RESUMO
Kif16A, a member of the kinesin-3 family of motor proteins, has been shown to play crucial roles in inducing mitotic arrest, apoptosis, and mitotic cell death. However, its roles during oocyte meiotic maturation have not been fully defined. In this study, we report that Kif16A exhibits unique accumulation on the spindle apparatus and colocalizes with microtubule fibers during mouse oocyte meiotic maturation. Targeted depletion of Kif16A using gene-targeting siRNA disrupts the progression of the meiotic cell cycle. Furthermore, Kif16A depletion leads to aberrant spindle assembly and chromosome misalignment in oocytes. Our findings also indicate that Kif16A depletion reduces tubulin acetylation levels and compromises microtubule resistance to depolymerizing drugs, suggesting its crucial role in microtubule stability maintenance. Notably, we find that the depletion of Kif16A results in a notably elevated incidence of defective kinetochore-microtubule attachments and the absence of BubR1 localization at kinetochores, suggesting a critical role for Kif16A in the activation of the spindle assembly checkpoint (SAC) activity. Additionally, we observe that Kif16A is indispensable for proper actin filament distribution, thereby impacting spindle migration. In summary, our findings demonstrate that Kif16A plays a pivotal role in regulating microtubule and actin dynamics crucial for ensuring both spindle assembly and migration during mouse oocyte meiotic maturation.
Assuntos
Cinesinas , Meiose , Microtúbulos , Oócitos , Fuso Acromático , Animais , Cinesinas/metabolismo , Cinesinas/genética , Meiose/fisiologia , Oócitos/metabolismo , Microtúbulos/metabolismo , Camundongos , Fuso Acromático/metabolismo , Feminino , Actinas/metabolismo , Cinetocoros/metabolismoRESUMO
BACKGROUND: To investigate the efficiency of a new method for the prevention of argentinian flag sign during the process of continuous, circular, and centered anterior capsulotomy (CCC) on the anterior capsule in cortically liquefied intumescent cataracts. This study was registered in an appropriate registry and the registration number of registration was xyy11[2022]-XJSFX-087; The date of of registration was 2022-04-29. METHODS: Preoperative examinations including slit-lamp examination, ocular A-scan ultrasonography, and Ultrasound Biomicroscopy (UBM) UBM were conducted on 61 patients with intumescent cataracts. Cases with cortically liquefied intumescent cataracts were selected and after staining with indocyanine green, the anterior chamber air bubble technique was used to compress the anterior capsule, and liquefied cortex was aspirated using a puncture needle. Corrected Distance Visual Acuity (CDVA) and intraocular pressure were recorded on postoperative days 1, 1 week, 1 month, and 6 months. Intraoperative and postoperative complications were documented and analyzed. RESULTS: Fifty eyes were identified as having cortically liquefied intumescent cataracts. No cases of the Argentinian flag sign occurred, and standard capsulorrhexis was achieved, facilitating smooth phacoemulsification. All patients achieved satisfactory outcomes at follow-ups of 1 day, 1 week, 1 month, and 6 months postoperatively. Mild corneal edema was observed in three cases on the first postoperative day, with no other complications noted. CONCLUSIONS: The anterior chamber air bubble technique combined with cortical fluid release technique can prevent the occurrence of the Argentinian flag sign in cortically liquefied intumescent cataracts, this method is simple, convenient and economic for the clinical promotion.
Assuntos
Câmara Anterior , Catarata , Facoemulsificação , Acuidade Visual , Humanos , Feminino , Masculino , Câmara Anterior/diagnóstico por imagem , Idoso , Pessoa de Meia-Idade , Acuidade Visual/fisiologia , Facoemulsificação/métodos , Microscopia Acústica , Ar , Capsulorrexe/métodos , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso de 80 Anos ou mais , Cápsula do Cristalino/cirurgia , Cápsula do Cristalino/diagnóstico por imagemRESUMO
OBJECTIVES: To investigate the differences in visual perception between children with autism spectrum disorder (ASD) and typically developing (TD) children when watching different intention videos, and to explore the feasibility of machine learning algorithms in objectively distinguishing between ASD children and TD children. METHODS: A total of 58 children with ASD and 50 TD children were enrolled and were asked to watch the videos containing joint intention and non-joint intention, and the gaze duration and frequency in different areas of interest were used as original indicators to construct classifier-based models. The models were evaluated in terms of the indicators such as accuracy, sensitivity, and specificity. RESULTS: When using eight common classifiers, including support vector machine, linear discriminant analysis, decision tree, random forest, and K-nearest neighbors (with K values of 1, 3, 5, and 7), based on the original feature indicators, the highest classification accuracy achieved was 81.90%. A feature reconstruction approach with a decision tree classifier was used to further improve the accuracy of classification, and then the model showed the accuracy of 91.43%, the specificity of 89.80%, and the sensitivity of 92.86%, with an area under the receiver operating characteristic curve of 0.909 (P<0.001). CONCLUSIONS: The machine learning model based on eye-tracking data can accurately distinguish ASD children from TD children, which provides a scientific basis for developing rapid and objective ASD screening tools.
Assuntos
Transtorno do Espectro Autista , Criança , Humanos , Transtorno do Espectro Autista/diagnóstico , Tecnologia de Rastreamento Ocular , Intenção , Algoritmos , Aprendizado de MáquinaRESUMO
The phycobilisome (PBS) is the major light-harvesting apparatus in cyanobacteria and red algae. It is a large multi-subunit protein complex of several megadaltons that is found on the stromal side of thylakoid membranes in orderly arrays. Chromophore lyases catalyse the thioether bond between apoproteins and phycobilins of PBSs. Depending on the species, composition, spatial assembly, and, especially, the functional tuning of different phycobiliproteins mediated by linker proteins, PBSs can absorb light between 450 and 650 nm, making them efficient and versatile light-harvesting systems. However, basic research and technological innovations are needed, not only to understand their role in photosynthesis but also to realise the potential applications of PBSs. Crucial components including phycobiliproteins, phycobilins, and lyases together make the PBS an efficient light-harvesting system, and these provide a scheme to explore the heterologous synthesis of PBS. Focusing on these topics, this review describes the essential components needed for PBS assembly, the functional basis of PBS photosynthesis, and the applications of phycobiliproteins. Moreover, key technical challenges for heterologous biosynthesis of phycobiliproteins in chassis cells are discussed.
Assuntos
Ficobilissomas , Rodófitas , Ficobilissomas/química , Ficobilissomas/metabolismo , Ficobilinas , Ficobiliproteínas/química , Ficobiliproteínas/metabolismo , Fotossíntese , Rodófitas/químicaRESUMO
Vulvovaginal candidiasis (VVC), a major gynecological disease with high recurrence rate, increases the risk of abortion, intrauterine infection, premature rupture of membranes, and premature birth in pregnancy. However, the exact pathogenesis of this disease has yet to be elucidated. To facilitate understanding of the pathogenesis of VVC in pregnancy, this study sought to establish an animal model of vaginal infection with Candida albicans in pregnant mice. Female mice were mated with male mice, and female mice were infected with C. albicans at E4.5 (embryonic day 4.5). The weight and abortion rate of pregnant mice at E0.5, E4.5, E8.5, E11.5, and E18.5 were recorded, respectively, as well as the weights of fetus and placenta on E18.5. Fetal weight at E18.5 and the weight growth rate in the experimental mice was lower than those in the control mice, but the placenta weight at E18.5 and the abortion rate in the experimental mice were increased with those of the control mice. Hematoxylin-eosin (H&E) staining, Gomori-Grocott staining and vaginal lavage culturing were conducted to verify that the experimental mice were infected with C. albicans. Differentially expressed gene IL-15 was screened out by polymerase chain reaction (PCR) array between the two groups. Enzyme-linked immunosorbent assay (ELISA) showed that IL-15 expression in plasma of the mice was decreased in the experimental group compared with the control group. RT-qPCR confirmed that IL-15 mRNA expression was increased in placental tissues, while mRNA expression of IL-15R/JAK1-JAK3/PI3K/PDK1/AKT/P70S6K-mTOR was decreased in placental tissues. In conclusion, this study demonstrated that VVC in BALB/c pregnant mice led to a series of adverse pregnancy outcomes that were related to changes in IL-15 and its downstream signaling pathways, which may indicate a potential therapy for VVC during pregnancy in humans.
Assuntos
Candidíase Vulvovaginal , Interleucina-15 , Animais , Candida albicans/genética , Candidíase Vulvovaginal/patologia , Feminino , Humanos , Interleucina-15/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Placenta/patologia , Gravidez , Resultado da Gravidez , RNA MensageiroRESUMO
In this study, fourteen new cholic acid (CA) derivatives were designed and synthesized, and the GloSensor cAMP accumulation assay indicated that all derivatives could activate the Takeda G protein-coupled receptor 5 (TGR5). Methylation of 7- and 12-hydroxyl groups in CA significantly increased TGR5 agonism for the new derivatives. For example, 7,12-dimethoxy derivative B1 exhibited 78-fold higher potency for TGR5 than the 7,12-dihydroxyl derivative A1 and 258-fold higher potency than CA itself. On the other hand, A1 positively modulated chenodeoxycholic acid (CDCA) functional activity in TGR5, whereas B1 did not show similar activity. Molecular docking experiments indicated that A1 formed a hydrogen bond between the 12-OH and amino acid Thr131 of TGR5, which is significant for its allosteric property. However, methylation at the 12-hydroxyl group in CA (derivative B1) disrupted this pivotal H-bond. Therefore, the free 12-hydroxyl group is essential for the CA derivatives in TGR5 allosteric agonism. Overall, we discovered a highly potent TGR5 agonist, B1, which can be used as lead compound for further study.
Assuntos
Ácidos e Sais Biliares , Receptores Acoplados a Proteínas G , Ácido Cólico/farmacologia , Proteínas de Ligação ao GTP/metabolismo , Simulação de Acoplamento Molecular , Receptores Acoplados a Proteínas G/metabolismoRESUMO
BACKGROUND: Chronic kidney disease (CKD) is prevalent in older adults. In the aging CKD population, cognitive frailty is more common, but its prevalence and associated risk factors need to be further investigated. METHODS: This is a cross-sectional study that enrolled patients aged ≥ 60 years with a diagnosis of CKD from January 2018 to February 2021. Patients were assessed for frailty and cognition with the FRAIL and the Mini-Mental State Examination (MMSE) scales and were divided into the cognitive frailty and non-cognitive frailty groups. Risk factors for cognitive frailty were identified by univariate and multivariate logistic regression analyses. A prediction model for cognitive frailty was built and a nomogram was plotted. The performance of the nomogram was evaluated by using a concordance index (C-index) and calibration plots. RESULTS: A total of 1015 older patients with CKD were enrolled, among whom 607 (59.8%) were males and 408 (40.2%) were females, with an age ranging from 60 to 98 years, and an cognitive frailty prevalence of 15.2%. The prevalence of cognitive frailty varied among the CKD stages 1-5, with rates of 4.7%, 7.5%, 13.8%, 18.5%, and 21.4%, respectively. Multivariate logistic regression analysis showed that age (OR = 1.11, 95%CI 1.08-1.14, p < 0.001), depression (OR = 2.52, 95%CI 1.54-4.11, p < 0.001), low social support (OR = 2.08, 95%CI 1.28-3.39, p = 0.003), Charlson comorbidity index (CCI) (OR = 1.92, 95%CI 1.70-2.18, p < 0.001), eGFR (OR = 0.98, 95%CI 0.96-0.99, p < 0.001) and albuminuria (OR = 5.93, 95%CI 3.28-10.74, p < 0.001) were independent risk factors affecting the association with cognitive frailty in older patients with CKD. A nomogram for assessing cognitive frailty was established and well-calibrated with a C-index of 0.91 (95%CI 0.89-0.94). CONCLUSIONS: The prevalence of cognitive frailty was higher in older patients having CKD. Advanced age, comorbidity, depression, low social support, eGFR and albuminuria were independent risk factors for CKD accompanied with cognitive frailty.
Assuntos
Fragilidade , Insuficiência Renal Crônica , Idoso , Albuminúria , Estudos Transversais , Feminino , Idoso Fragilizado/psicologia , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Avaliação Geriátrica , Humanos , Masculino , Prevalência , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologiaRESUMO
BACKGROUND: Maternal intrapartum fever has a serious impact on mother and child. However, the corresponding study seems to be in short. METHODS: The role of inflammatory cells in patients who were diagnosed with intrapartum fever lived in part of Eastern China was evaluated. The obstetrics outcomes, complete blood cell count (CBC) and thereby converted neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio, monocyte to lymphocyte ratio (MLR), and vaginal secretion were compared in different groups. RESULTS: Prepartum values of white blood cell (WBC), red blood cell (RBC), and hemoglobin (Hb) were all a little higher in the febrile group than in the afebrile group, and postpartum WBC in the afebrile group was still higher while postpartum RBC and Hb were inferior to non-fever maternity. Postpartum NLR and MLR were all higher in the fever group but not preferred overtly difference before delivery. Additionally, the comparison of WBC, RBC, Hb, platelets, neutrophils, and monocytes in prepartum and postpartum all showed significant differences. CONCLUSION: The parturition could bring about the value change of CBC and intrapartum fever might aggravate or alleviate this change. Besides, the intrapartum fever might not be caused mainly by infection and the difference between bacteria and fungus could reflect in the CBC.
Assuntos
Febre , Período Periparto/fisiologia , Complicações na Gravidez , Adulto , Contagem de Células Sanguíneas , China/epidemiologia , Estudos Transversais , Feminino , Febre/epidemiologia , Febre/fisiopatologia , Humanos , Recém-Nascido , Parto , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/fisiopatologia , Resultado da Gravidez/epidemiologiaRESUMO
Preterm birth (PTB) is a major cause of neonatal mortality, with a poorly understood etiology. The regular contraction of the myometrium was considered as contributing to the etiology of the onset of labor, especially PTB. Thus, studying the mechanism of myometrium contraction is very important for understanding the initiation of labor and also for preventing PTB. Using liquid chromatography-mass spectrometry, we found 322 significantly differential peptides in myometrium tissues between term nonlabor and term labor groups (absolute fold change ≥ 2 and P < .05). We next analyzed length, molecular weights, isoelectric point, and cleavage site of all the different peptides. We, next, analyzed the functions of different peptides through their precursor proteins by Gene Ontology, enrichment and canonical pathway analysis. The results indicated that the extracellular matrix (ECM) played a major role in biological process, the cellular component, and molecular function categories, and revealed that ECM remodeling played a vital role in myometrial contraction. In addition, some known signaling, such as corticotropin-releasing hormone signaling and calcium signaling were proven to be involved in this process. Ingenuity Pathways Analysis upstream regulator analysis suggested that some of the known molecules, which reportedly were very important in labor onset, were included, for example, nuclear factor κB, tubulin, and phosphoinositide 3-kinase. We also identified 23 peptides derived from the precursor protein TITIN, of which 21 peptides sequences from TITIN were located in functional domains. These results suggested that peptides play an important role in labor onset and provide further insight into PTB therapy.
Assuntos
Trabalho de Parto/metabolismo , Miométrio/metabolismo , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/metabolismo , Nascimento Prematuro/metabolismo , Adulto , Feminino , Humanos , Gravidez , ProteômicaRESUMO
A simple, specific and selective quantitative analysis of multi-components by single marker(QAMS) method for simultaneous determination of anthraquinones and anthraquinone glycosides in Polygonum multiflorum was developed. Four main anthraquinones and its glycosides, emodin, emodin-8-O-ß-D-glucoside, physcion and physcion-8-O-ß-D-glucoside were selected as analytes to evaluate the quality of P. multiflorum. Emodin was used as the internal standard, and the relative correction factors(RCFs) between emodin and the other three anthraquinones were calculated. Comparison of the contents of the four components in 30 batches of P. multiflorum from different regions and 12 batches decoction pieces from different manufacturers by QAMS and external standard method(ESM) showed that there was no significant difference between QAMS and ESM for quantification of the four main components by using relative error results, and the QAMS method was accurate and reliable, and had a good repeatability. In addition, compared with the results calculated by the difference method between total anthraquinone and free anthraquinone in the content determination of P. multiflorum in Chinese Pharmacopoeia, the results of direct determination combined anthraquinone by QAMS were very close to that by measured the external standard method. Therefore, simultaneous quantification of four main anthraquinones by using QAMS is suitable to evaluate the quality of P. multiflorum. Then the optimized assay method of the combined anthraquinone contents showed simple and feasible, which could be replaced and improved the quantification method of the combined anthraquinone in the current Chinese Pharmacopeia.
Assuntos
Antraquinonas/análise , Medicamentos de Ervas Chinesas/análise , Fallopia multiflora/química , Cromatografia Líquida de Alta Pressão , Glucosídeos , Compostos Fitoquímicos/análiseRESUMO
PURPOSE: To evaluate whether programmed intermittent epidural bolus (PIEB) reduces the incidence of maternal intra-partum fever compared with continuous epidural infusion (CEI) during labor. METHODS: Parturients were randomized to receive CEI (CEI group) or PIEB (PIEB group) with 10 ml per hour for epidural labor analgesia with 1500 subjects in each group. The maintaining dose of two groups is 0.08% ropivacaine with 0.4 µg/ml sufentanil, with patient-controlled epidural analgesia (PCEA) dose of 5 ml and lockout interval of 30 min. The incidence of maternal fever, pain score, epidural sensory levels, the number and proportion of PCEA demand, anesthetics consumption, satisfaction score, neonatal Apgar scale, and maternal and neonatal side effects were recorded. RESULTS: It was significantly lower of the incidence of maternal fever beginning at 4 h post-analgesia and continuing until delivery in the PIEB group than the CEI group (4 h: 2.6% vs. 4.2%; 5 h: 7.3% vs. 10.2%; delivery: 5.6% vs. 7.9%; 1 h post-delivery: 3.9% vs. 6.2%; 2 h post-delivery: 2.1 vs. 3.5%; total: 5.8% vs. 8.4% in PIEB and CEI, respectively). Compared with CEI group, pain scores at 3, 4, 5 h post-analgesia and delivery (3 h: 2 [1, 2] vs. 2 [1-3]; 4 h: 2 [2, 3] vs. 3 [2-4]; 5 h: 2 [2, 3] vs. 3 [2-4]; delivery: 3 [2-4] vs. 4 [3, 4] in PIEB and CEI, respectively), the number and proportion of PCEA demand (number: 0.7 ± 0.9 vs. 2.2 ± 1.9; proportion: 42.0% vs. 80.3% in PIEB and CEI, respectively), and anesthetics consumption significantly decreased in the PIEB group (Ropivacaine: 60 ± 13 mg vs. 76 ± 17 mg; Sufentanil: 26 ± 4 mg vs. 32 ± 6 mg in PIEB and CEI, respectively), without severe maternal and neonatal side effects and any difference in neonatal Apgar scale. The epidural sensory levels 2 h post-analgesia (2 h: 8[8, 9] vs. 9[8, 9] in PIEB and CEI) and satisfaction score (9 [9, 10] vs. 7 [6, 7] in PIEB and CEI) were significantly higher in the PIEB group compared with those in the CEI group. CONCLUSIONS: PIEB with 10 ml of 0.08% ropivacaine and 0.4 µg/ml sufentanil hourly provided a lower incidence of intra-partum fever with a better analgesic effect compared with CEI, without any severe maternal and neonatal adverse reactions.
Assuntos
Analgesia Epidural/métodos , Analgesia Obstétrica/métodos , Analgésicos/administração & dosagem , Anestésicos Locais/administração & dosagem , Febre/epidemiologia , Adulto , Analgesia Epidural/efeitos adversos , Analgesia Obstétrica/efeitos adversos , Método Duplo-Cego , Feminino , Febre/prevenção & controle , Humanos , Incidência , Trabalho de Parto , Paridade , Gravidez , Ropivacaina/administração & dosagem , Sufentanil/administração & dosagemAssuntos
Injúria Renal Aguda , Síndrome de Hipersensibilidade a Medicamentos , Eosinofilia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Alopurinol/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Eosinofilia/induzido quimicamente , Eosinofilia/diagnóstico , Supressores da Gota/efeitos adversos , HumanosRESUMO
Autophagy plays an important role in the development of diabetic retinopathy (DR). Retinal pigment epithelial (RPE) cells are the main cells involved in DR, a process in which hyperglycemia plays a crucial role. This study was conducted to investigate the protective effect of autophagy against high glucose-induced inflammatory response in ARPE-19 cells and its underlying mechanism. In the present study we subjected ARPE-19 cells to high glucose stress and showed that ARPE-19 cells respond to high glucose with an increase in autophagy. 3-methyladenine (3-MA) inhibited occurrence of autophagy and it leaded to the accumulation of damaged-mitochondria-producing-ROS, and the activation of NLRP3 inflammasome, and subsequently, caused IL-1ß secretion.
Assuntos
Autofagia/fisiologia , Proteínas de Transporte/metabolismo , Glucose/metabolismo , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico , Linhagem Celular , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/metabolismoRESUMO
BACKGROUND: The formation of scar-like fibrous tissue in age-related macular degeneration (AMD) is associated with hypoxia. Under hypoxia, retinal pigment epithelial (RPE) cells can secret more transforming growth factor-ß2 (TGF-ß2), which is determined to induce epithelial-mesenchymal transition (EMT) at certain concentrations. Whether hypoxia can induce EMT by stimulating RPE cell line secrets TGF-ß2 or not remains unknown. To gain a better understanding of the signaling mechanisms of fibrosis in AMD under hypoxic conditions, we investigated EMT in retinal pigment epithelial (RPE) cells and the effect of TGF-ß2 and Snail in this process. METHODS: Human RPE cell line (ARPE-19) was incubated with 5 % O2 for different periods of time. The expression of N-cadherin, α-smooth muscle actin (α-SMA), TGF-ß2 , and Snail were determined by Western blot and real-time PCR. Cell proliferation was assessed by CCK8 kit. RNA interference was used for multi-gene silencing of TGF-ß2 and Snail genes. RESULTS: N-cadherin was decreased and mesenchymal cell marker α-SMA was increased after the ARPE-19 cell line was incubated with 5 % O2. Meanwhile, the proliferation capability of the cell line was increased. TGF-ß2 and Snail expression were increased in a time-dependent manner under hypoxia. After multi-silencing TGF-ß2 and Snail genes, N-cadherin was increased and α-SMA was reduced. Meanwhile, the proliferation of the cell line was suppressed. CONCLUSIONS: Under hypoxic conditions, RPE cells undergo EMT. Endogenic TGF-ß2 and Snail are involved in this process. Furthermore, knockdown of both TGF-ß2 and Snail inhibited EMT to a greater extent than knockdown of either gene individually.
Assuntos
Transição Epitelial-Mesenquimal/fisiologia , Inativação Gênica/fisiologia , Hipóxia/metabolismo , Epitélio Pigmentado da Retina/citologia , Fatores de Transcrição/genética , Fator de Crescimento Transformador beta2/genética , Actinas/genética , Actinas/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Western Blotting , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular , Proliferação de Células , Humanos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Epitélio Pigmentado da Retina/metabolismo , Fatores de Transcrição da Família Snail , Fatores de Transcrição/metabolismo , Transfecção , Fator de Crescimento Transformador beta2/metabolismoRESUMO
PURPOSE: There is increasing evidence that suggests stromal cell-derived factor-1 (SDF-1) can induce a protective response against ischemic injury in various organs. In this study, we examined the expression of SDF-1 in a rat model of retinal ischemia-reperfusion (IR) injury. Further, we explored the effect of estrogen 17ß-estradiol (E2), and the role of estrogen receptor (ER) in regulating SDF-1 expression. METHODS: Retinal IR injury was established in Sprague-Dawley rats by elevating the intraocular pressure to 110 mmHg for 60 mins. Relative expression levels of SDF-1 mRNA and protein in the retina at 6 h, 12 h, and 24 h after reperfusion were determined by RT-PCR and western blot respectively. To investigate the influence of estrogen and ER on SDF-1 expression, E2 was administered intraperitoneally 30 mins before induction of ischemia, and the estrogen receptor antagonist ICI 182-780 was administered 1 h before E2 injection. RESULTS: SDF-1 expression in IR-injured retina is upregulated at 6 h, 12 h, and 24 h after injury, with maximum expression at 12 h. As expected, pretreatment of retinal IR rats with E2 enhanced the upregulation in SDF-1 expression after injury, through activation of the estrogen receptor. We proved this hypothesis by demonstrating that pretreatment of retinal IR rats with ICI 182-780 led to a partial decrease in E2-induced SDF-1 expression. CONCLUSIONS: Our findings suggest that 17ß-estradiol offers protection against retinal ischemic injury by inducing an upregulation in SDF-1 expression through activation of the estrogen receptor.
Assuntos
Quimiocina CXCL12/genética , Estradiol/farmacologia , Estrogênios/farmacologia , Regulação da Expressão Gênica/fisiologia , Receptores de Estrogênio/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Retina/efeitos dos fármacos , Animais , Western Blotting , Quimiocina CXCL12/metabolismo , Modelos Animais de Doenças , Estradiol/análogos & derivados , Antagonistas do Receptor de Estrogênio/farmacologia , Fulvestranto , Masculino , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Retina/metabolismo , Regulação para CimaRESUMO
BACKGROUND: Understanding and predicting others' behavior in a dynamic and rapidly changing world is a fundamental aspect of social interactions. However, it remains unclear as to whether children with autism spectrum disorder (ASD) could understand and predict goal-directed social actions. AIMS: To investigate the understanding of give-and-take interactions in children with ASD with the use of eye tracking. METHODS AND PROCEDURES: Experiment 1 and 2 investigated the understanding of giving and taking respectively in 5-to 8-year-old Chinese children with ASD and typically developing children by using the eye-tracking technology. OUTCOMES AND RESULTS: We found that children with ASD could predict actions, but they were less proficient in processing give-and-take interactions. Moreover, children with ASD showed impaired understanding of giving but not taking. CONCLUSIONS: These results indicate that the basic mechanisms of action prediction are intact in children with ASD whereas there may be deficits in the top-down social processing of the giving gesture.
Assuntos
Transtorno do Espectro Autista , Criança , Humanos , Pré-Escolar , Comportamento Social , Interação SocialRESUMO
BACKGROUND: Altered automatic attention cueing has been reported in autistic children. Yet less is known about how autistic children would respond when the social cue that directs attention occurs in an implied social interaction. METHODS: By using eye-tracking, the current study examined orienting responses to a socially-relevant target or a nonsocial target cued by a goal-directed social gesture in autistic children. Saccadic reaction time and pupillary responses were employed to measure gaze behavior and physiological arousal of autistic children. RESULTS: Both groups of children showed reflexive orienting to the target regardless of its sociality, whereas typically developing (TD) children exhibited faster gaze shift than autistic children when the target was a social stimulus. An increased pupil dilation was observed in autistic children in response to stimuli relative to TD children. Further, autistic children showed larger baseline pupil response. CONCLUSIONS: Autistic children show attenuated sensitivity to social targets and atypical pupil responses, which may be due to the dysfunction of locus coeruleus (LC) - norepinephrine (NE) system.
Assuntos
Atenção , Sinais (Psicologia) , Tecnologia de Rastreamento Ocular , Gestos , Pupila , Tempo de Reação , Humanos , Masculino , Atenção/fisiologia , Feminino , Criança , Pupila/fisiologia , Tempo de Reação/fisiologia , Transtorno Autístico/fisiopatologia , Transtorno Autístico/psicologia , Fixação Ocular/fisiologia , Estimulação Luminosa/métodos , Movimentos Sacádicos/fisiologiaRESUMO
Accumulating evidence suggests that individuals with autism spectrum disorder (ASD) show impairments in using contextual priors to predict others' actions and make intention inference. Yet less is known about whether and how children with ASD acquire contextual priors during action observation and how contextual priors relate to their action prediction and intention inference. To form proper contextual priors, individuals need to observe the social scenes in a reliable manner and focus on socially relevant information. By employing a data-driven scan path method and areas of interest (AOI)-based analysis, the current study investigated how contextual priors would relate to action prediction and intention understanding in 4-to-9-year-old children with ASD (N = 56) and typically developing (TD) children (N = 50) during free viewing of dynamic social scenes with different intentions. Results showed that children with ASD exhibited higher intra-subject variability when scanning social scenes and reduced attention to socially relevant areas. Moreover, children with high-level action prediction and intention understanding showed lower intra-subject variability and increased attention to socially relevant areas. These findings suggest that altered fixation patterns might restrain children with ASD from acquiring proper contextual priors, which has cascading downstream effects on their action prediction and intention understanding.
Assuntos
Atenção , Transtorno do Espectro Autista , Humanos , Transtorno do Espectro Autista/fisiopatologia , Transtorno do Espectro Autista/psicologia , Masculino , Feminino , Criança , Atenção/fisiologia , Pré-Escolar , Intenção , Percepção SocialRESUMO
Gaze abnormalities are well documented in infants at elevated risk for autism spectrum disorder (ASD). However, variations in experimental design and stimuli across studies have led to mixed results. The current meta-analysis aimed to identify which type of eye tracking task and stimulus are most effective at differentiating high-risk infants (siblings of children with ASD) who later meet diagnosis criteria from low-risk infants without familial autism. We synthesized 35 studies that used eye tracking to investigate gaze behavior in infants at high genetic risk for autism before 2 years of age. We found that stimulus features, regions of interest (ROIs) and study quality moderated effect sizes across studies. Overall, dynamic stimuli and socially-relevant regions in the social stimuli (i.e. the target and activity of characters' shared focus) reliably detected high-risk infants who later develop ASD. Attention disengagement task and stimuli depicting interactions between human and nonhuman characters could identify high-risk infants who later develop ASD and those who have autism-related symptoms but do not meet the diagnostic criteria as well. These findings provide sensitive and reliable early markers of ASD, which is helpful to develop objective and quantitative early autism screening and intervention tools.