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1.
Small ; : e2400292, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38659378

RESUMO

Aqueous Zn batteries employing mildly acidic electrolytes have emerged as promising contenders for safe and cost-effective energy storage solutions. Nevertheless, the intrinsic reversibility of the Zn anode becomes a focal concern due to the involvement of acidic electrolyte, which triggers Zn corrosion and facilitates the deposition of insulating byproducts. Moreover, the unregulated growth of Zn over cycling amplifies the risk of internal short-circuiting, primarily induced by the formation of Zn dendrites. In this study, a class of glucose-derived monomers and a block copolymer are synthesized through a building-block assembly strategy, ultimately leading to uncover the optimal polymer structure that suppresses the Zn corrosion while allowing efficient ion conduction with a substantial contribution from cation transport. Leveraging these advancements, remarkable enhancements are achieved in the realm of Zn reversibility, exemplified by a spectrum of performance metrics, including robust cycling stability without voltage overshoot and short-circuiting during 3000 h of cycling, stable operation at a high depth of charge/discharge of 75% and a high current density, >95% Coulombic efficiency over 2000 cycles, successful translation of the anode improvement to full cell performance. These polymer designs offer a transformative path based on the modular synthesis of polymeric coatings toward highly reversible Zn anode.

2.
Exp Cell Res ; 430(2): 113734, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37532123

RESUMO

Cerebral palsy (CP) is a movement and posture disorder that affects over 50 million people worldwide. Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation has emerged as an attractive therapeutic strategy for CP. The administration route appears to be crucial for hUC-MSC to provide adequate neuroprotection. Wistar rats were given hypoxia-ischemia to make the CP model on postnatal day 5. On postnatal day 21, DiR-labeled hUC-MSC were transplanted into the CP rats by intravenous, intrathecal, and lateral ventricle for cell tracking. Uninfused CP rats served as the negative control. The motor behavioral and pathological alteration was analyzed 11, 25, and 39 days after transplantation to assess motor function, immune inflammation, neurotrophy, and endogenous repair. In vivo imaging tracking techniques revealed that intravenous infusion resulted in fewer transplanted cells in the target brain than intrathecal and lateral ventricle infusion (p<0.05). Three different routes of hUC-MSC infusion improved the motor function of CP rats (p<0.05). At 11 days post-infusion, intrathecal infusion outperformed intravenous with a significant neurotrophic and oligodendrocyte maturation effect (p<0.05). Intrathecal infusion equaled lateral ventricle infusion after 25 days. At 39 days post-infusion, lateral ventricle infusion exceeded intravenous and intrathecal infusion with a significant immunosuppressive effect (p<0.05). Considering the improved effect and less trauma shown early in the intrathecal infusion, repeated intrathecal administration may ultimately lead to the greatest benefit.


Assuntos
Paralisia Cerebral , Transplante de Células-Tronco Mesenquimais , Ratos , Animais , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Ratos Wistar , Paralisia Cerebral/terapia , Rastreamento de Células , Isquemia , Cordão Umbilical
3.
Pharm Biol ; 62(1): 472-479, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38769628

RESUMO

CONTEXT: The Xihuang pill (XHP) is a traditional Chinese medicine formulation that has been historically used in the prevention and treatment of proliferative breast diseases. However, there is a lack of guidelines that offer recommendations for its clinical use. OBJECTIVE: The task force from the Chinese Guangdong Pharmaceutical Association aims to develop evidence-based guidelines for XHP to prevent and treat proliferative breast diseases. METHODS: We searched six Chinese and English electronic databases, including the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Wanfang Medical Database, PubMed, and Embase, up to November 1, 2022. Publications (case reports, clinical observation, clinical trials, reviews) on using XHP to treat proliferative breast diseases were manually searched. The search terms were Xihuang pill, hyperplasia of the mammary gland, breast lump, and mastalgia. The writing team developed recommendations based on the best available evidence. RESULTS: Treatment should be customized based on syndrome identification. We recommend using XHP for the prevention and treatment of breast hyperplasia disease when a patient presents the following syndromes: concurrent blood stasis syndrome, concurrent phlegm-stasis syndrome, and concurrent liver fire syndrome. Safety indicators, including blood analysis and liver and kidney function monitoring, should be performed regularly during treatment. CONCLUSIONS: Current clinical evidence suggests that XHP can be used as a standalone treatment or in conjunction with other medications to prevent and manage breast hyperplasia diseases. More randomized controlled studies are warranted to establish high-quality evidence of its use.


Assuntos
Doenças Mamárias , Medicamentos de Ervas Chinesas , Hiperplasia , Medicina Tradicional Chinesa , Humanos , Feminino , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/administração & dosagem , Doenças Mamárias/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , China
4.
Dev Neurosci ; 45(1): 8-18, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36323241

RESUMO

Cerebral palsy (CP) is a motor and postural disorder syndrome caused by the nonprogressive dysfunction of the developing brain. Previous studies strongly indicated that the Nogo-A gene might be related to the pathogenesis of CP. The objective of this research was to explore the relationship between Nogo-A polymorphisms (rs1012603, rs12464595, and rs2864052) and CP in Southern China. The Hardy-Weinberg equilibrium (HWE) testing, allele and genotype frequencies analysis, and haplotype association analysis were applied to the genotyping of 592 CP children and 600 controls. The results showed that the allele and genotype frequencies of rs1012603 of CP group were significantly different from the control group. The haplotype "TTGGG" was significantly associated with an increased risk of CP. The allele frequencies of rs1012603 were significant differences between CP with spastic diplegia, female CP cases, and controls. Furthermore, significant differences in allele and genotype frequencies were also noticed between GMFCS I of CP and controls for rs1012603, and significant differences in allele and genotype frequencies were observed between the ADL (>9) of CP and controls for rs1012603 and rs12464595. This study showed that the SNPs rs1012603 of Nogo-A were significantly correlated with CP, and the correlations were also found in spastic diplegia, GMFCS I of CP, ADL (>9) of CP, and female subgroups, indicating that Nogo-A might mainly affect mild types of CP and there might be sex-related differences.


Assuntos
Paralisia Cerebral , Criança , Feminino , Humanos , Estudos de Casos e Controles , Paralisia Cerebral/genética , China , Proteínas Nogo/genética , Polimorfismo de Nucleotídeo Único/genética , Masculino
5.
Small ; 19(26): e2300230, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36938705

RESUMO

As intelligent microsystems develop, many revolutionary applications, such as the swallowing surgeon proposed by Richard Feynman, are about to evolve. Nonetheless, integrable energy storage satisfying the demand for autonomous operations has emerged as a major obstacle to the deployment of intelligent microsystems. A reason for the lagging development of integrable batteries is the challenge of miniaturization through microfabrication procedures. Lithium batteries, generated by the most successful battery chemistry, are not stable in the air, thus creating major manufacturing challenges. Other cations (Na+ , Mg2+ , Al3+ , K+ ) are still in the early stages of development. In contrast, the superior stability of zinc batteries in the air brings high compatibility to microfabrication protocols and has already demonstrated excellent practicability in full-sized devices. To obtain energy-dense and high-power zinc microbatteries within square-millimeter or smaller footprints, sandwich, pillar, and Swiss-roll configurations are developed. Thin interdigital and fiber microbatteries find their applications being integrated into wearable devices and electronic skin. It is foreseeable that zinc microbatteries will find their way into highly integrated microsystems unlocking their full potential for autonomous operation. This review summarizes the material development, configuration innovation, and application-oriented integration of zinc microbatteries.

6.
Exp Lung Res ; 49(1): 49-62, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36719141

RESUMO

Purpose: Endoplasmic reticulum (ER) stress regulates mucus hypersecretion, and may activate downstream factors via TBK1 signaling to induce gene expression. However, it remains unclear whether ER stress promotes airway mucus secretion through the TBK1 pathway. We aimed to investigate the role of the TBK1 pathway in the regulation of MUC5AC expression in a mouse model of house dust mite (HDM)-induced allergic asthma. Materials and Methods: Mice with HDM-induced asthma and human bronchial epithelial BEAS-2B cells were treated with amlexanox, an anti-allergy drug (25 µM), or 4-PBA (10 mM). Tissue and cell samples were collected. Tissue samples were stained with hematoxylin and eosin (H&E) or periodic acid Schiff (PAS) to evaluate pathology. Protein expression was analyzed by western blotting and immunofluorescence. Results: Mice exposed to HDM presented ER stress and hypersecretion of mucus Muc5ac from airway epithelial cells (p < 0.001). Similar results were observed in BEAS-2B cells following exposure to HDM. Both in vivo and in vitro studies revealed that HDM-induced ER stress induced MUC5AC overexpression via TBK1 signaling. Amlexanox and 4-PBA markedly reduced mucus production and weakened the TBK1 signal, which mediates MUC5AC hypersecretion. Conclusion: TBK1 plays a pivotal role in HDM-induced ER stress, leading to overproduction of MUC5AC in the asthmatic airway epithelium. The overproduction of MUC5AC can be significantly decreased by inhibiting TBK1 or ER stress using 4-PBA. These findings highlight potential target-specific therapies for patients with chronic allergic asthma.


Assuntos
Asma , Pyroglyphidae , Humanos , Camundongos , Animais , Pyroglyphidae/metabolismo , Asma/metabolismo , Estresse do Retículo Endoplasmático , Epitélio/metabolismo , Proteínas Serina-Treonina Quinases , Mucina-5AC/genética , Mucina-5AC/metabolismo
7.
Brain ; 145(1): 119-141, 2022 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-34077496

RESUMO

Cerebral palsy is the most prevalent physical disability in children; however, its inherent molecular mechanisms remain unclear. In the present study, we performed in-depth clinical and molecular analysis on 120 idiopathic cerebral palsy families, and identified underlying detrimental genetic variants in 45% of these patients. In addition to germline variants, we found disease-related postzygotic mutations in ∼6.7% of cerebral palsy patients. We found that patients with more severe motor impairments or a comorbidity of intellectual disability had a significantly higher chance of harbouring disease-related variants. By a compilation of 114 known cerebral-palsy-related genes, we identified characteristic features in terms of inheritance and function, from which we proposed a dichotomous classification system according to the expression patterns of these genes and associated cognitive impairments. In two patients with both cerebral palsy and intellectual disability, we revealed that the defective TYW1, a tRNA hypermodification enzyme, caused primary microcephaly and problems in motion and cognition by hindering neuronal proliferation and migration. Furthermore, we developed an algorithm and demonstrated in mouse brains that this malfunctioning hypermodification specifically perturbed the translation of a subset of proteins involved in cell cycling. This finding provided a novel and interesting mechanism for congenital microcephaly. In another cerebral palsy patient with normal intelligence, we identified a mitochondrial enzyme GPAM, the hypomorphic form of which led to hypomyelination of the corticospinal tract in both human and mouse models. In addition, we confirmed that the aberrant Gpam in mice perturbed the lipid metabolism in astrocytes, resulting in suppressed astrocytic proliferation and a shortage of lipid contents supplied for oligodendrocytic myelination. Taken together, our findings elucidate novel aspects of the aetiology of cerebral palsy and provide insights for future therapeutic strategies.


Assuntos
Paralisia Cerebral , Deficiência Intelectual , Animais , Paralisia Cerebral/genética , Cognição , Estudos de Coortes , Comorbidade , Humanos , Deficiência Intelectual/complicações , Deficiência Intelectual/genética , Camundongos
8.
Dev Med Child Neurol ; 65(1): 86-93, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35674175

RESUMO

AIM: To compare the risks of adverse events 3 months after Onabotulinumtoxin-A and Lanbotulinumtoxin-A injections in children with cerebral palsy (CP) and to identify risk factors and associations. METHOD: A total of 1037 children (682 males, 355 females; mean age 5 years 2 months [SD 3 years]; age range 2 years-17 years 10 months) with CP underwent 1013 Onabotulinumtoxin-A injections and 418 Lanbotulinumtoxin-A injections from 2012 to 2021. Information was recorded in a purpose-built database. RESULTS: The adverse event rates of Onabotulinumtoxin-A and Lanbotulinumtoxin-A were reported as 13.92% and 11.96% respectively. Most adverse events were mild and self-limiting. Children in Gross Motor Function Classification System (GMFCS) levels IV to V had a higher risk of adverse events than those in GMFCS levels I to III (odds ratio [OR] [95% confidence interval {CI}] = 3.65 [1.56, 5.40], p < 0.01). The history of recent illness and higher dose increased the likelihood of adverse events (OR [95% CI] = 2.00 [1.55, 3.00] and 2.20 [1.53, 3.07] respectively, p < 0.01). Sex, age, and the number of injections had no significant effect on adverse event rates (p > 0.05). The incidence of upper respiratory tract infection and lower respiratory tract infection after injections was weakly correlated with the incidence before injections (r = 0.36 and r = 0.27 respectively, p < 0.01). INTERPRETATION: Occurrence of adverse events was similar between Onabotulinumtoxin-A and Lanbotulinumtoxin-A in children with CP. Dose, GMFCS level, and health background were risk factors. WHAT THIS PAPER ADDS: The prevalence of adverse events was similar between Onabotulinumtoxin-A and Lanbotulinumtoxin-A in children with cerebral palsy (CP). The prevalence of adverse events increased with the severity of CP and the injected dose. Sex, age, and number of injections had no significant effect on the prevalence of adverse events.


Assuntos
Toxinas Botulínicas Tipo A , Paralisia Cerebral , Criança , Masculino , Feminino , Humanos , Lactente , Pré-Escolar , Estudos Retrospectivos , Injeções , Incidência , Índice de Gravidade de Doença
9.
Nano Lett ; 22(16): 6692-6699, 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-35939782

RESUMO

We report the monolithic fabrication of twin microtube cavities by a nanomembrane origami method for achieving collective coupling of 3D confined optical modes. Owing to the well-aligned twin geometries, two sets of 3D confined optical modes in twin microtubes are spectrally and spatially matched, by which both the fundamental and higher-order axial modes are respectively coupled with each other. Multiple groups of the coupling modes provide multiple effective channels for energy exchange between coupled microcavities illustrated by the measured spatial optical field distributions. The spectral anticrossing and changing-over features of each group of coupled modes are revealed in experiments and calculations, indicating the occurrence of strong coupling. In addition, the simulated 3D mode profiles of twin microcavities confirm the collective strong coupling behavior, which shows good agreement with experiments. The collective coupling of 3D confined resonant modes promises broad applications in multichannel optical signal processing, nanophotonics, and 3D non-Hermitian systems.

10.
J Proteome Res ; 21(3): 671-682, 2022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-35018779

RESUMO

The long-term effect of botulinum neurotoxin A (BoNT-A) on children with cerebral palsy (CP) is unclear, and how the dynamic changes of metabolites impact the duration of effect remains unknown. To tackle this, we collected 120 plasma samples from 91 children with spastic CP for analysis, with 30 samples in each time point: prior to injection and 1, 3, and 6 months after injection. A total of 354 metabolites were identified across all the time points, 39 of which exhibited significant changes (with tentative IDs) (p values <0.05, VIP > 1). Principal component analysis and partial least-squares discriminant analysis disclosed a clear separation between different groups (p values <0.05). Network analysis revealed the coordinated changes of functional metabolites. Pathway analysis highlighted the metabolic pathways associated with energy consumption and glycine, serine, and threonine metabolism and cysteine and methionine metabolism. Collectively, our results identified the significant dynamic changes of plasma metabolite after BoNT-A injections on children with CP. Metabolic pathways associated with energy expenditure might provide a new perspective for the effect of BoNT-A in children with CP. Glycine, serine, and threonine metabolism and cysteine and methionine metabolism might be related to the duration of effect of BoNT-A.


Assuntos
Toxinas Botulínicas Tipo A , Paralisia Cerebral , Fármacos Neuromusculares , Toxinas Botulínicas Tipo A/uso terapêutico , Paralisia Cerebral/complicações , Paralisia Cerebral/tratamento farmacológico , Criança , Cisteína , Glicina , Humanos , Injeções Intramusculares , Metionina , Espasticidade Muscular/complicações , Espasticidade Muscular/tratamento farmacológico , Fármacos Neuromusculares/uso terapêutico , Serina , Treonina , Resultado do Tratamento
11.
Allergy ; 77(2): 483-498, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34365653

RESUMO

BACKGROUND: Alteration of commensal microbiota is highly correlated with the prevalence of allergic reactions to food in the gastrointestinal tract. The mechanisms by which microbiota modulate food allergen sensitization in the mucosal site are not fully understood. METHODS: We generate DCs specific knockout of retinoic acid receptor α (Rara) gene mice (DC KO Rara) to evaluate food sensitization. The bile acid-activated retinoic acid response was evaluated by flow cytometry, real-time RT-PCR and Illumina transcriptome sequencing. The global effect of Abx treatment on BA profiles in the mucosal lymph tissue mLN in mice was examined by UPLC-MS analysis. RESULTS: In this study, we demonstrate that depletion of commensal gut bacteria leads to enhanced retinoic acid (RA) signaling in mucosal dendritic cells (DCs). RA signaling in DCs is required for the production of food allergen-specific IgE and IgG1. Antibiotics induced an enlarged bile acid (BA) pool, and dysregulated BA profiles contributed to enhanced RA signaling in mucosal DCs. BA-activated RA signaling promoted DC upregulation of interferon I signature, RA signature, OX40L, and PDL2, which may lead to T helper 2 differentiation of CD4+ T cells. BA-activated RA signaling involved the farnesoid X receptor and RA receptor α (RARa) interaction. Depletion of bile acid reduces food allergen specific IgE and IgG1 levels in mice. CONCLUSION: Our research unveils a mechanism of food sensitization modulated by BA-RA signaling in DCs, which suggests a potential new approach for the intervention of food allergic reactions.


Assuntos
Hipersensibilidade Alimentar , Tretinoína , Alérgenos/farmacologia , Animais , Ácidos e Sais Biliares/farmacologia , Cromatografia Líquida , Células Dendríticas , Humanos , Imunoglobulina E , Imunoglobulina G , Camundongos , Espectrometria de Massas em Tandem , Tretinoína/farmacologia
12.
Nutr Neurosci ; 25(12): 2570-2576, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34663203

RESUMO

OBJECTIVES: To investigate the reproducibility, stability, internal consistency and the ability to grade malnutrition of Subjective Global Nutritional Assessment (SGNA) in outpatient children with cerebral palsy. METHODS: This was a part of a larger, cross-sectional study (ChiCTR2000033869) at the outpatient of a tertiary hospital. The recruitment and data collection of children with Cerebral Palsy aged from 1 to 18 years were from August 2020 to March 2021. The concurrent validity, inter-rater reliability, test-retest reliability and internal consistency of SGNA were tested. To analyze data, specificity, sensitivity, Kendall coefficient, Cohen's kappa coefficient, Spearman coefficient and Cronbach's α coefficient were used. RESULTS: The agreement between SGNA and anthropometric data was moderate to strong (k = 0.540-0.821). The sensitivity (71.70% to 89.74%) and specificity (77.67% to 91.03%) of SGNA to identify participants with z-score ≤-2 were good. The sensitivity of SGNA to identify participants with weight for age z-score ≤-3 was poor (30.00%). The interrater reliability (k = 0.703) and test-retest reliability (k = 0.779) were good. The item of edema was with poor agreement to SGNA nutritional grades (rs = 0.072), and after deleting it from SGNA, the Cronbach's α coefficient of SGNA increased from 0.736 to 0.871. FINDINGS: SGNA is good at identifying malnourished outpatient children with cerebral palsy, with excellent reproducibility and short-time stability. However, the ability to grade malnutrition is unsatisfactory. For further application in this group, a more appropriate item should be designed to replace the item of edema.


Assuntos
Paralisia Cerebral , Desnutrição , Criança , Humanos , Avaliação Nutricional , Reprodutibilidade dos Testes , Paralisia Cerebral/complicações , Pacientes Ambulatoriais , Estudos Transversais , Desnutrição/diagnóstico , Desnutrição/etiologia
13.
Small ; 16(35): e2002410, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32700453

RESUMO

Miniaturization of batteries lags behind the success of modern electronic devices. Neither the device volume nor the energy density of microbatteries meets the requirement of microscale electronic devices. The main limitation for pushing the energy density of microbatteries arises from the low mass loading of active materials. However, merely pushing the mass loading through increased electrode thickness is accompanied by the long charge transfer pathway and inferior mechanical properties for long-term operation. Here, a new spiral microelectrode upon stress-actuation accomplishes high mass loading but short charge transfer pathways. At a small footprint area of around 1 mm2 , a 21-fold increase of the mass loading is achieved while featuring fast charge transfer at the nanoscale. The spiral microelectrode delivers a maximum area capacity of 1053 µAh cm-2 with a retention of 67% over 50 cycles. Moreover, the energy density of the cylinder microbattery using the spiral microelectrode as the anode reaches 12.6 mWh cm-3 at an ultrasmall volume of 3 mm3 . In terms of the device volume and energy density, the cylinder microbattery outperforms most of the current microbattery technologies, and hence provides a new strategy to develop high-performance microbatteries that can be integrated with miniaturized electronic devices.

14.
Biochem Biophys Res Commun ; 511(3): 671-678, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30827505

RESUMO

Some patients with irritable bowel syndrome (IBS) have visceral hypersensitivity, which contributes to their abdominal pain. miRNA-29 was detected to be significantly upregulated in colonic tissues of patients with IBS. However, it is unknown whether miRNA-29a is involved in the visceral hypersensitivity pathogenesis of IBS. This study aimed to investigate whether miRNA-29a participates in visceral hypersensitivity in IBS. We investigated miRNA-29a in intestinal biopsies collected during endoscopy of patients with IBS (n = 10) and healthy volunteers (control) (n = 10). In addition, a water avoidance stress (WAS)-induced visceral hypersensitivity IBS mouse model was established. The abdominal withdrawal reflex (AWR) scores of mice in response to colorectal distention were used to assess visceral sensitivity. Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) was used to measure miRNA-29a levels. Immunofluorescence, RT-qPCR and western blot were used to measure 5-HT7 receptor (HTR7) levels. Bioinformatic analysis and luciferase reporter assays were used to detect the direct relationship between miRNA-29a and HTR7. Finally, alterations in the levels of HTR7 and miRNA-29a were measured in the human intestinal epithelial cell line NCM460 after transfection with miRNA-29a inhibitor or mimic. Intestinal tissues from patients with IBS and WAS-induced IBS mice had increased levels of miRNA-29a, but reduced levels of HTR7. MiRNA-29a knockout resulted in overexpression of HTR7 and attenuated visceral hyperalgesia in WAS-induced IBS mice. HTR7 was a direct target of miRNA-29a. Based on analyses of intestinal tissue samples from patients with IBS and WAS-induced miRNA-29a-/- mice, miRNA-29a plays a role in the visceral hyperalgesia pathogenesis of IBS, probably through regulating HTR7 expression.


Assuntos
Hiperalgesia/genética , Síndrome do Intestino Irritável/genética , MicroRNAs/genética , Receptores de Serotonina/genética , Animais , Linhagem Celular , Regulação para Baixo , Humanos , Hiperalgesia/complicações , Hiperalgesia/patologia , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/patologia , Camundongos Endogâmicos C57BL , MicroRNAs/análise , Receptores de Serotonina/análise , Regulação para Cima , Dor Visceral/complicações , Dor Visceral/genética , Dor Visceral/patologia
15.
Mediators Inflamm ; 2019: 3153240, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32082074

RESUMO

Higher concentrations of reactive oxygen species (ROS) have been associated with epithelial cell damage, cell shedding, and airway hyperresponsiveness. Previous studies have indicated that transforming growth factor-beta (TGF-ß) mediates ROS production and NADPH oxidase (NOX) activity. In our previous study, we also observed that TGF-ß3 increases mucus secretion in airway epithelial cells in an autophagy-dependent fashion. Although it is well known that the relationship between ROS and autophagy is cell context-dependent, the exact mechanism of action remains unclear. The following study examined whether ROS act as upstream of autophagy activation in response to TGF-ß3 induction. Using an allergic inflammation mouse model induced by house dust mite (HDM), we observed elevated lung amounts of TGF-ß3 accompanied by increased ROS levels. And we found that ROS levels were elevated and NOX4 expression was increased in TGF-ß3-induced epithelial cells, while the lack of NOX4 in the epithelial cells could reduce ROS generation and autophagy-dependent MUC5AC expression treated with TGF-ß3. Furthermore, our studies demonstrated that the Smad2/3 pathway was involved in TGF-ß3-induced ROS generation by promoting NOX4 expression. The inhibition of ROS generation by N-Acetyl-L-cysteine (NAC) resulted in a decrease in mucus expression and autophagy activity in vivo as well as in vitro. Finally, TGF-ß3-neutralizing antibody significantly reduced the ROS generation, mucus expression, and autophagy activity and also decreased the phosphorylation of Smad2 and Smad3. Taken together, the obtained results revealed that persistent TGF-ß3 activation increased ROS levels in a NOX4-dependent pathway and subsequently induced autophagy as well as MUC5AC expression in the epithelial cells.


Assuntos
Autofagia/efeitos dos fármacos , NADPH Oxidase 4/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Crescimento Transformador beta3/metabolismo , Acetilcisteína/farmacologia , Animais , Western Blotting , Linhagem Celular , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Mucina-5AC/metabolismo , NADPH Oxidase 4/genética , NADPH Oxidases/metabolismo , Pyroglyphidae/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos
16.
J Hepatol ; 68(6): 1123-1128, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29452204

RESUMO

BACKGROUND & AIM: Chronic infection with hepatitis B virus (HBV) in children is a serious health problem worldwide. How to treat children with immune-tolerant chronic hepatitis B infection, commonly characterized by hepatitis B e antigen (HBeAg) positivity, high viral load, normal or mildly elevated alanine aminotransferase and no or minimal inflammation in liver histology, remains unresolved. This trial aims to study the benefits of antiviral therapy in children with these characteristics. METHODS: This is a pilot open-label randomized controlled study. From May 2014 to April 2015, 69 treatment-naive chronically HBV-infected children, aged 1 to 16 years, who had immune-tolerant characteristics were recruited to this trial and randomly assigned, in a 2:1 ratio, to treatment group and control group. Patients in the treatment group received either interferon-α (IFN) monotherapy or consecutively received IFN monotherapy, combination therapy of IFN and lamivudine (LAM), and LAM therapy alone. All patients were observed until week 96. RESULTS: At baseline, epidemiological, biochemical, serological, virological and histological indices were consistent across the treatment and control groups. Of the 46 patients in the treatment group, 73.91% had undetectable serum HBV DNA, 32.61% achieved HBeAg seroconversion and 21.74% lost hepatitis B surface antigen (HBsAg) at the endpoint. No LAM resistance emerged at week 96. In the control group, only one (4.35%) patient underwent spontaneous HBeAg seroconversion and had undetectable serum HBV DNA during observation, and moreover, none developed HBsAg clearance. For all patients, no serious adverse events were observed. CONCLUSION: Antiviral treatment with a sequential combination of IFN and LAM resulted in a significant improvement in the rates of undetectable serum HBV DNA, HBeAg seroconversion and HBsAg loss in children with chronic HBV infection and immune-tolerant characteristics. LAY SUMMARY: There is a lack of data regarding treatment of immune-tolerant chronic hepatitis B (CHB). It remains unresolved how children with immune-tolerant CHB should be treated. This paper reports the outcomes from a pilot open-label randomized controlled trial on antiviral therapy in children with immune-tolerant characteristics. It shows that a sequential combination of interferon-α and lamivudine was beneficial.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/imunologia , Adolescente , Alanina Transaminase/sangue , Antivirais/administração & dosagem , Criança , Pré-Escolar , DNA Viral/sangue , Quimioterapia Combinada , Feminino , Anticorpos Anti-Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/virologia , Humanos , Tolerância Imunológica , Lactente , Interferon-alfa/administração & dosagem , Interferon-alfa/uso terapêutico , Lamivudina/administração & dosagem , Lamivudina/uso terapêutico , Masculino , Projetos Piloto , Soroconversão
17.
Appl Opt ; 57(16): 4677-4682, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29877377

RESUMO

Bessel beams with tunable spot size are desirable for many applications such as laser material processing, optical trapping, and imaging. In this paper, we report experimental and simulation results of using a segmented deformable mirror to generate zero- and higher-order Bessel beams that have a controllable transverse and longitudinal shape. The tilt angle and piston position of the mirror segments are optimized to recreate the phase structure of a reflective axicon. Zero-order Bessel beams are generated at various beam converging angles, and their core diameter, peak intensity, and depth-of-focus are found to agree with the calculated results. By applying a phase ramp along the azimuthal direction, the first-order Bessel beam is generated with the characteristic annular shape. Because deformable mirrors have low absorption and dispersion and operate at a fast frame rate, they are a promising candidate for spatial beam shaping of high-power ultrafast lasers, which are used in material processing applications.

18.
Int J Neurosci ; 126(3): 227-34, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26001202

RESUMO

AIM: To investigate the influence of onset age on the occurrence and progression of cognitive dysfunction using neuropsychological tests and the electrophysiological component P300 in both early-onset Parkinson's disease (EOPD) and late-onset Parkinson's disease (LOPD) patients. METHODS: A cohort of 76 EOPD patients and 166 LOPD patients was recruited for this study. Demographic information and clinical features, including age, disease duration, education level, family history, the Unified Parkinson's Disease Rating Scale, the Hoehn and Yahr stage, and depression scores were documented for each patient. The Mini-Mental State Examination, Montreal Cognitive Assessment (MoCA), Wechsler Adult Intelligence Scale - Revised, Chinese version (WAIS-RC) and Wechsler Memory Scale - Revised, Chinese version (WMS-RC) were used. In addition, P300 was also examined to assess cognitive function. RESULTS: Although EOPD patients had longer disease duration, their cognitive dysfunction progressed more slowly. The MoCA tests revealed that EOPD patients had higher scores in visuospatial function, attention, delayed recall, and orientation than the LOPD patients. The difference between the two groups on the WMS-RC test did not reach significance, whereas the scores in executive function, visuospatial function and attention as measured on the WAIS-RC test were significantly lower in the LOPD group. In addition, P300 latencies were markedly delayed and P300 amplitudes were reduced in the LOPD group. CONCLUSIONS: The current findings demonstrated that cognitive dysfunction progressed more slowly in the EOPD group. Although the LOPD patients exhibited shorter disease durations, their cognitive abilities, including executive function, visuospatial function and attention, may have been impaired.


Assuntos
Idade de Início , Atenção/fisiologia , Cognição/fisiologia , Função Executiva/fisiologia , Doença de Parkinson/psicologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/diagnóstico
19.
Wei Sheng Yan Jiu ; 45(5): 743-748, 2016 Sep.
Artigo em Zh | MEDLINE | ID: mdl-29903124

RESUMO

OBJECTIVE: To assess the relative validity of food frequency questionnaire( FFQ) for estimating dietary nutrients and food intakes. METHODS: Using random sampling methods to select 200 people from Minhang District and Jinshan District. Dietary intakes were estimated by weighed dietary records combining with 24 h dietary recalls( as reference method) and food frequency questionnaire. Relative validity were examined by T-test, Wilcoxon rank test and correlation analysis. RESULTS: The foods groups were the same in FFQ and 24 h dietary recalls. Correlated with daily intake of grains, beans and products, vegetables, cruciferous vegetables, fruits, meat and poultry, aquatic product, milk and products in two methods( Correlation coefficients: 0. 248- 1. 000). The daily food of energy, protein, fat, carbohydrate, cholesterol had significantly positive correlation in FFQ and 24 h dietary recalls( Correlation coefficients: 0. 209- 0. 340). No statistical difference in energy and fat. The daily food of Mg, K, P, Mn, I, Ca, Se had significantly positive correlation in two methods( Correlation coefficients: 0. 204-0. 419). No statistical difference in Mg, K, P, Mn, I. The daily food of vitamin B1、B2、C、niacin had significantly positive correlation in two methods( Correlation coefficients:0. 170- 0. 305). No statistical difference in vitamin B1、B2. CONCLUSION: Food frequency questionnaire can be used to evaluate dietary intakes of I, cruciferous vegetables, soy isoflavones, energy, fat, Mg, K, P, Mn, vitamin B1 and vitamin B2.


Assuntos
Registros de Dieta , Inquéritos sobre Dietas/normas , Dieta , Ingestão de Energia , Inquéritos e Questionários/normas , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes
20.
Neurol Sci ; 36(4): 571-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25370917

RESUMO

Monocyte chemoattractant protein-1 (MCP-1) and its receptor CC chemokine receptor-2 (CCR2) play important roles in neuroinflammation and they have been shown to be involved in Parkinson's disease (PD) pathogenesis. In addition, several studies have suggested a role for the MCP-1 and CCR2 genotypes in cognitive impairment and depression, which are common non-motor symptoms in PD patients. In this study, a cohort of 521 PD patients and 556 cases of healthy controls were recruited to investigate the association between the MCP-1 2518A/G (rs1064211) and CCR2 V64I (rs1799864) gene polymorphisms and PD risk in the Chinese population. We also analyze the influence of these genotypes on the cognitive function and depression in PD patients by comparing Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Wechsler Adult Intelligence Scale-Chinese Revision (WAIS-RC), Wechsler Memory Scale-Chinese Revision (WMS-RC) and Hamilton Depression Rating Scale (HAMD) ratings in 217 PD patients. Our results showed no significant differences in the genotype frequency between the PD group and the control group (P > 0.05). In addition, we also failed to find an influence of the MCP-1 and CCR2 genotypes on MMSE scores, MoCA scores, WAIS-RC scores, WMS-RC scores and HAMD scores in PD patients (P > 0.05). The MCP-1 and CCR2 gene polymorphisms may not be genetic risk factors for PD in the Han Chinese population, and they do not appear to influence cognitive function and depression in PD patients.


Assuntos
Quimiocina CCL2/genética , Predisposição Genética para Doença/genética , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores CCR2/genética , Idoso , Análise de Variância , Povo Asiático/etnologia , Povo Asiático/genética , Distribuição de Qui-Quadrado , Estudos de Coortes , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/etnologia , Escalas de Graduação Psiquiátrica
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