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1.
Cereb Cortex ; 34(7)2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38960703

RESUMEN

Schizophrenia, as a chronic and persistent disorder, exhibits working memory deficits across various stages of the disorder, yet the neural mechanisms underlying these deficits remain elusive with inconsistent neuroimaging findings. We aimed to compare the brain functional changes of working memory in patients at different stages: clinical high risk, first-episode psychosis, and long-term schizophrenia, using meta-analyses of functional magnetic resonance imaging studies. Following a systematic literature search, 56 whole-brain task-based functional magnetic resonance imaging studies (15 for clinical high risk, 16 for first-episode psychosis, and 25 for long-term schizophrenia) were included. The separate and pooled neurofunctional mechanisms among clinical high risk, first-episode psychosis, and long-term schizophrenia were generated by Seed-based d Mapping toolbox. The clinical high risk and first-episode psychosis groups exhibited overlapping hypoactivation in the right inferior parietal lobule, right middle frontal gyrus, and left superior parietal lobule, indicating key lesion sites in the early phase of schizophrenia. Individuals with first-episode psychosis showed lower activation in left inferior parietal lobule than those with long-term schizophrenia, reflecting a possible recovery process or more neural inefficiency. We concluded that SCZ represent as a continuum in the early stage of illness progression, while the neural bases are inversely changed with the development of illness course to long-term course.


Asunto(s)
Encéfalo , Imagen por Resonancia Magnética , Memoria a Corto Plazo , Esquizofrenia , Humanos , Memoria a Corto Plazo/fisiología , Esquizofrenia/fisiopatología , Esquizofrenia/diagnóstico por imagen , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Progresión de la Enfermedad , Trastornos de la Memoria/fisiopatología , Trastornos de la Memoria/etiología , Trastornos de la Memoria/diagnóstico por imagen , Psicología del Esquizofrénico , Mapeo Encefálico
2.
Mol Med ; 30(1): 147, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39266959

RESUMEN

BACKGROUND: The complex interplay between Sirtuin 1 (SIRT1) and FOXO3 in endometrial cancer (EC) remains understudied. This research aims to unravel the interactions of deacetylase SIRT1 and transcription factor FOXO3 in EC, focusing on their impact on mitophagy and hormone resistance. METHODS: High-throughput sequencing, cell experiments, and bioinformatics tools were employed to investigate the roles and interactions of SIRT1 and FOXO3 in EC. Co-immunoprecipitation (Co-IP) assay was used to assess the interaction between SIRT1 and FOXO3 in RL95-2 cells. Functional assays were used to assess cell viability, proliferation, migration, invasion, apoptosis, and the expression of related genes and proteins. A mouse model of EC was established to evaluate tumor growth and hormone resistance under different interventions. Immunohistochemistry and TUNEL assays were used to assess protein expression and apoptosis in tumor tissues. RESULTS: High-throughput transcriptome sequencing revealed a close association between SIRT1, FOXO3, and EC development. Co-IP showed a protein-protein interaction between SIRT1 and FOXO3. Overexpression of SIRT1 enhanced FOXO3 deacetylation and activity, promoting BNIP3 transcription and PINK1/Parkin-mediated mitophagy, which in turn promoted cell proliferation, migration, invasion, and inhibited apoptosis in vitro, as well as increased tumor growth and hormone resistance in vivo. These findings highlighted SIRT1 as an upstream regulator and potential therapeutic target in EC. CONCLUSION: This study reveals a novel molecular mechanism underlying the functional relevance of SIRT1 in regulating mitophagy and hormone resistance through the deacetylation of FOXO3 in EC, thereby providing valuable insights for new therapeutic strategies.


Asunto(s)
Neoplasias Endometriales , Proteína Forkhead Box O3 , Mitofagia , Sirtuina 1 , Femenino , Proteína Forkhead Box O3/metabolismo , Proteína Forkhead Box O3/genética , Humanos , Mitofagia/genética , Sirtuina 1/metabolismo , Sirtuina 1/genética , Animales , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Línea Celular Tumoral , Ratones , Acetilación , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Apoptosis/genética , Movimiento Celular , Resistencia a Antineoplásicos/genética
3.
Opt Lett ; 49(5): 1141-1144, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38426958

RESUMEN

Upconversion nanocomposites with multiple light-emitting centers have attracted great attention as functional materials, but their low efficiency limits their further applications. Herein, a novel, to the best of our knowledge, system for nanocomposites consisting of upconversion nanoparticles (UCNPs) and perovskite quantum dots (PeQDs) assembled with Ag nanoparticles (NPs) is proposed. Upconversion luminescence (UCL) operation from PeQDs is triggered by near-infrared (NIR) sensitization through Förster resonance energy transfer (FRET) and photon reabsorption (PR). Especially, the photoluminescence (PL) emission efficiency is found to be significantly enhanced due to the increased energy transfer efficiency and radiative decay rate in the UCNPs/CsPbBr3 nanocomposites. The results offer new opportunities to improve the UCL properties of perovskites and open new development in the fields of LED lighting, solar cells, biomedicine, and so on.

4.
Nanomedicine ; 58: 102748, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38663789

RESUMEN

Extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (AMSC-EVs) have been highlighted as a cell-free therapy due to their regenerative capability to enhance tissue and organ regeneration. Herein, we aimed to examine the mechanism of PF127-hydrogel@AMSC-EVs in promoting tracheal cartilage defect repair. Based on bioinformatics methods, SCNN1B was identified as a key gene for the osteogenic differentiation of AMSCs induced by AMSC-EVs. EVs were isolated from rat AMSCs and then loaded onto thermo-sensitive PF-127 hydrogel to develop PF127-hydrogel@AMSC-EVs. It was established that PF127-hydrogel@AMSC-EVs could effectively deliver SCNN1B into AMSCs, where SCNN1B promoted AMSC osteogenic differentiation. The promotive effect was evidenced by enhanced ALP activity, extracellular matrix mineralization, and expression of s-glycosaminoglycan, RUNX2, OCN, collagen II, PERK, and ATF4. Furthermore, the in vivo experiments revealed that PF127-hydrogel@AMSC-SCNN1B-EVs stimulated tracheal cartilage regeneration in rats through PERK/ATF4 signaling axis activation. Therefore, PF127-hydrogel@AMSC-SCNN1B-EVs may be a novel cell-free biomaterial to facilitate tracheal cartilage regeneration and cartilage injury repair.


Asunto(s)
Cartílago , Vesículas Extracelulares , Hidrogeles , Células Madre Mesenquimatosas , Tráquea , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Animales , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/química , Hidrogeles/química , Ratas , Tráquea/metabolismo , Cartílago/metabolismo , Regeneración , Poloxámero/química , Poloxámero/farmacología , Ratas Sprague-Dawley , Diferenciación Celular/efectos de los fármacos , Tejido Adiposo/citología , Tejido Adiposo/metabolismo , Osteogénesis/efectos de los fármacos , Masculino
5.
Int J Mol Sci ; 25(12)2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38928155

RESUMEN

Polymerase Chain Reaction (PCR) amplification is widely used for retrieving information from DNA storage. During the PCR amplification process, nonspecific pairing between the 3' end of the primer and the DNA sequence can cause cross-talk in the amplification reaction, leading to the generation of interfering sequences and reduced amplification accuracy. To address this issue, we propose an efficient coding algorithm for PCR amplification information retrieval (ECA-PCRAIR). This algorithm employs variable-length scanning and pruning optimization to construct a codebook that maximizes storage density while satisfying traditional biological constraints. Subsequently, a codeword search tree is constructed based on the primer library to optimize the codebook, and a variable-length interleaver is used for constraint detection and correction, thereby minimizing the likelihood of nonspecific pairing. Experimental results demonstrate that ECA-PCRAIR can reduce the probability of nonspecific pairing between the 3' end of the primer and the DNA sequence to 2-25%, enhancing the robustness of the DNA sequences. Additionally, ECA-PCRAIR achieves a storage density of 2.14-3.67 bits per nucleotide (bits/nt), significantly improving storage capacity.


Asunto(s)
Algoritmos , Reacción en Cadena de la Polimerasa , Reacción en Cadena de la Polimerasa/métodos , ADN/genética , Almacenamiento y Recuperación de la Información/métodos , Cartilla de ADN/genética , Secuencia de Bases
6.
Small ; 19(23): e2206929, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36905239

RESUMEN

Osteoarthritis (OA) is one of the most prevalent age-related degenerative diseases. With an increasingly aging global population, greater numbers of OA patients are providing clear economic and societal burdens. Surgical and pharmacological treatments are the most common and conventional therapeutic strategies for OA, but often fall considerably short of desired or optimal outcomes. With the development of stimulus-responsive nanoplatforms has come the potential for improved therapeutic strategies for OA. Enhanced control, longer retention time, higher loading rates, and increased sensitivity are among the potential benefits. This review summarizes the advanced application of stimulus-responsive drug delivery nanoplatforms for OA, categorized by either those that depend on endogenous stimulus (reactive oxygen species, pH, enzyme, and temperature), or those that depend on exogenous stimulus (near-infrared ray, ultrasound, magnetic fields). The opportunities, restrictions, and limitations related to these various drug delivery systems, or their combinations, are discussed in areas such as multi-functionality, image guidance, and multi-stimulus response. The remaining constraints and potential solutions that are represented by the clinical application of stimulus-responsive drug delivery nanoplatforms are finally summarized.


Asunto(s)
Nanopartículas , Osteoartritis , Humanos , Concentración de Iones de Hidrógeno , Sistemas de Liberación de Medicamentos/métodos , Osteoartritis/tratamiento farmacológico , Especies Reactivas de Oxígeno
7.
Opt Express ; 31(2): 2956-2966, 2023 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-36785297

RESUMEN

Advanced hybrid materials have attracted extensive attention in optoelectronics and photonics application due to their unique and excellent properties. Here, the multicolor upconversion luminescence properties of the hybrid materials composed of CsPbX3(X = Br/I) perovskite quantum dots and upconversion nanoparticles (UCNPs, core-shell NaYF4:25%Yb3+,0.5%Tm3+@NaYF4) is reported, achieving the upconversion luminescence with stable and bright of CsPbX3 perovskite quantum dots under 980 nm excitation. Compared with the nonlinear upconversion of multi-photon absorption in perovskite, UCNPs/CsPbX3 achieves lower power density excitation by using the UCNPs as the physical energy transfer level, meeting the demand for multi-color upconversion luminescence in optical applications. Also, the UCNPs/CsPbX3 combined with ultraviolet curable resin (UVCR) shows excellent water and air stability, which can be employed as multicolor fluorescent ink for screen printing security labels. Through the conversion strategy, the message of the security labels can be encrypted and decrypted by using UV light and a 980 nm continuous wave excitation laser as a switch, which greatly improves the difficulty of forgery. These findings provide a general method to stimulate photon upconversion and improve the stability of perovskite nanocrystals, which will be better applied in the field of anti-counterfeiting.

8.
Psychol Med ; 53(11): 5155-5166, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36046918

RESUMEN

BACKGROUND: Persistent psychological distress associated with the coronavirus disease 2019 (COVID-19) pandemic has been well documented. This study aimed to identify pre-COVID brain functional connectome that predicts pandemic-related distress symptoms among young adults. METHODS: Baseline neuroimaging studies and assessment of general distress using the Depression, Anxiety and Stress Scale were performed with 100 healthy individuals prior to wide recognition of the health risks associated with the emergence of COVID-19. They were recontacted for the Impact of Event Scale-Revised and the Posttraumatic Stress Disorder Checklist in the period of community-level outbreaks, and for follow-up distress evaluation again 1 year later. We employed the network-based statistic approach to identify connectome that predicted the increase of distress based on 136-region-parcellation with assigned network membership. Predictive performance of connectome features and causal relations were examined by cross-validation and mediation analyses. RESULTS: The connectome features that predicted emergence of distress after COVID contained 70 neural connections. Most within-network connections were located in the default mode network (DMN), and affective network-DMN and dorsal attention network-DMN links largely constituted between-network pairs. The hippocampus emerged as the most critical hub region. Predictive models of the connectome remained robust in cross-validation. Mediation analyses demonstrated that COVID-related posttraumatic stress partially explained the correlation of connectome to the development of general distress. CONCLUSIONS: Brain functional connectome may fingerprint individuals with vulnerability to psychological distress associated with the COVID pandemic. Individuals with brain neuromarkers may benefit from the corresponding interventions to reduce the risk or severity of distress related to fear of COVID-related challenges.


Asunto(s)
COVID-19 , Conectoma , Adulto Joven , Humanos , Pandemias , Conectoma/métodos , Encéfalo/diagnóstico por imagen , Ansiedad/epidemiología , Ansiedad/psicología , Imagen por Resonancia Magnética
9.
Inorg Chem ; 62(14): 5408-5414, 2023 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-36974353

RESUMEN

All-inorganic CsPbI2Br with outstanding thermal stability and excellent photoelectric properties is considered as a promising candidate for photovoltaic applications. However, the efficiency of CsPbI2Br perovskite solar cells (PSCs) is still much lower than that of their organic-inorganic hybrid counterparts or CsPbI3-based devices. Herein, we obtained an optimized CsPbI2Br PSC (0.09 cm2) with a champion efficiency of 17.38% and a record fill factor of 83.6% by introducing potassium anthraquinone-1,8-disulfonate (DAD) in the precursor solution. The synergistic effect between the electronegative functional groups and K+ ions in the DAD structure can not only effectively regulate the crystallization growth process to improve the crystalline quality and stability of photo-active CsPbI2Br but also optimize the energy level alignment and passivate the defects to improve the carrier transport properties. The efficiency of the corresponding large-area device (5 cm × 5 cm with an active area of 19.25 cm2) reached 13.20%. Moreover, the optimized CsPbI2Br PSC exhibited negligible hysteresis and enhanced long-term storage stability as well as thermal stability. Our method produces more stable photo-active CsPbI2Br with excellent photoelectric properties for industrial applications or perovskite/silicon tandem cells.

10.
J Immunol ; 207(1): 296-307, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-34183370

RESUMEN

Neddylation, a posttranslational modification in which NEDD8 is covalently attached to target proteins, has emerged as an endogenous regulator of innate immunity. However, the role of neddylation in methicillin-resistant Staphylococcus aureus (MRSA) infection remains unknown. In this study, we found that neddylation was activated after MRSA infection in vivo and in vitro. Inhibition of neddylation with MLN4924 promoted injury of liver and kidneys in C57BL/6 mice with MRSA bloodstream infection and increased mortality. Blockade of neddylation, either pharmacologically (MLN4924, DI591) or through the use of Uba3 small interfering RNA, inhibited Cullin3 neddylation and promoted Nrf2 accumulation, thus reducing reactive oxygen species (ROS) induction and bacterial killing ability in mouse peritoneal macrophages. In summary, our findings suggest that activation of neddylation in macrophages plays a critical protective role against MRSA infection by increasing ROS production, partially by signaling through the NEDD8-Cullin3-Nrf2-ROS axis. Furthermore, our results may provide a new non-antibiotic treatment strategy for MRSA infection through targeting of neddylation.


Asunto(s)
Macrófagos/inmunología , Staphylococcus aureus Resistente a Meticilina/inmunología , Especies Reactivas de Oxígeno/inmunología , Infecciones Estafilocócicas/inmunología , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Células 3T3 NIH
11.
Phys Chem Chem Phys ; 25(12): 8403-8411, 2023 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-36896835

RESUMEN

SnO2-based planar perovskite solar cells (PSCs) are considered as potential photovoltaic candidates due to their simple structures and cost-effective preparation processes. However, the extensive defects accumulated at the buried interface between perovskite and SnO2 greatly hinder the further improvement of PSC efficiency and stability. Herein, the potassium salt of anthraquinone-1,8-disulfonate (ASPS) is used as a novel multifunctional interfacial modifier to improve the carrier transport performance at the buried interface and optimize the quality of the upper perovskite light absorber layer (PVK) in PSCs. Owing to the synergistic effect of sulfonic acid groups, carbonyl groups and potassium ions in ASPS, the accumulated defects at the buried interface are passivated, the energy level arrangement of the interface is optimized, and the crystalline quality and optoelectronic properties of the PVK films are improved. As a result, the power conversion efficiency (PCE) improved significantly from 21.36% for the controlled device to 23.96% for the ASPS-modified device. Furthermore, the unencapsulated ASPS-modified device also exhibited better storage stability and thermal stability than the controlled device.

12.
BMC Public Health ; 23(1): 836, 2023 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-37158857

RESUMEN

BACKGROUND: The true incidence of acute gastrointestinal illness in China is underrecognized by surveillance systems. The aims of this study were to estimate the incidence and prevalence of self-reported AGI in the community of China, and to investigate sociodemographic and epidemiological determinants of AGI. METHODS: We conducted a 12-months cross-sectional population-based survey in eight provinces of China during 2014-2015. The survey determined the prevalence and incidence of acute gastrointestinal illness (AGI) in the total permanent resident population in China according to the census of the population in 2010. The random multilevel population sample was stratified by geographic, population, and socioeconomic status. We used a recommended case definition of AGI, with diarrhea (three loose or watery stools) and/or any vomiting in a four-week recall. A face-to-face survey was conducted by selecting the member in the household with the most recent birthday. RESULTS: Among 56,704 sampled individuals, 948 (1,134 person-time) fulfilled the case definition; 98.5% reported diarrhea. This corresponds to 2.3% (95% CI:1.9%-2.8%) of an overall standardized four-week prevalence and 0.3 (95% CI: 0.23-0.34) episodes per person-year of annual adjusted incidence rate. There was no significant difference between males and females. The incidence rates were higher among urban residents, and in the spring and summer. In the whole study period, 50% of the cases sought medical care, of which 3.9% were hospitalized and 14.3% provided a biological sample for laboratory identification of the causative agent. Children aged 0-4 and young adults aged 15-24, people living in rural areas and people who traveled frequently had higher prevalence of AGI. CONCLUSION: Results showed that AGI represents a substantial burden in China, and will contribute to the estimation of the global burden of AGI. Complemented with data on the etiologies of AGI, these estimates will form the basis to estimate the burden of foodborne diseases in China.


Asunto(s)
Diarrea , Vómitos , Niño , Femenino , Masculino , Adulto Joven , Humanos , Estudios Transversales , Prevalencia , Diarrea/epidemiología , China/epidemiología
13.
Nano Lett ; 22(6): 2309-2319, 2022 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-35238577

RESUMEN

Cartilage adheres to subchondral bone via a specific osteochondral interface tissue where forces are transferred from soft cartilage to hard bone without conferring fatigue damage over a lifetime of load cycles. However, the fine structure and mechanical properties of the osteochondral interface tissue remain unclear. Here, we identified an ultrathin ∼20-30 µm graded calcified region with two-layered micronano structures of osteochondral interface tissue in the human knee joint, which exhibited characteristic biomolecular compositions and complex nanocrystals assembly. Results from finite element simulations revealed that within this region, an exponential increase of modulus (3 orders of magnitude) was conducive to force transmission. Nanoscale heterogeneity in the hydroxyapatite, coupled with enrichment of elastic-responsive protein-titin, which is usually present in muscle, endowed the osteochondral tissue with excellent mechanical properties. Collectively, these results provide novel insights into the potential design for high-performance interface materials for osteochondral interface regeneration.


Asunto(s)
Cartílago Articular , Nanoestructuras , Huesos , Humanos , Articulación de la Rodilla , Ingeniería de Tejidos/métodos , Andamios del Tejido/química
14.
Phys Chem Chem Phys ; 24(36): 21697-21704, 2022 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-36069602

RESUMEN

The buried interface between a perovskite (PVK) light absorbing layer and an electron transport layer (ETL) plays an utmost important role in further improving the efficiency and stability of planar perovskite solar cells (PSCs). The interfacial properties greatly affect charge transport, perovskite crystal growth, and device stability. Herein, a variable structure broad-spectrum UV-284 absorber agent 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (HMBS) is introduced into PSCs based on SnO2 ETLs as an efficient multifunctional chemical linker to modify the buried interface properties. HMBS used to modify SnO2 can simultaneously suppress the surface trap states of ETLs, optimize the ETL/PVK interface energy level arrangement, and improve the crystallization quality of the upper perovskite films. Meanwhile, as an efficient UV absorber, HMBS can also greatly reduce the damage caused by UV light to perovskite films and thus improve the stability of devices. Consequently, HMBS-modified PSCs exhibit champion efficiencies of 23.42% (0.09 cm2) and 20.63% (1.00 cm2) along with remarkably enhanced UV stability. This work emphasizes the importance of appropriate interface treatment strategies for buried interface modification and provides an effective method for fabricating efficient and UV resistant perovskite photovoltaic devices.

15.
Eur J Clin Pharmacol ; 78(5): 793-799, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35079845

RESUMEN

PURPOSE: Clinical response to glucagon-like peptide-1 receptor agonists (GLP1RAs) varies considerably among patients with type 2 diabetes mellitus (T2DM). The aim of the current study was to examine the potential association between the genetic variants in GLP1R gene polymorphism with the therapeutic efficacy as well as gastrointestinal adverse drug reactions (ADRs) of GLP1RAs in Chinese T2DM patients. METHODS: Adult T2DM patients were eligible to participate in this prospective cohort study. Subjects received 12-week treatment with either exenatide (20 µg/day) or liraglutide (1.2 mg/day). GLP1R rs10305420 and rs3765467 genotyping was performed using the Sanger sequencing method. Clinical response to GLP1RAs was assessed in the patients who completed the 12-week treatment and defined by the change of fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and body mass index (BMI) from the baseline. RESULTS: A total of 176 subjects (mean age 50.9 ± 12.7 years, 111 men) were enrolled. The planned 12-week treatment was completed by 156 patients. HbA1c reduction was significantly larger in subjects carrying the rs3765467 GG genotype vs. GA + AA genotypes (1.7% ± 2.4% vs. 0.8% ± 1.8%; P = 0.002). Similarly, the 7.0% target HbA1c attainment rate was significantly higher in subjects carrying the rs3765467 GG genotype vs. GA + AA genotypes (50.9% vs. 23.8%; P = 0.002). Gastrointestinal ADRs did not differ significantly among different genotypes. CONCLUSION: GLP1R rs3765467 polymorphism is associated with therapeutic response to GLP1RAs in Chinese T2DM patients. HbA1c reduction is more pronounced in subjects with the GG genotype.


Asunto(s)
Diabetes Mellitus Tipo 2 , Receptor del Péptido 1 Similar al Glucagón , Adulto , China , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Receptor del Péptido 1 Similar al Glucagón/agonistas , Receptor del Péptido 1 Similar al Glucagón/genética , Hemoglobina Glucada/genética , Hemoglobina Glucada/uso terapéutico , Humanos , Hipoglucemiantes/efectos adversos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Estudios Prospectivos
16.
Xenobiotica ; 52(3): 312-321, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35395919

RESUMEN

Various factors, including genetic polymorphisms, drug-drug interactions, and patient characteristics influence the blood concentrations of tacrolimus in renal transplant patients. In the present study, we established a population pharmacokinetic model to explore the effect of combined use of Wuzhi capsules/echinocandins and the patients' biochemical parameters such as haematocrit on blood concentrations and target doses of tacrolimus in renal transplant patients with different CYP3A5 genotypes. The aim of the study was to propose an individualised tacrolimus administration regimen for early renal transplant recipients.In this retrospective cohort study, we included 240 renal transplant recipients within 21 days of surgery (174 males and 66 females, mean age 39.4 years), who received tacrolimus alone (n = 54), in combination with Wuzhi capsules (99) or caspofungin (57) or micafungin (30). We collected demographic characteristics, clinical indicators, CYP3A5 genotypes, and 1950 steady-state concentrations of tacrolimus and included them in population pharmacokinetic model. An additional 110 renal transplant recipients and 625 steady-state concentrations of tacrolimus were included for external validation of the model. The population pharmacokinetic model was established and Monte Carlo was used to simulate probabilities for achieving the target concentration for individual tacrolimus administration.A two-compartment model of first-order absorption and elimination was developed to describe the population pharmacokinetics of tacrolimus. CYP3A5 genotypes and co-administration of Wuzhi capsules, as well as time after renal transplantation and haematocrit, were important factors affecting the clearance of tacrolimus. We found no obvious change in trend in the scatter plot of tacrolimus clearance rate vs. haematocrit. The Monte Carlo simulation indicated the following recommended doses of tacrolimus alone: 0.14 mg⋅kg-1⋅d-1 for genotype CYP3A5*1*1, 0.12 mg⋅kg-1⋅d-1 for CYP3A5*1*3, and 0.10 mg⋅kg-1⋅d-1 for CYP3A5*3*3. For patients receiving the combination with Wuzhi capsules, the recommended doses of tacrolimus were 0.10 mg⋅kg-1⋅d-1 for CYP3A5*1*1, 0.08 mg⋅kg-1⋅d-1 for CYP3A5*1*3, and 0.06 mg⋅kg-1⋅d-1 for CYP3A5*3*3 genotypes. Caspofungin or micafungin had no effect on the clearance of tacrolimus in renal transplant recipients.The population pharmacokinetics of tacrolimus in renal transplant patients was evaluated and the individual administration regimen of tacrolimus was simulated. For early kidney transplant recipients receiving tacrolimus treatment, not only body weight, but also CYP3A5 genotypes and drugs used in combination should be considered when determining the target dose of tacrolimus.


Asunto(s)
Trasplante de Riñón , Tacrolimus , Adulto , Cápsulas , Caspofungina , Citocromo P-450 CYP3A/genética , Combinación de Medicamentos , Femenino , Genotipo , Humanos , Inmunosupresores/farmacocinética , Masculino , Micafungina , Polimorfismo de Nucleótido Simple , Estudios Retrospectivos , Tacrolimus/farmacocinética
17.
Mediators Inflamm ; 2022: 8457010, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35185385

RESUMEN

Glibenclamide displays an anti-inflammatory response in various pulmonary diseases, but its exact role in lipopolysaccharide- (LPS-) induced acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) remains unknown. Herein, we aimed to explore the effect of glibenclamide in vivo and in vitro on the development of LPS-induced ALI in a mouse model. LPS stimulation resulted in increases in lung injury score, wet/dry ratio, and capillary permeability in lungs, as well as in total protein concentration, inflammatory cells, and inflammatory cytokines including IL-1ß, IL-18 in bronchoalveolar lavage fluid (BALF), and lung tissues, whereas glibenclamide treatment reduced these changes. Meanwhile, the increased proteins of NLRP3 and Caspase-1/p20 after LPS instillation in lungs were downregulated by glibenclamide. Similarly, in vitro experiments also found that glibenclamide administration inhibited the LPS-induced upregulations in cytokine secretions of IL-1ß and IL-18, as well as in the expression of components in NLRP3 inflammasome in mouse peritoneal macrophages. Of note, glibenclamide had no effect on the secretion of TNF-α in vivo nor in vitro, implicating that its anti-inflammatory effect is relatively specific to NLRP3 inflammasome. In conclusion, glibenclamide alleviates the development of LPS-induced ALI in a mouse model via inhibiting the NLRP3/Caspase-1/IL-1ß signaling pathway, which might provide a new strategy for the treatment of LPS-induced ALI.


Asunto(s)
Lesión Pulmonar Aguda , Inflamasomas , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Animales , Gliburida/farmacología , Gliburida/uso terapéutico , Inflamasomas/metabolismo , Lipopolisacáridos/toxicidad , Pulmón/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Transducción de Señal
18.
Dev Genes Evol ; 231(1-2): 11-19, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33244643

RESUMEN

Germ cell-specific genes play an important role in establishing the reproductive system in sexual organisms and have been used as valuable markers for studying gametogenesis and sex differentiation. Previously, we isolated a vasa transcript as a germ cell marker to trace the origin and migration of germ cells in the oriental river prawn Macrobrachium nipponense. Here, we identified a new germ cell-specific marker MnTdrd RNA and assessed its temporal and spatial expression during oogenesis and embryogenesis. MnTdrd transcripts were expressed in high abundance in unfertilized eggs and embryos at cleavage stage and then dropped significantly during late embryogenesis, suggesting that MnTdrd mRNA is maternally inherited. In situ hybridization of ovarian tissue showed that MnTdrd mRNA was initially present in the cytoplasm of previtellogenic oocyte and localized to the perinuclear region as the accumulation of yolk in vitellogenic oocyte. Whole-mount in situ hybridization of embryos showed that MnTdrd-positive signals were only localized in one blastomere until 16-cell stage. In the blastula, there were approximately 16 MnTdrd-positive blastomeres. During embryonized-zoea stage, the MnTdrd-positive cells aggregated as a cluster and migrated to the genital rudiment which would develop into primordial germ cells (PGCs). The localized expression pattern of MnTdrd transcripts resembled that of the previously identified germ cell marker vasa, supporting the preformation mode of germ cell specification. Therefore, we concluded that MnTdrd, together with vasa, is a component of the germ plasm and might have critical roles in germ cell formation and differentiation in the prawn. Thus, MnTdrd can be used as a novel germ cell marker to trace the origin and migration of germ cells.


Asunto(s)
Linaje de la Célula , Células Germinativas/metabolismo , Palaemonidae/genética , Dominio Tudor , Animales , Blastómeros/metabolismo , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Oocitos/metabolismo , Palaemonidae/citología , Palaemonidae/crecimiento & desarrollo
19.
Opt Express ; 29(24): 40051-40060, 2021 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-34809355

RESUMEN

All-inorganic perovskite nanomaterials have attracted much attention recently due to their prominent optical performance and potential application for optoelectronic devices. The carriers dynamics of all-inorganic perovskites has been the research focus because the understanding of carriers dynamics process is of critical importance for improving the fluorescence conversion efficiency. While photophysical properties of excited carrier are usually measured at the macroscopic scale, it is necessary to probe the in-situ dynamics process at the nanometer scale and gain deep insights into the photophysical mechanisms and their localized dependence on the thin-film nanostructures. Stimulated emission depletion (STED) nanoscopy with super-resolution beyond the diffraction limit can directly provide explicit information at a single particle level or nanometer scale. Through this unique technique, we firstly study the in-situ dynamics process of single CsPbBr3 nanocrystals(NCs) and nanostructures embedded inside high-dense samples. Our findings reveal the different physical mechanisms of PL blinking and antibunching for single CsPbBr3 NCs and nanostructures that correlate with thin-film nanostructural features (e.g. defects, grain boundaries and carrier mobility). The insights gained into such nanostructure-localized physical mechanisms are critically important for further improving the material quality and its corresponding device performance.

20.
Anal Bioanal Chem ; 413(14): 3683-3693, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33825917

RESUMEN

How to achieve simultaneous and rapid detection of various mycotoxins in food has important practical significance in the field of food processing and safety. In this paper, a smartphone immunoassay system based on hydrogel microspheres has been constructed to quickly detect two mycotoxins at the same time. The rapid detection system was reflected in the following three processes: (1) rapid separation of free matter after direct competition reaction based on hydrogel solid-phase carrier particles; (2) rapid detection process based on efficient catalytic function of enzymes; (3) fast capture and analysis of images based on smartphone software. Ochratoxin A (OTA) and zearalenone (ZEN) are secondary toxic metabolites of fungi that can contaminate a wide range of foods and feeds. OTA and ZEN were used as detection model molecules to verify the feasibility of the intelligent rapid detection system. The entire detection process was within 30 min, and the results were analyzed in only 10 s. Detection limits of mycotoxins OTA and ZEN are 0.7711 ng L-1 and 1.0391 ng L-1. The recoveries of both mycotoxins ranged from 76.72 to 122.05%. This study provides a universal rapid detection method for on-site application of large-scale food security testing. Schematic diagram of the construction of the smartphone detection system: The system is divided into three parts: detection, image capture and analysis, and result.


Asunto(s)
Inmunoensayo/métodos , Micotoxinas/análisis , Ocratoxinas/análisis , Teléfono Inteligente , Zearalenona/análisis , Contaminación de Alimentos/análisis , Inmunoensayo/economía , Inmunoensayo/instrumentación , Límite de Detección , Factores de Tiempo
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