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1.
BMC Ecol Evol ; 24(1): 40, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38549102

RESUMO

BACKGROUND: Species and structural diversity are important for understanding the formation of forest communities, key ecological processes, and improving forest ecological functions and services, but their spatial characteristics have received little attention. Based on the spatial relationships among neighbouring trees, we proposed to divide trees within a structural unit into 15 structural types, and used the univariate distributions of the uniform angle index (W), mingling (M), and dominance (U), along with four common species diversity indices, to analyse the diversity of structural types in natural forests near the Tropic of Cancer. RESULTS: Only a portion of clumped class maintained aggregation, most exhibited a random pattern. Species mixture increased exponentially across distribution classes, and abundance and richness exhibited an initial increase followed by a slight decrease. The distribution patterns of mixture classes varied from highly clustered to random, and M distributions gradually shifted from an inverted J-shaped curve to a J-shaped curve. Abundance and richness exhibited an exponential distribution, whereas the Shannon-Wiener index increased linearly. The W distribution of differentiation classes approximated a normal distribution, whereas M distributions exhibited a J shape. The U distribution of each structure type was approximately 0.2. CONCLUSIONS: These results reveal the species and structural diversity characteristics of trees at the structural type level and expand our knowledge of forest biodiversity. The new method proposed here should significantly contribute to biodiversity monitoring efforts in terrestrial ecosystems, and suggests that higher standards for the simulation and reconstruction of stand structure, as well as thinning in near-natural forests, is warranted.


Assuntos
Ecossistema , Árvores , Florestas , Biodiversidade
3.
Neurol Sci ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38480645

RESUMO

BACKGROUND: Essential tremor (ET), a prevalent movement disorder, has an elusive pathogenesis. A reduction in ceruloplasmin (Cp) levels can be found in some patients with ET. In addition, some studies have suggested an association between ET and neurodegeneration. As a ferroxidase, Cp is critical for iron metabolism, protecting against oxidative stress and neurodegeneration. Iron metabolism dysregulation, linked to ferroptosis, has implications in neurodegenerative diseases. Yet, research on Cp and ET remains limited. OBJECTIVES: This study aims to elucidate the relationship between ET and serum Cp levels. METHODS: We collected demographic and clinical data from 62 patients with ET satisfying the diagnostic criteria and compared these to data from 100 healthy controls. RESULTS: The median Cp levels in ET patients were 21.5 (18.8, 23.9) mg/dL, significantly lower than those in controls (23.1 [(20.7, 25.7) mg/dL; P = 0.006]). A reduction in Cp levels emerged as a risk factor for ET incidence (odds ratio (OR) = 0.873, 95% confidence interval (CI), 0.795, 0.959; P = 0.005). The area under the receiver operating characteristic (ROC) curve for serum Cp levels to predict the onset of ET was 0.629 (95% CI, 0.537-0.720; P = 0.006), and the optimal cut-off value for Cp levels was 19.5 mg/dL with a sensitivity of 91% and a specificity of 33.9%. CONCLUSION: Our analysis suggests that reduced Cp levels are associated with ET. We speculate that reduced Cp levels may be involved in the pathogenesis of ET, which requires further studies.

4.
ACS Appl Mater Interfaces ; 16(8): 9713-9724, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38373060

RESUMO

Enhancing the performance of traditional pesticide formulations by improving their leaf surface wetting capabilities is a crucial approach for maximizing the pesticide efficiency. This study develops an emulsifiable concentrate (EC) of 4.5% ß-cypermethrin containing Brucea javanica oil (BJO). The incorporation of BJO aims to improve the leaf-wetting properties of the EC formulation and enhance its insecticidal effectiveness. The droplet size and emulsion characteristics of ß-CYP EC emulsion with varying concentrations of the emulsifier were evaluated, and changes after incorporating BJO were assessed to develop the optimal formulation. A comprehensive comparison was conducted among commercial 4.5% ß-cypermethrin EC (ß-CYP EC-1), 4.5% ß-cypermethrin EC with BJO (ß-CYP EC-2), and 4.5% ß-cypermethrin EC without BJO (ß-CYP EC-3). This comparison encompassed various factors including storage stability, insecticidal activity, cytotoxicity, and wetting performance on cabbage leaves. The results indicated that the ideal emulsifier concentration was 15% emulsifier 0201B. ß-CYP EC-2 demonstrated superior wetting properties on cabbage leaves (the wetting performance of ß-CYP EC-2 emulsion on cabbage leaves is 2.60 times that of the ß-CYP EC-1 emulsion), heightened insecticidal activity against the third larvae of Plutella xylostella [diamondback moth (DBM)] [the insecticidal activity of the ß-CYP EC-2 emulsion against the third larvae of DBM is 1.93 times that of the ß-CYP EC-1 emulsion (12 h)], and more obvious inhibitory effects on the proliferation of DBM embryo cells than the other tested formulations. These findings have significant implications for advancing pest control strategies and promoting sustainable and effective agricultural practices.


Assuntos
Brucea , Inseticidas , Piretrinas , Brucea javanica , Óleos de Plantas/farmacologia , Emulsões , Inseticidas/toxicidade
5.
Dalton Trans ; 52(44): 16442-16450, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37872811

RESUMO

Photoelectrochemical (PEC) water splitting for hydrogen production technology is considered as one of the most promising solutions to energy shortage and environmental remediation. TiO2/NiS nanorod arrays were successfully prepared using hydrothermal deposition followed by the successive ionic layer adsorption and reaction (SILAR) method. X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and photoluminescence (PL) spectra characterization studies indicate the successful deposition of NiS on TiO2 NRs. The NiS deposition on TiO2 was optimized by controlling the impregnation cycle. The optimal sample exhibits a photocurrent density of 1.16 mA cm-2 at 0.6 V vs. Ag/AgCl, which is a 1.9-fold enhancement over that of pristine TiO2 nanorod arrays. The enhanced photoelectrochemical performance can be attributed to two aspects. On the one hand, the (101) crystal plane of rutile TiO2 is the facet where photogenerated holes accumulate and is an efficient active plane for the oxygen evolution reaction; on the other hand, NiS is a narrow band gap semiconductor, and its deposition on TiO2 nanorods can further promote the separation and transport of photogenerated charge carriers.

6.
Int J Biol Macromol ; 253(Pt 4): 126947, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37734523

RESUMO

A chitosan-based nanoparticle was prepared using chitosan (CS) and O-carboxymethyl chitosan (O-CMCS). Our study revealed that chitosan/O-carboxymethyl chitosan/tebuconazole nanoparticles (CS/O-CMCS/TBA NPs) exhibited superior antifungal activity, foliar adhesion, and microbial target adhesion performance compared to commercial suspension concentrate (SC). The antifungal activity of CS/O-CMCS/TBA NPs against C. gloeosporioides, with a 3.13-fold increase in efficacy over TBA (SC). We also found that low concentrations of CS/O-CMCS NPs promoted the growth of C. gloeosporioides and enhanced the fungal catabolism of chitosan. Overall, the CS/O-CMCS/TBA NPs were found to possess the remarkable capability to selectively aggregate around pathogenic microorganisms and CS/O-CMCS NPs can enhance the fungal catabolism of chitosan. CS/O-CMCS/TBA NPs, as a "sugar-coated bomb", was a promising asset for effective plant disease management and pesticide utilization through the affinity of chitosan-based nanoparticles and C. gloeosporioides, enabling targeted delivery and targeted release of their encapsulated active ingredient, which was important for the development and application of biocompatible chitosan-based nanopesticides.


Assuntos
Quitosana , Fragaria , Nanopartículas , Portadores de Fármacos , Açúcares , Quitosana/farmacologia , Antifúngicos/farmacologia
7.
J Neurophysiol ; 130(3): 751-767, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37609701

RESUMO

The trapezoid body (TB) contains axons of neurons residing in the anteroventral cochlear nucleus (AVCN) that provide excitatory and inhibitory inputs to the main monaural and binaural nuclei in the superior olivary complex (SOC). To understand the monaural and binaural response properties of neurons in the medial and lateral superior olive (MSO and LSO), it is important to characterize the temporal firing properties of these inputs. Because of its exceptional low-frequency hearing, the chinchilla (Chinchilla lanigera) is one of the widely used small animal models for studies of hearing. However, the characterization of the output of its ventral cochlear nucleus to the nuclei of the SOC is fragmentary. We obtained responses of TB axons to stimuli typically used in binaural studies and compared these responses to those of auditory nerve (AN) fibers, with a focus on temporal coding. We found enhancement of phase-locking and entrainment, i.e., the ability of a neuron to fire action potentials at a certain stimulus phase for nearly every stimulus period, in TB axons relative to AN fibers. Enhancement in phase-locking and entrainment are quantitatively more modest than in the cat but greater than in the gerbil. As in these species, these phenomena occur not only in low-frequency neurons stimulated at their characteristic frequency but also in neurons tuned to higher frequencies when stimulated with low-frequency tones, to which complex phase-locking behavior with multiple modes of firing per stimulus cycle is frequently observed.NEW & NOTEWORTHY The sensitivity of neurons to small time differences in sustained sounds to both ears is important for binaural hearing, and this sensitivity is critically dependent on phase-locking in the monaural pathways. Although studies in cat showed a marked improvement in phase-locking from the peripheral to the central auditory nervous system, the evidence in rodents is mixed. Here, we recorded from AN and TB of chinchilla and found temporal enhancement, though more limited than in cat.


Assuntos
Axônios , Complexo Olivar Superior , Animais , Chinchila , Neurônios , Gerbillinae
8.
Dis Model Mech ; 15(10)2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36254682

RESUMO

Alzheimer's disease (AD) is the most common form of dementia, and risk-influencing genetics implicates microglia and neuroimmunity in the pathogenesis of AD. Induced pluripotent stem cell (iPSC)-derived microglia (iPSC-microglia) are increasingly used as a model of AD, but the relevance of historical immune stimuli to model AD is unclear. We performed a detailed cross-comparison over time on the effects of combinatory stimulation of iPSC-microglia, and in particular their relevance to AD. We used single-cell RNA sequencing to measure the transcriptional response of iPSC-microglia after 24 h and 48 h of stimulation with prostaglandin E2 (PGE2) or lipopolysaccharide (LPS)+interferon gamma (IFN-γ), either alone or in combination with ATPγS. We observed a shared core transcriptional response of iPSC-microglia to ATPγS and to LPS+IFN-γ, suggestive of a convergent mechanism of action. Across all conditions, we observed a significant overlap, although directional inconsistency to genes that change their expression levels in human microglia from AD patients. Using a data-led approach, we identify a common axis of transcriptomic change across AD genetic mouse models of microglia and show that only LPS provokes a transcriptional response along this axis in mouse microglia and LPS+IFN-γ in human iPSC-microglia. This article has an associated First Person interview with the first author of the paper.


Assuntos
Doença de Alzheimer , Microglia , Doença de Alzheimer/metabolismo , Animais , Dinoprostona/metabolismo , Modelos Animais de Doenças , Humanos , Interferon gama/metabolismo , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Microglia/patologia , Transcriptoma/genética
9.
Vet Immunol Immunopathol ; 235: 110201, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33735822

RESUMO

Among bloodsucking arthropods, hard tick is a vector of transmitting the most diverse human and animal pathogens, leading to an increasing number of manifestations worldwide. The development of the anti-tick vaccine has the potential to be an environmentally friendly and cost-effective option for tick management. We have previously demonstrated the induction of both humoral and cellular response against Hyalomma asiaticum (H. asiaticum) following immunization with recombinant cathepsin L-like cysteine protease from H. asiaticum tick (rHasCPL), and could control tick infestations. Interferon-gamma (IFN-γ), is an immunomodulatory factor that plays an important role in the regulation of adaptive immunity against infection. In the present study, recombinant BALB/c mouse IFN-γ (rMus-IFN-γ) was cloned and expressed using a prokaryotic expression system, and verified by Western blotting and IFN-γ-ELISA kit analysis. Female BALB/c mice (n = 12) were used for immunization using rHasCPL (100 µg) plus IFN-γ as adjuvant (10 µg). In immunized female BALB/c mice, the levels of anti-CPL antibodies as well as cytokines were determined using ELISA analysis. Protective efficacy of immunization was evaluated by larvae H. asiaticum challenge of immunized female BALB/c mice. Using rMus-IFN-γ as an adjuvant to rHasCPL vaccine (CPL + IFN-γ) promoted specific antibody IgG (IgG1 > IgG2a) and increased production of IFN-γ and IL-4 compared to immune rHasCPL group (CPL). The protected rate of immunized mice from tick challenge was significantly higher after immunization with CPL + IFN-γ (85.11 %) than with CPL (63.28 %). Immunization using CPL + IFN-γ promoted the activation of anti-HasCPL humoral and cellular immune responses, and could provide better protection against H. asiaticum infestation. This approach may could help develop a candidate vaccine for control tick infestations.


Assuntos
Catepsina L/imunologia , Cisteína Proteases/imunologia , Citocinas/imunologia , Imunoglobulina G/imunologia , Memória Imunológica , Interferon gama/imunologia , Ixodidae/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Catepsina L/genética , Feminino , Interferon gama/administração & dosagem , Interferon gama/genética , Ixodidae/enzimologia , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/imunologia , Vacinação
10.
AAPS PharmSciTech ; 21(8): 300, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33140142

RESUMO

PEGylated preparations will be cleared rapidly from blood circulation when they are administrated twice in the same animal at a time interval, referred to as the "accelerated blood clearance" (ABC) phenomenon. Commonly, the study of the ABC phenomenon was investigated in two aspects: induction phase and effectuation phase. Herein, we report the influence of physicochemical properties (PEG molecular weights) in the induction phase and effectuation phase on the ABC phenomenon. In the experiment, on one hand, PEGylated emulsions with different molecular weights of PEG (refer to PEn, n = 400, 600, 800, 1000, 2000, and 5000) were injected for the first dose (induction phase) and induced PE2000 to produce ABC phenomenon. On the other hand, after PE2000 injected, PEn was injected for the second dose (effectuation phase). The results indicated that PE2000 and PE5000 induced an intense ABC phenomenon by their long-circulating characteristic. Interestingly, PE400, PE600, PE800, and PE1000 produced a consistent ABC phenomenon but different circulation time. Apparently, the induction of the ABC phenomenon is not only determined by the circulation time but also by the PEG molecular weights. When PEn is in the effectuation phase, the extent of the ABC phenomenon was not positively related to the molecular weights of PEG, increasing first and then weaken with the increase of molecular weights of PEG. These suggest that the number of -(CH2CH2O)n- repeat units of PE2000 was more conducive to interact with anti-PEG IgM. The results reported here clearly indicate that both the PEG molecular weights of prior dose and the subsequent dose of emulsion strongly influence the extent of the ABC phenomenon. Taken together, our observations in this study complete the effect of PEG molecular weights at a different phase of the ABC phenomenon. Furthermore, our findings have a significant impact on the choice of molecular weights for PEGylated formulations for use in cross-administration.


Assuntos
Emulsões , Polietilenoglicóis/química , Animais , Lipossomos/química , Masculino , Peso Molecular , Polietilenoglicóis/farmacocinética , Ratos
11.
Parasit Vectors ; 13(1): 563, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172483

RESUMO

BACKGROUND: The ixodid tick Dermacentor marginatus is a vector of many pathogens wide spread in Eurasia. Studies of gene sequence on many tick species have greatly increased the information on tick protective antigen which might have the potential to function as effective vaccine candidates or drug targets for eco-friendly acaricide development. In the current study, RNA-seq was applied to identify D. marginatus sequences and analyze differentially expressed unigenes. METHODS: To obtain a broader picture of gene sequences and changes in expression level, RNA-seq was performed to obtain the whole-body transcriptome data of D. marginatus adult female ticks after engorgement and long-term starvation. Subsequently, the real-time quantitative PCR (RT-qPCR) was applied to validate the RNA-seq data. RESULTS: RNA-seq produced 30,251 unigenes, of which 32% were annotated. Gene expression was compared among groups that differed by status as newly molted, starved and engorged female adult ticks. Nearly one third of the unigenes in each group were differentially expressed compared to the other two groups, and the most numerous were genes encoding proteins involved in catalytic and binding activities and apoptosis. Selected up-regulated differentially expressed genes in each group were associated to protein, lipids, carbohydrate and chitin metabolism. Blood-feeding and long-term starvation also caused genes differentially expressed in the defense response and antioxidant response. RT-qPCR results indicated 6 differentially expressed transcripts showed similar trends in expression changes with RNA-seq results confirming that the gene expression profiles in transcriptome data is in consistent with RT-qPCR validation. CONCLUSIONS: Obtaining the sequence information of D. marginatus and characterizing the expression pattern of the genes involved in blood-feeding and during starvation would be helpful in understanding molecular physiology of D. marginatus and provides data for anti-tick vaccine and drug development for controlling the tick.


Assuntos
Dermacentor , Expressão Gênica , Transcriptoma , Animais , Dermacentor/genética , Dermacentor/metabolismo , Comportamento Alimentar , Feminino , Perfilação da Expressão Gênica , Filogenia , Inanição
12.
Exp Appl Acarol ; 82(2): 295-308, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32995924

RESUMO

Dermacentor marginatus is a widespread tick species and a vector of many pathogens in Eurasia. Due to the medical importance of D. marginatus, control measures are needed for this tick species. Currently tick control approaches rely mostly on acaricide application, whereas wrong and irrational acaricide use may result in drug resistance and residue problems. Vaccination as an alternative approach for tick control has been proven to be effective towards some tick species. However, immunization against D. marginatus has not yet reached satisfactory protection. The effort of in silico based analysis could predict antigenicity and identify candidates for anti-tick vaccine development. We carried out an in silico analysis of D. marginatus glutathione S-transferases (DmGSTs) in order to identify blood-feeding induced GSTs as antigens that can be used in anti-tick vaccine development. Phylogenetic analysis, linear B-cell epitope prediction, homology modeling, and conformational B-cell epitope mapping on the GST models were performed to identify highly antigenic DmGSTs. Relative gene expressions of the seven GSTs were profiled through real-time quantitative PCR (RT-qPCR) to outline GSTs up-regulated during blood feeding. The phylogenetic analysis indicated that the seven GSTs belonged to four classes of GST, including one in epsilon-class, one in zeta-class, one in omega-class, and four in mu-class. Linear B-cell epitope prediction revealed mu-class GSTs share similar conserved antigenic regions. The conformational B-cell epitope mapped on the homology model of the GSTs displayed that GSTs of mu-class showed stronger antigenicity than that of other classes. RT-qPCR revealed DmGSTM1 and DmGSTM2 were positively related to blood feeding. In sum, the data suggest that DmGSTM1 and DmGSTM2 could be tested for potential anti-tick vaccine trials.


Assuntos
Dermacentor/genética , Glutationa Transferase/genética , Filogenia , Animais , Feminino , Larva , Coelhos
13.
Nat Commun ; 11(1): 4614, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929069

RESUMO

The suprachiasmatic nucleus (SCN) is a complex structure dependent upon multiple mechanisms to ensure rhythmic electrical activity that varies between day and night, to determine circadian adaptation and behaviours. SCN neurons are exposed to glutamate from multiple sources including from the retino-hypothalamic tract and from astrocytes. However, the mechanism preventing inappropriate post-synaptic glutamatergic effects is unexplored and unknown. Unexpectedly we discovered that TRESK, a calcium regulated two-pore potassium channel, plays a crucial role in this system. We propose that glutamate activates TRESK through NMDA and AMPA mediated calcium influx and calcineurin activation to then oppose further membrane depolarisation and rising intracellular calcium. Hence, in the absence of TRESK, glutamatergic activity is unregulated leading to membrane depolarisation, increased nocturnal SCN firing, inverted basal calcium levels and impaired sensitivity in light induced phase delays. Our data reveals TRESK plays an essential part in SCN regulatory mechanisms and light induced adaptive behaviours.


Assuntos
Adaptação Ocular , Escuridão , Canais de Potássio/metabolismo , Núcleo Supraquiasmático/fisiologia , Animais , Comportamento Animal , Cálcio/metabolismo , Ácido Glutâmico/metabolismo , Luz , Potenciais da Membrana/efeitos da radiação , Camundongos Endogâmicos C57BL , Canais de Potássio/deficiência , Transdução de Sinais/efeitos da radiação , Núcleo Supraquiasmático/efeitos da radiação
14.
Stem Cell Res ; 47: 101909, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32745714

RESUMO

Using non-integrative reprogramming method, a human induced pluripotent stem cell (iPSC) line, ZZUNEUi005-A, was generated from a 36-year-old male patient with Wilson's disease, carrying a homozygous Pro992Leu mutation in the ATP7B gene. This cell line shows pluripotency both in vitro and in vivo and has a normal karyotype. Furthermore, we showed that this iPSC line could be differentiated into neural and hepatocyte-like cells.

15.
Anal Biochem ; 608: 113844, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32763304

RESUMO

In this work, a colorimetric aptamer-based method for detection of cadmium using gold nanoparticles modified MoS2 nanocomposites as enzyme mimic is established. In short, biotinylated Cd2+ aptamers are immobilized by biotin-avidin binding on the bottoms of the microplate, the complementary strands of Cd2+ aptamers are connected to the Au-MoS2 nanocomposites which have the function of enhanced peroxidase-like activity. The csDNA-Au-MoS2 signal probe and target Cd2+ compete for binding Cd2+ aptamer, the color change can be observed by addition of chromogenic substrate, thereby realizing visual detection of Cd2+. The absorbance of the solution at 450 nm has a clear linear relationship with the Cd2+ concentration. The linear range is 1-500 ng/mL, and the limit of detection is 0.7 ng/mL. The assay was used to test white wine samples, the results are consistent with those of atomic absorption spectrometry; which prove that this method can be used for detection of Cd2+ in real samples.


Assuntos
Aptâmeros de Nucleotídeos/química , Cádmio/análise , Cádmio/química , Cátions Bivalentes/análise , Cátions Bivalentes/química , Colorimetria/métodos , Nanocompostos/química , Compostos Cromogênicos/química , DNA Complementar/síntese química , DNA Complementar/química , Dissulfetos/química , Ensaios Enzimáticos/métodos , Ouro/química , Microscopia Eletrônica de Transmissão , Molibdênio/química , Oxirredução , Peroxidases/química , Espectrofotometria , Vinho/análise , Difração de Raios X
16.
Stem Cell Res ; 47: 101898, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32650241

RESUMO

Using a non-integrative reprogramming method, a human iPSC Line, ZZUNEUi002-A, was generated from a 22-year-old male patient with spinocerebellar ataxia type 3 /Machado-Joseph disease (SCA3/MJD). This cell line shows pluripotency both in vitro and vivo, and has a normal karyotype. The iPSC line could be used as a tool for mechanism researching and drug screening.

17.
Stem Cell Res ; 45: 101809, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32361313

RESUMO

Human iPSC Line, ZZUNEUi001-A, was generated from a healthy 38-year-old male individual, using non-integrating reprogramming methods. The resulting iPSCs were integration-free, expressed pluripotency stem cell markers, exhibited the potential for tri-lineage differentiation both in vitro and vivo, and maintained the normal karyotype. This cell line can be used as a control line for disease modelling.


Assuntos
Células-Tronco Pluripotentes Induzidas , Células-Tronco Pluripotentes , Adulto , Diferenciação Celular , Linhagem Celular , Reprogramação Celular , Humanos , Masculino
18.
AAPS PharmSciTech ; 21(3): 106, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32185548

RESUMO

To investigate the effect of polyethylene glycol (PEG) molecular weights on circulation time of PEGylated emulsions and the second injection of injected PEGylated emulsions, we studied the effect of molecular weights on the pharmacokinetic behavior of PEG-DSPE (modified emulsions with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-n-[methoxy (polyethyleneglycol)]) and PEG-CHMC (modified emulsions with poly(ethyleneglycol)-cholesteryl carbonate) emulsions in beagle dogs. The "accelerated blood clearance" (ABC) phenomenon was induced. Through this study, the contribution of PEG molecular weights on the ABC phenomenon was further clarified, and the results provided guidance for lessening or eliminating the ABC phenomenon. We injected different PEG-modified emulsions with 10% PEG-modified density into beagle dogs at 2 µmol phospholipids kg-1 and the blood samples were drawn after 1 min, 3 min, 5 min, 10 min, 15 min, 30 min, 60 min, 120 min, 240 min, 360 min, 600 min, and 24 h. Then, concentrations of the drug were assayed using high-performance liquid chromatography (HPLC). The results showed that the circulation times of PEG-DSPE-modified emulsions were significantly different because of the difference in molecular weights, whereas those of the PEG-CHMC modified emulsions were not. The spatial conformation of PEG with small molecular weights (PEG400, PEG600, and PEG800) was more likely to induce a strong ABC phenomenon. The results of our work suggest the interaction of circulation time and PEG molecular weights on the ABC phenomenon, implying that the spatial conformation of PEG has advantages that alleviate the ABC phenomenon. Importantly, the results have implications for the choice of molecular weights of PEG for PEGylated formulations.


Assuntos
Emulsões , Polietilenoglicóis/química , Animais , Cães , Cinética , Lipossomos/química , Masculino , Peso Molecular , Fosfatidiletanolaminas/química , Ratos Wistar
19.
Stem Cell Res ; 44: 101741, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32113134

RESUMO

Human IPSC Line, ZZUNEUi004-A, was generated from a 34-year-old male patient with Wilson's Disease carrying a homozygous Pro992Leu mutation in ATP7B gene, using non-integrative reprogramming method. This cell line shows pluripotency both in vitro and vivo, and has a normal karyotype.


Assuntos
Linhagem Celular , Degeneração Hepatolenticular , Células-Tronco Pluripotentes Induzidas , Adulto , ATPases Transportadoras de Cobre/genética , Degeneração Hepatolenticular/genética , Homozigoto , Humanos , Masculino , Mutação
20.
Stem Cell Res ; 41: 101664, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31783295

RESUMO

Human IPSC Line, ZZUNEUi003-A, was generated from a 32-year-old male patient with Wilson's Disease carrying a homozygous R778L mutation in ATP7B gene, using non-integrative reprogramming method. This cell line shows pluripotency both in vitro and vivo, and has a normal karyotype.


Assuntos
Técnicas de Cultura de Células/métodos , Linhagem Celular/patologia , ATPases Transportadoras de Cobre/genética , Degeneração Hepatolenticular/genética , Degeneração Hepatolenticular/patologia , Células-Tronco Pluripotentes Induzidas/patologia , Mutação/genética , Adulto , Sequência de Bases , Homozigoto , Humanos , Masculino
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