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1.
Heliyon ; 10(9): e29995, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38694098

RESUMEN

Rumor governance is an important guarantee for social stability and public safety. Based on the life cycle and crisis cycle model, this paper conducts a synergistic analysis of China's rumor governance policies and regulations and the core scientific research literature on rumor governance in WOS and CNKI. In this paper, we use the TF-IDF algorithm to count the word frequencies of 326 policy and regulation texts, the Jieba-RoBERTa-Kmeans model to cluster high-frequency keywords, and CiteSpace software and the LLR clustering algorithm are utilized to extract and cluster keywords from 391 documents in the WOS database and from 703 documents in the CNKI database. Based on the synergistic analysis of the life cycle model, it is found that the research on policies and regulations precedes the research on literature, and both are in the period of refinement.Based on the synergistic analysis using the co-occurrence comparison of subject terms in the crisis cycle model, it is found that there is a lack of research in the stages of prevention, monitoring, and governance, and this paper proposes the systematic governance mechanism and strategy for crisis resolution that conforms to the trend of life cycle evolution and is synergistic with policy and literature. This study has only selected Chinese policies and regulations, and the proposed governance strategies have not yet been verified in practice; future research can expand the scope and depth of the study and conduct empirical research and pilot projects.

2.
J Cancer Res Ther ; 19(1): 132-140, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37006053

RESUMEN

Purpose: To analyze the imaging characteristics of Xp11.2/TFE3 translocation renal cell carcinoma and explore the relationship between the pathological features and imaging findings. Materials and Methods: Imaging, pathological, and clinical data of 28 patients with Xp11.2 RCC were studied from August 2013 to November 2019. The imaging characteristics and morbidity of different group were also explored meanwhile. Results: Patients ranged from 3 to 83 years old and the median age was 47 years. Bilateral renal tumors were detected in 1 patient and unilateral in the rest 27 patients. Out of 29 tumors, 13 were in the left kidneys and 16 in the right. Tumor size ranged from 2.2 cm × 2.5 cm to 20.0 cm × 9.7 cm. Tumors were cystic component/necrosis (29/29,100%), renal capsule breakage (16/29, 55%), capsule (18/29, 62%), calcification (15/29, 52%), fat (4/29, 14%), and metastasis (10/29, 34%). Tumors showed moderate enhancement during renal corticomedullary phase and delayed enhancement during nephrographic and excretory phase. The solid parts showed hypointense on T2WI. The imaging characteristics did not have significant correlation with the age, the incidence of adolescent and children group was higher than adult group. Conclusion: Xp11.2 RCC is a well-defined mass with cystic component, the solid part of tumor showed hypointense on T2WI. Xp11.2 RCC showed moderate enhancement during the renal corticomedullary phase and delayed enhancement during the nephrographic phase and excretory phase. Xp11.2 RCC has a higher incidence in children.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Adulto , Adolescente , Niño , Humanos , Persona de Mediana Edad , Preescolar , Adulto Joven , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Translocación Genética , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Fusión Génica , Estudios Retrospectivos , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/genética , Neoplasias Renales/patología
3.
Endocr Pract ; 29(6): 428-435, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37004871

RESUMEN

OBJECTIVE: To develop and validate a risk stratification system for the prediction of malignancy in partially cystic thyroid nodules (PCTNs). METHODS: We retrospectively reviewed the sonography data of patients with PCTNs from 2 medical centers-Hangzhou Traditional Chinese Medicine Hospital and Hangzhou First People's Hospital-from January 2020 to December 2021. The independent risk factors for malignant PCTNs were evaluated using the univariate and multivariate logistic regression analyses. The nomogram prediction efficiency was assessed using the area under the curve and calibration curves. The decision curve analysis was used to determine the clinical value of the predictive model. RESULTS: A total of 285 patients were enrolled in this retrospective study, and of 301 PCTNs, 242 were benign and 59 were malignant. Younger age, hypoechoic, irregular margin, and microcalcifications were found to be the independent risk factors for malignant PCTNs. The area under the curve, sensitivity, and specificity were 0.860, 77.1%, and 84.7% in the training data set and 0.897, 91.7%, and 87.0% in the external validation data set, respectively. The total point of nomogram was >161, which showed the best to predict malignancy in PCTNs. CONCLUSION: Our findings demonstrated that the risk stratification system for the assessment of PCTNs showed good prediction capacities.


Asunto(s)
Neoplasias de la Tiroides , Nódulo Tiroideo , Humanos , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/patología , Estudios Retrospectivos , Ultrasonografía , Medición de Riesgo , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/patología , Nomogramas
4.
Micromachines (Basel) ; 14(2)2023 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-36838012

RESUMEN

In order to study the performance of ultra-fine 2,2', 4,4', 6,6'-hexanitrostilbene (HNS-IV) explosives initiated by a microflyer driven by microsized lead azide (Pb(N3)2), a corresponding simulation model was established in Autodyn software, and the accuracy of the simulation model was verified with a photonic Doppler velocimeter (PDV). Various influencing factors were studied in combination with the power flux-action time (Π-τ) initiation criterion. The results showed that the exponential growth rate of the flyer velocity decreased with an increase in the diameter and height of the lead azide and that the influence of the charge diameter was more obvious than that of the charge height. The flyer velocity increased linearly with the density of the lead azide. The velocity of the flyer also increased linearly with an increase in the shock wave impedance of the restraint materials, and the velocities of the flyer that corresponded to silicon and organic glass were lower than those of the metal materials. The flyer's velocity and power flux increased with a decrease in the flyer's density; when considering the flyer's velocity, power flux, and actual shear effect, titanium was the best material for the flyer. As the thickness of the flyer was decreased, the velocity and power flux of the flyer increased; under the premise of satisfying the forming effect, the thinner flyer was selected. When used as the material for the acceleration chamber, silicon showed a lower flyer velocity and power flux than sapphire, nickel, stainless steel, and other materials. With the increase in the acceleration chamber aperture, the exponentially declining trend in the flyer's velocity increased; when the aperture of the accelerating chamber was consistent with the diameter of the primary explosive, the power flux was the largest. Finally, the ability of the microflyer to initiate the HNS-IV was verified by a steel dent test.

5.
Acta Biochim Biophys Sin (Shanghai) ; 53(9): 1177-1188, 2021 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-34244711

RESUMEN

Stroke is the second leading cause of death and long-term disability worldwide, which lacks effective treatment. Perioperative stroke is associated with much higher rates of mortality and disability. The neuroprotective role of dexmedetomidine (Dex), a highly selective agonist of alpha2-adrenergic receptor, has been reported in a stroke rat model, and it was found that pretreatment of Dex before stroke could alleviate blood-brain barrier (BBB) breakdown. However, the underlying mechanisms are still unknown. As the brain endothelial cells are the main constituents of BBB and in high demand of energy, mitochondrial function of endothelial cells plays an important role in the maintenance of BBB. Given that dynamin-related protein 1 (Drp1) is a protein mediating mitochondrial fission, with mitochondrial fusion that balances mitochondrial morphology and ensures mitochondria function, the present study was designed to investigate the possible role of Drp1 in endothelial cells involved in the neuroprotective effects of Dex in ischemic stroke. Our results showed that preconditioning with Dex reduced infarction volume, alleviated brain water content and BBB damage, and improved neurological scores in middle cerebral artery occlusion rats. Meanwhile, Dex enhanced cell activity and decreased cell apoptosis in oxygen-glucose deprivation human brain microvascular endothelial cells in vitro. These protective effects of Dex were correlated with the mitochondrial morphology integrality of endothelial cells, mediated by increased phosphorylation of serine 637 in Drp1, and could be reversed by α2-adrenergic receptor antagonist Yohimbine and AMP-activated protein kinase inhibitor Compound C. These findings suggest new molecular pathways involved in the neuroprotective effects of Dex in ischemic stroke. As Dex is routinely used as a sedative drug clinically, our findings provide molecular evidence that it has perioperative neuroprotection from ischemic stroke.


Asunto(s)
Barrera Hematoencefálica/metabolismo , Dexmedetomidina/farmacología , Dinaminas/metabolismo , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Mitocondrias/metabolismo , Fármacos Neuroprotectores/farmacología , Adenilato Quinasa/antagonistas & inhibidores , Adenilato Quinasa/metabolismo , Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Antagonistas de Receptores Adrenérgicos alfa 2/uso terapéutico , Animales , Barrera Hematoencefálica/efectos de los fármacos , Línea Celular , Citocinas/metabolismo , Dexmedetomidina/uso terapéutico , Modelos Animales de Enfermedad , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Alcaloides Indólicos/farmacología , Alcaloides Indólicos/uso terapéutico , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/patología , Accidente Cerebrovascular Isquémico/etiología , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/patología , Masculino , Mitocondrias/efectos de los fármacos , Mitocondrias/patología , Dinámicas Mitocondriales/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Fosforilación/efectos de los fármacos , Ratas Sprague-Dawley , Proteína de la Zonula Occludens-1/metabolismo
6.
Neurochem Int ; 149: 105093, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34097989

RESUMEN

Inhibition of endoplasmic reticulum (ER) stress reduces blood-brain barrier (BBB) injury caused by ischemia/reperfusion (I/R), with indistinct mechanisms. Salvinorin A (SA) relieves I/R-induced BBB leakage; however, whether it is related to the suppression of ER stress is yet unclear. To address this question, we have used both a rat model of middle cerebral artery occlusion (MCAO) and human brain microvascular endothelial cells (HBMECs) with oxygen-glucose deprivation (OGD). SA was injected by tail vein at the terminal of ischemia; Norbinaltorphimine (NB), a kappa opioid antagonist, was administered 30 min prior to SA; 4-phenylbutyric acid (4-PBA), an ER stress inhibitor, was injected intraperitoneally after the onset of ischemia; adenylate-activated protein kinase (AMPK)-specific small interfering RNAs (siRNAs) were transfected to HBMECs before OGD. The assessment was as follows: infarct volume, brain water gain, Evans blue leakage, and modified neurological severity score (mNSS) after MCAO; HBMECs apoptosis rate and permeability, ER stress-related protein, and reactive oxygen species (ROS) and calcium levels after OGD. The results showed that SA significantly reduced the BBB leakage in vivo; SA relieved the apoptotic rates and ER stress in HBMECs, protected the permeability of HBMECs, and reduced ROS and calcium ion level after OGD. Moreover, the SA function was blocked by NB in vivo and AMPK- siRNAs in vitro. We conclude that SA mitigated BBB damage and HBMEC injury after I/R and alleviated ER stress in endothelial cells via AMPK pathway.


Asunto(s)
Barrera Hematoencefálica/efectos de los fármacos , Isquemia Encefálica/metabolismo , Diterpenos de Tipo Clerodano/uso terapéutico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Accidente Cerebrovascular Isquémico/metabolismo , Animales , Barrera Hematoencefálica/metabolismo , Encéfalo/citología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Isquemia Encefálica/tratamiento farmacológico , Permeabilidad Capilar/efectos de los fármacos , Permeabilidad Capilar/fisiología , Células Cultivadas , Diterpenos de Tipo Clerodano/farmacología , Estrés del Retículo Endoplásmico/fisiología , Células Endoteliales/metabolismo , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Masculino , Ratas , Ratas Sprague-Dawley
7.
Exp Neurol ; 322: 113045, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31461637

RESUMEN

Salvinorin A (SA) is a highly selective kappa opioid receptor (KOR) agonist that has significant protective effects on cerebrovascular function after ischemic stroke, but its underlying mechanism is still unclear. This study aimed to investigate whether KOR activation improves the morphology and function of intracellular mitochondria to protect endothelial cells after cerebral ischemia. A transient ischemic brain damage was generated by establishing middle cerebral artery occlusion (MCAO) model in male Sprague-Dawley rats and oxygen glucose deprivation (OGD) model in human brain microvascular endothelial cells (HBMECs). In vivo findings revealed that SA significantly reduced the infarct size, brain edema and Evans blue effusion after MCAO. In vitro findings revealed that SA improved the cell viability and decreased the apoptotic rates in HBMECs OGD model. SA also protected membrane potential and morphology of mitochondria, reduced the ROS level after OGD. SA function was blocked by KOR inhibitor norbinaltorphimine (NB). SA upregulated the phosphorylation levels of AMPK, and Mfn2 expression. Our findings suggest that SA effectively mitigated focal cerebral ischemic injury by activating KOR which potentially preserved mitochondrial function by up-regulating AMPK/Mfn2 in endothelial cells.


Asunto(s)
Isquemia Encefálica/patología , Diterpenos de Tipo Clerodano/farmacología , Células Endoteliales/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Adenilato Quinasa/metabolismo , Animales , Isquemia Encefálica/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Endoteliales/metabolismo , GTP Fosfohidrolasas/metabolismo , Humanos , Masculino , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores Opioides kappa/agonistas , Transducción de Señal/efectos de los fármacos
8.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(5): 609-613, 2019 May 30.
Artículo en Chino | MEDLINE | ID: mdl-31140428

RESUMEN

OBJECTIVE: To explore the value of interferon-inducible protein 10 (IP-10) in the auxiliary diagnosis of tuberculosis and the judgment of the severity of disease. METHODS: From February, 2013 to February, 2017, a total of 193 patients with TB admitted in our hospital and 84 healthy control subjects were recruited consecutively. The peripheral blood plasma levels of interferon-γ (IFN-γ) and IP-10 were detected using liquid phase chip (Luminex) technique. According to the number of lung fields affected by TB, the patients were divided into group A (with lesions in 1-2 lung fields), group B (3-4 lung fields) and group C (5-6 lung fields), The expressions of IFN-γ and IP-10 in 3 groups were compared. RESULTS: The plasma levels of IP-10 were significantly higher in TB patients than in the control subjects (P < 0.05), but IFN-γ levels were comparable between the two groups (P > 0.05). Among the TB patients, plasma IP-10 levels was the highest in group C (P < 0.05), and IFN-γ levels did not differ significantly among the 3 groups (P > 0.05). CONCLUSIONS: Plasma IP-10 has a certain reference value in the auxiliary diagnosis of active tuberculosis and the judgment of the severity of the disease.


Asunto(s)
Quimiocina CXCL10 , Tuberculosis Pulmonar , Antígenos Bacterianos , Biomarcadores/sangre , Quimiocina CXCL10/sangre , Humanos , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/diagnóstico
9.
J Neuroinflammation ; 15(1): 273, 2018 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-30236124

RESUMEN

BACKGROUND: Complex mechanisms participate in microglial activation after a traumatic brain injury (TBI). TBI can induce autophagy and apoptosis in neurons and glial cells, and moderate hypothermia plays a protective role in the acute phase of TBI. In the present study, we evaluated the effect of TBI and moderate hypothermia on microglial activation and investigated the possible roles of autophagy/apoptosis and toll-like receptor 4 (TLR4). METHODS: The TBI model was induced with a fluid percussion TBI device. Moderate hypothermia was achieved under general anesthesia by partial immersion in a water bath for 4 h. All rats were killed 24 h after the TBI. RESULTS: Our results showed downregulation of the microglial activation and autophagy, but upregulation of microglial apoptosis, upon post-TBI hypothermia treatment. The expression of TLR4 and downstream myeloid differentiation primary response 88 (MyD88) was attenuated. Moderate hypothermia reduced neural cell death post-TBI. CONCLUSIONS: Moderate hypothermia can reduce the number of activated microglia by inhibiting autophagy and promoting apoptosis, probably through a negative modulation between autophagy and apoptosis. Moderate hypothermia may attenuate the pro-inflammatory function of microglia by inhibiting the MyD88-dependent TLR4 signaling pathway.


Asunto(s)
Apoptosis/fisiología , Autofagia/fisiología , Lesiones Traumáticas del Encéfalo/terapia , Hipotermia Inducida , Microglía/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Receptor Toll-Like 4/fisiología , Animales , Encéfalo/patología , Lesiones Traumáticas del Encéfalo/patología , Proteínas de Unión al Calcio/metabolismo , Caspasa 3/metabolismo , Citocinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Lateralidad Funcional , Regulación de la Expresión Génica/fisiología , Masculino , Proteínas de Microfilamentos/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología
10.
Mol Med Rep ; 18(4): 3957-3964, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30106098

RESUMEN

Focal ischemia/reperfusion (I/R) injury induced cerebral inflammation, aggravates brain damage. The aim of the present study was to investigate the protective mechanisms of dexmedetomidine (DEX) on I/R brain injury in rats. Sprague­Dawley rats were divided to seven experimental groups (18 rats/group): Sham surgery; middle cerebral artery occlusion (MCAO) surgery (90 min); DEX10 [10 µg/kg intraperitoneal (i.p.) injection 30 min prior to MCAO]; DEX50 (50 µg/kg i.p. 30 min prior to MCAO); DEX100 (100 µg/kg i.p. 30 min prior to MCAO); DEX50+Yohimbine [YOH; 5 mg/kg 10 min prior to DEX (50 µg/kg i.p.) administration and MCAO] and YOH (5 mg/kg 40 min prior to MCAO). At 24 h post­MCAO surgery, neurological deficit was examined by staining damaged brain tissues with 2,3,5­triphenyltetrazolium chloride. Neuronal apoptosis in the cerebral cortex was histologically assessed by terminal deoxynucleotidyl­transferase­mediated dUTP nick end labeling staining, and the expression levels of phosphorylated (p)­AMP­activated protein kinase (AMPK; Thr172) was detected by western blotting. In addition, the expression levels of tumor necrosis factor (TNF)­α and interleukin (IL)­1ß were assessed by ELISA. At days 1, 2 and 5 following I/R, motor functions were assessed by an observer blinded to the study. The brain infarct size, neurological deficit scores, number of apoptotic neurons, expression levels of pro­inflammatory cytokines TNF­α and IL­1ß were increased following MCAO, whereas the motor function scores were reduced. Pretreatment with DEX prior to MCAO can reverse the effects induced by I/R. Compared with rats in the Sham group, the expression levels of p­AMPK were mildly increased in the MCAO group and highly increased in the three DEX­treatment groups. Pretreatment with YOH reversed the above effects of DEX and produced a similar level of cerebral I/R injury. The results demonstrated that precondition with DEX exhibited anti­inflammatory effects on brain ischemic injury mediated by AMPK signal pathway.


Asunto(s)
Adenilato Quinasa/metabolismo , Isquemia Encefálica/tratamiento farmacológico , Dexmedetomidina/uso terapéutico , Inflamación/patología , Daño por Reperfusión/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Isquemia Encefálica/enzimología , Isquemia Encefálica/patología , Isquemia Encefálica/fisiopatología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , Dexmedetomidina/farmacología , Activación Enzimática/efectos de los fármacos , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/patología , Inflamación/enzimología , Masculino , Actividad Motora/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Fosforilación/efectos de los fármacos , Ratas Sprague-Dawley , Daño por Reperfusión/enzimología , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología
11.
J BUON ; 23(2): 444-452, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29745091

RESUMEN

PURPOSE: Prostate cancer (PCa) is the most frequently malignant neoplasm in men. MicroRNAs (miRs) have been identified to play important biological roles in a variety of tumors. Several studies showed that miR-191 was involved in the development of different cancers, but its role in prostate cancer remains unclear. METHODS: Human PCa cell lines DU145, PC-3 and LNCAP, and benign prostate hyperplasia (BPH) and human prostate epithelial cell line RWPE-1 were used. The expression level of miR-191 in 48 paired prostate tumor and adjacent normal tissues was assessed along with the clinical patient features. Synthetic miR-191 mimics and inhibitors were used to overexpress or inhibit the miR-191 level. CCK8 and colony formation assay were used to evaluate the cell growth. The ability of cell invasion was studied by transwell assay. Dual-luciferase experiment was used to identify the target gene and western blot was performed to evaluate the protein level. RESULTS: miR-191 was overexpressed in PCa tissue samples compared to the normal group as well in PCa-derived cell lines. Upregulation miR-191 in PC-3 cells significantly promoted while downregulation miR-191 in DU145 cells retarded the cell proliferation and invasion. Furthermore, TIMP3 were proved to be a direct target gene of miR-191 and knockdown of TIMP3 reversed the function of miR-191 downregulation. CONCLUSION: This study demonstrated that miR-191 promoted the cell growth and invasion ability in prostate cancer through downregulating TIMP3 and might be a potential target for the biotherapy for PCa.


Asunto(s)
MicroARNs/genética , Hiperplasia Prostática/genética , Neoplasias de la Próstata/genética , Inhibidor Tisular de Metaloproteinasa-3/genética , Anciano , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Próstata , Hiperplasia Prostática/patología , Neoplasias de la Próstata/patología
12.
J Cell Mol Med ; 20(9): 1718-28, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27072810

RESUMEN

New vaccines are needed to combat Mycobacterium tuberculosis (MTB) infections. The currently employed Bacillus Calmette-Guérin vaccine is becoming ineffective, due in part to the emergence of multidrug-resistant tuberculosis (MDR-TB) strains and the reduced immune capacity in cases of HIV coinfection. CD8(+) T cells play an important role in the protective immunity against MTB infections, and the identification of immunogenic CD8(+) T cell epitopes specific for MTB is essential for the design of peptide-based vaccines. To identify CD8(+) T cell epitopes of MTB proteins, we screened a set of 94 MTB antigens for HLA class I A*11:01-binding motifs. HLA-A*11:01 is one of the most prevalent HLA molecules in Southeast Asians, and definition of T cell epitopes it can restrict would provide significant coverage for the Asian population. Peptides that bound with high affinity to purified HLA molecules were subsequently evaluated in functional assays to detect interferon-γ release and CD8(+) T cell proliferation in active pulmonary TB patients. We identified six novel epitopes, each derived from a unique MTB antigen, which were recognized by CD8(+) T cells from active pulmonary TB patients. In addition, a significant level of epitope-specific T cells could be detected ex vivo in peripheral blood mononuclear cells from active TB patients by an HLA-A*11:01 dextramer carrying the peptide Rv3130c194-204 (from the MTB triacylglycerol synthase Tgs1), which was the most frequently recognized epitope in our peptide library. In conclusion, this study identified six dominant CD8(+) T cell epitopes that may be considered potential targets for subunit vaccines or diagnostic strategies against TB.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Antígenos HLA-A/inmunología , Mycobacterium tuberculosis/inmunología , Adulto , Anciano , Alelos , Secuencia de Aminoácidos , Antígenos Bacterianos/inmunología , Proliferación Celular , Mapeo Epitopo , Epítopos de Linfocito T/química , Epítopos de Linfocito T/inmunología , Femenino , Humanos , Interferón gamma/metabolismo , Masculino , Persona de Mediana Edad , Péptidos/química , Péptidos/inmunología , Péptidos/metabolismo , Unión Proteica , Tuberculosis Pulmonar/inmunología , Tuberculosis Pulmonar/microbiología , Adulto Joven
13.
PLoS One ; 11(2): e0148885, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26881918

RESUMEN

The aim of this study was to establish plasma cytokine/chemokine profiles in patients with 3 different presentations of active tuberculosis (TB), compared to the profiles observed in bacillus Calmette-Guérin (BCG)-vaccinated healthy individuals and patients with other pulmonary diseases (non-TB patients). To this end, plasma samples were collected from 151 TB patients including 68 pulmonary TB (PTB), 43 endobronchial TB, and 40 tuberculosis pleurisy (TP) patients, as well as 107 no-TB cases including 26 non-TB patients and 81 BCG-vaccinated healthy controls. A liquid array-based multiplexed immunoassay was used to screen plasma samples for 20 distinct cytokines and chemokines. Multinomial logistic regression was used to analyze associations between cytokines/chemokines and TB/non-TB patients. Compared to our findings with the no-TB donors, the median plasma levels of the proinflammatory cytokines/chemokines TNF-α, IL-6, IP-10, IFN-γ, and MIP-1ß were significantly elevated in TB patients, suggesting their potential use as biomarkers for diagnosing TB patients. Further comparisons with healthy donors showed that only the median TNF-α plasma level was highly produced in the plasma of all 3 types of TB patients. Plasma IL-6 production was higher only in TP patients, while the plasma levels of IP-10, IFN-γ, and MIP-1ß were markedly enhanced in both PTB and TP patients. Unexpectedly, among the above cytokines/chemokines, MIP-1ß was also highly expressed in non-TB patients, compared with healthy donors. Our results suggested that TNF-α may be an ideal biomarker for diagnosing the 3 forms of TB presentation, while the other factors (IL-6, IP-10, MCP-1, and IFN-γ) can potentially facilitate differential diagnosis for the 3 TB presentation types. Further characterization of immune responses associated with different types of TB diseases will provide a basis for developing novel TB diagnostics.


Asunto(s)
Quimiocina CCL2/sangre , Quimiocina CXCL10/sangre , Interferón gamma/sangre , Interleucina-6/sangre , Tuberculosis Pulmonar/sangre , Factor de Necrosis Tumoral alfa/sangre , Adulto , Vacuna BCG/uso terapéutico , Diagnóstico Diferencial , Femenino , Humanos , Inmunoensayo , Masculino , Mycobacterium tuberculosis/patogenicidad , Tuberculosis Pulmonar/clasificación , Tuberculosis Pulmonar/patología
14.
Zhongguo Zhong Yao Za Zhi ; 33(3): 261-4, 2008 Feb.
Artículo en Chino | MEDLINE | ID: mdl-18536461

RESUMEN

OBJECTIVE: To establish a new method using AOTF-Near infrared spectroscopy (NIRS) for quick determination of tanshinone II(A) and salvianolic acid B in Fufang Danshen tablets. METHOD: HPLC was used as a reference method to determine the contents of tanshinone II(A) and salvianolic acid B in Fu Fang Dan Shen tablets. Multivariate calibration models based on PLS1 algorithm were developed to correlate the spectra and the corresponding values determined by the reference methods. RESULT: RMSECV (root-mean-square error of cross-validation) of the models for tanshinone II(A) and salvianolic acid B were 0.0103 and 0.1868 respectively. The correlation coefficients of the calibration models were 0.9873 and 0.9832 respectively. External validation with external validation samples proved that the relative coefficient of the predicted value and the truth value were R2 = 0.9743 and R2 = 0.9886 respectively, with measured recycle rates of 103.0% and 99.0%. CONCLUSION: NIRS can be used in the determination of tanshinone II(A) and salvianolic acid B, which sets up the foundation of product-line control of Fuang Danshen tablets.


Asunto(s)
Benzofuranos/análisis , Medicamentos Herbarios Chinos/química , Fenantrenos/análisis , Espectroscopía Infrarroja Corta/métodos , Comprimidos/química , Abietanos , Reproducibilidad de los Resultados
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