RESUMEN
BACKGROUND AND OBJECTIVE: Smoking is a leading cause of death in the world. Aberrant brain function has been repeatedly linked to tobacco smoking. However, little is known about insula-based resting-state functional connectivity (rsFC) in non-deprived tobacco-dependent smokers. This study characterized the correlation between insula-based rsFC and tobacco dependence severity in non-deprived smokers. METHODS: A total of 37 male smokers and 37 age-matched male non-smokers completed resting-state functional MRI (fMRI) scans. The insula-based rsFC differences between smokers and controls were investigated and the correlation between insula-based rsFC and FTND (Fagerström Test for Nicotine Dependence) scores were then assessed. RESULTS: Compared with controls, smokers showed significantly lower rsFC between orbitofrontal cortex, superior frontal gyrus, temporal lobe and insula. The rsFC between orbitofrontal cortex, temporal lobe, inferior parietal cortex, occipital lobe and insula was positively correlated with FTND. However, the rsFC between anterior cingulate cortex and insula was negatively correlated with FTND. CONCLUSION: Our findings suggest differences in brain functional connectivity between smokers and non-smokers. This study sheds new insights into the neural mechanisms of tobacco dependence.
Asunto(s)
Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/fisiopatología , Imagen por Resonancia Magnética , Fumar Tabaco/fisiopatología , Tabaquismo/diagnóstico por imagen , Tabaquismo/fisiopatología , Adulto , Estudios de Casos y Controles , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/fisiopatología , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/fisiopatología , Humanos , Masculino , Lóbulo Occipital/diagnóstico por imagen , Lóbulo Occipital/fisiopatología , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Parietal/fisiopatología , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiopatología , Descanso/fisiología , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/fisiopatología , Adulto JovenRESUMEN
Objective: To explore the mechanism by which the Wnt/ß-catenin pathway induces osteogenic differentiation of bone marrow-derived stem cells (BMSCs) in anhidrotic ectodermal dysplasia (AED) with an Ectodysplasin A (EDA)/EDA receptor (EDAR)/EDARADD mutation. Methods: An AED patient served as the AED group, whereas the other patients without AED were included in the normal group. Peripheral venous blood collected from the AED patient was subjected to whole-genome resequencing. BMSCs from the mandible of patients with AED and normal individuals were isolated and cultured in vitro. Cell proliferation assay was performed to compare the growth speed of BMSCs between the AED and normal groups. CHIR-99021, an activator of the Wnt/ß-catenin pathway and XAV-939, an inhibitor, was used to manage BMSCs in an osteogenic environment in both groups. The expression of ß-catenin was detected by quantitative polymerase chain reaction, while that of RUNX2 was detected by western blotting. Alizarin red was used for staining. Results: A novel mutation (c.152T > A in EDA) and two known mutations (c.1109T > C in EDAR and c.27G > A in EDARADD) were identified. The growth rate in the normal group was higher than that in the AED group. In the normal group, the number and size of calcified nodes and the expression of RUNX-2 increased with CHIR-99021 treatment, which could be inhibited by XAV-939. In contrast, CHIR-99021 inhibited osteogenesis in the AED group and this effect was promoted by XAV-939. Conclusion: Activation of the Wnt/ß-catenin pathway downregulates osteogenesis of BMSCs in AED patients with EDA/EDAR/EDARADD gene mutations. Further investigation in more AED patients is required, given the wide range of mutations involved in AED.
RESUMEN
Background: Cumulative evidence showed an association between gut microbiota and urticaria, but the causal relationship between them is unclear. We aimed to verify whether there is a causal relationship between the composition of gut microbiota and urticaria and explore whether the causal effect was bidirectional. Methods: We obtained genome-wide association studies (GWAS) summary data of 211 gut microbiota and urticaria from the most extensive available GWAS database. A bidirectional two-sample mendelian randomization (MR) study was used to test the causal relationship between the gut microbiota and urticaria. The MR analysis was primarily performed with the inverse variance weighted (IVW) method, and MR-Egger, weighted median (WM), and MR-PRESSO were performed as sensitivity analyses. Results: The Phylum Verrucomicrobia (OR 1.27, 95%CI 1.01 to 1.61; p = 0.04), Genus Defluviitaleaceae UCG011 (OR 1.29, 95%CI 1.04 to 1.59; p = 0.02), and Genus Coprococcus 3 (OR 1.44, 95%CI 1.02 to 2.05; p = 0.04) was a risk effect against urticaria. And Order Burkholderiales (OR 0.68, 95%CI 0.49 to 0.99; p = 0.04) and Genus Eubacterium xylanophilum group (OR 0.78, 95%CI 0.62 to 0.99; p = 0.04) were negatively associated with urticaria, suggesting a protective effect. At the same time, urticaria had a positively causal effect on gut microbiota (Genus Eubacterium coprostanoligenes group) (OR 1.08, 95%CI 1.01 to 1.16; p = 0.02). These findings showed no influence by heterogeneity or horizontal pleiotropy. Moreover, most sensitivity analyses showed results consistent with those of IVW analysis. Conclusion: Our MR study confirmed the potential causal relationship between gut microbiota and urticaria, and the causal effect was bidirectional. Nevertheless, these findings warrant further examination owing to the unclear mechanisms.
RESUMEN
OBJECTIVES: To explore the effect mechanism of electroacupuncture (EA) on functional constipation (FC) at the combined lower he-sea and front-mu points of large intestine based on enteric neuronal autophagy. METHODS: A total of 40 SPF Kunming mice were randomly divided into 5 groups (n = 8), i.e. a control group, a model group, an acupuncture group, a 3-methyl adenine (3-MA) group, and a 3-MA + acupuncture group. Except the control group, the FC model was established by gavage with compound diphenoxylate suspension for 14 days in the other 4 groups. After successful modeling, the mice of the acupuncture group and the 3-MA + acupuncture group received EA at bilateral "Tianshu" (ST 25) and "Shangjuxu" (ST 37), stimulated for 30 min with disperse-dense wave, 2 Hz/15 Hz of frequency, 1 mA of intensity. EA was delivered once daily. One course of treatment was composed of 5 days and 2 courses were needed, with an interval of 2 days. An intraperitoneal injection of 3-MA (15 mg/kg) was administered 30 min before EA in the mice of the 3-MA group and the 3-MA + acupuncture group, once daily. Before and after intervention, the time of the first black stool defecation and defecation behaviors in 6 h were observed in each group. After intervention, in every group, the small intestine propulsion rate was calculated, the colon tissue morphology was observed using HE staining, the ultrastructure of enteric neuronal autophagy was observed under transmission electron microscope, and the expressions of microtubule-associated protein 1 light chain 3 (LC3), Beclin-1 and neuronal nuclear antigen protein (NeuN) in neurons of colonic muscularis were determined by immunohistochemistry. RESULTS: Before intervention, when compared with those in the control group, the time of the first black stool defecation was prolonged (P<0.01, P<0.05), and numbers (P<0.01), wet weight (P<0.01, P<0.05) and water content (P<0.05, P<0.01) of stool in 6 h were reduced in the model, acupuncture, 3-MA and 3-MA + acupuncture groups. After intervention, compared with those in the control group, the time of the first black stool defecation was longer (P<0.05), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were decreased in the model group. The time of the first black stool defecation was shortened (P<0.01), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were increased in the acupuncture group when compared with those in the model group. The time of the first black stool defecation was extended (P<0.01), and numbers (P<0.01), wet weight (P<0.01) and water content (P<0.01) of stool in 6 h were declined in the 3-MA + acupuncture group in comparison with those in the acupuncture group. All layers of colon tissue were normal and intact in each group. When compared with the control group, the small intestine propulsion rate and the average optical density (OD) values of LC3, Beclin-1 and NeuN in neurons of colonic muscularis were decreased (P<0.01), and autophagosomes were dropped in the model group. In the acupuncture group, the small intestine propulsion rate and the average OD values of NeuN, LC3 and Beclin-1 in neurons of colonic muscularis increased (P<0.01,P<0.05), and autophagosomes were elevated when compared with those in the model group. The small intestine propulsion rate and the average OD values of NeuN, LC3 and Beclin-1 in neurons of colonic muscularis were dropped (P<0.05,P<0.01) in the 3-MA + acupuncture group in comparison with those in the acupuncture group. CONCLUSIONS: Electroacupuncture may promote enteric neuronal autophagy and increase the number of neurons so that the intestinal motility can be improved and constipation symptoms can be relieved in FC mice.
Asunto(s)
Electroacupuntura , Ratones , Animales , Beclina-1 , Puntos de Acupuntura , Estreñimiento/terapia , Intestino Delgado , Autofagia , AguaRESUMEN
OBJECTIVE: To investigate autophagy-related mechanisms of electroacupuncture (EA) action in improving gastrointestinal motility in mice with functional constipation (FC). METHODS: According to a random number table, the Kunming mice were divided into the normal control, FC and EA groups in Experiment I. The autophagy inhibitor 3-methyladenine (3-MA) was used to observe whether it antagonized the effects of EA in Experiment II. An FC model was established by diphenoxylate gavage. Then the mice were treated with EA stimulation at Tianshu (ST 25) and Shangjuxu (ST 37) acupoints. The first black stool defecation time, the number, weight, and water content of 8-h feces, and intestinal transit rate were used to assess intestinal transit. Colonic tissues underwent histopathological assessment, and the expressions of autophagy markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunohistochemical staining. The expressions of phosphoinositide 3-kinases (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway members were investigated by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. The relationship between enteric glial cells (EGCs) and autophagy was observed by confocal immunofluorescence microscopy, localization analysis, and electron microscopy. RESULTS: EA treatment shortened the first black stool defecation time, increased the number, weight, and water content of 8-h feces, and improved the intestinal transit rate in FC mice (P<0.01). In terms of a putative autophagy mechanism, EA treatment promoted the expressions of LC3 and Beclin-1 proteins in the colonic tissue of FC mice (P<0.05), with glial fibrillary acidic protein (GFAP) and LC3 significantly colocalized. Furthermore, EA promoted colonic autophagy in FC mice by inhibiting PI3K/AKT/mTOR signaling (P<0.05 or P<0.01). The positive effect of EA on intestinal motility in FC mice was blocked by 3-MA. CONCLUSION: EA treatment can inhibit PI3K/AKT/mTOR signaling in the colonic tissues of FC mice, thereby promoting EGCs autophagy to improve intestinal motility.
Asunto(s)
Electroacupuntura , Proteínas Proto-Oncogénicas c-akt , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Beclina-1 , Transducción de Señal , Estreñimiento/terapia , Serina-Treonina Quinasas TOR/metabolismo , Autofagia , Neuroglía/metabolismo , Mamíferos/metabolismoRESUMEN
Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase involved in cell proliferation, invasion, angiogenesis, and metastasis in various cancers, including hepatocellular carcinoma (HCC). However, the role and molecular mechanisms of EZH2 in HCC radiosensitivity remain unclear. Here, we show that EZH2 is upregulated in HCC cells and the aberrantly overexpressed EZH2 is associated with the poor prognosis of HCC patients. Using miRNA databases, we identified miR-138-5p as a regulator of EZH2. We also found that miR-138-5p was suppressed by EZH2-induced H3K27me3 in HCC cell lines. MiR-138-5p overexpression and EZH2 knockdown enhanced cellular radiosensitivity while inhibiting cell migration, invasion, and epithelial-mesenchymal transition (EMT). Analysis of RNA-seq datasets revealed that the hypoxia-inducible factor-1 (HIF-1) signaling pathway was the main enrichment pathway for differential genes after miR-138-5p overexpression or EZH2 knockdown. Expression level of HIF-1α was significantly suppressed after miR-138-5p overexpression or silencing of EZH2. HIF-1α silencing mitigated resistance of HCC cells and inhibited EMT. This study establishes the EZH2/miR-138-5p/HIF-1α as a potential therapeutic target for sensitizing HCC to radiotherapy.
Asunto(s)
Carcinoma Hepatocelular , Proteína Potenciadora del Homólogo Zeste 2 , Subunidad alfa del Factor 1 Inducible por Hipoxia , Neoplasias Hepáticas , MicroARNs , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/radioterapia , Línea Celular Tumoral , Proteína Potenciadora del Homólogo Zeste 2/genética , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/radioterapia , MicroARNs/genética , MicroARNs/metabolismo , Tolerancia a Radiación/genéticaRESUMEN
Epidermal growth factor (EGF) plays a role in male germ cell development, but the precise function is yet to be defined. This study shows that EGF stimulates rat spermatogonial proliferation in a dose-dependent manner and significantly increased the protein levels of phosphated c-Src (p-c-Src) and phosphated signal transducer and activator of transcription 3 (p-STAT3). Moreover, overexpression of c-Src tagged with enhanced green fluorescence protein (EGFP) in rat spermatogonial stem cells enhances the cell viability. In contrast, knockdown or inhibition of c-Src inhibits rat spermatogonial stem cell proliferation; EGF could not abrogate the inhibitory effect. Evidently, the content of p-STAT3 protein was increased in c-Src-expressing cells and decreased in c-Src-suppressing cells. Furthermore, knockdown or inhibition of STAT3 also suppressed cell viability; neither EGF nor increased c-Src could reverse the inhibitory effect. These results are the first evidence that EGF induces proliferation of rat spermatogonial stem cells through c-Src/STAT3 signal.
Asunto(s)
Factor de Crecimiento Epidérmico/farmacología , Proteínas Tirosina Quinasas/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Espermatogonias/citología , Células Madre/citología , Células Madre/enzimología , Animales , Proteína Tirosina Quinasa CSK , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Masculino , Fosforilación/efectos de los fármacos , Ratas , Factor de Transcripción STAT3/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Células Madre/efectos de los fármacos , Familia-src QuinasasRESUMEN
CdTe/ZnSe core/shell quantum dots were directly synthesized in an aqueous condition by heating a mixed solution of ZnCI2, NaHSe and CdTe QDs in the presence of mercaptosuccinic acid as a stabilizer. By controlling the size and composition, the CdTe/ZnSe QDs with emission wavelength ranging from 540 to 630 nm, high quantum yield (44%) and narrow full width at half maximum (FWHM) could be obtained. Characterization results with HRTEM, XRD and EDX have shown that the synthesized CdTe/ZnSe QDs have good monodispersity and a nice crystal structure, and exhibited better stability and less cytotoxicity as compared with CdTe QDs. Furthermore, luminescent QD-IgG bioprobes were produced to detect the breast cancer marker Her2 on the surface of fixed MCF-7 cancer cells for their optical imaging.
Asunto(s)
Compuestos de Cadmio/química , Puntos Cuánticos , Compuestos de Selenio/química , Telurio/química , Compuestos de Zinc/química , Neoplasias de la Mama/química , Neoplasias de la Mama/patología , Línea Celular Tumoral , Fluorescencia , Humanos , Microscopía Electrónica de Transmisión , Agua , Difracción de Rayos XRESUMEN
OBJECTIVE: To determine the content of total salvianolic acid in different vegetative organs of Salvia miltiorrhiza and discover the dynamic change rules of tanshinol, protocatechuic aldehyde, caffeic acid and total salvianolic acid during the whole process of grwth. METHODS: HPLC-ECD was used. The separation was performed on Zorbax SB-C18 (150 mm x 4.6 mm, 5.0 microm) column by gradient elution. The mobile phase consisted of CH3OH-0.4% aqueous phosphoric acid. The flow rate was 1.0 mL/min. The detection was done at 0.7 V and the column temperature was 30 degrees C. RESULTS: The highest content of total salvianolic acid in leaf was in June and gradually dropped off till the lowest in December; The content of total salvianolic acid in leaf gradually decreased along with the growing of the leaf. The content of total salvianolic acid in root was high and consistent from July to September, but gradually dropped off till the lowest in November. CONCLUSION: The leaves of Salvia miltiorrhiza can be harvested in strong growth period to achieve the comprehensive use of the herb.
Asunto(s)
Ácidos Cafeicos/metabolismo , Lactatos/metabolismo , Hojas de la Planta/metabolismo , Plantas Medicinales/metabolismo , Salvia miltiorrhiza/metabolismo , Benzaldehídos/metabolismo , Catecoles/metabolismo , Cromatografía Líquida de Alta Presión , Hojas de la Planta/crecimiento & desarrollo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Plantas Medicinales/crecimiento & desarrollo , Salvia miltiorrhiza/crecimiento & desarrollo , Estaciones del AñoRESUMEN
The mechanisms of brucellosis transmission are diverse and complex, especially the role of young animals in the spread of brucellosis has not been well studied. In this article, a new deterministic system that incorporates various stages of susceptible individuals and time delay of infection is proposed. Under general biological assumptions, the qualitative properties and stability of the system are studied, the results illustrate that the global dynamics of equilibrium points depend on the basic reproduction number R0: If R0≤1, animal brucellosis will eventually die out; and if R0>1, animal brucellosis is persistent and eventually tends to the endemic steady state. These results suggest that distributed time delay is harmless for the dynamics of the spread of brucellosis when R0 is greater than one or less than or equal to one. Finally, periodic phenomena are found by numerical analysis if the assumptions are not true.
Asunto(s)
Brucelosis/transmisión , Modelos Biológicos , Animales , Número Básico de Reproducción/estadística & datos numéricos , Brucelosis/epidemiología , Brucelosis/veterinaria , Simulación por Computador , Enfermedades Endémicas/estadística & datos numéricos , Enfermedades Endémicas/veterinaria , Humanos , Conceptos Matemáticos , Zoonosis/epidemiología , Zoonosis/transmisiónRESUMEN
BACKGROUND: For cancer, it is common that there is usually a dysregulation of the long noncoding RNA regulator of reprogramming (LncRNA ROR). To illustrate the application of LncRNA ROR, which serves as the prognostic marker for the malignant tumors, it is of great importance to conduct a meta-analysis. METHODS: There were 3 databases being applied. The data used were collected before January 5, 2018. These 3 databases include the OVID, PubMed, and Science databse. To further explore the association between the expression and survival of LncRNA ROR, it calculated the 95% confidence intervals (CIs) and hazard ratios (HRs). Meanwhile, the odds ratios (ORs) have been calculated for the evaluation of the correlation between the pathological and expression parameters of LncRNA ROR. RESULTS: There were 8 researches participated by 720 patients. According to the HR, it has been implied that there was a high LncRNA ROR expression related with the weak disease-free survival (DFS) (HRâ=â3.48, 95% CI, 2.24-5.41) and overall survival (OS) (HRâ=â2.47, 95% CI, 1.76-3.47) among the cancer patients with none dramatic heterogeneity. There was also a correlation among lymph node metastasis (ORâ=â5.38, 95% CI, 2.21-13.12), high tumor stage (ORâ=â3.80, 95% CI, 1.95-7.41), and larger tumor size (ORâ=â4.43, 95% CI, 1.26-15.51). CONCLUSIONS: Thus, it can be predicted about the lymph node metastasis and high tumor stage, larger tumor size, DFS, and poor OS based on the high LncRNA ROR. This suggests that high LncRNA ROR can be used as a new indicator of poor prognosis in cancer.
Asunto(s)
Neoplasias/genética , Neoplasias/patología , ARN Largo no Codificante/genética , Biomarcadores de Tumor , China , Humanos , Metástasis Linfática , Estadificación de Neoplasias , Análisis de Supervivencia , Carga TumoralRESUMEN
The present study aimed to investigate the effect of proto-oncogene c-src on the viability of rat spermatogonial stem cells from 9 day-old rat in vitro. MTT method was used to observe the viability of the spermatogonial stem cells treated with antisense c-src oligodeoxynucleotides (ODNs) in vitro; RT-PCR was utilized to observe the expression of c-src mRNA and Western blot was used to observe the protein expressions of pp60c-src and phosphorylated signal transducer and activator of transcription-3 (p-STAT3). Compared with that in control group, the viability of spermatogonial stem cells decreased by 8.1% (P<0.05) and the expression of c-src mRNA decreased significantly after treatment with 10 µmol/L antisense c-src ODNs for 12 h. Compared with that in the control group, the protein expressions of pp60c-src and p-STAT3 decreased by 33.8% and 45.3% (both P<0.01), respectively, in the spermatogonial stem cells after being transfected with antisense c-src ODNs. The results suggest that proto-oncogene c-src regulates the viability of rat spermatogonial stem cells through p-STAT3.
Asunto(s)
Proteínas Proto-Oncogénicas pp60(c-src)/metabolismo , Factor de Transcripción STAT3/metabolismo , Espermatogonias/citología , Células Madre/citología , Animales , Células Cultivadas , Genes src , Masculino , Fosforilación , ARN Mensajero , Ratas , Espermatogonias/metabolismo , Células Madre/metabolismo , TransfecciónRESUMEN
OBJECTIVE: To study the alterations and the clinical significance of peripheral lymphocyte subsets in patients with active cytomegalovirus (CMV) infection during the early stage of allogeneic peripheral blood stem cell transplantation (PBSCT) and to investigate the influence of active CMV infection on immunity. METHODS: K(3)-EDTA anticoagulated peripheral blood samples were collected weekly from 27 allogeneic PBSCT recipients in the first 3 months after PBSCT. CMV pp65 antigen in peripheral white blood cells were tested by indirect immunofluorescence assay, and lymphocyte subsets were detected by flow cytometry with specific fluorescent monoclonal antibodies. In the meantime lymphocyte subsets of 51 samples from healthy blood donors were tested as normal control values. RESULTS: CD(4)(+) T cell count for all recipients was significantly low throughout the first 3 months after PBSCT as compared with normal donors (P < 0.01). Of the 27 allogeneic PBSCT recipients, 5 had no active CMV infection, 10 had asymptomatic CMV active infection, 12 had symptomatic CMV infection. The average CD(4)(+) T cell counts (x 10(6)/L) for the different groups of patients were 328 +/- 203, 239 +/- 218 and 199 +/- 92; The average CD(8)(+) T cell counts (x 10(6)/L) were 400 +/- 380, 267 +/- 206 and 603 +/- 461, respectively. The average percentage of CD(4)(+) CD(28)(+) T cell subsets were (89.2 +/- 8.9)%, (84.2 +/- 10.1)% and (63.5 +/- 11.4)%, respectively. The recipients with asymptomatic CMV active infection were likely to have more natural killer (NK) cells as compared with those without active CMV infection (P < 0.01). The patients with symptomatic CMV infection had significantly lower CD(4)(+) cell count and higher CD(8)(+) cell count than those with asymptomatic CMV infection (P < 0.01). The percentage of CD(4)(+) CD(28)(+) cells was decreased significantly in the CMV active infection group (P < 0.01). CONCLUSIONS: CMV active infection could induce dramatic alterations in lymphocyte subsets lymphocyte subsets and host immunity for allogeneic PBSCT recipients. Therefore, the changes of lymphocyte subsets might serve as auxiliary parameters to predict active CMV infections in this kind of immunocompromised patients.
Asunto(s)
Infecciones por Citomegalovirus/inmunología , Trasplante de Células Madre de Sangre Periférica , Subgrupos de Linfocitos T/inmunología , Adolescente , Adulto , Recuento de Linfocito CD4 , Linfocitos T CD8-positivos/inmunología , Femenino , Humanos , Células Asesinas Naturales/inmunología , Masculino , Persona de Mediana Edad , Fosfoproteínas/sangre , Proteínas de la Matriz Viral/sangreAsunto(s)
Proteínas Quinasas Dependientes de Calcio-Calmodulina/antagonistas & inhibidores , Carcinoma/patología , Inhibidores Enzimáticos/farmacología , Flavonoides/farmacología , Neoplasias Ováricas/patología , Ciclo Celular/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-fos/metabolismoRESUMEN
We evaluated the correlation between computed tomography (CT) perfusion parameters and markers of angiogenesis in adrenal adenomas and non-adenomas to determine if perfusion CT can be used to distinguish between them. Thirty-four patients with pathologically-confirmed adrenal tumors (17 adenomas, 17 non-adenomas) received CT perfusion imaging before surgery. CT perfusion parameters (blood flow [BF], blood volume [BV], mean transit time [MTT], and permeability surface area product [PS]) were calculated. Tumor tissue sections were examined with immunohistochemical methods for vascular endothelial growth factor (VEGF) expression and microvessel density (MVD). The mean age of the 34 patients was 43 years. The median BV was significantly higher in adenomas than in non-adenomas [12.3 ml/100 g, inter-quartile range (IQR): 10.4 to 16.5 ml/100 g vs. 8.8 ml/100 g, IQR: 3.3 to 9.4 ml/100 g, p=0.001]. Differences in BF, MTT, and PS parameter values between adenomas and non-adenomas were not significant (p>0.05). The mean MVD was significantly higher in adenomas compared to non-adenomas (98.5 ± 28.5 vs. 53.5 ± 27.0, p<0.0001). Adenomas also expressed significantly higher median VEGF than non-adenomas (65%, IQR: 50 to 79% vs. 45%, IQR: 35 to 67%, p=0.02). A moderately strong correlation between BF and VEGF (r=0.53, p=0.03) and between BV and MVD among adenomas (r=0.57, p=0.02) exist. Morphology, MVD, and VEGF expression in adenomas differ significantly from non-adenomas. Of the CT perfusion parameters examined, both BF and BV correlate with MVD, but only BF correlates with VEGF, and only in adenomas. The significant difference in BV suggests that BV may be used to differentiate adenomas from non-adenomas. However, the small difference in BV shows that it may only be possible to use BV to identify adenomas vs. non-adenomas at extreme BV values.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/metabolismo , Neoplasias de las Glándulas Suprarrenales/patología , Adenoma Corticosuprarrenal/metabolismo , Adenoma Corticosuprarrenal/patología , Microvasos/patología , Neovascularización Patológica/patología , Factores de Crecimiento Endotelial Vascular/metabolismo , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Adenoma Corticosuprarrenal/diagnóstico por imagen , Adulto , Volumen Sanguíneo/fisiología , Femenino , Humanos , Masculino , Microvasos/diagnóstico por imagen , Microvasos/metabolismo , Neovascularización Patológica/diagnóstico por imagen , Neovascularización Patológica/metabolismo , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: CT perfusion imaging has been used in diagnosis and classification of tumors widely and in assess tumor angiogenesis in some organs. However, there are few reports describing CT perfusion imaging of adrenal gland tumors. OBJECTIVE: This study aimed to evaluate the application of CT perfusion imaging in analysis of angiogenesis in adrenal tumors and in diagnosis of adrenal tumors. PATIENTS AND METHODS: Forty four patients with adrenal gland tumors (26 with adenomas and 18 with nonadenomas) were enrolled in this study. CT scan of adrenal glands was performed with the perfusion of non-ionic contrast medium Ultravist. The obtained images were processed with deconvolution algorithms-based perfusion software and then perfusion parameter maps and values (blood flow, blood volume, mean transit time, and permeability surface-area production) were generated and analyzed respectively. RESULTS: Univariate multivariate logistic regression indicated that blood volume (OR: 1.261, 95% CI: 1.056, 1.505, P=0.010) was associated with the likelihood of adrenal adenoma. Receiver operating characteristic analysis showed that the blood volume value of ≥9.325 ml min(-1) 100 g(-1) predicted adrenal adenoma with sensitivity of 76.9% and specificity of 73.2%. In addition, permeability surface-area production in adenoma was higher than in non-adenoma (27.11±15.45 vs. 16.76±14.44 ml min(-1) 100 g(-1), P<0.05). The other parameters had no clear prognostic significance. CONCLUSIONS: CT perfusion imaging can quantitatively distinguish adrenal gland tumors with different histological characteristics. Especially, blood volume can be used in differentiating adrenal adenomas from nonadenomas.
Asunto(s)
Adenoma/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Neovascularización Patológica/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adenoma/patología , Neoplasias de las Glándulas Suprarrenales/patología , Algoritmos , Volumen Sanguíneo , Medios de Contraste , Diagnóstico Diferencial , Femenino , Humanos , Yohexol/análogos & derivados , Modelos Logísticos , Masculino , Persona de Mediana Edad , Neovascularización Patológica/patología , Curva ROC , Interpretación de Imagen Radiográfica Asistida por Computador , Sensibilidad y Especificidad , Programas InformáticosRESUMEN
IQGAPs, GTPase-activating proteins with an IQ motif, are thought to regulate many actin cytoskeleton-based activities through interactions with Cdc42 and Rac. Recently, Cdc42 was implicated in regulation of gastric parietal cell HCl secretion, and IQGAP2 was immunolocalized with Cdc42 to F-actin-rich intracellular canalicular membranes of isolated gastric parietal cells in primary culture. Here we sought to define distribution and localization of IQGAP1 and IQGAP2 in major oxyntic (acid-secreting) gastric mucosal cell types and to determine whether secretory agonists modulate these proteins. Differential staining protocols were used to identify different cell populations (parietal, chief, surface/pit, and mucous neck cells) in semi-intact glands isolated from rabbit gastric mucosae and to characterize these same cells after dispersion and fractionation on isopycnic density gradients with simultaneous staining for F-actin, H+-K+-ATPase, and GSII lectin-binding sites. There was a pronounced increase in intracellular F-actin staining in dispersed chief cells, apparently from internalization of F-actin-rich apical membranes that normally abut the gland lumen. Therefore, other membrane-associated proteins might also be redistributed by disruption of cell-cell contacts. Western blot analyses were used to quantitate relative concentrations of IQGAPs in defined mucosal cell fractions, and gastric glands were used for in situ localizations. We detected uniform levels of IQGAP2 expression in oxyntic mucosal cells with predominant targeting to regions of cell-cell contact and nuclei of all cell types. IQGAP2 was not detected in parietal cell intracellular canaliculi. IQGAP1 expression was variable and targeted predominantly to the cortex of chief and mucous neck cells. Parietal cells expressed little or no IQGAP1 vs. other mucosal cell types. Phosphoprotein affinity chromatography, isoelectric focusing, and phosphorylation site analyses indicated that both IQGAP1 and IQGAP2 are phosphoproteins potentially regulated by [Ca2+]i/PKC and cAMP signaling pathways, respectively. Stimulation of glands with carbachol, which elevates [Ca2+]i and activates PKC, induced apparent translocation of IQGAP1, but not IQGAP2, to apical poles of chief (zymogen) and mucous neck cells. This response was mimicked by PMA but not by ionomycin or by elevation of [cAMP]i with forskolin. Our observations support a novel, PKC-dependent role for IQGAP1 in regulated exocytosis and suggest that IQGAP2 may play a more general role in regulating cell-cell interactions and possibly migration within the gastric mucosa.