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1.
Elife ; 122024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592269

RESUMO

Visual detection is a fundamental natural task. Detection becomes more challenging as the similarity between the target and the background in which it is embedded increases, a phenomenon termed 'similarity masking'. To test the hypothesis that V1 contributes to similarity masking, we used voltage sensitive dye imaging (VSDI) to measure V1 population responses while macaque monkeys performed a detection task under varying levels of target-background similarity. Paradoxically, we find that during an initial transient phase, V1 responses to the target are enhanced, rather than suppressed, by target-background similarity. This effect reverses in the second phase of the response, so that in this phase V1 signals are positively correlated with the behavioral effect of similarity. Finally, we show that a simple model with delayed divisive normalization can qualitatively account for our findings. Overall, our results support the hypothesis that a nonlinear gain control mechanism in V1 contributes to perceptual similarity masking.


Assuntos
Macaca , Primatas , Animais , Mascaramento Perceptivo , Imagens com Corantes Sensíveis à Voltagem
2.
Drug Des Devel Ther ; 18: 1103-1114, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38618283

RESUMO

Purpose: Intravenous regional anesthesia (IVRA) using lidocaine provides effective localized analgesia but its duration is limited. The mechanism by which dexmedetomidine enhances lidocaine IVRA is unclear but may involve modulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Materials and Methods: Lidocaine IVRA with varying dexmedetomidine concentrations was performed in the tails of Sprague-Dawley rats. Tail-flick and tail-clamping tests assessed IVRA analgesia and anesthesia efficacy and duration. Contributions of α2 adrenergic receptors and HCN channels were evaluated by incorporating an α adrenergic receptor antagonist, the HCN channel inhibitor ZD7288, and the HCN channel agonist forskolin. Furthermore, whole-cell patch clamp electrophysiology quantified the effects of dexmedetomidine on HCN channels mediating hyperpolarization-activated cation current (Ih) in isolated dorsal root ganglion neurons. Results: Dexmedetomidine dose-dependently extended lidocaine IVRA duration and analgesia, unaffected by α2 receptor blockade. The HCN channel inhibitor ZD7288 also prolonged lidocaine IVRA effects, while the HCN channel activator forskolin shortened effects. In dorsal root ganglion neurons, dexmedetomidine concentration-dependently inhibited Ih amplitude and shifted the voltage-dependence of HCN channel activation. Conclusion: Dexmedetomidine prolongs lidocaine IVRA duration by directly inhibiting HCN channel activity, independent of α2 adrenergic receptor activation. This HCN channel inhibition represents a novel mechanism underlying the anesthetic and analgesic adjuvant effects of dexmedetomidine in IVRA.


Assuntos
Anestesia por Condução , Dexmedetomidina , Ratos , Animais , Lidocaína/farmacologia , Dexmedetomidina/farmacologia , Ratos Sprague-Dawley , Colforsina , Cátions
3.
Orthop Surg ; 16(4): 902-911, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38444378

RESUMO

OBJECTIVE: The best method for femoral fixation in anterior cruciate ligament reconstruction (ACLR) remains controversial. The study assesses the bone tunnel enlargement and clinical outcome in hamstring ACLR using cortical suspension or hybrid (cortical suspension and compression) femoral fixation. METHODS: From January 2010 to December 2021, 102 patients who underwent quadruple hamstring ACLR using cortical suspension (39 patients) or hybrid (63 patients) fixation on the femoral side were retrospectively analyzed. Clinical evaluation was conducted using the international knee documentation committee score, the Lysholm score, the Tegner activity level scale, the knee injury and osteoarthritis outcome score (quality of life score), the Lachman test, and the side-to-side difference by the KT-1000 arthrometer. The complications after the surgery were also evaluated. These data were compared at baseline and last follow-up. The diameters of the femoral tunnel were calculated at three sites: the width of the entrance of the femoral tunnel, 1 cm proximal to the entrance of the femoral tunnel and the largest diameter of the femoral tunnel on magnetic resonance imaging (MRI) coronal images. Bone tunnel widening data were contrasted between MRI images conducted at least 2 years and within 2 weeks after surgery. The morphology of bone tunnel enlargement was also observed and recorded. The categorical parameters were analyzed using the χ2-test and Fisher's exact test. The continuous variables conforming to a normal distribution were analyzed using Student's t-test, and the Mann-Whitney U-test was undertaken between the two groups without normal distribution. RESULTS: Both cortical suspension and hybrid femoral fixation in quadruple hamstring ACLR achieved significantly improved patient-reported outcome scores and knee stability compared to preoperative data. However, no significant differences were found between these two methods in clinical evaluations, postoperative complications, and patient-reported outcome scores. Although the mean diameter of the enlarged bone tunnel was lowered by an additional bioabsorbable interference screw fixation near the joint line, a statistically insignificant difference was found between the hybrid and cortical suspension fixation on the femoral side. There was no statistical difference in the distribution of enlarged bone tunnel morphology between groups. CONCLUSIONS: No significant difference was found in the bone tunnel enlargement and clinical outcome between cortical suspension and hybrid femoral fixation in ACLR using hamstring autograft.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Tendões dos Músculos Isquiotibiais , Humanos , Ligamento Cruzado Anterior , Estudos Retrospectivos , Qualidade de Vida , Tendões dos Músculos Isquiotibiais/transplante , Articulação do Joelho/cirurgia , Fêmur/cirurgia , Fêmur/patologia , Reconstrução do Ligamento Cruzado Anterior/métodos , Lesões do Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/patologia , Tíbia/cirurgia
4.
Nat Commun ; 15(1): 1271, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341403

RESUMO

Mesoscopic calcium imaging enables studies of cell-type specific neural activity over large areas. A growing body of literature suggests that neural activity can be different when animals are free to move compared to when they are restrained. Unfortunately, existing systems for imaging calcium dynamics over large areas in non-human primates (NHPs) are table-top devices that require restraint of the animal's head. Here, we demonstrate an imaging device capable of imaging mesoscale calcium activity in a head-unrestrained male non-human primate. We successfully miniaturize our system by replacing lenses with an optical mask and computational algorithms. The resulting lensless microscope can fit comfortably on an NHP, allowing its head to move freely while imaging. We are able to measure orientation columns maps over a 20 mm2 field-of-view in a head-unrestrained macaque. Our work establishes mesoscopic imaging using a lensless microscope as a powerful approach for studying neural activity under more naturalistic conditions.


Assuntos
Cálcio , Microscopia , Masculino , Animais , Primatas
5.
Heliyon ; 9(12): e22155, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38125500

RESUMO

Background: Polycystic ovary syndrome (PCOS) is a multifaceted endocrine and metabolic syndrome with complex origins and pathogenesis that has not yet been fully elucidated. Recently, the interconnection between gut microbiota and metabolic diseases has gained prominence in research, generating new insights into the correlation between PCOS and gut microbiota composition. However, the causal link between PCOS and gut microbiota remains relatively unexplored, indicating a crucial gap in current research. Methods: We conducted a two-sample Mendelian randomization analysis using summary statistics obtained from the MiBioGen Consortium's extensive genome-wide association studies (GWAS) meta-analysis, focusing on the gut microbiota. Summary statistics for PCOS were acquired from the FinnGen Consortium R7 release data. Various statistical approaches, including inverse variance weighted, MR-Egger, maximum likelihood, weighted model, and weighted median, have been employed to investigate the causal association between the gut microbiota and PCOS. Additionally, we performed a reverse causal analysis. Cochran's Q statistic was used to assess the heterogeneity of the instrumental variables. Regarding the relationships between PCOS and specific genera within the gut microbiota, a significance level of P < 0.05 was observed, but only when q ≥ 0.1. Results: Our analysis revealed that specific microbial genera, namely Bilophila (P = 4.62 × 10-3), Blautia (P = 0.02), and Holdemania (P = 0.04), displayed a protective effect against PCOS. Conversely, the presence of the Lachnospiraceae family of bacteria was associated with a detrimental effect on PCOS (P = 0.04). Furthermore, reverse Mendelian randomization analysis confirmed the significant influence of Lachnospiraceae on PCOS. No significant variations in instrumental variables or evidence of horizontal pleiotropy were observed. Conclusions: The results revealed a definitive causal link between PCOS and the presence of Bilophila, Blautia, Holdemania, and Lachnospiraceae in the gut microbiota. This discovery could provide pivotal insights, leading to novel preventive and therapeutic approaches for PCOS.

6.
Chem Res Toxicol ; 36(11): 1814-1825, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37906555

RESUMO

Hydroxyl radical (·OH)-initiated oxidation of isoprene, the most abundant nonmethane hydrocarbon in the atmosphere, is responsible for substantial amounts of secondary organic aerosol (SOA) within ambient fine particles. Fine particulate 2-methyltetrol sulfate diastereoisomers (2-MTSs) are abundant SOA products formed via acid-catalyzed multiphase chemistry of isoprene-derived epoxydiols with inorganic sulfate aerosols under low-nitric oxide conditions. We recently demonstrated that heterogeneous ·OH oxidation of particulate 2-MTSs leads to the particle-phase formation of multifunctional organosulfates (OSs). However, it remains uncertain if atmospheric chemical aging of particulate 2-MTSs induces toxic effects within human lung cells. We show that inhibitory concentration-50 (IC50) values decreased from exposure to fine particulate 2-MTSs that were heterogeneously aged for 0 to 22 days by ·OH, indicating increased particulate toxicity in BEAS-2B lung cells. Lung cells further exhibited concentration-dependent modulation of oxidative stress- and inflammatory-related gene expression. Principal component analysis was carried out on the chemical mixtures and revealed positive correlations between exposure to aged multifunctional OSs and altered expression of targeted genes. Exposure to particulate 2-MTSs alone was associated with an altered expression of antireactive oxygen species (ROS)-related genes (NQO-1, SOD-2, and CAT) indicative of a response to ROS in the cells. Increased aging of particulate 2-MTSs by ·OH exposure was associated with an increased expression of glutathione pathway-related genes (GCLM and GCLC) and an anti-inflammatory gene (IL-10).


Assuntos
Butadienos , Estresse Oxidativo , Humanos , Idoso , Espécies Reativas de Oxigênio , Oxirredução , Butadienos/toxicidade
7.
Biosensors (Basel) ; 13(10)2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37887133

RESUMO

In this paper, a tapered fiber bioprobe based on Mach-Zehnder interference (MZI) is proposed. To retain the highly sensitive straight-tapered fiber MZI sensing structure, we designed a U-shaped transmission fiber structure for the collection of optical sensing signals to achieve a miniature-insert-probe design. The spectrum responses from the conventional straight-tapered fiber MZI sensor and our proposed sensor were compared and analyzed, and experimental results showed that our proposed sensor not only has the same sensing capability as the straight-tapered fiber sensor, but also has the advantages of being flexible, convenient, and less liquid-consuming, which are attributed to the inserted probe design. The tapered fiber bioprobe obtained a sensitivity of 1611.27 nm/RIU in the refractive index detection range of 1.3326-1.3414. Finally, immunoassays for different concentrations of human immunoglobulin G were achieved with the tapered fiber bioprobe through surface functionalization, and the detection limit was 45 ng/mL. Our tapered fiber bioprobe has the insert-probe advantages of simpleness, convenience, and fast operation. Simultaneously, it is low-cost, highly sensitive, and has a low detection limit, which means it has potential applications in immunoassays and early medical diagnosis.


Assuntos
Técnicas Biossensoriais , Fibras Ópticas , Humanos , Interferometria/métodos , Refratometria/métodos , Imunoensaio
8.
Environ Pollut ; 339: 122731, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37839680

RESUMO

Polycyclic aromatic hydrocarbons (PAHs), in particular benzo [a]pyrene (BaP), have been identified as carcinogenic components of tobacco smoke. In mammals, the toxicological response to BaP-diol-epoxide is driven by cytochrome P450 (CYP1A1), a pathway which is absent in Caenorhabditis elegans. In contrast, in worms prominently the CYP-35 enzyme family seems to be induced after BaP exposure. In C. elegans, BaP exposure reduces the accumulation of lysosomal neutral lipids in a dose dependent manner and the deletion of cyp-35A2 results in a significant elevation of neutral lipid metabolism. A cyp-35A2:mCherry;unc-47:GFP dual-labelled reporter strain facilitated the identification of three potential upstream regulators that drive BaP metabolism in worms, namely elt-2, nhr-49 and fos-1. This newly described reporter line is a powerful resource for future large-scale RNAi regarding toxicology and lipid metabolism screens.


Assuntos
Proteínas de Caenorhabditis elegans , Carcinógenos Ambientais , Animais , Benzo(a)pireno/toxicidade , Benzo(a)pireno/metabolismo , Caenorhabditis elegans/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Lipídeos , Mamíferos/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores
9.
Opt Express ; 31(17): 28161-28173, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37710877

RESUMO

We propose a three-wavelength elliptically polarized light photoelasticity method for high efficiency and low-cost stress measurement. By illuminating the sample with two different forms of elliptically polarized light for each wavelength sources, twelve images are acquired. From these images, phase delay and the principal internal stress difference are precisely computed using developed algorithms. Our proposed method based on an LCD panel has the unrivalled advantage that elliptically polarized light can be automatically adjusted, which reduces the mechanical rotation of the system, in contrast to the traditional six-step phase-shifting photoelasticity method, which requires manual rotation for circularly polarized light. In addition, the system has the potential to theoretically expand the area of illumination infinitely, thereby expanding the measurement area. The viability of the suggested methods is confirmed with numerical simulation and stress measurement.

10.
Environ Sci Technol ; 57(38): 14182-14193, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37708377

RESUMO

Recent studies have shown that instantaneous gas-particle equilibrium partitioning assumptions fail to predict SOA formation, even at high relative humidity (∼85%), and photochemical aging seems to be one driving factor. In this study, we probe the minimum aging time scale required to observe nonequilibrium partitioning of semivolatile organic compounds (SVOCs) between the gas and aerosol phase at ∼50% RH. Seed isoprene SOA is generated by photo-oxidation in the presence of effloresced ammonium sulfate seeds at <1 ppbv NOx, aged photochemically or in the dark for 0.3-6 h, and subsequently exposed to fresh isoprene SVOCs. Our results show that the equilibrium partitioning assumption is accurate for fresh isoprene SOA but breaks down after isoprene SOA has been aged for as short as 20 min even in the dark. Modeling results show that a semisolid SOA phase state is necessary to reproduce the observed particle size distribution evolution. The observed nonequilibrium partitioning behavior and inferred semisolid phase state are corroborated by offline mass spectrometric analysis on the bulk aerosol particles showing the formation of organosulfates and oligomers. The unexpected short time scale for the phase transition within isoprene SOA has important implications for the growth of atmospheric ultrafine particles to climate-relevant sizes.


Assuntos
Poluentes Atmosféricos , Hemiterpenos , Material Particulado , Butadienos , Compostos Orgânicos , Aerossóis
11.
J Biomol Struct Dyn ; : 1-15, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37555593

RESUMO

Allosteric effectors play an important role in regulating the oxygen supply efficiency of hemoglobin for blood storage and disease treatment. However, allosteric effectors that are approved by the US FDA are limited. In this study, cefmetazole sodium (CS) was found to bind adult hemoglobin (HbA) from FDA library (1338 compounds) using surface plasmon resonance imaging high-throughput screening. Using surface plasmon resonance (SPR), the interaction between CS and HbA was verified. The oxygen dissociation curve of HbA after CS interaction showed a significant increase in P50 and theoretical oxygen-release capacity. Acid-base sensitivity (SI) exhibited a decreasing trend, although not significantly different. An oxygen dissociation assay indicated that CS accelerated HbA deoxygenation. Microfluidic modulated spectroscopy showed that CS changed the ratio of the alpha-helix to the beta-sheet of HbA. Molecular docking suggested CS bound to HbA's ß-chains via hydrogen bonds, with key amino acids being N282, K225, H545, K625, K675, and V544.The results of molecular dynamics simulations (MD) revealed a stable orientation of the HbA-CS complex. CS did not significantly affect the P50 of bovine hemoglobin, possibly due to the lack of Valß1 and Hisß2, indicating that these were the crucial amino acids involved in HbA's oxygen affinity. Competition between the 2,3-Diphosphoglycerate (2,3-DPG) and CS in the HbA interaction was also determined by SPR, molecular docking and MD. In summary, CS could interact with HbA and regulate the oxygen supply efficiency via forming stable hydrogen bonds with the ß-chains of HbA, and showed competition with 2,3-DPG.Communicated by Ramaswamy H. Sarma.

12.
Research (Wash D C) ; 6: 0205, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37521328

RESUMO

Infectious diseases severely threaten public health and global biosafety. In addition to transmission through the air, pathogenic microorganisms have also been detected in environmental liquid samples, such as sewage water. Conventional biochemical detection methodologies are time-consuming and cost-ineffective, and their detection limits hinder early diagnosis. In the present study, ultrafine plasmonic fiber probes with a diameter of 125 µm are fabricated for clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas)-12a-mediated sensing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Single-stranded DNA exposed on the fiber surface is trans-cleaved by the Cas12a enzyme to release gold nanoparticles that are immobilized onto the fiber surface, causing a sharp reduction in the surface plasmon resonance (SPR) wavelength. The proposed fiber probe is virus-specific with the limit of detection of ~2,300 copies/ml, and genomic copy numbers can be reflected as shifts in wavelengths. A total of 21 sewage water samples have been examined, and the data obtained are consistent with those of quantitative polymerase chain reaction (qPCR). In addition, the Omicron variant and its mutation sites have been fast detected using S gene-specific Cas12a. This study provides an accurate and convenient approach for the real-time surveillance of microbial contamination in sewage water.

13.
bioRxiv ; 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37503133

RESUMO

Visual detection is a fundamental natural task. Detection becomes more challenging as the similarity between the target and the background in which it is embedded increases, a phenomenon termed "similarity masking". To test the hypothesis that V1 contributes to similarity masking, we used voltage sensitive dye imaging (VSDI) to measure V1 population responses while macaque monkeys performed a detection task under varying levels of target-background similarity. Paradoxically, we find that during an initial transient phase, V1 responses to the target are enhanced, rather than suppressed, by target-background similarity. This effect reverses in the second phase of the response, so that in this phase V1 signals are positively correlated with the behavioral effect of similarity. Finally, we show that a simple model with delayed divisive normalization can qualitatively account for our findings. Overall, our results support the hypothesis that a nonlinear gain control mechanism in V1 contributes to perceptual similarity masking.

14.
ACS Nano ; 17(13): 12903-12914, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37384815

RESUMO

The urgent necessity for highly sensitive diagnostic tools has been accentuated by the ongoing mpox (monkeypox) virus pandemic due to the complexity in identifying asymptomatic and presymptomatic carriers. Traditional polymerase chain reaction-based tests, despite their effectiveness, are hampered by limited specificity, expensive and bulky equipment, labor-intensive operations, and time-consuming procedures. In this study, we present a clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a-based diagnostic platform with a surface plasmon resonance-based fiber tip (CRISPR-SPR-FT) biosensor. The compact CRISPR-SPR-FT biosensor, with a 125 µm diameter, offers high stability and portability, enabling exceptional specificity for mpox diagnosis and precise identification of samples with a fatal mutation site (L108F) in the F8L gene. The CRISPR-SPR-FT system can analyze viral double-stranded DNA from mpox virus without amplification in under 1.5 h with a limit of detection below 5 aM in plasmids and about 59.5 copies/µL when in pseudovirus-spiked blood samples. Our CRISPR-SPR-FT biosensor thus offers fast, sensitive, portable, and accurate target nucleic acid sequence detection.


Assuntos
Técnicas Biossensoriais , Humanos , Vírus da Varíola dos Macacos , Genótipo , Mutação , Pandemias
15.
J Phys Chem A ; 127(18): 4125-4136, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37129903

RESUMO

The phase states and glass transition temperatures (Tg) of secondary organic aerosol (SOA) particles are important to resolve for understanding the formation, growth, and fate of SOA as well as their cloud formation properties. Currently, there is a limited understanding of how Tg changes with the composition of organic and inorganic components of atmospheric aerosol. Using broadband dielectric spectroscopy, we measured the Tg of organic mixtures containing isoprene epoxydiol (IEPOX)-derived SOA components, including 2-methyltetrols (2-MT), 2-methyltetrol-sulfate (2-MTS), and 3-methyltetrol-sulfate (3-MTS). The results demonstrate that the Tg of mixtures depends on their composition. The Kwei equation, a modified Gordon-Taylor equation with an added quadratic term and a fitting parameter representing strong intermolecular interactions, provides a good fit for the Tg-composition relationship of complex mixtures. By combining Raman spectroscopy with geometry optimization simulations obtained using density functional theory, we demonstrate that the non-linear deviation of Tg as a function of composition may be caused by changes in the extent of hydrogen bonding in the mixture.

16.
Biotechnol J ; 18(9): e2300062, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37177911

RESUMO

Although the Mos1-mediated single-copy insertion (MosSCI) technique has been widely used to generate stable transgenic Caenorhabditis elegans strains, the link between stability of expression and integration site still needs to be explored. Here, experimental evidence is provided that transgenes are not able to match the level of transcription of their native counterpart, and that insertions at certain locations can result in an external stress-mediated increase in expression. Insertion site ttTi5605 on chromosome II was shown to be a superior location, at least when introducing reproduction related genes. Thus, this study provides a reference for the selection of an optimal site for MosSCI which provides acceptable expression performance whilst minimizing undesirable secondary effects.


Assuntos
Caenorhabditis elegans , Genoma , Animais , Animais Geneticamente Modificados/genética , Mutagênese Insercional , Transgenes/genética , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Genômica , Expressão Gênica
17.
Inflamm Res ; 72(6): 1161-1173, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37188940

RESUMO

OBJECTIVE AND DESIGN: Postoperative cognitive dysfunction (POCD) is a common complication following surgery among elderly patients. Emerging evidence demonstrates that neuroinflammation plays a pivotal role in the pathogenesis of POCD. This study tested the hypothesis that fluoxetine can protect against POCD by suppressing hippocampal neuroinflammation through attenuating TLR4/MyD88/NF-κB signaling pathway activation. SUBJECTS: Aged C57BL/6 J male mice (18 months old) were studied. TREATMENT: Aged mice were intraperitoneally injected with fluoxetine (10 mg/kg) or saline for seven days before splenectomy. In addition, aged mice received an intracerebroventricular injection of a TLR4 agonist or saline seven days before splenectomy in the rescue experiment. METHODS: On postoperative days 1, 3, and 7, we assessed hippocampus-dependent memory, microglial activation status, proinflammatory cytokine levels, protein levels related to the TLR4/MyD88/NF-κB signaling pathway, and hippocampal neural apoptosis in our aged mouse model. RESULTS: Splenectomy induced a decline in spatial cognition, paralleled by parameters indicating exacerbation of hippocampal neuroinflammation. Fluoxetine pretreatment partially restored the deteriorated cognitive function, downregulated proinflammatory cytokine levels, restrained microglial activation, alleviated neural apoptosis, and suppressed the increase in TLR4, MyD88, and p-NF-κB p65 in microglia. Intracerebroventricular injection of LPS (1 µg, 0.5 µg/µL) before surgery weakened the effect of fluoxetine. CONCLUSION: Fluoxetine pretreatment suppressed hippocampal neuroinflammation and mitigated POCD by inhibiting microglial TLR4/MyD88/NF-κB pathway activation in aged mice.


Assuntos
NF-kappa B , Complicações Cognitivas Pós-Operatórias , Camundongos , Masculino , Animais , NF-kappa B/metabolismo , Complicações Cognitivas Pós-Operatórias/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Fluoxetina/metabolismo , Receptor 4 Toll-Like/metabolismo , Doenças Neuroinflamatórias , Camundongos Endogâmicos C57BL , Transdução de Sinais , Citocinas/metabolismo , Microglia/metabolismo
18.
Molecules ; 28(5)2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36903296

RESUMO

Acute altitude hypoxia represents the cause of multiple adverse consequences. Current treatments are limited by side effects. Recent studies have shown the protective effects of resveratrol (RSV), but the mechanism remains unknown. To address this, the effects of RSV on the structure and function of hemoglobin of adult (HbA) were preliminarily analyzed using surface plasmon resonance (SPR) and oxygen dissociation assays (ODA). Molecular docking was conducted to specifically analyze the binding regions between RSV and HbA. The thermal stability was characterized to further validate the authenticity and effect of binding. Changes in the oxygen supply efficiency of HbA and rat RBCs incubated with RSV were detected ex vivo. The effect of RSV on the anti-hypoxic capacity under acute hypoxic conditions in vivo was evaluated. We found that RSV binds to the heme region of HbA following a concentration gradient and affects the structural stability and rate of oxygen release of HbA. RSV enhances the oxygen supply efficiency of HbA and rat RBCs ex vivo. RSV prolongs the tolerance times of mice suffering from acute asphyxia. By enhancing the oxygen supply efficiency, it alleviates the detrimental effects of acute severe hypoxia. In conclusion, RSV binds to HbA and regulates its conformation, which enhances oxygen supply efficiency and improves adaption to acute severe hypoxia.


Assuntos
Hemoglobinas , Hipóxia , Animais , Camundongos , Ratos , Resveratrol , Simulação de Acoplamento Molecular , Hemoglobinas/química , Oxigênio/química
19.
Front Neurol ; 13: 1034894, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36468044

RESUMO

Background: Body composition analysis is a valuable tool for assessing and monitoring the nutritional status of children with spinal muscular atrophy (SMA). This study was designed to compare the consistency of bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA), as the gold standard method for assessing body composition in clinical practice when treating children with type II and III SMA. Methods: From 2019 to 2021, we performed a retrospective analysis of body composition by DXA and BIA measurement methods in patients with type II and III SMA treated at a Chinese tertiary children's hospital. Fat mass (FM), muscle mass (MM), bone mineral content (BMC), and visceral fat area (VFA) were compared using paired sample t-tests. We calculated Lin's concordance correlation coefficient (CCC) and Spearman correlation coefficient to verify the correlation between DXA and BIA measurements. Bland-Altman analysis was used to assess the consistency of the two methods. Results: Fifty-seven children with type II and III SMA were recruited. Compared with body composition measured by DXA, the average FM measured by BIA is significantly lower (P <0.001), whereas the average MM, BMC, and VFA measured by BIA are significantly higher (P < 0.001) in children with SMA. Overall, the difference between MM (Delta [BIA-DAX] = 1.6 kg) and FM (Delta [BIA-DAX] = -1.6 kg) measured by DXA and BIA was minor, whereas the difference of VFA (Delta [BIA-DAX] = -43.5 cm) was significantly large. Correlation analysis indicated a substantial correlation of MM (CCC = 0.96 [95% confidence interval (CI) = 0.93-0.98], r = 0.967 [P < 0.0001]) and FM (CCC = 0.95 [95% CI = 0.92-0.97], r = 0.953 [P < 0.0001]), and poor correlation of BMC (CCC = 0.61 [95% CI = 0.42-0.75], r = 0.612 [P < 0.0001]) and VFA (CCC = 0.54 [95% CI = 0.33-0.70], r = 0.689 [P < 0.0001]) measurements between the two methods. The Bland-Altman analysis suggests that the majority of participants were within LOA. In addition, differences in MM and VFA measurements between BIA and DAX increased according to patients' increasing height, whereas differences in FM and BMC did not differ with height. Conclusion: BIA overestimates MM and underestimates the FM, BMC, and VFA in children with SMA compared with DXA measurements. Overall, the non-invasive, easy-to-use, and repeatable BIA measurements were found to be in good agreement with DXA measurements, especially for FM and MM, which are essential parameters for the nutritional evaluation of children with SMA.

20.
Int J Environ Health Res ; : 1-9, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36473101

RESUMO

A case-control study was conducted to examine the association of particulate matter exposure during the pre-natal (the first, second, and third trimesters. and the whole pregnancy) and post-natal periods (the first year after birth) with childhood asthma in Beijing, China. Multivariable logistic regressions showed that childhood asthma was significantly associated with exposures to PM2.5 and PM10 during the entire pregnancy, with ORs of 1.28(95%CI:1.06-1.56) and 1.21(95%CI:1.02-1.42), respectively. The highest association with a 10 µg/m3 increase in PM2.5 and PM10 were both seen for the second trimester, with ORs of 1.17(95% CI: 1.05-1.30) and 1.14(95% CI: 1.04-1.24). Subgroup analyses suggested that significant and positive effects were subject to be observed in children with a family history of atopy. This study added evidence that exposures to PM2.5 and PM10 during pregnancy might increase the risk of childhood asthma in seriously polluted area, highlighting stronger associations in the second trimester.

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