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1.
J Biol Chem ; : 107472, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38879005

RESUMEN

African swine fever virus (ASFV) causes severe disease in domestic pigs and wild boars, seriously threatening the development of the global pig industry. Type I interferon (IFN-I) is an important component of innate immunity, inducing the transcription and expression of antiviral cytokines by activating Janus-activated kinase-signal transducer and activation of transcription (JAK-STAT) signal transduction. However, the underlying molecular mechanisms by which ASFV antagonizes IFN-I signaling have not been fully elucidated. Therefore, using co-immunoprecipitation, confocal microscopy and dual luciferase reporter assay methods, we investigated these mechanisms and identified a novel ASFV immunosuppressive protein, pB475L, which interacts with the C-terminal domain of STAT2. Consequently, pB475L inhibited IFN-I signaling by inhibiting STAT1 and STAT2 heterodimerization and nuclear translocation. Furthermore, we constructed an ASFV-B475L7PM mutant strain by homologous recombination, finding that ASFV-B475L7PM attenuated the inhibitory effects on IFN-I signaling compared to wild-type ASFV. In summary, this study reveals a new mechanism by which ASFV impairs host innate immunity.

2.
Ann Neurol ; 96(1): 194-203, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38661030

RESUMEN

OBJECTIVE: Primary angiitis of the central nervous system (PACNS) is a rare vasculitis restricted to the brain, spinal cord, and leptomeninges. This study aimed to describe the imaging characteristics of patients with small vessel PACNS (SV-PACNS) using 7 T magnetic resonance imaging (MRI). METHODS: This ongoing prospective observational cohort study included patients who met the Calabrese and Mallek criteria and underwent 7 T MRI scan. The MRI protocol includes T1-weighted magnetization-prepared rapid gradient echo imaging, T2 star weighted imaging, and susceptibility-weighted imaging. Two experienced readers independently reviewed the neuroimages. Clinical data were extracted from the electronic patient records. The findings were then applied to a cohort of patients with large vessel central nervous system (CNS) vasculitis. RESULTS: We included 21 patients with SV-PACNS from December 2021 to November 2023. Of these, 12 (57.14%) had cerebral cortical microhemorrhages with atrophy. The pattern with microhemorrhages was described in detail based on the gradient echo sequence, leading to the identification of what we have termed the "coral-like sign." The onset age of patients with coral-like sign (33.83 ± 9.93 years) appeared younger than that of patients without coral-like sign (42.11 ± 14.18 years) (P = 0.131). Furthermore, the cerebral lesions in patients with cortical microhemorrhagic SV-PACNS showed greater propensity toward bilateral lesions (P = 0.03). The coral-like sign was not observed in patients with large vessel CNS vasculitis. INTERPRETATION: The key characteristics of the coral-like sign represent cerebral cortical diffuse microhemorrhages with atrophy, which may be an important MRI pattern of SV-PACNS. ANN NEUROL 2024;96:194-203.


Asunto(s)
Imagen por Resonancia Magnética , Vasculitis del Sistema Nervioso Central , Humanos , Masculino , Femenino , Vasculitis del Sistema Nervioso Central/diagnóstico por imagen , Vasculitis del Sistema Nervioso Central/patología , Vasculitis del Sistema Nervioso Central/complicaciones , Adulto , Persona de Mediana Edad , Estudios Prospectivos , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/patología , Adulto Joven , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Estudios de Cohortes , Adolescente
3.
Plant Physiol ; 194(1): 578-591, 2023 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-37638889

RESUMEN

Mitogen-activated protein kinase (MAPK/MPK) cascades are key signaling modules that regulate plant immunity. ENHANCED DISEASE RESISTANCE1 (EDR1) encodes a Raf-like MAPK kinase kinase (MAPKKK) that negatively regulates plant defense in Arabidopsis (Arabidopsis thaliana). The enhanced resistance of edr1 requires MAPK KINASE4 (MKK4), MKK5, and MPK3. Although the edr1 mutant displays higher MPK3/6 activation, the mechanism by which plants increase MAPK cascade activation remains elusive. Our previous study showed that MAPKKK5 is phosphorylated at the Ser-90 residue in edr1 mutants. In this study, we demonstrated that the enhanced disease resistance of edr1 required MAPKKK5. Phospho-dead MAPKKK5S90A partially impaired the resistance of edr1, and the expression of phospho-mimetic MAPKKK5S90D in mapkkk5-2 resulted in enhanced resistance to the powdery mildew Golovinomyces cichoracearum strain UCSC1 and the bacterial pathogen Pseudomonas syringae pv. tomato (Pto) strain DC3000. Thus, Ser-90 phosphorylation in MAPKKK5 appears to play a crucial role in disease resistance. However, MAPKKK5-triggered cell death was not suppressed by EDR1. Furthermore, activated MPK3 phosphorylated the N terminus of MAPKKK5, and Ser-90 was one of the phosphorylated sites. Ser-90 phosphorylation increased MAPKKK5 stability, and EDR1 might negatively regulate MAPK cascade activation by suppressing the MPK3-mediated feedback regulation of MAPKKK5. Taken together, these results indicate that MPK3 phosphorylates MAPKKK5 to enhance MAPK cascade activation and disease resistance in edr1 mutants.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Humanos , Resistencia a la Enfermedad/genética , Proteínas de Arabidopsis/metabolismo , MAP Quinasa Quinasa Quinasa 5/metabolismo , Mitógenos/metabolismo , Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Enfermedades de las Plantas/microbiología
4.
Artículo en Inglés | MEDLINE | ID: mdl-38453475

RESUMEN

BACKGROUND: Although trigeminal nerve involvement is a characteristic of multiple sclerosis (MS), its prevalence across studies varies greatly due to MRI resolution and cohort selection bias. The mechanism behind the site specificity of trigeminal nerve injury is still unclear. We aim to determine the prevalence of trigeminal nerve involvement in patients with MS in a consecutive 7T brain MRI cohort. METHODS: This observational cohort originates from an ongoing China National Registry of Neuro-Inflammatory Diseases. Inclusion criteria were the following: age 18 years or older, diagnosis of MS according to the 2017 McDonald criteria and no clinical relapse within the preceding 3 months. Each participant underwent 7T MAGNETOM Terra scanner (Siemens, Erlangen, Germany), using a 32-channel phased array coil at Beijing Tiantan Hospital. T1-weighted magnetisation-prepared rapid acquisition gradient echoes, fluid-attenuated inversion recovery (FLAIR) and fluid and white matter suppression images were used to identify lesions. FLAIR* and T2* weighted images were used to identify central vein sign (CVS) within the trigeminal lesions. RESULTS: 120 patients underwent 7T MRI scans between December 2021 and May 2023. 19/120 (15.8%) patients had a total of 45 trigeminal lesions, of which 11/19 (57.9%) were bilateral. The linear lesions extended along the trigeminal nerve, from the root entry zone (REZ) (57.8%, 26/45) to the pontine-medullary nucleus (42.2%, 19/45). 26.9% (7/26) of the lesions in REZ showed a typical central venous sign. CONCLUSION: In this 7T MRI cohort, the prevalence of trigeminal nerve involvement was 15.8%. Characteristic CVS was detected in 26.9% of lesions in REZ. This suggests an inflammatory demyelination mechanism of trigeminal nerve involvement in MS.

5.
Sensors (Basel) ; 24(7)2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38610255

RESUMEN

In recent years, biomedical optics technology has developed rapidly. The current widespread use of biomedical optics was made possible by the invention of optical instruments. The advantages of being non-invasive, portable, effective, low cost, and less susceptible to system noise have led to the rapid development of functional near-infrared spectroscopy (fNIRS) technology for hemodynamics detection, especially in the field of functional brain imaging. At the same time, laboratories and companies have developed various fNIRS-based systems. The safety, stability, and efficacy of fNIRS systems are key performance indicators. However, there is still a lack of comprehensive and systematic evaluation methods for fNIRS instruments. This study uses the fNIRS system developed in our laboratory as the test object. The test method established in this study includes system validation and performance testing to comprehensively assess fNIRS systems' reliability. These methods feature low cost and high practicality. Based on this study, existing or newly developed systems can be comprehensively and easily evaluated in the laboratory or workspace.


Asunto(s)
Tecnología Biomédica , Espectroscopía Infrarroja Corta , Humanos , Reproducibilidad de los Resultados , Encéfalo/diagnóstico por imagen , Laboratorios
6.
Bioorg Med Chem Lett ; 96: 129533, 2023 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-37865282

RESUMEN

Cytochrome P450 (CYP)1B1 has been identified to be specifically overexpressed in several solid tumors, thus it's a potential target for the detection of tumors. Based on the 2-Phenylquinazolin CYP1B1 inhibitors, we designed and synthesized several positron emission computed tomography (PET) imaging probes targeting CYP1B1. Through IC50 determinations, most of these probes exhibited good affinity and selectivity to CYP1B1. Considering their affinity, solubility, and their 18F labeling methods, we chose compound 5c as the best candidate. The 18F radiolabeling of [18F] 5c was easy to handle with good radiolabeling yield and radiochemical purity. In vitro and in vivo stability study indicated that probe [18F]5c has good stability. In cell binding assay, [18F]5c could be specifically taken up by tumor cells, especially HCT-116 cells. Although the tumor-blood (T/B) and tumor-muscle (T/M) values and PET imaging results were unsatisfied, it is still possible to develop PET probes targeting CYP1B1 by structural modification on the basis of 5c in the future.


Asunto(s)
Tomografía de Emisión de Positrones , Radiofármacos , Línea Celular Tumoral , Tomografía de Emisión de Positrones/métodos , Radiofármacos/farmacología , Radiofármacos/química , Radioisótopos de Flúor
7.
J Clin Apher ; 38(4): 368-375, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36420568

RESUMEN

BACKGROUND: The value of double filtration plasmapheresis (DFPP) in severe hypertriglyceridemia-induced pancreatitis (sHTGP) is controversial. This study aimed to investigate the efficacy of DFPP on clinical outcomes in patients with sHTGP and the costs associated with the procedure. METHODS: Patients who underwent DFPP after admission between January 2016 and December 2021 were recruited. Data on lipid profile, clinical parameters, and costs were retrospectively collected and analyzed. RESULTS: Fifty sHTGP patients who received DFPP were enrolled. All of the lipid profile were significantly reduced and maintained a downward trend. The APACHE II score on admission was higher and the reduction after DFPP was more obvious (P < 0.05) in patients with higher triglyceride (TG) levels (≥33.9 mmol/L) than in patients with lower TG levels. More material fees were expended in the higher TG group due to more DFPP sessions (P < 0.05), but no significant differences existed in total hospital costs between the two groups. CONCLUSION: DFPP could rapidly and effectively reduce TGs to a safe level. APACHE II score reduction was obvious in patients with TGs ≥33.9 mmol/L and was associated with lipid profile changes. DFPP may benefit sHTGP patients with a TG level higher than the current initiation threshold.


Asunto(s)
Hiperlipidemias , Hipertrigliceridemia , Pancreatitis , Humanos , Estudios Retrospectivos , Hipertrigliceridemia/complicaciones , Hipertrigliceridemia/terapia , Pancreatitis/complicaciones , Pancreatitis/terapia , Plasmaféresis/métodos , Lípidos , Filtración
8.
Plant J ; 108(3): 672-689, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34396631

RESUMEN

The loss of function of exocyst subunit EXO70B1 leads to autoimmunity, which is dependent on TIR-NBS2 (TN2), a truncated intracellular nucleotide-binding and leucine-rich repeat receptor (NLR). However, how TN2 triggers plant immunity and whether typical NLRs are required in TN2-activated resistance remain unclear. Through the CRISPR/Cas9 gene editing system and knockout analysis, we found that the spontaneous cell death and enhanced resistance in exo70B1-3 were independent of the full-length NLR SOC3 and its closest homolog SOC3-LIKE 1 (SOC3-L1). Additionally, knocking out SOC3-L1 or TN2 did not suppress the chilling sensitivity conferred by chilling sensitive 1-2 (chs1-2). The ACTIVATED DISEASE RESISTANCE 1 (ADR1) family and the N REQUIREMENT GENE 1 (NRG1) family have evolved as helper NLRs for many typical NLRs. Through CRISPR/Cas9 gene editing methods, we discovered that the autoimmunity of exo70B1-3 fully relied on ADR1s, but not NRG1s, and ADR1s contributed to the upregulation of TN2 transcript levels in exo70B1-3. Furthermore, overexpression of TN2 also led to ADR1-dependent autoimmune responses. Taken together, our genetic analysis highlights that the truncated TNL protein TN2-triggered immune responses require ADR1s as helper NLRs to activate downstream signaling, revealing the importance and complexity of ADR1s in plant immunity regulation.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/inmunología , Arabidopsis/microbiología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Enfermedades de las Plantas/inmunología , Arabidopsis/citología , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Ascomicetos/patogenicidad , Autoinmunidad , Muerte Celular , Resistencia a la Enfermedad/genética , Resistencia a la Enfermedad/inmunología , Regulación de la Expresión Génica de las Plantas , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas NLR/genética , Proteínas NLR/metabolismo , Enfermedades de las Plantas/microbiología , Inmunidad de la Planta , Plantas Modificadas Genéticamente , Pseudomonas syringae/patogenicidad , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/inmunología , Proteínas de Transporte Vesicular/metabolismo
9.
Plant Cell Physiol ; 63(10): 1405-1413, 2022 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-35859340

RESUMEN

Ubiquitination is an essential posttranslational modification and plays a crucial role in regulating plant immunity by modulating protein activity, stability, abundance and interaction. Recently, major breakthroughs have been made in understanding the mechanisms associated with the regulation of immune signaling by ubiquitination. In this mini review, we highlight the recent advances in the role of ubiquitination in fine-tuning the resistance activated by plant pattern recognition receptors (PRRs) and intracellular nucleotide-binding site and leucine-rich repeat domain receptors (NLRs). We also discuss current understanding of the positive regulation of plant immunity by ubiquitination, including the modification of immune negative regulators and of the guardee proteins monitored by NLRs.


Asunto(s)
Inmunidad de la Planta , Transducción de Señal , Inmunidad de la Planta/fisiología , Ubiquitinación , Procesamiento Proteico-Postraduccional , Plantas
10.
FASEB J ; 35(2): e21183, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33184978

RESUMEN

Calcific aortic valve disease (CAVD) is the most common valvular heart disease in adults. The cellular mechanisms of CAVD are still unknown, but accumulating evidence has revealed that osteogenic differentiation of human valve interstitial cells (hVICs) plays an important role in CAVD. Thus, we aimed to investigate the function of estrogen-related receptor α (ERRα) in the osteogenic differentiation of hVICs. We found that the level of ERRα was significantly increased in CAVD samples compared to normal controls. In addition, ERRα was significantly upregulated during hVIC osteogenic differentiation in vitro. Gain- and loss-of-function experiments were performed to identify the function of ERRα in hVIC calcification in vitro. Inhibition of endogenous ERRα attenuated hVIC calcification, whereas overexpression of ERRα in hVICs promoted this process. RNA sequencing results suggested that heme oxygenase-1 (Hmox1) was a downstream target of ERRα, which was further confirmed by western blotting. Additionally, we also found that downregulation of Hmox1 by shHmox1 efficiently reversed the inhibition of calcification induced by ERRα shRNA in hVICs. ChIP-qPCR and luciferase assays indicated that Hmox1 was negatively regulated by ERRα. We found that overexpression of Hmox1 or its substrates significantly inhibited hVIC calcification in vitro. In conclusion, we found that knockdown of ERRα can inhibit hVIC calcification through upregulating Hmox1 and that ERRα and Hmox1 are potential targets for the treatment of CAVD.


Asunto(s)
Estenosis de la Válvula Aórtica/metabolismo , Válvula Aórtica/patología , Calcinosis/metabolismo , Técnicas de Silenciamiento del Gen , Hemo-Oxigenasa 1/metabolismo , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Anciano , Válvula Aórtica/metabolismo , Estenosis de la Válvula Aórtica/patología , Calcinosis/patología , Diferenciación Celular/genética , Femenino , Células HEK293 , Hemo-Oxigenasa 1/genética , Humanos , Masculino , Persona de Mediana Edad , Osteogénesis/genética , Transfección , Regulación hacia Arriba/genética , Calcificación Vascular , Receptor Relacionado con Estrógeno ERRalfa
11.
Indoor Air ; 32(7): e13062, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35904389

RESUMEN

As more and more people stay inside the building for a long time, the indoor environment has a great effect on their health, mood, and work efficiency. Electroencephalography (EEG) signals reflect electrical activity originating from neuronal firing when a task or activity is performed. Since there was no study on the effect of indoor air on nerves, this study utilized EEG to preliminarily explore the brain functions of subjects during working memory tasks with different difficulties. The subjects were divided into two groups according to the volatile organic compounds (VOCs) as odor irritants in the air. We expected to find the difference in subjects' EEG signals between VOCs and low-VOCs. The EEG signals from 60 electrodes were analyzed by event-related potential (ERP), event-related spectral power (ERSP), and correlation network methods to describe the brain activity. We compared the results of subjects in VOCs and low-VOCs and found significant differences between ERP and ERSP in the alpha band during a simple working memory task. Subjects were more sensitive to the VOCs in simple tasks than in complex tasks. Our work provided evidence of odor effects on brain functions and could be used to guide the design of indoor odor in home, offices, and classrooms.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire Interior , Compuestos Orgánicos Volátiles , Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Encéfalo , Electroencefalografía , Monitoreo del Ambiente/métodos , Humanos , Memoria a Corto Plazo , Pintura , Compuestos Orgánicos Volátiles/análisis
12.
J Mol Cell Cardiol ; 150: 54-64, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33045251

RESUMEN

AIMS: Calcific aortic valve disease (CAVD) is a primary cause of cardiovascular mortality; however, its mechanisms are unknown. Currently, no effective pharmacotherapy is available for CAVD. Aldo-keto reductase family 1 member B (Akr1B1) has been identified as a potential therapeutic target for valve interstitial cell calcification. Herein, we hypothesized that inhibition of Akr1B1 can attenuate aortic valve calcification. METHODS AND RESULTS: Normal and degenerative tricuspid calcific valves from human samples were analyzed by immunoblotting and immunohistochemistry. The results showed significant upregulation of Akr1B1 in CAVD leaflets. Akr1B1 inhibition attenuated calcification of aortic valve interstitial cells in osteogenic medium. In contrast, overexpression of Akr1B1 aggravated calcification in osteogenic medium. Mechanistically, using RNA sequencing (RNAseq), we revealed that Hippo-YAP signaling functions downstream of Akr1B1. Furthermore, we established that the protein level of the Hippo-YAP signaling effector active-YAP had a positive correlation with Akr1B1. Suppression of YAP reversed Akr1B1 overexpression-induced Runx2 upregulation. Moreover, YAP activated the Runx2 promoter through TEAD1 in a manner mediated by ChIP and luciferase reporter systems. Animal experiments showed that the Akr1B1 inhibitor epalrestat attenuated aortic valve calcification induced by a Western diet in LDLR-/- mice. CONCLUSION: This study demonstrates that inhibition of Akr1B1 can attenuate the degree of calcification both in vitro and in vivo. The Akr1B1 inhibitor epalrestat may be a potential treatment option for CAVD.


Asunto(s)
Aldehído Reductasa/metabolismo , Aldo-Ceto Reductasas/metabolismo , Estenosis de la Válvula Aórtica/enzimología , Estenosis de la Válvula Aórtica/patología , Válvula Aórtica/enzimología , Válvula Aórtica/patología , Calcinosis/enzimología , Calcinosis/patología , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Aldehído Reductasa/antagonistas & inhibidores , Animales , Válvula Aórtica/efectos de los fármacos , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Inhibidores Enzimáticos/farmacología , Técnicas de Silenciamiento del Gen , Humanos , Lentivirus/metabolismo , Ratones , Osteogénesis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Factores de Transcripción/metabolismo , Proteínas Señalizadoras YAP
13.
J Neurol Neurosurg Psychiatry ; 92(7): 709-716, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33687975

RESUMEN

BACKGROUND: Brain structural alterations and their clinical significance of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) have not been determined. METHODS: We recruited 35 MOGAD, 38 aquaporin 4 antibody positive neuromyelitis optica spectrum diseases (AQP4+ NMOSD), 37 multiple sclerosis (MS) and 60 healthy controls (HC) who underwent multimodal brain MRI from two centres. Brain lesions, volumes of the whole brain parenchyma, cortical and subcortical grey matter (GM), brainstem, cerebellum and cerebral white matter (WM) and diffusion measures (fractional anisotropy, FA and mean diffusivity, MD) were compared among the groups. Associations between the MRI measurements and the clinical variables were assessed by partial correlations. Logistic regression was performed to differentiate MOGAD from AQP4+ NMOSD and MS. RESULTS: In MOGAD, 19 (54%) patients had lesions on MRI, with cortical/juxtacortical (68%) as the most common location. MOGAD and MS showed lower cortical and subcortical GM volumes than HC, while AQP4+ NMOSD only demonstrated a decreased cortical GM volume. MS demonstrated a lower cerebellar volume, a lower FA and an increased MD than MOGAD and HC. The subcortical GM volume was negatively correlated with Expanded Disability Status Scale in MOGAD (R=-0.51; p=0.004). A combination of MRI and clinical measures could achieve an accuracy of 85% and 93% for the classification of MOGAD versus AQP4+ NMOSD and MOGAD versus MS, respectively. CONCLUSION: MOGAD demonstrated cortical and subcortical atrophy without severe WM rarefaction. The subcortical GM volume correlated with clinical disability and a combination of MRI and clinical measures could separate MOGAD from AQP4+ NMOSD and MS.


Asunto(s)
Autoanticuerpos , Encéfalo/diagnóstico por imagen , Esclerosis Múltiple/diagnóstico por imagen , Glicoproteína Mielina-Oligodendrócito/inmunología , Neuromielitis Óptica/diagnóstico por imagen , Adulto , Acuaporina 4/inmunología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/inmunología , Neuromielitis Óptica/inmunología , Adulto Joven
14.
Mult Scler ; 27(9): 1350-1363, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33054621

RESUMEN

BACKGROUND: The impact of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) on brain structure and function is unknown. OBJECTIVES: The aim of this study was to study the multimodal brain MRI alterations in MOGAD and to investigate their clinical significance. METHODS: A total of 17 MOGAD, 20 aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders (AQP4 + NMOSD), and 28 healthy controls (HC) were prospectively recruited. Voxel-wise gray matter (GM) volume, fractional anisotropy (FA), mean diffusivity (MD), and degree centrality (DC) were compared between groups. Clinical associations and differential diagnosis were determined using partial correlation and stepwise logistic regression. RESULTS: In comparison with HC, MOGAD had GM atrophy in frontal and temporal lobe, insula, thalamus, and hippocampus, and WM fiber disruption in optic radiation and anterior/posterior corona radiata; DC decreased in cerebellum and increased in temporal lobe. Compared to AQP4 + NMOSD, MOGAD presented lower GM volume in postcentral gyrus and decreased DC in cerebellum. Hippocampus/parahippocampus atrophy associated with Expanded Disability Status Scale (R = -0.55, p = 0.04) and California Verbal Learning Test (R = 0.62, p = 0.031). The differentiation of MOGAD from AQP4 + NMOSD achieved an accuracy of 95% using FA in splenium of corpus callosum and DC in occipital gyrus. CONCLUSION: Distinct structural and functional alterations were identified in MOGAD. Hippocampus/parahippocampus atrophy associated with clinical disability and cognitive impairment.


Asunto(s)
Acuaporina 4 , Neuromielitis Óptica , Encéfalo/diagnóstico por imagen , Sustancia Gris/diagnóstico por imagen , Humanos , Glicoproteína Mielina-Oligodendrócito , Neuromielitis Óptica/diagnóstico por imagen
15.
Adv Exp Med Biol ; 1269: 71-75, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33966197

RESUMEN

Cupping therapy is a promising method to cure or reduce symptoms of some diseases including muscle pain/tenderness/fatigue. Although the applications of cupping therapy have a thousand-year history in traditional Chinese medicine and have been spread to other countries in recent years, cupping therapy is something like a black box, and the unskilled user can hardly control it due to the absence of physiological observations. In this study, we developed a NIRS instrument with three probes to detect the blood-oxygen level of the skin tissue where the cupping therapy is being carried out. Each probe includes two detection channels. One of the probes is embedded in the cup to monitor the hemodynamic parameters in the cupping site, and the other two probes are placed outside, surrounding the cupping site. Using this monitor, we can observe the changes in oxy-hemoglobin ([HbO2]), deoxy-hemoglobin ([Hb]), and total hemoglobin ([tHb]), as well as the heart rate, calculated from the change curves of [HbO2] during cupping therapy in real time. Therefore, the doctor or other users can see the impact of cupping on the tissues to which it is applied which should facilitate the development and understanding of the application of cupping.


Asunto(s)
Hemodinámica , Espectroscopía Infrarroja Corta , Hemoglobinas/análisis , Oxígeno , Oxihemoglobinas/análisis
16.
J Integr Plant Biol ; 63(2): 327-339, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32877006

RESUMEN

Mitogen-activated protein kinase (MAPK) cascades are highly conserved signaling modules that regulate plant immune responses. The Arabidopsis thaliana Raf-like MAPK kinase kinase ENHANCED DISEASE RESISTANCE1 (EDR1) is a key negative regulator of plant immunity that affects the protein levels of MKK4 and MKK5, two important MAPK cascade members, but the underlying mechanism is poorly understood. Here, genome-wide phosphorylation analysis demonstrated that the E3 ligase KEEP ON GOING (KEG) is phosphorylated in the edr1 mutant but not the wild type, suggesting that EDR1 negatively affects KEG phosphorylation. The identified phosphorylation sites in KEG appear to be important for its accumulation. The keg-4 mutant, a previously identified edr1 suppressor, enhances susceptibility to the powdery mildew pathogen Golovinomyces cichoracearum. In addition, MKK4 and MKK5 protein levels are reduced in the keg-4 mutant. Furthermore, we demonstrate that MKK4 and MKK5 associate with full-length KEG, but not with truncated KEG-RK or KEG-RKA, and that KEG ubiquitinates and mediates the degradation of MKK4 and MKK5. Taken together, these results indicate that MKK4 and MKK5 protein levels are regulated by KEG via ubiquitination, uncovering a mechanism by which plants fine-tune immune responses by regulating the homeostasis of key MAPK cascade members via ubiquitination and degradation.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimología , Arabidopsis/inmunología , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Inmunidad de la Planta , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación , Secuencia de Aminoácidos , Arabidopsis/microbiología , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Ascomicetos/fisiología , Proteínas Fluorescentes Verdes/metabolismo , Modelos Biológicos , Mutación/genética , Fosforilación , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/microbiología , Unión Proteica , Ubiquitina-Proteína Ligasas/química
17.
New Phytol ; 227(2): 529-544, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32119118

RESUMEN

The plasma membrane (PM)-localized receptor kinase FLAGELLIN SENSING 2 (FLS2) recognizes bacterial flagellin or its immunogenic epitope flg22, and initiates microbe-associated molecular pattern-triggered immunity, which inhibits infection by bacterial pathogens. The localization, abundance and activity of FLS2 are under dynamic control. Here, we demonstrate that Arabidopsis thaliana EXO70B1, a subunit of the exocyst complex, plays a critical role in FLS2 signaling that is independent of the truncated Toll/interleukin-1 receptor-nucleotide binding sequence protein TIR-NBS2 (TN2). In the exo70B1-3 mutant, the abundance of FLS2 protein at the PM is diminished, consistent with the impaired flg22 response of this mutant. EXO70B1-GFP plants showed increased FLS2 accumulation at the PM and therefore enhanced FLS2 signaling. The EXO70B1-mediated trafficking of FLS2 to the PM is partially independent of the PENETRATION 1 (PEN1)-containing secretory pathway. In addition, EXO70B1 interacts with EXO70B2, a close homolog of EXO70B1, and both proteins associate with FLS2 and contribute to the accumulation of FLS2 at the PM. Taken together, our data suggest that the exocyst complex subunits EXO70B1 and EXO70B2 regulate the trafficking of FLS2 to the PM, which represents a new layer of regulation of FLS2 function in plant immunity.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Membrana Celular , Flagelina , Homeostasis , Proteínas Quinasas/genética , Proteínas de Transporte Vesicular
19.
Adv Exp Med Biol ; 923: 187-193, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27526142

RESUMEN

Near-infrared spectroscopy (NIRS), as a non-invasive optical imaging method, has been widely used in psychology research. Working memory (WM) is an extensively researched psychological concept related to the temporary storage and processing of information. Many neuropsychological studies demonstrate that several brain areas of prefrontal cortex (PFC) are engaged during verbal WM tasks. The gender-based differences in WM remains under dispute. To better understand the active module and gender differences in PFC activity patterns during verbal WM tasks, we investigated the blood oxygenation changes of the PFC in 15 healthy subjects using a homemade multichannel continuous-wave NIRS instrument, while performing a verbal n-back task. We employed traditional activation and novel connectivity analyses simultaneously. Males had a higher level of oxygenation activity and connectivity in PFC than females. Only the results of females revealed a leftward lateralization in the 2-back task.


Asunto(s)
Mapeo Encefálico/métodos , Ondas Encefálicas , Memoria a Corto Plazo , Oximetría/métodos , Consumo de Oxígeno , Oxígeno/sangre , Corteza Prefrontal/fisiología , Espectroscopía Infrarroja Corta , Conducta Verbal , Adulto , Biomarcadores/metabolismo , Femenino , Voluntarios Sanos , Humanos , Masculino , Pruebas Neuropsicológicas , Valor Predictivo de las Pruebas , Corteza Prefrontal/metabolismo , Factores Sexuales , Procesamiento de Señales Asistido por Computador , Adulto Joven
20.
Adv Exp Med Biol ; 923: 231-237, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27526148

RESUMEN

The Stroop task was used to investigate the role of phonological processing in semantic access for written Chinese language. Fourteen children were recruited to perform the Stroop task, using color characters, their homophones and neutral characters as stimuli. Near-infrared spectroscopy (NIRS) was used to measure the brain activation in the prefrontal cortex (PFC) during the task. In view of better sensitivity, oxy-hemoglobin was chosen to indicate the task activation. In behavioral performance, there was a significant classical Stroop interference effect as indexed by longer response time and higher error rate for the color task than the neutral task, whereas there was no evident interference effect for the color homophones. The NIRS data agreed with the behavioral data, and showed a significant Stroop effect only for the color characters in the bilateral PFC. These results suggested that phonology may not play an important role in semantic activation of Chinese characters for children.


Asunto(s)
Mapeo Encefálico/métodos , Oximetría/métodos , Consumo de Oxígeno , Oxígeno/sangre , Fonética , Corteza Prefrontal/fisiología , Lectura , Semántica , Espectroscopía Infrarroja Corta , Test de Stroop , Biomarcadores/sangre , Niño , Conducta Infantil , Visión de Colores , Femenino , Humanos , Masculino , Oxihemoglobinas/metabolismo , Estimulación Luminosa , Corteza Prefrontal/metabolismo , Tiempo de Reacción
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