RESUMEN

PURPOSE: Ovarian cancer (OC) is a common malignancy, and IFN-γ, a multifunctional cytokine, is unveiled to impede the multiplication and enhance apoptosis in diverse tumor cells in previous research. Nonetheless, its function and mechanism in OC are blurred. METHODS: OC cell lines SKOV3 and OVCAR3 were dealt with different concentrations (0-40 ng/ml) of IFN-γ. CCK-8 experiment was utilized to examine cell multiplication; Flow cytometry was executed to detect apoptosis and cell cycle; Wound healing assay was utilized to detect cell migration; and Transwell experiment was implemented to examine cell invasion. qRT-PCR analysis was applied to detect STAT5, STAT3, JAK2 and JAK3 mRNA expression in OC cell lines. Western blot experiment was applied to detect the protein and phosphorylation levels of SOCS1, STAT5 and STAT3. RESULTS: IFN-γ suppressed OC cell multiplication in a concentration-dependent manner. Relative to the control group, IFN-γ restrained OC cell migration, invasion, enhanced apoptosis and prevented cell transformation from G0/G1 to S phase. Further analysis revealed that IFN-γ up-modulated SOCS1 expression and impeded STAT5 and STAT3 protein phosphorylation levels, and knockdown of SOCS1 partially counteracted the inhibitory effect of IFN-γ on STAT5 and STAT3 protein phosphorylation levels. CONCLUSION: IFN-γ represses OC progression by facilitating SOCS1 to suppress STAT3 and STAT5 protein phosphorylation.

Asunto(s)

Interferón gamma/fisiología , Janus Quinasa 2/fisiología , Neoplasias Ováricas/patología , Factor de Transcripción STAT5/fisiología , Transducción de Señal , Proteína 1 Supresora de la Señalización de Citocinas/fisiología , Progresión de la Enfermedad , Femenino , Humanos , Factor de Transcripción STAT3

RESUMEN

PURPOSE: Increasing evidence suggested that microRNA plays an important role in ovarian cancer. In this study, the role of miR-92 in ovarian cancer was investigated. METHODS: In this study, miR-92 expression in clinical sample was evaluated, role of miR-92 was investigated in vitro, and underlying mechanism was investigated using Chip, co-IP, and western blot. RESULTS: In this study, we show that miR-92 is overexpressed in ovarian cancer tissue compared with normal cancer tissue. Transfection of miR-92 increased proliferation of ovarian cancer cell, and increased migration capacity and colony formation were observed after miR-92 transfection; we found that expression of LATS2 was decreased by miR-92, and this was further confirmed by luciferase assay, which proved that miR-92 is targeting 3' of the endogenous LATS2 gene. Downregulation of LATS2 resulted in increased translocation of YAP1 and upregulation of PD-L1, which subsequently suppressed NK cell function and promoted T cell apoptosis. Moreover, co-transfection of YAP1-targeted shRNA could relieve miR-92-induced immune suppression effect. Mechanically, immunoprecipitation (IP) was used to show that LATS2 interacted with YAP1 and subsequently limited nuclear translocation of YAP1; chromatin immunoprecipitation (ChIP) was used to confirm that YAP1 could bind to enhancer region of PD-L1 to enhance transcription activity of PD-L1. CONCLUSIONS: Our data revealed a novel mechanism which finally resulted in immune suppression in ovarian cancer.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales/metabolismo , Antígeno B7-H1/metabolismo , Células Asesinas Naturales/inmunología , MicroARNs/metabolismo , Neoplasias Ováricas/inmunología , Proteínas Serina-Treonina Quinasas/metabolismo , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Núcleo Celular/metabolismo , Proliferación Celular , Regulación hacia Abajo , Elementos de Facilitación Genéticos , Femenino , Silenciador del Gen , Humanos , Inmunidad Celular , Inmunoprecipitación , Células Madre Neoplásicas , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Proteínas Serina-Treonina Quinasas/genética , ARN Interferente Pequeño , Transducción de Señal , Linfocitos T/fisiología , Proteínas Supresoras de Tumor/genética , Regulación hacia Arriba , Proteínas Señalizadoras YAP

RESUMEN

BACKGROUND: Surgery is becoming more practical and effective than conservative treatment in improving the poor outcomes of patients with breast cancer liver metastasis (BCLM). However, there is no generally acknowledged set of standards for identifying BCLM candidates who will benefit from surgery. METHODS: Between January 2011 and September 2018, 67 female BCLM patients who underwent partial hepatectomy were selected for analysis in the present study. Prognostic factors after hepatectomy were determined. Univariate and multivariate analyses were performed to identify predictors of overall survival (OS) and intrahepatic recurrence-free survival (IHRFS). RESULTS: The 1-, 3- and 5-year OS of patients treated with surgery was 93.5%, 73.7% and 32.2%, respectively, with a median survival time of 57.59 months. The Pringle manoeuvre [hazard radio (HR) = 0.117, 95% CI0.015-0.942, p = 0.044] and an increased interval between breast surgery and BCLM diagnosis (HR0.178, 95% CI 0.037-0.869, p = 0.033) independently predicted improved overall survival for BCLM patients. The 1-, 2- and 3-year IHRFS of patients who underwent surgery was 62.8, 32.6% and 10.9%, respectively, with a median intrahepatic recurrence-free survival time of 13.47 months. Moderately differentiated tumours (HR 0.259, 95% CI 0.078-0.857, p = 0.027) and the development of liver metastasis more than 2 years after breast surgery (HR 0.270, 95% CI 0.108-0.675, p = 0.005) might be predictors of increased IHRFS. CONCLUSIONS: An interval of more than 2 years between breast cancer surgery and liver metastasis seems to be an indication of liver surgery in BCLM patients. The Pringle manoeuvre and moderately differentiated tumours are potential predictors associated with OS and IHRFS, respectively, as benefits from liver resection. Studies with increased sample sizes are warranted to validate our results.

Asunto(s)

Neoplasias de la Mama/patología , Hepatectomía/métodos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Adulto , Anciano , Neoplasias de la Mama/cirugía , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Persona de Mediana Edad , Factores de Tiempo

RESUMEN

Bactrocera cucurbitae (Coquillett) (Diptera: Tephritidae) is an important pest of vegetables in Asia, the Middle East, Africa, and Hawaii. High temperature can significantly influence B. cucurbitae reproduction. The effect of short-term high-temperature exposure on proteins that affect oviposition was analyzed by proteomics. Among six key target genes for oviposition, the expression of Vitellogenin-1, Vitellogenin-2, and Vitellogenin receptor was similar in B. cucurbitae exposed to higher temperature compared to controls. However, levels of Vitellogenin-3 were reduced. Juvenile hormone (Jh)-inducible protein was downregulated and then upregulated, while the expression of Jh-epoxide hydrolase-2 showed the opposite Jh-inducible protein trend. Therefore, short-term high-temperature stress can cause differential expression of proteins related to oviposition in B. cucurbitae, which in turn further triggers the hormesis of oviposition. High-temperature conditions have become more frequent because of climate warming and are predicted to continue. The data indicate that climate effects on insect reproduction pose a significant threat to agriculture in a world of increasing population.

Asunto(s)

Genes de Insecto , Calor , Oviposición , Proteoma/genética , Tephritidae/fisiología , Animales , Femenino , Proteómica , Análisis de Secuencia de ARN , Tephritidae/genética

RESUMEN

Human enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD), particularly in infants and children below 4 years of age. Shikonin is a bioactive compound with anti-inflammatory, antiviral, and antibacterial activities derived from the roots of the Chinese medicinal herb Lithospermum erythrorhizon. This study aimed to examine the antiviral activity of PMM-034, a shikonin ester derivative, against EV71 in rhabdomyosarcoma (RD) cells. Cytotoxicity of PMM-034 on RD cells was determined using WST-1 assay. Dose- and time-dependent effects of PMM-034 on EV71 replication in RD cells were determined using plaque reduction assay. mRNA expression levels of EV71/VP1 and pro-inflammatory cytokines (IL-1ß, IL-6, IL-8, and TNF-α) were determined by real-time RT-PCR, and EV71/VP1 and phospho-p65 protein expressions were determined by western blot analysis. PMM-034 exhibited only weak cytotoxicity against RD cells. However, PMM-034 exhibited significant antiviral activity against EV71 in RD cells with 50% inhibitory concentration of 2.31 µg/mL. The VP1 mRNA and protein levels were significantly reduced in cells treated with PMM-034. Furthermore, relative mRNA expression levels of IL-1ß, IL-6, IL-8, and TNF-α significantly decreased in the cells treated with PMM-034, while the phospho-p65 protein expression was also significantly lower in the treated cells. These results indicated that PMM-034 suppressed the expressions of pro-inflammatory cytokines in RD cells, exhibiting antiviral activity against EV71, as evidenced by the reduced VP1 mRNA and protein levels in PMM-034-treated cells. Thus, PMM-034 is a promising candidate for further development as an EV71 inhibitor.

Asunto(s)

Antivirales/farmacología , Enterovirus Humano A/efectos de los fármacos , Naftoquinonas/farmacología , Rabdomiosarcoma/virología , Western Blotting , Línea Celular Tumoral , Citocinas/análisis , Relación Dosis-Respuesta a Droga , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa , Pruebas de Toxicidad , Ensayo de Placa Viral , Replicación Viral/efectos de los fármacos

RESUMEN

Human enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD), particularly in infants and children below 4 years of age. Shikonin is a bioactive compound with anti-inflammatory, antiviral, and antibacterial activities derived from the roots of the Chinese medicinal herb Lithospermum erythrorhizon. This study aimed to examine the antiviral activity of PMM-034, a shikonin ester derivative, against EV71 in rhabdomyosarcoma (RD) cells. Cytotoxicity of PMM-034 on RD cells was determined using WST-1 assay. Dose- and time-dependent effects of PMM-034 on EV71 replication in RD cells were determined using plaque reduction assay. mRNA expression levels of EV71/VP1 and pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) were determined by real-time RT-PCR, and EV71/VP1 and phospho-p65 protein expressions were determined by western blot analysis. PMM-034 exhibited only weak cytotoxicity against RD cells. However, PMM-034 exhibited significant antiviral activity against EV71 in RD cells with 50% inhibitory concentration of 2.31 μg/mL. The VP1 mRNA and protein levels were significantly reduced in cells treated with PMM-034. Furthermore, relative mRNA expression levels of IL-1β, IL-6, IL-8, and TNF-α significantly decreased in the cells treated with PMM-034, while the phospho-p65 protein expression was also significantly lower in the treated cells. These results indicated that PMM-034 suppressed the expressions of pro-inflammatory cytokines in RD cells, exhibiting antiviral activity against EV71, as evidenced by the reduced VP1 mRNA and protein levels in PMM-034-treated cells. Thus, PMM-034 is a promising candidate for further development as an EV71 inhibitor.

Asunto(s)

Humanos , Antivirales/farmacología , Enterovirus Humano A/efectos de los fármacos , Naftoquinonas/farmacología , Rabdomiosarcoma/virología , Western Blotting , Línea Celular Tumoral , Citocinas/análisis , Relación Dosis-Respuesta a Droga , Reacción en Cadena en Tiempo Real de la Polimerasa , Pruebas de Toxicidad , Ensayo de Placa Viral , Replicación Viral/efectos de los fármacos

RESUMEN

OBJECTIVE: To analyze the clinical characteristics, outcome and diagnosis of two cases of imported children Zika virus infection in China. METHOD: A retrospective analysis was performed on clinical characteristics, treatment and outcome of two cases of imported children with Zika virus infection in February 2016 in Enping People's Hospital of Guangdong. RESULT: Two cases of children with imported Zika virus infection resided in an affected area of Venezuela, 8-year-old girl and her 6 year-old brother. The main findings on physical examination included the following manifestations: fever, rash, and conjunctivitis. The rash was first limited to the abdomen, but extended to the torso, neck and face, and faded after 3-4 d. The total number of white blood cells was not high and liver function was normal. The diagnosis of two cases of Zika virus infection was confirmed by the expert group of Guangdong Provincial Center for Disease Control and Prevention, according to the epidemiological history, clinical manifestations and Zika virus nucleic acid detection results.Treatment of Zika virus infection involves supportive care. Two Zika virus infection children had a relatively benign outcome. CONCLUSION: At present, Zika virus infection in children is an imported disease in China. No specific therapy is available for this disease. Information on long-term outcomes among infants and children with Zika virus disease is limited, routine pediatric care is advised for these infants and children.

Asunto(s)

Infección por el Virus Zika/diagnóstico , Virus Zika/aislamiento & purificación , Niño , China , Exantema , Femenino , Fiebre , Humanos , Masculino , Estudios Retrospectivos , Venezuela

RESUMEN

We sought to determine the efficacy of atomized paclitaxel liposome inhalation treatment of pulmonary fibrosis in a bleomycin-induced rat model. Forty male Sprague-Dawley rats were randomly divided into four groups: healthy control, pulmonary fibrosis without treatment, paclitaxel liposome inhalation-treated, and intravenous paclitaxel liposome-treated. Fibrosis was induced by bleomycin injection. A total of 20 mg/kg paclitaxel liposome was administered by inhalation every other day for a total of 10 doses. The intravenous group received 5 mg/kg paclitaxel liposome on days 1, 7, 14, and 21. We observed the general condition, weight change, survival index, and pathological changes in the lung tissue of the rats. Quantitative analysis of collagen types I and III and transforming growth factor (TGF)-ß1 expression in the lungs was also performed. The paclitaxel liposome inhalation and intravenous delivery methods improved survival index and pulmonary fibrosis Ashcroft score, and decreased the thickness of the alveolar interval. No obvious difference was found between the two groups. Compared with the untreated group, paclitaxel liposome inhalation and intravenous injection significantly reduced the levels of collagen types I and III and TGF-ß1 expression equally. In conclusion, atomized paclitaxel liposome inhalation protects against severe pulmonary fibrosis in a bleomycin-induced rat model. This delivery method has less systemic side effects and increased safety over intravenous injection.

Asunto(s)

Liposomas , Paclitaxel/uso terapéutico , Fibrosis Pulmonar/tratamiento farmacológico , Administración por Inhalación , Animales , Bleomicina/toxicidad , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Inyecciones Intravenosas , Masculino , Paclitaxel/administración & dosificación , Fibrosis Pulmonar/etiología , Ratas , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo

RESUMEN

B chromosomes are dispensable and co-exist with autosomal and sex chromosomes. The karyotype of the Chinese raccoon dog (Nyctereutes procyonoides procyonoides) comprises 0-4 B chromosomes. The proto-oncogene KIT is found on all B chromosomes of the Chinese raccoon dog. In the present study, partial DNA and mRNA sequences of KIT were amplified and sequenced from four individuals containing B chromosomes. Sequence analyses revealed that polymorphisms including single nucleotide polymorphisms (SNPs) and inserts/deletions were rich in the KIT gene of Chinese raccoon dog at the genomic level. However, no polymorphism was detected at the mRNA level. A comparison of mRNA sequences from Chinese raccoon dogs with the corresponding sequences derived from arctic fox and dog, which do not contain B chromosomes, revealed the mRNA sequences of the 10 SNPs to be identical between these three species. Therefore, these findings suggest that KIT located on the B chromosomes in Chinese raccoon dog lacks transcriptional activity.

Asunto(s)

Cromosomas de los Mamíferos , Mutación INDEL , Polimorfismo de Nucleótido Simple , Proteínas Proto-Oncogénicas c-kit/genética , Perros Mapache/genética , Transcripción Genética , Animales , Secuencia de Bases , Proteínas Proto-Oncogénicas c-kit/química , Proteínas Proto-Oncogénicas c-kit/metabolismo , Perros Mapache/metabolismo , Alineación de Secuencia , Análisis de Secuencia

RESUMEN

We investigated the effects of kinase insert domain receptor (KDR) gene silencing on the proliferation of A549 cells and their sensitivity to erlotinib. A KDR small interfering RNA (siRNA) sequence was designed and synthesized; then, it was transfected into A549 cells using Lipofectamine(TM) 2000. KDR mRNA and protein expression after KDR gene silencing was detected by reverse transcription polymerase chain reaction and western blotting; the A549 cell cycle was detected by flow cytometry. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and colony formation assay were performed to determine the sensitivity of A549 cells to erlotinib after KDR gene silencing. After 48h of KDR gene silencing, there was a significant decrease in KDR gene and protein expression (P < 0.05). The A549 cell cycle was arrested at the G0/G1 phase, and the number of cells in the S phase decreased; the difference was statistically significant (P < 0.05). In the KDR gene silencing group, the sensitivity of A549 cells to erlotinib was significantly enhanced (P < 0.05). KDR siRNA can significantly silence the KDR gene in A549 cells, inhibit the proliferation of A549 cells, and enhance their sensitivity to erlotinib.

Asunto(s)

Adenocarcinoma/tratamiento farmacológico , Clorhidrato de Erlotinib/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Células A549 , Adenocarcinoma del Pulmón , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos , Silenciador del Gen , Humanos , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Sales de Tetrazolio , Tiazoles , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo

RESUMEN

In this study, we examined the effect of cetuximab (epidermal growth factor receptor monoclonal antibody) combined with afatinib (epidermal growth factor receptorand human epidermal growth factor receptor 2 tyrosine kinase irreversible inhibitor) on the apoptosis of A549 cells and on kinase domain receptor (KDR) and aquaporin 1 (AQP1) expression in A549 cells. A549 cells were cultured in RPMI-1640 and then divided into 4 groups: control group, 1-nM cetuximab group, 25-µM afatinib group, and 1-nM cetuximab + 25-µM afatinib group. After incubation for 48 h, the cell inhibition rate, cell cycle distribution, and invasive ability of A549 cells before and after treatment were examined using MTT, flow cytometry, and transwell assays, respectively. Gene and protein expression levels of KDR and AQP1 were detected by reverse transcription-polymerase chain reaction and western blot analysis. Cetuximab and afatinib significantly inhibited A549 cell growth. Their combination produced greater growth inhibition (P < 0.01). Cetuximab and afatinib both induced the apoptosis of A549 cells, and their combination produced a higher apoptosis rate (P < 0.01). Compared with monotherapy, cetuximab in combination with afatinib induced G1 phase arrest and downregulated the gene and protein expression of KDR and AQP1 (P < 0.05). Cetuximab in combination with afatinib synergistically inhibited the growth and migration of cells and downregulated the gene and protein expression of KDR and AQP1, indicating that a combination of cetuximab and afatinib is a potential strategy for lung cancer therapy.

Asunto(s)

Antineoplásicos/farmacología , Acuaporina 1/metabolismo , Cetuximab/farmacología , Neoplasias Pulmonares/metabolismo , Quinazolinas/farmacología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Afatinib , Acuaporina 1/genética , Línea Celular Tumoral , Sinergismo Farmacológico , Humanos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética

RESUMEN

The objective of this study was to examine the effect of high-intensity exercise on interleukin-15 (IL-15) expression in rabbit synovia. We utilized 24 New Zealand white rabbits, which were randomly divided equally into high-intensity exercise and control groups. The former were forced to run for 60 min/day over 4 weeks at the speed of 30 m/min. The histological changes of cartilage and knee joint synovia were investigated with hematoxylin and eosin staining. Immunohistochemistry and enzyme-linked immunosorbent assays were performed to measure IL-15 expression. From these analyses, we identified knee articular cartilage damage and synovitis in the high-intensity exercise group. This group also exhibited higher IL-15 expression in their synovial fluid and tissues than was observed in the control group (P < 0.05). These results suggested that high-intensity exercise might lead to synovitis and articular cartilage damage, and that IL-15 overexpression in synovia might be associated with post-traumatic osteoarthritis.

Asunto(s)

Interleucina-15/metabolismo , Condicionamiento Físico Animal , Líquido Sinovial/metabolismo , Animales , Cartílago Articular/metabolismo , Condrocitos/metabolismo , Ensayo de Inmunoadsorción Enzimática , Inmunohistoquímica , Conejos , Membrana Sinovial/metabolismo

RESUMEN

The aim of this study was to investigate the impact of high intensity exhaustive exercise on nitric oxide (NO), malondialdehyde (MDA), and superoxide dismutase (SOD) expression in rats with knee osteoarthritis. Sprague Dawley rats were randomly divided into control (N = 5) and model (N = 35) groups; the model group was further divided into quiet (N = 5), low- (N = 15) and high- (N = 15) intensity exhaustive exercise groups. The low- and high-intensity groups were randomly divided into pre-exercise (N = 5), immediate post-exercise (N = 5), and 24-h post-exercise (N = 5) groups according to different time points for detection. NO, MDA, and SOD levels were compared between each group. The SOD levels in the quiet, low-, and high-intensity exhaustive exercise groups were lower than that in the control group, whereas the NO and MDA levels were higher in the former groups than in the controls (P < 0.05). The SOD level in the 24-h post-low intensity exhaustive exercise group was higher than that in the 24-h post-high intensity exhaustive exercise group, whereas the NO and MDA levels were lower in the 24-h post-low intensity than in the post-high intensity exercise group (P < 0.05). Overall, the results demonstrated that with the increase of exercise intensity, the SOD activity in the rats with knee osteoarthritis decreased gradually, whereas the MDA and NO levels gradually increased. Thus, the greater the exercise intensity, the more serious the impact on knee osteoarthritis.

Asunto(s)

Malondialdehído/metabolismo , Actividad Motora/fisiología , Óxido Nítrico/metabolismo , Osteoartritis de la Rodilla/metabolismo , Superóxido Dismutasa/metabolismo , Animales , Masculino , Oxidación-Reducción , Ratas , Ratas Sprague-Dawley

RESUMEN

The fat mass- and obesity-associated gene (FTO) is involved in energy metabolism, but little is known about the chicken FTO gene. The objective of the current study was to detect chicken FTO expression patterns in the hypothalamus, liver, and skeletal muscle during development, and analyze the effects of age and breed on FTO expression. Real-time quantitative polymerase chain reaction results revealed that chicken FTO mRNA was expressed in all of the tissues tested. Chicken FTO exhibited tissue- and breed-specific patterns in the recessive White Plymouth Rock chicken and the Qingyuan partridge chicken. The highest FTO expression level was in the hypothalami of 1-week-old chicks. FTO mRNA was expressed more in the breast muscles and livers of recessive White Plymouth Rock chickens than those of Qingyuan partridge chickens at 1 and 8 weeks of age. These results indicate that FTO probably plays a significant role in energy metabolism at 1 week old, when chicks have undergone metabolic adaptations from yolk dependence to the utilization of exogenous feed.

Asunto(s)

Proteínas Aviares/genética , Pollos/genética , Regulación del Desarrollo de la Expresión Génica , Metabolismo de los Lípidos/genética , Carne , ARN Mensajero/genética , Animales , Proteínas Aviares/metabolismo , Peso Corporal , Cruzamiento , Embrión de Pollo , Pollos/crecimiento & desarrollo , Metabolismo Energético/genética , Femenino , Hipotálamo/crecimiento & desarrollo , Hipotálamo/metabolismo , Hígado/crecimiento & desarrollo , Hígado/metabolismo , Masculino , Músculo Esquelético/crecimiento & desarrollo , Músculo Esquelético/metabolismo , Especificidad de Órganos , ARN Mensajero/metabolismo , Especificidad de la Especie

RESUMEN

To study the role of boswellic acid in reducing asthma phenotype severity and the relationship between the expression of pSTAT6 and GATA3, thirty-six mice were randomly divided into normal control group, asthma group, and boswellic acid group (treatment group). The asthma model was established through an intraperitoneal injection of sensitization liquid (0.15 mL aluminum hydroxide gel at 88.67 mg/mL and 0.05 mg ovalbumin). pSTAT6 and GATA3 expression levels in peripheral blood were detected by reverse transcription-polymerase chain reaction and Western blot analysis. pSTAT6 and GATA3 gene expressions in the asthmatic group were significantly higher than in the normal control group; they were markedly lower in the treatment group than the asthma group, and there was no significant difference when compared with the normal control group. The pSTAT6 expressions in the asthma, control and treatment groups were 2.256 ± 0.125, 0.524 ± 0.210, and 0.897 ± 0.134 at gray level, respectively. The GATA3 expressions in the asthma, control, and treatment groups were 3.521 ± 0.631, 0.435 ± 0.136, and 0.743 ± 0.149 at gray level, respectively. pSTAT6 and GATA3 expression levels were similar in the treatment and control groups. GATA3 expression had a positive correlation with pSTAT6 expression. Boswellic acid may improve asthma symptoms by inhibiting pSTAT6 expression, which consequently reduces GATA3 expression.

Asunto(s)

Asma/tratamiento farmacológico , Asma/patología , Regulación hacia Abajo/efectos de los fármacos , Factor de Transcripción GATA3/genética , Factor de Transcripción STAT6/antagonistas & inhibidores , Triterpenos/uso terapéutico , Animales , Asma/genética , Factor de Transcripción GATA3/metabolismo , Masculino , Ratones Endogámicos BALB C , Fenotipo , Fosforilación/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factor de Transcripción STAT6/genética , Factor de Transcripción STAT6/metabolismo , Triterpenos/farmacología

RESUMEN

We aimed to evaluate the effect of melatonin on myo-cardial cell oncosis in the myocardial ischemia/reperfusion injury rat, and the role of the mitochondrial permeability transition pore (MPTP) therein. Sprague Dawley rats (N = 60) were randomly divided into five groups of 12 rats each: control, ischemia/reperfusion (I/R), melatonin treatment (MT), melatonin treatment + atractyloside (MT+ATR), and atractyloside (ATR). We prepared the myocardial ischemia/reperfusion model by reperfusion after the left anterior descending coronary artery was ligated for 30 min. The MT rats were given a 10 mg/kg MT intra-venous injection immediately thereafter; the MT+ATR rats were also given a 5 mg/kg ATR intravenous injection 15 min before the ischemia; the ATR rats were given the ATR injection only. After 2-h re-perfusion, myocardial tissue was extracted, the infarction size was determined, and myocardial ultrastructures were observed using electron microscopy. The expression level of the preoncosis receptor (porimin), which can induce membrane injury, was determined by western blot; the nicotinamide adenine dinucleotide (NAD(+)) content was determined spectrophotometrically. The four treatment groups showed upregulat-ed expression of myocardial porimin, increased myocardial infarction size, and reduced NAD(+) content (P < 0.05). Compared with the I/R and MT+ATR groups, MT rats showed downregulated expression of myo-cardial porimin, reduced myocardial infarct size, and increased myo-cardial cell NAD(+) content (P < 0.05). The above indices between the ATR and MT+ATR groups were not significantly different (P > 0.05). Thus, MT might protect myocardial ischemia/reperfusion rats by inhibiting MPTP opening and reducing myocardial cell oncosis.

Asunto(s)

Melatonina/farmacología , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Miocardio/patología , Animales , Masculino , Poro de Transición de la Permeabilidad Mitocondrial , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Miocardio/ultraestructura , NAD/metabolismo , Ratas Sprague-Dawley , Receptores de Superficie Celular/metabolismo

RESUMEN

To investigate the effects of probucol on the treatment of spinal cord injury in rat, 80 rats were randomly divided into two groups of 40: a group treated with probucol and a control group. Allen's method was used to establish a rat model of spinal cord injury. After establishment, probucol (500 mg·kg(-1)·day(-1)) was intraperitoneally injected into the treatment group rats for 1 week, while the same amount of saline was used to treat the control group. On days 1, 7, 14, 21, and 28 after treatment, the function of rats' spinal cord was evaluated according to the Bresnahan locomotor rating scale. Serum protein and mRNA levels of the cytokines [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-17] were measured using enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively. Protein levels of IFN-γ, TNF-α, IL-17, and the downstream markers signal transducer and activator of transcription (STAT)-1 and STAT-3 were measured using western blot. In addition, the oxidative stress-related parameters, superoxide dismutase (SOD) and malondialdehyde (MDA), were also measured. It was found that compared to control group, rats from the treatment group had significantly lower levels of IFN-γ, TNF-α, and IL-17 (P < 0.05) on days 1 and 7, as well as lower MDA levels and higher SOD activity on days 7, 21, and 28 (P < 0.05). In summary, probucol improved the recovery of locomotion function after spinal cord injury in rats through downregulation of inflammation and upregulation of anti-oxidative activity.

Asunto(s)

Fármacos Neuroprotectores/uso terapéutico , Probucol/uso terapéutico , Traumatismos de la Médula Espinal/tratamiento farmacológico , Animales , Western Blotting , Citocinas/sangre , Femenino , Inflamación/sangre , Inflamación/patología , Mediadores de Inflamación/metabolismo , Malondialdehído/metabolismo , Actividad Motora/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Probucol/farmacología , Ratas Wistar , Recuperación de la Función/efectos de los fármacos , Traumatismos de la Médula Espinal/sangre , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/cirugía , Superóxido Dismutasa/metabolismo

RESUMEN

Brain cancer stem cells are a subset of tumor cells present in several types of brain tumor that evade treatment regimens and are responsible for tumor recurrence. Recent reports on several tumors have suggested that Hoechst 33342 dye exclusion is a powerful technique for isolating cancer stem cell-like side population (SP) cells. In the present study, we attempted to isolate the SP cells from medulloblastoma, a malignant brain tumor in children. The tumor samples obtained were subjected to fluorescence-activated cell sorting analysis for SP cell isolation. Further, the SP cells were characterized by a sphere-formation assay and analyzed for expression of stem cell genes by reverse transcription-polymerase chain reaction (RT-PCR). Using flow cytometry, we isolated 2.9% of cancer stem-like SP cells from malignant medulloblastoma, which was reduced to 0.4% in the presence of verapamil, an inhibitor of ABC transporter. These SP cells undergo rapid proliferation and have a high tendency to form tumor spheres when compared with non-SP cells. Further, RT-PCR analysis revealed that the isolated SP cells have increased expression of neural stem cell markers such as nestin, Notch1, and the ABC transporter protein ABCG2. Therefore, our findings suggest that SP cells of medulloblastoma share the characteristics of cancer stem cells. The increased expression of stem cell markers and ABCG2 protein may function collectively and be responsible for drug and apoptosis resistance, as well as tumor recurrence and invasion.

Asunto(s)

Meduloblastoma/patología , Células Madre Neoplásicas/fisiología , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Línea Celular Tumoral , Proliferación Celular , Preescolar , Expresión Génica , Humanos , Meduloblastoma/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Receptor Notch1/genética , Receptor Notch1/metabolismo , Células de Población Lateral/metabolismo , Esferoides Celulares/metabolismo

RESUMEN

We examined the value of serum procalcitonin (PCT), C-reactive protein (CRP), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) for predicting the survival of patients with early-onset stroke associated pneumonia (EOP). A total of 207 stroke patients were enrolled, and 91 developed EOP. Upon admission, serum PCT, CRP, sTREM-1 levels, clinical pulmonary infection score, and Acute Physiology and Chronic Health Evaluation II score were all significantly higher in patients with EOP than in those without EOP (P < 0.05). Of the 91 patients who developed EOP, 39 (42.9%) died (non-survivors) within 28 days. The Acute Physiology and Chronic Health Evaluation II score on admission was significantly higher in non-survivors than in survivors (P < 0.05). Serum PCT and sTREM-1 levels were slightly elevated on days 1, 3, and 5 in non-survivors and gradually decreased in survivors. Serum PCT, sTREM-1, and CRP levels were all significantly higher in non-survivors than in survivors on days 1, 3, and 5 (P < 0.05). The sensitivity and specificity of PCT for predicting the outcome of EOP were 84.6 and 71.2%, the sensitivity and specificity of sTREM-1 were 71.8 and 92.3%, and the sensitivity and specificity of sTREM-1 combined with PCT were 74.4 and 96.2%. Serum PCT combined with sTREM-1 accurately predicted the outcome of EOP patients, and dynamic monitoring of serum PCT and sTREM-1 levels is necessary.

Asunto(s)

Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Calcitonina/sangre , Células Mieloides/metabolismo , Neumonía/complicaciones , Precursores de Proteínas/sangre , Receptores Inmunológicos/metabolismo , Accidente Cerebrovascular/complicaciones , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Péptido Relacionado con Gen de Calcitonina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía/sangre , Accidente Cerebrovascular/sangre , Tasa de Supervivencia , Adulto Joven

RESUMEN

The insulin-like growth factor 2 receptor gene (IGF2R) encodes a transmembrane protein receptor and acts to sequester and degrade excess circulating insulin-like growth factor 2, which is critical for normal mammalian growth and development. Thus, IGF2R may serve as a candidate gene underlying growth trait in the common carp. In this study, we isolated the intron one of common carp IGF2R and detected the diversity in 3 continuous generations of FFRC strain common carp. A total of 8 loci were detected within this region, which were named in accordance with their location (i.e., Loc84, Loc106, Loc119, Loc130, Loc145, Loc163, Loc167, and Loc265). Loc106, Loc119, and Loc145 were moderately polymorphic; while Loc84, Loc130, Loc163, Loc167, and Loc265 exhibited slight level of polymorphism. However, significant differences between polymorphism information content values were not observed among the different generations. For Loc145, all generations deviated from Hardy-Weinberg equilibrium. The total number of significant linkage disequilibria for all generations equaled 40. Among them, 4 pairs were detected in each population, while 8 pairs were found in the 2nd and 3rd generations. For Loc130, the G/T genotype exhibited higher body weight when compared to that of the G/G genotype. The frequency of the homozygous G/G genotype reached 87.96%; thus, we can improve FFRC strain common carp growth performance by increasing the percentage of the G/T genotype within a breeding population. Therefore, the G/T genotype could be used as a molecular marker for superior growth traits.

Asunto(s)

Carpas/crecimiento & desarrollo , Carpas/genética , Intrones/genética , Polimorfismo de Nucleótido Simple/genética , Receptor IGF Tipo 2/genética , Animales , Peso Corporal/genética , Sitios Genéticos , Heterocigoto , Desequilibrio de Ligamiento/genética , Filogenia , Reacción en Cadena de la Polimerasa