RESUMO
Neuroinflammation has been proven to drive cognitive impairment associated with neurodegenerative diseases. It has been demonstrated that mitochondrial dysfunction is associated with cognitive impairment caused by neuroinflammation. We hypothesized that the transfer of exogenous mitochondria may be beneficial to the therapy of cognitive impairment induced by neuroinflammation. In the study, the effect of exogenous mitochondria on cognitive impairment induced by neuroinflammation was investigated. The results showed that mitochondrial treatment ameliorated the cognitive performance of lipopolysaccharide (LPS)-treated mice. Additionally, mitochondrial therapy attenuated neuronal injury and down-regulated the expression of proinflammatory cytokines, including TNF-α and pro- and cleaved IL-1ß, and the expression of Iba-1 and GFAP in the hippocampus and cortex of LPS-treated mice. Additionally, mitochondrial treatment increased mitochondrial ΔΨm, ATP level, and SOD activity and attenuated MDA level and ROS production in the brains of LPS-treated mice. The study reports the beneficial effect of mitochondrial treatment against cognitive impairment of LPS-treated mice, thereby providing a potential strategy for the treatment of cognitive impairment caused by neuroinflammation.
RESUMO
OBJECTIVE: Ferroptosis represents a form of regulated cellular death dependent upon iron and lipid peroxidation derivatives, holding considerable implications for cerebral and neurologic pathologies. In the present study, we endeavored to elucidate the molecular mechanisms governing ferroptosis and appraise the therapeutic value of electrical stimulation of median nerve in addressing cognitive impairments following traumatic brain injury (TBI), employing a rodent model. METHODS: In this study, we established a rat model to investigate the cognitive impairments resulting from TBI, followed by the application of median nerve stimulation (MNS). Initially, rats received an intraperitoneal injection of Erastin (2 mg/kg) prior to undergoing MNS. After 24 h of MNS treatment, the rats were subjected to an open field test to evaluate their cognitive and motor functions. Subsequently, we conducted biochemical assays to measure the serum levels of GSH, MDA and SOD. The structural integrity and cellular morphology of hippocampal tissue were examined through H&E staining, Nissl staining and transmission electron microscopy. Additionally, we assessed the expression levels of proteins crucial for neuronal health and function in the hippocampus, including VEGF, SLC7A11, GPX4, Nrf2, α-syn, NEUN and PSD95. RESULTS: Compared to the control group, rats in the stimulation group demonstrated enhanced mobility, reduced levels of tissue damage, a decrease in MDA concentration, and increased levels of GSH and SOD. Additionally, there was a significant upregulation in the expression of proteins critical for cellular defense and neuronal health, including GPX4, SLC7A11, Nrf2, VEGF, α-syn, NEUN, and PSD95 proteins. Conversely, rats in the Erastin group demonstrated decreased mobility, exacerbated pathological tissue damage, elevated MDA concentration, and decreased levels of GSH and SOD. There was also a notable decrease in the expression of GPX4, SLC7CA11, Nrf2, and VEGF proteins. The expression levels of α-syn, NEUN, and PSD95 were similarly diminished in the Erastin group. Each of these findings was statistically significant, indicating that MNS exerts neuroprotective effect in the hippocampal tissue of rats with TBI by inhibiting the ferroptosis pathway. CONCLUSION: (1) MNS may enhance the cognitive and behavioral performance of rats after TBI; (2) MNS can play a neuroprotective role by promoting the expression of nerve injury-related proteins, alleviating oxidative stress and ferroptosis process; (3) MNS may inhibit ferroptosis of neuronal cells by activating Nrf2/ GPX4 signaling pathway, thereby improving cognitive impairment in TBI rats.
Assuntos
Lesões Encefálicas Traumáticas , Disfunção Cognitiva , Modelos Animais de Doenças , Ferroptose , Nervo Mediano , Fator 2 Relacionado a NF-E2 , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular , Animais , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/terapia , Ratos , Masculino , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Disfunção Cognitiva/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Hipocampo/metabolismo , Terapia por Estimulação Elétrica/métodos , Superóxido Dismutase/metabolismo , Glutationa/metabolismo , Malondialdeído/metabolismo , Estresse Oxidativo , Proteínas do Tecido Nervoso/metabolismo , Antígenos NuclearesRESUMO
DNA methylation is a form of epigenetic regulation, having pivotal parts in controlling cellular expansion and expression levels within genes. Although blood DNA methylation has been studied in humans and other species, its prominence in cattle is largely unknown. This study aimed to methodically probe the genomic methylation map of Xinjiang brown (XJB) cattle suffering from bovine respiratory disease (BRD), consequently widening cattle blood methylome ranges. Genome-wide DNA methylation profiling of the XJB blood was investigated through whole-genome bisulfite sequencing (WGBS). Many differentially methylated regions (DMRs) obtained by comparing the cases and controls groups were found within the CG, CHG, and CHH (where H is A, T, or C) sequences (16,765, 7502, and 2656, respectively), encompassing 4334 differentially methylated genes (DMGs). Furthermore, GO/KEGG analyses showed that some DMGs were involved within immune response pathways. Combining WGBS-Seq data and existing RNA-Seq data, we identified 71 significantly differentially methylated (DMGs) and expressed (DEGs) genes (p < 0.05). Next, complementary analyses identified nine DMGs (LTA, STAT3, IKBKG, IRAK1, NOD2, TLR2, TNFRSF1A, and IKBKB) that might be involved in the immune response of XJB cattle infected with respiratory diseases. Although further investigations are needed to confirm their exact implication in the involved immune processes, these genes could potentially be used for a marker-assisted selection of animals resistant to BRD. This study also provides new knowledge regarding epigenetic control for the bovine respiratory immune process.
Assuntos
Metilação de DNA , Predisposição Genética para Doença , Bovinos , Animais , Epigênese Genética , Doenças dos Bovinos/genética , Complexo Respiratório Bovino/genéticaRESUMO
Objective: This multi-center cross-sectional study aimed to delineate latent profiles of benefit finding (BF) in individuals undergoing maintenance hemodialysis (MHD) in Shanghai and examine associations between these BF profiles, social support, and coping style. Methods: A total of 384 individuals undergoing MHD (mean age = 57.90, SD = 13.36) were assessed using the Benefit Finding Scale, Simplified Coping Style Questionnaire, and Perceived Social Support Scale. Latent profile analysis (LPA) identified distinct BF categories. Analysis of variance (ANOVA) evaluated the correlation between BF groups and demographic variables, while the relationship between BF, social support, and coping style was tested through correlation and multiple regression analyses. Results: LPA identified three BF groups: rich BF (54.17%), moderate BF (41.14%), and poor BF (4.69%). Regression analyses indicated that positive coping and social support are protective factors for BF. Additionally, older age and heightened understanding of MHD correlated with higher BF levels. Conclusion: The findings highlighted the importance of recognizing different BF profiles in individuals on MHD and working toward promoting BF levels in the rich BF and moderate BF groups, while helping the poor BF group to identify and address their challenges. Medical professionals should consider interventions tailored to individual psychological profiles to improve mental health and quality of life outcomes in this population.
RESUMO
BACKGROUND: Mitochondrial dysfunction plays a vital role in the progression of vascular dementia (VaD). We hypothesized that transfer of exogenous mitochondria might be a beneficial strategy for VaD treatment. OBJECTIVE: The study was aimed to investigate the role of mitochondrial therapy in cognitive function of VaD. METHODS: The activity and integrity of isolated mitochondria were detected using MitoTracker and Janus Green B staining assays. After VaD mice were intravenously injected with exogenous mitochondria, Morris water maze and passive avoidance tests were used to detect cognitive function of VaD mice. Haematoxylin and eosin, Nissl, TUNEL, and Golgi staining assays were utilized to measure neuronal and synaptic injury in the hippocampus of VaD mice. Detection kits were performed to detect mitochondrial membrane potential (ΔΨ), SOD activity and the levels of ATP, ROS, and MDA in the brains of VaD mice. RESULTS: The results showed that isolated mitochondria were intact and active. Mitochondrial therapy could ameliorate cognitive performance of VaD mice. Additionally, mitochondrial administration could attenuate hippocampal neuronal and synaptic injury, improve mitochondrial ΔΨ, ATP level and SOD activity, and reduce ROS and MDA levels in the brains of VaD mice. CONCLUSIONS: The study reports profitable effect of mitochondrial therapy against cognitive impairment of VaD, making mitochondrial treatment become a promising therapeutic strategy for VaD.
Assuntos
Disfunção Cognitiva , Demência Vascular , Camundongos , Animais , Demência Vascular/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Cognição , Disfunção Cognitiva/metabolismo , Superóxido Dismutase/metabolismo , Mitocôndrias , Trifosfato de Adenosina/metabolismo , Aprendizagem em Labirinto/fisiologia , Hipocampo/metabolismoRESUMO
Three-dimensional (3D) hollow carbon is one of advanced nanomaterials widely applied in oxygen reduction reaction (ORR). Herein, iron niobate (FeNb2O6) nanoparticles supported on metal-organic frameworks (MOFs)-derived 3D N-doped interconnected open carbon cages (FeNb2O6/NICC) were prepared by methanol induced assembly and pyrolysis strategy. During the fabrication process, the evaporation of methanol promoted the assembly and cross linkage of ZIF-8, rather than individual particles. The assembled ZIF-8 particles worked as in-situ sacrificial templates, in turn forming hierarchically interconnected open carbon cages after high-temperature pyrolysis. The as-made FeNb2O6/NICC showed a positive onset potential of 1.09 V and a half-wave potential of 0.88 V for the ORR, outperforming commercial Pt/C under the identical conditions. Later on, the as-built Zn-air battery with the FeNb2O6/NICC presented a greater power density of 100.6 mW cm-2 and durable long-cycle stability by operating for 200 h. For preparing 3D hollow carbon materials, this synthesis does not require a tedious removal process of template, which is more convenient than traditional method with silica and polystyrene spheres as templates. This work affords an exceptional example of developing 3D N-doped interconnected hollow carbon composites for energy conversion and storage devices.
RESUMO
Enhancement of oxidative stress and resultant neuronal injury play important roles in initiating cognitive impairment during the aging process. Thus, attenuating oxidative injury is regarded as a profitable therapeutic strategy for age-associated cognitive impairment. Previous studies showed that gliclazide (Gli) had a protective role in neuronal injury from cerebral ischemia/reperfusion (I/R) injury. However, whether Gli has a profitable effect on age-associated cognitive impairment remains largely unclear. The present study showed that Gli held the potential to attenuate neuronal apoptosis in D-gal-induced senescent cells and aging mice. Additionally, Gli could alleviate synaptic injury and cognitive function in D-gal-induced aging mice. Further study showed that Gli could attenuate oxidative stress in D-gal-induced senescent cells and aging mice. The p38 MAPK pathway was predicted as the downstream target of Gli retarding oxidative stress using in silico analysis. Further studies revealed that Gli attenuated D-gal-induced phosphorylation of p38 and facilitated Nrf2 nuclear expression, indicating that the anti-oxidative property of Gli may be associated with the p38 MAPK pathway. The study demonstrates that Gli has a beneficial effect on ameliorating D-gal-induced neuronal injury and cognitive impairment, making this compound a promising agent for the prevention and treatment of age-associated cognitive impairment.
RESUMO
This Fructus,study including and aimed to construct a rapid and nondestructive detection flavonoid,model betaine,for and of the content vitamin of(Vit four four quality C).index components Lycium barbarum polysaccharide,of inL ycii rawma total and C Hyperspectral data quantitative of terials modelswere powder developed Lycii using Fructus partial were squares effects collected,regression raw based LSR),on the support content vector the above components,the forest least(P regression compared,(SVR),the and effects random three regression(RFR)were algorithms.also The Four spectral predictive commonly data of the materialsand powder were were applied and of spectral quantitative for models reduction.compared.used were pre-processing screened methods feature to successive pre-process projection the raw algorithm data(SPA),noise competitive Thepre-processed for bands using adaptive reweigh ted sampling howed(CARS),the and maximal effects relevance based and raw minimal materials redundancy and(MRMR)were algorithms Following to optimize multiplicative the models.scatter The correction Based resultss(MS that prediction SPA on feature the powder prediction similar.PLSR C)denoising sproposed and integrated for model,screening the the coefficient bands,determination the effect(R_C~2)of(MSC-SPA-PLSR)coefficient was optimal.of on(R_P~2)thi of of calibration flavonoid,and and of all determination greater prediction0.83,L.barbarum inconte nt prediction of polysaccharide,total mean betaine,of Vit C were than smallest In the compared study,root with mean other prediction content squareserror models of the calibration(RMSEC)residual and deviation root squares was error2.46,prediction2.58,(RMSEP)and were the,and prediction(RPD)2.50,developed3.58,achieve respectively.rapid this the the quality mod el(MSC-SPA-PLSR)fourcomponents based Fructus,on hyperspectral which technology was approach to rapid and effective detection detection of the of Lycii in Lycii provided a new to the and nondestructive of of Fructus.
Assuntos
Betaína , Espectroscopia de Luz Próxima ao Infravermelho , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Pós , Análise dos Mínimos Quadrados , Algoritmos , FlavonoidesRESUMO
Immunotherapy is a revolutionized therapeutic strategy for tumor treatment attributing to the rapid development of genomics and immunology, and immune checkpoint inhibitors have successfully achieved responses in numbers of tumor types, including hematopoietic malignancy. However, acute myeloid leukemia (AML) is a heterogeneous disease and there is still a lack of systematic demonstration to apply immunotherapy in AML based on PD-1/PD-L1 blockage. Thus, the identification of molecules that drive tumor immunosuppression and stratify patients according to the benefit from immune checkpoint inhibitors is urgently needed. Here, we reported that STAT5 was highly expressed in the AML cohort and activated the promoter of glycolytic genes to promote glycolysis in AML cells. As a result, the increased-lactate accumulation promoted E3BP nuclear translocation and facilitated histone lactylation, ultimately inducing PD-L1 transcription. Immune checkpoint inhibitor could block the interaction of PD-1/PD-L1 and reactive CD8+ T cells in the microenvironment when co-culture with STAT5 constitutively activated AML cells. Clinically, lactate accumulation in bone marrow was positively correlated with STAT5 as well as PD-L1 expression in newly diagnosed AML patients. Therefore, we have illustrated a STAT5-lactate-PD-L1 network in AML progression, which demonstrates that AML patients with STAT5 induced-exuberant glycolysis and lactate accumulation may be benefited from PD-1/PD-L-1-based immunotherapy.
Assuntos
Histonas , Leucemia Mieloide Aguda , Humanos , Linfócitos T CD8-Positivos , Receptor de Morte Celular Programada 1 , Antígeno B7-H1 , Inibidores de Checkpoint Imunológico/uso terapêutico , Fator de Transcrição STAT5/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Terapia de Imunossupressão , Lactatos/uso terapêutico , Microambiente TumoralRESUMO
Bovine respiratory disease (BRD) is one of the major health issues in the cattle industry, resulting in significant financial crises globally. There is currently no good treatment, and cattle are made resistant to pneumonia through disease-resistant breeding. The serial blood samples from six Xinjiang brown (XJB) calves were collected for the RNA sequencing (RNA-seq). The obtained six samples were grouped into two groups, in each group as infected with BRD and healthy calves, respectively. In our study, the differential expression mRNAs were detected by using RNA-seq and constructed a protein-protein interaction (PPI) network related to the immunity in cattle. The key genes were identified by protein interaction network analysis, and the results from RNA-seq were verified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 488 differentially expressed (DE) mRNAs were identified. Importantly, the enrichment analysis of these identified DEGs classified them as mainly enriched in the regulation and immune response processes. The 16 hub genes were found to be related to immune pathways categorized by PPIs analysis. Results revealed that many hub genes were related to the immune response to respiratory disease. These results will provide the basis for a better understanding of the molecular mechanism of bovine resistance to BRD.
RESUMO
Animal genotyping by means of genome-wide association studies is important for connecting phenotypes of interest with their underlying genetics in livestock. However, the use of whole genome sequencing to investigate chest circumference (CC) in donkeys has rarely been reported. We aimed to use the genome-wide association study approach to detect significant single nucleotide polymorphisms (SNPs) and key genes associated with chest circumference traits in Xinjiang donkeys. We assessed 112 Xinjiang donkeys in this study. The chest circumference of each was measured 2 h before milking. We re-sequenced blood samples from the Xinjiang donkeys, and genome-wide association study analyses were performed using a mixed model with the PLINK, GEMMA, and REGENIE programs. We tested 38 donkeys for candidate SNPs for genome-wide association study using three software programs. Additionally, 18 SNP markers reached genome-wide significance (p < 1.61 × 10-9). On the basis of these, 41 genes were identified. Previously proposed candidate genes for CC traits were supported by this study, including NFATC2 (Nuclear Factor of Activated T Cells 2), PROP1 (PROP Paired-Like Homeobox 1), UBB (Ubiquitin B), and HAND2 (Heart and Neural Crest Derivatives Expressed 2). These promising candidates provide a valuable resource for validating potential meat production genes and will facilitate the development of high-yielding Xinjiang donkey breeds through marker-assisted selection or gene editing.
Assuntos
Equidae , Estudo de Associação Genômica Ampla , Animais , Equidae/genética , Fenótipo , Genoma , Fatores de Transcrição , TecnologiaRESUMO
BACKGROUND: The hypereosinophilic syndrome (HES) is a group of rare blood disorders characterized by persistent eosinophilia and damage to multiple organs. HES can be either primary, secondary or idiopathic. Secondary HES are commonly caused by parasitic infections, allergic reactions or cancer. We described a pediatric case of HES associated with liver damage and multiple thrombi. A 12-year-old boy with eosinophilia was complicated with severe thrombocytopenia, liver damage, portal vein, splenic vein, and superior mesenteric vein thromboses. The thrombi recanalized after treatment with methylprednisolone succinate and low molecular weight heparin. No side effects appeared after 1-month. CONCLUSIONS: Corticosteroids should be used at an early stage of HES to prevent further damage to vital organs. Anticoagulants should be recommended only in cases with thrombosis which should be actively screened as a part of evaluation of end organ damage.
Assuntos
Síndrome Hipereosinofílica , Hepatopatias , Trombose , Masculino , Humanos , Criança , Veia Porta/diagnóstico por imagem , Veia Esplênica/diagnóstico por imagem , Veias Mesentéricas/diagnóstico por imagem , Trombose/etiologia , Síndrome Hipereosinofílica/complicações , Síndrome Hipereosinofílica/diagnóstico , Síndrome Hipereosinofílica/tratamento farmacológicoRESUMO
This study determined the surface electromyography (sEMG) characteristics of healthy Chinese adults during swallowing to provide a reference for the clinical differential diagnosis of swallowing and dysphagia. sEMG was performed on 187 healthy adults to obtain quantitative information on normal pharyngeal swallowing. The evaluated parameters included the timing and amplitude of sEMG activity in the submental and infrahyoid muscles. A normative database was constructed for the timing and amplitude of muscle activity during pharyngeal swallowing. Results indicated that the duration of sEMG activity was related to the age of the patient; the duration gradually increasing with age. Similarly, the duration of the sEMG activity was associated with the type of swallowing. The duration of the sEMG activity was similar for dry and wet swallowing but was significantly different for excessive swallowing. The mean amplitude of sEMG activity for the submental and infrahyoid muscles was not significantly associated with patient age. A significant correlation between the mean amplitude of sEMG activity and the types of normal swallowing was observed in infrahyoid, but not in submental muscle activity. This study is the first report on the establishment of a normative database for the duration and amplitude of muscle activity based on sEMG analysis of pharyngeal swallowing in healthy Chinese adults.
Assuntos
Transtornos de Deglutição , Deglutição , Adulto , Humanos , Deglutição/fisiologia , Eletromiografia/métodos , População do Leste Asiático , Transtornos de Deglutição/diagnóstico , Músculos do PescoçoRESUMO
BACKGROUND: Hypertensive disorders of pregnancy (HDP) is associated with an increased risk of adverse outcomes. The fetal middle cerebral artery (MCA) and umbilical artery (UA) blood flow detected by ultrasound are recommended to evaluate the oxygenation of the fetus. It is necessary to analyze the relationship between MCA & UA doppler indices or cerebroplacental ratio (CPR) and fetal outcomes and describe MCA and UA blood flow values across gestation. METHODS: Hospital-based retrospective case-control study during 2016 to 2020. 800 singleton pregnant women: 400 normotensive control, 219 gestational hypertension (GH), and 181 preeclampsia (PE)/eclampsia (EC). An analysis of the outcomes of mothers and neonates was performed. The fetal MCA and UA blood flow values across gestation were established, and MCA-resistance index (RI) and CPR were used to predict fetal distress and small for gestational age (SGA). RESULTS: In the normotensive control, GH and PE/EC groups, the mean gestational age (GA) was 38.9 ± 1.2 weeks, 39.0 ± 1.0 weeks, and 38.6 ± 1.3 weeks respectively, and the mean birth weight (BW) was 3.195 ± 0.387 kilograms, 3.198 ± 0.428 kilograms, and 2.987 ± 0.544 kilograms respectively. There were differences in GA, BW, fetal distress, SGA and intraventricular hemorrhage I-II between the hypertension group and normotensive control group (p < 0.05). The MCA-RI (sensitivity: 70.1%, specificity: 64.3%) and MCA-RI (sensitivity: 52.4%, specificity: 84.6%) were the best indices to predict fetal distress and SGA, respectively during GA of 35-40 weeks. CONCLUSIONS: Fetal MCA blood flow values and CPR are of great benefit for obstetricians to evaluate the status of fetus evidentially in singleton pregnancy.
Assuntos
Hipertensão Induzida pela Gravidez , Pré-Eclâmpsia , Recém-Nascido , Gravidez , Feminino , Humanos , Lactente , Artéria Cerebral Média/diagnóstico por imagem , Estudos Retrospectivos , Estudos de Casos e Controles , Artérias Umbilicais/diagnóstico por imagem , Sofrimento Fetal , Feto/diagnóstico por imagem , Idade Gestacional , Retardo do Crescimento Fetal , Peso ao Nascer , Ultrassonografia Doppler , Ultrassonografia Pré-NatalRESUMO
Oxygen reduction reaction (ORR) on cathode severely suffers from sluggish kinetics in zinc-air batteries. Therefore, substantial efforts have been made to prepare advanced electrocatalysts for facilitating the ORR. Herein, we synthesized FeCo alloyed nanocrystals entrapped in N-doped graphitic carbon nanotubes on nanosheets (FeCo-N-GCTSs) by 8-aminoquinoline coordination-induced pyrolysis, whose morphology, structures, and property were characterized in details. Impressively, the obtained FeCo-N-GCTSs catalyst showed a positive onset potential (Eonset = 1.06 V) and half-wave potential (E1/2 = 0.88 V), revealing excellent ORR activity. Further, the FeCo-N-GCTSs assembled zinc-air battery displayed the maximum power density of 133 mW cm-2 and negligible gap change in the discharge-charge voltage plot over 288 h (ca. 864 cycles) at 5 mA cm-2, outperforming the Pt/C + RuO2 based counterpart. This work provides a facile route for construction of high-efficiency, durable and low-cost nanocatalysts for the ORR in fuel cells and rechargeable Zn-air batteries.
RESUMO
Heavy metal ion (HMI) in wastewater is a kind of resource that is wrongly placed. Recovery of heavy metal from lead-acid wastewater desires efficient and reusable functional materials. In this paper, graphene oxide-like with diazanyl groups (GOLA) was synthesized by a nucleophilic substitution reaction of graphene oxide-like with hydroxyl groups (GOLH) with diazane. GOLA exhibited good stability and recyclability in wastewater. The maximal adsorption capacity (qmax) values of GOLA for Pb(II), Cd(II), Cu(II), Ni(II), and Cr(III) ions were 505.80, 401.99, 83.48, 82.29, and 147.77 mg/g, respectively. The equilibrium time of GOLA adsorbing HMIs was 20 min. GOLA was employed to recover lead ions from lead-acid wastewater to give Pb(OH)2 and reusable water. Therefore, this paper provides a useful method of recycling lead from lead-acid wastewater.
Assuntos
Metais Pesados , Poluentes Químicos da Água , Águas Residuárias , Chumbo , Poluentes Químicos da Água/análise , Metais Pesados/análise , Água , Adsorção , Cinética , Concentração de Íons de HidrogênioRESUMO
Donkey milk has high nutritional and medicinal value, but there are few researches in donkey milk traits, especially on genome. The whole lactation of 89 donkeys was recorded and it was found that Xinjiang donkey had good lactation performance while great differences among individuals. In our previous study, four genes including LGALS2, NUMB, ADCY8 and CA8 were identified as milk-associated with Chinese Kazakh house, based on Equine 670k Chip genomic analysis. And then 15 SNPs of the four key genes were conducted for genotyping in Xinjiang donkey in this study, one of Chinese indigenous breed, 14 SNPs were successful classified. And those SNPs were correlation analysis with milk yield of Xinjiang donkeys. The results showed that NUMB g.46709914T > G was significantly correlated with daily milk yield of Xinjiang donkey in the early, middle, and late periods, while ADCY8 g.48366302T > C, CA8 g.89567442T > G and CA8 g.89598328T > A were significantly correlated with lactation in the late periods. These results indicate that NUMB g.46709914T > G can be as markers of candidate genes for lactating traits in donkeys, SNPs of ADCY8 and CA8 as potential. Our findings will not only help confirm key genes for donkey milk traits, but also provide future for genomic selection in donkeys.
Assuntos
Equidae , Leite , Feminino , Cavalos , Animais , Equidae/genética , Lactação/genética , Fenótipo , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
The aim of this study was to investigate the selection signatures at a genome-wide level in 'Pishan' sheep using Specific Locus Amplified Fragment (SLAF)-seq. Blood samples from 126 ewes were sequenced using SLAF tags, and the ovarian tissues from 8 ewes (Bashbay sheep, a single litter size group (SG group); 'Pishan' sheep, double litter size group (DG group)) were collected to detect expression levels by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Selection signature analysis was performed using global fixation index (Fst) and nucleotide diversity (π) ratio. A total of 1,192,168 high-quality SLAFs were identified. Notably, 2380 candidate regions under selection using two approaches were identified. A total of 2069 genes were identified, which were involved in dopaminergic synapses, thyroid hormone synthesis, ovarian steroidogenesis and thyroid hormone signalling pathways. Furthermore, Growth Differentiation Factor 9 (GDF9), Period Circadian Regulator 2 (PER2), Thyroid Stimulating Hormone Receptor (TSHR), and Nuclear Receptor Coactivator 1 (NCOA1) reside within these regions and pathways. The expression levels of GDF9 and PER2 genes in sheep tissue of the DG group were significantly higher than those in the SG group. These genes are interesting candidates for litter size and provide a starting point for further identification of conservation strategies for 'Pishan' sheep.
Assuntos
Polimorfismo de Nucleotídeo Único , Hormônios Tireóideos , Gravidez , Ovinos/genética , Animais , Feminino , Tamanho da Ninhada de Vivíparos/genética , Sequência de BasesRESUMO
Previous studies have shown mitochondrial dysfunction in various acute kidney injuries and chronic kidney diseases. Lipoic acid exerts potent effects on oxidant stress and modulation of mitochondrial function in damaged organ. In this study we investigated whether alpha lipoamide (ALM), a derivative of lipoic acid, exerted a renal protective effect in a type 2 diabetes mellitus mouse model. 9-week-old db/db mice were treated with ALM (50 mg·kg-1·d-1, i.g) for 8 weeks. We showed that ALM administration did not affect blood glucose levels in db/db mice, but restored renal function and significantly improved fibrosis of kidneys. We demonstrated that ALM administration significantly ameliorated mitochondrial dysfunction and tubulointerstitial fibrotic lesions, along with increased expression of CDX2 and CFTR and decreased expression of ß-catenin and Snail in kidneys of db/db mice. Similar protective effects were observed in rat renal tubular epithelial cell line NRK-52E cultured in high-glucose medium following treatment with ALM (200 µM). The protective mechanisms of ALM in diabetic kidney disease (DKD) were further explored: Autodock Vina software predicted that ALM could activate RXRα protein by forming stable hydrogen bonds. PROMO Database predicted that RXRα could bind the promoter sequences of CDX2 gene. Knockdown of RXRα expression in NRK-52E cells under normal glucose condition suppressed CDX2 expression and promoted phenotypic changes in renal tubular epithelial cells. However, RXRα overexpression increased CDX2 expression which in turn inhibited high glucose-mediated renal tubular epithelial cell injury. Therefore, we reveal the protective effect of ALM on DKD and its possible potential targets: ALM ameliorates mitochondrial dysfunction and regulates the CDX2/CFTR/ß-catenin signaling axis through upregulation and activation of RXRα. Schematic figure illustrating that ALM alleviates diabetic kidney disease by improving mitochondrial function and upregulation and activation of RXRα, which in turn upregulated CDX2 to exert an inhibitory effect on ß-catenin activation and nuclear translocation. RTEC renal tubular epithelial cell. ROS Reactive oxygen species. RXRα Retinoid X receptor-α. Mfn1 Mitofusin 1. Drp1 dynamic-related protein 1. MDA malondialdehyde. 4-HNE 4-hydroxynonenal. T-SOD Total-superoxide dismutase. CDX2 Caudal-type homeobox transcription factor 2. CFTR Cystic fibrosis transmembrane conductance regulator. EMT epithelial mesenchymal transition. α-SMA Alpha-smooth muscle actin. ECM extracellular matrix. DKD diabetic kidney disease. Schematic figure was drawn by Figdraw ( www.figdraw.com ).
Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Ácido Tióctico , Animais , Camundongos , Ratos , beta Catenina/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/patologia , Transição Epitelial-Mesenquimal , Fibrose/tratamento farmacológico , Fibrose/metabolismo , Glucose/metabolismo , Rim/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Ácido Tióctico/farmacologia , Ácido Tióctico/uso terapêutico , Receptor X Retinoide alfa/efeitos dos fármacos , Receptor X Retinoide alfa/metabolismoRESUMO
Brain aging is closely related to neurodegenerative diseases. Circular RNAs (circRNAs) are a type of conserved RNAs with covalently closed continuous loops. Emerging evidence has shown that circRNAs are implicated in the biology of brain aging and the pathology of age-related neurodegenerative diseases. Here, we summarize current studies on circRNAs associated with brain aging and neurodegenerative diseases by discussing their expression features, pathophysiological roles, and mechanisms of action. We also discuss the potential challenges of circRNA-based therapy against brain aging and neurodegenerative diseases, as well as their potential as diagnostic biomarkers of neurodegenerative diseases. The review provides insights into current progress in the functions of circRNAs in the process of brain aging and neurodegenerative diseases. © 2022 The Pathological Society of Great Britain and Ireland.