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Hydrogel dressings with multiple functions are ideal options for wound repair. This study developed hydrogel dressings by interpenetrating the physically crosslinked xanthan gum (XG)/carboxylated chitosan (CCS) network and the chemically crosslinked polyacrylamide (PAAm) network via a one-pot method. The XG-CCS/PAAm hydrogels were found to display tunable mechanical properties, due to the formation of strong network structure. The hydrogels exhibited the strongest tensile strength of 0.6â¯MPa at an XG/CCS ratio of 40/60, while the largest compressive strength of 4.5â¯MPa is achieved at an XG/CCS ratio of 60/40. Moreover, the hydrogel with an XG/CCS ratio of 60/40 exhibited desirable adhesion strength on porcine skin, which was 3.7â¯kPa. It also had a swelling ratio, as high as 1200â¯%. After loading with cephalexin, the XG-CCS/PAAm hydrogels can deliver the antibacterial drugs following a first-order kinetic. As a result, both E. coli and S. aureus can be completely inactivated by the cefalexin-loaded hydrogels after 12â¯h. Furthermore, the XG-CCS/PAAm hydrogels were found to exhibit excellent biocompatibility as well as effective wound healing ability, as proven by the in vitro and in vivo tests. In this regard, XG-CCS/PAAm hydrogels can act as promising multifunctional wound dressings.
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Abnormal proliferation, migration, and foam cell formation of Vascular smooth muscle cells (VSMCs) each play a role in the development of atherosclerosis (AS). Schisandrin (Sch) is the active lignan ingredient with broad-spectrum pharmacological effects. However, the role of Sch in the AS process is not clear. Therefore, this study was proposed to explore the therapeutic effect and potential mechanism of Sch on VSMCs. Ox-LDL was selected to create an atherosclerosis injury environment for VSMCs and macrophages. The MTT assay, Oil red O staining, wound healing, transwell experiments and ELISA were used to investigate the phenotype effects of Sch. Network pharmacology, molecular docking, flow cytometry, and western blot were used to investigate the underlying mechanisms of Sch on AS progression. Our findings implied that Sch treatment inhibited the proliferation and migration of VSMCs, and suppressed the ROS production and inflammatory cytokines up-regulation of VSMCs and macrophages. Moreover, Sch reduced lipid uptake and foam cell formation through downregulating LOX-1. Mechanistically, we found that Sch can inhibit the activation of JAK2/STAT3 signaling by targeting JAK2, and arrest cell cycle in GO/G1 phase. In summary, Sch can inhibit VSMCs proliferation and migration by arresting cell cycle and targeting JAK2 to regulating the JAK2/STAT3 pathway. Sch may serve as a potential drug for patients with AS.
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Movimiento Celular , Proliferación Celular , Ciclooctanos , Janus Quinasa 2 , Lignanos , Músculo Liso Vascular , Compuestos Policíclicos , Factor de Transcripción STAT3 , Transducción de Señal , Janus Quinasa 2/metabolismo , Factor de Transcripción STAT3/metabolismo , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/citología , Lignanos/farmacología , Transducción de Señal/efectos de los fármacos , Ciclooctanos/farmacología , Compuestos Policíclicos/farmacología , Humanos , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Puntos de Control del Ciclo Celular/efectos de los fármacos , Animales , Aterosclerosis/patología , Aterosclerosis/metabolismo , Aterosclerosis/tratamiento farmacológicoRESUMEN
Enhancing the antitumor immune response and targeting ability of oncolytic viruses will improve the effect of tumor immunotherapy. Through infecting neural stem cells (NSCs) with a capsid dual-modified oncolytic adenovirus (CRAd), we obtained and characterized the "oncolytic extracellular vesicles" (CRAdEV) with improved targeted infection and tumor killing activity compared with CRAd. Both ex vivo and in vivo studies revealed that CRAdEV activated innate immune cells and importantly enhanced the immunomodulatory effect compared to CRAd. We found that CRAdEV effectively increased the number of DCs and activated CD4+ and CD8+ T cells, significantly increased the number and activation of B cells, and produced higher levels of tumor-specific antibodies, thus eliciting enhanced antitumor activity compared with CRAd in a B16 xenograft immunocompetent mice model. This study provides a novel approach to oncolytic adenovirus modification and demonstrates the potential of "oncolytic extracellular vesicles" in antitumor immunotherapy.
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Adenoviridae , Vesículas Extracelulares , Viroterapia Oncolítica , Virus Oncolíticos , Animales , Ratones , Adenoviridae/genética , Viroterapia Oncolítica/métodos , Humanos , Línea Celular Tumoral , Inmunoterapia , Células-Madre Neurales/inmunología , Inmunomodulación/efectos de los fármacos , Melanoma Experimental/inmunología , Melanoma Experimental/terapia , Melanoma Experimental/patología , Linfocitos T CD8-positivos/inmunologíaRESUMEN
In the current study, a novel crude polysaccharide (cNCEP) was extracted from N. commune Vaucher utilizing ultrasonic-assisted extraction (UAE) with 60 % ethanol, employing response surface methodology. The optimal yield of cNCEP was determined to be 8.07 ± 0.08 mg/g, achieved through ultrasonic-assisted extraction under the conditions of a material-to-liquid ratio of 1:22, temperature of 56 °C, power of 570 W, and duration of 147 min. Subsequent purification of NCEP via Sephadex G75 resulted in a novel polysaccharide with a molecular weight of 20.466 kDa. NCEP exhibited significant scavenging activites against DPPH and hydroxyl radicals, as well as notable in vitro immunomodulatory properties. Furthermore, the mechanisms underlying the immunomodulatory effects of NCEP, involving enhancement of immunity, were investigated, revealing potential regulation of MAPK and TLR4-IRF7-NF-κB signaling pathways through RNA-Seq and Western blot analyses. These findings highlight the promising potential of NCEP as an organic immunomodulatory agent and functional food ingredient.
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Factores Inmunológicos , Peso Molecular , Nostoc commune , Ondas Ultrasónicas , Nostoc commune/química , Factores Inmunológicos/farmacología , Factores Inmunológicos/química , Factores Inmunológicos/aislamiento & purificación , Fraccionamiento Químico/métodos , Animales , Polisacáridos/química , Polisacáridos/farmacología , Polisacáridos/aislamiento & purificación , Ratones , Células RAW 264.7 , Transducción de Señal/efectos de los fármacosRESUMEN
(-)-Epicatechin gallate (ECG) is beneficial to the treatment of cardiovascular diseases (CVDs), especially atherosclerosis (AS) through antioxidant stress, but there is a lack of detailed mechanism research. In this study, the therapeutic target of ECG was determined by crossing the drug target and disease target of CVDs and AS. The combination ability of ECG with important targets was verified by Discovery Studio software. The abnormal proliferation of vascular smooth muscle cells (VSMCs) induced by Ang-II and the oxidative damage of AML 12 induced by H2O2 were established to verify the reliability of ECG intervention on the target protein. A total of 120 ECG targets for the treatment of CVDs-AS were predicted by network pharmacology. The results of molecular docking showed that ECG has strong binding force with VEGFA, MMP-9, CASP3 and MMP-2 domains. In vitro experiments confirmed that ECG significantly reduced the expression of VEGFA, MMP-9, CASP3 and MMP-2 in Ang-II-induced VSMCs, and also blocked the abnormal proliferation, oxidative stress and inflammatory reaction of VSMCs by inhibiting the phosphorylation of PI3K signaling pathway. At the same time, ECG also interfered with H2O2-induced oxidative damage of AML 12 cells, decreased the expression of ROS and MDA and cell foaming, and increased the activities of antioxidant enzymes such as SOD, thus playing a protective role.
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Aterosclerosis , Catequina , Proliferación Celular , Peróxido de Hidrógeno , Simulación del Acoplamiento Molecular , Músculo Liso Vascular , Estrés Oxidativo , Estrés Oxidativo/efectos de los fármacos , Catequina/análogos & derivados , Catequina/farmacología , Proliferación Celular/efectos de los fármacos , Aterosclerosis/metabolismo , Aterosclerosis/patología , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/citología , Peróxido de Hidrógeno/farmacología , Humanos , Transducción de Señal/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/efectos de los fármacos , Línea Celular , Factor A de Crecimiento Endotelial Vascular/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Animales , Angiotensina II/farmacología , Metaloproteinasa 9 de la Matriz/metabolismo , Antioxidantes/farmacologíaRESUMEN
Natural products have been widely recognized in clinical treatment because of their low toxicity and high activity. It is worth paying attention to modifying the biopolymer into nanostructures to give natural active ingredients additional targeting effects. In this study, based on the multifunctional modification of ß-cyclodextrin (ß-CD), a nanoplatform encapsulating the unstable drug (-)-epicatechin gallate (ECG) was designed to deliver to atherosclerotic plaques. Acetalization cyclodextrin (PH-CD), which responds to low-pH environments, and hyaluronic acid cyclodextrin, which targets the CD44 receptor on macrophage membranes, were synthesized from ß-CD and hyaluronic acid using acetalization and transesterification, respectively. The resulting dual-carrier nanoparticles (Double-NPs) loaded with ECG were prepared using a solvent evaporation method. The Double-NPs effectively scavenged reactive oxygen species, promoted macrophage migration, inhibited macrophage apoptosis, and suppressed abnormal proliferation and migration of vascular smooth muscle cells. Furthermore, the Double-NPs actively accumulated in atherosclerotic plaques in ApoE-/- mice fed with a high-fat diet, leading to a reduced plaque area, inflammatory infiltration, and plaque instability. Our findings demonstrate that the newly developed ECG nanopreparation represents an effective and safe nanotherapy for diseases such as atherosclerosis.
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Aterosclerosis , Ácido Hialurónico , Nanopartículas , beta-Ciclodextrinas , Ácido Hialurónico/química , Animales , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/prevención & control , Ratones , beta-Ciclodextrinas/química , Nanopartículas/química , Catequina/análogos & derivados , Catequina/química , Catequina/farmacología , Células RAW 264.7 , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Apoptosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Portadores de Fármacos/química , Movimiento Celular/efectos de los fármacos , Humanos , Placa Aterosclerótica/tratamiento farmacológico , Placa Aterosclerótica/prevención & control , Proliferación Celular/efectos de los fármacosRESUMEN
BACKGROUND AND OBJECTIVES: Noninvasive and accurate biomarkers of neurologic Wilson disease (NWD), a rare inherited disorder, could reduce diagnostic error or delay. Excessive subcortical metal deposition seen on susceptibility imaging has suggested a characteristic pattern in NWD. With submillimeter spatial resolution and increased contrast, 7T susceptibility-weighted imaging (SWI) may enable better visualization of metal deposition in NWD. In this study, we sought to identify a distinctive metal deposition pattern in NWD using 7T SWI and investigate its diagnostic value and underlying pathophysiologic mechanism. METHODS: Patients with WD, healthy participants with monoallelic ATP7B variant(s) on a single chromosome, and health controls (HCs) were recruited. NWD and non-NWD (nNWD) were defined according to the presence or absence of neurologic symptoms during investigation. Patients with other diseases with comparable clinical or imaging manifestations, including early-onset Parkinson disease (EOPD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and neurodegeneration with brain iron accumulation (NBIA), were additionally recruited and assessed for exploratory comparative analysis. All participants underwent 7T T1, T2, and high-resolution SWI scanning. Quantitative susceptibility mapping and principal component analysis were performed to illustrate metal distribution. RESULTS: We identified a linear signal intensity change consisting of a hyperintense strip at the lateral border of the globus pallidus in patients with NWD. We termed this feature "hyperintense globus pallidus rim sign." This feature was detected in 38 of 41 patients with NWD and was negative in all 31 nNWD patients, 15 patients with EOPD, 30 patients with MSA, 15 patients with PSP, and 12 patients with NBIA; 22 monoallelic ATP7B variant carriers; and 41 HC. Its sensitivity to differentiate between NWD and HC was 92.7%, and specificity was 100%. Severity of the hyperintense globus pallidus rim sign measured by a semiquantitative scale was positively correlated with neurologic severity (ρ = 0.682, 95% CI 0.467-0.821, p < 0.001). Patients with NWD showed increased susceptibility in the lenticular nucleus with high regional weights in the lateral globus pallidus and medial putamen. DISCUSSION: The hyperintense globus pallidus rim sign showed high sensitivity and excellent specificity for diagnosis and differential diagnosis of NWD. It is related to a special metal deposition pattern in the lenticular nucleus in NWD and can be considered as a novel neuroimaging biomarker of NWD. CLASSIFICATION OF EVIDENCE: The study provides Class II evidence that the hyperintense globus pallidus rim sign on 7T SWI MRI can accurately diagnose neurologic WD.
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Degeneración Hepatolenticular , Imagen por Resonancia Magnética , Humanos , Degeneración Hepatolenticular/diagnóstico por imagen , Degeneración Hepatolenticular/metabolismo , Femenino , Masculino , Adulto , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Adulto Joven , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , ATPasas Transportadoras de Cobre/metabolismo , ATPasas Transportadoras de Cobre/genética , Cobre/metabolismo , Adolescente , Globo Pálido/diagnóstico por imagen , Globo Pálido/metabolismoRESUMEN
BACKGROUND: Systemic inflammatory response syndrome (SIRS) is an uncontrolled systemic inflammatory response. Proanthocyanidins (PC) is a general term of polyphenol compounds widely existed in blueberry fruits and can treat inflammation-related diseases. This study aimed to explore the regulatory effect of PC on lipopolysaccharide (LPS)-induced systemic inflammation and its potential mechanism, providing effective strategies for the further development of PC. METHODS: Here, RAW264.7 macrophages were stimulated with LPS to establish an inflammation model in vitro, while endotoxin shock mouse models were constructed by LPS in vivo. The function of PC was investigated by MTT, ELISA kits, H&E staining, immunohistochemistry, and Western blot analysis. RESULTS: Functionally, PC could demonstrate the potential to mitigate mortality in mice with endotoxin shock, as well as attenuated the levels of inflammatory cytokines (IL-6, TNF-α) and biochemical indicators (AST, ALT, CRE and BUN). Moreover, it had a significant protective effect on lung and kidney tissues damage. Mechanistically, PC exerted anti-inflammatory effects by inhibiting the activation of the NF-κB/NLRP3 signaling pathway. CONCLUSION: PC might have the potential ability of anti-inflammatory effects via modulation of the NF-κB/NLRP3 signaling pathway.
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Antiinflamatorios , Arándanos Azules (Planta) , FN-kappa B , Proteína con Dominio Pirina 3 de la Familia NLR , Proantocianidinas , Transducción de Señal , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proantocianidinas/farmacología , Ratones , Transducción de Señal/efectos de los fármacos , FN-kappa B/metabolismo , Arándanos Azules (Planta)/química , Células RAW 264.7 , Antiinflamatorios/farmacología , Masculino , Lipopolisacáridos/toxicidad , Lipopolisacáridos/farmacología , Choque Séptico/tratamiento farmacológico , Choque Séptico/metabolismo , Choque Séptico/inducido químicamenteRESUMEN
BACKGROUND: The incidence of non-suicidal self-injury (NSSI) has been on the rise in recent years. Studies have shown that people with NSSI have difficulties in emotion regulation and cognitive control. In addition, some studies have investigated the cognitive emotion regulation of people with NSSI which found that they have difficulties in cognitive emotion regulation, but there was a lack of research on cognitive emotion regulation strategies and related neural mechanisms. METHODS: This study included 117 people with NSSI (age = 19.47 ± 5.13, male = 17) and 84 non-NSSI participants (age = 19.86 ± 4.14, male = 16). People with NSSI met the DSM-5 diagnostic criteria, and non-NSSI participants had no mental or physical disorders. The study collected all participants' data of Cognitive Emotion Regulation Questionnaire (CERQ) and functional magnetic resonance imaging (fMRI) to explore the differences in psychological performance and brain between two groups. Afterwards, Machine learning was used to select the found differential brain regions to obtain the highest correlation regions with NSSI. Then, Allen's Human Brain Atlas database was used to compare with the information on the abnormal brain regions of people with NSSI to find the genetic information related to NSSI. In addition, gene enrichment analysis was carried out to find the related pathways and specific cells that may have differences. RESULTS: The differences between NSSI participants and non-NSSI participants were as follows: positive refocusing (t = -4.74, p < 0.01); refocusing on plans (t = -4.11, p < 0.01); positive reappraisal (t = -9.22, p < 0.01); self-blame (t = 6.30, p < 0.01); rumination (t = 3.64, p < 0.01); catastrophizing (t = 9.10, p < 0.01), and blaming others (t = 2.52, p < 0.01), the precentral gyrus (t = 6.04, pFDR < 0.05) and the rolandic operculum (t = -4.57, pFDR < 0.05). Rolandic operculum activity was negatively correlated with blaming others (r = -0.20, p < 0.05). Epigenetic results showed that excitatory neurons (p < 0.01) and inhibitory neurons (p < 0.01) were significant differences in two pathways, "trans-synaptic signaling" (p < -log108) and "modulation of chemical synaptic transmission" (p < -log108) in both cells. CONCLUSIONS: People with NSSI are more inclined to adopt non-adaptive cognitive emotion regulation strategies. Rolandic operculum is also abnormally active. Abnormal changes in the rolandic operculum of them are associated with non-adaptive cognitive emotion regulation strategies. Changes in the excitatory and inhibitory neurons provide hints to explore the abnormalities of the neurological mechanisms at the cellular level of them. Trial registration number NCT04094623.
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Regulación Emocional , Imagen por Resonancia Magnética , Conducta Autodestructiva , Humanos , Conducta Autodestructiva/psicología , Conducta Autodestructiva/fisiopatología , Masculino , Femenino , Regulación Emocional/fisiología , Adulto , Adulto Joven , Adolescente , Cognición/fisiología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Encuestas y CuestionariosRESUMEN
Acquired pure red cell aplasia (PRCA) is anemia associated with the absence of erythroblasts and is characterized by persistent and easy recurrence. However, the underlying mechanisms of acquired PRCA remain obscure, and the role of gene mutations in the pathogenesis of acquired PRCA is not fully characterized. In the present study, we detected thirty newly diagnosed patients with acquired PRCA using whole exome sequencing, and a potential role for STK10 in acquired PRCA was uncovered. The mRNA levels of STK10 in three patients with STK10 mutations were decreased. These three patients had a poor response to immunosuppressive therapy and two died in the follow-up period. Here we report that knockdown of STK10 inhibits erythroid differentiation and promotes apoptosis of K562 cells. We show that knockdown of STK10 resulted in inhibition of ribosome biogenesis and reduced ribosome levels in K562 cells. We also show that the p53 signaling pathway is activated by knockdown of STK10. Our results imply that ribosome biogenesis downregulation together with pathological p53 activation prevents normal erythropoiesis. Our study uncovers a new pathophysiological mechanism leading to acquired PRCA driven by STK10 mutations.
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Eritropoyesis , Mutación , Proteínas Serina-Treonina Quinasas , Aplasia Pura de Células Rojas , Ribosomas , Humanos , Eritropoyesis/genética , Aplasia Pura de Células Rojas/genética , Proteínas Serina-Treonina Quinasas/genética , Células K562 , Masculino , Femenino , Ribosomas/metabolismo , Ribosomas/genética , Persona de Mediana Edad , Anciano , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Apoptosis , Técnicas de Silenciamiento del Gen , AdultoRESUMEN
Mycobacterium chelonae and Sporothrix globosa, both of which are opportunistic pathogens, have been proved to be possible multidrug resistant. However, are all recurring symptoms in chronic infections related to decreasing susceptibility? Here we report a case of sporotrichosis secondary to M. chelonae infection. In addition, we find that the blackish-red spots under the dermoscopic view can be employed as a signal for the early identification and regression of subcutaneous fungal infection.
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Infecciones por Mycobacterium no Tuberculosas , Mycobacterium chelonae , Sporothrix , Esporotricosis , Sporothrix/aislamiento & purificación , Sporothrix/genética , Sporothrix/efectos de los fármacos , Esporotricosis/microbiología , Humanos , Mycobacterium chelonae/aislamiento & purificación , Infecciones por Mycobacterium no Tuberculosas/microbiología , Masculino , Coinfección/microbiologíaRESUMEN
Inflammation and oxidative stress (OS) are the major pathogenic characteristics of acute kidney injury (AKI). Studies have shown that Schisandrin (Sch) could regulate inflammatory disease. However, the function and mechanism of Sch in AKI progression are still unknown. Here, we investigated Sch's potential effects and mechanism on mice's renal damage and macrophages induced by lipopolysaccharide (LPS). Sch decreased LPS-induced inflammatory factor production while increasing the activity of related antioxidant enzymes in macrophages and mouse kidney tissues. Hematoxylin and eosin staining revealed that Sch may have the ability to profoundly inhibit inflammatory cell invasion and tissue damage caused by LPS in renal tissue. Furthermore, Western blot and immunohistochemical studies showed that Sch exerted its effects mainly through up-regulation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 and inhibition of Toll-like receptor 4âmitogen-activated protein kinases/nuclear factor-kappa B pathways. Collectively, this study illustrates that Sch suppresses LPS-stimulated AKI by descending inflammation and OS, illuminating prospective AKI treatment options.
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Background: Multiple system atrophy (MSA) is a disease with diverse symptoms and the commonly used classifications, MSA-P and MSA-C, do not cover all the different symptoms seen in MSA patients. Additionally, these classifications do not provide information about how the disease progresses over time or the expected outcome for patients. Objective: To explore clinical subtypes of MSA with a natural disease course through a data-driven approach to assist in the diagnosis and treatment of MSA. Methods: We followed 122 cases of MSA collected from 3 hospitals for 3 years. Demographic characteristics, age of onset, clinical signs, scale assessment scores, and auxiliary examination were collected. Age at onset; time from onset to assisted ambulation; and UMSARS I, II, and IV, COMPASS-31, ICARS, and UPDRS III scores were selected as clustering elements. K-means, partitioning around medoids, and self-organizing maps were used to analyze the clusters. Results: The results of all three clustering methods supported the classification of three MSA subtypes: The aggressive progression subtype (MSA-AP), characterized by mid-to-late onset, rapid progression and severe clinical symptoms; the typical subtype (MSA-T), characterized by mid-to-late onset, moderate progression and moderate severity of clinical symptoms; and the early-onset slow progression subtype (MSA-ESP), characterized by early-to-mid onset, slow progression and mild clinical symptoms. Conclusions: We divided MSA into three subtypes and summarized the characteristics of each subtype. According to the clustering results, MSA patients were divided into three completely different types according to the severity of symptoms, the speed of disease progression, and the age of onset.
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Progresión de la Enfermedad , Atrofia de Múltiples Sistemas , Humanos , Atrofia de Múltiples Sistemas/clasificación , Atrofia de Múltiples Sistemas/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Análisis por Conglomerados , Edad de Inicio , Índice de Severidad de la EnfermedadRESUMEN
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.
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Imagen por Resonancia Magnética , Esclerosis Múltiple , Nervio Trigémino , Humanos , Masculino , Femenino , Adulto , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Persona de Mediana Edad , Nervio Trigémino/diagnóstico por imagen , Nervio Trigémino/patología , Estudios de Cohortes , Enfermedades del Nervio Trigémino/diagnóstico por imagen , Adulto JovenRESUMEN
Confronting the threat of environment uranium pollution, decades of research have yielded advanced and significant findings in uranium bioremediation, resulting in the accumulation of tremendous amount of high-quality literature. In this study, we analyzed over 10,000 uranium reduction-related papers published from 1990 to the present in the Web of Science based on bibliometrics, and revealed some critical information on knowledge structure, thematic evolution and additional attention. Methods including contribution comparison, co-occurrence and temporal evolution analysis are applied. The results of the distribution and impact analysis of authors, sources, and journals indicated that the United States is a leader in this field of research and China is on the rise. The top keywords remained stable, primarily focused on chemicals (uranium, iron, plutonium, nitrat, carbon), characters (divers, surfac, speciat), and microbiology (microbial commun, cytochrome, extracellular polymeric subst). Keywords related to new strains, reduction mechanisms and product characteristics demonstrated the strongest uptrend, while some keywords related to mechanism and performance were clearly emerging in the past 5 years. Furthermore, the evolution of the thematic progression can be categorized into three stages, commencing with the discovery of the enzymatic reduction of hexavalent uranium to tetravalent uranium, developing in the groundwater remediation process at uranium-contaminated sites, and delving into the research on microbial reduction mechanisms of uranium. For future research, enhancing the understanding of mechanisms, improving uranium removal performance, and exploring practical applications can be considered. This study provides unique insights into microbial uranium reduction research, providing valuable references for related studies in this field.
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Agua Subterránea , Uranio , Uranio/análisis , Hierro , Biodegradación Ambiental , Agua Subterránea/química , BibliometríaRESUMEN
In this paper, Pd-catalyzed [4+2] decarboxylative cycloaddition of 4-vinylbenzodioxinones with barbiturate-derived alkenes has been developed, leading to various spirobarbiturate-chromane derivatives in high yields with excellent diastereo- and enantioselectivities. The scale-up reaction and further derivation of the product were demonstrated. A plausible reaction mechanism was also proposed.
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ETHNOPHARMACOLOGICAL RELEVANCE: Bletilla striata, a traditional medicinal plant, has been utilized as a folk medicine for many years because of its superior biological activity in China. However, Bletilla striata polysaccharide (BSP) has received less attention, and its specific mechanism for ameliorating pulmonary fibrosis is completely unclear. AIMS OF THE STUDY: In this study, we aim to assess BSP on the treatment of PF and explore potential mechanisms. MATERIALS AND METHODS: BSP was successfully extracted and purified from Bletilla striata. The mechanisms were assessed in bleomycin-induced pulmonary fibrosis model and lung fibroblasts activated by transforming growth factor-ß1 (TGF-ß1). Histological analysis, immunofluorescence, Western blot and flow cytometry were used to explore the alterations after BSP intervention. RESULTS: The results in vivo showed an anti-PF effect of BSP treatment, which reduced pathogenic damages. Furthermore, TGF-ß1-induced abnormal migration and upregulated expression of collagen I (COL1A1), vimentin and α-smooth muscle actin (α-SMA) were suppressed by BSP in L929 cells. Moreover, the abnormal proliferation was retarded by inhibiting the cell cycle of G1 to S phase. Immunofluorescence assay showed that BSP activated autophagy and played an antifibrotic role by inhibiting the expression of p62 and phospho-mammalian target of rapamycin (p-mTOR). Last but not least, the suppression of TGF-ß1/Smad signaling pathway was critical for BSP to perform therapeutic effects in vitro and in vivo. CONCLUSION: The possible mechanisms were involved in improving ECM deposition, regulating cell migration and proliferation, and promoting cellular autophagy. Briefly, all of the above revealed that BSP might be a novel therapy for treating pulmonary fibrosis.
Asunto(s)
Fibrosis Pulmonar , Humanos , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Pulmón/metabolismo , Transducción de Señal , Bleomicina , Polisacáridos/farmacología , Polisacáridos/uso terapéuticoRESUMEN
Severe acute pancreatitis (SAP) is an inflammatory disease of the pancreas with a high mortality rate. Macrophages play a crucial role in the pathogenesis of pancreatitis. Tectoridin (Tec) is a highly active isoflavone with anti-inflammatory pharmacological activity. However, the role of Tec in the SAP process is not known. The purpose of this study was to investigate the therapeutic effect and potential mechanism of Tec on SAP. To establish SAP mice by intraperitoneal injection of caerulein and Lipopolysaccharide (LPS), the role of Tec in the course of SAP was investigated based on histopathology, biochemical indicators of amylase and lipase and inflammatory factors. The relationship between Tec and macrophage polarization was verified by immunofluorescence, real-time quantitative PCR and Western blot analysis. We then further predicted the possible targets and signal pathways of action of Tec by network pharmacology and molecular docking, and validated them by in vivo and in vitro. In this study, we demonstrated that Tec significantly reduced pancreatic injury in SAP mice, and decreased serum levels of amylase and lipase. The immunofluorescence and Western blot analysis showed that Tec promoted macrophage M2 polarization. Network pharmacology and molecular docking predicted that Tec may target ERK2 for the treatment of SAP, and in vivo and in vitro experiments proved that Tec inhibited the ERK MAPK signal pathway. In summary, Tec can target ERK2, promote macrophage M2 polarization and attenuate pancreatic injury, Tec may be a potential drug for the treatment of SAP.