoptosis by means of regulating the abnormal expression of Bax mRNA in brain.
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Enfermedad de Alzheimer/fisiopatología , Medicamentos Herbarios Chinos/farmacología , Aprendizaje por Laberinto/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteína X Asociada a bcl-2/genética , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides , Animales , Apoptosis/efectos de los fármacos , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Combinación de Medicamentos , Medicamentos Herbarios Chinos/aislamiento & purificación , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Masculino , Plantas Medicinales/química , ARN Mensajero/genética , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
OBJECTIVE: To study the mechanism of TX0201, an effective fraction extracted from Tiaoxin recipe in regulating apoptosis associated genes in brain tissue of rat analogue model of Alzheimer's disease (AD) induced by beta-amyloid protein 25-35 (Abeta 25-35). METHODS: The model of AD was induced by bilateral amygdala injection of Abeta 25-35 to study the spatial memory capacity using Morris water maze test, and by means of RT-PCR and immunohistochemistry assay, the expressions of beta-amyloid precursor protein (APP), apoptosis correlative genes (bcl-2, bax), and apoptosis signal transduction molecule (Caspase-3) in the brain, and the effect of TX0201 on expressions of these genes were examined. RESULTS: In AD model group, the spatial capacity was damaged significantly. Caspase-3 and the expression of APP mRNA and bax/bcl-2 mRNA were increased in the cortex and hippocampus; TX0201 ameliorated all the pathologic changes mentioned above. CONCLUSION: TX0201 could improve the oriented learning and memory capacity in AD rats by decreasing bax/bcl-2 and down-regulating Caspase-3 to reduce neurocyte apoptosis, suggesting that effective regulation of neuron apoptosis associated genes may be one of the mechanisms of TX0201.
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Enfermedad de Alzheimer/metabolismo , Caspasa 3/biosíntesis , Fitoterapia , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteína X Asociada a bcl-2/biosíntesis , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/genética , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Masculino , Proteínas Proto-Oncogénicas c-bcl-2/genética , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Proteína X Asociada a bcl-2/genéticaRESUMEN
OBJECTIVE: To explore the therapeutic mechanism of Tiaoxin Recipe (TXR) and Bushen Recipe (BSR) in treating Alzheimer's disease (AD). METHODS: Sixty patients with AD were divided into 3 groups according to their MMSE and ADL scores before treatment, using randomized block design. They were treated separately with TXR, BSR and Donepezil (Dp) for 12 weeks. The changes of MMSE score, ADL score, neuro-psychology amount table score, including FOM, RVR, DS and BD, as well as the overall operational evaluation before and after treatment were analyzed. RESULTS: The recognition and daily life capacity of patients in the 3 groups were improved after treatment. MMSE score in the TXR group increased from 16.10 +/- 1.94 scores before treatment to 17.90 +/- 2.59 scores after treatment, in the BSR group, from 16.15 +/- 2.16 to 17.50 +/- 2.59, and in the Dp group, from 17.35 +/- 1.90 to 19.60 +/- 3.39, all showed significant difference (all P < 0.01). Change of ADL score showed that in TXR from 43.10 +/- 3.86 to 41.50 +/- 4.40, in the BSR group from 43.30 +/- 4.53 to 41.60 +/- 4.12 and in the Dp group, from 42.95 +/- 3.58 to 40.60 +/- 5.23, which also showed significant difference (P < 0.05 or P < 0.01). Moreover, increase of FOM, RVR and DS score was shown in the TXR and the Dp group, and increase of RVR and BD score was shown in the BSR group with significant difference in comparison of corresponding score before and after treatment, inter-groups comparison showed significant difference of FOM score between the BSR and the Dp group (P < 0.01). Overall operational evaluation (total effective rate) in the TXR group was 70%, in the BSR group 65% and in Dp group 75%, with no significant difference among them. CONCLUSION: TXR and BSR are effective TCM drugs in treating AD.