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1.
Cell ; 163(1): 230-45, 2015 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-26365490

RESUMEN

Embryonic stem cells (ESCs) repress the expression of exogenous proviruses and endogenous retroviruses (ERVs). Here, we systematically dissected the cellular factors involved in provirus repression in embryonic carcinomas (ECs) and ESCs by a genome-wide siRNA screen. Histone chaperones (Chaf1a/b), sumoylation factors (Sumo2/Ube2i/Sae1/Uba2/Senp6), and chromatin modifiers (Trim28/Eset/Atf7ip) are key determinants that establish provirus silencing. RNA-seq analysis uncovered the roles of Chaf1a/b and sumoylation modifiers in the repression of ERVs. ChIP-seq analysis demonstrates direct recruitment of Chaf1a and Sumo2 to ERVs. Chaf1a reinforces transcriptional repression via its interaction with members of the NuRD complex (Kdm1a, Hdac1/2) and Eset, while Sumo2 orchestrates the provirus repressive function of the canonical Zfp809/Trim28/Eset machinery by sumoylation of Trim28. Our study reports a genome-wide atlas of functional nodes that mediate proviral silencing in ESCs and illuminates the comprehensive, interconnected, and multi-layered genetic and epigenetic mechanisms by which ESCs repress retroviruses within the genome.


Asunto(s)
Células Madre Embrionarias/virología , Retrovirus Endógenos/genética , Provirus/genética , Animales , Factor 1 de Ensamblaje de la Cromatina/genética , Factor 1 de Ensamblaje de la Cromatina/metabolismo , Células Madre de Carcinoma Embrionario/virología , Epigénesis Genética , Ratones , Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/metabolismo
2.
Proc Natl Acad Sci U S A ; 120(26): e2214842120, 2023 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-37339216

RESUMEN

Transplantation of stem cell-derived retinal pigment epithelial (RPE) cells is considered a viable therapeutic option for age-related macular degeneration (AMD). Several landmark Phase I/II clinical trials have demonstrated safety and tolerability of RPE transplants in AMD patients, albeit with limited efficacy. Currently, there is limited understanding of how the recipient retina regulates the survival, maturation, and fate specification of transplanted RPE cells. To address this, we transplanted stem cell-derived RPE into the subretinal space of immunocompetent rabbits for 1 mo and conducted single-cell RNA sequencing analyses on the explanted RPE monolayers, compared to their age-matched in vitro counterparts. We observed an unequivocal retention of RPE identity, and a trajectory-inferred survival of all in vitro RPE populations after transplantation. Furthermore, there was a unidirectional maturation toward the native adult human RPE state in all transplanted RPE, regardless of stem cell resource. Gene regulatory network analysis suggests that tripartite transcription factors (FOS, JUND, and MAFF) may be specifically activated in posttransplanted RPE cells, to regulate canonical RPE signature gene expression crucial for supporting host photoreceptor function, and to regulate prosurvival genes required for transplanted RPE's adaptation to the host subretinal microenvironment. These findings shed insights into the transcriptional landscape of RPE cells after subretinal transplantation, with important implications for cell-based therapy for AMD.


Asunto(s)
Degeneración Macular , Transcriptoma , Adulto , Animales , Humanos , Conejos , Degeneración Macular/genética , Degeneración Macular/terapia , Células Madre , Células Epiteliales , Pigmentos Retinianos
3.
Small ; : e2401345, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38767495

RESUMEN

Novel binder designs are shown to be fruitful in improving the electrochemical performance of silicon (Si)-based anodes. However, issues with mechanical damage from dramatic volume change and poor lithium-ion (Li+) diffusion kinetics in Si-based materials still need to be addressed. Herein, an aqueous self-repairing borate-type binder (SBG) with a web-like architecture and high ionic conductivity is designed for Si and SiO electrodes. The 3D web-like architecture of the SBG binder enables uniform stress distribution, while its self-repairing ability promotes effective stress dissipation and mechanical damage repair, thereby enhancing the damage tolerance of the electrode. The tetracoordinate boron ions ( - BO 4 - $ - {\mathrm{BO}}_4^ - $ ) in the SBG binder boosts the Li transportation kinetics of Si-based electrodes. Based on dynamic covalent and ionic conductive boronic ester bonds, the diverse requirements of the binder, including uniform stress distribution, self-repairing ability, and high ionic conductivity, can be met by simple components. Consequently, the proposed straightforward multifunction design strategy for binders based on dynamic boron chemistry provides valuable insights into fabricating high-performance Si-based anodes.

4.
Small ; 20(16): e2306989, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38032164

RESUMEN

Hybrid organic-inorganic perovskite (HOIP) ferroelectric materials have great potential for developing self-powered electronic transducers owing to their impressive piezoelectric performance, structural tunability and low processing temperatures. Nevertheless, their inherent brittle and low elastic moduli limit their application in electromechanical conversion. Integration of HOIP ferroelectrics and soft polymers is a promising solution. In this work, a hybrid organic-inorganic rare-earth double perovskite ferroelectric, [RM3HQ]2RbPr(NO3)6 (RM3HQ = (R)-N-methyl-3-hydroxylquinuclidinium) is presented, which possesses multiaxial nature, ferroelasticity and satisfactory piezoelectric properties, including piezoelectric charge coefficient (d33) of 102.3 pC N-1 and piezoelectric voltage coefficient (g33) of 680 × 10-3 V m N-1. The piezoelectric generators (PEG) based on composite films of [RM3HQ]2RbPr(NO3)6@polyurethane (PU) can generate an open-circuit voltage (Voc) of 30 V and short-circuit current (Isc) of 18 µA, representing one of the state-of-the-art PEGs to date. This work has promoted the exploration of new HOIP ferroelectrics and their development of applications in electromechanical conversion devices.

5.
Microb Pathog ; 187: 106513, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38147968

RESUMEN

Since pseudorabies (PR) re-emerged and rapidly spread in China at the end of 2011, researchers have focused on effective vaccine strategies to prevent and control pseudorabies virus (PRV) infection in pig herds. Due to the extensive application of an attenuated vaccine based on the Bartha-K61 strain isolated in Hungary in 1961 and the variation of the PRV strain, it has been suggested that traditional vaccines based on the Bartha-K61 strain offer only partial protection against variant strains. It was therefore evaluated whether the Porcilis® Begonia vaccine, which is based on the NIA-3 strain with deletions in the gE and TK genes, is efficacious against experimental infection with the virulent, contemporary Chinese PRV strain ZJ01. In this study, piglets were vaccinated with Porcilis® Begonia through either the intradermal (ID) route or the intramuscular (IM) route and subsequently challenged intranasally with strain ZJ01 at 4 weeks post-vaccination. An unvaccinated challenge group and an unvaccinated/nonchallenged group were also included in the study. All animals were monitored for 14 days after challenge. Vaccinated and negative control pigs stayed healthy during the study, while the unvaccinated control animals developed lesions associated with PRV ZJ01 challenge, and 44% of these pigs died before the end of the experiment. This study demonstrated that ID or IM vaccination of pigs with a vaccine based on the NIA-3 strain Porcilis® Begonia clinically protects against fatal PRV challenge with the ZJ01 strain.


Asunto(s)
Begoniaceae , Herpesvirus Suido 1 , Enfermedades de los Porcinos , Vacunas Virales , Porcinos , Animales , Herpesvirus Suido 1/genética , Vacunas contra la Seudorrabia , Anticuerpos Antivirales , Vacunación/veterinaria , Vacunas Virales/genética
6.
Exp Dermatol ; 33(1): e14926, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37702410

RESUMEN

Systemic lupus erythematosus (SLE) is an autoimmune disease in which defective T cells, immune complex deposition and other immune system alterations contribute to pathological changes of multiple organ systems. The vitamin D metabolite c is a critical immunomodulator playing pivotal roles in the immune system. Epidemiological evidence indicates that vitamin D deficiency is correlated with the severity of SLE. Our aim is to investigate the effects of 1,25(OH)2D3 (VitD3) on the activation of myeloid dendritic cells (mDCs) by autologous DNA-containing immune complex (DNA-ICs), and the effects of VitD3 on immune system balance during SLE. We purified DNA-ICs from the serum of SLE patients and isolated mDCs from normal subjects. In vitro studies showed that DNA-ICs were internalized and consumed by mDCs. VitD3 blocked the effects of DNA-ICs on RelB, IL-10 and TNF-α in mDCs. Further analysis indicated that DNA-ICs stimulated histone acetylation in the RelB promoter region, which was inhibited by VitD3. Knockdown of the histone deacetylase 3 gene (HDAC3) blocked these VitD3-mediated effects. Co-culture of mDCs and CD4+ T cells showed that VitD3 inhibited multiple processes mediated by DNA-ICs, including proliferation, downregulation of IL-10, TGF-ß and upregulation of TNF-α. Moreover, VitD3 could also reverse the effects of DNA-IC-induced imbalance of CD4+ CD127- Foxp3+ T cells and CD4+ IL17+ T cells. Taken together, our results indicated that autologous DNA-ICs stimulate the activation of mDCs in the pathogenesis of SLE, and VitD3 inhibits this stimulatory effects of DNA-ICs by negative transcriptional regulation of RelB gene and maintaining the Treg/Th17 immune cell balance. These results suggest that vitamin D may have therapeutic value for the treatment of SLE.


Asunto(s)
Colecalciferol , Lupus Eritematoso Sistémico , Humanos , Colecalciferol/farmacología , Interleucina-10 , Complejo Antígeno-Anticuerpo , Factor de Necrosis Tumoral alfa , Inflamación , Vitamina D/farmacología , Células Dendríticas/metabolismo , ADN
7.
Int Immunol ; 35(10): 483-495, 2023 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-37465957

RESUMEN

Systemic lupus erythematosus (SLE) involves disorders of innate and adaptive immune pathways. Tax1-binding protein 1 (TAX1BP1) modulates the production of antibodies in B cells and the T-cell cycle by regulating the NF-κB signaling pathway. However, the potential association of TAX1BP1 with SLE and its role in monocytes/macrophages have not been fully elucidated. In this study, we utilized whole-exome sequencing (WES) in combination with Sanger sequencing and identified 16 gene mutations, including in TAX1BP1, in an SLE family. TAX1BP1 protein expression with western blotting detection was reduced in SLE patients and correlated with disease activity negatively. Furthermore, RNA sequencing and 4D Label-Free Phosphoproteomic analysis were employed to characterize the transcriptome and phosphoproteome profiles in THP-1 and THP-1-differentiated M1 macrophages with TAX1BP1 knockdown. Silencing of TAX1BP1 in THP-1 and THP-1-differentiated M1 macrophages led to an increase in cluster of differentiation 80 (CD80) expression and differential changes in CD14 and CD16 expression, as assessed by flow cytometry. Additionally, western blot analysis showed that knockdown of TAX1BP1 led to a reduction in TRAF6 and p-p65 in THP-1-differentiated macrophages, with or without lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-α stimulation. Taken together, our findings suggest that TAX1BP1 participates in SLE activity by regulating antigen presentation in monocytes and inflammatory responses in M1 macrophages.


Asunto(s)
Lupus Eritematoso Sistémico , Monocitos , Humanos , Monocitos/metabolismo , Macrófagos , FN-kappa B/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas de Neoplasias/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo
8.
FASEB J ; 37(11): e23244, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37823602

RESUMEN

The mitotic quiescence of prospermatogonia is the event known to occur during genesis of the male germline and is tied to the development of the spermatogenic lineage. The regulatory mechanisms and the functional importance of this process have been demonstrated in mice; however, regulation of this process in human and domestic animal is still largely unknown. In this study, we employed single-cell RNA sequencing to identify transcriptional signatures of prospermatogonia and major somatic cell types in testes of goats at E85, E105, and E125. We identified both common and specific Gene Ontology categories, transcription factor regulatory networks, and cell-cell interactions in cell types from goat testis. We also analyzed the transcriptional dynamic changes in prospermatogonia, Sertoli cells, Leydig cells, and interstitial cells. Our datasets provide a useful resource for the study of domestic animal germline development.


Asunto(s)
Cabras , Análisis de Expresión Génica de una Sola Célula , Masculino , Animales , Humanos , Ratones , Cabras/genética , Testículo/metabolismo , Espermatogénesis/genética , Células de Sertoli/metabolismo , Células Germinativas , Análisis de la Célula Individual , Transcriptoma
9.
J Eur Acad Dermatol Venereol ; 38 Suppl 6: 26-36, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38419560

RESUMEN

BACKGROUND: Noninvasive energy-based device (NI-EBD) aesthetic procedures has recently gained widespread usage for treating various skin conditions, enhancing skin texture and performing rejuvenation-related procedures. However, practically all NI-EBD procedures result in variable degrees of damage to the skin barrier, inducing pathological and physiological processes such as oxidative stress and inflammation, and only a small percentage of individuals possess the innate ability to restore it. OBJECTIVE: To introduce the concept of integrated skincare and establish standardized operational procedures for perioperative integrated skincare, and furnish a theoretical basis for clinical diagnosis and treatment performed by professional medical aestheticians. METHODS: The author leveraged domestic and international guidelines, clinical practice expertise and evidence-based research, adapting them to suit the specific circumstances in China. RESULTS: The consensus were provided four parts, including concept and essence of integrated skincare, integrated skincare significance during the perioperative phase of NI-EBD procedures, active ingredients and functions of effective skincare products, standardized perioperative skincare procedure for NI-EBD procedures and precautions. For the standardized perioperative skincare procedure, four recommendations were listed according to different stages during NI-EBD procedures. CONCLUSION: These recommendations create the 'Expert Consensus on Perioperative Integrated Skincare for Noninvasive Energy-Based Device Aesthetic Procedures in Clinical Practice in China'.


Asunto(s)
Técnicas Cosméticas , Humanos , China , Atención Perioperativa , Consenso , Rejuvenecimiento , Cuidados de la Piel/métodos , Envejecimiento de la Piel , Estética
10.
Ecotoxicol Environ Saf ; 274: 116196, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38461575

RESUMEN

Deltamethrin (DM) is a highly effective and widely used pyrethroid pesticide. It is an environmental factor affecting public and occupational health and exerts direct toxic effects on the central nervous system. As the major target organs for neurotoxicity of DM, the hippocampus and the cerebellum are critical to the learning and motor function. Pregnant Wistar rats were randomly divided into four groups and gavaged at doses of 0, 1, 4or 10 mg/kg/d DM from gestational day (GD) 0 to postnatal day (PN) 21. The PC12 cells were selected to further verify the regulatory mechanisms of DM on the neurodevelopmental injury. We found that maternal exposure to DM caused learning, memory and motor dysfunction in male offspring. Maternal exposure to DM induced the decrease in the density of hippocampal dendritic spines in male offspring through the reduced expression of M1 mAchRs, which in turn reduced the mediated AKT/mTOR signaling pathway, contributing to the inhibition of dynamic changes of GluA1. Meanwhile, DM exposure inhibited the BDNF/TrkB signaling pathway, thereby reducing phosphorylation of stathmin and impairing cerebellar purkinje cell dendrite growth and development. Taken together, maternal exposure to DM during pregnancy and lactation could impair neurodevelopment of male offspring.


Asunto(s)
Exposición Materna , Nitrilos , Efectos Tardíos de la Exposición Prenatal , Piretrinas , Embarazo , Ratas , Animales , Humanos , Femenino , Masculino , Exposición Materna/efectos adversos , Ratas Wistar , Efectos Tardíos de la Exposición Prenatal/metabolismo , Lactancia , Hipocampo/metabolismo
11.
Molecules ; 29(12)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38930897

RESUMEN

This study investigated the mechanism by which fucoxanthin acts as a novel ferroptosis inducer to inhibit tongue cancer. The MTT assay was used to detect the inhibitory effects of fucoxanthin on SCC-25 human tongue squamous carcinoma cells. The levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and total iron were measured. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to assess glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor 2 (Nrf2), Keap1, solute carrier family 7 member 11 (SLC7A11), transferrin receptor protein 1 (TFR1), p53, and heme oxygenase 1 (HO-1) expression. Molecular docking was performed to validate interactions. Compared with the control group, the activity of fucoxanthin-treated SCC-25 cells significantly decreased in a dose- and time-dependent manner. The levels of MMP, GSH, and SOD significantly decreased in fucoxanthin-treated SCC-25 cells; the levels of ROS, MDA, and total iron significantly increased. mRNA and protein expression levels of Keap1, GPX4, Nrf2, and HO-1 in fucoxanthin-treated cells were significantly decreased, whereas levels of TFR1 and p53 were significantly increased, in a concentration-dependent manner. Molecular docking analysis revealed that binding free energies of fucoxanthin with p53, SLC7A11, GPX4, Nrf2, Keap1, HO-1, and TFR1 were below -5 kcal/mol, primarily based on active site hydrogen bonding. Our findings suggest that fucoxanthin can induce ferroptosis in SCC-25 cells, highlighting its potential as a treatment for tongue cancer.


Asunto(s)
Ferroptosis , Hemo-Oxigenasa 1 , Simulación del Acoplamiento Molecular , Factor 2 Relacionado con NF-E2 , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Xantófilas , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , Ferroptosis/efectos de los fármacos , Xantófilas/farmacología , Xantófilas/química , Hemo-Oxigenasa 1/metabolismo , Hemo-Oxigenasa 1/genética , Línea Celular Tumoral , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias de la Lengua/tratamiento farmacológico , Neoplasias de la Lengua/metabolismo , Neoplasias de la Lengua/patología , Receptores de Transferrina/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+/genética , Superóxido Dismutasa/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Antígenos CD
12.
Angew Chem Int Ed Engl ; 63(2): e202313590, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-37814153

RESUMEN

The ability to generate and manipulate photoluminescence (PL) behavior has been of primary importance for applications in information security. Excavating novel optical effects to create more possibilities for information encoding has become a continuous challenge. Herein, we present an unprecedented PL temporary quenching that highly couples with thermodynamic phase transition in a hybrid crystal (DMML)2 MnBr4 (DMML=N,N-dimethylmorpholinium). Such unusual PL behavior originates from the anomalous variation of [MnBr4 ]2- tetrahedrons that leads to non-radiation recombination near the phase transition temperature of 340 K. Remarkably, the suitable detectable temperature, narrow response window, high sensitivity, and good cyclability of this PL temporary quenching will endow encryption applications with high concealment, operational flexibility, durability, and commercial popularization. Profited from these attributes, a fire-new optical encryption model is devised to demonstrate high confidential information security. This unprecedented optical effect would provide new insights and paradigms for the development of luminescent materials to enlighten future information encryption.

13.
Angew Chem Int Ed Engl ; : e202409796, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958031

RESUMEN

Out-of-plane polarization is a highly desired property of two-dimensional (2D) ferroelectrics for application in vertical sandwich-type photoferroelectric devices, especially in ultrathin ferroelectronic devices. Nevertheless, despite great advances that have been made in recent years, out-of-plane polarization remains unrealized in the 2D hybrid double perovskite ferroelectric family. Here, from our previous work 2D hybrid double perovskite HQERN ((S3HQ)4EuRb(NO3)8, S3HQ = S-3-hydroxylquinuclidinium), we designed a molecular strategy of F-substitution on organic component to successfully obtain FQERN ((S3FQ)4EuRb(NO3)8, S3FQ = S-3-fluoroquinuclidinium) showing circularly polarized luminescence (CPL) response. Remarkably, compared to the monopolar axis ferroelectric HQERN, FQERN not only shows multiferroicity with the coexistence of multipolar axis ferroelectricity and ferroelasticity but also realizes out-of-plane ferroelectric polarization and a dramatic enhancement of Curie temperature of 94 K. This is mainly due to the introduction of F-substituted organic cations, which leads to a change in orientation and a reduction in crystal lattice void occupancy. Our study demonstrates that F-substitution is an efficient strategy to realize and optimize ferroelectric functional characteristics, giving more possibility of 2D ferroelectric materials for applications in micro-nano optoelectronic devices.

14.
Angew Chem Int Ed Engl ; 63(14): e202319650, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38275283

RESUMEN

Luminescent ferroelectrics are holding exciting prospect for integrated photoelectronic devices due to potential light-polarization interactions at electron scale. Integrating ferroelectricity and long-lived afterglow emission in a single material would offer new possibilities for fundamental research and applications, however, related reports have been a blank to date. For the first time, we here achieved the combination of notable ferroelectricity and afterglow emission in an organic-inorganic hybrid material. Remarkably, the presented (4-methylpiperidium)CdCl3 also shows noticeable antiferroelectric behavior. The implementation of cationic customization and halogen engineering not only enables a dramatic enhancement of Curie temperature of 114.4 K but also brings a record longest emission lifetime up to 117.11 ms under ambient conditions, realizing a leapfrog improvement of at least two orders of magnitude compared to reported hybrid ferroelectrics so far. This finding would herald the emergence of novel application potential, such as multi-level density data storage or multifunctional sensors, towards the future integrated optoelectronic devices with multitasking capabilities.

15.
Crit Rev Toxicol ; 53(4): 229-243, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37417402

RESUMEN

Pyrethroids (PYRs) are a group of synthetic organic chemicals that mimic natural pyrethrins. Due to their low toxicity and persistence in mammals, they are widely used today. PYRs exhibit higher lipophilicity than other insecticides, which allows them to easily penetrate the blood-brain barrier and directly induce toxic effects on the central nervous system. Several studies have shown that the cerebellum appears to be one of the regions with the largest changes in biomarkers. The cerebellum, which is extremely responsive to PYRs, functions as a crucial region for storing motor learning memories. Exposure to low doses of various types of PYRs during rat development resulted in diverse long-term effects on motor activity and coordination functions. Reduced motor activity may result from developmental exposure to PYRs in rats, as indicated by delayed cerebellar morphogenesis and maturation. PYRs also caused adverse histopathological and biochemical changes in the cerebellum of mothers and their offspring. By some studies, PYRs may affect granule cells and Purkinje cells, causing damage to cerebellar structures. Destruction of cerebellar structures and morphological defects in Purkinje cells are known to be directly related to functional impairment of motor coordination. Although numerous data support that PYRs cause damage to cerebellar structures, function and development, the mechanisms are not completely understood and require further in-depth studies. This paper reviews the available evidence on the relationship between the use of PYRs and cerebellar damage and discusses the mechanisms of PYRs.


Asunto(s)
Insecticidas , Piretrinas , Ratas , Animales , Piretrinas/toxicidad , Insecticidas/toxicidad , Cerebelo , Células de Purkinje/fisiología , Encéfalo , Mamíferos
16.
Pharm Res ; 40(12): 3043-3058, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37914843

RESUMEN

PURPOSE: This study aimed to prepare a stable irinotecan liposome (CPT-11 liposome) and evaluate its antitumor efficacy in a range of tumor models. METHODS: CPT-11 liposome was prepared with a Z-average particle size of 110 ~ 120 nm and high entrapment efficiency (> 95%) and had a good stability within 18 months. Then the antitumor efficacy was studied in human colon (Ls-174t), gastric (NCI-N87), pancreatic (BxPC-3) and small cell lung (NCI-H526) cancer xenograft models. The toxicity of high-dose CPT-11 liposome was also evaluated in Beagle dogs. RESULTS: The results showed that the anti-tumor effects of CPT-11 liposome were markedly superior (at least 10 times higher) to those of the CPT-11 injection group in all four xenograft models. The tissue distribution test in the Ls-174t model further demonstrated that the CPT-11 liposome could alter the plasma and tissue distribution of CPT-11, increase the exposure level of its active metabolite SN-38 in tumor, and ultimately improve antitumor efficiency. Meanwhile, CPT-11 liposome showed a much less toxicity than CPT-11 injection in beagle dogs. CONCLUSIONS: Overall, the CPT-11 liposome may be developed as a new clinical alternative for the cancer patients.


Asunto(s)
Antineoplásicos Fitogénicos , Neoplasias , Humanos , Animales , Perros , Irinotecán , Liposomas , Camptotecina/farmacología , Camptotecina/uso terapéutico , Modelos Animales de Enfermedad , Antineoplásicos Fitogénicos/uso terapéutico
17.
Anal Bioanal Chem ; 415(18): 4533-4543, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37017725

RESUMEN

Recently, the good physical and chemical properties, well-defined pore architectures, and designable topologies have made microporous organic networks (MONs) excellent potential candidates in high-performance liquid chromatography (HPLC). However, their superior hydrophobic structures restrict their application in the reversed-phase mode. To solve this obstacle and to expand the application of MONs in HPLC, we realized the thiol-yne "click" postsynthesis of a novel hydrophilic MON-2COOH@SiO2-MER (MER denotes mercaptosuccinic acid) microsphere for reversed-phase/hydrophilic interaction mixed-mode chromatography. SiO2 was initially decorated with MON-2COOH using 2,5-dibromoterephthalic acid and tetrakis(4-ethynylphenyl)methane as monomers, and MER was then grafted via thiol-yne click reaction to yield MON-2COOH@SiO2-MER microspheres (5 µm) with a pore size of ~1.3 nm. The -COOH groups in 2,5-dibromoterephthalic acid and the post-modified MER molecules considerably improved the hydrophilicity of pristine MON and enhanced the hydrophilic interactions between the stationary phase and analytes. The retention mechanisms of the MON-2COOH@SiO2-MER packed column were fully discussed with diverse hydrophobic and hydrophilic probes. Benefiting from the numerous -COOH recognition sites and benzene rings within MON-2COOH@SiO2-MER, the packed column exhibited good resolution for the separation of sulfonamides, deoxynucleosides, alkaloids, and endocrine-disrupting chemicals. A column efficiency of 27,556 plates per meter was obtained for the separation of gastrodin. The separation performance of the MON-2COOH@SiO2-MER packed column was also demonstrated by comparing with those of MON-2COOH@SiO2, commercial C18, ZIC-HILIC, and bare SiO2 columns. This work highlights the good potential of the thiol-yne click postsynthesis strategy to construct MON-based stationary phases for mixed-mode chromatography.


Asunto(s)
Alcaloides , Dióxido de Silicio , Dióxido de Silicio/química , Cromatografía Líquida de Alta Presión/métodos , Alcaloides/análisis , Interacciones Hidrofóbicas e Hidrofílicas , Compuestos de Sulfhidrilo , Cromatografía de Fase Inversa/métodos
18.
J Asian Nat Prod Res ; 25(5): 429-437, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-35930443

RESUMEN

Two new monoterpenoid indole alkaloids 3-hydroxylochnerine (1) and 10-hydroxyvinorine (2) were isolated from the roots of Rauvolfia yunnanensis. Their structures were elucidated based on the analysis of spectroscopic data and ECD calculation. Both compounds exhibited potent antimicrobial activity against Bacillus subtilis and Escherichia coli, and their activities were comparable to the well-known antibacterial drug berberine.


Asunto(s)
Antiinfecciosos , Rauwolfia , Alcaloides de Triptamina Secologanina , Alcaloides de Triptamina Secologanina/química , Rauwolfia/química , Estructura Molecular , Antiinfecciosos/farmacología , Antibacterianos/farmacología , Alcaloides Indólicos
19.
J Pediatr Nurs ; 70: 47-53, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36801624

RESUMEN

PURPOSE: To modify and translate the Parents' Perceptions of Satisfaction with Care from Pediatric Nurse Practitioners instrument into Chinese, culturally adapt and initially test it to assess parental satisfaction with care from all levels of pediatric nurses in a pediatric inpatient care context. DESIGN AND METHODS: The instrument was translated and culturally adapted following a standardized guideline for the translation and cross-cultural adaptation of self-report measures. Content validity, discriminative validity, internal consistency and test-retest reliability were examined. RESULTS: Four main issues were identified in the translation and cultural adaptation stage. Modifications were therefore made to the Chinese Parents' Perceptions of Satisfaction with Care from Pediatric Nurses instrument. The item-level content validity indexes for the Chinese instrument ranged between 0.83 and 1.0. The Cronbach's alpha coefficient was 0.95, and the intra-class correlation coefficient for test-retest reliability was 0.44. CONCLUSION: The Chinese Parents' Perceptions of Satisfaction with Care from Pediatric Nurses instrument has good content validity and internal consistency and can be considered a suitable clinical evaluation tool to measure parental satisfaction with care from pediatric nurses in pediatric inpatient settings in China. PRACTICE IMPLICATIONS: The instrument is anticipated to be useful in strategic planning for Chinese nurse managers responsible for patient safety and quality of care. Additionally, it has the potential to serve as a tool to enable international comparisons in parental satisfaction with care from pediatric nurses after further testing.


Asunto(s)
Enfermeras Pediátricas , Humanos , Niño , Reproducibilidad de los Resultados , China , Autoinforme , Padres , Psicometría , Encuestas y Cuestionarios
20.
Sheng Li Xue Bao ; 75(2): 231-240, 2023 Apr 25.
Artículo en Zh | MEDLINE | ID: mdl-37089097

RESUMEN

Persistent neurogenesis exists in the subventricular zone (SVZ) of the ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus in the adult mammalian brain. Adult endogenous neurogenesis not only plays an important role in the normal brain function, but also has important significance in the repair and treatment of brain injury or brain diseases. This article reviews the process of adult endogenous neurogenesis and its application in the repair of traumatic brain injury (TBI) or ischemic stroke, and discusses the strategies of activating adult endogenous neurogenesis to repair brain injury and its practical significance in promoting functional recovery after brain injury.


Asunto(s)
Hemorragia Encefálica Traumática , Encéfalo , Accidente Cerebrovascular Isquémico , Neurogénesis , Adulto , Animales , Humanos , Encéfalo/fisiología , Encéfalo/fisiopatología , Hipocampo/fisiología , Hipocampo/fisiopatología , Mamíferos/fisiología , Neurogénesis/fisiología , Hemorragia Encefálica Traumática/fisiopatología , Hemorragia Encefálica Traumática/terapia , Accidente Cerebrovascular Isquémico/fisiopatología , Accidente Cerebrovascular Isquémico/terapia , Recuperación de la Función , Médula Espinal/fisiología , Médula Espinal/fisiopatología
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