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1.
Proc Natl Acad Sci U S A ; 121(6): e2305947121, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38289952

RESUMO

Optic neuropathies, characterized by injury of retinal ganglion cell (RGC) axons of the optic nerve, cause incurable blindness worldwide. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) represent a promising "cell-free" therapy for regenerative medicine; however, the therapeutic effect on neural restoration fluctuates, and the underlying mechanism is poorly understood. Here, we illustrated that intraocular administration of MSC-sEVs promoted both RGC survival and axon regeneration in an optic nerve crush mouse model. Mechanistically, MSC-sEVs primarily targeted retinal mural cells to release high levels of colony-stimulating factor 3 (G-CSF) that recruited a neural restorative population of Ly6Clow monocytes/monocyte-derived macrophages (Mo/MΦ). Intravitreal administration of G-CSF, a clinically proven agent for treating neutropenia, or donor Ly6Clow Mo/MΦ markedly improved neurological outcomes in vivo. Together, our data define a unique mechanism of MSC-sEV-induced G-CSF-to-Ly6Clow Mo/MΦ signaling in repairing optic nerve injury and highlight local delivery of MSC-sEVs, G-CSF, and Ly6Clow Mo/MΦ as therapeutic paradigms for the treatment of optic neuropathies.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Traumatismos do Nervo Óptico , Camundongos , Animais , Axônios/metabolismo , Fator Estimulador de Colônias de Granulócitos/metabolismo , Regeneração Nervosa/fisiologia , Traumatismos do Nervo Óptico/terapia , Traumatismos do Nervo Óptico/metabolismo , Células Ganglionares da Retina/fisiologia , Células-Tronco Mesenquimais/metabolismo , Vesículas Extracelulares/metabolismo , Macrófagos/metabolismo
2.
J Infect Dis ; 229(6): 1866-1877, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38262678

RESUMO

BACKGROUND: Active case finding (ACF) is a potentially promising approach for the early identification and treatment of tuberculosis patients. However, evidence on its cost-effectiveness, particularly in low- and middle-income countries, remains limited. This study evaluates the cost-effectiveness of a community-based ACF practice in Shenzhen, China. METHODS: We employed a Markov model-based decision analytic method to assess the costs and effectiveness of 3 tuberculosis detection strategies: passive case finding (PCF), basic ACF, and advanced ACF. The analysis was conducted from a societal perspective on a dynamic cohort over a 20-year horizon, focusing on active tuberculosis (ATB) prevalence and the incremental cost-effectiveness ratio (ICER). RESULTS: Compared to the PCF strategy, the basic and advanced ACF strategies effectively reduced ATB cases by 6.8 and 10.2 per 100 000 population, respectively, by the final year of this 20-year period. The ICER for the basic and advanced ACF strategies were ¥14 757 and ¥8217 per quality-adjusted life-year, respectively. Both values fell below the cost-effectiveness threshold. CONCLUSIONS: Our findings indicate that the community-based ACF screening strategy, which targets individuals exhibiting tuberculosis symptoms, is cost-effective. This underscores the potential benefits of adopting similar community-based ACF strategies for symptomatic populations in tuberculosis-endemic areas.


Assuntos
Análise Custo-Benefício , Cadeias de Markov , Tuberculose , Humanos , China/epidemiologia , Tuberculose/diagnóstico , Tuberculose/economia , Tuberculose/epidemiologia , Programas de Rastreamento/economia , Programas de Rastreamento/métodos , Prevalência
3.
Prostate ; 84(2): 212-220, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37899678

RESUMO

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common condition that affects the quality of life of older men. Specific micronutrients, including retinol, retinyl esters, carotenoids, vitamin E, and vitamin C, have antioxidant and anti-inflammatory properties. However, the correlation between serum concentrations of these micronutrients and BPH is unclear. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES), which included 2067 representative US men. BPH was assessed using the self-reported questionnaire. This association was explored by adjusting for confounders using multivariate logistic regression. RESULTS: After fully adjusting for confounders, for every 0.01 µmol/L increase in serum retinyl esters, the risk of BPH increased by 2% (OR = 1.02; 95% CI: 1.01-1.03; p = 0.006). Based on the Bonferroni-corrected p-value, we found this correlation to be significant. One µmol/L increase in total carotenoids was associated with a 22% increase in BPH risk (OR = 1.22; 95% CI: 1.03-1.46; p = 0.025). By analyzing the correlation between different types of carotenoids and BPH, we also found that ß-carotenoids (OR = 1.43; 95% CI: 1.03-1.99; p = 0.036) was also positively correlated with BPH. The subgroup analysis revealed a positive correlation between serum vitamin E (OR = 1.02; 95% CI: 1.00-1.04; p = 0.018) and BPH in men under 60 years of age. Serum retinyl ester (OR = 1.02; 95% CI: 1.01-1.04; p = 0.008) and carotenoid (OR = 1.52; 95% CI: 1.22-1.87; p < 0.001) concentrations were positively correlated with BPH in men over 60 years of age. CONCLUSION: Our study suggests that excessive serum retinyl esters, total carotenoids, and especially ß-carotenoids are potential risk factors for BPH, and this association should be further investigated.


Assuntos
Hiperplasia Prostática , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Hiperplasia Prostática/epidemiologia , Inquéritos Nutricionais , Qualidade de Vida , Micronutrientes , Ésteres de Retinil , Carotenoides , Vitamina E
4.
Appl Opt ; 63(9): 2140-2147, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38568565

RESUMO

The peripheral retinal refractive state plays an important role in eye growth and development and is closely related to the development of myopia. Existing methods for measuring the peripheral retinal refractive state are cumbersome and can only detect in a limited range. To address the above shortcomings, this paper proposes a retinal refractive state detection method using optical refractive compensation imaging. First, a series of defocus images is captured using an optical system, and then the images are enhanced and filtered. Subsequently, the Sobel function is applied to calculate sharpness, and the asymmetric Gaussian (AG) model is employed for peak fitting, allowing for the determination of the fundus retina's overall refractive compensation value. We performed consistency analysis on the central and peripheral diopters with autorefractor KR-8900 (Topcon, Japan) and WAM-5500 (Grand Seiko, Japan), respectively. The intraclass correlation coefficients (ICCs) are all greater than 0.9, showing good consistency. This is a promising alternative to the current techniques for assessing the refraction of the peripheral retina.

5.
Ecotoxicol Environ Saf ; 277: 116357, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38677073

RESUMO

Polystyrene microplastics (PS-MPs) are new types of environmental pollutant that have garnered significant attention in recent years since they were found to cause damage to the human respiratory system when they are inhaled. The pulmonary fibrosis is one of the serious consequences of PS-MPs inhalation. However, the impact and underlying mechanisms of PS-MPs on pulmonary fibrosis are not clear. In this study, we studied the potential lung toxicity and PS-MPs-developed pulmonary fibrosis by long-term intranasal inhalation of PS-MPs. The results showed that after exposing to the PS-MPs, the lungs of model mouse had different levels of damage and fibrosis. Meanwhile, exposing to the PS-MPs resulted in a markedly decrease in glutathione (GSH), an increase in malondialdehyde (MDA), and iron overload in the lung tissue of mice and alveolar epithelial cells (AECs). These findings suggested the occurrence of PS-MP-induced ferroptosis. Inhibitor of ferroptosis (Fer-1) had alleviated the PS-MPs-induced ferroptosis. Mechanically, PS-MPs triggered cell ferroptosis and promoted the development of pulmonary fibrosis via activating the cGAS/STING signaling pathway. Inhibition of cGAS/STING with G150/H151 attenuated pulmonary fibrosis after PS-MPs exposure. Together, these data provided novel mechanistic insights of PS-MPs-induced pulmonary fibrosis and a potential therapeutic paradigm.


Assuntos
Células Epiteliais Alveolares , Ferroptose , Proteínas de Membrana , Microplásticos , Poliestirenos , Fibrose Pulmonar , Transdução de Sinais , Ferroptose/efeitos dos fármacos , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Poliestirenos/toxicidade , Camundongos , Transdução de Sinais/efeitos dos fármacos , Microplásticos/toxicidade , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/patologia , Proteínas de Membrana/metabolismo , Masculino , Camundongos Endogâmicos C57BL
6.
Clin Oral Investig ; 28(1): 93, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38217671

RESUMO

OBJECTIVES: A digitally designed stent was invented to assist vestibuloplasty and free gingival graft (FGG) after jaw reconstruction. This study aimed to compare the effects of conventional soft-tissue management comprising vestibuloplasty combined with FGG and modified soft-tissue management using a digitally designed stent on the vestibular sulcus depth (VD), keratinised-tissue width (KTW) and peri-implant tissue health in patients undergoing jaw reconstruction. MATERIALS AND METHODS: This prospective cohort study enrolled patients who underwent jaw reconstruction using a fibular flap, iliac flap, or onlay bone graft followed by implant-supported rehabilitation at the Peking University School and Hospital of Stomatology between May 2019 and July 2022. Patients in the stent group received digitally designed stents following vestibuloplasty combined with FGG for peri-implant soft-tissue management. Patients in the control group underwent a conventional vestibuloplasty combined with FGG. VD and KTW were evaluated immediately after implant loading (T2) and 1 year after implant loading (T3), and the atrophy rates of VD and KTW were calculated. Peri-implant clinical parameters were evaluated at T3. Comparisons between the groups were performed using the Mann-Whitney U test. The effects of age, sex, primary disease, reconstruction type, reconstructed jaw and the number and location of implants on VD and KTW were evaluated using linear regression analysis. RESULTS: There were no significant differences in the atrophy rates of VD and KTW between the stent and control groups at T2 and T3 (both P ≥ 0.05). There were no significant differences in peri-implant clinical parameters between the stent and control groups at T3 (P ≥ 0.05). Reconstruction type, location of implants and primary disease influenced VD, and reconstruction type and age influenced KTW. CONCLUSIONS: There was no significant difference in the maintenance of VD and KTW after jaw reconstruction between soft-tissue management using a digitally designed stent and the conventional method. Further, digitally designed stents do not affect peri-implant tissue health. CLINICAL RELEVANCE: Digitally designed stents can simplify clinical procedures without adverse effects on peri-implant tissue health, but they do not promote keratinized mucosa augmentation and vestibuloplasty.


Assuntos
Implantes Dentários , Humanos , Gengiva/transplante , Estudos Prospectivos , Stents , Atrofia
7.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(1): 4-8, 2024 Feb 18.
Artigo em Chinês | MEDLINE | ID: mdl-38318889

RESUMO

Oral diseases concern almost every individual and are a serious health risk to the population. The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour. Based on the principle of "learning from the nature", Deng Xuliang's group of Peking University School and Hospital of Stomatology has proposed a new concept of "microstructural biomimetic design and tissue adaptation of tooth/jaw materials" to address the worldwide problems of difficulty in treating dentine hypersensitivity, poor prognosis of restoration of tooth defects, and vertical bone augmentation of alveolar bone after tooth loss. The group has broken through the bottleneck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects, and invented key technologies such as crystalline/amorphous multi-level assembly, ion-transportation blocking, and multi-physical properties of the micro-environment reconstruction, etc. The group also pioneered the cationic-hydrogel desensitizer, digital stump and core integrated restorations, and developed new crown and bridge restorative materials, gradient functionalisation guided tissue regeneration membrane, and electrically responsive alveolar bone augmentation restorative membranes, etc. These products have established new clinical strategies for tooth/jaw defect repair and achieved innovative results. In conclusion, the research results of our group have strongly supported the theoretical improvement of stomatology, developed the technical system of oral hard tissue restoration, innovated the clinical treatment strategy, and led the progress of the stomatology industry.


Assuntos
Biônica , Restauração Dentária Permanente , Doenças da Boca , Humanos
8.
J Neurochem ; 165(6): 907-919, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37158660

RESUMO

Myasthenia gravis (MG) is an antibody-mediated autoimmune disorder characterized by fluctuation of fatigue and weakness of muscle. Due to the heterogeneity of the course of MG, available biomarkers for prognostic prediction are urgently needed. Ceramide (Cer) was reported to participate in immune regulation and many autoimmune diseases, but its effects on MG remain undefined. This study aimed to investigate the ceramides expression levels in MG patients and their potential as novel biomarkers of disease severity. Levels of plasma ceramides were determined by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Severity of disease was assessed by quantitative MG scores (QMGs), MG-specific activities of daily living scale (MG-ADLs) and 15-item MG quality of Life (MG-QOL15). The concentrations of serum interleukin-1ß (IL-1ß), IL-6, IL-17A, and IL-21 were determined by enzyme-linked immunosorbent assay (ELISA), and the proportions of circulating memory B cells and plasmablasts were detected by flow-cytometry assay. Four plasma ceramides levels we studied were detected higher in MG patients. And three of them (C16:0-Cer, C18:0-Cer, and C24:0-Cer) were positively associated with QMGs. In addition, receiver operating characteristic (ROC) analysis suggested that plasma ceramides have a good ability of differentiating MG from HCs. Importantly, only C18:0-Cer was shown to be positively associated with the concentration of serum IL and circulating memory B cells, and the decrease in plasma C18:0-Cer paralleled the clinical improvement of patients with MG. All together, our data suggest that ceramides may play an important role in the immunopathological mechanism of MG, and C18:0-Cer has the potential to be a novel biomarker for disease severity in MG.


Assuntos
Ceramidas , Miastenia Gravis , Humanos , Ceramidas/metabolismo , Cromatografia Líquida , Atividades Cotidianas , Qualidade de Vida , Espectrometria de Massas em Tandem , Biomarcadores , Miastenia Gravis/diagnóstico , Gravidade do Paciente
9.
Clin Immunol ; 255: 109764, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37683903

RESUMO

Vitiligo is the most common disorder of depigmentation, which is caused by multiple factors like metabolic abnormality, oxidative stress and the disorders of immune. In recent years, several studies have used untargeted metabolomics to analyze differential metabolites in patients with vitiligo, however, the subjects in these studies were all in plain area. In our study, multivariate analysis indicated a distinct separation between the healthy subjects from plateau and plain areas in electrospray positive and negative ions modes, respectively. Similarly, a distinct separation between vitiligo patients and healthy controls from plateau and plain areas was detected in the two ions modes. Among the identified metabolites, the serum levels of sphingosine 1-phosphate (S1P) were markedly higher in vitiligo patients compare to healthy subjects in plain and markedly higher in healthy subjects in plateau compare to those in plain. There are significant differences in serum metabolome between vitiligo patients and healthy subjects in both plateau and plain areas, as well as in healthy subjects from plateau and plain areas. S1P metabolism alteration may be involved in the pathogenesis of vitiligo.


Assuntos
Vitiligo , Humanos , Voluntários Saudáveis , Metabolômica , Metaboloma , Análise Multivariada
10.
Opt Express ; 31(17): 27136-27146, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37710794

RESUMO

This paper presents a method for measuring the optical assembly results based on multi-beam biaxial LiDAR. This method analyzes the optical assembly parameters of a LiDAR system affecting the LiDAR operation, and an experimental measurement system is built using a collimator to simulate the infinity imaging field. An InGaAs infrared camera is used to take pictures of the laser spot from the LiDAR transmitter and receiver, and then fit the laser spot images with Gaussian equations to calculate the biaxial LiDAR optical assembly results. Finally, the possible effecting factors of LiDAR alignment results are analyzed. This method is experimentally proven to achieve the measurement of the optical assembly results of a large scale multi-beam LiDAR. The possibility of further optimizing the measurement method by shaping the transmit laser is also reported.

11.
Langmuir ; 39(32): 11448-11458, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37535862

RESUMO

Nanoparticles (NPs) exhibit great potential to improve various properties of viscoelastic surfactant (VES) fracturing fluids in the development of low-permeability reservoirs. In the present study, the amphiphilic Janus NPs (JANPs) were fabricated via the Pickering emulsion method and employed to construct the novel JA12C (JANPs with dodecyl hydrophobic carbon chains)-assisted VES fracturing fluid (JAVES). The successful fabrication of JANPs was confirmed via Fourier transform infrared spectroscopy (FTIR) measurements and water contact angle tests. The rheology behavior of the VES fracturing fluid incorporating various SiO2 NPs including hydrophilic SiO2 NPs (HLNPs), JA8C (JANPs with octyl hydrophobic carbon chains), and JA12C was systematically investigated. It was revealed that the additional JA12C significantly improved the tolerance and proppant suspension properties. To explore the subsequent oil recovery performance of various gel breaking liquids, the formation wettability and the oil-water interfacial tension (IFT) were studied after the evaluation of breaking properties and formation damage properties of various fracturing fluids. The results suggested that the JAVES gel breaking liquid showed remarkable wettability alternation capability and moderate oil-water IFT reduction ability, which can partially reduce the impact on reservoir permeability. Moreover, the formation mechanism of the JAVES was proposed by molecular dynamics simulations at the molecular level, which was further visually verified via the cryo-TEM images. The improved viscoelasticity of developed the JAVES with moderate interfacial activity is advantageous to enhance subsequent oil recovery.

12.
Genome ; 66(8): 212-223, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37094380

RESUMO

The Xuefeng black bone chicken (XFBC) represents an important poultry genetic resource. However, the darkness in breast muscle is heterogeneous. The molecular genetic mechanisms underlying melanogenesis of breast muscle in XFBC remains unclear. This study used RNA-seq to compare the difference in transcriptome between hyperpigmentation and hypopigmentation of breast muscle. Six cDNA libraries were constructed for hyperpigmentation and hypopigmentation groups in XFBC. We identified 395 differently expressed genes (DEGs) between hyperpigmentation and hypopigmentation group (P < 0.05, |log2FC|≥1). Gene ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated several differentially enriched biological functions and pathways involved in melanogenesis of the breast muscle. Gene set enrichment analysis (GSEA) GO analysis identified two significant gene sets, including the pathways of pigment metabolic process and transmembrane receptor protein tyrosine kinase activity. GSEA-KEGG analysis identified the process of tyrosine metabolism and several genes related with melanogenesis in breast muscle of the XFBC. The protein-protein interaction network was constructed and eight genes were clustered in the module. We identified nine hub genes, including TYR, TYRP1, DCT, GPR143, MLANA, SLC24A5, GPNMB, MLPH, and EDNRB2. Taken together, the DEGs and hub genes identified in the study provide a solid basis for the study of the genetic regulatory mechanisms involved the melanogenesis in the breast muscle of the XFBC.


Assuntos
Galinhas , Melaninas , Animais , Galinhas/genética , Melaninas/genética , Melaninas/metabolismo , Transcriptoma , Biologia Computacional , Músculos/metabolismo , Perfilação da Expressão Gênica , Redes Reguladoras de Genes
13.
Aging Male ; 26(1): 2275775, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37897234

RESUMO

BACKGROUND: The relationship between uric acid (UA) and benign prostatic hyperplasia (BPH) is controversial and has rarely been studied in American populations. METHODS: Data from two cycles of the National Health and Nutrition Examination Surveys, comprising data from 2005 to 2008, were used. The majority of BPH were identified by self-report. We investigated the relationship between UA and BPH using univariate and multivariate logistic regression analyses. RESULTS: 2,845 participants were enrolled in the study, including 531 participants with BPH and 2,314 controls. After fully adjusting for all confounders, the risk of developing BPH was reduced by 18% for every 100 µmol/L increase in UA (OR = 0.82, 95% CI: 0.69-0.97, p = 0.023). Participants in the highest quartile of UA were found to have a reduced likelihood of developing BPH (ORQ4vs1 = 0.61, 95% CI: 0.41-0.91) in comparison to those in the lowest quartile of UA. Subgroup analyses found that among those younger than 60 years, non-Hispanic whites, former smokers, heavy drinkers, those without diabetes, or those with hypertension, high UA remained negatively associated with BPH. CONCLUSIONS: The above results suggest that UA may be a potential protective factor for BPH, but the mechanism needs to be further explored.


Assuntos
Hipertensão , Hiperplasia Prostática , Masculino , Humanos , Estados Unidos/epidemiologia , Hiperplasia Prostática/epidemiologia , Ácido Úrico , Fatores de Risco , Inquéritos Nutricionais
14.
Inorg Chem ; 62(31): 12329-12336, 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37478416

RESUMO

Propyne/propylene separation is important in the petrochemical industry but challenging due to their similar physical properties and close molecular sizes. Metal-organic frameworks (MOFs) are a class of promising adsorbents for light hydrocarbon separations. Among them, the so-called "flexible-robust" MOFs combine the advantages of flexibility and rigidity in structure and could show enhanced gas separation selectivity as well as improved gas uptake at low pressure. Interpenetrated MOFs offer a platform to explore the "flexible-robust" feature of MOFs based on their subnetwork displacement in the process of gas adsorption. Herein, we present two hydrolytically stable MOFs (BUT-308 and BUT-309) with interpenetrated structures and fascinating propyne/propylene separation performance. BUT-308 is composed of interpenetrated 2D Cu(BDC-NH2)BPB layers (H2BDC-NH2 = 2-aminobenzene-1,4-dicarboxylic acid; BPB = 1,4-bis(4-pyridyl)benzene), while BUT-309 consists of twofold interpenetrated 3D pillared-layer Cu2(BDC-NH2)2(BPB-CF3) nets (BPB-CF3 = 2-trifluoromethyl-1,4-bis(4-pyridyl)benzene). Gas adsorption measurements showed that BUT-309 was a "flexible-robust" adsorbent with multistep adsorption isotherms for C3H4 rather than C3H6 at a wide temperature range. The guest-dependent pore-opening behavior endows BUT-309 with high potential in the C3H4/C3H6 separation. The C3H4 adsorption measurements of BUT-309 at 273-323 K showed that the lowering of the temperature induced the pore-opening action at lower pressure. Column breakthrough experiments further confirmed the capability of BUT-309 for the efficient removal of C3H4 from a C3H4/C3H6 binary gas, and the C3H6 processing capacity at 273 K (15.7 cm3 g-1) was higher than that at 298 K (35.2 cm3 g-1). This work shows a rare example of "flexible-robust" MOFs and demonstrated its high potential for C3H4/C3H6 separation.

15.
J Nat Prod ; 86(3): 533-540, 2023 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-36787528

RESUMO

The aggregation of the neuronal protein α-synuclein (α-syn) is intrinsically linked to the development and progression of Parkinson's disease (PD). Recently we screened the MeOH extracts from 283 marine invertebrates for α-syn binding activity using an affinity mass spectrometry (MS) binding assay and found that the extract of the ascidian Polycarpa procera displayed activity. A subsequent bioassay-guided purification led to the isolation of one new α-syn aggregation inhibitory butenolide procerolide E (3) and one new α-syn aggregation inhibitory diphenylbutyrate methyl procerolate A (5). Herein we report the structure elucidation of procerolide E (3) and methylprocerolate A (5) and α-syn aggregation inhibitory activity of procerolides C-E (1-3), methyl procerolate A (5) and procerone A (4). We also report the α-syn binding activity of 3-bromo-4-methoxyphenylacetamide (6) and a synthetic butenolide library, which has allowed us to determine α-syn aggregation inhibitory structure-activity relationships for this class of compounds.


Assuntos
Doença de Parkinson , Urocordados , Animais , Humanos , alfa-Sinucleína/metabolismo , Urocordados/metabolismo , Doença de Parkinson/metabolismo
16.
Dig Dis Sci ; 68(6): 2276-2284, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36725765

RESUMO

BACKGROUND: Per Oral Endoscopic Myotomy (POEM) is a minimally invasive treatment for achalasia with results comparable to laparoscopic Heller myotomy (LHM). Studies have described the development of proficiency for endoscopists learning to perform POEM, and societies have defined educational and technical objectives for advanced endoscopy fellows in training. However, there is limited guidance on the organizational strategy and educational plan necessary to develop an achalasia service with POEM expertise. AIMS: We aim to outline the steps for design and implementation of a successful POEM program. METHODS: We reported our experience developing a multi-disciplinary clinical program for POEM and the steps taken to achieve procedural proficiency. We also reported our technical success (successful tunneling into the gastric cardia and myotomy of LES muscle fibers) and clinical success (post-procedure Eckardt score ≤ 3) at 3-6 months and 12 months post-procedure. Adverse events were classified per the ASGE lexicon for endoscopic adverse events. RESULTS: After creating a multi-disciplinary clinical program for achalasia and completing procedural proficiency for POEM, our technical success rate was 100% and clinical success rate 90% for the first 41 patients. One adverse event (2.4%) occurred, moderate in severity per the American Society of Gastrointestinal Endoscopy (ASGE) lexicon for adverse endoscopic events. CONCLUSION: In this study, we outlined the steps involved to establish a POEM service in a large integrated healthcare system. Prior competency in interventional endoscopy, procedural training models, POEM observation and education, proctorship, and interdisciplinary patient care are recommended.


Assuntos
Acalasia Esofágica , Miotomia de Heller , Miotomia , Cirurgia Endoscópica por Orifício Natural , Humanos , Acalasia Esofágica/cirurgia , Endoscopia Gastrointestinal , Miotomia/métodos , Resultado do Tratamento , Cirurgia Endoscópica por Orifício Natural/métodos , Esfíncter Esofágico Inferior/cirurgia
17.
J Clin Periodontol ; 50(2): 252-264, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36274052

RESUMO

AIM: This study sought to investigate associations of 25-hydroxyvitamin D (25(OH)D) metabolites with periodontitis and to assess causality using Mendelian randomization (MR). MATERIALS AND METHODS: This study included 7246 participants of the National Health and Nutrition Examination Survey, 2009-2012. The association of periodontitis with 25(OH)D metabolites was assessed using multivariable logistic regression analysis. Two-sample MR for 25(OH)D, 25(OH)D3 , and C3-epi-25(OH)D3 with periodontitis (n = 17,353 cases/28,210 controls) was conducted. The principal analysis employed the inverse-variance-weighted (IVW) approach. We controlled for horizontal pleiotropy using five additional methods. RESULTS: Based on the observational study, each 1-point increase in standard deviation of 25(OH)D lowered the risk of periodontitis by 15% (OR = 0.85, 95% confidence interval [CI]: 0.78-0.93, p = .006) after multivariable adjustment. A similar relationship was observed between 25(OH)D3 and periodontitis (OR = 0.88, 95% CI: 0.80-0.97, p = .031). Furthermore, a potential non-linear association was found between periodontitis and both 25(OH)D and 25(OH)D3 . However, C3-epi-25(OH)D3 was not found to be associated with periodontitis risk. IVW-MR showed that periodontitis risk was not significantly associated with genetically increased levels of 25(OH)D (OR = 1.02, 95% CI: 0.90-1.16, p = .732), 25(OH)D3 (OR = 1.04, 95% CI: 0.93-1.17, p = .472), or C3-epi-25(OH)D3 (OR = 1.11, 95% CI: 0.87-1.41, p = .400). The pleiotropy-robust MR approaches yielded similar results after we had eliminated the variants with horizontal pleiotropy risk. CONCLUSIONS: Cross-sectional observational analysis identified significant relationships between periodontitis with 25(OH)D metabolites, while findings based on MR study did not support a causal role.


Assuntos
Análise da Randomização Mendeliana , Periodontite , Humanos , Inquéritos Nutricionais , Análise da Randomização Mendeliana/métodos , Estudos Transversais , Periodontite/genética , Polimorfismo de Nucleotídeo Único , Estudo de Associação Genômica Ampla
18.
Neurol Sci ; 44(11): 3877-3884, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37402938

RESUMO

Myasthenia gravis (MG) is a classic autoimmune neuromuscular disease with strong clinical heterogeneity. The concept of subgroup classification was proposed to guide the precise treatment of MG. Subgroups based on serum antibodies and clinical features include ocular MG, early-onset MG with AchR antibodies, late-onset MG with AchR antibodies, thymoma-associated MG, MuSK-associated MG, LRP4-associated MG, and seronegative MG. However, reliable objective biomarkers are still needed to reflect the individualized response to therapy. MicroRNAs (miRNAs) are small non-coding RNA molecules which can specifically bind to target genes and regulate gene expression at the post-transcriptional level, and then influence celluar biological processes. MiRNAs play an important role in the pathogenesis of autoimmune diseases, including MG. Several studies on circulating miRNAs in MG have been reported. However, there is rare systematic review to summarize the differences of these miRNAs in different subgroups of MG. Here, we summarize the potential role of circulating miRNAs in different subgroups of MG to promote personalized medicine.


Assuntos
MicroRNA Circulante , MicroRNAs , Miastenia Gravis , Neoplasias do Timo , Humanos , Receptores Colinérgicos , MicroRNA Circulante/genética , Medicina de Precisão , Autoanticorpos , Receptores Proteína Tirosina Quinases , MicroRNAs/genética
19.
Aging Ment Health ; 27(1): 54-69, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35132883

RESUMO

OBJECTIVES: Mental health for older people has become a major social concern. Literature has shown that older people, especially when they become empty nesters-when a parent lives alone or lives with his/her spouse after the youngest child leaves home-may start to develop various mental health problems due to reduced contacts with their children.Using fixed-effects, multivariate regression with a difference-in-differences approach and propensity score matching, this paper examines the relationship between being an empty nester and mental health among older people in China, and the moderating effects of social contact and contact with one's children in terms of mental health. Our data come from the China Health and Retirement Longitudinal Study of 2011, 2013, 2015 and 2018. RESULTS: We found that, in the short term, the mental health of older people may not be affected after they became empty nesters. But in the longer term, if they did not have regular contact with their children, their mental health would deteriorate with time. Social contact, especially cognitive activities, was beneficial to the mental health of the older empty nesters. We also found that for older empty nesters with disabilities, frequent social contact and contact with their children were more important. CONCLUSION: We urge the government to promote community-based social activities for older people, especially for those with functional limitations.


Assuntos
Depressão , Saúde Mental , Humanos , Masculino , Feminino , Idoso , Depressão/epidemiologia , Estudos Longitudinais , Inquéritos e Questionários , China/epidemiologia
20.
Opt Express ; 30(8): 13810-13824, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35472986

RESUMO

In this paper, a node splitting optimized canonical correlation forest algorithm for sea fog detection is proposed by using active and passive satellites. The traditional canonical correlation forest (CCF) algorithm insufficiently accounts for the spectral characteristics and the reliability of each classifier during integration. To deal with the problem, the information gain rate of node entropy is used as the splitting criterion, and the spectral characteristics of clouds and fogs are also combined into the model generation process. The proposed algorithm was verified using the meteorological station data and compared with five state-of-the-art algorithms, which demonstrated that the algorithm has the best performance in sea fog detection and can identify mist better.

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