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During development, melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) become light sensitive much earlier than rods and cones. IpRGCs project to many subcortical areas, whereas physiological functions of these projections are yet to be fully elucidated. Here, we found that ipRGC-mediated light sensation promotes synaptogenesis of pyramidal neurons in various cortices and the hippocampus. This phenomenon depends on activation of ipRGCs and is mediated by the release of oxytocin from the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) into cerebral-spinal fluid. We further characterized a direct connection between ipRGCs and oxytocin neurons in the SON and mutual projections between oxytocin neurons in the SON and PVN. Moreover, we showed that the lack of ipRGC-mediated, light-promoted early cortical synaptogenesis compromised learning ability in adult mice. Our results highlight the importance of light sensation early in life on the development of learning ability and therefore call attention to suitable light environment for infant care.
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Oxitocina , Células Ganglionares de la Retina , Animales , Encéfalo/metabolismo , Humanos , Ratones , Células Ganglionares de la Retina/fisiología , Opsinas de Bastones/metabolismoRESUMEN
Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) has been consistently identified in various environmental media and biological specimens. Current understanding of the in vivo toxicities of TDCIPP is limited, especially for potential for neurotoxic and cognitive impairment effects. To better evaluate the potential adverse effect of the chemical on learning and memory, Sprague Dawley (SD) rats were administered TDCIPP via gavage at doses of 40, 120, and 360 mg/kg/day for a period of 90 days. Quantitative proteomic analysis, immunohistochemistry, and Western blotting were employed to assess alterations in proteins following exposure to TDCIPP. An open field test and the Morris Water Maze were used to assess anxiety and spatial learning memory capacity. Administration of TDCIPP induced anxiety and cognitive impairments in rats. Additionally, a noteworthy decrease in the number of neurons was observed in the hippocampal CA3 and dentate gyrus (DG) regions. Proteomic and bioinformatic analyses revealed dysregulation of numerous hippocampal proteins, particularly those associated with synapses (PKN1) or oxidative stress (GSTM4, NQO1, and BMAL1), which was further confirmed by Western blot analysis. In sum, the cognitive impairment of rats caused by TDCIPP exposure was associated with dysregulation of synaptic and oxidative stress-related proteins.
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Organofosfatos , Compuestos Organofosforados , Proteómica , Ratas , Animales , Compuestos Organofosforados/toxicidad , Ratas Sprague-Dawley , Estrés OxidativoRESUMEN
This paper presents a new broadband ocean bottom seismograph (OBS) developed by the SUSTech OBS lab for passive-source seafloor seismic observations. This instrument, called Pankun, has several key features that set it apart from traditional OBS instruments. In addition to the seismometer-separated scheme, these features include a unique shielding structure to minimize current-induced noise, a compact gimbal for accurate leveling, and low power consumption for extended operation on the seafloor. The design and testing of Pankun's primary components are thoroughly described in this paper. The instrument has been successfully tested in the South China Sea, demonstrating its ability to record high-quality seismic data. The anti-current shielding structure of Pankun OBS has the potential to improve low-frequency signals, particularly on the horizontal components, in seafloor seismic data.
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Exactitud de los Datos , Ruido , Océanos y Mares , ChinaRESUMEN
Alzheimer's disease (AD) is characterized by amyloid plaques and neurofibrillary tangles accompanied by progressive neurite loss. Mitochondria play pivotal roles in AD development. PRDX3 is a mitochondrial peroxide reductase critical for H2O2 scavenging and signal transduction. In this study, we found that PRDX3 knockdown (KD) in the N2a-APPswe cell line promoted retinoic acid (RA)-induced neurite outgrowth but did not reduce the viability of cells damaged by tert-butyl hydroperoxide (TBHP). We found that knocking down PRDX3 expression induced dysregulation of more than one hundred proteins, as determined by tandem mass tag (TMT)-labeled proteomics. A Gene Ontology (GO) analysis revealed that the dysregulated proteins were enriched in protein localization to the plasma membrane, the lipid catabolic process, and intermediate filament cytoskeleton organization. A STRING analysis showed close protein-protein interactions among dysregulated proteins. The expression of Annexin A1 (ANXA1), serine (Ser)-/threonine (Thr)-protein phosphatase 2A catalytic subunit alpha isoform (PP2A) and glutathione S-transferase Mu 2 (GSTM2) was significantly upregulated in PRDX3-KD N2a-APPswe cell lines, as verified by western blotting. Our study revealed, for the first time, that PRDX3 may play important roles in neurite outgrowth and AD development.
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Enfermedad de Alzheimer , Proyección Neuronal , Peroxiredoxina III , Enfermedad de Alzheimer/metabolismo , Línea Celular Tumoral , Humanos , Peróxido de Hidrógeno/metabolismo , Neuritas/metabolismo , Proyección Neuronal/genética , Peroxiredoxina III/genética , Peroxiredoxina III/metabolismo , ProteómicaRESUMEN
OBJECTIVES: Higher static magnetic field (SMF) enables higher imaging capability in magnetic resonance imaging (MRI), which encourages the development of ultra-high field MRIs above 20 T with a prerequisite for safety issues. However, animal tests of ≥ 20 T SMF exposure are very limited. The objective of the current study is to evaluate mice behaviour consequences of 3.5-23.0 T SMF exposure. METHODS: We systematically examined 112 mice for their short- and long-term behaviour responses to a 2-h exposure of 3.5-23.0 T SMFs. Locomotor activity and cognitive functions were measured by five behaviour tests, including balance beam, open field, elevated plus maze, three-chamber social recognition, and Morris water maze tests. RESULTS: Besides the transient short-term impairment of the sense of balance and locomotor activity, the 3.5-23.0 T SMFs did not have long-term negative effects on mice locomotion, anxiety level, social behaviour, or memory. In contrast, we observed anxiolytic effects and positive effects on social and spatial memory of SMFs, which is likely correlated with the significantly increased CaMKII level in the hippocampus region of high SMF-treated mice. CONCLUSIONS: Our study showed that the short exposures to high-field SMFs up to 23.0 T have negligible side effects on healthy mice and may even have beneficial outcomes in mice mood and memory, which is pertinent to the future medical application of ultra-high field SMFs in MRIs and beyond. KEY POINTS: ⢠Short-term exposure to magnetic fields up to 23.0 T is safe for mice. ⢠High-field static magnetic field exposure transiently reduced mice locomotion. ⢠High-field static magnetic field enhances memory while reduces the anxiety level.
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Campos Magnéticos , Imagen por Resonancia Magnética , Animales , Cognición , Imagen por Resonancia Magnética/efectos adversos , RatonesRESUMEN
AIM: Human herpesvirus 6 (HHV-6) is neurophilic, and its relationship with Alzheimer's disease (AD) remains controversial. This study aimed to examine the relationships between HHV-6 and cognitive abilities in elderly people aged 60 years or above from communities in Shenzhen. METHODS: We recruited participants from 10 community health service centers in Shenzhen. Participants were divided into case and control groups according to Mini-Mental State Examination (MMSE) scale standards and were included in this study with 1:1 matching based on sex and age (± 3 years). The HHV-6 gene was detected by real-time fluorescent quantitative PCR, and the HHV-6 copy number was quantified. RESULTS: A total of 580 participants (cases, n = 290; controls, n = 290), matched for gender and age was included in this study. A positive HHV-6 test was not associated with a significant difference in global cognitive performance (ORadjusted = 1.651, 95% CI = 0.671-4.062). After adjusting for gender, age, education, Pittsburgh Sleep Quality Index (PSQI) score, homocysteine (Hcy) and glycosylated hemoglobin (HbA1c), the results of multiple linear regression showed that there was a statistically negative correlation between HHV-6 copy number and orientation (ßadjusted = -0.974, p = 0.013), attention and calculation (ßadjusted = -1.840, p < 0.001), and language (ßadjusted = -2.267, p < 0.001). The restricted cubic spline (RCS) model results showed that there was a nonlinear dose-response relationship between HHV-6 log10-transformed copies and orientation (poverall = 0.003, pnonliner = 0.045), attention and calculation (poverall < 0.001, pnonliner < 0.001), and language (poverall < 0.001, pnonliner = 0.016). CONCLUSIONS: HHV-6 infection significantly associated with orientation, attention and calculation, and language in elderly individuals.
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Enfermedad de Alzheimer , Herpesvirus Humano 6 , Infecciones por Roseolovirus , Anciano , Humanos , Herpesvirus Humano 6/genética , Infecciones por Roseolovirus/complicaciones , Enfermedad de Alzheimer/complicaciones , China , CogniciónRESUMEN
Effective treatment to prevent or arrest the advance of Alzheimer disease (AD) has yet to be discovered. We investigated whether OligonolR, an FDA-approved flavanol-rich extract prepared from lychee fruit and green tea, exerted beneficial effects relevant to AD in a triple transgenic male mouse model of AD (3×Tg-AD). At 9 months of age, untreated 3×Tg-AD mice vs. wild-type (WT) controls displayed cognitive deficits in behavioral assays and, at 12 months, elevated levels of hippocampal amyloid beta-protein (Aß), amyloid precursor protein (APP), tau phosphorylation, and pro-inflammatory cytokines. 3×Tg-AD mice given Oligonol showed fewer cognitive deficits and attenuated pathological indices at 12 months. Oligonol treatment of 3×Tg-AD mice modulated expression of some critical brain proteins that involve multiple pathways relevant to mitochondrial dysfunction, proteasomal failure, endoplasmic reticulum (ER) stress and synaptic impairment. Together, these results demonstrate that continuous Oligonol treatment attenuates AD-like pathology and cognitive impairment of 3×Tg-AD mice and set the stage for clinical trials of this flavanol-rich plant extract in patients with early AD.
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Enfermedad de Alzheimer/tratamiento farmacológico , Catequina/análogos & derivados , Disfunción Cognitiva/tratamiento farmacológico , Litchi/química , Fenoles/administración & dosificación , Extractos Vegetales/administración & dosificación , Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animales , Catequina/administración & dosificación , Modelos Animales de Enfermedad , Flavonoides/administración & dosificación , Frutas/química , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Humanos , Masculino , Ratones , Ratones Transgénicos , Mutación/genética , Fosforilación/efectos de los fármacos , Té/química , Transgenes/genética , Proteínas tau/genética , Proteínas tau/metabolismoRESUMEN
Lipophilic shellfish toxins (LSTs) can cause human illness and therefore represent a serious threat to public health. Shellfish are the main dietary source of LSTs, but very few studies have appraised dietary exposure to LSTs through shellfish consumption in China. We measured levels of multiple LSTs in shellfish samples sold in the principal wholesale seafood market in the southern coastal city of Shenzhen, and we estimated the potential for acute and chronic LST exposure of the Shenzhen population via ingestion of shellfish. LST contamination data were obtained from a total of 14 species of 188 commercial samples. Eleven individual LSTs, namely okadaic acid (OA), dinophysis toxin-1 and -2 (DTX1 and DTX2), pectenotoxin-2 (PTX2), yessotoxin and homo yessotoxin (YTX and hYTX), azaspiracid-1, -2 and -3 (AZA1, AZA2, AZA3), spirolides (SPXs), and gymnodimine (GYM), were determined using liquid chromatography electrospray-ionization tandem mass spectrometry (LC-ESI-MS/MS). More than two thirds of samples showed undetectable LSTs, while the detection rates (the proportion of samples with detectable LSTs) of individual LSTs ranged from 0% to 45.7%. Most shellfish samples had lower levels of LST contamination than the corresponding limits of detection (LODs), while some samples had levels of hYTX and GYM that exceeded the limits of quantification (LOQs). Overall, levels of LSTs in the 188 samples were below the regulatory limits set by most countries. Acute and chronic exposures of LST were estimated by a point-estimate modeling method that combined sample contamination data with consumption data from dietary survey of Shenzhen residents and consumption figures proposed by EFSA, the European Food Safety Authority. Seasonal variations in LST concentrations were noted in some instances. Overall, the estimated acute exposure to LSTs based on consumption of large-size shellfish portions and the maximum LSTs contamination level were below the provisional acute reference doses (ARfDs) proposed by the EFSA. Chronic exposure estimates based on mean and 99th percentile consumption of shellfish by Shenzhen residents and mean LSTs contamination levels in the collected samples were from 2452 to 74 times lower than those associated with estimated acute exposure levels.
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Exposición Dietética/análisis , Exposición Dietética/estadística & datos numéricos , Contaminación de Alimentos/análisis , Contaminación de Alimentos/estadística & datos numéricos , Mariscos/análisis , Animales , Cromatografía Liquida , Dinoflagelados/química , Humanos , Toxinas Marinas/análisis , Alimentos Marinos/análisis , Espectrometría de Masas en TándemRESUMEN
Trichloroethylene (TCE) is a ubiquitous toxicant widespread in our environment. Exposure to TCE can cause severe liver damage. In previous studies, we detected an abnormal elevation of SET (a protein encoded by the SETgene in humans) which was observed in human HL-7702 cells (L-02 hepatocytes) under the treatment of TCE. Moreover, further study indicated that SET acts as an important mediator in TCE-induced hepatocyte apoptosis. The major functions of SET have been elucidated, while the regulatory mechanism responsible for modulation of SET remains unclear. In this study, four major microRNA-related databases were used to screen and identify 6 candidate microRNAs involved in the regulation of SET. Subsequent verification indicated that miR-21 and miR-199b-5p were decreased in TCE-treated L-02 cells, suggesting that miR-21 and miR-199b-5p (miR199b for short) miR199b potentially regulate SET expression. Additionally, the dual-luciferase system revealed that only miR199b could directly bind to untranslated region (3'-UTR) of the SETgene. Modulation of SET by miR199b was verified through overexpression and knockdown of miR199b in L-02 cells. Assessment of apoptosis indicated that elevated miR199b attenuated TCE-induced apoptosis, while reduced miR199b enhanced it. In summary, this study suggests that in cultured hepatocytes, TCE-induced suppression of miR199b drives SET induction, which further mediates the response to TCE.
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Proteínas de Unión al ADN/metabolismo , Hepatocitos/metabolismo , Chaperonas de Histonas/metabolismo , MicroARNs/genética , Apoptosis/efectos de los fármacos , Apoptosis/genética , Línea Celular , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Humanos , MicroARNs/metabolismo , Tricloroetileno/efectos adversos , Tricloroetileno/farmacologíaRESUMEN
The potent neurotoxin saxitoxin produced by both marine and freshwater phytoplankton causes paralytic shellfish poisoning syndrome. The toxicity and mode of action of the acute exposure of high-dose saxitoxin have been intensively studied for decades; however, the potential risk of exposure of low-dose saxitoxin remained to be uncovered. Here we present a proteomics study of murine neuroblastoma N2A cell with low-dose saxitoxin exposure (1 nM and 10 nM, 24-h intoxication). Differential proteins were profiled by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). A total of 9 proteins, including 14-3-3 beta (1433B), alpha enolase (ENO1) and cofilin 2 (CFL2), were altered by the low-dose saxitoxin exposure. We further validated the expressions of 1433B, ENO1 and CFL2 by Western blot analysis and the enzyme-linked immunosorbent assay. These 9 proteins involve cell apoptotic pathways, cell skeleton maintenance, membrane potentials and mitochondrial functions. Modulation of these 9 proteins by low-dose saxitoxin exposure could correlate to the reports on genotoxicity and neurotoxicity induced by saxitoxin. This study also suggested other potential risks of saxitoxin.
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Neuroblastoma/metabolismo , Neuronas/efectos de los fármacos , Proteoma/efectos de los fármacos , Saxitoxina/toxicidad , Proteínas 14-3-3/metabolismo , Animales , Western Blotting , Línea Celular Tumoral , Cofilina 2/metabolismo , Relación Dosis-Respuesta a Droga , Ensayo de Inmunoadsorción Enzimática , Ratones , Neuroblastoma/patología , Neuronas/metabolismo , Neuronas/patología , Fosfopiruvato Hidratasa/metabolismo , Proteoma/metabolismo , Proteómica/métodos , Medición de Riesgo , Transducción de Señal/efectos de los fármacos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Pruebas de Toxicidad/métodos , Electroforesis Bidimensional Diferencial en GelRESUMEN
Trichloroethylene (TCE), a halogenated organic solvent widely used in industries, is known to cause severe hepatotoxicity. However, the mechanisms underlying TCE hepatotoxicity are still not well understood. It is predicted that membrane proteins are responsible for key biological functions, and recent studies have revealed that TCE exposure can induce abnormal levels of membrane proteins in body fluids and cultured cells. The aim of this study is to investigate the TCE-induced alterations of membrane proteins profiles in human hepatic L-02 liver cells. A comparative membrane proteomics analysis was performed in combination with two-dimensional fluorescence difference gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry. A total of 15 proteins were identified as differentially expressed (4 upregulated and 11 downregulated) between TCE-treated cells and normal controls. Among this, 14 of them are suggested as membrane-associated proteins by their transmembrane domain and/or subcellular location. Furthermore, the differential expression of ß subunit of adenosine triphosphate synthase (ATP5B) and prolyl 4-hydroxylase, ß polypeptide (P4HB) were verified by Western blot analysis in TCE-treated L-02 cells. Our work not only reveals the association between TCE exposure and altered expression of membrane proteins but also provides a novel strategy to discover membrane biomarkers and elucidate the potential mechanisms involving with membrane proteins response to chemical-induced toxic effect.
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Proteínas de la Membrana/análisis , Proteínas de la Membrana/metabolismo , Proteoma/efectos de los fármacos , Proteómica/métodos , Tricloroetileno/toxicidad , Línea Celular , Electroforesis en Gel Bidimensional , Humanos , Hígado/citología , Proteínas de la Membrana/clasificación , Proteoma/análisis , Proteoma/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
Breast cancer is the most malignant tumor for women, however, the mechanisms underlying this devastating disease remain unclear. SET is an endogenous inhibitor of protein phosphatase 2A (PP2A) and involved in many physiological and pathological processes. SET could promote the occurrence of tumor through inhibiting PP2A. In this study, we explore the role of SET in the migration and invasion of breast cancer cells MDA-MB-231 and ZR-75-30. The stable suppression of SET expression through lentivirus-mediated RNA interference (RNAi) was shown to inhibit the growth, migration and invasion of breast cancer cells. Knockdown of SET increases the activity and expression of PP2Ac and decrease the expression of matrix metalloproteinase 9 (MMP-9). These data demonstrate that SET may be involved in the pathogenic processes of breast cancer, indicating that SET can serve as a potential therapeutic target for the treatment of breast cancer.
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Neoplasias de la Mama/patología , Neoplasias de la Mama/fisiopatología , Chaperonas de Histonas/antagonistas & inhibidores , Factores de Transcripción/antagonistas & inhibidores , Neoplasias de la Mama/terapia , Línea Celular Tumoral , Movimiento Celular/genética , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Proteínas de Unión al ADN , Femenino , Técnicas de Silenciamiento del Gen , Chaperonas de Histonas/genética , Chaperonas de Histonas/fisiología , Humanos , Metaloproteinasa 9 de la Matriz/metabolismo , Invasividad Neoplásica/genética , Invasividad Neoplásica/fisiopatología , Invasividad Neoplásica/prevención & control , Proteína Fosfatasa 2/antagonistas & inhibidores , Proteína Fosfatasa 2/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/genética , Factores de Transcripción/genética , Factores de Transcripción/fisiologíaRESUMEN
Trichloroethylene (TCE), a major occupational and environmental pollutant, has been recently associated with aberrant epigenetic changes in experimental animals and cultured cells. TCE is known to cause severe hepatotoxicity; however, the association between epigenetic alterations and TCE-induced hepatotoxicity are not yet well explored. DNA methylation, catalyzed by enzymes known as DNA methyltransferases (DNMT), is a major epigenetic modification that plays a critical role in regulating many cellular processes. In this study, we analyzed the TCE-induced effect on global DNA methylation and DNMT enzymatic activity in human hepatic L-02 cells. A sensitive and quantitative method combined with liquid chromatography and electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) was validated and utilized for assessing the altered DNA methylation in TCE-induced L-02 cells. Quantification was accomplished in multiple reaction monitoring (MRM) mode by monitoring a transition pair of m/z 242.1 (molecular ion)/126.3 (fragment ion) for 5-mdC and m/z 268.1/152.3 for dG. The correlation coefficient of calibration curves between 5-mdC and dG was higher than 0.9990. The intra-day and inter-day relative standard derivation values (RSD) were on the range of 0.53-7.09% and 0.40-2.83%, respectively. We found that TCE exposure was able to significantly decrease the DNA methylation and inhibit DNMT activity in L-02 cells. Our results not only reveal the association between TCE exposure and epigenetic alterations, but also provide an alternative mass spectrometry-based method for rapid and accurate assessment of chemical-induced altered DNA methylation in mammal cells.
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Metilación de ADN/genética , Metilasas de Modificación del ADN/metabolismo , ADN/efectos de los fármacos , ADN/genética , Epigénesis Genética/genética , Hepatocitos/fisiología , Tricloroetileno/toxicidad , Línea Celular , Cromatografía Líquida de Alta Presión/métodos , Metilación de ADN/efectos de los fármacos , Epigénesis Genética/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Humanos , Mutágenos/toxicidad , Espectrometría de Masa por Ionización de Electrospray/métodosRESUMEN
OBJECTIVE: To reveal the role of poly-ADP-ribosylation and DNA methylation in carcinogenic process induced induced by Cr (VI), and to discuss the relations between them. METHODS: The pre-established Poly (ADP-ribose) glycohydrolase (PARG) deficient cells and 16HBE cells were treated with different concentrations of Cr (VI), and the changes of total genomic DNA methylation level in different groups were detected by methylation immunofluorescent detection, as well as the changes of the activity of methyltransferases. Moreover, RT-PCR and western blotting method were applied to analyze the changes of expression of DNMT1, DNMT3a, DNMT3b and MBD2, upon the protein level. RESULTS: After treated by Cr(VI) for 24 h, the healthy 16HBE cells showed a significant lower level of genomic DNA methylation; however, there was no significant changes (P > 0.05) found in PARG deficient cells by immunofluorescence assay. When the dose of Cr (VI) reached 5.0 µmol/L, the activity of methyltransferases in 16HBE cells and PARG deficient cells (49.33 ± 2.65, 80.05 ± 2.05) decreased by 20% and 50% comparing with contrast group (99.27 ± 1.10, 99.30 ± 0.60) . After treated by Cr (VI) for 24 h, the expression of mRNA and protein level among DNMT1, DNMT3a, DNMT3b and MBD2 decreased significantly in healthy 16HBE cells; and the expression of DNMT1 and DNMT3a decreased in PARG deficiency cells. The relevant expression levels of mRNA of DNMT1 were separately (0.99 ± 0.09), (0.79 ± 0.10), (0.59 ± 0.13) and (0.39 ± 0.02) (F = 247.17, P < 0.01), the expression levels of protein were separately (1.00 ± 0.03), (0.69 ± 0.15), (0.65 ± 0.10) and (0.55 ± 0.13) (F = 214.12, P < 0.01), the expression levels of DNMT3a mRNA were separately (1.00 ± 0.04) , (0.93 ± 0.11) , (0.79 ± 0.07) , (0.59 ± 0.05) (F = 498.16, P < 0.01) , and the expression levels of protein were separately (1.00 ± 0.14) , (0.97 ± 0.11) , (0.79 ± 0.17) , (0.57 ± 0.15) (F = 390.11, P < 0.01) when the dose of Cr (VI) at 0, 0.3, 1.2 and 5.0 µmol/L. However, there were no significant changes of expression found in DNMT3b and MBD2. CONCLUSION: Poly-ADP-ribosylation could regulate the activity of DNMT3b and MBD2, protect cells against the DNA methylation alteration induced by Cr(VI) and maintain the global genomic DNA methylation level.
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Cromo/toxicidad , Metilación de ADN/efectos de los fármacos , Células Epiteliales/metabolismo , Poli Adenosina Difosfato Ribosa/metabolismo , Línea Celular , ADN (Citosina-5-)-Metiltransferasa 1 , ADN (Citosina-5-)-Metiltransferasas/metabolismo , ADN Metiltransferasa 3A , Proteínas de Unión al ADN/metabolismo , Genoma , Humanos , ARN Mensajero/genética , ADN Metiltransferasa 3BRESUMEN
Objective: To identify plasma lipid characteristics associated with premetabolic syndrome (pre-MetS) and metabolic syndrome (MetS) and provide biomarkers through machine learning methods. Methods: Plasma lipidomics profiling was conducted using samples from healthy individuals, pre-MetS patients, and MetS patients. Orthogonal partial least squares-discriminant analysis (OPLS-DA) models were employed to identify dysregulated lipids in the comparative groups. Biomarkers were selected using support vector machine recursive feature elimination (SVM-RFE), random forest (rf), and least absolute shrinkage and selection operator (LASSO) regression, and the performance of two biomarker panels was compared across five machine learning models. Results: In the OPLS-DA models, 50 and 89 lipid metabolites were associated with pre-MetS and MetS patients, respectively. Further machine learning identified two sets of plasma metabolites composed of PS(38:3), DG(16:0/18:1), and TG(16:0/14:1/22:6), TG(16:0/18:2/20:4), and TG(14:0/18:2/18:3), which were used as biomarkers for the pre-MetS and MetS discrimination models in this study. Conclusion: In the initial lipidomics analysis of pre-MetS and MetS, we identified relevant lipid features primarily linked to insulin resistance in key biochemical pathways. Biomarker panels composed of lipidomics components can reflect metabolic changes across different stages of MetS, offering valuable insights for the differential diagnosis of pre-MetS and MetS.
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Síndrome Metabólico , Humanos , Síndrome Metabólico/metabolismo , Lipidómica/métodos , Lípidos , Aprendizaje Automático , BiomarcadoresRESUMEN
Supercapacitors (SCs), as new energy storage devices with low cost and high performance, urgently require an electrode material with good pore structure and developed graphitization. Herein, we report a 3D hierarchical porous structured carbon aerogel (CA) obtained via dissolving-gelling and a subsequent carbonizing process. The gelling process was realized by using different types of anti-solvents. The carbon aerogel-acetic acid (CA-AA) has a specific surface area of 616.97 m2 g-1 and a specific capacitance of 138 F g-1 which is superior to cellulose-based active carbon. The CA was assembled into a SC, which showed excellent cycle stability. After charging and discharging 5000 times at the current density of 1 A g-1, the capacitance retention ratio of CA-AA reaches 102%. In addition, CA-AA has an energy density of 10.06 W h kg-1 when the power density is 181.06 W kg-1. It provides a choice for non-activation to effectively regulate the porous structure of biomass carbon materials.
RESUMEN
Background: In recent years, an increasing number of observational studies have reported the impact of air pollution on autoimmune diseases (ADs). However, no Mendelian randomization (MR) studies have been conducted to investigate the causal relationships. To enhance our understanding of causality, we examined the causal relationships between particulate matter (PM) and nitrogen oxides (NOx) and ADs. Methods: We utilized genome-wide association study (GWAS) data on PM and NOx from the UK Biobank in European and East Asian populations. We also extracted integrated GWAS data from the Finnish consortium and the Japanese Biobank for two-sample MR analysis. We employed inverse variance weighted (IVW) analysis to assess the causal relationship between PM and NOx exposure and ADs. Additionally, we conducted supplementary analyses using four methods, including IVW (fixed effects), weighted median, weighted mode, and simple mode, to further investigate this relationship. Results: In the European population, the results of MR analysis suggested a statistically significant association between PM2.5 and psoriasis only (OR = 3.86; 95% CI: 1.89-7.88; PIVW < 0.00625), while a potential association exists between PM2.5-10 and vitiligo (OR = 7.42; 95% CI: 1.02-53.94; PIVW < 0.05), as well as between PM2.5 and systemic lupus erythematosus (OR = 68.17; 95% CI: 2.17-2.1e+03; PIVW < 0.05). In East Asian populations, no causal relationship was found between air pollutants and the risk of systemic lupus erythematosus and rheumatoid arthritis (PIVW > 0.025). There was no pleiotropy in the results. Conclusion: Our results suggest a causal association between PM2.5 and psoriasis in European populations. With the help of air pollution prevention and control, the harmful progression of psoriasis may be slowed.
Asunto(s)
Contaminación del Aire , Enfermedades Autoinmunes , Lupus Eritematoso Sistémico , Psoriasis , Humanos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/genética , Contaminación del Aire/efectos adversos , Material Particulado/efectos adversos , Psoriasis/etiología , Psoriasis/genéticaRESUMEN
Stress response is a fundamental mechanism for cell survival, providing protection under unfavorable conditions. Mitochondrial stress, in particular, can trigger mitophagy, a process that restores cellular health. Exhaustive exercise (EE) is a form of acute mitochondrial stress. The objective of this current study is to investigate the impact of EE on tau pathology in pR5 mice, as well as the potential underlying mechanisms. To evaluate this, we examined the levels of total and phosphorylated tau in the hippocampus of pR5 mice, both with and without EE treatment. Furthermore, the application of weighted correlation network analysis (WGCNA) was employed to identify protein modules associated with the phenotype following the proteomic experiment. The findings of our study demonstrated a significant decrease in tau phosphorylation levels upon EE treatment, in comparison to the pR5 group. Moreover, the proteomic analysis provided additional insights, revealing that the mitigation of tau pathology was primarily attributed to the modulation of various pathways, such as translation factors and oxidative phosphorylation. Additionally, the analysis of heatmaps revealed a significant impact of EE treatment on the translation process and electron transport chain in pR5 mice. Furthermore, biochemical analysis provided further confirmation that EE treatment effectively modulated the ATP level in pR5 mice. In conclusion, our study suggests that the observed decrease in tau phosphorylation resulting from EE treatment may primarily be attributed to its regulation of the translation process and enhancement of mitochondrial function.
Asunto(s)
Enfermedad de Alzheimer , Fenómenos Biológicos , Ratones , Animales , Ratones Transgénicos , Fosforilación , Proteínas tau/genética , Proteínas tau/metabolismo , Transporte de Electrón , Proteómica , Fosforilación Oxidativa , Procesamiento Proteico-Postraduccional , Enfermedad de Alzheimer/genéticaRESUMEN
Background: Hyperuricemia is a common complication of type 2 diabetes mellitus and can lead to serious consequences such as gout and kidney disease. Methods: Patients with type 2 diabetes mellitus from six different communities in Fuzhou were recruited from June to December 2022. Questionnaires, physical examinations, and laboratory tests were conducted to collect data on various variables. Variable screening steps were performed using univariate and multivariate stepwise regression, least absolute shrinkage and selection operator (LASSO) regression, and Boruta feature selection. The dataset was divided into a training-testing set (80%) and an independent validation set (20%). Six machine learning models were built and validated. Results: A total of 8243 patients with type 2 diabetes mellitus were included in this study. According to Occam's razor method, the LASSO regression algorithm was determined to be the optimal risk factors selection method, and nine variables were identified as parameters for the risk assessment model. The absence of diabetes medication and elevated fasting blood glucose levels exhibited a negative correlation with the risk of hyperuricemia. Conversely, seven other variables demonstrated a positive association with the risk of hyperuricemia among patients diagnosed with type 2 diabetes mellitus. Among the six machine learning models, the artificial neural network (ANN) model demonstrated the highest performance. It achieved an areas under curve of 0.736, accuracy of 68.3%, sensitivity of 65.0%, specificity of 72.2%, precision of 73.6% and F1-score of 69.0%. Conclusions: We developed an ANN model to better evaluate the risk of hyperuricemia in the type 2 diabetes population. In the type 2 diabetes population, women should pay particular attention to their uric acid levels, and type 2 diabetics should not neglect their obesity level, blood pressure, kidney function and lipid profile during their regular medical check-ups, in order to do their best to avoid the risks associated with the combination of type 2 diabetes and hyperuricemia.
RESUMEN
Alzheimer's disease is the most common form of dementia and is characterized by cognitive impairment. The disruption of autophagosome-lysosome function has been linked to the pathogenesis of Alzheimer's disease. Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) is a widely used organophosphorus flame retardant that has the potential to cause neuronal damage. We found that TDCIPP significantly increased the expression of ß-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), presenilin-1 (PS1) and Aß42. Proteomic studies with TMT labeling revealed changes in the profiles of N2a-APPswe cells after exposure to TDCIPP. Proteomic and bioinformatics analyses revealed that lysosomal proteins were dysregulated in N2a-APPswe cells after treatment with TDCIPP. The LC3, P62, CTSD, and LAMP1 levels were increased after TDCIPP exposure, and dysregulated protein expression was validated by Western blotting. The exposure to TDCIPP led to the accumulation of autophagosomes, and this phenomenon was enhanced in the presence of chloroquine (CQ). Our results revealed for the first time that TDCIPP could be a potential environmental risk factor for AD development. The inhibition of autophagosome-lysosome fusion may have a significant impact on the generation of Aß1-42 in response to TDCIPP.