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Inflammatory bowel disease (IBD) is a chronic, debilitating condition with limited therapeutic options. Dietary components like blueberries have emerged as potential modulators of inflammation and tissue repair in gastrointestinal diseases. This study investigated endoplasmic reticulum (ER) stress-mediated apoptosis mediated protective effects of blueberries in ameliorating dextran sulfate sodium (DSS)-induced IBD. Firstly, a total of 86 anthocyanin compounds were identified in blueberry extract by LC-MS spectroscopy, including 35 cyanidin, 9 delphinidin, 14 malvidin, 10 peonidin, and 9 petunidin. Then, the animal study showed that blueberry supplementation notably ameliorated DSS-induced IBD symptoms, as evidenced by improved histopathological scores and a reduced disease activity index (DAI) score. Additionally, blueberries attenuated ER stress by inhibiting the colonic PERK/eIF2α/ATF4/CHOP signaling pathway. Furthermore, blueberries inhibited the expression of the pro-apoptotic protein, caspase-3, and decreased colonic apoptosis, as evidenced by TUNEL assay results. However, it did not affect the expression of anti-apoptotic proteins, bcl-2 and bcl-xl. Finally, blueberries enhanced the intestinal barrier by upregulating ZO-1, claudin-1, occludin, and E-cadherin. In conclusion, blueberries demonstrate therapeutic potential against DSS-induced IBD-like symptoms in mice, possibly by regulating ER stress-mediated apoptosis pathways. These findings suggest that blueberries might be an effective dietary intervention for IBD management.
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OBJECTIVES: To explore the impact of social support on CF and further clarify the mediating role of self-efficacy among Geriatric Services and Management interns. METHODS: A cross-sectional survey study examined social support, self-efficacy and CF in 592 interns in Geriatric Services and Management from 46 institutions in China. RESULT: The level of CF among Geriatric Services and Management interns is low but about one-third of the respondents is at high risk of CF. Social support was positively correlated with self-efficacy (ß = 0.114, P < 0.01). Social support significantly reduced CF (ß = -0.322, P < 0.01). Similarly, self-efficacy had significant direct effects on CF (ß = -0.497, P < 0.01). Additionally, self-efficacy played a partial mediating role in the relationship between social support and CF. CONCLUSION: Social support can directly affect the CF of Geriatric Services and Management interns and indirectly through self-efficacy. Accordingly, It is necessary to strengthen social support and self-efficacy to relieve CF among Geriatric Services and Management interns.
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Neuropathic pain (NP) is a chronic pain caused by injury or disease of the somatosensory nervous system, or it can be directly caused by disease. It often presents with clinical features like spontaneous pain, hyperalgesia, and dysesthesia. At present, voltage-gated calcium ion channels (VGCCs) are known to be closely related to the development of NP, especially the α2δ subunit. The α2δ subunit is a regulatory subunit of VGCCs. It exists mainly in the brain and peripheral nervous system, especially in nerve cells, and it plays a crucial part in regulating presynaptic and postsynaptic functions. Furthermore, the α2δ subunit influences neuronal excitation and pain signaling by promoting its expression and localization through binding to VGCC-related subunits. The α2δ subunit is widely used in the management of NP as a target of antiepileptic drugs gabapentin and pregabalin. Although drug therapy is one of the treatments for NP, its clinical application is limited due to the adverse reactions caused by drug therapy. Therefore, further research on the therapeutic target α2δ subunit is needed, and attempts are made to obtain an effective treatment for relieving NP without side effects. This review describes the current associated knowledge on the function of the α2δ subunit in perceiving and modulating NP.
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Cranberry is abundantly rich in anthocyanins, a type of flavonoid with potent antioxidant properties and the resistance against certain diseases. In this study, anthocyanin-rich cranberry extract was extracted, purified, and its components were analyzed. 92.18 % of anthocyanins was obtained and the total content of anthocyanins was 302.62 mg/g after AB-8 resin purification. Quantification analysis showed that the extract mainly contained cyanidin-3-galactoside, procyanidin B2 and procyanidin B4. Then we explored its effects on dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD) in mice. The supplementation of cranberry extract resulted in an alleviation of IBD symptoms, evidenced by improvements in the disease activity index (DAI), restoration of colon length and colonic morphology. Cranberry extract reversed the elevated iron and malondialdehyde (MDA) levels and restored glutathione (GSH) levels in IBD mice. Further analysis revealed that cranberry modulated ferroptosis-associated genes and reduced expression of pro-inflammatory cytokines. Although cranberry influenced the intestinal flora balance by reducing Proteobacteria and Escherichia-Shigella, and increasing Lactobacillus, as well as enhancing SCFAs content, these effects were not entirely dependent on intestinal flora modulation, as indicated by antibiotic intervention and fecal microbiota transplantation (FMT) experiments. In conclusion, our findings suggest that the beneficial impact of cranberry extract on IBD may primarily involve the regulation of colonic ferroptosis, independent of significant alterations in intestinal flora.
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Pulmonary hypertension (PH) is a chronic progressive vascular disease characterized by abnormal pulmonary vascular resistance and pulmonary artery pressure. The major structural alteration during PH is pulmonary vascular remodelling, which is mainly caused by the imbalance between proliferation and apoptosis of pulmonary vascular cells. Previously, it was thought that apoptosis was the only type of programmed cell death (PCD). Soon afterward, other types of PCD have been identified, including autophagy, pyroptosis, ferroptosis and necroptosis. In this review, we summarize the role of the above five forms of PCD in mediating pulmonary vascular remodelling, and discuss their guiding significance for PH treatment. The current review could provide a better understanding of the correlation between PCD and pulmonary vascular remodelling, contributing to identify new PCD-associated drug targets for PH.
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Apoptose , Hipertensão Pulmonar , Remodelação Vascular , Humanos , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Animais , Necroptose , Transdução de Sinais , Autofagia , Ferroptose , Artéria Pulmonar/patologia , Artéria Pulmonar/metabolismo , PiroptoseRESUMO
The mutual interactions of endoplasmic reticulum (ER) resident proteins in the ER maintain its functions, prompting the protein folding, modification, and transportation. Here, a new method, named YST-PPI (YESS-based Split fast TEV protease system for Protein-Protein Interaction) was developed, targeting the characterization of protein interactions in ER. YST-PPI method integrated the YESS system, split-TEV technology, and endoplasmic reticulum retention signal peptide (ERS) to provide an effective strategy for studying ER in situ PPIs in a fast and quantitative manner. The interactions among 15 ER-resident proteins, most being identified molecular chaperones, of S. cerevisiae were explored using the YST-PPI system, and their interaction network map was constructed, in which more than 74 interacting resident protein pairs were identified. Our studies also showed that Lhs1p plays a critical role in regulating the interactions of most of the ER-resident proteins, except the Sil1p, indicating its potential role in controlling the ER molecular chaperones. Moreover, the mutual interaction revealed by our studies further confirmed that the ER-resident proteins perform their functions in a cooperative way and a multimer complex might be formed during the process.
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Retículo Endoplasmático , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Retículo Endoplasmático/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Chaperonas Moleculares/metabolismo , Chaperonas Moleculares/genética , Mapas de Interação de Proteínas , Mapeamento de Interação de Proteínas/métodosRESUMO
Microglia respond to stressors by secreting cytokines or growth factors, playing a crucial role in maintaining brain homeostasis. While the antidepressant-like effects of Polygonatum sibiricum polysaccharides (PSPs) have been observed in mice, their potential effectiveness involving microglial regulation remains unknown. This study investigates the antidepressant-like mechanism of PSP by regulating microglial phenotype and signaling pathways in the prefrontal cortex of chronic restraint stress (CRS)-induced mice. PSP was extracted, purified, characterized, and orally administered to CRS mice. High-performance gel permeation chromatography (HPGPC) revealed that PSP has a molecular weight of 5.6 kDa. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) showed that PSP exhibited a layered structure with densely packed, irregular surfaces. PSP treatment significantly increased sucrose preference (low: 71%, p < 0.01; medium: 69%, p < 0.05; high: 75%, p < 0.001 vs. CRS: 58%) and reduced immobility time (low: 74 s, p < 0.01; medium: 68 s, p < 0.01; high: 79 s, p < 0.05 vs. CRS: 129 s), indicating the alleviation of depressive-like behaviors. PSP inhibited microglial activation (PSP, 131/mm2 vs. CRS, 173/mm2, p = 0.057), reversing CRS-induced microglial hypertrophy and hyper-ramification. Furthermore, PSP inactivated microglial activation by inhibiting NLRP3/ASC/caspase-1/IL-1ß signaling pathways, increasing BDNF synthesis and activating brain-derived neurotrophic factor (BDNF)-mediated neurogenesis (PSP, 80/per DG vs. CRS, 49/per DG, p < 0.01). In conclusion, PSP exerts antidepressant-like effects through the regulation of microglial activity and neuroinflammatory pathways, indicating it as a potential natural compound for depression treatment.
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Different empathic responses are often reported in autism but remain controversial. To investigate which component of empathy is most affected by autism, we examined the affective, cognitive, and motivational components of empathy in 25 5- to 8-year-old autistic and 27 neurotypical children. Participants were presented with visual stimuli depicting people's limbs in painful or nonpainful situations while their eye movements, pupillary responses, and verbal ratings of pain intensity and empathic concern were recorded. The results indicate an emotional overarousal and reduced empathic concern to others' pain in autism. Compared with neurotypical children, autistic children displayed larger pupil dilation accompanied by attentional avoidance to others' pain. Moreover, even though autistic children rated others in painful situations as painful, they felt less sorry than neurotypical children. Interestingly, autistic children felt more sorry in nonpainful situations compared with neurotypical children. These findings demonstrated an emotional overarousal in response to others' pain in autistic children, and provide important implications for clinical practice aiming to promote socio-emotional understanding in autistic children.
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Transtorno Autístico , Emoções , Empatia , Dor , Humanos , Empatia/fisiologia , Masculino , Criança , Feminino , Dor/psicologia , Dor/fisiopatologia , Transtorno Autístico/psicologia , Transtorno Autístico/fisiopatologia , Transtorno Autístico/complicações , Emoções/fisiologia , Pré-Escolar , Movimentos Oculares/fisiologia , Pupila/fisiologiaRESUMO
BACKGROUND: Streptococcus suis is an important zoonotic pathogen. Biofilm formation largely explains the difficulty in preventing and controlling S. suis. However, little is known about the molecular mechanism of S. suis biofilm formation. RESULTS: In this study, transcriptomic and metabolomic analyses of S. suis in biofilm and planktonic states were performed to identify key genes and metabolites involved in biofilm formation. A total of 789 differential genes and 365 differential metabolites were identified. By integrating transcriptomics and metabolomics, five main metabolic pathways were identified, including amino acid pathway, nucleotide metabolism pathway, carbon metabolism pathway, vitamin and cofactor metabolism pathway, and aminoacyl-tRNA biosynthesis metabolic pathway. CONCLUSIONS: These results provide new insights for exploring the molecular mechanism of S. suis biofilm formation.
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Biofilmes , Streptococcus suis , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Redes e Vias Metabólicas/genética , Metaboloma , Metabolômica , Multiômica , Streptococcus suis/genética , Streptococcus suis/metabolismo , TranscriptomaRESUMO
The deficit in social interaction skills among individuals with autism spectrum disorder (ASD) is strongly influenced by personal experiences and social environments. Neuroimaging studies have previously highlighted the link between social impairment and brain activity in ASD. This study aims to develop a method for assessing and identifying ASD using a social cognitive game-based paradigm combined with electroencephalo-graphy (EEG) signaling features. Typically developing (TD) participants and autistic preadolescents and teenagers were recruited to participate in a social game while 12-channel EEG signals were recorded. The EEG signals underwent preprocessing to analyze local brain activities, including event-related potentials (ERPs) and time-frequency features. Additionally, the global brain network's functional connectivity between brain regions was evaluated using phase-lag indices (PLIs). Subsequently, machine learning models were employed to assess the neurophysiological features. Results indicated pronounced ERP components, particularly the late positive potential (LPP), in parietal regions during social training. Autistic preadolescents and teenagers exhibited lower LPP amplitudes and larger P200 amplitudes compared to TD participants. Reduced theta synchronization was also observed in the ASD group. Aberrant functional connectivity within certain time intervals was noted in the ASD group. Machine learning analysis revealed that support-vector machines achieved a sensitivity of 100%, specificity of 91.7%, and accuracy of 95.8% as part of the performance evaluation when utilizing ERP and brain oscillation features for ASD characterization. These findings suggest that social interaction difficulties in autism are linked to specific brain activation patterns. Traditional behavioral assessments face challenges of subjectivity and accuracy, indicating the potential use of social training interfaces and EEG features for cognitive assessment in ASD.
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Transtorno do Espectro Autista , Eletroencefalografia , Potenciais Evocados , Aprendizado de Máquina , Humanos , Transtorno do Espectro Autista/fisiopatologia , Adolescente , Eletroencefalografia/métodos , Criança , Masculino , Feminino , Potenciais Evocados/fisiologia , Córtex Cerebral/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Jogos de Vídeo , Algoritmos , Smartphone , Interação SocialRESUMO
A growing number of studies have associated walkability and greenspace exposure with greater physical activity (PA) in women during pregnancy. However, most studies have focused on examining women's residential environments and neglected exposure in locations outside the home neighborhood. Using 350 person-days (N = 55 participants) of smartphone global positioning system (GPS) location and accelerometer data collected during the first and third trimesters and 4-6 months postpartum from 55 Hispanic pregnant women from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study, we examined the day-level effect of women's exposure to walkability and greenspace on their PA outcomes during pregnancy and in the early postpartum period. Moderate-to-vigorous physical activity [MVPA] minutes per day was assessed using accelerometers. Walkability and greenspace were measured using geographic information systems (GIS) within women's daily activity spaces (i.e., places visited and routes taken) recorded using a smartphone GPS and weighted by time spent. We used a generalized linear mixed-effects model to estimate the effects of daily GPS-derived environmental exposures on day-level MVPA minutes. Results showed that women engaged in 23% more MVPA minutes on days when they had some versus no exposure to parks and open spaces in activity spaces (b = 1.23; 95%CI: 1.02-1.48). In addition, protective effects of daily greenspace and walkability exposure on MVPA were stronger in the first and third trimesters, among first-time mothers, and among women who had high pre-pregnancy body mass index (BMI) and lived in least-safe neighborhoods. Our results suggest that daily greenspace and walkability exposure are important for women's PA and associated health outcomes during pregnancy and early postpartum.
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OBJECTIVE: To investigate global optimisation of anterior acetabular column pinning channels can be achieved based on large density point cloud data. METHODS: Data were collected on the CT scans of the normal pelvis in 40 adults from January 2022 to January 2023, including 22 males and 18 females, aged 20 to 54 years old. Medical imaging data from three of the samples were selected for experimental study. In planning access for anterior acetabular column pinning, to address the issue of whether the current CAD planning methods were advanced or not, four combinations of the same point cloud acquisition channels, different directional line creation software, and the same 3D design and virtual experiment software were proposed: Mimics+Imageware+UG, Mimics+3DReshaper+UG, Mimics+ZEISS Quality Suite+UG and Mimics+Design X+UG, and directional lines created based on the centroid point set and solid point cloud of the secondary pruning model, respectively, and it applied to the planning of the left anterior column pinning channel of the three acetabular samples. The maximum internally connected cylinder without acetabular socket and pubic bone penetration was used as a safe passage for nailing of the anterior acetabular column to evaluate the advancement of each method. RESULTS: The fitting effect of the directional line was better than that of the unnoised solid point cloud when the central point set with obvious relevant features was selected as the sample points;and the combination of Mimics+Imageware+UG and Mimics+3DReshaper+UG could efficiently and stably obtain the desirable planning results when planning with the central point set, respectively, in the three acetabular samples 1, 2, 3. The maximum internal joint circle diameters obtained in samples 1, 2, and 3 were 10.35 mm, 9.62 mm, and 9.24 mm;and when the directional lines were based on the solid point cloud the combined methods of Mimics+ZEISS Quality Suite+UG and Mimics+Design X+UG were not applicable;whereas the Mimics+3DReshaper+UG the solid point cloud denoising planning method could stably obtain the maximum value of the safe channel for nail placement, and the maximum internal joint circle diameters obtained in acetabular samples 1, 2, and 3 are 10.66 mm, 10.96 mm, and 9.48 mm, respectively. CONCLUSION: It is recommended that the nail placement channel planners use robust Mimics+Imageware+UG or Mimics+3DReshaper+UG centre point set planning method, and if there is enough time, it is recommended to use the solid point cloud denoising planning method of Mimics+3DReshaper+UG in order to obtain the maximum value of safe channels for nail placement.
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Acetábulo , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Acetábulo/cirurgia , Acetábulo/diagnóstico por imagem , Pinos Ortopédicos , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
OBJECTIVE: To explore the potential action mechanism of Huotu Jiji Pellets (HJP) in the treatment of erectile dysfunction (ED) based on network pharmacology and molecular docking. METHODS: We identified the main effective compounds and active molecular targets of HJP from the database of Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Integrative Pharmacology-Based Research Platform of Traditional Chinese Medicine (TCMIP) and the therapeutic target genes of ED from the databases of Genecards. Then we obtained the common targets of HJP and ED using the Venny software, constructed a protein-protein interaction (PPI) network of HJP acting on ED, and screened out the core targets with the Cytoscape software. Lastly we performed GO functional enrichment and KEGG pathway enrichment analyses of the core targets followed by molecular docking of HJP and the core targets using Chem3D and AutoDock Tools and QuickVina-W software. RESULTS: A total of 64 effective compounds, 822 drug-related targets, 1 783 disease-related targets and 320 common targets were obtained in this study. PPI network analysis showed that the core targets of HJP for ED included ESR1, HSP90AA1, SRC, and STAT3. GO functional enrichment analysis indicated the involvement of the core targets in such biological processes as response to xenobiotic stimulus, positive regulation of kinase activity, and positive regulation of MAPK cascade. KEGG pathway enrichment analysis suggested that PI3K-Akt, apoptosis, MAPK, HIF-1, VEGF, autophagy and other signaling pathways may be related to the mechanism of HJP acting on ED. Molecular docking prediction exhibited a good docking activity of the key active molecules of HJP with the core targets. CONCLUSION: This study showed that HJP acted on ED through multi-components, multi-targets and multi-pathways, which has provided some evidence and reference for the clinical treatment and subsequent studies of the disease.
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Medicamentos de Ervas Chinesas , Disfunção Erétil , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Farmacologia em Rede , Mapas de Interação de Proteínas , Masculino , Disfunção Erétil/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Transdução de SinaisRESUMO
Autistic individuals encounter challenges in recognizing emotional expressions of others. Pupillary response has been proposed as an indicator of arousal dysregulation or cognitive load. The pupillary response of autistic individuals during socio-affective tasks remains unclear. This study investigated pupillary response in autistic adults when viewing emotional faces/eyes and recognizing emotions during the Reading the Mind in the Eyes Test (RMET) and watching interpersonal touch scenes in the social touch task. The study included 98 participants diagnosed with autism spectrum disorder and 37 typically developing controls (TD). Pupil size was measured using the Tobii X2-30 Eye Tracker. The results showed that autistic adults had larger maximal pupil sizes, smaller minimal pupil sizes, and greater change rates of pupil size, particularly during the RMET Eyes task. Clinical correlations revealed that attention switching difficulty positively correlated with mean pupil size in TD participants, while social communication deficits positively correlated with mean pupil size in autistic participants. In conclusion, our findings suggest atypical pupillary responses in autistic adults during socio-affective tasks, indicating heightened cognitive demand. Further investigation is necessary to understand the underlying mechanisms and their association with autistic traits.
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Ginsenoside Rb1, known as gypenoside III, exerts antidepressant-like effects in previous studies. It has also been indicated that ginsenoside Rb1 regulated neuroinflammation via inhibiting NF-κB signaling. According to the evidence that astrocytes can regulate microglia and neuroinflammation by secreting complement C3, the present study aimed to demonstrate the molecular mechanisms underlying ginsenoside Rb1-induced antidepressant-like effects from the astrocytic and microglial complement C3 pathway. The complement C3 mediated mechanism of ginsenoside Rb1 was investigated in mice exposed to chronic restraint stress (CRS). The results showed that ginsenoside Rb1 reversed the depressive-like behaviors in CRS. Treatment with ginsenoside Rb1 reduced both the number of astrocytes and microglia. In addition, ginsenoside Rb1 suppressed TLR4/NF-κB/C3 signaling in the astrocytes of the hippocampus. Furthermore, ginsenoside Rb1 attenuated the contents of synaptic protein including synaptophysin and PSD95 in microglia, suggesting the inhibition of microglia-mediated synaptic elimination caused by CRS. Importantly, ginsenoside Rb1 also maintained the dendritic spines in mice. In conclusion, our results demonstrate that ginsenoside Rb1 produces the antidepressant-like effects by inhibiting astrocyte TLR4/NF-κB/C3 signaling to covert microglia from a pro-inflammatory phenotype (amoeboid) towards an anti-inflammatory phenotype (ramified), which inhibit the synaptic pruning in the hippocampus.
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Astrócitos , Complemento C3 , Depressão , Ginsenosídeos , Microglia , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Camundongos , Depressão/tratamento farmacológico , Depressão/metabolismo , Masculino , Complemento C3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Camundongos Endogâmicos C57BL , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Receptor 4 Toll-Like/metabolismo , Estresse Psicológico/metabolismo , Estresse Psicológico/tratamento farmacológico , NF-kappa B/metabolismoRESUMO
Histone lysine crotonylation, an evolutionarily conserved modification differing from acetylation, exerts pivotal control over diverse biological processes. Among these are gene transcriptional regulation, spermatogenesis, and cell cycle processes. However, the dynamic changes and functions of histone crotonylation in preimplantation embryonic development in mammals remain unclear. Here, we show that the transcription coactivator P300 functions as a writer of histone crotonylation during embryonic development. Depletion of P300 results in significant developmental defects and dysregulation of the transcriptome of embryos. Importantly, we demonstrate that P300 catalyzes the crotonylation of histone, directly stimulating transcription and regulating gene expression, thereby ensuring successful progression of embryo development up to the blastocyst stage. Moreover, the modification of histone H3 lysine 18 crotonylation (H3K18cr) is primarily localized to active promoter regions. This modification serves as a distinctive epigenetic indicator of crucial transcriptional regulators, facilitating the activation of gene transcription. Together, our results propose a model wherein P300-mediated histone crotonylation plays a crucial role in regulating the fate of embryonic development.
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Blastocisto , Proteína p300 Associada a E1A , Desenvolvimento Embrionário , Regulação da Expressão Gênica no Desenvolvimento , Histonas , Lisina , Histonas/metabolismo , Animais , Desenvolvimento Embrionário/genética , Feminino , Camundongos , Proteína p300 Associada a E1A/metabolismo , Proteína p300 Associada a E1A/genética , Blastocisto/metabolismo , Lisina/metabolismo , Humanos , Processamento de Proteína Pós-Traducional , Regiões Promotoras Genéticas , Epigênese Genética , MasculinoRESUMO
Introduction: Humanization is typically adopted to reduce the immunogenicity of murine antibodies generated by hybridoma technology when used in humans. Methods: Two different strategies of antibody humanization are popularly employed, including "complementarity determining region (CDR) grafting" and "framework (FR) shuffling" to humanize a murine antibody against human programmed death-1 (PD-1), XM PD1. In CDR-grafting humanization, the CDRs of XM PD-1, were grafted into the human FR regions with high homology to the murine FR counterparts, and back mutations of key residues were performed to retain the antigen-binding affinities. While in FR-shuffling humanization, a combinatorial library of the six murine CDRs in-frame of XM PD-1 was constructed to a pool of human germline FRs for high-throughput screening for the most favorable variants. We evaluated many aspects which were important during antibody development of the molecules obtained by the two methods, including antibody purity, thermal stability, binding efficacy, predicted humanness, and immunogenicity, along with T cell epitope prediction for the humanized antibodies. Results: While the ideal molecule was not achieved through CDR grafting in this particular instance, FR-shuffling proved successful in identifying a suitable candidate. The study highlights FR-shuffling as an effective complementary approach that potentially increases the success rate of antibody humanization. It is particularly noted for its accessibility to those with a biological rather than a computational background. Discussion: The insights from this comparison are intended to assist other researchers in selecting appropriate humanization strategies for drug development, contributing to broader application and understanding in the field.
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Regiões Determinantes de Complementaridade , Receptor de Morte Celular Programada 1 , Animais , Humanos , Camundongos , Receptor de Morte Celular Programada 1/imunologia , Regiões Determinantes de Complementaridade/imunologia , Regiões Determinantes de Complementaridade/genética , Anticorpos Monoclonais Humanizados/imunologia , Epitopos de Linfócito T/imunologiaRESUMO
Seahorses are increasingly recognized for their nutritional potential, which underscores the necessity for comprehensive biochemical analyses. This study aims to investigate the fatty acid and amino acid compositions of eight seahorse species, including both genders of Hippocampus trimaculatus, Hippocampus kelloggi, Hippocampus abdominalis, and Hippocampus erectus, to evaluate their nutritional value. We employed Gas Chromatography-Mass Spectrometry (GC-MS) and High-Performance Liquid Chromatography (HPLC) to analyze the fatty acid and amino acid profiles of the seahorse species. GC-MS was used to detect 34 fatty acid methyl esters, while HPLC provided detailed amino acid profiles. GC-MS analysis demonstrated high precision with relative standard deviations (RSDs) generally below 2.53 %, satisfactory repeatability (RSDs from 6.55 % to 8.73 %), and stability (RSDs below 2.82 %). Recovery rates for major fatty acids ranged from 98.73 % to 109.12 %. HPLC analysis showed strong separation of amino acid profiles with theoretical plate numbers exceeding 5000. Precision tests yielded RSDs below 1.23 %, with reproducibility and stability tests showing RSDs below 2.73 % and 2.86 %, respectively. Amino acid recovery rates ranged from 97.58 % to 104.66 %. Nutritional analysis revealed significant variations in fatty acid content among the species. Female H. erectus showed higher levels of hexadecanoic acid and saturated fatty acids, while male H. abdominalis had lower concentrations of n-3 full cis 4,7,10,13,16,19-docosahexaenoic acid (DHA). Total lipid yields varied from 3.2491 % to 12.3175 %, with major fatty acids constituting 17.9717 %-74.6962 % of total lipids. In conclusion, this study provides essential insights into the fatty acid and amino acid composition of seahorses, supporting their potential as valuable dietary supplements. The differences between genders in specific fatty acids suggest a nuanced nutritional profile that could be exploited for targeted dietary applications. Further research is needed to explore the seasonal and environmental variations affecting seahorse biochemical composition.
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BACKGROUND: Serum neurofilament light chain (sNfL) has been identified as a biomarker for neurologic diseases. However, sNfL remains unknown to be responsible for depression. AIMS: The aim of this research was to explore the relationship between sNfL levels and depression in US adults. METHODS: In this cross-sectional survey of the general population, we investigated representative data involving 10,175 participants from the 2013-2014 cycle of the National Health and Nutrition Examination Survey (NHANES). Depression was diagnosed using the Patient Health Questionnaire-9 (PHQ-9). The effect of related factors on depression was analyzed by conducting a univariate analysis. Stratified analysis was utilized to detect the stability and sensitivity of the relationship. After adjusting for race, education, marital status, smoking status, body mass index (BMI), sleep duration, income, and a history of hypertension, sedentary behavior and stroke, multivariable linear regression was performed to demonstrate the correlation between sNfL and depression. RESULTS: A total of 1301 individuals between the ages of 20 and 75 were involved in this investigation, of which 108 (8.3%) were diagnosed with depression. A significant positive correlation between sNfL and depression among adults in the US was observed by conducting univariable analyses. After adjusting for confounding factors, the multivariate analyses indicated that elevated sNfL levels might play a pivotal role in the development of depression (odds ratio (OR) = 3.0; 95% confidence interval (CI): (1.5, 6.1), P = 0.002). CONCLUSION: These results indicated that sNfL is closely linked to depression in a nationally representative individual. However, further studies are needed to confirm the biological mechanism as well as the clinical implications of sNfL and depression.