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1.
FEBS Open Bio ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39054261

RESUMO

Although most cognitive impairments induced by prolonged alcohol consumption tend to improve within the initial months of abstinence, there is evidence suggesting certain cognitive deficits may persist. This study aimed to investigate the impact of aerobic exercise on learning and memory in alcohol use disorder (AUD) mice following a period of abstinence from alcohol. We also sought to assess the levels of monoamine neurotransmitters in the hippocampus. To this end, we established an AUD mouse model through a two-bottle choice (sucrose fading mode and normal mode) and chronic intermittent alcohol vapor (combined with intraperitoneal injection) and randomly allocated mice into exercise groups to undergo treadmill training. Learning and memory abilities were assessed through the Morris water maze test and spontaneous activity was evaluated using the open field test. The levels of dopamine, norepinephrine, serotonin, and brain-derived neurotrophic factor in the hippocampus were quantified using enzyme-linked immunoassay (ELISA) kits. The findings reveal that after cessation of alcohol consumption, learning and memory abilities in AUD mice did not completely return to normal levels. The observed enhancement of cognitive functions in AUD mice through aerobic exercise may be attributed to restoring levels of monoamine neurotransmitters in the hippocampus, boosting brain-derived neurotrophic factor (BDNF) concentrations, and facilitating an increase in hippocampal mass. These results offer empirical evidence to support aerobic exercise as a viable therapeutic strategy to alleviate cognitive deficits associated with AUD.

2.
Mol Immunol ; 171: 105-114, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38820902

RESUMO

Chlamydia trachomatis (CT) is the leading cause of bacterial sexually transmitted diseases worldwide, which can cause diseases such as pelvic inflammatory disease, and cervical and fallopian tube inflammation, and poses a threat to human health. Rosmarinic acid (RosA) is an active ingredient of natural products with anti-inflammatory and immunomodulatory effects. This study aimed to investigate the role of RosA in inhibiting autophagy-regulated immune cells-CD8+ T cells via the Ras/Raf/MEK/ERK signaling pathway in a CT-infected mouse model. Mice were inoculated with CT infection solution vaginally, and the mechanistic basis of RosA treatment was established using H&E staining, flow cytometry, immunofluorescence, transmission electron microscopy, and western blot. The key factors involved in RosA treatment were further validated using the MEK inhibitor cobimetinib. Experimental results showed that both RosA and the reference drug azithromycin could attenuate the pathological damage to the endometrium caused by CT infection; flow cytometry showed that peripheral blood CD8+ T cells increased after CT infection and decreased after treatment with RosA and the positive drug azithromycin (positive control); immunofluorescence showed that endometrial CD8 and LC3 increased after CT infection and decreased after RosA and positive drug treatment; the results of transmission electron microscopy showed that RosA and the positive drug azithromycin inhibited the accumulation of autophagosomes; western bolt experiments confirmed the activation of autophagy proteins LC3Ⅱ/Ⅰ, ATG5, Beclin-1, and p62 after CT infection, as well as the inhibition of Ras/Raf/MEK/ERK signaling. RosA and azithromycin inhibition of autophagy proteins activates Ras/Raf/MEK/ERK signaling. In addition, the MEK inhibitor cobimetinib attenuated RosA's protective effect on endometrium by further activating CD8+ T cells on a CT-induced basis, while transmission electron microscopy, immunofluorescence, and western blots showed that cobimetinib blocked ERK signals activation and further induced phagocytosis on a CT-induced basis. These data indicated that RosA can activate the Ras/Raf/MEK/ERK signaling pathway to inhibit autophagy, and RosA could also regulate the activation of immune cells-CD8+T cells to protect the reproductive tract of CT-infected mice.


Assuntos
Autofagia , Linfócitos T CD8-Positivos , Infecções por Chlamydia , Chlamydia trachomatis , Cinamatos , Depsídeos , Sistema de Sinalização das MAP Quinases , Ácido Rosmarínico , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Feminino , Infecções por Chlamydia/imunologia , Infecções por Chlamydia/tratamento farmacológico , Chlamydia trachomatis/efeitos dos fármacos , Chlamydia trachomatis/imunologia , Camundongos , Depsídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Cinamatos/farmacologia , Proteínas ras/metabolismo , Quinases raf/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
3.
Neurosci Biobehav Rev ; 162: 105695, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38710424

RESUMO

Predicting repetitive transcranial magnetic stimulation (rTMS) treatment outcomes in major depressive disorder (MDD) could reduce the financial and psychological risks of treatment failure. We systematically reviewed and meta-analyzed studies that leveraged neurophysiological and neuroimaging markers to predict rTMS response in MDD. Five databases were searched from inception to May 25, 2023. The primary meta-analytic outcome was predictive accuracy pooled from classification models. Regression models were summarized qualitatively. A promising marker was identified if it showed a sensitivity and specificity of 80% or higher in at least two independent studies. Searching yielded 36 studies. Twenty-two classification modeling studies produced an estimated area under the summary receiver operating characteristic curve of 0.87 (95% CI = 0.83-0.92), with 86.8% sensitivity (95% CI = 80.6-91.2%) and 81.9% specificity (95% CI = 76.1-86.4%). Frontal theta cordance measured by electroencephalography is closest to proof of concept. Predicting rTMS response using neurophysiological and neuroimaging markers is promising for clinical decision-making. However, replications by different research groups are needed to establish rigorous markers.


Assuntos
Transtorno Depressivo Maior , Neuroimagem , Estimulação Magnética Transcraniana , Humanos , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/fisiopatologia , Eletroencefalografia , Resultado do Tratamento
4.
Lasers Med Sci ; 39(1): 89, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38453744

RESUMO

Various treatment modalities have been applied to atrophic scars. Fractional CO2 laser treatment has attracted increasingly more attention because of its quicker recovery time and fewer side effects. However, its limitation of sculpting the edge is an urgent shortcoming. In order to achieve a more effective result with fewer complications, we have integrated ultrapulse CO2 and fractional CO2 lasers to for the treatment of facial atrophic scars. The study included 25 patients (10 males and 15 females) diagnosed with moderate to severe atrophic scars between August 2020 and July 2022. All subjects underwent the same surgical treatment. The effects were assessed at baseline, 1 week, 1 month, and 3 months using photographic evidence. Objective evaluation of the results was conducted using a quartile grading scale, while the subjects' satisfaction and any adverse events were also recorded. The patients in the study underwent more than two laser sessions (2-5), resulting in substantial improvement in their appearance. The time interval between each session was 3-6 months. The majority of the patients (19/25, 76%) had a significant or even excellent improvement. Any adverse events observed, such as erythema, superficial crusting, and PIH, were of a mild nature and temporary in duration. This treatment combined two CO2 lasers is an effective and safe choice for atrophic scars in Asians.


Assuntos
Acne Vulgar , Lasers de Gás , Masculino , Feminino , Humanos , Cicatriz/patologia , Dióxido de Carbono , Resultado do Tratamento , Acne Vulgar/complicações , Eritema/etiologia , Lasers de Gás/uso terapêutico , Atrofia/complicações
5.
Dalton Trans ; 53(11): 5133-5146, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38380458

RESUMO

The adjustment of crystal symmetry and intramolecular magnetic coupling is of great importance for the construction of high-performance single-molecule magnets. By using an aggregation-induced-emission-active pyridine-carbohydrazone-based Schiff base ligand and phosphine oxides, four dinuclear and one one-dimensional DyIII-based complexes, [Dy2(TPE-pc)2(Bu3PO)2Cl2]·2CH3CN·2H2O (1), [Dy2(TPE-pc)2(Cy3PO)2Cl2] (2), [Dy2(TPE-pc)2(MePA)2Cl2]·2CH3OH (3), [Dy2(TPE-pc)2(Ph3PO)2Cl2]2 (4) and [Dy2(TPE-pc)2(DPPO)Cl2]n (5) (H2TPE-pc = (E)-N'-(2-hydroxy-5-(1,2,2-triphenylvinyl)benzylidene)picolinohydrazide, MePA = N-phenyl-N',N''-bis(morpholinyl) phosphoric triamide, DPPO = piperazine-1,4-diylbis(diphenyl phosphine oxide)), were isolated. All complexes are made up of an enol oxygen-bridged Dy2 unit, where DyIII ions possess a pentagonal bipyramidal geometry with pseudo D5h symmetry. Magnetic measurements reveal that intramolecular DyIII-DyIII couplings are ferromagnetic and all complexes display a significant slow magnetic relaxation phenomenon below 30 K under a zero dc field. Ab initio calculations indicate that the anisotropic magnetic axes of all DyIII ions are approximately perpendicular to the higher-order symmetric axes in all complexes, and that DyIII-DyIII magnetic couplings along the magnetic axes effectively suppress the ground state quantum tunneling effect of magnetization and promote the occurrence of slow magnetic relaxation. Raman relaxation prevails in all complexes. In addition, the H2TPE-pc ligand shows an aggregation-induced emission (AIE) effect; however, all complexes exhibit an aggregation-caused quenching (ACQ) phenomenon.

6.
Nat Struct Mol Biol ; 31(2): 232-245, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38177673

RESUMO

Autophagy is a lysosome-dependent degradation pathway essential for cellular homeostasis, which decreases with age. However, it is unclear how aging induces autophagy decline. Here we show the role of protein S-palmitoylation in autophagy. We identify the palmitoyl acyltransferase DHHC5 as a regulator of autophagy by mediating the palmitoylation of beclin 1, which in turn promotes the formation of ATG14L-containing class III phosphatidylinositol-3-kinase complex I and its lipid kinase activity by promoting the hydrophobic interactions between beclin 1 and adapter proteins ATG14L and VPS15. In aging brains of human and nonhuman primate, the levels of DHHC5 exhibit a marked decrease in expression. We show that DHHC5 deficiency in neurons leads to reduced cellular protein homeostasis in two established murine models of Alzheimer's disease, which exaggerates neurodegeneration in an autophagy-dependent manner. These findings identify reduction of DHHC5-mediated beclin 1 S-palmitoylation as an underlying mechanism by which aging induces autophagy decline.


Assuntos
Aciltransferases , Proteínas Reguladoras de Apoptose , Autofagia , Proteína Beclina-1 , Lipoilação , Animais , Humanos , Camundongos , Aciltransferases/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Proteínas de Membrana/metabolismo , Fosforilação
7.
Indian J Ophthalmol ; 72(Suppl 2): S162-S166, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38271412

RESUMO

The purpose of this study is to examine the viability, precision, and consistency of a computer-based optokinetic nystagmus analyzer (nystagmus meter) for diagnosing eyesight in preschoolers. A total of 59 subjects who could pass the log of minimum angle of resolution (LogMAR) visual acuity chart were divided into three groups by age, 4-, 5-, and 6-year-old groups, and their visual acuity was tested with nystagmus meter. The percentage of children in each age group that could be detected by nystagmus was recorded along with the differences between these groups. The correlation between the test results from the two methods was found for each age group using the correlation coefficient method. Repeated measurements were used to assess the two visual acuity values of the measured nystagmus, and the repeatability of the two measurement techniques for different age groups was compared. The overall measurability of the visual acuity detected by nystagmus was 93.22%, and the measurability of the 4-, 5-, and 6-year-old groups was 90%, 95%, and 94.74%, respectively. There was no statistically significant difference in the measurability of subjects among all age groups (P = 1.0). The outcomes of the LogMAR visual acuity chart had a negative correlation with the visual acuity measured by the nystagmus meter. The overall correlation coefficient R value was -0.80, and the correlation coefficient R value of the 4-, 5-, and 6-year-old groups was -0.79, -0.76, and -0.87, respectively. The nystagmus meter has good feasibility, accuracy, and stability in visual acuity testing and can be used for visual acuity testing in children.


Assuntos
Nistagmo Optocinético , Nistagmo Patológico , Humanos , Pré-Escolar , Nistagmo Patológico/diagnóstico , Acuidade Visual , Testes Visuais , Computadores
8.
Proc Natl Acad Sci U S A ; 121(6): e2320383121, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38289948

RESUMO

Rett syndrome (RTT) is a devastating neurodevelopmental disorder primarily caused by mutations in the methyl-CpG binding protein 2 (Mecp2) gene. Here, we found that inhibition of Receptor-Interacting Serine/Threonine-Protein Kinase 1 (RIPK1) kinase ameliorated progression of motor dysfunction after onset and prolonged the survival of Mecp2-null mice. Microglia were activated early in myeloid Mecp2-deficient mice, which was inhibited upon inactivation of RIPK1 kinase. RIPK1 inhibition in Mecp2-deficient microglia reduced oxidative stress, cytokines production and induction of SLC7A11, SLC38A1, and GLS, which mediate the release of glutamate. Mecp2-deficient microglia release high levels of glutamate to impair glutamate-mediated excitatory neurotransmission and promote increased levels of GluA1 and GluA2/3 proteins in vivo, which was reduced upon RIPK1 inhibition. Thus, activation of RIPK1 kinase in Mecp2-deficient microglia may be involved both in the onset and progression of RTT.


Assuntos
Síndrome de Rett , Animais , Camundongos , Ácido Glutâmico/metabolismo , Inflamação/genética , Inflamação/metabolismo , Proteína 2 de Ligação a Metil-CpG/metabolismo , Camundongos Knockout , Microglia/metabolismo , Síndrome de Rett/metabolismo
9.
Huan Jing Ke Xue ; 44(9): 4809-4818, 2023 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-37699800

RESUMO

Based on OMI remote sensing satellite data, the temporal and spatial characteristics of tropospheric ozone (O3), nitrogen dioxide (NO2), and formaldehyde (HCHO) concentrations in East China from 2005 to 2021 were analyzed, and the backward trajectory (HYSPLIT) model was used to explore their sources. The results showed that ① during the 17 years, the tropospheric O3 concentration steadily increased, reached the maximum value in 2010, and then showed a fluctuating and undulating state. NO2 showed an increasing trend from 2005 to 2012 and slowly decreased from 2012 to 2021. The average HCHO concentration showed an increasing trend from 1.15×1016molec·cm-2 in 2005 to 1.8×1016 molec·cm-2 in 2021. ② In terms of spatial characteristics, the concentrations of the three pollutants generally showed a pattern of high concentration in the north and low concentration in the south, with a high concentration in the north, uncharacteristic concentration in the middle, and low concentration in the south. ③ The sensitivity of O3 was as follows:η<2.3 in spring, which belonged to the VOCs control area; η<4.2 in summer, showing that most areas were NOx-VOCs coordinated control areas and a few areas were VOCs control areas; η<4.2 in autumn, which was primarily controlled by VOCs, with a few of them being NOx-VOC synergistic control areas; and η<2.3 in winter, which was a VOCs-controlled area. VOCs were primarily controlled in Shandong Province. ④ Owing to the high concentration of O3 in Shandong Province from 2005 to 2021, Jinan, the capital city of Shandong Province in 2021, was selected for ozone source analysis. The O3 concentration increased in Jinan in 2021 owing to two aspects. First, the long-distance air transportation primarily originated from Lianyungang City in Jiangsu Province and Cangzhou City in Hebei Province. Second, the close air mass transport originated from the pollution of cities near Jinan and the economic zones of the Yellow Sea and Bohai Sea, and the aggregation analysis results corresponded with those of the potential source contribution factor algorithm (PSCF) and the weighted trajectory analysis (CWT).

10.
ACS Appl Mater Interfaces ; 15(32): 38693-38706, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37542464

RESUMO

Inspired by life's interaction networks, ongoing efforts are to increase complexity and responsiveness of multicomponent interactions in the system for sensing, programmable control, or information processing. Although exquisite preparation of single uniform-morphology nanomaterials has been extremely explored, the potential value of facile and one-pot preparation of multimorphology nanomaterials has been seriously ignored. Here, multimorphological silver nanomaterials (M-AgN) prepared by one pot can form interaction networks with various analytes, which can be successfully realized from multimode and multianalyte colorimetric sensing to molecular information technology (logic computing and security). The interaction of M-AgN with multianalytes not only induces multisignal responses (including color, absorbance, and wavelength shift) for sensing metal ions (Cr3+, Hg2+, and Ni2+) but also can controllably reshape its four morphologies (nanodots, nanoparticles, nanorods, and nanotriangles). By abstracting binary relationships between analytes and response signals, multicoding parallel logic operations (including simple logic gates and cascaded circuits) can be performed. In addition, taking advantage of natural concealment and molecular response characteristics of M-AgN nanosystems can also realize molecular information encoding, encryption, and hiding. This research not only promotes the construction and application of multinano interaction systems based on multimorphology and multicomponent nanoset but also provides a new imagination for the integration of sensing, logic, and informatization.

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