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1.
Clin Chim Acta ; 565: 119966, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39278524

RESUMEN

BACKGROUND: Allergen testing has emerged as a pivotal component in prevention and treatment strategies for allergic diseases among children and the utilization of specific IgE (sIgE) through a fully automated chemiluminescent microarray immunoassay (CLMIA) has emerged as a promising trend in the simultaneous detection of multiple allergenic components of children. METHODS: The accuracy and reliability of CLMIA were verified using children's serum samples that concentrated on allergens. the allergens. The clinical diagnostic practicability of CLMIA was assessed through comprehensive evaluations including measurements of the limit of detection (LOD), intra-batch, and inter-batch precision, linearity analysis, the cross-contamination rate, and the concordance rate with the Phadia system. RESULTS: After the optimization process of CLMIA, the LODs for allergens were calculated to be below 0.01 kU/L, demonstrating the high sensitivity of CLMIA. All components exhibited good linearity within the range of 0.1-100.0 kU/L and the coefficient of determinations (R2 > 0.99). The data of intra-batch precision (<10 %) and inter-batch data (<15 %) illustrated the high reproducibility of CLMIA. The cross-contamination rates for allergens (<0.5 %) showed the high accuracy of CLMIA without interfering. The positive concordance rate between CLMIA and the Phadia system exceeds 90 % with a good negative concordance rate (>85 %) and the Kappa coefficients (>0.8), suggesting the close alignment of CLMIA and the Phadia system and showing the satisfactory clinical potential of CLMIA in children's allergy disease. CONCLUSIONS: The application of CLMIA has been promising in allergen testing, especially for detecting multiple allergenic components in children.

3.
BMC Health Serv Res ; 24(1): 1126, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39334322

RESUMEN

BACKGROUND: Monitoring hand hygiene compliance (HHC) of healthcare providers (HCPs) in healthcare facilities is critical for hand hygiene (HH) promotion. However, less is known about the cost and effectiveness of different HHC monitoring tools. In this study, we aimed to compare various health economic indicators corresponding to electronic system-based monitoring (ESM) and manual paper-based monitoring (MPM) for HHC to provide evidence-based advice for HHC monitoring measures targeted selecting. METHODS: A before and after study in 40 clinical departments with 4,524 healthcare providers was conducted from December 2022 to January 2023 (MPM implementation phase) and March 2023 to May 2023 (ESM implementation phase). The cost-effectiveness, cost-efficiency, the extent of the Hawthorne effect, and indirect cost-benefit of the two monitoring methods were compared. RESULTS: The total cost spent on ESM for the 40 departments (17,702.92 CNY) was 4,123.76 CNY lower than that of MPM (21,826.68 CNY). The HHC of MPM (80.16%) was higher than that of ESM (69.82%) (p < 0.01). In high- and medium-risk departments, the cost-effectiveness ratio of ESM (7,977.90 CNY and 13,794.60 CNY, respectively) was lower than that of MPM (9,039.61 CNY and 14,549.05 CNY, respectively). In low-risk departments, the cost-effectiveness ratio of ESM (3,910.77 CNY) was higher than that of MPM (3,899.06 CNY). Compared with ESM, the incremental cost of MPM in all departments was 4,123.76 CNY, the incremental effectiveness was 10.34%, and the incremental cost-effectiveness ratio was 39,881.62 CNY. Between the two monitoring methods, the efficiency of ESM (48.11%) in all departments was higher than that of MPM (14.20%) (p < 0.01). The cost-efficiency ratio of MPM in all departments (155,775.56 CNY) was higher than that of ESM (36,796.76 CNY). The extent of Hawthorne effect of MPM of HHC in all departments (43.99%) was higher than that of ESM (35.69%) (p < 0.01). When ESM was used as the HHC monitoring approach, the HAI rates (1.39%) in all departments were higher than that when MPM was used (1.34%) (p = 0.562). When the payment willingness was less than 40,000 CNY, the ESM method was the better option for cost-effectiveness; When the input exceeded this threshold, the MPM method was the better option for cost-effectiveness. CONCLUSIONS: ESM exhibited notable advantages over MPM in terms of cost-effectiveness, cost-efficiency, cost-benefit, and the Hawthorne effect.


Asunto(s)
Análisis Costo-Beneficio , Adhesión a Directriz , Higiene de las Manos , Humanos , Higiene de las Manos/economía , Higiene de las Manos/normas , Adhesión a Directriz/estadística & datos numéricos , Personal de Salud/economía
4.
Environ Geochem Health ; 46(11): 427, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39316269

RESUMEN

Tetracycline Resistance Genes (TRGs) have received widespread attention in recent years, as they are a novel environmental pollutant that can rapidly accumulate and migrate in soil plant systems through horizontal gene transfer (HGT), posing a potential threat to food safety and public health. This article systematically reviews the pollution sources, enrichment, and migration characteristics of TRGs in soil. The main sources of TRGs include livestock manure and contaminated wastewater, especially in intensive farming environments where TRGs pollution is more severe. In soil, TRGs diffuse horizontally between bacteria and migrate to plant tissues through mechanisms such as plasmid conjugation, integron mediation, and phage transduction. The migration of TRGs is not limited to the soil interior, and increasing evidence suggests that they can also enter the plant system through plant root absorption and the HGT pathway of endophytic bacteria, ultimately accumulating in plant roots, stems, leaves, fruits, and other parts. This process has a direct impact on human health, especially when TRGs are found in crops such as vegetables, which may be transmitted to the human body through the food chain. In addition, this article also deeply analyzed various factors that affect the migration of TRGs, including the residual level of tetracycline in soil, the type and concentration of microorganisms, heavy metal pollution, and the presence of new pollutants such as microplastics. These factors significantly affect the enrichment rate and migration mode of TRGs in soil. In addition, two technologies that can effectively eliminate TRGs in livestock breeding environments were introduced, providing reference for healthy agricultural production. The article concludes by summarizing the shortcomings of current research on TRGs, particularly the limited understanding of TRG migration pathways and their impact mechanisms. Future research should focus on revealing the migration mechanisms of TRGs in soil plant systems and developing effective control and governance measures to reduce the environmental transmission risks of TRGs and ensure the safety of ecosystems and human health.


Asunto(s)
Transferencia de Gen Horizontal , Microbiología del Suelo , Contaminantes del Suelo , Resistencia a la Tetraciclina , Resistencia a la Tetraciclina/genética , Plantas/microbiología , Humanos , Bacterias/genética , Bacterias/efectos de los fármacos , Suelo/química , Tetraciclina/farmacología
5.
World J Stem Cells ; 16(8): 811-823, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39219725

RESUMEN

BACKGROUND: Pulmonary fibrosis is one of the main reasons for the high mortality rate among acute respiratory distress syndrome (ARDS) patients. Mesenchymal stromal cell-derived microvesicles (MSC-MVs) have been shown to exert antifibrotic effects in lung diseases. AIM: To investigate the effects and mechanisms of MSC-MVs on pulmonary fibrosis in ARDS mouse models. METHODS: MSC-MVs with low hepatocyte growth factor (HGF) expression (siHGF-MSC-MVs) were obtained via lentivirus transfection and used to establish the ARDS pulmonary fibrosis mouse model. Following intubation, respiratory mechanics-related indicators were measured via an experimental small animal lung function tester. Homing of MSC-MVs in lung tissues was investigated by near-infrared live imaging. Immunohistochemical, western blotting, ELISA and other methods were used to detect expression of pulmonary fibrosis-related proteins and to compare effects on pulmonary fibrosis and fibrosis-related indicators. RESULTS: The MSC-MVs gradually migrated and homed to damaged lung tissues in the ARDS model mice. Treatment with MSC-MVs significantly reduced lung injury and pulmonary fibrosis scores. However, low expression of HGF (siHGF-MSC-MVs) significantly inhibited the effects of MSC-MVs (P < 0.05). Compared with the ARDS pulmonary fibrosis group, the MSC-MVs group exhibited suppressed expression of type I collagen antigen, type III collagen antigen, and the proteins transforming growth factor-ß and α-smooth muscle actin, whereas the siHGF-MVs group exhibited significantly increased expression of these proteins. In addition, pulmonary compliance and the pressure of oxygen/oxygen inhalation ratio were significantly lower in the MSC-MVs group, and the effects of the MSC-MVs were significantly inhibited by low HGF expression (all P < 0.05). CONCLUSION: MSC-MVs improved lung ventilation functions and inhibited pulmonary fibrosis in ARDS mice partly via HGF mRNA transfer.

6.
Front Genet ; 15: 1407202, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38966008

RESUMEN

Defective oocyte maturation is a common cause of female infertility. The loss of the zona pellucida (ZP) represents a specific condition of impaired oocyte maturation. The extracellular matrix known as the ZP envelops mammalian oocytes and preimplantation embryos, exerting significant influence on oogenesis, fertilization, and embryo implantation. However, the genetic factors leading to the loss of the ZP in oocytes are not well understood. This study focused on patients who underwent oocyte retrieval surgery after ovarian stimulation and were found to have abnormal oocyte maturation without the presence of the ZP. Ultrasonography was performed during the surgical procedure to evaluate follicle development. Peripheral blood samples from the patient were subjected to exome sequencing. Here, a novel, previously unreported heterozygous mutation in the ZP1 gene was identified. Within the ZP1 gene, we discovered a novel heterozygous mutation (ZP1 NM_207341.4:c.785A>G (p.Y262C)), specifically located in the trefoil domain. Bioinformatics comparisons further revealed conservation of the ZP1-Y262C mutation across different species. Model predictions of amino acid mutations on protein structure and cell immunofluorescence/western blot experiments collectively confirmed the detrimental effects of the ZP1-Y262C mutation on the function and expression of the ZP1 protein. The ZP1-Y262C mutation represents the novel mutation in the trefoil domain of the ZP1 protein, which is associated with defective oocyte maturation in humans. Our report enhances comprehension regarding the involvement of ZP-associated genes in female infertility and offers enriched understanding for the genetic diagnosis of this condition.

7.
Mar Pollut Bull ; 205: 116643, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38950513

RESUMEN

Growing economic and industrial activities have put a large strain on the marine environment and ecosystem, presenting the marine economy with a tradeoff between economic expansion and environmental conservation. Though the Porter hypothesis depicts a win-win situation, it is crucial to consider the conditions under which environmental regulations generate positive effects. This paper is to study how the synergy between market-based and government-based environmental regulations affects marine economic resilience, whereas maintaining economic resilience is a prerequisite for promoting innovation and productivity. The findings indicate that each 1 % increase in the synergistic level of environmental regulations resulted in a 0.234 % improvement in marine economic resilience. The heterogeneity tests indicate that the relationship is still significant if the marine economy characterizes high industrial diversity, high industrial upgrading, and large scale, while environmental regulation in coastal provinces that marine industrial structure is not advanced negatively affects marine economic resilience.


Asunto(s)
Conservación de los Recursos Naturales , Ecosistema , Política Ambiental
8.
Heliyon ; 10(13): e33642, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39027539

RESUMEN

Chitosan is a biocompatible, non-toxic and renewable natural basic polysaccharide that can be cross-linked and reacted with Ce(IV) to form a physiologically active chitosan-Ce(IV) complex. To investigate this novel complex and its potential to hydrolyze phosphate ester bonds, chitosan-cerium complex microspheres resin (CS-CCMR) was prepared from chitosan and ceric ammonium nitrate by reversed-phase suspension cross-linking polymerization. CS-CCMR was characterized, its ability to hydrolyze disodium p-nitrobenzene phosphate (PNPP2Na) and organophosphorus pesticides was investigated, and the hydrolytic mechanism was explored. CS-CCMR was composed of dark yellow microspheres with smooth surfaces and dense pores. It was found that CS-CCMR contained 4.507 mg/g Ce(IV), indicating that coordination polymerization between Ce(IV) and chitosan was successful. The presence of Ce(IV) in CS-CCMR was confirmed by multiple analytical methods and it was found that coordination of Ce(IV) by chitosan was mediated by the nitrogen atom of the amino group and the oxygen atom of the hydroxyl group of chitosan. It was shown that CS-CCMR efficiently hydrolyzed the phosphate ester bonds of PNPP2Na and five organophosphorus pesticides. Hydrolysis of PNPP2Na is potentially accomplished by charge neutralization and nucleophilic substitution. The mechanism of parathion degradation by CS-CCMR involves modification of the nitro group to give aminoparathion, followed by cleavage of the P-O bond to generate diazinphos. Consequently, the novel chitosan-Ce(IV) complex exhibits great efficiency for hydrolysis of phosphate ester bonds and CS-CCMR is expected to be developed as an agent to reduce the possibility of contamination of fruit and vegetable drinks by organophosphorus pesticides.

9.
Inorg Chem ; 63(35): 16177-16185, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39001841

RESUMEN

Monitoring levels of excessive aluminum ions (Al3+) is crucial as it can harm the immune system, reduce enzyme activity, cause cell death, and damage environmental and biological systems. Developing a fast and efficient Al3+ ion determination method is the key to addressing this issue. In this work, red-emitting fluorescent copper nanoclusters (CuNCs) were synthesized using N-acetyl-l-cysteine (NAC) as a ligand and CuCl2·2H2O through a facile procedure. The NAC-CuNCs exhibited a large Stokes shift and displayed remarkable luminescence properties. A method for detecting Al3+ through a fluorescence probe was proposed. Its fluorescence mechanism was also explored. The probe showed rapid responsiveness (within 1 min) to Al3+ ion determination. The detection limit for Al3+ was found to be 19.7 nM, which is significantly lower than the WHO's value and most reports, with a linear range of 0-52.9 µM. The determination of Al3+ concentrations in actual water using the fluorescence probe yielded satisfactory outcomes. Moreover, the visual detection of Al3+ ions was also achieved through a smartphone, which can enhance its fast and practical detection.

10.
Neural Netw ; 178: 106394, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38823070

RESUMEN

Stereo matching cost constrains the consistency between pixel pairs. However, the consistency constraint becomes unreliable in ill-posed regions such as occluded or ambiguous regions of the images, making it difficult to explore hidden correspondences. To address this challenge, we introduce an Error-area Feature Refinement Mechanism (EFR) that supplies context features for ill-posed regions. In EFR, we innovatively obtain the suspected error region according to aggregation perturbations, then a simple Transformer module is designed to synthesize global context and correspondence relation with the identified error mask. To better overcome existing texture overfitting, we put forward a Dual-constraint Cost Volume (DCV) that integrates supplementary constraints. This effectively improves the robustness and diversity of disparity clues, resulting in enhanced details and structural accuracy. Finally, we propose a highly accurate stereo matching network called Error-rectify Feature Guided Stereo Matching Network (ERCNet), which is based on DCV and EFR. We evaluate our model on several benchmark datasets, achieving state-of-the-art performance and demonstrating excellent generalization across datasets. The code is available at https://github.com/dean7liu/ERCNet_2023.


Asunto(s)
Algoritmos , Redes Neurales de la Computación , Procesamiento de Imagen Asistido por Computador/métodos , Humanos , Reconocimiento de Normas Patrones Automatizadas/métodos
11.
BMC Med Educ ; 24(1): 624, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38840091

RESUMEN

BACKGROUND: The incidence of mental health problems among medical graduate students is much higher than among students of other disciplines. This can have adverse consequences for the medical students themselves as well as their future patients. This study aims to understand the pressures faced by Chinese medical students and the current status of mental health education. It also propose recommendations for the current situation and prospects for the future. METHOD: The authors conducted in-depth semi-structured interviews with 22 master's students from five medical schools during November 2023. All interview sessions were recorded and transcribed verbatim. The transcriptions were analyzed using the Colaizzi's seven-step method. RESULT: Three main themes were extracted from the students' statements: sources of psychological stress, ways to cope with stress, and perspectives on mental health education. The study showed that current mental health education in China is mostly in the form of printed mental health education manuals and mental health lectures, and there is no active tiered intervention for students at different levels. It is suggested that reforms should be made to shift to a model where the school proactively identifies problems and intervenes based on feedback. CONCLUSION: This study reveals the widespread psychological stress and shortcomings in current education methods. To address these challenges, institutions should develop tailored interventions, including tiered support systems, open dialogue promotion, and resilience training. Future research should focus on evaluating innovative interventions' effectiveness, ultimately fostering a supportive environment that enhances students' success and contributes to a healthier healthcare workforce.


Asunto(s)
Adaptación Psicológica , Investigación Cualitativa , Estrés Psicológico , Estudiantes de Medicina , Humanos , China , Estudiantes de Medicina/psicología , Masculino , Femenino , Adulto , Entrevistas como Asunto , Salud Mental , Educación de Postgrado en Medicina , Habilidades de Afrontamiento , Pueblos del Este de Asia
12.
J Leukoc Biol ; 116(4): 890-900, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38776408

RESUMEN

This study aimed to investigate whether changes in presepsin, procalcitonin, high-sensitivity C-reactive protein, and interleukin 6 levels predict mortality in septic patients in the intensive care unit. This study enrolled septic patients between November 2020 and December 2021. Levels of presepsin, procalcitonin, high-sensitivity C-reactive protein, and interleukin 6 were measured on the first (PSEP_0, PCT_0, hsCRP_0, IL-6_0) and third days (PSEP_3, PCT_3, hsCRP_3, IL-6_3). Follow-up was performed on days 3, 7, 14, 21, and 28 after enrollment. The outcome was all-cause death. The study included 119 participants, and the mortality was 18.5%. In univariable Cox proportional hazards regression analysis, ΔPSEP (= PSEP_3 - PSEP_0) > 211.49 pg/mL (hazard ratio, 2.70; 95% confidence interval, 1.17-6.22), ΔPCT (= PCT_3 - PCT_0) > -0.13 ng/mL (hazard ratio, 7.31; 95% confidence interval, 2.68-19.80), ΔhsCRP (= hsCRP_3 - hsCRP_0) > -19.29 mg/L (hazard ratio, 6.89; 95% confidence interval, 1.61-29.40), and ΔIL-6 (= IL-6_3 - IL-6_0) > 1.00 pg/mL (hazard ratio, 3.13; 95% confidence interval, 1.35-7.24) indicated an increased risk of mortality. The composite concordance index for alterations in all 4 distinct biomarkers was highest (concordance index, 0.83; 95% confidence interval, 0.76-0.91), suggesting the optimal performance of this panel in mortality prediction. In decision curve analysis, compared with the Acute Physiology and Chronic Health Evaluation II and Sequential (sepsis-related) Organ Failure Assessment scores, the combination of the 4 biomarkers had a larger net benefit. Interestingly, interleukin 6 was predominantly produced by monocytes upon lipopolysaccharide stimulation in peripheral blood mononuclear cells. ΔPSEP, ΔPCT, ΔhsCRP, and ΔIL-6 are reliable biomarkers for predicting mortality in septic patients in the intensive care unit, and their combination has the best performance.


Asunto(s)
Biomarcadores , Proteína C-Reactiva , Unidades de Cuidados Intensivos , Interleucina-6 , Receptores de Lipopolisacáridos , Fragmentos de Péptidos , Polipéptido alfa Relacionado con Calcitonina , Sepsis , Humanos , Interleucina-6/sangre , Masculino , Receptores de Lipopolisacáridos/sangre , Femenino , Sepsis/mortalidad , Sepsis/sangre , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Anciano , Persona de Mediana Edad , Fragmentos de Péptidos/sangre , Polipéptido alfa Relacionado con Calcitonina/sangre , Biomarcadores/sangre , Pronóstico
13.
Cell Prolif ; : e13647, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38605678

RESUMEN

Major zygotic genome activation (ZGA) occurs at the late 2-cell stage and involves the activation of thousands of genes, supporting early embryonic development. The reasons underlying the regulation of ZGA are not clear. Acetylation modifications of histone tails promote transcriptional activation, and the maternal deletion of H4K16ac leads to failure in ZGA. GATAD2B is one of the core subunits of the nucleosome remodelling and histone deacetylation (NuRD) complex. Our research has shown that GATAD2B exhibits specific nucleus localization and high protein expression from the late 2-cell stage to the 8-cell stage. This intriguing phenomenon prompted us to investigate the relationship between GATAD2B and the ZGA. We discovered a distinctive pattern of GATAD2B, starting from the late 2-cell stage with nuclear localization. GATAD2B depletion resulted in defective embryonic development, including increased DNA damage at morula, decreased blastocyst formation rate, and abnormal differentiation of ICM/TE lineages. Consistent with the delay during the cleavage stage, the transcriptome analysis of the 2-cell embryo revealed inhibition of the cell cycle G2/M phase transition pathway. Furthermore, the GATAD2B proteomic data provided clear evidence of a certain association between GATAD2B and molecules involved in the cell cycle pathway. As hypothesized, GATAD2B-deficient 2-cell embryos exhibited abnormalities in ZGA during the maternal-to-embryonic transition, with lower expression of the major ZGA marker MERVL. Overall, our results demonstrate that GATAD2B is essential for early embryonic development, in part through facilitating ZGA.

14.
Int J Nanomedicine ; 19: 2611-2623, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38505166

RESUMEN

Background: The photodynamic therapy (PDT) showed promising potential in treating tongue squamous cell carcinoma (TSCC). The Food and Drug Administration approved Verteporfin (Ver) is a powerful alternative in this field for its penetrating power and high production of reactive oxygen species (ROS). However, its applications in the treatment of TSCC are still rare. Methods: Ver was loaded onto Poly (lactic-co-glycolic acid) (PLGA) nanoparticles, followed by the modification with RGD peptide as the ligand. The nanostructured was named as RPV. In vitro assessments were conducted to evaluate the cytotoxicity of RPV through the Live/Dead assay analysis and Cell Counting Kit-8 (CCK-8) assay. Using the reactive oxygen species assay kit, the potential for inducing targeted tumor cell death upon laser irradiation by promoting ROS production was investigated. In vivo experiments involved with the biological distribution of RPV, the administration with RPV followed by laser irradiation, and the measurement of the tumor volumes. Immunohistochemical analysis was used to detect the Ki-67 expression, and apoptosis induced by RPV-treated group. Systemic toxicity was evaluated through hematoxylin-eosin staining and blood routine analysis. Real-time monitoring was employed to track RPV accumulation at tumor sites. Results: The in vitro assessments demonstrated the low cytotoxicity of RPV and indicated its potential for targeted killing TSCC cells under laser irradiation. In vivo experiments revealed significant tumor growth inhibition with RPV treatment and laser irradiation. Immunohistochemical analysis showed a notable decrease in Ki-67 expression, suggesting the effective suppression of cell proliferation, and TUNEL assay indicated the increased apoptosis in the RPV-treated group. Pathological examination and blood routine analysis revealed no significant systemic toxicity. Real-time monitoring exhibited selective accumulation of RPV at tumor sites. Conclusion: The findings collectively suggest that RPV holds promise as a safe and effective therapeutic strategy for TSCC, offering a combination of targeted drug delivery with photodynamic therapy.


Asunto(s)
Carcinoma de Células Escamosas , Nanopartículas , Fotoquimioterapia , Neoplasias de la Lengua , Humanos , Verteporfina/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Neoplasias de la Lengua/tratamiento farmacológico , Neoplasias de la Lengua/metabolismo , Neoplasias de la Lengua/patología , Especies Reactivas de Oxígeno/metabolismo , Antígeno Ki-67 , Línea Celular Tumoral , Lengua/metabolismo , Lengua/patología , Fármacos Fotosensibilizantes
15.
Adv Biol (Weinh) ; 8(5): e2400028, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38463014

RESUMEN

Emerging evidence has implicated nicotinamide adenine dinucleotide (NAD+) metabolism in various inflammatory diseases. In the study, the role of NAD+ metabolism in Complete Freund's Adjuvant (CFA)-evoked inflammatory pain and the underlying mechanisms are investigated. The study demonstrated that CFA induced upregulation of nicotinamide phosphoribosyltransferase (NAMPT) in dorsal root ganglia (DRG) without significant changes in the spinal cord. Inhibition of NAMPT expression by intrathecal injection of NAMPT siRNA alleviated CFA-induced pain-like behavior, decreased NAD+ contents in DRG, and lowered poly-(ADP-ribose) polymerase 1 (PARP1) activity levels. These effects are all reversed by the supplement of nicotinamide mononucleotide (NMN). Inhibition of PARP1 expression by intrathecal injection of PARP1 siRNA alleviated CFA-induced pain-like behavior, while elevated NAD+ levels of DRG. The analgesic effect of inhibiting NAMPT/NAD+/PARP1 axis can be attributed to the downregulation of the NF-κB/IL-1ß inflammatory pathway. Double immunofluorescence staining showed that the expression of NAMPT/NAD+/PARP1 axis is restricted to DRG neurons. In conclusion, PARP1 activation in response to CFA stimulation, fueled by NAMPT-derived NAD+, mediates CFA-induced inflammatory pain through NF-κB/IL-1ß inflammatory pathway.


Asunto(s)
Ganglios Espinales , NAD , Nicotinamida Fosforribosiltransferasa , Poli(ADP-Ribosa) Polimerasa-1 , Nicotinamida Fosforribosiltransferasa/metabolismo , Nicotinamida Fosforribosiltransferasa/genética , Animales , Ganglios Espinales/metabolismo , Ganglios Espinales/efectos de los fármacos , NAD/metabolismo , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Poli(ADP-Ribosa) Polimerasa-1/genética , Masculino , Ratones , Adyuvante de Freund , Inflamación/metabolismo , Citocinas/metabolismo , Dolor/metabolismo , FN-kappa B/metabolismo
16.
Pain ; 165(9): 2035-2043, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38537053

RESUMEN

ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) is a promising technology to reduce chronic pain. Investigating the mechanisms of rTMS analgesia holds the potential to improve treatment efficacy. Using a double-blind and placebo-controlled design at both stimulation and pharmacologic ends, this study investigated the opioidergic mechanisms of rTMS analgesia by abolishing and recovering analgesia in 2 separate stages across brain regions and TMS doses. A group of 45 healthy participants were equally randomized to the primary motor cortex (M1), the dorsolateral prefrontal cortex (DLPFC), and the Sham group. In each session, participants received an intravenous infusion of naloxone or saline before the first rTMS session. Participants then received a second dose of rTMS session after the drugs were metabolized at 90 minutes. M1-rTMS-induced analgesia was abolished by naloxone compared with saline and was recovered by the second rTMS run when naloxone was metabolized. In the DLPFC, double but not the first TMS session induced significant pain reduction in the saline condition, resulting in less pain compared with the naloxone condition. In addition, TMS over the M1 or DLPFC selectively increased plasma concentrations of ß-endorphin or encephalin, respectively. Overall, we present causal evidence that opioidergic mechanisms are involved in both M1-induced and DLPFC-rTMS-induced analgesia; however, these are shaped by rTMS dosage and the release of different endogenous opioids.


Asunto(s)
Analgesia , Naloxona , Estimulación Magnética Transcraneal , Humanos , Estimulación Magnética Transcraneal/métodos , Masculino , Femenino , Adulto , Método Doble Ciego , Analgesia/métodos , Adulto Joven , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Corteza Prefontal Dorsolateral/fisiología , Corteza Motora/fisiología , Corteza Motora/efectos de los fármacos , Manejo del Dolor/métodos , Dimensión del Dolor/métodos , betaendorfina/sangre , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/fisiología , Corteza Prefrontal/metabolismo
17.
Anal Methods ; 16(14): 2063-2070, 2024 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-38505942

RESUMEN

Sunset Yellow (SY) is a widely used food coloring in the food industry. However, exceeding the allowable limit of this dye poses a significant threat to human health. To address this issue, we developed Lycium ruthenicum-derived nitrogen-doped carbon dots (N-CDs) with a stable blue fluorescence through hydrothermal treatment for SY determination. The quantum yield (QY) of these N-CDs was found to be up to 10.63%. Physical characterization of N-CDs was performed using various spectroscopic techniques to confirm their excellent photostability and non-toxic properties. Furthermore, the presence of SY had a substantial quenching effect on the fluorescence intensity (F0/F) of the N-CDs. Leveraging this observation, we developed a fluorescent sensor for the determination of SY in the concentration range of 0.05 to 35.0 µM, with a limit of detection (LOD, 3σ/K) of 17 nM. The excellent fluorescent sensor also showed satisfactory results in the practical drink samples. Moreover, the stability and cytotoxicity of N-CDs as a fluorescent probe were studied. Finally, the N-CDs were applied to cell imaging using A549 cells.


Asunto(s)
Compuestos Azo , Puntos Cuánticos , Humanos , Fluorescencia , Puntos Cuánticos/toxicidad , Puntos Cuánticos/química , Carbono/química , Nitrógeno/química , Biomasa
18.
Polymers (Basel) ; 16(5)2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38475350

RESUMEN

The sluggish commercial application of proton exchange membrane fuel cells (PEMFCs) with low Pt loading is chiefly hindered by concentration polarization loss, particularly at high current density regions. Addressing this, our study concentrates on the ionomer membranes in the cathode catalyst layer (CCL) and explores the potential of incorporating additional hydrophilic or hydrophobic components to modify these ionomers. Therefore, an all-atom model was constructed and for the ionomer and hydrophilic and hydrophobic modifications were implemented via incorporating SiO2 and PTFE, respectively. The investigation was conducted via molecular dynamics (MD) simulations to predict the morphology and structure of the ionomer and analyze the kinetic properties of oxygen molecules and protons. The simulation results elaborate that the hydrophilic and hydrophobic modifications favor the phase separation and the self-diffusion coefficients of oxygen molecules and protons are enhanced. Considering the hydration level of the ionomer films, hydrophilic modification facilitates mass transfer under low-hydration-level conditions, while hydrophobic modification is more effective in optimizing mass transfer as the hydration level increases. The optimal contents of SiO2 and PTFE for each hydration level in this work are 9.6% and 45%, respectively. This work proposes a reliable model and presents a detailed analysis of hydrophilic and hydrophobic modifications, which provides theoretical guidance for quantitative preparations of various composite membranes.

19.
Ann Hepatol ; 29(4): 101475, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38331384

RESUMEN

INTRODUCTION AND OBJECTIVES: Acute liver injury (ALI) is characterized by massive hepatocyte death with high mortality and poor prognosis. Hepatocyte pyroptosis plays a key role in the physiopathological processes of ALI, which can damage mitochondria and release NLRP3 inflammasome particles, causing systemic inflammatory responses. Z-DNA Binding Protein 1 (ZBP1) is a sensor that induces cell death. Here, we investigated whether ZBP1 participates in hepatocyte pyroptosis and explored the possible pathogenesis of ALI. MATERIALS AND METHODS: Hepatocyte pyrotosis was induced with lipopolysaccharide (LPS) and nigericin (Nig), and the expression of Zbp1 (ZBP1) was examined by western blot analysis and RT-qPCR. Further, we transfected AML-12 (LO2 and HepG2) cell lines with Zbp1 (ZBP1) siRNA. After ZBP1 was silenced, LDH release and flow cytometry were used to measure the cell death; Western blot analysis and RT-qPCR were used to detect the marker of NLRP3 inflammasome activation and pyroptosis. We also detected the expression of mitochondrial linear rupture marker phosphoglycerate mutase family member 5 (PGAM5) using western blot analysis and reactive oxygen species (ROS) using the DCFH-DA method. RESULTS: The expression of ZBP1 was up-regulated in LPS/Nig-induced hepatocytes. Si-Zbp1 (Si-ZBP1) inhibited NLRP3 inflammasome activation and pyroptosis in LPS/Nig-induced hepatocytes. Moreover, ZBP1 silencing inhibited the expression of PGAM5 by reducing ROS production. CONCLUSIONS: ZBP1 promotes hepatocellular pyroptosis by modulating mitochondrial damage, which facilitates the extracellular release of ROS.


Asunto(s)
Hepatocitos , Lipopolisacáridos , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Especies Reactivas de Oxígeno , Animales , Humanos , Células Hep G2 , Hepatocitos/metabolismo , Hepatocitos/patología , Inflamasomas/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Nigericina/farmacología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Fosfoproteínas Fosfatasas , Especies Reactivas de Oxígeno/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Transducción de Señal
20.
Fish Shellfish Immunol ; 146: 109398, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38244822

RESUMEN

Hexagrammos otakii is favored by consumers and aquaculture practitioners because of its strong adaptability and fast growth. However, recently, frequent outbreaks of diseases in the breeding of H. otakii have led to significant economic losses, especially due to bacterial diseases, which limit the healthy breeding of H. otakii. As a luminescent Gram-negative bacterium, Vibrio harveyi is the main pathogenic bacteria of H. otakii. In this study, the histopathology and label-free quantitative proteomics analysis were performed to reveal the changes of skin mucus proteins in H. otakii after infection with V. harveyi. The histopathological changes in the skin of H. otakii showed that when the bacteria were injected into the epithelial cells, it caused an increase in the number of mucous cells and a certain degree of damage and deformation in skin. Moreover, the quantitative proteomics analysis revealed a total of 364 differentially expressed proteins (DEPs), and these DEPs were found to be involved in environmental information processing, metabolism, infectious diseases: bacteria, replication and repair. More importantly, the enrichment analysis of the DEPs revealed that these different proteins were mainly targeted immune-related pathways. After infection of bacteria, the host's immune ability will be weakened, causing V. harveyi to enter the organism more easily, resulting in increased mucus in H. otakii, which will eventually lead to a decline in its physical function. These results provided an insight into a series of physiological changes after the bacterial infection of fish at the proteomic level and basic data for further exploration of the potential mechanism of skin mucus. Taken together, the results indicated more opportunities for the future designs and discoveries of effective antibacterial vaccines and antibacterial drugs for H. otakii.


Asunto(s)
Enfermedades de los Peces , Perciformes , Vibriosis , Vibrio , Animales , Proteómica , Vibrio/fisiología , Proteínas , Moco , Antibacterianos/farmacología
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