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1.
J Virol ; 97(3): e0197722, 2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-36815839

RESUMEN

African swine fever (ASF) is an acute and severe infectious disease caused by the ASF virus (ASFV). The mortality rate of ASF in pigs can reach 100%, causing huge economic losses to the pig industry. Here, we found that ASFV protein MGF505-7R inhibited the beta interferon (IFN-ß)-mediated Janus-activated kinase-signal transducer and activation of transcription (JAK-STAT) signaling. Our results demonstrate that MGF505-7R inhibited interferon-stimulated gene factor 3 (ISGF3)-mediated IFN-stimulated response element (ISRE) promoter activity. Importantly, we observed that MGF505-7R inhibits ISGF3 heterotrimer formation by interacting with interferon regulatory factor 9 (IRF9) and inhibits the nuclear translocation of ISGF3. Moreover, to demonstrate the role of MGF505-7R in IFN-I signal transduction during ASFV infection, we constructed and evaluated ASFV-ΔMGF505-7R recombinant viruses. ASFV-ΔMGF505-7R restored STAT2 and STAT1 phosphorylation, alleviated the inhibition of ISGF3 nuclear translocation, and showed increased susceptibility to IFN-ß, unlike the parental GZ201801 strain. In conclusion, our study shows that ASFV protein MGF505-7R plays a key role in evading IFN-I-mediated innate immunity, revealing a new mode of evasion for ASFV. IMPORTANCE ASF, caused by ASFV, is currently prevalent in Eurasia, with mortality rates reaching 100% in pigs. At present, there are no safe or effective vaccines against ASFV. In this study, we found that the ASFV protein MGF505-7R hinders IFN-ß signaling by interacting with IRF9 and inhibiting the formation of ISGF3 heterotrimers. Of note, we demonstrated that MGF505-7R plays a role in the immune evasion of ASFV in infected hosts and that recombinant viruses alleviated the effect on type I IFN (IFN-I) signaling and exhibited increased susceptibility to IFN-ß. This study provides a theoretical basis for developing vaccines against ASFV using strains with MGF505-7R gene deletions.


Asunto(s)
Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Interferón Tipo I , Subunidad gamma del Factor 3 de Genes Estimulados por el Interferón , Replicación Viral , Animales , Fiebre Porcina Africana/inmunología , Fiebre Porcina Africana/virología , Virus de la Fiebre Porcina Africana/genética , Virus de la Fiebre Porcina Africana/inmunología , Inmunidad Innata , Interferón Tipo I/inmunología , Subunidad gamma del Factor 3 de Genes Estimulados por el Interferón/inmunología , Transducción de Señal , Porcinos , Proteínas Virales/genética , Proteínas Virales/inmunología , Replicación Viral/fisiología , Transporte Activo de Núcleo Celular/genética , Evasión Inmune/genética
2.
J Magn Reson Imaging ; 59(1): 340-349, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37183874

RESUMEN

BACKGROUND: Global brain health has gained increasing attention recently. Imaging markers of brain frailty have been related to functional outcomes in previous studies on anterior circulation; however, little data are available on imaging markers and posterior circulation. PURPOSE: To investigate the impact of brain frailty on functional outcomes in patients with acute perforating artery infarction (PAI) of the posterior circulation. STUDY TYPE: Prospective. POPULATION: One hundred patients (60.78 ± 9.51 years, 72% men) with acute posterior circulation PAI (determined by diffusion-weighted magnetic resonance imaging (MRI)/time-of-flight MR angiography). FIELD STRENGTH/SEQUENCE: T1- and T2-weighted fast spin echo, T2-weighted fluid-attenuated inversion recovery, diffusion-weighted echo planar, gradient echo (susceptibility-weight imaging), and 3D time-of-flight MR angiography sequences at 3.0 T. ASSESSMENT: Periventricular and deep white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS) in the basal ganglia and centrum semiovale area, lacunes, cerebral microbleeds (CMB), and total brain frailty score by calculating the above imaging characters were rated visually by three radiologists with 9, 10, and 11 years of experience and one neuroradiologist with 12. Infarction volume was assessed using baseline diffusion-weighted imaging (DWI) data obtained within 24 hours of symptom onset. A modified Rankin Scale (mRS) score >1 on day 90 defined an adverse functional outcome. Associations between the imaging markers of brain frailty and functional outcomes were assessed. STATISTICAL TESTS: Fisher's exact test, Mann-Whitney U test, and multivariable binary logistic regression. A P value <0.05 was considered statistically significant. RESULTS: Adverse prognoses (mRS > 1) were observed in 34 (34%) patients. Infarction volume, periventricular WMH, deep WMH, basal ganglia EPVS, CMB, and the brain frailty score were significantly associated with adverse functional outcomes. An increased brain frailty score was significantly associated with unfavorable mRS score on day 90 (odds ratio 1.773, 95% confidence interval 1.237-2.541). DATA CONCLUSION: Advanced MRI imaging markers of brain frailty, individually or combined as a total brain frailty score, were associated with worse functional outcomes after acute posterior circulation PAI. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.


Asunto(s)
Fragilidad , Masculino , Humanos , Femenino , Estudios Prospectivos , Fragilidad/diagnóstico por imagen , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Arterias , Infarto
3.
Eur Radiol ; 34(9): 6026-6035, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38337069

RESUMEN

OBJECTIVES: We aim to investigate whether cerebral small vessel disease (cSVD) imaging markers correlate with deep medullary vein (DMV) damage in small vessel occlusion acute ischemic stroke (SVO-AIS) patients. METHODS: The DMV was divided into six segments according to the regional anatomy. The total DMV score (0-18) was calculated based on segmental continuity and visibility. The damage of DMV was grouped according to the quartiles of the total DMV score. Neuroimaging biomarkers of cSVD including white matter hyperintensity (WMH), cerebral microbleed (CMB), perivascular space (PVS), and lacune were identified. The cSVD score were further analyzed. RESULTS: We included 229 SVO-AIS patients, the mean age was 63.7 ± 23.1 years, the median NIHSS score was 3 (IQR, 2-6). In the severe DMV burden group (the 4th quartile), the NIHSS score grade (6 (3-9)) was significantly higher than other groups (p < 0.01). The grade scores for basal ganglia PVS (BG-PVS) were positively correlated with the degree of DMV (R = 0.67, p < 0.01), rather than centrum semivole PVS (CS-PVS) (R = 0.17, p = 0.1). In multivariate analysis, high CMB burden (adjusted odds ratio [aOR], 25.38; 95% confidence interval [CI], 1.87-345.23) was associated with severe DMV scores. In addition, BG-PVS was related to severe DMV burden in a dose-dependent manner: when BG-PVS score was 3 and 4, the aORs of severe DMV burden were 18.5 and 12.19, respectively. CONCLUSION: The DMV impairment was associated with the severity of cSVD, which suggests that DMV burden may be used for risk stratification in SVO-AIS patients. CLINICAL RELEVANCE STATEMENT: The DMV damage score, based on the association between small vessel disease and the deep medullary veins impairment, is a potential new imaging biomarker for the prognosis of small vessel occlusion acute ischemic stroke, with clinical management implications. KEY POINTS: • The damage to the deep medullary vein may be one mechanism of cerebral small vessel disease. • Severe burden of the basal ganglia perivascular space and cerebral microbleed is closely associated with significant impairment to the deep medullary vein. • The deep medullary vein damage score may reflect a risk of added vascular damage in small vessel occlusion acute ischemic stroke patients.


Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Femenino , Persona de Mediana Edad , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Anciano , Venas Cerebrales/diagnóstico por imagen , Venas Cerebrales/patología , Imagen por Resonancia Magnética/métodos , Bulbo Raquídeo/diagnóstico por imagen , Bulbo Raquídeo/irrigación sanguínea , Bulbo Raquídeo/patología , Estudios Retrospectivos
4.
Bioorg Chem ; 149: 107500, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38823310

RESUMEN

This study aimed to develop the first dual-target small molecule inhibitor concurrently targeting Discoidin domain receptor 1 (DDR1) and Epidermal growth factor receptor (EGFR), which play a crucial interdependent roles in non-small cell lung cancer (NSCLC), demonstrating a synergistic inhibitory effect. A series of innovative dual-target inhibitors for DDR1 and EGFR were discovered. These compounds were designed and synthesized using structural optimization strategies based on the lead compound BZF02, employing 4,6-pyrimidine diamine as the core scaffold, followed by an investigation of their biological activities. Among these compounds, D06 was selected and showed micromolar enzymatic potencies against DDR1 and EGFR. Subsequently, compound D06 was observed to inhibit NSCLC cell proliferation and invasion. Demonstrating acceptable pharmacokinetic performance, compound D06 exhibited its anti-tumor activity in NSCLC PC-9/GR xenograft models without apparent toxicity or significant weight loss. These collective results showcase the successful synthesis of a potent dual-targeted inhibitor, suggesting the potential therapeutic efficacy of co-targeting DDR1 and EGFR for DDR1/EGFR-positive NSCLC.


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Proliferación Celular , Receptor con Dominio Discoidina 1 , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Receptores ErbB , Neoplasias Pulmonares , Inhibidores de Proteínas Quinasas , Humanos , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Receptor con Dominio Discoidina 1/antagonistas & inhibidores , Receptor con Dominio Discoidina 1/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/síntesis química , Animales , Estructura Molecular , Ratones , Descubrimiento de Drogas , Ratones Desnudos , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Neoplasias Experimentales/metabolismo , Línea Celular Tumoral , Ratones Endogámicos BALB C
5.
Clin Exp Pharmacol Physiol ; 51(8): e13907, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38965675

RESUMEN

OBJECTIVE: Most cases of hepatocellular carcinoma (HCC) arise as a consequence of cirrhosis. In this study, our objective is to construct a comprehensive diagnostic model that investigates the diagnostic markers distinguishing between cirrhosis and HCC. METHODS: Based on multiple GEO datasets containing cirrhosis and HCC samples, we used lasso regression, random forest (RF)-recursive feature elimination (RFE) and receiver operator characteristic analysis to screen for characteristic genes. Subsequently, we integrated these genes into a multivariable logistic regression model and validated the linear prediction scores in both training and validation cohorts. The ssGSEA algorithm was used to estimate the fraction of infiltrating immune cells in the samples. Finally, molecular typing for patients with cirrhosis was performed using the CCP algorithm. RESULTS: The study identified 137 differentially expressed genes (DEGs) and selected five significant genes (CXCL14, CAP2, FCN2, CCBE1 and UBE2C) to construct a diagnostic model. In both the training and validation cohorts, the model exhibited an area under the curve (AUC) greater than 0.9 and a kappa value of approximately 0.9. Additionally, the calibration curve demonstrated excellent concordance between observed and predicted incidence rates. Comparatively, HCC displayed overall downregulation of infiltrating immune cells compared to cirrhosis. Notably, CCBE1 showed strong correlations with the tumour immune microenvironment as well as genes associated with cell death and cellular ageing processes. Furthermore, cirrhosis subtypes with high linear predictive scores were enriched in multiple cancer-related pathways. CONCLUSION: In conclusion, we successfully identified diagnostic markers distinguishing between cirrhosis and hepatocellular carcinoma and developed a novel diagnostic model for discriminating the two conditions. CCBE1 might exert a pivotal role in regulating the tumour microenvironment, cell death and senescence.


Asunto(s)
Biomarcadores de Tumor , Carcinoma Hepatocelular , Cirrosis Hepática , Neoplasias Hepáticas , Aprendizaje Automático , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/genética , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Diagnóstico Diferencial , Regulación Neoplásica de la Expresión Génica , Perfilación de la Expresión Génica , Análisis de Secuencia por Matrices de Oligonucleótidos
6.
J Magn Reson Imaging ; 57(4): 1241-1247, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-35849055

RESUMEN

BACKGROUND: Arterial spin labeling (ASL) has shown potential for the assessment of penumbral tissue in patients with acute ischemic stroke (AIS). The postlabeling delay (PLD) parameter is sensitive to arterial transit delays and influences cerebral blood flow measurements. PURPOSE: To assess the impact of ASL acquisition at different PLDs for penumbral tissue quantification and to compare their performance regarding assisting patient selection for endovascular treatment with dynamic susceptibility contrast MRI (DSC-MRI) as the reference method. STUDY TYPE: Retrospective. POPULATION: A total of 53 patients (59.98 ± 12.60 years, 32% women) with AIS caused by internal carotid or middle cerebral artery occlusion. FIELD STRENGTH/SEQUENCE: A 3-T, three-dimensional pseudo-continuous ASL with fast-spin echo readout. ASSESSMENT: Hypoperfusion volume was measured using DSC-MRI and ASL with PLDs of 1.500 msec and 2.500 msec, respectively. Eligibility for endovascular treatment was retrospectively determined according to the imaging criteria of the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke trial (DEFUSE 3). STATISTICAL TESTS: Kruskal-Wallis tests, Bland-Altman plots, Cohen's kappa, and receiver operating characteristic analyses were used. The threshold for statistical significance was set at P Ë‚ 0.05. RESULTS: Hypoperfusion volume for ASL with a PLD of 1.500 msec was significantly larger than that for DSC-MRI, while the hypoperfusion volume for a PLD of 2.500 msec was not significantly different from that of DSC-MRI (P = 0.435). Bland-Altman plots showed that the mean volumetric error between the hypoperfusion volume measured by DSC-MRI and ASL with PLDs of 1.500/2.500 msec was -107.0 mL vs. 4.49 mL. Cohen's kappa was 0.679 vs. 0.773 for DSC-MRI and ASL, respectively, with a PLD of 1.500/2.500 msec. The sensitivity and specificity for ASL with a PLD of 1.500/2.500 msec in identifying patients eligible for treatment were 89.74% vs. 97.44% and 92.86% vs. 64.29%, respectively. DATA CONCLUSION: In AIS, PLDs for ASL acquisition may have a considerable impact on the quantification of the hypoperfusion volume. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.


Asunto(s)
Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Femenino , Masculino , Estudios Retrospectivos , Imagen por Resonancia Magnética , Arterias , Marcadores de Spin , Circulación Cerebrovascular/fisiología
7.
Eur Radiol ; 32(8): 5436-5445, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35278120

RESUMEN

OBJECTIVES: The prognostic value of fluid-attenuated inversion recovery vessel hyperintensity (FVH) remains controversial in acute ischemic stroke (AIS). The objective was to investigate whether the presence of FVH could predict long-term functional outcomes in patients with AIS receiving medical therapy. METHODS: Consecutive AIS patients with anterior circulation large vessel stenosis (LVS) in multiple centers between January 2019 and December 2020 were studied. Presence of FVH was identified and evaluated as FVH (+). Quantification of FVH was performed using an FVH-Alberta Stroke Program Early CT Score (ASPECTS) system and divided into grades: FVH-ASPECTS of 0 = grade 0; 1-2 = grade 1; 3-7 = grade 2. Poor functional outcome was defined as modified Rankin scale > 2 at 3 months. RESULTS: Overall, 175 patients were analyzed (age, 64.31 ± 13.47 years; men, 65.1%), and 78.9% patients presented with FVH. Larger infarct volume (19.90 mL vs. 5.50 mL, p < 0.001), higher rates of FVH (+) (92.0% vs. 65.9%, p < 0.001), and higher FVH grades (grade 2, 34.5% vs. 10.2%, p < 0.001) were more prone to be observed in patients with poor functional outcomes. FVH (+) with infarct volume larger than 6.265 mL (adjusted odds ratio [aOR] 6.03, 95% confidence interval [CI] 1.82-19.98) and FVH grade (grade 1, aOR 3.07, 95% CI 1.12-8.43; grade 2, aOR 5.80, 95% CI 1.59-21.11) were independently associated with poor functional outcomes. CONCLUSION: FVH (+) combined with large infarct volume and high FVH grade can predict poor long-term functional outcomes in patients with LVS who receive medical therapy. KEY POINTS: • FVH is expected to be a contrast agent-independent alternative for assessing hemodynamic status in the acute stage of stroke. • FVH (+) and high FVH grade, quantified by FVH-ASPECTS rating system and grades, are associated with large infarct volume. • The combination of FVH and DWI-based infarct volume has independent predictive value for long-term functional outcomes in AIS patients with large artery stenosis treated with medical therapy.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Anciano , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/tratamiento farmacológico , Constricción Patológica , Humanos , Infarto , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico
8.
J Gastroenterol Hepatol ; 29(4): 742-8, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24224980

RESUMEN

BACKGROUND AND AIM: This study sought to investigate the effects of hypothermia induced by adenosine 5'-monophosphate (5'-AMP) on L-arginine (L-Arg)-induced acute pancreatitis in rats. METHODS: The rats were divided into four groups: the control group, the acute pancreatitis group, the 5'-AMP pretreatment group, and the 5'-AMP posttreatment group. Rats in all groups, except for the control group, received two injections of 2.5 g/kg body weight (intraperitoneally) L-Arg, with an interval of 1 h between the injections. Subsequently, the rats were observed to assess whether hypothermia induced by 5'-AMP could effectively inhibit inflammation associated with L-Arg-induced acute pancreatitis in rats. RESULTS: Hypothermia induced by 5'-AMP produced protective effects in our acute pancreatitis model. These effects exhibited the following manifestations: (i) a significant reduction in rat mortality rates; (ii) a significant decrease in the occurrence of pancreatic edema; (iii) significant reductions in serum amylase (P < 0.001), interleukin-6 (P < 0.001), interleukin-1ß (P < 0.001) and tumor necrosis factor-α (P < 0.001); (iv) the significant inhibition of nuclear factor-κB (NF-κB) activation in rats that were pre- and posttreated with 5'-AMP compared with rats that were only injected with L-Arg; and (v) significant decreases in the occurrence of pancreatic interstitial edema, inflammatory cell infiltration, hemorrhage, and acinar cell necrosis. CONCLUSIONS: Hypothermia induced by 5'-AMP could inhibit the acute inflammatory reaction and NF-κB activation associated with acute pancreatitis.


Asunto(s)
Adenosina Monofosfato/uso terapéutico , Arginina/efectos adversos , Modelos Animales de Enfermedad , Hipotermia Inducida , Pancreatitis/inducido químicamente , Pancreatitis/terapia , Enfermedad Aguda , Adenosina Monofosfato/administración & dosificación , Amilasas/sangre , Animales , Mediadores de Inflamación/metabolismo , Interleucina-1beta , Interleucina-6/metabolismo , Masculino , FN-kappa B/metabolismo , Pancreatitis/genética , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/metabolismo
9.
J Transl Int Med ; 12(2): 197-208, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38779116

RESUMEN

Background and Objectives: The Alberta Stroke Program CT Score (ASPECTS) is a widely used rating system for assessing infarct extent and location. We aimed to investigate the prognostic value of ASPECTS subregions' involvement in the long-term functional outcomes of acute ischemic stroke (AIS). Materials and Methods: Consecutive patients with AIS and anterior circulation large-vessel stenosis and occlusion between January 2019 and December 2020 were included. The ASPECTS score and subregion involvement for each patient was assessed using posttreatment magnetic resonance diffusion-weighted imaging. Univariate and multivariable regression analyses were conducted to identify subregions related to 3-month poor functional outcome (modified Rankin Scale scores, 3-6) in the reperfusion and medical therapy cohorts, respectively. In addition, prognostic efficiency between the region-based ASPECTS and ASPECTS score methods were compared using receiver operating characteristic curves and DeLong's test. Results: A total of 365 patients (median age, 64 years; 70% men) were included, of whom 169 had poor outcomes. In the reperfusion therapy cohort, multivariable regression analyses revealed that the involvement of the left M4 cortical region in left-hemisphere stroke (adjusted odds ratio [aOR] 5.39, 95% confidence interval [CI] 1.53-19.02) and the involvement of the right M3 cortical region in right-hemisphere stroke (aOR 4.21, 95% CI 1.05-16.78) were independently associated with poor functional outcomes. In the medical therapy cohort, left-hemisphere stroke with left M5 cortical region (aOR 2.87, 95% CI 1.08-7.59) and caudate nucleus (aOR 3.14, 95% CI 1.00-9.85) involved and right-hemisphere stroke with right M3 cortical region (aOR 4.15, 95% CI 1.29-8.18) and internal capsule (aOR 3.94, 95% CI 1.22-12.78) affected were related to the increased risks of poststroke disability. In addition, region-based ASPECTS significantly improved the prognostic efficiency compared with the conventional ASPECTS score method. Conclusion: The involvement of specific ASPECTS subregions depending on the affected hemisphere was associated with worse functional outcomes 3 months after stroke, and the critical subregion distribution varied by clinical management. Therefore, region-based ASPECTS could provide additional value in guiding individual decision making and neurological recovery in patients with AIS.

10.
Rheumatol Int ; 33(8): 2085-92, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23408150

RESUMEN

To investigate whether the hypothermia induced by Adenosine 5'-Monophosphate (5'-AMP) could attenuate early stage injury in a rat acute gouty arthritis model. Ankle joint injection with monosodium urate monohydrate crystals (MSU crystals) in hypothermia rat model which was induced by 5'-AMP and then observe whether hypothermia induced by 5'-AMP could be effectively inhibit the inflammation on acute gouty arthritis in rats. AMP-induced hypothermia has protective effects on our acute gouty arthritis, which was demonstrated by the following criteria: (1) a significant reduction in the ankle swelling (p < 0.001); (2) a significant decrease in the occurrence of leukocyte infiltration and mild hemorrhage; (3) a significant reduction in the presence of serum Interleukin-1ß (IL-1ß, p < 0.001) and metalloproteinase-9 (MMP-9, p < 0.001); and (4) a significant inhibition in the Nuclear Factor -κappaB (NF-κB) activity (p < 0.001). AMP-induced hypothermia could inhibit acute inflammation reaction and protect the synovial tissue against acute injury in a rat acute gouty arthritis model.


Asunto(s)
Artritis Gotosa/terapia , Hiperuricemia/terapia , Hipotermia Inducida/métodos , Animales , Articulación del Tobillo/metabolismo , Articulación del Tobillo/patología , Artritis Gotosa/inducido químicamente , Artritis Gotosa/metabolismo , Artritis Gotosa/patología , Modelos Animales de Enfermedad , Hiperuricemia/inducido químicamente , Hiperuricemia/metabolismo , Hiperuricemia/patología , Interleucina-1beta/sangre , Masculino , Metaloproteinasa 9 de la Matriz/sangre , FN-kappa B/metabolismo , Ratas , Ratas Wistar , Membrana Sinovial/metabolismo , Membrana Sinovial/patología , Ácido Úrico
11.
CNS Neurosci Ther ; 29(4): 1024-1033, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36650639

RESUMEN

AIMS: Our purpose is to assess the role of cerebral small vessel disease (SVD) in prediction models in patients with different subtypes of acute ischemic stroke (AIS). METHODS: We enrolled 398 small-vessel occlusion (SVO) and 175 large artery atherosclerosis (LAA) AIS patients. Functional outcomes were assessed using the modified Rankin Scale (mRS) at 90 days. MRI was performed to assess white matter hyperintensity (WMH), perivascular space (PVS), lacune, and cerebral microbleed (CMB). Logistic regression (LR) and machine learning (ML) were used to develop predictive models to assess the influences of SVD on the prognosis. RESULTS: In the feature evaluation of SVO-AIS for different outcomes, the modified total SVD score (Gain: 0.38, 0.28) has the maximum weight, and periventricular WMH (Gain: 0.07, 0.09) was more important than deep WMH (Gain: 0.01, 0.01) in prognosis. In SVO-AIS, SVD performed better than regular clinical data, which is the opposite of LAA-AIS. Among all models, eXtreme gradient boosting (XGBoost) method with optimal index (OI) has the best performance to predict excellent outcome in SVO-AIS. [0.91 (0.84-0.97)]. CONCLUSIONS: Our results revealed that different SVD markers had distinct prognostic weights in AIS patients, and SVD burden alone may accurately predict the SVO-AIS patients' prognosis.


Asunto(s)
Aterosclerosis , Enfermedades de los Pequeños Vasos Cerebrales , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/terapia , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Costo de Enfermedad , Aprendizaje Automático , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/terapia
12.
Transl Stroke Res ; 14(1): 73-82, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-35877061

RESUMEN

The interaction effect between collateral circulation and ischemic core size on stroke outcomes has been highlighted in acute ischemic stroke (AIS). However, biomarkers that assess the magnitude of this interaction are still lacking. We aimed to present a new imaging marker, the collateral-core ratio (CCR), to quantify the interaction effect between these factors and evaluate its ability to predict functional outcomes using machine learning (ML) in AIS. Patients with AIS caused by anterior circulation large vessel occlusion (LVO) were recruited from a prospective multicenter study. CCR was calculated as collateral perfusion volume/ischemic core volume. Functional outcomes were assessed using the modified Rankin Scale (mRS) at 90 days. An ML model was built and tested with a tenfold cross-validation using nine clinical and four imaging variables with mRS score 3-6 as unfavorable outcomes. Among 129 patients, CCR was identified as the most important variable. The prediction model incorporating clinical factors, ischemic core volume, collateral perfusion volume, and CCR showed better discriminatory power in predicting unfavorable outcomes than the model without CCR (mean C index 0.853 ± 0.108 versus 0.793 ± 0.133, P = 0.70; mean net reclassification index 52.7% ± 32.7%, P < 0.05). When patients were divided into two groups based on their CCR value with a threshold of 0.73, unfavorable outcomes were significantly more prevalent in patients with CCR ≤ 0.73 than in those with CCR > 0.73. CCR is a robust predictor of functional outcomes, as identified by ML, in patients with acute LVO. The prediction model that incorporated CCR improved the model's ability to identify unfavorable outcomes. ClinicalTrials.gov Identifier: NCT02580097.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/complicaciones , Isquemia Encefálica/complicaciones , Isquemia Encefálica/diagnóstico por imagen , Estudios Prospectivos , Estudios Retrospectivos , Accidente Cerebrovascular/etiología , Circulación Colateral
13.
Mediators Inflamm ; 2012: 459617, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23024464

RESUMEN

We have built a rat's model to investigate whether the hypothermia induced by adenosine 5'-monophosphate (5'-AMP) (AIH) could attenuate acute lung injury induced by LPS in rats. We detected the inflammatory cytokine levels in the plasma and bronchoalveolar lavage fluid samples, and we analyzed the pathological changes in the lungs. We have found that AIH can effectively inhibit acute inflammatory reactions and protect the lung from acute injury induced by LPS in rats.


Asunto(s)
Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Adenosina Monofosfato/uso terapéutico , Hipotermia/inducido químicamente , Lipopolisacáridos/toxicidad , Lesión Pulmonar Aguda/sangre , Lesión Pulmonar Aguda/metabolismo , Animales , Hipotermia/sangre , Hipotermia/metabolismo , Interleucina-10/sangre , Interleucina-10/metabolismo , Interleucina-1beta/sangre , Interleucina-1beta/metabolismo , Interleucina-6/sangre , Interleucina-6/metabolismo , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/metabolismo
14.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 3): o689-90, 2012 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-22412582

RESUMEN

In the centrosymmetric title compound, C(12)H(10)O(2)S(2), the alkyl chains adopt a fully extended all-trans conformation with respect to the C(thio-phene)-C bond. The non-H atoms of the mol-ecule are nearly planar, with a maximum deviation of 0.063 (2) Šfrom the mean plane of the constituent atoms. In the crystal, symmetry-related mol-ecules are linked via pairs of C-H⋯π contacts [H-centroid distances of the thio-phene units = 2.79 (9) and 2.82 (4) Å], in turn inter-digitating with each other along the bc plane, thus leading to an inter-woven two-dimensional network.

15.
RSC Adv ; 12(9): 5677-5685, 2022 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-35425547

RESUMEN

Peri-implant surgical site infection is a significant challenge in oral implant surgery. Numerous surface functionalization methods, including electrophoretic deposition, have been studied to functionalize implant surfaces to prevent peri-implantitis. However, it is still challenging to load anti-inflammatory agents having negative charges into electrophoretic deposition membranes. The present study aimed to use water-soluble chitosan derivatives to fabricate negatively charged carboxymethyl chitosan/gelatin (CMCG) composite membranes on titanium (Ti) substrates via anodic electrophoretic deposition (AED). Membranes incorporating different amounts of gelatin were labeled as CMC, CMCG4, CMCG6, and CMCG8. X-ray diffraction and Fourier transform infrared spectroscopy tests verified that CMCG could be deposited on Ti disks via AED. The result of the contact angle test showed that groups incorporating gelatin had a certain degree of hydrophobicity. After rehydration, the membranes swelled by approximately 200% in weight. Fluorescence microscopy and scanning electron microscopy images showed that bone marrow stromal cells (BMSCs) on membranes stretched well, showing a good cell adhesion ability. The CCK-8 test demonstrated that CMCG6 had the highest proliferation rate. Cell apoptosis studies showed that CMCG could inhibit apoptosis of BMSCs statistically. It suggests that the CMCG membrane fabricated by AED would be a potent candidate for surface functionalization of biomaterials with negative charges.

16.
Artículo en Inglés | MEDLINE | ID: mdl-29857412

RESUMEN

Nursing staff has designed and developed this system for elderly patients to simplify the working process of nursing staff. The system was developed using Microsoft Excel 2010 and its in-house Excel VBA (Visual Basic for Applications) tools, it was developed by VBA-trained nursing staff to develop a skin dryness evaluation system for senile patients. The system is useful to managing dry skin among elderly patients. The participation of nursing staff in the design of information system plays a very important role in the feasibility of the software.


Asunto(s)
Demencia , Enfermedades de la Piel/terapia , Programas Informáticos , Anciano , Humanos , Pacientes
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