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2.
Food Chem ; 463(Pt 1): 141013, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39243614

RESUMO

Aflatoxins, zearalenone and its metabolites, as representative hazard mycotoxins cause adverse effects on food safety and human health. Developing a sensitive and reliable extraction and detection method is of great importance for monitoring their residue and exposure levels. In contrast to traditional trial-and-error selection steps, 4,4',4″-(1,3,5-triazine-2,4,6-triyl) trianiline covalent-bonding with 2,5-dihydroxyterephthalaldehyde, namely TAPT-OH-COF was screened as a potential adsorbent utilizing density functional theory calculations prior to the synthesis procedure. After experimental verification, magnetic TAPT-OH-COFs were prepared, characterized and applied for the extraction of aflatoxins, zearalenone and its metabolites from food and biological samples, coupled with high-performance liquid chromatography tandem mass spectrophy detection. Under the optimal conditions, the developed method exhibited low limits of quantification (0.05-0.50 µg/kg), satisfactory recoveries (75.8 %-110.9 %) and good precision with intraday and interday relative standard deviations (RSDs) not exceeding 12.2 %. This study may provide great potential for the selection of candidate adsorbents for multi-mycotoxins extraction from complex samples.

3.
Food Chem X ; 24: 101797, 2024 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-39290752

RESUMO

Cereals are frequently contaminated by aflatoxins (AFs). The objective of this study was to develop an efficient extraction materials for rapidly extracting and detecting AFs. A novel amino-functionalized benzodiimidazole linkage magnetic covalent organic framework (Fe3O4@BB-COF) was simply fabricated by one-step cyclization and aromatization. The Fe3O4@BB-COF, having multiple N-containing active sites, exhibited excellent extraction capability towards AFs due to synergistic interactions, including the π-π interactions, hydrogen bonding interactions, polar interactions, electrostatic interactions and Lewis acid-base interactions. The Fe3O4@BB-COF based MSPE method for detecting aflatoxins has advantages of simple operation, short extraction time (6 min), and low material consumption (2 mg). This method exhibited satisfactory linearity (0.05-20 µg/kg), and sensitivity (0.01-0.45 µg/L for the detection limits) and accuracy (76.8-97.1 % for recovery) and was successfully applied for extracting and detecting AFs in cereals.

4.
Int J Biol Macromol ; 279(Pt 1): 134829, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39208887

RESUMO

Flexible chitosan-based membranes were prepared by casting/solvent evaporation method using chitosan flocks as raw material. To improve mechanical and biological properties, chitosan microspheres (CMs) were prepared and integrated to form the composite membranes. Two different anti-bacterial drugs, e.g., tetracycline hydrochloride (TH) and silver sulfadiazine (AgSD), were loaded into the CMs and composite membranes to enhance their anti-bacterial properties. Furthermore, composite membranes were alternately coated by multi-layers of oxidized alginate (OAlg) and carboxymethyl chitosan (CMCS) via the layer-by-layer self-assembly and Schiff-base cross-linking. Our results demonstrated that the microspheres and multi-layer coatings could improve the swelling, water vapor transmission and hydrophilicity of the composite membranes. The chitosan microspheres and multi-layer coatings increased the tensile strength and decreased the elongation at the break of the membranes. Our composite membrane had better mechanical properties, slow drug release, anti-bacterial properties, which could promote cell proliferation. This composite membrane has great application potential in inhibiting bacterial infection and promoting wound regeneration.

5.
Adv Mater ; : e2405372, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39135403

RESUMO

Hydrogel electrode interfaces have shown tremendous promise in the acquisition of surface electromyography (EMG) signals. However, the perspiration or moisture environments will trigger the deadhesion between hydrogel electrodes and human skin. Despite the hydrophobic/hydrophilic surfaces can perform the anti-moisture or adhesion respectively, it remains a challenge to integrally form a Janus hydrogel with homogeneous mechanical elasticity and electronic performance. Herein, a surface induction strategy is proposed to approach the hydrophobic/hydrophilic hydrogel surfaces. The hydrophobic interaction between surfactants and molds regulates the distribution of hydrophobic/hydrophilic monomers on the surface. The hydrophobic molds induce a hydrophilic hydrogel surface, while the hydrophilic molds induce a hydrophobic surface. It presents a new phenomenon of reversal wettability inducing and optional hydrogel surfaces. The integral Janus hydrogel can be easily obtained by the hydrophilic molds. Balance of adhesion, elasticity, and conductivity endows the hydrogel electrode patch with durable conformal adhesion and high-fidelity EMG signals even in the sweaty epidermis due to the asymmetric wettability surfaces. This hydrogel performs the quantitative description of muscle strength and accurate fatigue assessment. It offers a reliable candidate for future practical applications in continuous digital healthcare and intelligent human-machine interaction, even the Metaverse.

6.
bioRxiv ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39091749

RESUMO

Across mammalian species, new mothers undergo considerable behavioral changes to nurture their offspring and meet the caloric demands of milk production1-5. While many neural circuits underlying feeding and parenting behaviors are well characterized6-9, it is unclear how these different circuits interact and adapt during lactation. Here, we characterized the transcriptomic changes in the arcuate nucleus (ARC) and the medial preoptic area (MPOA) of the mouse hypothalamus in response to lactation and hunger. Furthermore, we showed that heightened appetite in lactating mice was accompanied by increased activity of hunger-promoting agouti-related peptide (AgRP) neurons in the ARC. To assess the strength of hunger versus maternal drives, we designed a conflict assay where female mice chose between a food source or a chamber containing pups and nesting material. Although food-deprived lactating mothers prioritized parenting over feeding, hunger reduced the duration and disrupted the sequences of parenting behaviors in both lactating and virgin females. We discovered that ARCAgRP neurons directly inhibit bombesin receptor subtype-3 (BRS3) neurons in the MPOA, a population that governs both parenting and satiety. Selective activation of this ARCAgRP to MPOABRS3 circuit shifted behaviors from parenting to food-seeking. Thus, hypothalamic networks are modulated by physiological states and work antagonistically during the prioritization of competing motivated behaviors.

7.
Chemistry ; : e202402636, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39109460

RESUMO

In this work, we report the syntheses of three Pt(II) emitters, namely, Pt4N1, Pt4N2, and Pt4N3, to which their tetradentate chelates were assembled by linking two pyrazolate chelates with a single xylenylamino entity. Functionalization of Pt4N1 was achieved upon the addition of electronegative CF3 substituent on pyridinyl groups and switching to more electron-deficient pyrazinyl groups in giving Pt4N2 and Pt4N3, respectively. The vertically arranged xylenylamino entity has effectively suppressed the inter-molecular π-π stacking and Pt⋅⋅⋅Pt interaction, as shown by the single crystal X-ray structural analyses. Upon fabrication of OLED devices, Pt4N2 and Pt4N3 based devices delivered efficient cyan and green emission, with an EQEmax of 15.2 % and 11.2 %, respectively, affirming the successfulness of the tetradentate chelating strategy.

8.
Lung ; 202(5): 659-672, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39153120

RESUMO

PURPOSE: Over 550 loci have been associated with human pulmonary function in genome-wide association studies (GWAS); however, the causal role of most remains uncertain. Single nucleotide polymorphisms in a disintegrin and metalloprotease domain 19 (ADAM19) are consistently related to pulmonary function in GWAS. Thus, we used a mouse model to investigate the causal link between Adam19 and pulmonary function. METHODS: We created an Adam19 knockout (KO) mouse model and validated the gene targeting using RNA-Seq and RT-qPCR. Mouse body composition was assessed using dual-energy X-ray absorptiometry. Mouse lung function was measured using flexiVent. RESULTS: Contrary to prior publications, the KO was not neonatal lethal. KO mice had lower body weight and shorter tibial length than wild-type (WT) mice. Their body composition revealed lower soft weight, fat weight, and bone mineral content. Adam19 KO had decreased baseline respiratory system elastance, minute work of breathing, tissue damping, tissue elastance, and forced expiratory flow at 50% forced vital capacity but higher FEV0.1 and FVC. Adam19 KO had attenuated tissue damping and tissue elastance in response to methacholine following LPS exposure. Adam19 KO also exhibited attenuated neutrophil extravasation into the airway after LPS administration compared to WT. RNA-Seq analysis of KO and WT lungs identified several differentially expressed genes (Cd300lg, Kpna2, and Pttg1) implicated in lung biology and pathogenesis. Gene set enrichment analysis identified negative enrichment for TNF pathways. CONCLUSION: Our murine findings support a causal role of ADAM19, implicated in human GWAS, in regulating pulmonary function.


Assuntos
Proteínas ADAM , Estudo de Associação Genômica Ampla , Pulmão , Animais , Feminino , Humanos , Masculino , Camundongos , Proteínas ADAM/genética , Composição Corporal/genética , Modelos Animais de Doenças , Pulmão/metabolismo , Camundongos Knockout , Polimorfismo de Nucleotídeo Único , Testes de Função Respiratória , Capacidade Vital
9.
Development ; 151(13)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38953252

RESUMO

Spermatogonial stem cell (SSC) self-renewal and differentiation provide foundational support for long-term, steady-state spermatogenesis in mammals. Here, we have investigated the essential role of RNA exosome associated DIS3 ribonuclease in maintaining spermatogonial homeostasis and facilitating germ cell differentiation. We have established male germ-cell Dis3 conditional knockout (cKO) mice in which the first and subsequent waves of spermatogenesis are disrupted. This leads to a Sertoli cell-only phenotype and sterility in adult male mice. Bulk RNA-seq documents that Dis3 deficiency partially abolishes RNA degradation and causes significant increases in the abundance of transcripts. This also includes pervasively transcribed PROMoter uPstream Transcripts (PROMPTs), which accumulate robustly in Dis3 cKO testes. In addition, scRNA-seq analysis indicates that Dis3 deficiency in spermatogonia significantly disrupts RNA metabolism and gene expression, and impairs early germline cell development. Overall, we document that exosome-associated DIS3 ribonuclease plays crucial roles in maintaining early male germ cell lineage in mice.


Assuntos
Fertilidade , Espermatogônias , Testículo , Animais , Masculino , Camundongos , Diferenciação Celular , Complexo Multienzimático de Ribonucleases do Exossomo/metabolismo , Complexo Multienzimático de Ribonucleases do Exossomo/genética , Exossomos/metabolismo , Fertilidade/genética , Infertilidade Masculina/genética , Camundongos Knockout , Estabilidade de RNA/genética , Células de Sertoli/metabolismo , Espermatogênese , Espermatogônias/metabolismo , Espermatogônias/citologia , Testículo/metabolismo
10.
Nat Methods ; 21(7): 1349-1363, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38849569

RESUMO

The Long-read RNA-Seq Genome Annotation Assessment Project Consortium was formed to evaluate the effectiveness of long-read approaches for transcriptome analysis. Using different protocols and sequencing platforms, the consortium generated over 427 million long-read sequences from complementary DNA and direct RNA datasets, encompassing human, mouse and manatee species. Developers utilized these data to address challenges in transcript isoform detection, quantification and de novo transcript detection. The study revealed that libraries with longer, more accurate sequences produce more accurate transcripts than those with increased read depth, whereas greater read depth improved quantification accuracy. In well-annotated genomes, tools based on reference sequences demonstrated the best performance. Incorporating additional orthogonal data and replicate samples is advised when aiming to detect rare and novel transcripts or using reference-free approaches. This collaborative study offers a benchmark for current practices and provides direction for future method development in transcriptome analysis.


Assuntos
Perfilação da Expressão Gênica , RNA-Seq , Humanos , Animais , Camundongos , RNA-Seq/métodos , Perfilação da Expressão Gênica/métodos , Transcriptoma , Análise de Sequência de RNA/métodos , Anotação de Sequência Molecular/métodos
11.
Langmuir ; 40(27): 13773-13783, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38920266

RESUMO

Cartilage defects in large joints are a common occurrence in numerous degenerative diseases, especially in osteoarthritis. The hydrogel-on-metal composite has emerged as a potential candidate material, as hydrogels, to some extent, replicate the composition of human articular cartilage consisting of collagen fibers and proteoglycans. However, achieving tough bonding between the hydrogel and titanium alloy remains a significant challenge due to the swelling of the hydrogel in a liquid medium. This swelling results in reduced interfacial toughness between the hydrogel and titanium alloy, limiting its potential clinical applications. Herein, our approach aimed to achieve durable bonding between a hydrogel and a titanium alloy composite in a swollen state by modifying the surface texture of the titanium alloy. Various textures, including circular and triangular patterns, with dimple densities ranging from 10 to 40%, were created on the surface of the titanium alloy. Subsequently, poly(vinyl alcohol) (PVA) hydrogel was deposited onto the textured titanium alloy using a casting-drying method. Our findings revealed that PVA hydrogel on the textured titanium alloy with a 30% texture density exhibited the highest interfacial toughness in the swollen state, measuring at 1300 J m-2 after reaching equilibrium swelling in deionized water, which is a more than 2-fold increase compared to the hydrogel on a smooth substrate. Furthermore, we conducted an analysis of the morphologies of the detached hydrogel from the textured titanium alloy after various swelling durations. The results indicated that interfacial toughness could be enhanced through mechanical interlocking, facilitated by the expanded volume of the hydrogel protrusions as the swelling time increased. Collectively, our study demonstrates the feasibility of achieving tough bonding between a hydrogel and a metal substrate in a liquid environment. This research opens up promising avenues for designing soft/hard heterogeneous materials with strong adhesive properties.

12.
Nat Commun ; 15(1): 4664, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38821968

RESUMO

Using a transfer printing technique, we imprint a layer of a designated near-infrared fluorescent dye BTP-eC9 onto a thin layer of Pt(II) complex, both of which are capable of self-assembly. Before integration, the Pt(II) complex layer gives intense deep-red phosphorescence maximized at ~740 nm, while the BTP-eC9 layer shows fluorescence at > 900 nm. Organic light emitting diodes fabricated under the imprinted bilayer architecture harvest most of Pt(II) complex phosphorescence, which undergoes triplet-to-singlet energy transfer to the BTP-eC9 dye, resulting in high-intensity hyperfluorescence at > 900 nm. As a result, devices achieve 925 nm emission with external quantum efficiencies of 2.24% (1.94 ± 0.18%) and maximum radiance of 39.97 W sr-1 m-2. Comprehensive morphology, spectroscopy and device analyses support the mechanism of interfacial energy transfer, which also is proved successful for BTPV-eC9 dye (1022 nm), making bright and far-reaching the prospective of hyperfluorescent OLEDs in the near-infrared region.

13.
Front Nutr ; 11: 1385159, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628273

RESUMO

Introduction: Functional dyspepsia (FD), also known as non-ulcerative dyspepsia, is a common digestive system disorder. Methods: In this study, an FD model was established using hunger and satiety disorders combined with an intraperitoneal injection of L-arginine. Indices used to evaluate the efficacy of hawthorn in FD mice include small intestinal propulsion rate, gastric residual rate, general condition, food intake, amount of drinking water, gastric histopathological examination, and serum nitric oxide (NO) and gastrin levels. Based on the intestinal flora and their metabolites, short-chain fatty acids (SCFAs), the mechanism of action of Crataegi Fructus (hawthorn) on FD was studied. The fecal microbiota transplantation test was used to verify whether hawthorn altered the structure of the intestinal flora. Results: The results showed that hawthorn improved FD by significantly reducing the gastric residual rate, increasing the intestinal propulsion rate, the intake of food and drinking water, and the levels of gastrointestinal hormones. Simultaneously, hawthorn elevated substance P and 5-hydroxytryptamine expression in the duodenum, reduced serum NO levels, and increased vasoactive intestinal peptide expression in the duodenum. Notably, hawthorn increased the abundance of beneficial bacteria and SCFA-producing bacteria in the intestines of FD mice, decreased the abundance of conditional pathogenic bacteria, and significantly increased the SCFA content in feces. Discussion: The mechanism by which hawthorn improves FD may be related to the regulation of intestinal flora structure and the production of SCFAs.

14.
Res Sq ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38659817

RESUMO

Purpose: Over 550 loci have been associated with human pulmonary function in genome-wide association studies (GWAS); however, the causal role of most remains uncertain. Single nucleotide polymorphisms in a disintegrin and metalloprotease domain 19 (ADAM19) are consistently related to pulmonary function in GWAS. Thus, we used a mouse model to investigate the causal link between Adam19 and pulmonary function. Methods: We created an Adam19 knockout (KO) mouse model and validated the gene targeting using RNA-Seq and RT-qPCR. Contrary to prior publications, the KO was not neonatal lethal. Thus, we phenotyped the Adam19 KO. Results: KO mice had lower body weight and shorter tibial length than wild type (WT). Dual-energy X-ray Absorptiometry indicated lower soft weight, fat weight, and bone mineral content in KO mice. In lung function analyses using flexiVent, compared to WT, Adam19 KO had decreased baseline respiratory system elastance, minute work of breathing, tissue damping, tissue elastance, and forced expiratory flow at 50% forced vital capacity but higher FEV0.1 and FVC. Adam19 KO had attenuated tissue damping and tissue elastance in response to methacholine following LPS exposure. Adam19 KO also exhibited attenuated neutrophil extravasation into the airway after LPS administration compared to WT. RNA-Seq analysis of KO and WT lungs identified several differentially expressed genes (Cd300lg, Kpna2, and Pttg1) implicated in lung biology and pathogenesis. Gene set enrichment analysis identified negative enrichment for TNF pathways. Conclusion: Our murine findings support a causal role of ADAM19, implicated in human GWAS, in regulating pulmonary function.

15.
Angew Chem Int Ed Engl ; 63(23): e202403317, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38578721

RESUMO

We demonstrate directed translocation of ClO4 - anions from cationic to neutral binding site along the synthetized BPym-OH dye molecule that exhibits coupled excited-state intramolecular proton-transfer (ESIPT) and charge-transfer (CT) reaction (PCCT). The results of steady-state and time-resolved spectroscopy together with computer simulation and modeling show that in low polar toluene the excited-state redistribution of electronic charge enhanced by ESIPT generates the driving force, which is much stronger than by CT reaction itself and provides more informative gigantic shifts of fluorescence spectra signaling on ultrafast ion motion. The associated with ion translocation red-shifted fluorescence band (at 750 nm, extending to near-IR region) appears at the time ~83 ps as a result of electrochromic modulation of PCCT reaction. It occurs at substantial delay to PCCT that displayed fluorescence band at 640 nm and risetime of <200 fs. Thus, it becomes possible to visualize the manifestations of light-triggered ion translocation and of its driving force by fluorescence techniques and to separate them in time and energy domains.

16.
Cell Rep ; 43(4): 113973, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38507406

RESUMO

We identified and validated a collection of circular RNAs (circRNAs) in Drosophila melanogaster. We show that depletion of the pro-viral circRNA circATP8B(2), but not its linear siblings, compromises viral infection both in cultured Drosophila cells and in vivo. In addition, circATP8B(2) is enriched in the fly gut, and gut-specific depletion of circATP8B(2) attenuates viral replication in an oral infection model. Furthermore, circATP8B(2) depletion results in increased levels of reactive oxygen species (ROS) and enhanced expression of dual oxidase (Duox), which produces ROS. Genetic and pharmacological manipulations of circATP8B(2)-depleted flies that reduce ROS levels rescue the viral replication defects elicited by circATP8B(2) depletion. Mechanistically, circATP8B(2) associates with Duox, and circATP8B(2)-Duox interaction is crucial for circATP8B(2)-mediated modulation of Duox activity. In addition, Gαq, a G protein subunit required for optimal Duox activity, acts downstream of circATP8B(2). We conclude that circATP8B(2) regulates antiviral defense by modulating Duox expression and Duox-dependent ROS production.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , RNA Circular , Espécies Reativas de Oxigênio , Animais , Espécies Reativas de Oxigênio/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Drosophila melanogaster/imunologia , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Replicação Viral , RNA/metabolismo , RNA/genética , NADPH Oxidases/metabolismo , NADPH Oxidases/genética , Oxidases Duais/metabolismo , Oxidases Duais/genética
17.
Sci Rep ; 14(1): 7028, 2024 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528062

RESUMO

Accurate indel calling plays an important role in precision medicine. A benchmarking indel set is essential for thoroughly evaluating the indel calling performance of bioinformatics pipelines. A reference sample with a set of known-positive variants was developed in the FDA-led Sequencing Quality Control Phase 2 (SEQC2) project, but the known indels in the known-positive set were limited. This project sought to provide an enriched set of known indels that would be more translationally relevant by focusing on additional cancer related regions. A thorough manual review process completed by 42 reviewers, two advisors, and a judging panel of three researchers significantly enriched the known indel set by an additional 516 indels. The extended benchmarking indel set has a large range of variant allele frequencies (VAFs), with 87% of them having a VAF below 20% in reference Sample A. The reference Sample A and the indel set can be used for comprehensive benchmarking of indel calling across a wider range of VAF values in the lower range. Indel length was also variable, but the majority were under 10 base pairs (bps). Most of the indels were within coding regions, with the remainder in the gene regulatory regions. Although high confidence can be derived from the robust study design and meticulous human review, this extensive indel set has not undergone orthogonal validation. The extended benchmarking indel set, along with the indels in the previously published known-positive set, was the truth set used to benchmark indel calling pipelines in a community challenge hosted on the precisionFDA platform. This benchmarking indel set and reference samples can be utilized for a comprehensive evaluation of indel calling pipelines. Additionally, the insights and solutions obtained during the manual review process can aid in improving the performance of these pipelines.


Assuntos
Benchmarking , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Biologia Computacional , Controle de Qualidade , Mutação INDEL , Polimorfismo de Nucleotídeo Único
18.
Food Funct ; 15(3): 1583-1597, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38240189

RESUMO

Osteoporosis (OP) is a systemic disorder characterized by decreased bone mass as well as deteriorated microarchitecture. Although OP in men is common, it has received much less attention than that in women. Ginseng, a famous traditional herb in Asia, is used to strengthen and repair bones by invigorating vital bioenergy and maintaining body homeostasis in dietary intake and clinical applications. However, there is currently no study investigating the impact of ginseng and its active compounds on male osteoporosis. In this study, RNA sequencing and bioinformatic analysis were conducted to reveal the influence of Ginsenoside-Rb2 on RAW264.7 cells and its underlying signaling pathways. The potential anti-osteoporosis effects of Rb2 as well as its molecular mechanisms were elucidated in RAW264.7 cells and BMMs by TRAP staining, F-actin belt staining, qRT-PCR and WB. Moreover, orchiectomy (ORX) was utilized to demonstrate the influence of Rb2 on bone mass loss in vivo by micro-CT scanning, and H&E, TRAP, and IHC staining. The results suggested that Rb2 suppressed osteoclastogenesis and mitigated bone loss in orchiectomy mice through NF-κB/MAPK signaling pathways. These findings indicate that ginseng as well as its active component Rb2 have potential therapeutic value in the management of osteoporosis in men.


Assuntos
Ginsenosídeos , Osteoporose , Feminino , Masculino , Humanos , Animais , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Osteogênese , Ginsenosídeos/metabolismo , Osteoclastos , Orquiectomia , Transdução de Sinais , Osteoporose/tratamento farmacológico , Osteoporose/genética , Osteoporose/metabolismo , Ligante RANK/metabolismo
19.
PLoS One ; 19(1): e0296699, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38232086

RESUMO

The cancer hazard associated with lifetime exposure to radiofrequency radiation (RFR) was examined in Sprague Dawley (SD) rats at the Ramazzini Institute (RI), Italy. There were increased incidences of gliomas and cardiac schwannomas. The translational relevance of these rare rat tumors for human disease is poorly understood. We examined the genetic alterations in RFR-derived rat tumors through molecular characterization of important cancer genes relevant for human gliomagenesis. A targeted next-generation sequencing (NGS) panel was designed for rats based on the top 23 orthologous human glioma-related genes. Single-nucleotide variants (SNVs) and small insertion and deletions (indels) were characterized in the rat gliomas and cardiac schwannomas. Translational relevance of these genetic alterations in rat tumors to human disease was determined through comparison with the Catalogue of Somatic Mutations in Cancer (COSMIC) database. These data suggest that rat gliomas resulting from life-time exposure to RFR histologically resemble low grade human gliomas but surprisingly no mutations were detected in rat gliomas that had homology to the human IDH1 p.R132 or IDH2 p.R172 suggesting that rat gliomas are primarily wild-type for IDH hotspot mutations implicated in human gliomas. The rat gliomas appear to share some genetic alterations with IDH1 wildtype human gliomas and rat cardiac schwannomas also harbor mutations in some of the queried cancer genes. These data demonstrate that targeted NGS panels based on tumor specific orthologous human cancer driver genes are an important tool to examine the translational relevance of rodent tumors resulting from chronic/life-time rodent bioassays.


Assuntos
Neoplasias Encefálicas , Glioma , Neurilemoma , Exposição à Radiação , Humanos , Ratos , Animais , Ratos Sprague-Dawley , Glioma/genética , Glioma/patologia , Mutação , Neurilemoma/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Isocitrato Desidrogenase/genética , Neoplasias Encefálicas/patologia
20.
Neurotherapeutics ; 21(2): e00317, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38266580

RESUMO

Pink1 (PTEN-induced putative kinase 1) is a protein associated with maintaining mitochondrial function and integrity and has been reported to mediate neurodegeneration and neuroinflammation. While the role of Pink1 in intracerebral hemorrhage (ICH)-related neurological deficits and inflammatory responses is not deciphered. Congenic blood was transfused into the left corpus striatum to construct the ICH model in C57/BL6 wild-type (WT) and Pink1-/- mice. The relative expression of Pink1, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-2, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, Cd86, nitric oxide synthase 2 (Nos2), Cd206, arginase 1 (Arg-1), and IL-10 was detected with qRT-PCR, Western blotting, or ELISA. Mouse neurological deficit scores (mNSS) and water content were detected, and an open-field test was performed to assay anxiety-like behavior. Remarkably decreased Pink1 expression and increased MIP-2, IL-1ß, MCP-1, and TNF-α expression were observed after 12 â€‹h, 24 â€‹h, 48 â€‹h, 72 â€‹h, and 7 â€‹d post-ICH induction in the ipsilateral injury hemispheres. Pink1 deficiency could further up-regulate mNSS scores, brain water content, MIP-2, MCP-1, IL-1ß, and TNF-α in the ipsilateral injury hemispheres. On the other hand, Pink1 deficiency could decrease the number of center cross, the velocity, and the total distance traveled in open field test. Pink1 deficiency could further up-regulate the mRNA levels of pro-inflammatory (M1) molecules (Cd86, Nos2), and down-regulate the relative expression of anti-inflammatory (M2) molecules (Cd206, Arg-1, and IL-10). Pink1 deficiency deteriorates neurological deficits and inflammatory responses after ICH, which can be considered as a treatment target.


Assuntos
Interleucina-10 , Fator de Necrose Tumoral alfa , Animais , Camundongos , Encéfalo/metabolismo , Hemorragia Cerebral/complicações , Hemorragia Cerebral/genética , Hemorragia Cerebral/metabolismo , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/metabolismo , Água/metabolismo , Proteínas Quinases/genética , Proteínas Quinases/metabolismo
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