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1.
Adv Mater ; : e2408301, 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39375988

RESUMEN

Here, a rechargeable carbon fluoride battery is demonstrated with unprecedented high rate and long life by oxygen doping and electrolyte formulation. The introductions of Mn2+-O catalyst and porous structure during the oxidation process of CFx cathode can promote the splitting of Li-F during charging. By further modulating the electrolyte with triphenylantimony chloride (TSbCl) as anion acceptor and CsF as product modulator, the more readily dissociable CsLiF2 product instead of LiF is preferentially formed, and the TSbCl-salt protection interface is constructed to confine Li-F based products and reduce fluoride loss at cathode side. These effects endow Li-CFx batteries with durable reversible conversion reaction (for at least 600 cycles), ultrahigh rate performance (e.g., 364 mAh g-1 at 20 A g-1) and low charging plateau voltage down to 3.2 V. The cathode exhibits the maximum power density of 38342 W kg-1 and energy density of 1012 Wh kg-1. Furthermore, this Li-CFx system demonstrates the promising prospects for applications in view of its low temperature operation (e.g., 280 mAh g-1 at -20 °C), low self-discharge ability, large-scale pouch cell fabrication and high cathode loading (5-6 mg cm-2), enabling it to move beyond previous role as primary battery and into new role as fast-charging rechargeable battery with high energy density.

2.
Chembiochem ; : e202400670, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39365708

RESUMEN

Over the last four decades, research on DNA as a functional material has primarily  focused on its predictable conformation and programmable interaction. However, its low energy consumption, high responsiveness and sensitivity also make it ideal for designing specific signaling pathways, and enabling the development of molecular computers. This review mainly discusses recent advancements  in the utilization of DNA nanotechnology for molecular computer, encompassing applications in storage, cryptography and logic circuits. It elucidates the challenges encountered in the application process and presents solutions exemplified by representative works. Lastly, it delineates the challenges and opportunities within this filed.

3.
Ibrain ; 10(3): 266-289, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39346788

RESUMEN

Amyloid-ß (Aß) is a pivotal biomarker in Alzheimer's disease (AD), attracting considerable attention from numerous researchers. There is uncertainty regarding whether clearing Aß is beneficial or harmful to cognitive function. This question has been a central topic of research, especially given the lack of success in developing Aß-targeted drugs for AD. However, with the Food and Drug Administration's approval of Lecanemab as the first anti-Aß medication in July 2023, there is a significant shift in perspective on the potential of Aß as a therapeutic target for AD. In light of this advancement, this review aims to illustrate and consolidate the molecular structural attributes and pathological ramifications of Aß. Furthermore, it elucidates the determinants influencing its expression levels while delineating the gamut of extant Aß-targeted pharmacotherapies that have been subjected to clinical or preclinical evaluation. Subsequently, a comprehensive analysis is presented, dissecting the research landscape of Aß across the domains above, culminating in the presentation of informed perspectives. Concluding reflections contemplate the supplementary advantages conferred by nanoparticle constructs, conceptualized within the framework of multivalent theory, within the milieu of AD diagnosis and therapeutic intervention, supplementing conventional modalities.

4.
BMC Cancer ; 24(1): 1104, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39237862

RESUMEN

BACKGROUND: The purpose of this retrospective study was to compare the safety and feasibility of single-intercostal totally minimally invasive Ivor Lewis esophagectomy (MIIE) with those of multiple-intercostal MIIE. METHODS: Between January 2016 and December 2022, clinical data were collected for 528 patients who successfully underwent totally minimally invasive esophagectomy. Among these patients, 294 underwent MIIE, with 200 undergoing the single-intercostal approach and 94 undergoing the multiple-intercostal approach. Propensity score matching (PSM) was applied to the cohort of 294 patients. Subsequently, perioperative outcomes and other pertinent clinical data were analyzed retrospectively. RESULTS: A total of 294 patients were subjected to PSM, and 89 groups of patient data (178 persons in total) were well balanced and included in the follow-up statistics. Compared to the multiple intercostal group, the single intercostal group had a shorter operative time (280 min vs. 310 min; p < 0.05). Moreover, there was no significant difference in the incidence of major perioperative complications (p > 0.05). The total number of lymph nodes sampled (25.30 vs. 27.55, p > 0.05) and recurrent laryngeal nerve lymph nodes sampled on the both sides (p > 0.05) did not significantly differ. The single intercostal group had lower postoperative long-term usage of morphine (0,0-60 vs. 20,20-130; p < 0.01), total temporary addition (10,0-30 vs. 20,20-40; p < 0.01) and temporary usage in the first 3 days after surgery (0,0-15 vs. 10,10-20; p < 0.01) than did the multicostal group.There were no significant differences in age, sex, tumor location or extent of lymphadenectomy or in the clinical factors between the single-intercostal group (p > 0.05). CONCLUSIONS: Both techniques can be used for the treatment of esophageal cancer. Compared to multiple intercostal MIIE, the feasibility of which has been proven internationally, the single intercostal technique can also be applied to patients of different age groups and sexes and with different tumor locations. It can provide surgeons with an additional surgical option. TRIAL REGISTRATION: This study was retrospectively registered by the Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine, and written informed consent was exempted from ethical review. The registration number was 20,230,326. The date of registration was 2023.03.26.


Asunto(s)
Neoplasias Esofágicas , Esofagectomía , Humanos , Masculino , Femenino , Estudios Retrospectivos , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Esofagectomía/métodos , Esofagectomía/efectos adversos , Persona de Mediana Edad , Anciano , Toracoscopía/métodos , Toracoscopía/efectos adversos , Tempo Operativo , Estudios de Factibilidad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Puntaje de Propensión , Escisión del Ganglio Linfático/métodos , Resultado del Tratamiento , Adulto
5.
Nano Lett ; 24(39): 12263-12270, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39303068

RESUMEN

A unary system is the most conceptually concise design for conducting self-assembly. However, in most DNA-guided self-assembly schemes, a unary system has rarely been adopted because of the inherent challenge of strictly decoupling the monomer synthesis process from the assembly process, which may directly lead to the inaccurate control over assembly. Herein, we provide a multi-stimulus-triggered assembly strategy based on the DNA origami structure, which allows the unary system to realize controllable crystallization and phase transition by exerting allosteric stimuli. We intentionally introduced a specific DNA stimulus to convert the self-aggregation of functionalized groups into the connection of nearby monomers, thus producing multidimensional high-quality crystals. Furthermore, this unary system can undergo a phase transition from simple cubic to face-centered cubic with the introduction of more cation stimuli. We believe that this dynamic stimulation strategy can offer a novel solution for fabricating materials with on-demand modulation.


Asunto(s)
ADN , Nanoestructuras , Transición de Fase , ADN/química , Nanoestructuras/química , Cristalización , Conformación de Ácido Nucleico , Nanotecnología/métodos
6.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 41(4): 742-750, 2024 Aug 25.
Artículo en Chino | MEDLINE | ID: mdl-39218600

RESUMEN

Understanding the mass transfer behaviors in hollow fiber membrane module of artificial liver is important for improving toxin removal efficiency. A three-dimensional numerical model was established to study the mass transfer of small molecule bilirubin and macromolecule bovine serum albumin (BSA) in the hollow fiber membrane module. Effects of tube-side flow rate, shell-side flow rate, and hollow fiber length on the mass transfer of bilirubin and BSA were discussed. The simulation results showed that the clearance of bilirubin was significantly affected by both convective and diffusive solute transport, while the clearance of macromolecule BSA was dominated by convective solute transport. The clearance rates of bilirubin and BSA increasd with the increase of tube-side flow rate and hollow fiber length. With the increase of shell-side flow rate, the clearance rate of bilirubin first rose rapidly, then slowly rose to an asymptotic value, while the clearance rate of BSA gradually decreased. The results can provide help for designing structures of hollow fiber membrane module and operation parameters of clinical treatment.


Asunto(s)
Bilirrubina , Hígado Artificial , Membranas Artificiales , Albúmina Sérica Bovina , Albúmina Sérica Bovina/química , Bilirrubina/metabolismo , Animales , Bovinos , Humanos
7.
Cell Rep Med ; 5(10): 101744, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39317190

RESUMEN

This study develops an observational model to assess kidney function recovery and xenogeneic immune responses in kidney xenotransplants, focusing on gene editing and immunosuppression. Two brain-dead patients undergo single kidney xenotransplantation, with kidneys donated by minipigs genetically modified to include triple-gene knockouts (GGTA1, ß4GalNT2, CMAH) and human gene transfers (hCD55 or hCD55/hTBM). Renal xenograft functions are fully restored; however, immunosuppression without CD40-CD154 pathway blockade is ineffective in preventing acute rejection by day 12. This rejection manifests as both T cell-mediated rejection and antibody-mediated rejection (AMR), confirmed by natural killer (NK) cell and macrophage infiltration in sequential xenograft biopsies. Despite donor pigs being pathogen free before transplantation, xenografts and recipient organs test positive for porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) by the end of the observation period, indicating reactivation and contributing to significant immunopathological changes. This study underscores the critical need for extended clinical observation and comprehensive evaluation using deceased human models to advance xenograft success.


Asunto(s)
Animales Modificados Genéticamente , Galactosiltransferasas , Rechazo de Injerto , Trasplante de Riñón , Porcinos Enanos , Trasplante Heterólogo , Animales , Porcinos , Humanos , Trasplante Heterólogo/métodos , Rechazo de Injerto/inmunología , Rechazo de Injerto/genética , Trasplante de Riñón/métodos , Galactosiltransferasas/genética , Xenoinjertos , Riñón/patología , Riñón/inmunología , Células Asesinas Naturales/inmunología
8.
Cancer Lett ; 604: 217243, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39260669

RESUMEN

This study evaluated the cellular heterogeneity and molecular mechanisms of hepatocellular carcinoma (HCC). Single cell RNA sequencing (scRNA-seq), transcriptomic data, histone lactylation-related genes were collected from public databases. Cell-cell interaction, trajectory, pathway, and spatial transcriptome analyses were executed. Differential expression and survival analyses were conducted. Western blot, Real-time reverse transcription PCR (qRT-PCR), and Cell Counting Kit 8 (CCK8) assay were used to detect the expression of αSMA, AKR1B10 and its target genes, and verify the roles of AKR1B10 in HCC cells. Hepatic stellate cell (HSC) subgroups strongly interacted with tumor cell subgroups, and their spatial distribution was heterogeneous. Two candidate prognostic genes (AKR1B10 and RMRP) were obtained. LONP1, NPIPB3, and ZSWIM6 were determined as AKR1B10 targets. Besides, the expression levels of AKR1B10 and αSMA were significantly increased in LX-2 + HepG2 and LX-2 + HuH7 groups compared to those in LX-2 group, respectively. sh-AKR1B10 significantly inhibited the HCC cell proliferation and change the expression of AKR1B10 target genes, Bcl-2, Bax, Pan Kla, and H3K18la at protein levels. Our findings unveil the pivotal role of HSCs in HCC pathogenesis through regulating histone lactylation.


Asunto(s)
Carcinoma Hepatocelular , Regulación Neoplásica de la Expresión Génica , Células Estrelladas Hepáticas , Histonas , Neoplasias Hepáticas , Análisis de la Célula Individual , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Histonas/metabolismo , Histonas/genética , Análisis de la Célula Individual/métodos , Proliferación Celular/genética , Células Hep G2 , Perfilación de la Expresión Génica/métodos , Línea Celular Tumoral , Aldo-Ceto Reductasas/genética , Aldo-Ceto Reductasas/metabolismo , Transcriptoma , Análisis de Secuencia de ARN/métodos
10.
Life Sci ; 355: 123000, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39168238

RESUMEN

BACKGROUND: Lung ischemia-reperfusion injury (LIRI) poses a significant challenge in various clinical scenarios. Despite extensive research on the pathogenesis and potential treatments of LIRI, there is a notable absence of bibliometric analysis. MATERIALS AND METHODS: We summarized the results of LIRI research through two searches on the Web of Science, covering data from 1979 to 2023 with topic words "lung" and "reperfusion injury". The collected data were analyzed and visualized based on country, author(s), and keywords by bibliometric software. The keyword "programmed cell death" was further added to explore the hotspot of the LIRI research field. RESULTS: The initial analysis of 1648 research articles showed a total of 40 countries and 7031 researchers were involved in the publications, with America being the most productive country in the research field of LIRI. Keyword analysis revealed that the evolving focus of LIRI research has progressively transitioned from, lung transplantation, primary graft dysfunction, inflammation, oxidative stress, and ex vivo lung perfusion to cell death. Subsequently, 212 publications specifically addressing programmed cell death (PCD) in LIRI were identified, which clarified the recent hotspot of the LIRI field. CONCLUSION: With closer international cooperation and increasing research scale, the LIRI research focused mainly on the pathogenesis and potential therapeutic interventions for LIRI. PCD in LIRI is becoming a trending topic and will continue to be a hotspot in this field. Our study may offer valuable guidance for future research endeavors concerning LIRI.


Asunto(s)
Bibliometría , Daño por Reperfusión , Daño por Reperfusión/patología , Humanos , Animales , Pulmón/patología , Investigación Biomédica/tendencias , Investigación Biomédica/métodos , Apoptosis , Lesión Pulmonar/patología
11.
Food Sci Nutr ; 12(8): 5518-5529, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39139936

RESUMEN

Chicken claw products with their unique texture are loved by consumers, and cooking is a key step to affect the taste of chicken claw consumption, through the moderate hydrolysis of proteins and a series of physicochemical changes, so that the chicken claw gets tender and presents a crispy taste, but the current research on the optimal cooking conditions for chicken claw is still relatively small. In the present work, combinations of time (11, 13, 15, 17, and 19 min) and temperature (82, 86, 90, 94, and 98°C) were applied to the cooking of chicken claws. The effects of different cooking conditions on the quality characteristics of chicken claws were investigated, with special emphasis on the cooking loss rate, color, texture properties, lipid oxidation, myofibrillar fragmentation index (MFI), and total sulfhydryl content. The results showed that the cooking loss rate, lipid oxidation, and MFI value of chicken claws gradually increased, and the total color difference (∆E), puncture force, shear force, and total sulfhydryl content gradually decreased with the increase of cooking temperature and cooking time. Overall, chicken claws cooked at 86, 90, and 94°C for 15 and 17 min had better texture and flavor.

12.
Sci Rep ; 14(1): 19279, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164273

RESUMEN

Causal discovery with prior knowledge is important for improving performance. We consider the incorporation of marginal causal relations, which correspond to the presence or absence of directed paths in a causal model. We propose the Marginal Prior Causal Knowledge PC (MPPC) algorithm to incorporate marginal causal relations into a constraint-based structure learning algorithm. We provide the theorems of conditional independence properties by combining observational data and marginal causal relations. We compare the MPPC algorithm with other structure learning methods in both simulation studies and real-world networks. The results indicate that, compare with other constraint-based structure learning methods, MPPC algorithm can incorporate marginal causal relations and is more effective and more efficient.

13.
Biostatistics ; 25(4): 1210-1232, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39002146

RESUMEN

Coordinate-based meta-analysis combines evidence from a collection of neuroimaging studies to estimate brain activation. In such analyses, a key practical challenge is to find a computationally efficient approach with good statistical interpretability to model the locations of activation foci. In this article, we propose a generative coordinate-based meta-regression (CBMR) framework to approximate a smooth activation intensity function and investigate the effect of study-level covariates (e.g. year of publication, sample size). We employ a spline parameterization to model the spatial structure of brain activation and consider four stochastic models for modeling the random variation in foci. To examine the validity of CBMR, we estimate brain activation on 20 meta-analytic datasets, conduct spatial homogeneity tests at the voxel level, and compare the results to those generated by existing kernel-based and model-based approaches. Keywords: generalized linear models; meta-analysis; spatial statistics; statistical modeling.


Asunto(s)
Metaanálisis como Asunto , Neuroimagen , Humanos , Neuroimagen/métodos , Neuroimagen/estadística & datos numéricos , Modelos Estadísticos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Análisis Espacial
14.
J Sports Sci ; 42(11): 981-992, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38967313

RESUMEN

The number of runners and the incidence of running-related injuries (RRIs) are on the rise. Real-time biofeedback gait retraining offers a promising approach to RRIs prevention. However, due to the diversity in study designs and reported outcomes, there remains uncertainty regarding the efficacy of different forms of feedback on running gait biomechanics. Three databases: MEDLINE, PUBMED, and SPORTDiscus were searched to identify relevant studies published up to March 2024, yielding 4646 articles for review. The quality of the included studies was assessed using the Downs and Black Quality checklist. Primary outcomes, including Peak Tibial Acceleration (PTA), Vertical Average Loading Rate (VALR), and Vertical Instantaneous Loading Rate (VILR), were analysed through meta-analysis. 24 studies met the inclusion criteria and were analysed in this review.17 used visual biofeedback (VB) while 14 chose auditory biofeedback (AB). The meta-analysis revealed a reduction in loading variables both immediately following the intervention and after extended training, with both visual and auditory feedback. Notably, the decrease in loading variables was more pronounced post-training and VB proved to be more effective than AB. Real-time biofeedback interventions are effective in lowering loading variables associated with RRIs. The impact is more substantial with sustained training, and VB outperforms AB in terms of effectiveness.


Asunto(s)
Biorretroalimentación Psicológica , Marcha , Carrera , Humanos , Carrera/lesiones , Carrera/fisiología , Marcha/fisiología , Fenómenos Biomecánicos , Traumatismos en Atletas/prevención & control , Aceleración
15.
Int J Mol Sci ; 25(11)2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38891958

RESUMEN

The plant MADS-box transcription factor family is a major regulator of plant flower development and reproduction, and the AGAMOUS-LIKE11/SEEDSTICK (AGL11/STK) subfamily plays conserved functions in the seed development of flowering plants. Camellia japonica is a world-famous ornamental flower, and its seed kernels are rich in highly valuable fatty acids. Seed abortion has been found to be common in C. japonica, but little is known about how it is regulated during seed development. In this study, we performed a genome-wide analysis of the MADS-box gene the in C. japonica genome and identified 126 MADS-box genes. Through gene expression profiling in various tissue types, we revealed the C/D-class MADS-box genes were preferentially expressed in seed-related tissues. We identified the AGL11/STK-like gene, CjSTK, and showed that it contained a typical STK motif and exclusively expressed during seed development. We found a significant increase in the CjSTK expression level in aborted seeds compared with normally developing seeds. Furthermore, overexpression of CjSTK in Arabidopsis thaliana caused shorter pods and smaller seeds. Taken together, we concluded that the fine regulation of the CjSTK expression at different stages of seed development is critical for ovule formation and seed abortion in C. japonica. The present study provides evidence revealing the regulation of seed development in Camellia.


Asunto(s)
Camellia , Regulación de la Expresión Génica de las Plantas , Proteínas de Dominio MADS , Proteínas de Plantas , Semillas , Camellia/genética , Camellia/metabolismo , Camellia/crecimiento & desarrollo , Semillas/genética , Semillas/crecimiento & desarrollo , Proteínas de Dominio MADS/genética , Proteínas de Dominio MADS/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Filogenia , Arabidopsis/genética , Arabidopsis/metabolismo , Perfilación de la Expresión Génica , Familia de Multigenes , Genoma de Planta , Estudio de Asociación del Genoma Completo
16.
Cancer Lett ; 593: 216960, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38762194

RESUMEN

Extracellular vesicles (EVs) have been the subject of an exponentially growing number of studies covering their biogenesis mechanisms, isolation and analysis techniques, physiological and pathological roles, and clinical applications, such as biomarker and therapeutic uses. Nevertheless, the heterogeneity of EVs both challenges our understanding of them and presents new opportunities for their potential application. Recently, the EV field experienced a wide range of advances. However, the challenges also remain huge. This review focuses on the recent progress and difficulties encountered in the practical use of EVs in clinical settings. In addition, we also explored the concept of EV heterogeneity to acquire a more thorough understanding of EVs and their involvement in cancer, specifically focusing on the fundamental nature of EVs.


Asunto(s)
Biomarcadores de Tumor , Vesículas Extracelulares , Neoplasias , Humanos , Vesículas Extracelulares/metabolismo , Neoplasias/patología , Neoplasias/terapia , Neoplasias/metabolismo , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Animales
17.
Planta ; 260(1): 3, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38767800

RESUMEN

MAIN CONCLUSION: Transcription factors MhMYB1 and MhMYB2 correlate with monoterpenoid biosynthesis pathway in l-menthol chemotype of Mentha haplocalyx Briq, which could affect the contents of ( -)-menthol and ( -)-menthone. Mentha haplocalyx Briq., a plant with traditional medicinal and edible uses, is renowned for its rich essential oil content. The distinct functional activities and aromatic flavors of mint essential oils arise from various chemotypes. While the biosynthetic pathways of the main monoterpenes in mint are well understood, the regulatory mechanisms governing different chemotypes remain inadequately explored. In this investigation, we identified and cloned two transcription factor genes from the M. haplocalyx MYB family, namely MhMYB1 (PP236792) and MhMYB2 (PP236793), previously identified by our research group. Bioinformatics analysis revealed that MhMYB1 possesses two conserved MYB domains, while MhMYB2 contains a conserved SANT domain. Yeast one-hybrid (Y1H) analysis results demonstrated that both MhMYB1 and MhMYB2 interacted with the promoter regions of MhMD and MhPR, critical enzymes in the monoterpenoid biosynthesis pathway of M. haplocalyx. Subsequent virus-induced gene silencing (VIGS) of MhMYB1 and MhMYB2 led to a significant reduction (P < 0.01) in the relative expression levels of MhMD and MhPR genes in the VIGS groups of M. haplocalyx. In addition, there was a noteworthy decrease (P < 0.05) in the contents of ( -)-menthol and ( -)-menthone in the essential oil of M. haplocalyx. These findings suggest that MhMYB1 and MhMYB2 transcription factors play a positive regulatory role in ( -)-menthol biosynthesis, consequently influencing the essential oil composition in the l-menthol chemotype of M. haplocalyx. This study serves as a pivotal foundation for unraveling the regulatory mechanisms governing monoterpenoid biosynthesis in different chemotypes of M. haplocalyx.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Mentha , Mentol , Monoterpenos , Proteínas de Plantas , Factores de Transcripción , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Mentha/genética , Mentha/metabolismo , Monoterpenos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mentol/metabolismo , Aceites Volátiles/metabolismo , Vías Biosintéticas/genética , Regiones Promotoras Genéticas/genética
18.
J Pharmacokinet Pharmacodyn ; 51(4): 305, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38802683

RESUMEN

Authors' Response to Letter to Editor from Hinpetch Daungsupawong and Viroj Wiwanitkit.

19.
Theranostics ; 14(7): 2794-2815, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38773984

RESUMEN

Rationale: Idiopathic pulmonary fibrosis (IPF) is an irreversible, fatal interstitial lung disease lacking specific therapeutics. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the nicotinamide adenine dinucleotide (NAD) salvage biosynthesis pathway and a cytokine, has been previously reported as a biomarker for lung diseases; however, the role of NAMPT in pulmonary fibrosis has not been elucidated. Methods: We identified the NAMPT level changes in pulmonary fibrosis by analyzing public RNA-Seq databases, verified in collected clinical samples and mice pulmonary fibrosis model by Western blotting, qRT-PCR, ELISA and Immunohistochemical staining. We investigated the role and mechanism of NAMPT in lung fibrosis by using pharmacological inhibition on NAMPT and Nampt transgenic mice. In vivo macrophage depletion by clodronate liposomes and reinfusion of IL-4-induced M2 bone marrow-derived macrophages (BMDMs) from wild-type mice, combined with in vitro cell experiments, were performed to further validate the mechanism underlying NAMPT involving lung fibrosis. Results: We found that NAMPT increased in the lungs of patients with IPF and mice with bleomycin (BLM)-induced pulmonary fibrosis. NAMPT inhibitor FK866 alleviated BLM-induced pulmonary fibrosis in mice and significantly reduced NAMPT levels in bronchoalveolar lavage fluid (BALF). The lung single-cell RNA sequencing showed that NAMPT expression in monocytes/macrophages of IPF patients was much higher than in other lung cells. Knocking out NAMPT in mouse monocytes/macrophages (Namptfl/fl;Cx3cr1CreER) significantly alleviated BLM-induced pulmonary fibrosis in mice, decreased NAMPT levels in BALF, reduced the infiltration of M2 macrophages in the lungs and improved mice survival. Depleting monocytes/macrophages in Namptfl/fl;Cx3cr1CreER mice by clodronate liposomes and subsequent pulmonary reinfusion of IL-4-induced M2 BMDMs from wild-type mice, reversed the protective effect of monocyte/macrophage NAMPT-deletion on lung fibrosis. In vitro experiments confirmed that the mechanism of NAMPT engaged in pulmonary fibrosis is related to the released NAMPT by macrophages promoting M2 polarization in a non-enzyme-dependent manner by activating the STAT6 signal pathway. Conclusions: NAMPT prompts bleomycin-induced pulmonary fibrosis by driving macrophage M2 polarization in mice. Targeting the NAMPT of monocytes/macrophages is a promising strategy for treating pulmonary fibrosis.


Asunto(s)
Bleomicina , Citocinas , Fibrosis Pulmonar Idiopática , Macrófagos , Nicotinamida Fosforribosiltransferasa , Animales , Femenino , Humanos , Masculino , Ratones , Acrilamidas , Citocinas/metabolismo , Modelos Animales de Enfermedad , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/inducido químicamente , Pulmón/patología , Pulmón/metabolismo , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Ratones Transgénicos , Nicotinamida Fosforribosiltransferasa/metabolismo , Piperidinas/farmacología
20.
Heliyon ; 10(10): e30728, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38770296

RESUMEN

To enhance the operability of the rat orthotopic left lung transplantation model, we implemented several improvements and meticulously detailed the procedure. One hundred and thirty-one healthy male Sprague Dawley rats, weighing between 250 and 300 g, were utilized, with 64 serving as donors, 64 as recipients, and 3 as sham controls. We employed a modified three-cuff technique for the orthotopic left lung transplantation. Notably, our modified perfusion method could prevent donor lung edema, while waist-shaped cuffs minimized suture slippage during anastomosis. Additionally, positioning the recipient rat in a slightly left-elevated supine position during anastomosis reduced tension on the lung hilum, thus mitigating the risk of vascular laceration. The introduction of a unique two-person anastomosis technique significantly reduced operation time and substantially improved success rates. Furthermore, maximizing inflation of donor lungs both during preservation and surgery minimized the occurrence of postoperative atelectasis. Various other procedural refinements contributed to the enhanced operability of our model. Sixty-four rat orthotopic left lung transplantations were performed with only one surgical failure observed. The acquisition time for donor lungs averaged (19 ± 4) minutes, while (11 ± 1) minutes were allocated for donor lung hilum anatomy and cuff installation. Recipient thoracotomy and left lung hilar anatomy before anastomosis required (24 ± 8) minutes, with anastomosis itself taking (31 ± 6) minutes. Remarkably, the survival rate at the 4-h postoperative mark stood at 96.7 %. Even six months post-operation, transplanted left rat lungs continued to exhibit proper inflation and contraction rhythms, displaying signs of chronic pathological changes. In summary, our modified rat model of orthotopic left lung transplantation demonstrates robust operability, significantly reducing surgical duration, improving operation success rates, and enhancing postoperative survival rates. Furthermore, its long-term survival capacity enables the simulation of acute and chronic disease processes following lung transplantation.

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