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BACKGROUND: Obstructive sleep apnoea (OSA) is a sleep-disordered breathing characterized by intermittent hypoxia (IH) that may cause cognitive dysfunction. However, the impact of IH on molecular processes involved in cognitive function remains unclear. METHODS: C57BL / 6 J mice were exposed to either normoxia (control) or IH for 6 weeks. DNA hydroxymethylation was quantified by hydroxymethylated DNA immunoprecipitation (hMeDIP) sequencing. ten-eleven translocation 1 (Tet1) was knocked down by lentivirus. Specifically, cognitive function was assessed by behavioral experiments, pathological features were assessed by HE staining, the hippocampal DNA hydroxymethylation was examined by DNA dot blot and immunohistochemical staining, while the Wnt signaling pathway and its downstream effects were studied using qRT-PCR, immunofluorescence staining, and Luminex liquid suspension chip analysis. RESULTS: IH mice showed pathological changes and cognitive dysfunction in the hippocampus. Compared with the control group, IH mice exhibited global DNA hydroxylmethylation in the hippocampus, and the expression of three hydroxylmethylases increased significantly. The Wnt signaling pathway was activated, and the mRNA and 5hmC levels of Wnt3a, Ccnd2, and Prickle2 were significantly up-regulated. Further caused downstream neurogenesis abnormalities and neuroinflammatory activation, manifested as increased expression of IBA1 (a marker of microglia), GFAP (a marker of astrocytes), and DCX (a marker of immature neurons), as well as a range of inflammatory cytokines (e.g. TNFa, IL3, IL9, and IL17A). After Tet1 knocked down, the above indicators return to normal. CONCLUSION: Activation of Wnt signaling pathway by hippocampal Tet1 is associated with cognitive dysfunction induced by IH.
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Disfunção Cognitiva , Hipocampo , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas , Apneia Obstrutiva do Sono , Via de Sinalização Wnt , Animais , Hipocampo/metabolismo , Hipocampo/patologia , Camundongos , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/genética , Via de Sinalização Wnt/fisiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Disfunção Cognitiva/etiologia , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/patologia , Masculino , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/patologia , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Metilação de DNA , Proteínas de Ligação a DNARESUMO
Background: Alterations gastrointestinal diseases (GDs) were reported in individuals with obstructive sleep apnea (OSA), however, the genetic background between OSA and GDs is still unclear. Methods: This investigation employed Mendelian randomization (MR) analyses to evaluate the causal effect between OSA and 19 types of GDs (gastroesophageal reflux disease (GERD), ulcerative colitis, celiac disease, Crohn's disease, chronic gastritis, irritable bowel syndrome, primary biliary cholangitis, diverticular disease, gastroduodenal ulcer, acute pancreatitis, non-alcoholic fatty liver disease, primary sclerosing cholangitis, cirrhosis, calculus of bile duct, calculus of gallbladder, pancreatic cancer, gastric cancer, colorectal cancer, and esophageal cancer). The inverse-variance weighted (IVW) method was used to evaluate the main effects model of causality. Results: This MR study suggests that OSA may play a causal role inflammation-related GDs (GERD, PIVW=5.94×10-9; gastroduodenal ulcer, PIVW=1×10-4; chronic gastritis, PIVW=0.0214; ulcerative colitis, PIVW=0.0296), and gallstones (calculi of the gallbladder, PIVW=0.0429; calculi of the bile duct, PIVW=0.0068). After accounting for obesity, type 2 diabetes, smoking, and alcohol consumption, the multivariate MR (MVMR) analysis identified that OSA is an independent risk factor for GERD, gastroduodenal ulcer, and calculus of the bile duct. The reverse MVMR analysis showed a causal effect of GERD on OSA. Besides, we did not find that the predisposition to OSA was associated with 4 cancers. Conclusion: This MR analysis provides compelling evidence of an independent causal relationship between genetically predicted OSA and an elevated risk of inflammation-related GDs. Besides, no causal association was observed between OSA and cancers. Further studies should be carried out to verify our findings.
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Introduction: Chronic intermittent hypoxia (CIH) can negatively affect hippocampal function through various molecular mechanisms. Protein acetylation, a frequently occurring modification, plays crucial roles in synaptic plasticity and cognitive processes. However, the global protein acetylation induced by CIH in the hippocampus and its specific effects on hippocampal function and behavior remain poorly understood. Methods: To address this gap, we conducted a study using liquid chromatography-tandem mass spectrometry to analyze the lysine acetylome and proteome of the hippocampus in healthy adult mice exposed to intermittent hypoxia for 4 weeks (as a CIH model) compared to normoxic mice (as a control). Results: We identified and quantified a total of 2,184 lysine acetylation sites in 1,007 proteins. Analysis of these acetylated proteins revealed disturbances primarily in oxidative phosphorylation, the tricarboxylic acid (TCA) cycle, and glycolysis, all of which are localized exclusively to mitochondria. Additionally, we observed significant changes in the abundance of 21 proteins, some of which are known to be associated with cognitive impairments. Discussion: This study helps to elucidate the molecular mechanisms underlying CIH-induced changes in protein acetylation in the hippocampus. By providing valuable insights into the pathophysiological processes associated with CIH and their impacts on hippocampal function, our findings contribute to a better understanding of the consequences of CIH-induced changes in protein acetylation in the hippocampus and the potential role of CIH in cognitive impairment.
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Objective: The objective of this study was to investigate the effectiveness of a machine learning algorithm in diagnosing OSA in children based on clinical features that can be obtained in nonnocturnal and nonmedical environments. Patients and methods: This study was conducted at Beijing Children's Hospital from April 2018 to October 2019. The participants in this study were 2464 children aged 3-18 suspected of having OSA who underwent clinical data collection and polysomnography(PSG). Participants' data were randomly divided into a training set and a testing set at a ratio of 8:2. The elastic net algorithm was used for feature selection to simplify the model. Stratified 10-fold cross-validation was repeated five times to ensure the robustness of the results. Results: Feature selection using Elastic Net resulted in 47 features for AHI ≥5 and 31 features for AHI ≥10 being retained. The machine learning model using these selected features achieved an average AUC of 0.73 for AHI ≥5 and 0.78 for AHI ≥10 when tested externally, outperforming models based on PSG questionnaire features. Linear Discriminant Analysis using the selected features identified OSA with a sensitivity of 44% and specificity of 90%, providing a feasible clinical alternative to PSG for stratifying OSA severity. Conclusions: This study shows that a machine learning model based on children's clinical features effectively identifies OSA in children. Establishing a machine learning screening model based on the clinical features of the target population may be a feasible clinical alternative to nocturnal OSA sleep diagnosis.
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Background: Rhoptry organelle proteins (ROPs) secreted by apicomplexan parasites play important roles during parasites invasion and survival in host cells, and are potential vaccine candidates against apicomplexan diseases. Eimeria tenella (E. tenella) is one of the most noteworthy apicomplexan species, which causes hemorrhagic pathologies. Although dozens of putative E. tenella ROP sequences are annotated, most ROP proteins are not well studied. Methods: In this study, an E. tenella ROP21 gene was identified and the recombinant EtROP21 protein (rEtROP21) was expressed in Escherichia coli. The developmental expression levels, localization, and protective efficacy against E. tenella infection in chickens were studied. Results: An EtROP21 gene fragment with an open reading frame (ORF) of 981 bp was obtained from the Beijing strain of E. tenella. The rEtROP21 has a molecular weight of approximately 50 kDa and was recognized by rEtROP21-immunized mouse serum. Two specific protein bands, about 43 KDa and 95 KDa in size, were detected in the whole sporozoite proteins using the rEtROP21-immunized chicken serum. RT-qPCR analysis of the E. tenella ROP21 gene (EtROP21) revealed that its mRNA levels were higher in merozoites and sporozoites than in sporulated and unsporulated oocysts. Immunofluorescence and immunoelectron analyses showed that the EtROP21 protein predominantly localizes in the bulb region of rhoptries distributed at anterior, posterior, and perinuclear regions of E. tenella sporozoites. Immunization and challenge experiments revealed that immunizing chickens with rEtROP21 significantly increased their average body weight gain while decreasing mean lesion score and oocyst output (P <0.05). When compared with the challenged control group, the rEtROP21-immunized group was associated with a significantly higher relative weight gain (90.2%) and a greater reduction in oocyst output (67%) (P <0.05). The anticoccidial index of the rEtROP21-immunized group was 163.2. Chicken serum ELISA revealed that the levels of the specific anti- rEtROP21 antibody, IFN-γ, and IL-4 were significantly higher in the rEtROP21-immunized group than in the challenged control group (P <0.05). Conclusion: These results indicate that rEtROP21 can induce a high level of specific immune response and it is a potential candidate for the development of vaccines against E. tenella infection in chickens.
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Coccidiose , Eimeria tenella , Animais , Camundongos , Proteínas de Protozoários , Coccidiose/prevenção & controle , Coccidiose/veterinária , Galinhas , Proteínas Recombinantes , Esporozoítos , Oocistos/metabolismoRESUMO
Herein, we demonstrated the unique advantage of a mechanochemical reaction to prepare a salt with hard and soft acid and base ions concurrently by solution synthesis owing to the soft acid preferring to combine with the soft base and vice versa. We prepared Bu4N1-xLixMnxPb1-xI3 (x = 0.011-0.14) by mechanochemical synthesis. The doping induced a structural phase transition at â¼342 K and much enhancement of ionic conduction above 342 K for all co-doped hybrids regarding Bu4NPbI3 because of the voids around the Mn2+/Li+ ions by doping.
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PURPOSE: Obstructive sleep apnea (OSA) is a serious type of obstructive sleep-disordered breathing (SDB) that can cause a series of adverse effects on children's cardiovascular, growth, cognition, etc. The gold standard for diagnosis is polysomnography (PGS), which is used to assess the prevalence of OSA by obtaining the apnea-hypopnea index (AHI), but this diagnosis method is expensive and needs to be performed in a specialized laboratory, making it difficult to be of benefit to children with suspected OSA on a large scale. Our goal was to use a machine learning method to identify children with OSA of varying severity using data on children's nighttime heart rate and blood oxygen data. METHODS: This study included 3139 children who received diagnostic PSG with suspected OSA. Age, sex, BMI, 3 % oxygen depletion index (ODI), average nighttime heart rate and fastest heart rate were used as predictive features. Data sets were established with AHI ≥ 1, AHI ≥ 5, and AHI ≥ 10 as the diagnostic criteria for mild, moderate and severe OSA, and the samples of each data set were randomly divided into a training set and a test set at a ratio of 8:2. An OSA diagnostic model was established based on the XGBoost algorithm, and the ability of the machine learning model to diagnose OSA children with different severities was evaluated through different classification ability evaluation indicators. As a comparison, traditional classifier Logistic Regression was used to perform the same diagnostic task. The SHAP algorithm was used to evaluate the role of these features in the classification task. RESULTS: We established a diagnostic model of OSA in children based on the XGBoost algorithm. On the test set, the AUCs of the model for diagnosing mild, moderate, and severe OSA were 0.95, 0.88, and 0.88, respectively, and the classification accuracy was 90.45 %, 85.67 %, and 89.81 %, respectively, perform better than Logistic Regression classifiers. ODI is the most important feature in all classification tasks, and a higher fastest heart rate and ODI make the model tend to classify samples as positive. A high BMI value caused the model to tend to classify samples as positive in the mild and moderate classification tasks and as negative in the classification task with severe OSA. CONCLUSION: Using heart rate and blood oxygen data as the main features, a machine learning diagnostic model based on the XGBoost algorithm can accurately identify children with OSA at different severities. This diagnostic modality reduces the number of signals and the complexity of the diagnostic process compared to PSG, which could benefit children with suspected OSA who do not have the opportunity to receive a diagnostic PSG and provide a diagnostic priority reference for children awaiting a diagnostic PSG.
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Oxigênio , Apneia Obstrutiva do Sono , Criança , Humanos , Algoritmos , Frequência Cardíaca , Polissonografia/métodosRESUMO
Zirconium-based metal-organic frameworks (Zr-MOFs) have been demonstrated as potent catalysts for the hydrolytic detoxification of organophosphorus nerve agents and their simulants. However, the practical implementation of these Zr-MOFs is limited by the poor processability of their powdered form and the necessity of water media buffered by a volatile liquid base in the catalytic reaction. Herein, we demonstrate the efficient solid-state hydrolysis of a nerve agent simulant (dimethyl-4-nitrophenyl phosphate, DMNP) catalyzed by Zr-MOF-based mixed matrix membranes. The mixed matrix membranes were fabricated by incorporating MOF-808 into the blending matrix of poly(vinylidene fluoride) (PVDF), poly(vinylpyrrolidone) (PVP), and imidazole (Im), in which MOF-808 provides highly active catalytic sites, the hydrophilic PVP helps to retain water for promoting the hydrolytic reaction, and Im serves as a base for catalytic site regeneration. Impressively, the mixed matrix membranes displayed excellent catalytic performance for the solid-state hydrolysis of DMNP under high humidity, representing a significant step toward the practical application of Zr-MOFs in chemical protective layers against nerve agents.
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Estruturas Metalorgânicas , Agentes Neurotóxicos , Polímeros , Organofosfatos , ÁguaRESUMO
Introduction: Epstein-Barr virus (EBV) is a highly dangerous virus that is globally prevalent and closely linked to the development of nasopharyngeal cancer (NPC). Plasma EBV DNA analysis is an effective strategy for early detection, prognostication and monitoring of treatment response of NPC. Methods: Here, we present a novel molecular diagnostic technique termed EBV-MCDA-LFB, which integrates multiple cross displacement amplification (MCDA) with nanoparticle-based lateral flow (LFB) to enable simple, rapid and specific detection of EBV. In the EBV-MCDA-LFB system, a set of 10 primers was designed for rapidly amplifying the highly conserved tandem repeat BamHI-W region of the EBV genome. Subsequently, the LFB facilitate direct assay reading, eliminating the use of extra instruments and reagents. Results: The outcomes showed that the 65°C within 40 minutes was the optimal reaction setting for the EBV-MCDA system. The sensitivity of EBV-MCDA-LFB assay reached 7 copies per reaction when using EBV recombinant plasmid, and it showed 100% specificity without any cross-reactivity with other pathogens. The feasibility of the EBV-MCDA-LFB method for EBV detection was successfully validated by 49 clinical plasma samples. The complete detection process, consisting of rapid template extraction (15 minutes), MCDA reaction (65°C for 40 minutes), and LFB result reading (2 minutes), can be finalized within a 60-minutes duration. Discussion: EBV-MCDA-LFB assay designed here is a fast, extremely sensitive and specific technique for detecting EBV in field and at the point-of-care (PoC), which is especially beneficial for countries and regions with a high prevalence of the disease and limited economic resources.
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Infecções por Vírus Epstein-Barr , Nanopartículas , Neoplasias Nasofaríngeas , Humanos , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/diagnóstico , Reações CruzadasRESUMO
The development of proton conductors capable of working at above 100 °C is of great significance for proton exchange membrane electrolysis cells (PEMECs) and proton exchange membrane fuel cells (PEMFCs) but remains to be an enormous challenge to date. In this work, we demonstrate for the first time that the N-doped porous carbon derived from metal-organic frameworks (MOFs) with great superiority can be exploited for high-performing proton conductors at above 100 °C. Through the pyrolysis of ZIF-8, the N-doped porous carbon (ZIF-8-C) featuring high chemical resistance to Fenton's reagent was readily prepared and then served as a robust host to accommodate H3PO4 molecules for proton transport. Upon impregnation with H3PO4, the resulting PA@ZIF-8-C exhibits low water swelling and high proton conduction of over 10-2 S cm-1 at a temperature above 100 °C, which is superior to many reported proton conductors. This work provides a new approach for the design of high-performing proton conductors at above 100 °C.
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Estruturas Metalorgânicas , Carbono , Prótons , Porosidade , Membrana CelularRESUMO
Allergic rhinitis (AR) is a series of reactions to allergen mediated by immunoglobulin E (IgE) and is one of the most common allergic diseases that affects children. Traditional Chinese Medicine, due to its diverse regulatory functions, may offer new strategies for AR therapy. Huanggui Tongqiao Granules (HTG) is a Chinese formula consisting of twelve herbs and has long been prescribed for patients with AR. The aim of this study is to determine the possible targets and action mechanisms of HTG for the AR treatment. SymMap database and TMNP algorithm were employed to show that interferon-gamma (IFN-gamma), acting as a molecular link between immunity and neural circuits, is the involved key target. The enrichment of immune and virus-related signaling pathways indicated the neuroimmunomodulatory potential of HTG. Then, AR mouse model was established by ovalbumin (OVA) challenge and was used to verify the therapeutic effects of HTG in vivo. HTG significantly relieved AR symptoms and nasal mucosal inflammation, reduced OVA-specific IgE levels and balanced IFN-gamma/IL-4 ratio. Moreover, transcriptional profile based on clinical data presented that blood cell-specific IFN-gamma co-expressed gene module (BIM) was underexpressed in AR patients, further validating the potential of IFN-gamma as target for AR. Collectively, these findings suggest that HTG could be a promising candidate drug for AR.
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Mucosa Nasal , Rinite Alérgica , Camundongos , Animais , Mucosa Nasal/metabolismo , Camundongos Endogâmicos BALB C , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/metabolismo , Imunoglobulina E , Ovalbumina , Interferon gama/metabolismo , Modelos Animais de Doenças , Algoritmos , Citocinas/metabolismoRESUMO
PURPOSE: This systematic review aims to assess the night-to-night variability (NtNV) in respiratory sleep parameters in children and the accuracy of diagnosing obstructive sleep apnea (OSA) in children based on a single-night sleep study. METHODS: The PubMed, EMBASE, and Cochrane Library databases were searched until March 8, 2021. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42021239838). RESULTS: Our study included 395 patients from 5 articles. The mean (SD) age of all included patients was 11.78 (4.05) years. AHI was reported for 325 participants in 4 studies, and the mean change between two consecutive nights was -0.13 [95% CI: -0.40, 0.14] events per hour. The mean change in OAI was -0.07 [95% CI: -0.27, 0.12] events per hour in 187 participants across 3 studies. Based on the diagnostic criteria used, three studies reported that the diagnostic rates of OSA patients in a single-night sleep study were 83%, 84.6%, and 91%. The NtNV in AHI in children with severe and moderate OSA was greater than that in children with mild OSA (3.35 [95% CI: 0.07, 6.62] events per hour vs -0.15 [95% CI: -0.42, 0.12] events per hour), and these children with more severe OSA may have shown a higher AHI on the first night. CONCLUSIONS: The NtNV in AHI was not statistically significant in the group sample of children. However, there were significant differences in NtNV in AHI between children with mild and moderate-to-severe OSA. Individual NtNV in respiratory sleep parameters may cause children to be misdiagnosed by single-night diagnostic sleep studies.
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Apneia Obstrutiva do Sono , Criança , Humanos , Polissonografia , Sistema Respiratório , Sono , Apneia Obstrutiva do Sono/diagnósticoRESUMO
Crystalline porous materials, such as metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), have been demonstrated to be versatile material platforms for the development of solid proton conductors. However, most crystalline porous proton conductors suffer from decreasing proton conductivity with increasing temperature due to releasing water molecules, and this disadvantage severely restricts their practical application in electrochemical devices. In this work, for the first time, hydrophilic carbon dots (CDs) were utilized to hybridize with high proton conductivity MOF-802, which is a model of MOF proton conductors, aiming to improve its water-retention capacity and thus enhance proton conduction. The resultant CDs@MOF-802 exhibits impregnable proton conduction with increasing temperature, and the proton conductivity reaches 10-1 S cm-1, much superior to that of MOF-802, making CDs@MOF-802 one of the most efficient MOF proton conductors reported so far. This study provides a new strategy to improve the water-retention capacity of porous proton conductors and further realize excellent proton conduction.
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Metal-organic frameworks (MOFs) provided a versatile platform for the development of new solid protonic electrolytes but faced great challenges regarding their low chemical stability and poor moisture retention capacity. Herein, we presented the proton-conducting study for zirconium-based MOF-802, revealing that MOF-802 possessed excellent features of extra aqueous and acidic stabilities and room-temperature superprotonic conduction with a proton conductivity of 1.05 × 10-2 S cm-1 at 288 K under 98% relative humidity (RH). Unfortunately, due to the liberation of water molecules from pores/channels, the proton conductivity of MOF-802 dropped significantly at the temperature above 318 K. To solve this issue, for the first time, MOF-802 was hybridized with poly(vinyl alcohol) (PVA) to form MOF-802@PVA hydrogel composites, where the moisture retention capacity of MOF-802 was greatly improved, giving the high room-temperature proton conductivity over 10-3 S cm-1 under ambient humidity. This work paves a new way to improve the moisture retention capacity and proton-conducting performances of porous proton conductors.
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Aim: To explore the roles of lncRNA NONHSAT177112.1 in the inflammatory injury of human cardiomyocytes (HCMs) induced by lipopolysaccharide (LPS). Materials & methods: The sublocalization of NONHSAT177112.1 was detected by FISH. HCMs were stimulated with LPS to induce inflammatory injury. NONHSAT177112.1 expression was detected by quantitative real-time PCR. Cell apoptosis and viability were detected by flow cytometry and CCK-8 assays. The expression of inflammatory cytokines and myocardial enzymes were detected by PCR and ELISA. Results: NONHSAT177112.1 is expressed in the nucleus and cytoplasm. NONHSAT177112.1 showed dynamic expression that first increased and then decreased during LPS stimulation. NONHSAT177112.1 knockdown reversed the promotion effect of LPS on inflammatory injury. Conversely, NONHSAT177112.1 overexpression exerted the opposite effects. Conclusion: NONHSAT177112.1 aggravates inflammatory injury in LPS-treated HCMs.
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Apoptose , Inflamação/patologia , Lipopolissacarídeos/efeitos adversos , Miócitos Cardíacos/patologia , RNA Longo não Codificante/genética , Sobrevivência Celular , Células Cultivadas , Humanos , Inflamação/etiologia , Inflamação/metabolismo , MicroRNAs/genética , Miócitos Cardíacos/imunologia , Miócitos Cardíacos/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Transdução de SinaisRESUMO
Protein-polyphenol-polysaccharide non-covalent ternary complexes possess many unique structural and functional properties. However, rare work is available to fabricate the neutral polysaccharide-based ternary complexes. Herein, the ternary complexes composed of lactoferrin (LF), oat ß-glucan (OG), and curcumin (Cur) with three binding sequences were successfully developed through self-assembly technique and spray drying technique, respectively. Spray drying could enhance the extent of the intermolecular associations among LF, OG, and Cur, leading to the formation of ternary complexes with smaller particle sizes and lower turbidities. Cur can be loaded in LF-OG complexes to form an amorphous complex through the intermolecular interactions (mainly hydrophobic interactions and hydrogen bonding). The ternary complexes can be used as potential emulsifiers to stabilize oil-in-water Pickering emulsions. The emulsifying capacity (to enhance physical stability) of the complexes was in the order as follows: the spray-dried ternary complexes > the spray-dried LF-OG complexes > the self-assembled ternary complexes > the self-assembled LF-OG complexes. The structural and functional properties (e.g., emulsifying property) of OG-based ternary complexes can be controlled by adjusting the binding sequences. These results will broaden our current understanding of protein-polyphenol-polysaccharide ternary complexes and provide more applications of OG in food, cosmetics, and pharmaceutical industries.
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Curcumina/química , Emulsificantes/química , Emulsões/química , Lactoferrina/química , Secagem por Atomização , beta-Glucanas/química , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Polifenóis , PolissacarídeosRESUMO
Being the center of the hypothalamus-pituitary-ovary (HPO) axis, the pituitary plays a key role in the onset of puberty. Recent studies show that circular RNAs (circRNAs) can perform as miRNA sponges to regulate development in animals. However, the function of pituitary-derived circRNAs in first estrus remains unclear in pigs. In this study, we performed a genome-wide identification and characterization of circRNAs using pituitaries from Landrace × Yorkshire crossbred pigs at three stages: pre-, in-, and post-puberty, to describe such pituitary-derived circRNAs in pigs. A total of 5148 circRNAs were found in the gilts' pituitaries, averaging 18 682 bp in genomic distance, which consisted of approximately 91% exonic, 6% intergenic, and 3% intronic circRNAs. Furthermore, 158 novel circRNAs were identified for the first time and classified as putative pituitary-specific circRNAs. Their expression levels during the onset of puberty, significantly exceeded those of the other circRNAs, and the parental genes of these putative pituitary-specific circRNAs were enriched in "ssc04917: prolactin signaling pathway," "ssc04080: neuroactive ligand-receptor interaction," and "ssc04728: dopaminergic synapse" pathways, all of which were consistent with pituitary functioning. Additionally, 17 differentially regulated circRNAs were found and investigated for their potential interaction with miRNAs, along with genes, by constructing a circRNA-targeted miRNA-gene network. Taken together, these results provide new insight into the circRNA-mediated timing of puberty in gilts at the pituitary level.
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In female mammals, the abnormal apoptosis of ovarian granulosa cells (GCs) impairs follicular development and causes reproductive dysfunction. Many studies have indicated that the FGFR1 gene of the PI3K signaling pathway and the p65 subunit of the transcription factor NF-κB may regulate the proliferation and apoptosis of GCs involved in follicular development. However, little is known about whether p65 regulates the transcription of FGFR1, as well as the biological effects of p65 and FGFR1 on the survival of GCs and follicular development. In porcine follicles and GCs, we found that p65 and FGFR1 were exclusively expressed in the GCs of follicles, and the mRNA and protein levels of p65 and FGFR1 significantly increased from small to large follicles. Both p65 and FGFR1 were found to activate the PI3K signaling pathway, and the expressions of proliferation markers (PCNA and MKI67) and the anti-apoptotic gene BCL2 were significantly increased by p65 and FGFR1. Furthermore, both p65 and FGFR1 were observed to promote cell proliferation and inhibit the cell apoptosis of GCs, and p65 was confirmed to bind at the -348/-338 region of FGFR1 to positively regulate its transcription. Moreover, p65 was further found to enhance the pro-proliferation and anti-apoptotic effects of FGFR1. Taken together, p65 may target the -348/-338 region of FGFR1, promote the transcription of FGFR1, and enhance the pro-proliferation effect and anti-apoptotic effect of FGFR1 to facilitate the growth of follicles. This study will provide useful information for further investigations on the p65-mediated-FGFR1 signaling pathway during folliculogenesis in mammals.
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Células da Granulosa/fisiologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Fator de Transcrição RelA/fisiologia , Animais , Proliferação de Células/genética , Sobrevivência Celular/genética , Células Cultivadas , Feminino , Regulação da Expressão Gênica , Oogênese/genética , Folículo Ovariano/citologia , Folículo Ovariano/metabolismo , Ovário/citologia , Ovário/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , SuínosRESUMO
Long non-coding RNA (lncRNA) has been associated with human diseases. To study the role of lncRNA in the pathogenic mechanism of acute fulminant myocarditis (AFM), we used a microarray to analyze lncRNA and messenger RNA (mRNA) expression in leukocyte samples from AFM patients and normal children. In total, using a 2/0.5-fold change and P < 0.05 as the cutoff criteria, we found that 3,101 lncRNAs and 2,170 mRNAs were differentially expressed in AFM patients. Quantitative real-time polymerase chain reaction (RT-qPCR) analysis was used to verify the microarray data. Eight differentially expressed molecules were randomly selected, including 3 upregulated lncRNAs, 3 downregulated lncRNAs, and 2 upregulated mRNAs. Among them, 7 expression profiles were consistent with the microarray results. Gene Ontology enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were used to investigate the biological functions of these genes. Establishment of a lncRNA-mRNA co-expression network and lncRNA target predication were performed to study the molecular interactions of these molecules. Our study is the first to use microarrays to examine the lncRNA and mRNA expression profiles associated with AFM, and the results indicate that the immune system plays an important role in AFM. These findings may provide a new perspective for the pathogenesis, diagnosis, and therapy of AFM.
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Aim: To assess differential expression profiles of circular RNAs (circRNAs) and explore their possible functions in children with fulminant myocarditis. Materials & methods: circRNA microarray experiments were carried out for determining differential expression profiles of circRNAs in three children with fulminant myocarditis and three healthy volunteers. Functional analysis and circRNA-miRNA-mRNA interaction network building were conducted to study biological functions. Results: This work identified 2281 upregulated and 892 downregulated circRNAs. Further assessment confirmed hsa_circ_0071542 upregulation (2.5-fold) in fulminant myocarditis. Functional analysis demonstrated the differentially expressed circRNAs mainly contributed to inflammation and immunity. Conclusion: circRNAs might have substantial roles in pediatric fulminant myocarditis, and hsa_circ_0071542 could serve as a promising biomarker.