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1.
J Org Chem ; 2024 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-39396198

RESUMO

A palladium-catalyzed annulation reaction of bay-diiodinated arenes with o-chloroaromatic carboxylic acids was established. This approach enables the synthesis of a variety of polycyclic aromatic compounds, especially polyalkoxy-substituted polycyclic aromatic compounds, frequently found in discotic liquid-crystalline materials. The investigations indicate that the product 2,3,8,9,12,13-hexakis(hexyloxy)-5-azadibenzo[fg,op]tetracene demonstrates favorable room-temperature liquid-crystalline properties.

2.
Transl Psychiatry ; 14(1): 415, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39362869

RESUMO

Chronic hypobaric hypoxia at high altitudes can impair cognitive functions, especially causing deficits in learning and memory, which require therapeutic intervention. Here, we showed that mice subjected to hypobaric hypoxia (simulating an altitude of 5000 m) for one month experienced significant cognitive impairment, accompanied by increased biomarker levels of oxidative stress in the brain and blood. Oral administration of a novel formulation of edaravone, a free radical scavenger approved for the treatment of ischaemic stroke and amyotrophic lateral sclerosis, significantly alleviated oxidative stress and cognitive impairments caused by chronic hypobaric hypoxia. Furthermore, oral edaravone treatment also mitigated neuroinflammation and restored hippocampal neural stem cell exhaustion. Additionally, periostin (Postn) is vital in the cognitive deficits caused by chronic hypobaric hypoxia and may be a molecular target of edaravone. In conclusion, our results suggest that oxidative stress plays a crucial role in the cognitive deficits caused by chronic hypobaric hypoxia and that oral edaravone is a potential medicine for protecting against cognitive deficits caused by chronic hypobaric hypoxia in high-altitude areas.


Assuntos
Altitude , Disfunção Cognitiva , Edaravone , Hipóxia , Estresse Oxidativo , Animais , Edaravone/farmacologia , Edaravone/administração & dosagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/prevenção & controle , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Masculino , Hipóxia/complicações , Hipóxia/tratamento farmacológico , Hipóxia/metabolismo , Antioxidantes/farmacologia , Antioxidantes/administração & dosagem , Camundongos Endogâmicos C57BL , Administração Oral , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Modelos Animais de Doenças , Sequestradores de Radicais Livres/administração & dosagem , Sequestradores de Radicais Livres/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo
3.
J Med Chem ; 67(19): 17101-17123, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39298383

RESUMO

TNFα and related inflammatory factor antibody drugs have been orchestrated for the treatment of inflammatory bowel disease (IBD). However, antibody drugs elicited inevitable disadvantages and small molecule drugs are in an urgent need. Herein, we described the discovery, design, synthesis, and SAR studies from furanone glycoside compound Phoenicein (hit) isolated from Chimonanthus salicifolius to D228 (lead). Remarkably, D228 exhibited good inhibitory activity on B and T lymphocyte and excellent anti-IBD efficacy in vivo. Mechanistically, D228 alleviated the inflammation response by downregulating the MyD88/TRAF6/p38 signaling. Importantly, the relationship of D228, Phoenicein, and their aglycone 7a was deduced: D228 could be considered as a prodrug and metabolized to intermediate Phoenicein. In turn, Phoenicein released their shared active aglycone 7a. Additionally, D228 demonstrated good and balanced profiles of safety and efficacy both in vitro and in vivo. These results suggested that D228 could be used as an ideal lead and potentially utilized for IBD chemotherapy.


Assuntos
Furanos , Glicosídeos , Doenças Inflamatórias Intestinais , Animais , Glicosídeos/química , Glicosídeos/farmacologia , Glicosídeos/uso terapêutico , Glicosídeos/isolamento & purificação , Doenças Inflamatórias Intestinais/tratamento farmacológico , Camundongos , Relação Estrutura-Atividade , Furanos/química , Furanos/farmacologia , Furanos/uso terapêutico , Furanos/isolamento & purificação , Humanos , Camundongos Endogâmicos C57BL , Descoberta de Drogas , Masculino
4.
J Asthma ; : 1-9, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39225308

RESUMO

BACKGROUND AND OBJECTIVE: Asthma is a heterogeneous respiratory disease characterized by airway hyper-responsiveness and reversible airflow blockage. There is ongoing debate about the impact of vitamin D on asthma. This research is focused on investigating the correlation between serum levels of 25-hydroxyvitamin D and asthma. METHODS: This cross-sectional study comprised 22,708 eligible participants. Data on asthma and serum 25-hydroxyvitamin D levels from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 were analyzed. Serum 25-hydroxyvitamin D levels were the main factor, with the presence of asthma as the outcome variable. Weighted logistic regression was utilized to investigate the relationship between serum levels of 25-hydroxyvitamin D and asthma, while accounting for factors such as age, gender, race, length of time in US, annual family income, education level, high-density lipoprotein, low-density lipoprotein, triglycerides, and cholesterol. RESULTS: Upon adjusting all variables in model III, epi-25-hydroxyvitamin D3 displayed a negative correlation with current asthma at the lower quartile Q1 (0.784, [0.697 to 0.922]), Q2 (0.841, [0.729 to 0.946]), Q3 (0.396, [0.240 to 0.653]) when compared to the highest quartile Q4 level. However, no significant difference was observed between asthma and 25-hydroxyvitamin D2, as well as 25-hydroxyvitamin D3. CONCLUSIONS: In the U.S. population, elevated levels of epi-25-hydroxyvitamin D3 are correlated with an increased risk of developing existing asthma. However, it is important to interpret this finding carefully given the constraints of cross-sectional studies.

5.
Front Pharmacol ; 15: 1431846, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39221144

RESUMO

Background: Keloid is a fibroproliferative disease with unsatisfactory therapeutic effects and a high recurrence rate. exosomes produced by adipose-derived mesenchymal stem cells (ADSC-Exos) have attracted significant interest due to their ability to treat fibrosis. However, the molecular mechanisms of ADSC-Exos in keloids remain inconclusive. Objective: Our study revealed the relationship between ferroptosis and fibrosis in keloids. Subsequently, this study aimed to explore further the anti-fibrotic effect of ADSC-Exos on keloids through ferroptosis and the potential underlying mechanisms. Methods: To investigate the impact of ferroptosis on keloid fibrosis, Erastin and ferrostatin-1 (fer-1) were utilized to treat keloid fibroblast. Keloid keloids treated with Erastin and fer-1 were cocultured with ADSC-Exos to validate the impact of ferroptosis on the effect of ADSC-Exos on keloid anti-ferrotic protein, peroxidase 4 (GPX4) and anti-fibrotic effects in vivo and in vitro by Western blot, as well as variations in iron metabolite expression, malondialdehyde (MDA), liposomal peroxidation (LPO) and glutathione (GSH) were analyzed. The effect of solute carrier family 7-member 11 (SLC7A11) silencing on ADSC-Exo-treated keloid fibroblast was investigated. Results: Iron metabolite dysregulation was validated in keloids. Fibrosis progression is enhanced by Erastin-induced ferroptosis. The anti-fibrotic effects of ADSC-Exos and fer-1 are related to their ability to prevent iron metabolism. ADSC-Exos effectively suppressed keloid fibrosis progression and increased GSH and GPX4 gene expression. Additionally, the use of Erastin limits the effect of ADSC-Exos in keloids. Furthermore, the effect of ADSC-Exos on keloids was associated with SLC7A11-GPX4 signaling pathway. Conclusion: We demonstrated a new potential mechanism by which anti-ferroptosis inhibits the progression of keloid fibrosis and identified an ADSC-Exo-based keloid therapeutic strategy. Resisting the occurrence of ferroptosis and the existence of the SLC7A11-GPX4 signaling pathway might serve as a target for ADSC-Exos.

6.
Biotechnol Bioeng ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39289816

RESUMO

3D bioprinting technology is widely used in biomedical fields such as tissue regeneration and constructing pathological model. The prevailing printing technique is extrusion-based bioprinting. In this printing method, the bioink needs to meet both printability and functionality, which are often conflicting requirements. Therefore, this study has developed an innovative microvalve-based equipment, incorporating components such as pressure control, a three-dimensional motion platform, and microvalve. Here, we present a droplet-based method for constructing complex three-dimensional structures. By leveraging the rapid switching characteristics of the microvalve, this equipment can achieve precise printing of bio-materials with viscosities as low as 10mPa·s, significantly expanding the biofabrication window for bioinks. This technology is of great significance for 3D bioprinting in tissue engineering and lays a solid foundation for the construction of complex artificial organ tissues.

7.
Artigo em Inglês | MEDLINE | ID: mdl-39228046

RESUMO

Aims: Succinate, a metabolite in the tricarboxylic acid cycle, is increasingly recognized to play essential roles in inflammation by functioning either as an intracellular or extracellular signaling molecule. However, the role and mechanisms of succinate in inflammation remain elusive. Here, we investigated the mechanism underlying the effects of succinate on neuroinflammation in intracerebral hemorrhage (ICH) models. Results: We unexpectedly found that succinate robustly inhibited neuroinflammation and conferred protection following ICH. Mechanistically, the oxidation of succinate by succinate dehydrogenase (SDH) drove reverse electron transport (RET) at mitochondrial complex I, leading to mitochondrial superoxide production in microglia. Complex I-derived superoxides, in turn, activated uncoupling protein 2 (UCP2). By using mice with specific deletion of UCP2 in microglia/macrophages, we showed that UCP2 was needed for succinate to inhibit neuroinflammation, confer protection, and activate downstream 5'-adenosine monophosphate-activated protein kinase (AMPK) following ICH. Moreover, knockdown of SDH, complex I, or AMPK abolished the therapeutic effects of succinate following ICH. Innovation and Conclusion: We provide evidence that driving complex I RET to activate UCP2 is a novel mechanism of succinate-mediated intracellular signaling and a mechanism underlying the inhibition of neuroinflammation by succinate.

8.
J Multidiscip Healthc ; 17: 4493-4506, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39319050

RESUMO

Purpose: The development of "Internet + nursing services" can effectively solve the problem of population aging, and grassroots nurses are the primary providers of such services in rural areas. This study aimed to analyze the factors affecting grassroots nurses' risk perception of "Internet + nursing services" and construct a predictive model. Patients and Methods: A multicenter cross-sectional study of 2220 nurses from 27 secondary hospitals and 36 community health centers in Hubei Province was conducted from August to December 2023 using a multi-stage cluster sampling method. Information was collected through a structured anonymous questionnaire. A Chi-square test, a Welch t-test, and binary logistic regression analyses were employed to determine independent risk factors for grassroots nurses' risk perception of "Internet + nursing services", and a nomogram was constructed. Receiver operating characteristic curves, calibration curves, and decision curves were plotted to evaluate the discrimination, calibration, and clinical effectiveness of the nomogram. Results: A total of 2050 valid questionnaires were collected, demonstrating that 51.95% of grassroots nurses thought that "Internet + nursing services" was a medium-high risk. Age, other sources of income, knowledge about "Internet + nursing services", personal safety, physical function, occupational exposure, social psychosocial, and time risk (P<0.05) were independent risk factors for grassroots nurses' risk perception. The area under the receiver operating characteristic curve of the nomogram was 0.939. The calibration and decision curve analyses demonstrated good calibration ability and clinical application values. Conclusion: The prediction model constructed in this study has good prediction ability. Most grassroots nurses believe that "Internet + nursing services" are risky and influenced by several factors. It is suggested that the government and hospitals should formulate a unified charging standard, improve the safety guarantee, and gradually eliminate the concerns of grassroots nurses.

9.
J Med Internet Res ; 26: e58278, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39302714

RESUMO

BACKGROUND: International Classification of Diseases codes are widely used to describe diagnosis information, but manual coding relies heavily on human interpretation, which can be expensive, time consuming, and prone to errors. With the transition from the International Classification of Diseases, Ninth Revision, to the International Classification of Diseases, Tenth Revision (ICD-10), the coding process has become more complex, highlighting the need for automated approaches to enhance coding efficiency and accuracy. Inaccurate coding can result in substantial financial losses for hospitals, and a precise assessment of outcomes generated by a natural language processing (NLP)-driven autocoding system thus assumes a critical role in safeguarding the accuracy of the Taiwan diagnosis related groups (Tw-DRGs). OBJECTIVE: This study aims to evaluate the feasibility of applying an International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), autocoding system that can automatically determine diagnoses and codes based on free-text discharge summaries to facilitate the assessment of Tw-DRGs, specifically principal diagnosis and major diagnostic categories (MDCs). METHODS: By using the patient discharge summaries from Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUCHH) from April 2019 to December 2020 as a reference data set we developed artificial intelligence (AI)-assisted ICD-10-CM coding systems based on deep learning models. We constructed a web-based user interface for the AI-assisted coding system and deployed the system to the workflow of the certified coding specialists (CCSs) of KMUCHH. The data used for the assessment of Tw-DRGs were manually curated by a CCS with the principal diagnosis and MDC was determined from discharge summaries collected at KMUCHH from February 2023 to April 2023. RESULTS: Both the reference data set and real hospital data were used to assess performance in determining ICD-10-CM coding, principal diagnosis, and MDC for Tw-DRGs. Among all methods, the GPT-2 (OpenAI)-based model achieved the highest F1-score, 0.667 (F1-score 0.851 for the top 50 codes), on the KMUCHH test set and a slightly lower F1-score, 0.621, in real hospital data. Cohen κ evaluation for the agreement of MDC between the models and the CCS revealed that the overall average κ value for GPT-2 (κ=0.714) was approximately 12.2 percentage points higher than that of the hierarchy attention network (κ=0.592). GPT-2 demonstrated superior agreement with the CCS across 6 categories of MDC, with an average κ value of approximately 0.869 (SD 0.033), underscoring the effectiveness of the developed AI-assisted coding system in supporting the work of CCSs. CONCLUSIONS: An NLP-driven AI-assisted coding system can assist CCSs in ICD-10-CM coding by offering coding references via a user interface, demonstrating the potential to reduce the manual workload and expedite Tw-DRG assessment. Consistency in performance affirmed the effectiveness of the system in supporting CCSs in ICD-10-CM coding and the judgment of Tw-DRGs.


Assuntos
Algoritmos , Classificação Internacional de Doenças , Processamento de Linguagem Natural , Humanos , Taiwan , Inteligência Artificial
10.
Chem Sci ; 15(31): 12264-12269, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39118606

RESUMO

Metal oxides are promising (photo)electrocatalysts for sustainable energy technologies due to their good activity and abundant resources. Their applications such as photocatalytic water splitting predominantly involve aqueous interfaces under electrochemical conditions, but in situ probing oxide-water interfaces is proven to be extremely challenging. Here, we present an electrochemical scanning tunneling microscopy (EC-STM) study on the rutile TiO2(110)-water interface, and by tuning surface redox chemistry with careful potential control we are able to obtain high quality images of interfacial structures with atomic details. It is interesting to find that the interfacial water exhibits an unexpected double-row pattern that has never been observed. This finding is confirmed by performing a large scale simulation of a stepped interface model enabled by machine learning accelerated molecular dynamics (MLMD) with ab initio accuracy. Furthermore, we show that this pattern is induced by the steps present on the surface, which can propagate across the terraces through interfacial hydrogen bonds. Our work demonstrates that by combining EC-STM and MLMD we can obtain new atomic details of interfacial structures that are valuable to understand the activity of oxides under realistic conditions.

11.
Zhongguo Zhong Yao Za Zhi ; 49(13): 3421-3431, 2024 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-39041114

RESUMO

DNA G-quadruplex(G4) is a guanine-rich single-stranded DNA sequence that spontaneously folds into a spherical four-stranded DNA secondary structure in oncogene promoter sequences and telomeres. G4s are highly associated with the occurrence and development of cancer and have emerged as promising anticancer targets. Natural products have long been important sources of anticancer drug development. In recent years, significant progress has been made in the discovery of natural drugs targeting DNA G4s, with many DNA G4s have been confirmed as promising targets of natural products, including MYC-G4, KRAS-G4, PDGFR-ß-G4, BCL-2-G4, VEGF-G4, and telomeric G4. This review summarizes the research progress in discovering natural small molecules that target DNA G4s and their binding mechanisms. It also discusses the opportunities of and challenges in developing drugs targeting DNA G4s. This review will serve as a valuable reference for the research on natural products, particularly in the development of novel antitumor medications.


Assuntos
Produtos Biológicos , Quadruplex G , Quadruplex G/efeitos dos fármacos , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Humanos , Animais , DNA/química , DNA/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Antineoplásicos/química , Antineoplásicos/farmacologia
12.
J Environ Sci (China) ; 146: 186-197, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38969447

RESUMO

As an important means to solve water shortage, reclaimed water has been widely used for landscape water supply. However, with the emergence of large-scale epidemic diseases such as SARS, avian influenza and COVID-19 in recent years, people are increasingly concerned about the public health safety of reclaimed water discharged into landscape water, especially the pathogenic microorganisms in it. In this study, the water quality and microorganisms of the Old Summer Palace, a landscape water body with reclaimed water as the only replenishment water source, were tracked through long-term dynamic monitoring. And the health risks of indicator microorganisms were analyzed using Quantitative Microbial Risk Assessment (QMRA). It was found that the concentration of indicator microorganisms Enterococcus (ENT), Escherichia coli (EC) and Fecal coliform (FC) generally showed an upward trend along the direction of water flow and increased by more than 0.6 log at the end of the flow. The concentrations of indicator microorganisms were higher in summer and autumn than those in spring. And there was a positive correlation between the concentration of indicator microorganisms and COD. Further research suggested that increased concentration of indicator microorganisms also led to increased health risks, which were more than 30% higher in other areas of the park than the water inlet area and required special attention. In addition, (water) surface operation exposure pathway had much higher health risks than other pathways and people in related occupations were advised to take precautions to reduce the risks.


Assuntos
Microbiologia da Água , Medição de Risco , Qualidade da Água , Escherichia coli/isolamento & purificação , Abastecimento de Água , Monitoramento Ambiental , Enterococcus/isolamento & purificação , Humanos
13.
Autism Res ; 17(8): 1572-1585, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38975627

RESUMO

Accumulating evidence suggests that individuals with autism spectrum disorder (ASD) show impairments in using contextual priors to predict others' actions and make intention inference. Yet less is known about whether and how children with ASD acquire contextual priors during action observation and how contextual priors relate to their action prediction and intention inference. To form proper contextual priors, individuals need to observe the social scenes in a reliable manner and focus on socially relevant information. By employing a data-driven scan path method and areas of interest (AOI)-based analysis, the current study investigated how contextual priors would relate to action prediction and intention understanding in 4-to-9-year-old children with ASD (N = 56) and typically developing (TD) children (N = 50) during free viewing of dynamic social scenes with different intentions. Results showed that children with ASD exhibited higher intra-subject variability when scanning social scenes and reduced attention to socially relevant areas. Moreover, children with high-level action prediction and intention understanding showed lower intra-subject variability and increased attention to socially relevant areas. These findings suggest that altered fixation patterns might restrain children with ASD from acquiring proper contextual priors, which has cascading downstream effects on their action prediction and intention understanding.


Assuntos
Atenção , Transtorno do Espectro Autista , Humanos , Transtorno do Espectro Autista/fisiopatologia , Transtorno do Espectro Autista/psicologia , Masculino , Feminino , Criança , Atenção/fisiologia , Pré-Escolar , Intenção , Percepção Social
14.
Acta Biomater ; 185: 173-189, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39025391

RESUMO

Tumor behavior, including its response to treatments, is influenced by interactions between mesenchymal and malignant cells, as well as their spatial arrangement. To study tumor biology and evaluate anticancer drugs, accurate 3D tumor models are essential. Here, we developed an in vitro biomimetic hepatoma microenvironment model by combining an extracellular matrix (3DM-7721). Initially, the internal grid structure, composed of 10/6 % GelMA/gelatin loaded with SMMC-7721 cells, was printed using 3D bioprinting. The external component consisted of fibroblasts and human umbilical vein endothelial cells loaded with 10/3 % GelMA/gelatin. A control model (3DP-7721) lacked external cell loading. GelMA/gelatin hydrogels provided robust structural support and biocompatibility. The SMMC-7721 cells in the 3DM-7721 model exhibit superior tumor-associated gene expression and proliferation characteristics when compared to the 3DP-7721 model. Furthermore, the 3DM-7721 type exhibited increased resistance to anticancer agents. SMMC-7721 cells in the 3DM-7721 model exhibit significant tumorigenicity in nude mice. The 3DM-7721 model group showed pathological characteristics of malignant tumors, with a high degree of deterioration, and a significant positive correlation between malignant tumor-related gene pathways. This high-fidelity 3DM-7721 tumor microenvironment model is invaluable for studying tumor progression, devising effective treatment strategies, and discovering drugs. STATEMENT OF SIGNIFICANCE.


Assuntos
Antineoplásicos , Bioimpressão , Carcinoma Hepatocelular , Neoplasias Hepáticas , Camundongos Nus , Impressão Tridimensional , Microambiente Tumoral , Humanos , Microambiente Tumoral/efeitos dos fármacos , Animais , Bioimpressão/métodos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Camundongos , Gelatina/química , Camundongos Endogâmicos BALB C , Proliferação de Células/efeitos dos fármacos
15.
Global Spine J ; : 21925682241270090, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39078998

RESUMO

STUDY DESIGN: Biomechanical testings and finite element analysis. OBJECTIVES: This study aims to investigate how annulus fibrosus (AF) incision size (RIS, Ratio of incision width to AF height) and shape affect intervertebral disc (IVD) biomechanics. METHODS: A validated finite element model of lumbar spines simulated various incisions in the middle-right posterior region of the AF, with different sizes and shapes. Simulations included axial compression, flexion, extension, bending, and rotation. Parameters assessed included stability, re-herniation, and IVD degeneration by analyzing stress, height, Intradiscal pressure (IDP), and the range of motion (ROM). RESULTS: Incision increased AF stress and ROM under 3 Nm moment, with values rising as RIS increased. RIS exceeding 40% resulted in a 20% AF stress increase during compression and extension, while RIS over 50% led to over 20% AF stress increase during other motions. Incision stress also increased with higher RIS, particularly surpassing 50% RIS. IDP rose across all incision shapes. Endplate stress increased (9.9%-48.9%) with larger incisions, with average increases of 12.8%, 12.7%, 30.5%, and 22.8% for circular, oval, square, and rectangular incisions. Compression and rotation minimally affected NP pressure (<15%), while flexion (19.8%-38.8%) and bending (18.5%-43.9%) had a more pronounced effect. ROM increased with RIS (20.0% ∼ 77.4%), especially with an incision RIS exceeding 40%. CONCLUSIONS: AF injury elevates AF stress, reduces spine stability, heightens degeneration risk with increasing RIS. Reherniation risk rises when RIS exceeds 40%. Circular or oval incisions maintain spine biomechanics better than square or rectangular ones.

16.
Cells ; 13(12)2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38920670

RESUMO

Proinflammatory T-lymphocytes recruited into the brain and spinal cord mediate multiple sclerosis (MS) and currently there is no cure for MS. IFN-γ-producing Th1 cells induce ascending paralysis in the spinal cord while IL-17-producing Th17 cells mediate cerebellar ataxia. STAT1 and STAT3 are required for Th1 and Th17 development, respectively, and the simultaneous targeting of STAT1 and STAT3 pathways is therefore a potential therapeutic strategy for suppressing disease in the spinal cord and brain. However, the pharmacological targeting of STAT1 and STAT3 presents significant challenges because of their intracellular localization. We have developed a STAT-specific single-domain nanobody (SBT-100) derived from camelids that targets conserved residues in Src homolog 2 (SH2) domains of STAT1 and STAT3. This study investigated whether SBT-100 could suppress experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We show that SBT-100 ameliorates encephalomyelitis through suppressing the expansion of Th17 and Th1 cells in the brain and spinal cord. Adoptive transfer experiments revealed that lymphocytes from SBT-100-treated EAE mice have reduced capacity to induce EAE, indicating that the immunosuppressive effects derived from the direct suppression of encephalitogenic T-cells. The small size of SBT-100 makes this STAT-specific nanobody a promising immunotherapy for CNS autoimmune diseases, including multiple sclerosis.


Assuntos
Encefalomielite Autoimune Experimental , Anticorpos de Domínio Único , Células Th17 , Animais , Feminino , Camundongos , Camelídeos Americanos , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/terapia , Encefalomielite Autoimune Experimental/tratamento farmacológico , Camundongos Endogâmicos C57BL , Doenças Neuroinflamatórias/imunologia , Doenças Neuroinflamatórias/tratamento farmacológico , Anticorpos de Domínio Único/farmacologia , Anticorpos de Domínio Único/imunologia , Anticorpos de Domínio Único/uso terapêutico , Medula Espinal/patologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/imunologia , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/metabolismo , Células Th1/imunologia , Células Th1/efeitos dos fármacos , Células Th17/imunologia , Células Th17/efeitos dos fármacos
17.
World J Clin Cases ; 12(16): 2765-2772, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38899311

RESUMO

BACKGROUND: Older spine surgery patients have a high incidence of debilitation, which can be managed with certain exercises. AIM: To investigate the current status and influencing factors related to the knowledge of exercise intervention among patients and professionals. METHODS: Descriptive research methods were used to classify and summarize patients and professionals' perceptions and factors affecting exercise interventions. Data were analysed using the Colaizzi seven-step analysis method to distill and refine themes. RESULTS: A total of 7 themes were identified: (1) The current status of patients' exercise is unsatisfactory; (2) patients' health literacy is low, coupled with a lack of social and family support; (3) there are numerous challenges with systematic exercise interventions; (4) healthcare professionals acknowledge the importance and need for exercise interventions; (5) there's a pronounced willingness among patients to participate in exercise intervention programs; (6) healthcare professionals believe that exercise interventions are beneficial; and (7) participants offered invaluable insights and suggestions on perioperative exercise during spinal surgery. CONCLUSION: To investigate the current status and influencing factors related to the knowledge of exercise intervention among patients and the related healthcare professionals to provide a reference for the construction of exercise management programs for these patients.

18.
Ecotoxicol Environ Saf ; 280: 116557, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38850695

RESUMO

Decabromodiphenyl ether (BDE-209) is an organic compound that is widely used in rubber, textile, electronics, plastics and other industries. It has been found that BDE-209 has a destructive effect on the reproductive system of mammals. However, the effect of BDE-209 exposure on oocyte quality and whether there is a viable salvage strategy have not been reported. Here, we report that murine oocytes exposed to BDE-209 produce a series of meiostic defects, including increased fragmentation rates and decreased PBE. Furthermore, exposure of oocytes to BDE-209 hinders mitochondrial function and disrupts mitochondrial integrity. Our observations show that supplementation with NMN successfully alleviated the meiosis impairment caused by BDE-209 and averted oocyte apoptosis by suppressing ROS generation. In conclusion, our findings suggest that NMN supplementation may be able to alleviate the oocyte quality impairment induced by BDE-209 exposure, providing a potential strategy for protecting oocytes from environmental pollutant exposure.


Assuntos
Éteres Difenil Halogenados , Oócitos , Espécies Reativas de Oxigênio , Animais , Éteres Difenil Halogenados/toxicidade , Oócitos/efeitos dos fármacos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Feminino , Apoptose/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Meiose/efeitos dos fármacos , Retardadores de Chama/toxicidade
19.
Inorg Chem ; 63(24): 11459-11469, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38842950

RESUMO

The performance of covalent-organic frameworks (COFs) for the photocatalytic extraction of uranium is greatly limited by the number of adsorption sites. Herein, inspired by electronegative redox reactions, we designed a nitrogen-oxygen rich pyrazine connected COF (TQY-COF) with multiple redox sites as a platform for extracting uranium via combining superaffinity and enhanced photoinduction. The preorganized bisnitrogen-bisoxygen donor configuration on TQY-COF is entirely matched with the typical geometric coordination of hexavalent uranyl ions, which demonstrates high affinity (tetra-coordination). In addition, the presence of the carbonyl group and pyrazine ring effectively stores and controls electron flow, which efficaciously facilitates the separation of e-/h+ and enhances photocatalytic performance. The experimental results show that TQY-COF removes up to 99.8% of uranyl ions from actual uranium mine wastewater under the light conditions without a sacrificial agent, and the separation coefficient reaches 1.73 × 106 mL g-1 in the presence of multiple metal ions, which realizes the precise separation in the complex environment. Importantly, DFT calculations further elucidate the coordination mechanism of uranium and demonstrate the necessity of the presence of N/O atoms in the photocatalytic adsorption of uranium.

20.
Spine J ; 24(10): 2002-2012, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38914373

RESUMO

BACKGROUND CONTEXT: Large annulus fibrosus (AF) defects often lead to a high rate of reherniation, particularly in the medial AF region, which has limited self-healing capabilities. The increasing prevalence of herniated discs underscores the need for effective repair strategies. PURPOSE: The objectives of this study were to design an AF repair technique to reduce solve the current problems of insufficient mechanical properties and poor sealing capacity. STUDY DESIGN: In vitro biomechanical experiments and finite element analysis. METHODS: The materials used in this study were patches and hydrogels with good biocompatibility and sufficient mechanical properties to withstand loading in the lumbar spine. Five repair techniques were assessed in this study: hydrogel filler (HF), AF patch medial barrier (MB), AF patch medial barrier and hydrogel filler (MB&HF), AF patch medial-lateral barrier (MLB), and AF patch medial-lateral barrier and hydrogel filler (MLB&HF). The repair techniques were subjected to in vitro testing (400 N axial compression and 0-500 N fatigue loading at 5Hz) and finite element analysis (400 N axial compression) to evaluate the effectiveness at repairing large AF defects. The evaluation included repair tightness, spinal stability, and fatigue resistance. RESULTS: From the in vitro testing, the failure load of the repair techniques was in the following order HF MLB >MB&HF >MLB&HF. CONCLUSIONS: The combined use of patches and hydrogels exhibited promising mechanical properties postdiscectomy, providing a promising solution for addressing large AF defects and improving disc stability. CLINICAL SIGNIFICANCE: This study introduces a promising method for repairing large annular fissure (AF) defects after disc herniation, combining patch repair with a hydrogel filler. These techniques hold potential for developing clinical AF repair products to address this challenging issue.


Assuntos
Anel Fibroso , Hidrogéis , Deslocamento do Disco Intervertebral , Anel Fibroso/cirurgia , Deslocamento do Disco Intervertebral/cirurgia , Hidrogéis/administração & dosagem , Humanos , Análise de Elementos Finitos , Fenômenos Biomecânicos , Recidiva , Animais , Vértebras Lombares/cirurgia
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