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1.
Proc Natl Acad Sci U S A ; 121(18): e2307090121, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38648487

RESUMEN

G protein-coupled receptors (GPCRs) transduce the effects of many neuromodulators including dopamine, serotonin, epinephrine, acetylcholine, and opioids. The localization of synthetic or endogenous GPCR agonists impacts their action on specific neuronal pathways. In this paper, we show a series of single-protein chain integrator sensors that are highly modular and could potentially be used to determine GPCR agonist localization across the brain. We previously engineered integrator sensors for the mu- and kappa-opioid receptor agonists called M- and K-Single-chain Protein-based Opioid Transmission Indicator Tool (SPOTIT), respectively. Here, we engineered red versions of the SPOTIT sensors for multiplexed imaging of GPCR agonists. We also modified SPOTIT to create an integrator sensor design platform called SPOTIT for all GPCRs (SPOTall). We used the SPOTall platform to engineer sensors for the beta 2-adrenergic receptor (B2AR), the dopamine receptor D1, and the cholinergic receptor muscarinic 2 agonists. Finally, we demonstrated the application of M-SPOTIT and B2AR-SPOTall in detecting exogenously administered morphine, isoproterenol, and epinephrine in the mouse brain via locally injected viruses. The SPOTIT and SPOTall sensor design platform has the potential for unbiased agonist detection of many synthetic and endogenous neuromodulators across the brain.

2.
Environ Int ; 185: 108573, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38484609

RESUMEN

BACKGROUND: Air pollution is a global health concern, with fine particulate matter (PM2.5) constituents posing potential risks to human health, including children's neurodevelopment. Here we investigated associations between exposure during pregnancy and infancy to specific traffic-related PM2.5 components with Autism Spectrum Disorder (ASD) diagnosis. METHODS: For exposure assessment, we estimated PM2.5 components related to traffic exposure (Barium [Ba] as a marker of brake dust and Zinc [Zn] as a tire wear marker, Black Carbon [BC]) and oxidative stress potential (OSP) markers (Hydroxyl Radical [OPOH] formation, Dithiothreitol activity [OPDTT], reactive oxygen species [ROS]) modeled with land use regression with co-kriging based on an intensive air monitoring campaign. We assigned exposures to a cohort of 444,651 children born in Southern California between 2016 and 2019, among whom 11,466 ASD cases were diagnosed between 2018 and 2022, Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained with logistic regression for single pollutant and PM2.5 mass co-adjusted models, also adjusting for sociodemographic characteristics. RESULTS: Among PM2.5 components, we found the strongest positive association with ASD for our brake wear marker Ba (ORper IQR = 1.29, 95 % CI: 1.24, 1.34). This was followed by an increased risk for all PM2.5 oxidative stress potential markers; the strongest association was with ROS formation (ORper IQR = 1.22, 95 % CI: 1.18, 1.25). PM2.5 mass was linked to ASD in Hispanic and Black children, but not White children, while traffic-related PM2.5 and OSP markers increased ASD risk across all groups. In neighborhoods with the lowest socioeconomic status (SES), associations with ASD were stronger for all examined pollutants compared to higher SES areas. CONCLUSIONS: Our findings suggest that brake wear-related PM2.5 and PM2.5 OSP are associated with ASD diagnosis in Southern California. These results suggest that strategies aimed at reducing the public health impacts of PM2.5 need to consider specific sources.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Trastorno del Espectro Autista , Niño , Embarazo , Femenino , Humanos , Contaminantes Atmosféricos/análisis , Trastorno del Espectro Autista/etiología , Trastorno del Espectro Autista/inducido químicamente , Especies Reactivas de Oxígeno , Contaminación del Aire/análisis , Material Particulado/análisis , Polvo , California/epidemiología , Metales , Estrés Oxidativo , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis
3.
Artículo en Inglés | MEDLINE | ID: mdl-37951286

RESUMEN

In recent years, carbon nanotubes (CNTs) have gained tremendous attention due to their widespread application. Previous research indicated that carbon nanomaterials can affect the toxicity of some pollutants. In this study, we investigated the influence of multi-walled CNTs (MWCNTs) on the toxicity of ZnO nanoparticles (ZnONPs) in the intestine of common carp (Cyprinus carpio). After four-week exposure, histopathological observation and TUNEL assay showed concentration ratio-dependent intestinal lesions and apoptosis, with the most severe in the HSC-ZnONPs group (50 mg L-1 ZnONPs and 2.5 mg L-1 MWCNTs), less severe in the ZnONPs group (50 mg L-1 ZnONPs) and the least in the LSC-ZnONPs group (50 mg L-1 ZnONPs and 0.25 mg L-1 MWCNTs). Furthermore, ICP-OES indicated that intercellular zinc accumulation was significantly decreased by the presence of the MWCNTs, which suggested the varied contribution of ZnONPs to intestine injury in different groups. Moreover, 16 s rDNA sequencing revealed that ZnONPs alone and in combination with MWCNTs significantly altered the microbial community diversity and composition of the gut microbiota compared with controls. In addition, the predominant phylum, class, order, family, and genus were significantly different among these groups. In conclusion, the influence of MWCNTs on the toxicity of ZnONPs was related to the concentration and concentration ratio of the mixture.


Asunto(s)
Carpas , Microbiota , Nanotubos de Carbono , Óxido de Zinc , Animales , Óxido de Zinc/toxicidad , Nanotubos de Carbono/toxicidad , Intestinos , Apoptosis
4.
Environ Health Perspect ; 131(10): 107012, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37878796

RESUMEN

BACKGROUND: Although many studies have linked prenatal exposure to PM2.5 to adverse birth outcomes, little is known about the effects of exposure to specific constituents of PM2.5 or mechanisms that contribute to these outcomes. OBJECTIVES: Our objective was to investigate effects of oxidative potential and PM2.5 metal components from non-exhaust traffic emissions, such as brake and tire wear, on the risk of preterm birth (PTB) and term low birth weight (TLBW). METHODS: For a birth cohort of 285,614 singletons born in Los Angeles County, California, in the period 2017-2019, we estimated speciated PM2.5 exposures modeled from land use regression with cokriging, including brake and tire wear related metals (barium and zinc), black carbon, and three markers of oxidative potential (OP), including modeled reactive oxygen species based on measured iron and copper (ROS), OH formation (OPOH), and dithiothreitol (DTT) loss (OPDTT). Using logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for PTB and TLBW with speciated PM2.5 exposures and PM2.5 mass as continuous variables scaled by their interquartile range (IQR). RESULTS: For both metals and oxidative potential metrics, we estimated increased risks for PTB (ORs ranging from 1.01 to 1.03) and TLBW (ORs ranging from 1.02 to 1.05) per IQR exposure increment that were robust to adjustment for PM2.5 mass. Associations for PM2.5 mass, black carbon, metal components, and oxidative potential (especially ROS and OPOH) with adverse birth outcomes were stronger in Hispanic, Black, and mixed-race or Native American women. DISCUSSION: Our results indicate that exposure to PM2.5 metals from brake and tire wear and particle components that contribute to oxidative potential were associated with an increased risk of PTB and TLBW in Los Angeles County, particularly among Hispanic, Black, and mixed-race or Native American women. Thus, reduction of PM2.5 mass only may not be sufficient to protect the most vulnerable pregnant women and children from adverse effects due to traffic source exposures. https://doi.org/10.1289/EHP12196.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Nacimiento Prematuro , Niño , Recién Nacido , Femenino , Humanos , Embarazo , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Los Angeles/epidemiología , Especies Reactivas de Oxígeno , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/inducido químicamente , Metales , Carbono , Estrés Oxidativo , Contaminación del Aire/análisis
5.
Expert Opin Drug Deliv ; 20(11): 1467-1488, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37814582

RESUMEN

INTRODUCTION: Intravenous nanocrystals (INCs) have shown intrinsic advantages in antitumor applications, particularly their properties of high drug loading, low toxicity, and controllable size. Therefore, it has a very bright application prospect as a drug delivery system. AREAS COVERED: The ideal formulation design principles, fabrication, solidification, in vivo fate of INCs, the applications in drug delivery system (DDS) and the novel applications are covered in this review. EXPERT OPINION: It is vital to select a suitable formulation and fabrication method to produce a stable and sterile INCs. Besides, the type of stabilizers and physical characteristics can also influence the in vivo fate of INCs, which is worthy of further studying. Based on wide researches about applications of INCs in cancer, biomimetic INCs are concerned increasingly for its favorable compatibility. The output of these studies suggested that INCs-based drug delivery could be a novel strategy for addressing the delivery of the drug that faces solubility, bioavailability, and toxicity problems.


Asunto(s)
Nanopartículas , Neoplasias , Humanos , Sistemas de Liberación de Medicamentos/métodos , Preparaciones Farmacéuticas/química , Disponibilidad Biológica , Nanopartículas/química , Solubilidad , Neoplasias/tratamiento farmacológico
6.
Chemosphere ; 345: 140421, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37839741

RESUMEN

The metal organic frameworks (MOFs) are considered as the effective adsorbents for phosphate removal, while their ultrafine powders limit their practical application. In this study, we fabricate two chitosan (CS) gel beads added with different cerium-based MOFs and coated with PDA for phosphate adsorption. The MOFs doped in beads are CM1 and CM2, in which the Ce(III)/Ce(IV) ratio is 0.36 and 1.46, indicating CM2 is Ce(III) dominated and more suitable for phosphate removal. However, during the process of preparing gel beads, the mixture of chitosan and CM1/CM2 are added drop-by-drop to NaOH solution, leading to the decrease of Ce(III) contents in both of the two beads on account of oxidization. On this basis, in order to improve the phosphate uptake performance and enhance the mechanical strength, polydopamine (PDA) is applied to be coated on the outside. The adsorption capacities of CS-CM1 and CS-CM2 are no more than 20 mg/g higher than that of pure CS, which is also quite equal with the phosphate uptake of CS@PDA (63 mg/g). Due to the reduction of PDA, the content of Ce(III) increasing evidently in the two adsorbents. The maximum phosphate adsorption capacities are 146.8 mg/g and 114.8 mg/g for CS-CM1@PDA and CS-CM2@PDA, respectively. CS-CM2@PDA exhibits the largest treatment volume of ∼1166 BV in the fix-bed column study, much higher than that of CS-CM1@PDA (976 BV). The main reason is that Ce(III) could form binding with phosphate through ligand exchange and precipitation. Those inner-sphere interactions are much stronger than the electrostatic attraction between Ce(IV) and phosphate. Thus, due to this strong affinity, CS-CM2@PDA possessing a higher content of Ce(III) can capture phosphate more easier at low concentration. In summary, owing to reduction of PDA, the Cerium-based MOFs are successfully introduced in CS to realize excellent phosphate removal and exhibit a great prospect in application.


Asunto(s)
Cerio , Quitosano , Estructuras Metalorgánicas , Contaminantes Químicos del Agua , Fosfatos/química , Cerio/química , Quitosano/química , Adsorción , Contaminantes Químicos del Agua/química , Cinética
7.
Int J Biol Macromol ; 253(Pt 4): 127003, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37739280

RESUMEN

Fusion protein which encompasses more than one functional component, has become one of the most important representatives of macromolecular drugs for disease treatment since that monotherapy itself might not be effective enough to eradicate the disease. In this study, we sought to construct a bifunctional antibody fusion protein by fusing anti-PCSK9 scFv with Exendin-4 for simultaneously lowering both LDL-C and TG. Firstly, three Ex4-anti-PCSK9 scFv fusion proteins were constructed by genetically connecting the C-terminal of Exendin-4 to the N-terminal of anti-PCSK9 scFv through various flexible linker peptides (G4S)n (n = 2, 3, 4). After soluble expression in E. coli, the most potent Ex4-(G4S)4-anti-PCSK9 scFv fusion protein was selected based on in vitro activity assays. Then, we investigated the in vivo therapeutic effects of Ex4-(G4S)4-anti-PCSK9 scFv on the serum lipid profile and bodyweight changes as well as underlying molecular mechanism in HFD-fed C57BL/6 mice. The data showed that Ex4-(G4S)4-anti-PCSK9 scFv exhibits enhanced effects of lowering both LDL-C and TG in serum, reducing food intake and body weight via blocking PCSK9/LDLR, activating AMPK/SREBP-1 pathways, and up-regulating sirt6. Conclusively, Ex4-(G4S)4-anti-PCSK9 has the potential to serve as a promising therapeutic agent for effectively treating dyslipidemia with high levels of both LDL-C and TG.


Asunto(s)
Escherichia coli , Proproteína Convertasa 9 , Ratones , Animales , Proproteína Convertasa 9/genética , Proproteína Convertasa 9/metabolismo , Exenatida/farmacología , LDL-Colesterol , Escherichia coli/genética , Escherichia coli/metabolismo , Ratones Endogámicos C57BL , Transducción de Señal
8.
Nanomaterials (Basel) ; 13(18)2023 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-37764551

RESUMEN

As one of the most widely used nanomaterials, CeO2 nanoparticles (NPs) might be released into the aquatic environment. In this paper, the interaction of CeO2 NPs and Ce3+ ions (0~10 mg/L) with duckweed (Lemna minor L.) was investigated. CeO2 NPs significantly inhibited the root elongation of duckweed at concentrations higher than 0.1 mg/L, while the inhibition threshold of Ce3+ ions was 0.02 mg/L. At high doses, both reduced photosynthetic pigment contents led to cell death and induced stomatal deformation, but the toxicity of Ce3+ ions was greater than that of CeO2 NPs at the same concentration. According to the in situ distribution of Ce in plant tissues by µ-XRF, the intensity of Ce signal was in the order of root > old frond > new frond, suggesting that roots play a major role in the uptake of Ce. The result of XANES showed that 27.6% of Ce(IV) was reduced to Ce(III) in duckweed treated with CeO2 NPs. We speculated that the toxicity of CeO2 NPs to duckweed was mainly due to its high sensitivity to the released Ce3+ ions. To our knowledge, this is the first study on the toxicity of CeO2 NPs to an aquatic higher plant.

9.
Nat Methods ; 20(10): 1454-1455, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37640937
10.
bioRxiv ; 2023 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-37398137

RESUMEN

GPCRs transduce the effects of many neuromodulators including dopamine, serotonin, epinephrine, acetylcholine, and opioids. The localization of synthetic or endogenous GPCR agonists impacts their action on specific neuronal pathways. In this paper, we show a series of single-protein chain integrator sensors to determine GPCR agonist localization in the whole brain. We previously engineered integrator sensors for the mu and kappa opioid receptor agonists called M- and K-SPOTIT, respectively. Here, we show a new integrator sensor design platform called SPOTall that we used to engineer sensors for the beta-2-adrenergic receptor (B2AR), the dopamine receptor D1, and the cholinergic receptor muscarinic 2 agonists. For multiplexed imaging of SPOTIT and SPOTall, we engineered a red version of the SPOTIT sensors. Finally, we used M-SPOTIT and B2AR-SPOTall to detect morphine, isoproterenol, and epinephrine in the mouse brain. The SPOTIT and SPOTall sensor design platform can be used to design a variety of GPCR integrator sensors for unbiased agonist detection of many synthetic and endogenous neuromodulators across the whole brain.

11.
Sci Total Environ ; 900: 165736, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-37495143

RESUMEN

Reactive oxygen species (ROS) play a central role in chemistry in cloud water, as well as in other aqueous phases such as lung fluid and in wastewater treatment. Recently, work simulating nascent cloud droplets showed that aerosol particles produce a large burst of OH radicals when they first take up water. This activity stops abruptly, within two minutes. The source of the OH radicals is not well understood, but it likely includes the aqueous phase chemistry of ROS and/or organic hydroperoxides and redox active metals such as iron and copper. ROS and their precursors are in general highly reactive and labile, and thus may not survive during traditional sampling methods, which typically involve multi-hour collection on a filter or direct sampling into water or another collection liquid. Further, these species may further decay during storage. Here, we develop a technique to grow aerosol particles into small droplets and capture the droplets directly into a vial containing the terephthalate probe in water, which immediately scavenges OH radicals produced by aerosol particles. The method uses a Liquid Spot Sampler. Extensive characterization of the approach reveals that the collection liquid picks up substantial OH/OH precursors from the gas phase. This issue is effectively addressed by adding an activated carbon denuder. We then compared OH formation measured with the direct-to-reagent approach vs. filter collection. We find that after a modest correction for OH formed in the collection liquid, the samples collected into the reagent produce about six times those collected on filters, for both PM2.5 and total suspended particulate. This highlights the need for direct-to-reagent measurement approaches to accurately quantify OH production from ambient aerosol particles.

12.
J Child Neurol ; 38(6-7): 454-465, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37431191

RESUMEN

In this study, we reviewed the safety and efficacy of botulinum toxin type A (BoNT-A) injection with respect to motor development in children with spastic cerebral palsy aged <2 years. Randomized controlled trials of BoNT-A published between July 1993 and May 2021 were searched in PubMed, WANFANG, CNKI (Chinese National Knowledge Infrastructure), and Cochrane Library Central Register of Controlled Trials using keywords "Botulinum Toxin," "cerebral palsy," "nao xing tan huan," "nao tan," and "rou du du su." The 11-item PEDro Scale was used to rate the quality of all the identified studies. Twelve studies, involving 656 subjects, met the inclusion criteria, and of these, 2 involved patients aged <2 years. Treatment safety was assessed based on adverse event (AE) number and frequency, and efficacy was assessed based on spasticity, range of movement, and motor development. We observed that 3 self-limiting adverse events that were frequently reported included weakness, dysesthesia of the skin, and pain at the injection site. Moreover, there was a significant decrease in the incidence of spasticity and a notable improvement in the range of movement of BoNT-A-treated patients. Therefore, BoNT-A injection shows great safety and efficacy in the treatment of children with cerebral palsy aged <2 years.


Asunto(s)
Toxinas Botulínicas Tipo A , Parálisis Cerebral , Fármacos Neuromusculares , Niño , Humanos , Toxinas Botulínicas Tipo A/efectos adversos , Parálisis Cerebral/complicaciones , Fármacos Neuromusculares/efectos adversos , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/etiología , Dolor , Resultado del Tratamiento
13.
Ann Hematol ; 102(11): 3115-3124, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37400729

RESUMEN

The objective of this study was to develop a nomogram including parameters assessed by 18F-FDG PET/CT and clinical parameters for patients with diffuse large B-cell lymphoma (DLBCL) to predict progression-free survival (PFS). A total of 181 patients with pathologically diagnosed DLBCL at Sichuan Cancer Hospital and Institute from March 2015 to December 2020 were enrolled in this retrospective study. The area under the receiver operating characteristic (ROC) curve (AUC) was used to calculate the optimal cutoff values of the semiquantitative parameters (SUVmax, TLG, MTV, and Dmax) for PFS. A nomogram was constructed according to multivariate Cox proportional hazards regression. The predictive and discriminatory capacities of the nomogram were then measured using the concordance index (C-index), calibration plots, and Kaplan-Meier curves. The predictive and discriminatory capacities of the nomogram and the International Prognostic Index of the National Comprehensive Cancer Network (NCCN-IPI) were compared via the C-index and AUC. Multivariate analysis demonstrated that male gender and pretreatment Ann Arbor stage III-IV, non-GCB, elevated lactate dehydrogenase (LDH), number of extranodal organ involvement (Neo)>1, MTV≥152.8 cm3, and Dmax ≥53.9 cm were associated with unfavorable PFS (all p<0.05). The nomogram, including gender, Ann Arbor stage, pathology type, Neo, LDH levels, MTV, and Dmax, showed good prediction accuracy, with a C-index of 0.760 (95% CI: 0.727-0.793), which was higher than that of NCCN-IPI (0.710; 95% CI: 0.669-751). The calibration plots for 2-year demonstrated good consistency between the predicted and observed probabilities for survival time. We established a nomogram including MTV, Dmax, and several clinical parameters to predict the PFS of patients with DLBCL, and the nomogram showed better predictability and higher accuracy than NCCN-IPI.

14.
J Adolesc ; 95(5): 1017-1032, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37016571

RESUMEN

INTRODUCTION: Despite much cross-sectional research linking prosocial behavior and meaning in life, few studies have investigated the longitudinal relationship between these two constructs. The article examines the bidirectional longitudinal association between prosocial behavior and meaning in life among junior high school students. METHODS: A prospective design was adopted, incorporating three measurement occasions (with approximately 6-month intervals, from 2020 to 2021). Data were collected from 764 students (mean age = 12.46, SD = 0.64 years, and 51.4% girls). All participants responded to a questionnaire survey that included the Chinese Meaning in Life Questionnaire (MLQ-C) and Prosocial Tendencies Measure (PTM-C). Cross-lagged panel models were used to analyze the data. RESULTS: (1) Prosocial behavior predicted positively the presence of meaning over time and vice-versa. (2) There was no bidirectional association between the search for meaning and prosocial behavior. (3) There was no gender difference in the bidirectional relationship between meaning in life and prosocial behavior. CONCLUSIONS: These findings suggest that educators should highlight the presence of meaning in adolescent life education from a long-term perspective and encourage students to engage in more prosocial activities.


Asunto(s)
Altruismo , Conducta Social , Adolescente , Femenino , Humanos , Niño , Masculino , Estudios Transversales , Estudiantes , Escolaridad
15.
Anal Chem ; 95(15): 6391-6398, 2023 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-37019686

RESUMEN

The development of nanotechnology has transformed many cutting-edge studies related to single-molecule analysis into nanoparticle (NP) detection with a single-NP sensitivity and ultrahigh resolution. While laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been successful in quantifying and tracking NPs, its quantitative calibration remains a major challenge due to the lack of suitable standards and the uncertain matrix effects. Herein, we frame a new approach to prepare quantitative standards via precise synthesis of NPs, nanoscale characterization, on-demand NP distribution, and deep learning-assisted NP counting. Gold NP standards were prepared to cover the mass range from sub-femtogram to picogram levels with sufficient accuracy and precision, thus establishing an unambiguous relationship between the sampled NP number in each ablation and the corresponding mass spectral signal. Our strategy facilitated for the first time the study of the factors affecting particulate sample capture and signal transductions in LA-ICP-MS analysis and culminated in the development of an LA-ICP-MS-based method for absolute NP quantification with single-NP sensitivity and single-cell quantification capability. The achievements would herald the emergence of new frontiers cut across a spectrum of toxicological and diagnostic issues related to NP quantification.


Asunto(s)
Terapia por Láser , Nanopartículas , Espectrometría de Masas/métodos , Análisis Espectral , Rayos Láser
16.
Antioxidants (Basel) ; 12(3)2023 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-36978814

RESUMEN

BACKGROUND: Iron regulatory proteins (IRPs) maintain cellular iron homeostasis. Due to aberrant tissue-iron distribution, Irp2-deficient mice suffer microcytic anemia and neurodegeneration, while iron overload occurs in the liver and intestine. We previously found that Irp2 deficiency-induced Hif2 plays an important role in neurodegeneration. METHODS: To test the role of Hif2 in Irp2 deficiency-induced anemia, we used Irp2 global knockout mice. Following Hif2 inhibition, routine blood tests, iron availability in bone marrow, histological assays, and biochemical analysis were performed to assess anemia improvement and tissue iron distribution. RESULTS: We found that Hif2 inhibition improved anemia. The increased iron bioavailability for erythropoiesis was mainly derived from hepatic iron release, and secondly from enhanced intestinal absorption. We further demonstrate that nuclear receptor coactivator 4 (Ncoa4) was upregulated for iron release via the process of ferritinophagy. The released iron was utilized not only for intracellular Fe-S biogenesis but also for erythropoiesis after being exported from the liver to circulation. The hepatic iron export reduced hepcidin expression to further support iron absorption through the hepcidin-ferroportin axis to alleviate intestinal iron overload. CONCLUSION: Irp2 not only regulates cellular iron homeostasis but also tissue iron distribution by managing the involvement of Hif2-Ncoa4.

17.
BMC Ophthalmol ; 23(1): 87, 2023 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-36879221

RESUMEN

BACKGROUND: To quantitatively investigate corneal changes and the correlation between corneal densitometry (CD) and endothelial parameters after phacovitrectomy. METHODS: Thirty-eight eyes with idiopathic full-thickness macular holes (iFTMHs) and cataracts underwent phacovitrectomy. Examinations were conducted at baseline and Day 1, Day 7, Month 1, and Month 3 postoperatively. CD and central corneal thickness (CCT) were measured using Pentacam. Corneal endothelial cell density (ECD), coefficient of variation (CV), and hexagonality (HEX) were measured using specular microscopy. RESULTS: ECD and HEX significantly decreased after surgery and the change in HEX occurred prior to CV. CCT increased immediately after surgery and recovered 3 months postoperatively. CD values increased significantly 1 day after surgery and then gradually decreased. For CD in the 0-2 mm zone, it took 1 month to recover in the central and posterior layers and 3 months in the anterior and total layers. For CD in the 2-6 mm zone, the central layer recovered at Day 7, the anterior and total layers recovered at 1 month, and the posterior layer did not recover until 3 months postoperatively. The CD within all layers in the 0-2 mm zone was positively correlated with CCT. Posterior CD in the 0-2 mm zone was negatively correlated with ECD and HEX. CONCLUSIONS: CD is not only correlated with CCT, ECD, and HEX but also reflects the state of the whole cornea and each layer. CD can be an objective, rapid, and noninvasive tool that reflects corneal health and undetectable edema and monitors the process of lesion repair. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (31/10/2021, ChiCTR2100052554).


Asunto(s)
Catarata , Córnea , Humanos , Catarata/complicaciones , Córnea/diagnóstico por imagen , Córnea/cirugía , Densitometría , Examen Físico
18.
Molecules ; 28(4)2023 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-36838784

RESUMEN

With the widespread applications of manufactured nanoparticles (NPs), there are increasing concerns about their potential adverse effects on the environment and living systems. Many studies demonstrated that NPs could significantly affect the growth and development of crop plants. However, knowledge regarding the impacts of NPs on crop quality is rather limited. In this study, the effects of CeO2 NPs (25, 75, and 225 mg Ce/kg) and CeCl3 (25 mg Ce/kg) on the nutritional components of soil-cultivated corn and soybean plants were evaluated. Both treatments tended to decrease the dry weight of grain per plant, while only 225 mg/kg CeO2 NPs on soybean and CeCl3 on corn showed statistical significance compared with the respective control. CeO2 NPs at 225 mg/kg significantly decreased the content of starch in the corn kernels by 18.2% but increased total phenols in soybean seeds by 18.4%. Neither CeO2 NPs nor CeCl3 significantly affected the contents of minerals in corn kernels except for Zn. However, in the case of soybean, the two treatments tended to decrease the contents of P, Zn, Mn, and Mo but increase the content of S. Overall, the results suggest that CeO2 NPs and Ce3+ ions showed similar but not identical effects on corn and soybean plants. CeO2 NPs affect the nutritional quality of crop plants in a species-dependent manner.


Asunto(s)
Cerio , Nanopartículas del Metal , Nanopartículas , Zea mays , Cerio/farmacología , Valor Nutritivo
19.
Small Methods ; 7(6): e2201623, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36840644

RESUMEN

Silicon-based anodes have been considered as ideal candidates for next-generation Li-ion batteries. However, the rapid cyclability decay due to significant volume expansion limits its commercialization. Besides, the instable interface further aggravates the degradation. Carbon coating is one effective way to improve the electrochemical performance.The coating integrity may be a critical index for core-shell structure electrode materials. Herein, the coating integrity of SiOx @C composite is tested by a developed selective alkali dissolution, further quantitatively depicted by a proposed index of alkali solubility α. The effect of coating integrity on electrochemical performance reveals that SiOx dissolution loss has a significant impact on the overall electrode structure stability and interface property. Because of the side reaction between uncoated active SiOx and electrolyte, the quadratic decrease of initial coulombic efficiency and increase of solid electrolyte interphase thickness with the rise of alkali solubility are closely related to the generated F content induced by active material loss, further supported by the obvious linear rise of Li2 SiF6 fraction, leads to the linear increase of interface impedance and volume expansion rate, which may take primarily responsibility for the performance decay. This work propels the fundamental understanding on the interface failure mechnism and inspires rational high-performance electrode material design.

20.
Pharmacol Res ; 189: 106707, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36822452

RESUMEN

Acute graft-versus-host disease (aGvHD) is considered a result of "cytokine storm." Targeted therapeutic interventions on cytokines via ubiquitination regulatory pathways may provide a potential approach for aGvHD treatment. Ubiquitin-specific peptidase 11 (USP11) has been reported to play key roles in a variety of physiopathological processes by regulating the stability and function of several vital protein molecules. However, its role in aGvHD remains unclear. In this study, we identified USP11 was associated with aGvHD in patients. In the aGvHD mouse model, the colon and liver were more seriously affected in recipient mice who received USP11 wt bone marrow (BM) cells and eased after the donor was treated with a USP11 inhibitor or received USP11 ko BM cells. In mouse models, IL-6 was identified as a major effecter in accelerating aGvHD induced by USP11. In the cell model, IL-6 mRNA transcript was affected by USP11. In addition, USP11 also inhibited IL-6 degradation by affecting IL-6 ubiquitination. Furthermore, the positive correlation between USP11 and IL-6 was confirmed in the GvHD patients' samples. Collectively, all results indicated that USP11 played a critical role in the onset and progression of aGvHD. USP11 might be a potential target for aGvHD treatment.


Asunto(s)
Enfermedad Injerto contra Huésped , Interleucina-6 , Animales , Ratones , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Citocinas/uso terapéutico , Enfermedad Aguda
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