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Teleost testis development during the annual cycle involves dramatic changes in cellular compositions and molecular events. In this study, the testicular cells derived from adult black rockfish at distinct stages - regressed, regenerating and differentiating - were meticulously dissected via single-cell transcriptome sequencing. A continuous developmental trajectory of spermatogenic cells, from spermatogonia to spermatids, was delineated, elucidating the molecular events involved in spermatogenesis. Subsequently, the dynamic regulation of gene expression associated with spermatogonia proliferation and differentiation was observed across spermatogonia subgroups and developmental stages. A bioenergetic transition from glycolysis to mitochondrial respiration of spermatogonia during the annual developmental cycle was demonstrated, and a deeper level of heterogeneity and molecular characteristics was revealed by re-clustering analysis. Additionally, the developmental trajectory of Sertoli cells was delineated, alongside the divergence of Leydig cells and macrophages. Moreover, the interaction network between testicular micro-environment somatic cells and spermatogenic cells was established. Overall, our study provides detailed information on both germ and somatic cells within teleost testes during the annual reproductive cycle, which lays the foundation for spermatogenesis regulation and germplasm preservation of endangered species.
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Espermatogônias , Testículo , Adulto , Masculino , Humanos , Células Intersticiais do Testículo , Células de Sertoli , EspermatogêneseRESUMO
Gastric cancer (GC) is a major global health concern with poor outcomes. Heterogeneous nuclear ribonucleoprotein U (HNRNPU) is a multifunctional protein that participates in pre-mRNA packaging, alternative splicing regulation, and chromatin remodeling. Its potential role in GC remains unclear. In this study, the expression characteristics of HNRNPU were analyzed by The Cancer Genome Atlas data, Gene Expression Omnibus data, and then further identified by real-time quantitative PCR and immunohistochemistry using tissue specimens. From superficial gastritis, atrophic gastritis, and hyperplasia to GC, the in situ expression of HNRNPU protein gradually increased, and the areas under the curve for diagnosis of GC and its precancerous lesions were 0.911 and 0.847, respectively. A nomogram integrating HNRNPU expression, lymph node metastasis, and other prognostic indicators exhibited an area under the curve of 0.785 for predicting survival risk. Knockdown of HNRNPU significantly inhibited GC cell proliferation, migration, and invasion and promoted apoptosis in vitro. In addition, RNA-sequencing analysis showed that HNRNPU could affect alternative splicing events in GC cells, with functional enrichment analysis revealing that HNRNPU may exert malignant biological function in GC progression through alternative splicing regulation. In summary, the increased expression of HNRNPU was significantly associated with the development of GC, with a good performance in diagnosing and predicting the prognostic risk of GC. Functionally, HNRNPU may play an oncogenic role in GC by regulating alternative splicing.
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Neoplasias Gástricas , Humanos , Processamento Alternativo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas Grupo U/genética , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismoRESUMO
BACKGROUND: Due to its enormous biomass, Antarctic krill (Euphausia superba) plays a crucial role in the Antarctic Ocean ecosystem. In recent years, Antarctic krill has found extensive application in aquaculture, emerging as a sustainable source of aquafeed with ideal nutritional profiles. However, a comprehensive study focused on the detailed effects of dietary Antarctic krill on aquaculture animals, especially farmed marine fishes, is yet to be demonstrated. RESULTS: In this study, a comparative experiment was performed using juvenile P. leopardus, fed with diets supplemented with Antarctic krill (the krill group) or without Antarctic krill (the control group). Histological observation revealed that dietary Antarctic krill could reduce lipid accumulation in the liver while the intestine exhibited no obvious changes. Enzyme activity measurements demonstrated that dietary Antarctic krill had an inhibitory effect on oxidative stress in both the intestine and the liver. By comparative transcriptome analysis, a total of 1,597 and 1,161 differentially expressed genes (DEGs) were identified in the intestine and liver, respectively. Functional analysis of the DEGs showed multiple enriched terms significantly related to cholesterol metabolism, antioxidants, and immunity. Furthermore, the expression profiles of representative DEGs, such as dhcr7, apoa4, sc5d, and scarf1, were validated by qRT-PCR and fluorescence in situ hybridization. Finally, a comparative transcriptome analysis was performed to demonstrate the biased effects of dietary Antarctic krill and astaxanthin on the liver of P. leopardus. CONCLUSIONS: Our study demonstrated that dietary Antarctic krill could reduce lipid accumulation in the liver of P. leopardus, enhance antioxidant capacities in both the intestine and liver, and exhibit molecular-level improvements in lipid metabolism, immunity, and antioxidants. It will contribute to understanding the protective effects of Antarctic krill in P. leopardus and provide insights into aquaculture nutritional strategies.
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Bass , Euphausiacea , Animais , Antioxidantes , Euphausiacea/genética , Ecossistema , Hibridização in Situ Fluorescente , Perfilação da Expressão Gênica , Dieta , Bass/genética , Lipídeos , Regiões AntárticasRESUMO
Growing evidence indicates that activation of cannabinoid type 2 (CB2) receptors protects dopamine neurons in the pathogenesis of Parkinson's disease (PD). However, the mechanisms underlying neuroprotection mediated by CB2 receptors are still elusive. In this study, we investigated the effects of CB2 receptor activation on 6-hydroxydopamine (6-OHDA)-induced dopamine neuron degeneration and iron accumulation in the substantia nigra (SN) of rats. We found that treatment with JWH133, a selective CB2 receptor agonist, significantly improved the apomorphine (APO)-induced rotational behavior in 6-OHDA-treated rats. The decreased numbers of tyrosine hydroxylase (TH)-positive neurons and reduced TH protein expression in the lesioned SN of rats were effectively restored by JWH133. Moreover, we found that JWH133 inhibited the increase of iron-staining cells in the lesioned SN of rats. To explore the protective mechanisms of activation of CB2 receptors on dopamine neurons, we further observed the effect of JWH133 on 1-methyl-4-phenylpyridinium (MPP+)-treated primary cultured ventral mesencephalon (VM) neurons from rats. We found that JWH133 significantly inhibited the increase of intracellular reactive oxygen species (ROS), the activation of Caspase-3, the decrease of mitochondrial transmembrane potential (ΔΨm), and the decrease of Bcl-2/Bax protein expression caused by MPP+ treatment. JWH133 also inhibited the MPP+-induced upregulation of divalent metal transporter-1 (DMT1) and downregulation of ferroportin 1 (FPN1). Furthermore, JWH133 also suppressed the MPP+-accelerated iron influx in the VM neurons. These results suggest that activation of CB2 receptor suppresses MPP+-induced cellular iron accumulation and prevents neurodegeneration.NEW & NOTEWORTHY Expression of cannabinoid type 2 receptors (CB2Rs) was discovered on dopamine neurons in recent years. The role of CB2R expressed on dopamine neurons in the pathogenesis of Parkinson's disease (PD) has not been fully elucidated. The content of iron accumulation in the brain is closely related to the progress of PD. We verified the inhibitory effect of CB2R on iron deposition in dopamine neurons through experiments, which provided a new idea for the treatment of PD.
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Canabinoides , Neurônios Dopaminérgicos , Ferro , Oxidopamina , Ratos Sprague-Dawley , Receptor CB2 de Canabinoide , Animais , Masculino , Canabinoides/farmacologia , Ratos , Ferro/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Receptor CB2 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/agonistas , Substância Negra/metabolismo , Substância Negra/efeitos dos fármacos , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/induzido quimicamente , Tirosina 3-Mono-Oxigenase/metabolismo , Modelos Animais de Doenças , Fármacos Neuroprotetores/farmacologia , Agonistas de Receptores de Canabinoides/farmacologiaRESUMO
The leopard coral grouper (Plectropomus leopardus), which has become increasingly popular in consumption due to its bright body color and great nutritional, holds a high economic and breeding potential. However, in recent years, the P.leopardus aquaculture industry has been impeded by the nervous necrosis virus (NNV) outbreak, leading to widespread mortality among fry and juvenile grouper. However, the genetic basis of resistance to NNV in P. leopardus remains to be investigated. In the present study, we conducted a genome-wide association analysis (GWAS) on 100 resistant and 100 susceptible samples to discover variants and potential genes linked with NNV resistance. For this study, 157,926 high-quality single nucleotide polymorphisms (SNPs) based on whole genome resequencing were discovered, and eighteen SNPs loci linked to disease resistance were discovered. We annotated six relevant candidate genes, including sik2, herc2, pip5k1c, npr1, mybpc3, and arhgap9, which showed important roles in lipid metabolism, oxidative stress, and neuronal survival. In the brain tissues of resistant and susceptible groups, candidate genes against NNV infection showed significant differential expression. The results indicate that regulating neuronal survival or pathways involved in lipid metabolism may result in increased resistance to NNV. Understanding the molecular mechanisms that lead to NNV resistance will be beneficial for the growth of the P. leopardus breeding sector. Additionally, the identified SNPs could be employed as biomarkers of disease resistance in P. leopardus, which will facilitate the selective breeding of grouper.
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Antozoários , Bass , Nodaviridae , Infecções por Vírus de RNA , Animais , Bass/genética , Estudo de Associação Genômica Ampla/veterinária , Polimorfismo de Nucleotídeo Único , Resistência à Doença/genética , Nodaviridae/fisiologia , Infecções por Vírus de RNA/veterináriaRESUMO
BACKGROUND: Chronic kidney disease (CKD), often coexisting with various systemic disorders, may increase the risk of falls. Our study aimed to assess the prevalence and risk of falls among patients with CKD in China. METHODS: We included patients with/without CKD from China Health and Retirement Longitudinal Study (CHARLS). Our primary outcome was the occurrence of fall accidents within the past 2 years. To enhance the robustness of our findings, we employed a multivariable logistic regression model, conducted propensity score analysis, and applied an inverse probability-weighting model. RESULTS: A total of 12,658 participants were included, the prevalence of fall accident rates were 17.1% (2,028/11,837) among participants without CKD and 24.7% (203/821) among those with CKD. In the inverse probability-weighting model, participants with CKD exhibited higher fall accident rates (OR = 1.28, 95% CI: 1.08-1.53, p = 0.005 ). Sensitivity and subgroup analysis showed the results still stable. CONCLUSIONS: The population in China afflicted with CKD has a significantly heightened risk of experiencing falls, underscoring the crucial importance of intensifying efforts in assessing and preventing fall risks.
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Insuficiência Renal Crônica , Aposentadoria , Humanos , Estudos Longitudinais , Acidentes por Quedas , Insuficiência Renal Crônica/epidemiologia , China/epidemiologiaRESUMO
The nutritional components and quality of milk are influenced by the rumen microbiota and its metabolites at different lactation stages. Hence, rumen fluid and milk samples from 6 dairy cows fed the same diet were collected during peak lactation, early mid-lactation, and later mid-lactation. Untargeted metabolomics and 16S rRNA sequencing were applied for analyzing milk and rumen metabolites, as well as rumen microbial composition, respectively. The levels of lipid-related metabolites, l-glutamate, glucose-1-phosphate, and acetylphosphate in milk exhibited lactation-dependent attenuation. Maltol, N-acetyl-d-glucosamine, and choline, which are associated with milk flavor or coagulation properties, as well as l-valine, lansioside A, clitocine, and ginsenoside La, increased significantly in early mid-lactation and later mid-lactation, especially in later mid-lactation. The obvious increase in rumen microbial diversities (ACE and Shannon indices) were observed in early mid-lactation compared with peak lactation. Twenty-one differential bacterial genera of the rumen were identified, with Succinivibrionaceae_UCG-001, Candidatus Saccharimonas, Fibrobacter, and SP3-e08 being significantly enriched in peak lactation. Rikenellaceae_RC9_gut_group, Eubacterium_ruminantium_group, Lachnospira, Butyrivibrio, Eubacterium_hallii_group, and Schwartzia were most significantly enriched in early mid-lactation. In comparison, only 2 bacteria (unclassified_f__Prevotellaceae and Prevotellaceae_UCG-001) were enriched in later mid-lactation. For rumen metabolites, LysoPE(16:0), l-glutamate, and l-tyrosine had higher levels in peak lactation, whereas PE(17:0/0:0), PE(16:0/0:0), PS(18:1(9Z)/0:0), l-phenylalanine, dulcitol, 2-(methoxymethyl)furan, and 3-phenylpropyl acetate showed higher levels in early mid-lactation and later mid-lactation. Multiomics-integrated analysis revealed that a greater abundance of Fibrobacter contributed to phospholipid content in milk by increasing ruminal acetate, l-glutamate, and LysoPE(16:0). Prevotellaceae_UCG-001 and unclassified_f_Prevotellaceae provide substrates for milk metabolites of the same category by increasing ruminal l-phenylalanine and dulcitol contents. These results demonstrated that milk metabolomic fingerprints and critical functional metabolites during lactation, and the key bacteria in rumen related to them. These findings provide new insights into the development of functional dairy products.
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Lactação , Microbiota , Leite , Rúmen , Animais , Feminino , Bovinos , Rúmen/metabolismo , Rúmen/microbiologia , Leite/química , Dieta/veterinária , RNA Ribossômico 16S , MultiômicaRESUMO
To meet the goal of the Paris Agreement, China pledges to realize the "Dual Carbon" targets by 2060. As the capital of China, Beijing plays a leading role in becoming zero-emission or carbon neutral in the future. We project the pollutants emissions of building sector based on current strict clean air policies (PO scenario) and China's carbon neutrality target by 2060 (CN scenario) from 2019 to 2050. Results show that PM2.5 concentration will increase by 2.62 µg/m3 under PO scenario; under the CN scenario, ozone concentration will increase by 2.53 µg/m3 but PM2.5 concentration will reduce by 9.04 µg/m3. It is projected that China carbon neutrality goals could avoid 11.12% of PM2.5-related health burden; With strict clean air policies, health burdens of ozone (3.9%) and PM2.5 (4.1%) could be avoided, respectively. This study highlights the importance of achieving co-benefits of air quality and public health.
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Caring for aging parents is fulfilling for adult children but comes at the cost of impacting their health and finances. Employing Bronfenbrenner's bioecological model, this study examines the mediating role of healthcare hardship in the association between caregiving and health, while also investigating the sources of support that could mitigate the adverse effects of caregiving. Using the Survey of Health Retirement in Europe, the study reveals that while there is no sufficient evidence for a direct impact of caregiving on health through healthcare hardship, there is a significant link between caregiving and healthcare hardship. Additionally, having a support system is associated with reduced healthcare hardship. Notably, men seem to benefit more from social support compared to women. The study indicates that adult children make sacrifices, risking their own well-being to care for their parents. It emphasizes the importance of a strong support network to mitigate these negative caregiving effects.
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Vesicle trafficking is a fundamental cellular process that ensures proper material exchange between organelles in eukaryotic cells, and multisubunit tethering complexes (MTCs) are essential in this process. The heterohexameric homotypic fusion and protein sorting (HOPS) complex, which functions in the endolysosomal pathway, is a member of MTCs. Despite its critical role, the complex composition and low-expression level of HOPS have made its expression and purification extremely challenging. In this study, we present a highly efficient strategy for overexpressing and purifying HOPS from Saccharomyces cerevisiae. We achieved HOPS overexpression by integrating a strong promoter TEF1 before each subunit using the gRNA-tRNA array for CRISPR-Cas9 (GTR-CRISPR) system. The HOPS complex was subsequently purified using Staphylococcus aureus protein A (ProtA) affinity purification and size-exclusion chromatography, resulting in high purity and homogeneity. We obtained two-fold more HOPS using this method than that obtained using the commonly used GAL1 promoter-controlled HOPS overexpression. Negative staining electron microscopy analysis confirmed the correct assembly of HOPS. Notably, we also successfully purified two other MTCs, class C core vacuole/endosome tethering (CORVET) and Golgi-associated retrograde protein (GARP) using this approach. Our findings facilitate further in vitro biochemical characterization and functional studies of MTCs and provide a useful guide for the preparation of other heterogenic multisubunit complexes.
Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo , Endossomos/genética , Endossomos/metabolismo , Transporte Proteico , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMO
BACKGROUND: Growing evidence indicates that cannabinoid type 2 (CB2) receptor activation inhibits neuroinflammation in the pathogenesis of Parkinson's disease (PD). Nonetheless, the precise mechanisms of CB2 receptor-mediated neuroprotection have not been fully elucidated. The differentiation of microglia from the M1 to M2 phenotype plays a vital role in neuroinflammation. METHODS: In the present study, we investigated the effect of CB2 receptor activation on the M1/M2 phenotypic transformation of microglia treated with 1-methyl-4-phenylpyridinium (MPP+). The M1 phenotype microglia markers, including inducible nitric oxide (iNOS), interleukin 6 (IL-6), and CD86, and the M2 phenotype microglia markers, including arginase-1 (Arg-1), IL-10, and CD206, were detected by western blots and flow cytometry. The levels of phosphoinositide-3-kinase (PI3K)/Akt and nuclear factor erythroid 2-related factor 2 (Nrf2) were determined by Western blots. Subsequent addition of Nrf2 inhibitors initially revealed the specific mechanism by which CB2 receptors affect phenotypic changes in microglia. RESULTS: Our results showed that pretreatment with JWH133 significantly inhibited the MPP+-induced up-regulation of M1 phenotype microglia markers. Meanwhile, JWH133 increased the levels of M2 phenotype microglia markers. JWH133-mediated effects were blocked by co-treatment with AM630. Mechanism studies found that MPP+ treatment downregulated PI3K, Akt phosphorylated proteins, and nuclear Nrf2 protein. JWH133 pretreatment promoted PI3K/Akt activation and facilitated nuclear translocation of Nrf2, which was reversed by the PI3K inhibitor. Further studies showed that Nrf2 inhibitors inverted the effect of JWH133 on microglia polarization. CONCLUSION: The results indicate that CB2 receptor activation promotes MPP+-induced microglia transformation from M1 to M2 phenotype through PI3K/Akt/Nrf2 signaling pathway.
Assuntos
Canabinoides , Microglia , Humanos , Microglia/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , 1-Metil-4-fenilpiridínio/farmacologia , 1-Metil-4-fenilpiridínio/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Doenças Neuroinflamatórias , Receptor CB2 de Canabinoide/genética , Transdução de Sinais , Canabinoides/farmacologia , Canabinoides/metabolismoRESUMO
Post-traumatic stress disorder (PTSD) is a serious psychiatric disorder, and there is an association between it and the development of cardiovascular disease. The aim of this study was to explore whether there is a glutamatergic pathway connecting the medial habenula (MHb) with the rostral ventrolateral medulla (RVLM) that is involved in the regulation of cardiovascular function in a rat model of PTSD. Vesicular glutamate transporter 2 (VGLUT2)-positive neurons in the MHb region were retrogradely labeled with FluoroGold (FG) by the double-labeling technique of VGLUT2 immunofluorescence and FG retrograde tracing. Rats belonging to the PTSD model group were microinjected with artificial cerebrospinal fluid (ACSF) or kynurenic acid (KYN; a nonselective glutamate receptor blocker) into their RVLM. Subsequently, with electrical stimulation of MHb, the discharge frequency of the RVLM neurons, heart rate, and blood pressure were found to be significantly increased after microinjection of ACSF using an in vivo multichannel synchronous recording technology; however, this effect was inhibited by injection of KYN. The expression of N-methyl-D-aspartic acid (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits was significantly increased in RVLM of PTSD model rats analyzed by the Western blotting technique. These findings suggest that there may be a glutamatergic pathway connection between MHb and RVLM and that this pathway may be involved in the regulation of cardiovascular function in the PTSD model rats, by acting on NMDA and AMPA receptors in the RVLM.
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Habenula , Transtornos de Estresse Pós-Traumáticos , Humanos , Ratos , Animais , Transtornos de Estresse Pós-Traumáticos/metabolismo , N-Metilaspartato/metabolismo , N-Metilaspartato/farmacologia , Habenula/metabolismo , Bulbo/metabolismo , Pressão Sanguínea , Ácido Glutâmico/metabolismo , Ácido Glutâmico/farmacologiaRESUMO
Fibroblast growth factors (FGFs) are short polypeptides that play essential roles in various cellular biological processes, including cell migration, proliferation, and differentiation, as well as tissue regeneration, immune response, and organogenesis. However, studies focusing on the characterization and function of FGF genes in teleost fishes are still limited. In this study, we identified and characterized expression patterns of 24 FGF genes in various tissues of embryonic and adult specimens of the black rockfish (Sebates schlegelii). Nine FGF genes were found to play essential roles in myoblast differentiation, as well as muscle development and recovery in juvelines of S. schlegelii. Moreover, sex-biased expression pattern of multiple FGF genes was recorded in the species' gonads during its development. Among them, expression of the FGF1 gene was recorded in interstitial and sertoli cells of testes, promoting germ-cell proliferation and differentiation. In sum, the obtained results enabled systematic and functional characterization of FGF genes in S. schlegelii, laying a foundation for further studies on FGF genes in other large teleost fishes.
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Proteínas de Peixes , Perciformes , Animais , Proteínas de Peixes/genética , Regulação da Expressão Gênica , Fatores de Crescimento de Fibroblastos/metabolismo , Perciformes/genética , Peixes/genética , FilogeniaRESUMO
Post-traumatic stress disorder (PTSD) has been reported to be associated with a higher risk of cardiovascular disease. The amygdala may have an important role in regulating cardiovascular function. This study aims to explore the effect of amygdala glutamate receptors (GluRs) on cardiovascular activity in a rat model of PTSD. A compound stress method combining electrical stimulation and single prolonged stress was used to prepare the PTSD model, and the difference of weight gain before and after modeling and the elevated plus maze were used to assess the PTSD model. In addition, the distribution of retrogradely labeled neurons was observed using the FluoroGold (FG) retrograde tracking technique. Western blot was used to analyze the changes of amygdala GluRs content. To further investigate the effects, artificial cerebrospinal fluid (ACSF), non-selective GluR blocker kynurenic acid (KYN) and AMPA receptor blocker CNQX were microinjected into the central nucleus of the amygdala (CeA) in the PTSD rats, respectively. The changes in various indices following the injection were observed using in vivo multi-channel synchronous recording technology. The results indicated that, compared with the control group, the PTSD group exhibited significantly lower weight gain (P < 0.01) and significantly decreased ratio of open arm time (OT%) (P < 0.05). Retrograde labeling of neurons was observed in the CeA after microinjection of 0.5 µL FG in the rostral ventrolateral medulla (RVLM). The content of AMPA receptor in the PTSD group was lower than that in the control group (P < 0.05), while there was no significant differences in RVLM neuron firing frequency and heart rate (P > 0.05) following ACSF injection. However, increases in RVLM neuron firing frequency and heart rate were observed after the injection of KYN or CNQX into the CeA (P < 0.05) in the PTSD group. These findings suggest that AMPA receptors in the amygdala are engaged in the regulation of cardiovascular activity in PTSD rats, possibly by acting on inhibitory pathways.
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Transtornos de Estresse Pós-Traumáticos , Ratos , Animais , Ratos Sprague-Dawley , Receptores de AMPA , 6-Ciano-7-nitroquinoxalina-2,3-diona/metabolismo , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Receptores de Glutamato/metabolismo , Tonsila do Cerebelo , Aumento de Peso , Bulbo/fisiologia , Pressão SanguíneaRESUMO
The Dual-Disposition Model proposes to understand psychopathy through two dispositions (i.e., threat sensitivity and poor inhibitory control) with distinct etiological substrates. In the current study, we examined the predictive contributions of threat sensitivity, poor inhibitory control, and their interaction to emotion dysregulation in 694 Chinese undergraduates based on the Disinhibition subscale of Triarchic Psychopathy Measure, Behavioral Inhibition System Scale, and Difficulties in Emotion Regulation Scale. Our results suggested that two dispositions have independent contributions to emotion dysregulation. Additionally, interactive effects of two dispositions were found for emotion awareness, impulse control, emotional acceptance, and limited emotion regulation strategies when upset. These provide evidence that deficits associated with poor inhibitory control can be selectively suppressed by low threat sensitivity or exacerbated by high threat sensitivity. Training individuals with high psychopathic dispositions to focus on their emotional state might be able to enhance their ability of emotion regulation.
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Transtorno da Personalidade Antissocial , Emoções , Transtorno da Personalidade Antissocial/psicologia , Emoções/fisiologia , Humanos , Inibição PsicológicaRESUMO
PURPOSE: The purpose of this study was to investigate the effect of FNDC5 expression levels in hepatocellular carcinoma on the phenotypic changes of macrophages in tumor tissues. METHODS: In this study, we established an in vitro co-culture system of hepatocellular carcinoma cells and macrophages. Then we performed overexpression or knockdown of FNDC5 gene in hepatocellular carcinoma cells to observe the effect of changes in FNDC5 expression level on the phenotypic changes of THP-1 macrophages. And the conclusions obtained in the in vitro assay were further validated by a subcutaneous tumorigenic nude mice model. RESULTS: Our findings suggest that elevated FNDC5 expression in hepatocellular carcinoma cells lead to an increased M2 phenotype and decreased M1 phenotype in macrophages. This effect may be achieved by elevating PPARγ levels in macrophages while decreasing NF-κB and NLRP3 levels. These changes could be reversed by using PPARγ inhibitors. CONCLUSION: We preliminarily demonstrated that FNDC5 in hepatocellular carcinoma cells promotes the polarization of M2 macrophages by affecting the PPARγ/NF-κB/NLRP3 pathway.
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Carcinoma Hepatocelular/genética , Fibronectinas/genética , Neoplasias Hepáticas/genética , NF-kappa B/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , PPAR gama/genética , Anilidas/farmacologia , Animais , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Diferenciação Celular , Linhagem Celular Tumoral , Técnicas de Cocultura , Fibronectinas/antagonistas & inibidores , Fibronectinas/metabolismo , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Nus , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , PPAR gama/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Análise de Sobrevida , Células THP-1 , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Serotonin 1A receptors (5-HT1ARs) are implicated in the control of mood, cognition, and memory and in various neuropsychiatric disorders such as depression and anxiety. As such, understanding the regulation of 5-HT1ARs will inform the development of better treatment approaches. We previously demonstrated 5-HT1ARs are SUMOylated by SUMO1 in the rat brain. Agonist stimulation increased SUMOylation and was further enhanced when combined with 17ß-estradiol-3-benzoate (EB), which are treatments that cause the transient and prolonged desensitization of 5-HT1AR signaling, respectively. In the current study, we identified the protein inhibitor of activated STAT (PIAS)xα as the enzyme that facilitates SUMOylation, and SENP2 as the protein that catalyzes the deSUMOylation of 5-HT1ARs. We demonstrated that PIASxα significantly increased in the membrane fraction of rats co-treated with EB and an agonist, compared to either the EB-treated or vehicle-treated groups. The acute treatment with an agonist alone shifted the location of SENP2 from the membrane to the cytoplasmic fraction, but it has little effect on PIASxα. Hence, two separate mechanisms regulate SUMOylation and the activity of 5-HT1ARs by an agonist and EB. The effects of EB on 5-HT1AR SUMOylation and signaling may be related to the higher incidence of mood disorders in women during times with large fluctuations in estrogens. Targeting the SUMOylation of 5-HT1ARs could have important clinical relevance for the therapy for several neuropsychiatric disorders in which 5-HT1ARs are implicated.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Estradiol/análogos & derivados , Proteínas Inibidoras de STAT Ativados/metabolismo , Receptor 5-HT1A de Serotonina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Linhagem Celular , Membrana Celular/metabolismo , Citoplasma/metabolismo , Estradiol/administração & dosagem , Estradiol/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Ratos , Sumoilação/efeitos dos fármacos , Regulação para CimaRESUMO
Pax3 and Pax7 are members of the Pax gene family which are essential for embryo and organ development. Both genes have been proved to be markers of muscle satellite cells and play key roles in the process of muscle growth and repair. Here, we identified two Pax3 genes (SsPax3a and SsPax3b) and two Pax7 genes (SsPax7a and SsPax7b) in a marine teleost, black rockfish (Sebastes schlegelii). Our results showed SsPax3 and SsPax7 marked distinct populations of muscle satellite cells, which originated from the multi-cell stage and somite stage, respectively. In addition, we constructed a muscle injury model to explore the function of these four genes during muscle repair. Hematoxylin-eosin (H-E) of injured muscle sections showed new-formed myofibers occurred at 16 days post-injury (dpi). ISH (in situ hybridization) analysis demonstrated that the expression level of SsPax3a and two SsPax7 genes increased gradually during 0-16 dpi and peaked at 16 dpi. Interestingly, SsPax3b showed no significant differences during the injury repair process, indicating that the satellite cells labeled by SsPax3b were not involved in muscle repair. These results imply that the muscle stem cell populations in teleosts are more complicated than in mammals. This lays the foundation for future studies on the molecular mechanism of indeterminant growth and muscle repair of large fish species.
Assuntos
Proteínas de Peixes/metabolismo , Peixes/metabolismo , Músculo Esquelético/fisiologia , Fator de Transcrição PAX3/metabolismo , Fator de Transcrição PAX7/metabolismo , Regeneração/fisiologia , Células Satélites de Músculo Esquelético/metabolismo , Animais , Músculo Esquelético/citologia , Células Satélites de Músculo Esquelético/citologiaRESUMO
Hydrogen is regarded to be one of the most promising renewable and clean energy sources. Finding a highly efficient and cost-effective catalyst to generate hydrogen via water splitting has become a research hotspot. Two-dimensional materials with exotic structural and electronic properties have been considered as economical alternatives. In this work, 2D SnSe films with high quality of crystallinity were grown on a mica substrate via molecular beam epitaxy. The electronic property of the prepared SnSe thin films can be easily and accurately tuned in situ by three orders of magnitude through the controllable compensation of Sn atoms. The prepared film normally exhibited p-type conduction due to the deficiency of Sn in the film during its growth. First-principle calculations explained that Sn vacancies can introduce additional reactive sites for the hydrogen evolution reaction (HER) and enhance the HER performance by accelerating electron migration and promoting continuous hydrogen generation, which was mirrored by the reduced Gibbs free energy by a factor of 2.3 as compared with the pure SnSe film. The results pave the way for synthesized 2D SnSe thin films in the applications of hydrogen production.