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1.
J Int Med Res ; 52(3): 3000605241233157, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38546265

RESUMO

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) constitutes a group of autoimmune neuroinflammatory conditions that are characterized by positive serum MOG-immunoglobulin G antibodies. The relationship between MOGAD and immune factors remains unclear. Herein, we report a man in his early 30s who initially presented symptoms of headache and low-grade fever persisting for 20 days. The patient experienced isolated meningitis onset and had recurrent meningitis as the primary clinical feature, which manifested as low-grade fever, headache, and neck rigidity. Although cranial magnetic resonance imaging showed no abnormalities, immunotherapy was promptly administered upon diagnosing MOGAD through positive MOG-specific antibody testing of cerebrospinal and serum fluids. Notably, the patient's symptoms exhibited rapid improvement following treatment. Although meningitis is traditionally associated with infectious diseases, it can also occur in antibody-related autoimmune diseases that affect the central nervous system. Consequently, MOGAD should be considered in cases of aseptic meningitis with an unknown etiology, to facilitate definitive diagnosis and enhance patient prognosis.


Assuntos
Doenças Autoimunes , Meningite , Humanos , Masculino , Autoanticorpos , Cefaleia , Meningite/diagnóstico , Glicoproteína Mielina-Oligodendrócito , Adulto
2.
Animals (Basel) ; 14(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38473062

RESUMO

The number of vertebrae is a crucial economic trait that can significantly impact the carcass length and meat production in animals. However, our understanding of the quantitative trait loci (QTLs) and candidate genes associated with the vertebral number in sheep (Ovis aries) remains limited. To identify these candidate genes and QTLs, we collected 73 Ujimqin sheep with increased numbers of vertebrae (T13L7, T14L6, and T14L7) and 23 sheep with normal numbers of vertebrae (T13L6). Through high-throughput genome resequencing, we obtained a total of 24,130,801 effective single-nucleotide polymorphisms (SNPs). By conducting a selective-sweep analysis, we discovered that the most significantly selective region was located on chromosome 7. Within this region, we identified several genes, including VRTN, SYNDIG1L, LTBP2, and ABCD4, known to regulate the spinal development and morphology. Further, a genome-wide association study (GWAS) performed on sheep with increased and normal vertebral numbers confirmed that ABCD4 is a candidate gene for determining the number of vertebrae in sheep. Additionally, the most significant SNP on chromosome 7 was identified as a candidate QTL. Moreover, we detected two missense mutations in the ABCD4 gene; one of these mutations (Chr7: 89393414, C > T) at position 22 leads to the conversion of arginine (Arg) to glutamine (Gln), which is expected to negatively affect the protein's function. Notably, a transcriptome expression profile in mouse embryonic development revealed that ABCD4 is highly expressed during the critical period of vertebral formation (4.5-7.5 days). Our study highlights ABCD4 as a potential major gene influencing the number of vertebrae in Ujimqin sheep, with promising prospects for future genome-assisted breeding improvements in sheep.

3.
Gene ; 910: 148310, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38401832

RESUMO

With the change in diet structure, individuals prefer to consume mutton with less fat. However, sheep tail has a lot of fat. We identified a breed of low-fat short-tailed sheep (i.e., Hulunbuir short-tailed sheep). It is necessary to develop an animal model that can promote research on the potential mechanisms of the short-tail phenotype in sheep, which results from the TBXT gene c.G334T mutation. To create animal models, we selected mice as experimental animals. Mouse embryos lacking the TBXT protein, which crucially regulates mouse embryonic development, cannot develop normally. We utilized CRISPR/Cas9 gene editing technology to generate site-specific mutation (c.G334T) in the TBXT gene of mice, and found that the mouse TBXT mutation (c.G334T) leads to a short-tail phenotype. Furthermore, we investigated the interaction between TBXT and Wnt signaling pathways. The expressions of TBXT, Axin2, Dkk1, Wnt3, Wnt3a, and Wnt5a were discovered to be significantly different between mutant embryos and wild embryos by obtaining mouse embryos at various developmental stages and examining the expression relationship between the TBXT and Wnt signaling pathway-related components in all of these embryos. Therefore, as a transcription factor, TBXT regulates the expression of the aforementioned Wnt signaling pathway components by forming a regulatory network for the normal development of mouse embryos. This study enriches the research on the functional role of the TBXT in the development of mouse embryos and the mechanism by which the short-tailed phenotype in sheep develops.


Assuntos
Sistemas CRISPR-Cas , Cauda , Gravidez , Feminino , Camundongos , Animais , Ovinos/genética , Desenvolvimento Embrionário/genética , Fenótipo , Edição de Genes/métodos
4.
Sci Rep ; 14(1): 3738, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355782

RESUMO

An immune-related gene signature (IRGS) was established to better understand the molecular and immunologic characteristics of microsatellite instable (MSI) and microsatellite stable (MSS) endometrial carcinoma (EC), and provide potential immunotherapy directions for MSS patients. Top 20 immune-related hub genes were screened by weight gene coexpression network analysis (WGCNA), and an IRGS was further established through Cox regression analysis. The molecular and immune characteristics were clarified in IRGS high and low risk groups. Expression and MS status validation of the IRGS were conducted through quantitative real-time Polymerase Chain Reaction (rt-qPCR) and immunohistochemistry (IHC) analysis. The IRGS includes 2 oncogenes (AGTR1 and HTR3C) and 2 tumor suppressor genes (CD3E and SERPIND1). Patients in IRGS high-risk group were more with MSS status, higher tumor grade, later FIGO stage, serous histology and elder ages compared with IRGS low-risk group (P < 0.05). Besides, patients in MSS group were more FIGO stages II-IV (42.7% vs. 26%), serous histology (35.7% vs. 5.3%) and with higher IRGS risk score (1.51 ± 3.11 vs. 1.02 ± 0.67) (P < 0.05) than patients in MSI group. Furthermore, patients in IRGS high-risk group had higher tumor purity, more Macrophages M1 and Macrophages M2 infiltrating, higher proportion of Macrophages M2 and Dendritic cells activated, lower proportion of T cells regulatory (Tregs), lower tumor mutation burden (TMB). Correspondingly, subjects in IRGS low-risk group had higher immunphenoscores than IRGS high-risk group. The relative mRNA level of AGTR1 and HTR3C were gradually increase, while CD3E and SERPIND1 were reversed in rt-qPCR. Through IHC experiments, AGTR1(69.2% vs 30%, P = 0.074) and HTR3C (76.9% vs 30%, P = 0.024) had higher positive staining rates in ECs than non-ECs. While SERPIND1 (84.6% vs 20%, P = 0.003) and CD3E (61.5% vs 40%, P = 0.000) had higher positive staining rates in non-ECs. IRGS is a potential diagnostic and prognostic biomarker for EC. IRGS low risk group might benefit from immune checkpoint inhibitors, while IRGS high risk group deserve other potential immunotherapy.


Assuntos
Neoplasias do Endométrio , Oncogenes , Humanos , Feminino , Idoso , Fatores de Risco , Imunoterapia , Instabilidade de Microssatélites , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/terapia , Repetições de Microssatélites/genética , Prognóstico
5.
Cancer Med ; 13(3): e6875, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38205938

RESUMO

BACKGROUND: Cervical cancer (CC) has become the fourth most common cancer worldwide and it is mainly caused by the infection of human papillomavirus (HPV), especially high-risk HPV16. Aberrant miRNA expression in CC is closely related to HPV16 infection, and the regulation of HPV16 E6 expression can affect a variety of miRNA expression. This study aims to exploring the miRNAs involved in E6 regulation in CC. METHODS: Our study screened differentially expressed miRNAs in cervical cells of HPV16 infected and uninfected cervical cancer patients by analyzing the GSE81137 dataset of the gene expression omnibus database (GEO), and identified miR-320a that plays an anti-tumor role and is associated with good prognosis of cervical cancer. Explore the effect of HPV16 E6 on the expression of miR-320a in cervical cancer, and verify whether HPV16 E6 regulates the downstream target gene TOP2A expression through miR-320a, thereby affecting cervical cancer cell proliferation, apoptosis, migration, invasion, and EMT in vitro and in vivo. RESULTS: The bioinformatic methods selected the miR-320a, which was differentially expressed in cervical cells from HPV16-infected patients compared to uninfected patients. We further demonstrated that miR-320a level was regulated by HPV16 E6, which promoted the CC cell proliferation, migration, invasion, and inhibited apoptosis. In addition, we predicted the downstream target genes of miR-320a and confirmed that TOP2A was one of its targeting proteins. Moreover, HPV16 E6 promoted the TOP2A expression in CC cells through down-regulating miR-320a, leading to promoting CC development. CONCLUSIONS: We confirmed that HPV16 E6 promoted the TOP2A expression through down-regulation of miR-320a, thus promoting CC development, and the HPV16 E6/miR-320a/TOP2A axis may perform as a potential target for CC treatment.


Assuntos
MicroRNAs , Neoplasias do Colo do Útero , Feminino , Humanos , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias do Colo do Útero/patologia
6.
Nature ; 625(7993): 175-180, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38093006

RESUMO

Oxytocin (OXT), a nine-amino-acid peptide produced in the hypothalamus and released by the posterior pituitary, has well-known actions in parturition, lactation and social behaviour1, and has become an intriguing therapeutic target for conditions such as autism and schizophrenia2. Exogenous OXT has also been shown to have effects on body weight, lipid levels and glucose homeostasis1,3, suggesting that it may also have therapeutic potential for metabolic disease1,4. It is unclear, however, whether endogenous OXT participates in metabolic homeostasis. Here we show that OXT is a critical regulator of adipose tissue lipolysis in both mice and humans. In addition, OXT serves to facilitate the ability of ß-adrenergic agonists to fully promote lipolysis. Most surprisingly, the relevant source of OXT in these metabolic actions is a previously unidentified subpopulation of tyrosine hydroxylase-positive sympathetic neurons. Our data reveal that OXT from the peripheral nervous system is an endogenous regulator of adipose and systemic metabolism.


Assuntos
Tecido Adiposo , Lipólise , Neurônios , Ocitocina , Animais , Humanos , Camundongos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Agonistas Adrenérgicos beta/farmacologia , Lipólise/efeitos dos fármacos , Neurônios/metabolismo , Ocitocina/metabolismo , Ocitocina/farmacologia , Tirosina 3-Mono-Oxigenase/metabolismo
7.
Heliyon ; 9(12): e22461, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38125541

RESUMO

The bleomycin-induced pulmonary fibrosis mouse model is commonly used in idiopathic pulmonary fibrosis research, but its cellular and molecular changes and efficiency as a model at the molecular level are not fully understood. In this study, we used spatial transcriptome technology to investigate the cellular and molecular changes in the lungs of bleomycin-induced pulmonary fibrosis mouse models. Our analyses revealed cell dynamics during fibrosis in epithelial cells, mesenchymal cells, immunocytes, and erythrocytes with their spatial distribution available. We confirmed the differentiation of the alveolar type II (AT2) cell type expressing Krt8, and we inferred their trajectories from both the AT2 cells and club cells. In addition to the fibrosis process, we also noticed evidence of self-resolving, especially to identify possible self-resolving related genes, including Prkca. Our findings provide insights into the cellular and molecular mechanisms underlying fibrosis resolution and represent the first spatiotemporal transcriptome dataset of the bleomycin-induced fibrosis mouse model.

8.
J Immunol Res ; 2023: 5532617, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37965271

RESUMO

Lung squamous cell carcinoma (LUSC) is associated with poor clinical prognosis and lacks available targeted agents. GPC3 is upregulated in LUSC. Our study aimed to explore the roles of GPC3 in LUSC and the antitumor effects of HLA-A2-restricted GPC3 antigenic peptide-sensitized dendritic cell (DC)-induced cytotoxic T lymphocytes (CTLs) on LUSC. LUSC cells with GPC3 knockdown and overexpression were built using lentivirus packaging, and cell viability, clone formation, apoptosis, cycle, migration, and invasion were determined. Western blotting was used to detect the expression of cell cycle-related proteins and PI3K-AKT pathway-associated proteins. Subsequently, HLA-A2-restricted GPC3 antigenic peptides were predicted and synthesized by bioinformatic databases, and DCs were induced and cultured in vitro. Finally, HLA-A2-restricted GPC3 antigenic peptide-modified DCs were co-cultured with T cells to generate specific CTLs, and the killing effects of different CTLs on LUSC cells were studied. A series of cell function experiments showed that GPC3 overexpression promoted the proliferation, migration, and invasion of LUSC cells, inhibited their apoptosis, increased the number of cells in S phase, and reduced the cells in G2/M phase. GPC3 knockdown downregulated cyclin A, c-Myc, and PI3K, upregulated E2F1, and decreased the pAKT/AKT level. Three HLA-A2-restricted GPC3 antigenic peptides were synthesized, with GPC3522-530 FLAELAYDL and GPC3102-110 FLIIQNAAV antigenic peptide-modified DCs inducing CTL production, and exhibiting strong targeted killing ability in LUSC cells at 80 : 1 multiplicity of infection. GPC3 may advance the onset and progression of LUSC, and GPC3522-530 FLAELAYDL and GPC3102-110 FLIIQNAAV antigenic peptide-loaded DC-induced CTLs have a superior killing ability against LUSC cells.


Assuntos
Carcinoma de Células Escamosas , Linfócitos T Citotóxicos , Humanos , Antígeno HLA-A2/metabolismo , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Peptídeos , Células Dendríticas , Pulmão , Glipicanas/genética
9.
Phys Rev Lett ; 131(15): 153601, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37897755

RESUMO

Nonlinear mechanical resonators display rich and complex dynamics and are important in many areas of fundamental and applied sciences. Here, we present a general strategy to generate mechanical nonlinearities for trapped particles by transverse driving in a funnel-shaped potential. Employing a trapped ion platform, we study the nonlinear oscillation, bifurcation, and hysteresis of a single calcium ion and demonstrate a 20-fold enhancement of the signal from a zeptonewton-magnitude harmonic force through the effect of vibrational resonance. Our results represent a first step in combining the rich nonlinear dynamics with the precision control over mechanical motions offered by atomic physics and open up possibilities for exploiting nonlinear mechanical phenomena in the quantum regime.

11.
Anim Reprod Sci ; 256: 107306, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37541020

RESUMO

The process of testis development in mammals is accompanied by the proliferation and maturation of Sertoli, Leydig and germ cells. Spermatogenesis depends on hormone regulation, which must bind to a receptor to exert its biological effects. The changes in Hu sheep testis cell composition and FSHR, LHR and AR expression during different developmental stages are unclear (newborn, puberty and adulthood). To address this, using single-cell RNA sequencing, we analyzed testis cell composition and hormone receptor expression changes during three important developmental stages of Hu sheep. We observed significant changes in the composition of somatic and germ cells in different Hu sheep testis developmental stages. Furthermore, we analyzed the FSHR, LHR and AR distribution and expression changes at three important periods and verified them by qRT-PCR and immunofluorescence. Our results suggest that after birth, the proportion of germ cells increased gradually, peaking in adulthood; the proportion of Sertoli cells decreased gradually, reaching the lowest in adulthood; and the proportion of Leydig cells increased and then decreased, reaching the lowest in adulthood. In addition, FSHR, LHR and AR are mainly located in Sertoli, Leydig and germ cells. LHR and FSHR expression decreased with increasing age, while AR expression increased and then decreased with increasing age.


Assuntos
Receptores do FSH , Testículo , Masculino , Animais , Ovinos , Testículo/metabolismo , Receptores do FSH/genética , Receptores do FSH/metabolismo , Células Intersticiais do Testículo/metabolismo , Células de Sertoli/metabolismo , Hormônios/metabolismo , Mamíferos
12.
FASEB J ; 37(8): e23084, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37410073

RESUMO

Spermatogenesis is a highly organized process by which undifferentiated spermatogonia self-renew and differentiate into spermatocytes and spermatids. The entire developmental process from spermatogonia to sperm occurs within the seminiferous tubules. Spermatogenesis is supported by the close interaction of germ cells with Sertoli cells. In this study, testicular tissues were collected from Hu sheep at 8 timepoints after birth: 0, 30, 90, 180, 270, 360, 540, and 720 days. Immunofluorescence staining and histological analysis were used to explore the development of male germ cells and Sertoli cells in the Hu sheep testes at these timepoints. The changes in seminiferous tubule diameter and male germ cells in the Hu sheep testes at these different developmental stages were analyzed. Then, specific molecular markers were used to study the proliferation and differentiation of spermatogonia, the timepoint of spermatocyte appearance, and the maturation and proliferation of Sertoli cells in the seminiferous tubules. Finally, the formation of the blood-testes barrier was studied using antibodies against the main components of the blood-testes barrier, ß-catenin, and ZO-1. These findings not only increased the understanding of the development of the Hu sheep testes, but also laid a solid theoretical foundation for Hu sheep breeding.


Assuntos
Células de Sertoli , Testículo , Masculino , Animais , Ovinos , Sêmen , Espermatogênese , Espermatogônias
13.
Cell Metab ; 35(5): 770-785.e5, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-36965483

RESUMO

Restricting caloric intake effectively reduces body weight, but most dieters fail long-term adherence to caloric deficit and eventually regain lost weight. Hypothalamic circuits that control hunger drive critically determine body weight; yet, how weight loss sculpts these circuits to motivate food consumption until lost weight is regained remains unclear. Here, we probe the contribution of synaptic plasticity in discrete excitatory afferents on hunger-promoting AgRP neurons. We reveal a crucial role for activity-dependent, remarkably long-lasting amplification of synaptic activity originating from paraventricular hypothalamus thyrotropin-releasing (PVHTRH) neurons in long-term body weight control. Silencing PVHTRH neurons inhibits the potentiation of excitatory input to AgRP neurons and diminishes concomitant regain of lost weight. Brief stimulation of the pathway is sufficient to enduringly potentiate this glutamatergic hunger synapse and triggers an NMDAR-dependent gaining of body weight that enduringly persists. Identification of this activity-dependent synaptic amplifier provides a previously unrecognized target to combat regain of lost weight.


Assuntos
Fome , Hipotálamo , Humanos , Fome/fisiologia , Proteína Relacionada com Agouti/metabolismo , Hipotálamo/metabolismo , Neurônios/metabolismo , Peso Corporal
14.
Food Chem ; 411: 135456, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-36669340

RESUMO

Oat supplementation of the ruminant diet can improve growth performance and meat quality traits, but the role of muscle metabolites has not been evaluated. This study aimed to establish whether oat grass supplementation (OS) of Small-tail Han sheep improved growth performance and muscle tissue metabolites that are associated with better meat quality and flavor. After 90-day, OS fed sheep had higher live-weight and carcass-weight, and lower carcass fat. Muscle metabolomics analysis showed that OS fed sheep had higher levels of taurine, l-carnitine, inosine-5'-monophospgate, cholic acid, and taurocholic acid, which are primarily involved in taurine and hypotaurine metabolism, purine metabolism, and bile acid biosynthesis and secretion, decreased fat accumulation and they promote functional or flavor metabolites. OS also increased muscle levels of amino acids that are attributed to better quality and flavorsome mutton. These findings provided further evidence for supplementing sheep with oat grass to improve growth performance and meat quality.


Assuntos
Aminoácidos , Avena , Ovinos , Animais , Aminoácidos/análise , Avena/metabolismo , Cauda/química , Cauda/metabolismo , Composição Corporal , Ácidos Graxos/análise , Dieta/veterinária , Músculos/metabolismo , Carne/análise , Suplementos Nutricionais/análise , Taurina/metabolismo , Taurina/farmacologia , Ração Animal/análise
15.
Environ Pollut ; 317: 120621, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36395912

RESUMO

Groundwater pollution risk assessment is an important part of environmental assessment. Although it has been developed for many years, there has not yet been a multi-dimensional method that takes into account long time series and spatial factors. We proposed a new method combines the advantages of remote sensing cloud computing, long-term groundwater modeling simulation and GIS technology to solve it efficiently. A coastal industrial park in Hainan was used as the study area. The depth of groundwater level, rainfall, topography and geomorphology, soil moisture, pollution source, pollution toxicity and other more than 10 parameters were used as the indexes. A comprehensive model with remote sensing cloud computing, DRASTIC model and Modflow + MT3DMS was established to assess the pollution risk from 2014 to 2021. The multi-year results indicated that the risk assessment of groundwater pollution was usually on the vertical coastal direction, and the risk increased from far away to near coast. With the discharge of pollutants in the industrial park, the pollution risk in the area 5 km away from the centre increased year by year until it became stable in 2019, and the risk in the centre of the park reached 1 level, covered an area of up to 145400 square metres, accounted for 0.012% of the whole study area. The assessment results in 2020 and 2021 fluctuate slightly compared with those in 2019. Therefore, in terms of groundwater resource protection and resource management, it is necessary to focus on the detection of pollution in the coastal zone and the pollution within 5 km of the centre to strictly control pollution discharge. In this study, the comprehensive assessment includes surface indicators, subsurface indicators, and pollutant indicators. Finally, we achieve a multivariate, spatial and long time series groundwater pollution risk assessment system, which is a new groundwater environmental impact assessment (GEIA) system.


Assuntos
Monitoramento Ambiental , Água Subterrânea , Monitoramento Ambiental/métodos , Poluição Ambiental , Solo , Medição de Risco/métodos
16.
Front Genet ; 14: 1327258, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38274112

RESUMO

Background: Preconception or prenatal carrier screening plays an important role in reproductive decision-making, but current research on hereditary deafness is limited. This study aimed to investigate the carrier frequencies of common deafness genes in the Chinese population who underwent carrier screening and to follow up on pregnancy outcomes in high-chance couples. Methods: Individual females or couples in preconception or early pregnancy were recruited from two hospitals in China. Carrier screening for common deafness genes in the Chinese population, including the GJB2 and SLC26A4 genes, was performed using next-generation sequencing technology. Genetic counseling was provided to subjects before and after testing. Results: Of the 9,993 subjects screened, the carrier rate was 2.86% for the GJB2 gene and 2.63% for the SLC26A4 gene. The variant with the highest carrier frequency in GJB2 was c.235delC (1.89%), and c.919-2A>G (1.08%) in SLC26A4. Of the six high-chance couples, four made alternative reproductive decisions (three with prenatal diagnosis and one with preimplantation genetic testing), with consequent termination of the birth of two affected fetuses. Conclusion: These findings confirmed the clinical utility of preconception or prenatal carrier screening for hereditary deafness.

17.
Animals (Basel) ; 12(21)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36359082

RESUMO

Beta-defensin-1 (BD-1) is among the class of antibacterial peptides that are rich in disulfide bonds, have direct antibacterial activity and showed enhanced expression following external stimulation. However, existing research studies only treated BD-1 to cell models without stimulation from pathogen-associated molecular patterns (PAMPs), which will further influence our understanding of the role of BD-1. In this study, we map the tissue distribution of Equus BD-1 (i.e., eBD-1, ass BD-1, and mule BD-1) and compare their expression levels in various tissues. We further characterize the three kinds of Equus BD-1 by analyzing their full-length cDNA. We showed that eBD-1, ass BD-1, and mule BD-1 have an identical (100%) open reading frame (ORF). The ORF encoding OEBD-1 expressed the ORF in the E. coli Top10 expression system. This expression system was combined with an S. aureus-infected J774A.1 macrophage cell line to determine the influence on innate immune mediator expression. Using this expression model system, it was determined that the OEBD-1 protein enhanced IL-6 and TNF-α secretion. It can also promote TLR2, IL-1ß, CCL2, CCL7, CXCL10 and NF-κB p65 mRNA expression. Moreover, OEBD-1 upregulates phosphorylation of ATK, Syk and IκB-α. In addition, OEBD-1 enhances the macrophage's ability to phagocytose S. aureus. In conclusion, Equus BD-1 was shown to play an essential role in macrophage-involved innate immune responses in an in vitro system.

18.
Front Bioeng Biotechnol ; 10: 970859, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159693

RESUMO

Rapid and accurate prediction of interaction force is an effective way to enhance the compliant control performance. However, whether individual muscles or a combination of muscles is more suitable for interaction force prediction under different contraction tasks is of great importance in the compliant control of the wearable assisted robot. In this article, a novel algorithm that is based on sEMG and KPCA-DRSN is proposed to explore the relationship between interaction force prediction and sEMG signals. Furthermore, the contribution of each muscle to the interaction force is assessed based on the predicted results. First of all, the experimental platform for obtaining the sEMG is described. Then, the raw sEMG signal of different muscles is collected from the upper arm during different contractions. Meanwhile, the output force is collected by the force sensor. The Kernel Principal Component Analysis (KPCA) method is adopted to remove the invalid components of the raw sEMG signal. After that, the processed sequence is fed into the Deep Residual Shrinkage Network (DRSN) to predict the interaction force. Finally, based on the prediction results, the contribution of each sEMG signal from different muscles to the interaction force is evaluated by the mean impact value (MIV) indicator. The experimental results demonstrate that our methods can automatically extract the valid features of sEMG signal and provided fast and efficient prediction. In addition, the single muscle with the largest MIV index could predict the interaction force faster and more accurately than the muscle combination in different contraction tasks. The finding of our research provides a solid evidence base for the compliant control of the wearable robot.

19.
Animals (Basel) ; 12(17)2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36077890

RESUMO

Dosage compensation is a mechanism first proposed by Susumu Ohno, whereby X inactivation balances X gene output between males (XY) and females (XX), while X upregulation balances X genes with autosomal gene output. These mechanisms have been actively studied in Drosophila and mice, but research regarding them lags behind in domestic species. It is unclear how the X chromosome is regulated in the sheep male germline. To address this, using single-cell RNA sequencing, we analyzed testes in three important developmental stages of sheep. We observed that the total RNA per cell from X and autosomes peaked in SSCs and spermatogonia and was then reduced in early spermatocytes. Furthermore, we counted the detected reads per gene in each cell type for X and autosomes. In cells experiencing dose compensation, close proximity to MSL (male-specific lethal), which is regulated the active X chromosome and was observed. Our results suggest that there is no dose compensation in the pre-meiotic germ cells of sheep testes and, in addition, MSL1 and MSL2 are expressed in early germ cells and involved in regulating mammalian X-chromosome inactivation and activation.

20.
Cell Mol Biol (Noisy-le-grand) ; 68(3): 339-346, 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35988168

RESUMO

This study was to investigate the effect of microcirculation disturbance of PVP on HBD epithelial cells in rats undergoing liver transplantation and to explore the postoperative rejection reduction by nanocarriers mediation. For this aim, adult male rats weighing 210-250 g, were fed cleanly and were subjected to liver transplantation. 3 days after the surgery, the rats were randomly divided into three groups based on different intervention factors: group A (HAL), group B (HAMI combined with HAL), and group C (control). The three groups of rats were divided into three subgroups according to the duration of the University of Wisconsin (UW) solution (UW time) used to preserve the donor organs for transplantation, which were 2h, 8h, and 16h, respectively. In addition, the RNA sequence of rat class-II transactivator (CIITA) the rat was searched, and the target interference sequence was designed concerning the RNA. Results showed that the carrier nanoparticles were spherical without obvious oxygen vacancies, the distribution was relatively tight and concentrated, and the main particle size was 50-140 nm. As the mass ratio of HGPAE to DNA increased, the mobility speed of the nanocarrier/shRNA plasmid complex decreased due to the decrease in surface charge. When the mass ratio reached 90:1, the mobility of the complex was completely blocked, suggesting that the DNA was completely compounded. The counts of PCNA, CK-19, F-VIII-Ag, VEGFA, VEGFB, and VEGFC in the 3 groups all showed a downward trend with the increase of UW time; the count in group B was lower than that of groups A and C. In the PCNA count statistics, there was no obvious difference between group A and group B at UW8h, but there were differences in contrast to group C (p<0.05). It was concluded that the blood supply of the microcirculation of the PVP was extremely important for the transplanted liver tissue. When the blood vessels around the HBD of the rat were completely ischemic, the HBD epithelial cells became the most important target of damage, and the proliferation and changes of the HBD epithelial cells can be directly observed. In addition, the nanocarrier-mediated genes were applied to discuss postoperative rejection. The expression of class-II MHC-II gene in nanocarrier CIITA-shRNA was inhibited, which interfered with the recipient's immune recognition of the graft, thereby reducing the intensity of the rejection reaction and relieving the rejection reaction.


Assuntos
Transplante de Fígado , Microcirculação , Animais , Ductos Biliares , Células Epiteliais , Rejeição de Enxerto/tratamento farmacológico , Fígado/metabolismo , Fígado/cirurgia , Transplante de Fígado/métodos , Masculino , Sistemas de Liberação de Fármacos por Nanopartículas/farmacologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , RNA Interferente Pequeno/metabolismo , Ratos
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