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1.
Hum Brain Mapp ; 41(1): 67-79, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31517428

RESUMO

An increasing number of studies in patients with generalized tonic-clonic seizures (GTCS) have reported the alteration of functional connectivity (FC) in many brain networks. However, little is known about the underlying temporal variability of FC in large-scale brain functional networks in patients. Recently, dynamic FC could provide novel insight into the physiological mechanisms in the brain. Here, we recruited 63 GTCS and 65 age- and sex-matched healthy controls. Dynamic FC approaches were used to evaluate alterations in the temporal variability of FC in patients at the region- and network-levels. In addition, two kinds of brain templates (>102 and > 103 regions) and two kinds of temporal variability FC approaches were adopted to verify the stability of the results. Patients showed increased FC variability in regions of the default mode network (DMN), ventral attention network (VAN) and motor-related areas. The DAN, VAN, and DMN illustrated enhanced FC variability at the within-network level. In addition, increased FC variabilities between networks were found between the DMN and cognition-related networks, including the VAN, dorsal attention network and frontal-parietal network in GTCS. Meanwhile, the alterations in FC variability were relatively consistent across different methods and templates. Therefore, the consistent alteration of FC variability would reflect a dynamic restructuring of the large-scale brain networks in patients with GTCS. Overly frequent information communication among cognition-related networks, especially in the DMN, might play a role in the epileptic activity and/or cognitive dysfunction in patients.

2.
ACS Omega ; 4(4): 6138-6143, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31459758

RESUMO

Carbon monoxide (CO) has long been recognized as a metabolic waste and toxic gas and is also the most common asphyxiating poison that seriously endangers human health. Thus, an adsorption material with high CO adsorption capability is urgently needed. In this study, carbon xerogels (CXs) doped with CuCl were prepared via a sol-gel method and a facile soaking process. The CuCl-doped CXs show the highest CO adsorption capacity of 12.04 cc/g, which is much higher than those of the undoped CXs and activated carbon. Such a high adsorption capacity of the CuCl-doped CXs is not only because of their high porosity but also because of the chemical adsorption induced by CuCl. Moreover, these CuCl-doped CXs exhibit high desorption rate (∼79%), which is beneficial for repeatability.

3.
J Drug Target ; : 1-10, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31429596

RESUMO

Background and purpose: The present study aimed to explore the feasibility and efficacy of the targeted non-invasive implantation of mesenchymal stromal cells (MSCs) by low-intensity ultrasound-targeted microbubble destruction (LI-UTMD) assisted blood-brain barrier (BBB) opening and its improvement on neurobehavioural outcomes in brain ischaemic rats. Methods: A transcranial irradiation of low-intensity ultrasound by diagnostic devices was performed, and lipid microbubbles (MBs) and MSCs were simultaneously infused. Then, the MSC transmigration from brain vessels to parenchyma was demonstrated, and MSCs were statistically analysed on days 1, 4, 7 and 14. Behavioural function was statistically analysed. Results: The extra-vascular leakage of lanthanum and EB was observed at the brain ischaemic area receiving ultrasound. MSCs were observed at the ultrasound irradiated brain hemisphere, and the number of MSCs in LI-UTMD assisted MSCs group was significantly higher than that in the MSCs group (p < .01). The attachment, traversing and trans-migration of MSCs across the BBB were recorded. Neuro-behavioural function was improved with this approach. Conclusions: The transcranial irradiation of low intensity ultrasound targeted MBs destruction on brain ischaemic rats might be a safe and efficient BBB opening approach to prompt the successful delivery of MSCs into the targeted area of brain ischaemia, and ameliorate neurological function.

4.
Nat Commun ; 10(1): 2914, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266968

RESUMO

The deubiquitylase OTUD3 plays a suppressive role in breast tumorigenesis through stabilizing PTEN protein, but its role in lung cancer remains unclear. Here, we demonstrate that in vivo deletion of OTUD3 indeed promotes breast cancer development in mice, but by contrast, it slows down KrasG12D-driven lung adenocarcinoma (ADC) initiation and progression and markedly increases survival in mice. Moreover, OTUD3 is highly expressed in human lung cancer tissues and its higher expression correlates with poorer survival of patients. Further mechanistic studies reveal that OTUD3 interacts with, deubiquitylates and stabilizes the glucose-regulated protein GRP78. Knockdown of OTUD3 results in a decrease in the level of GRP78 protein, suppression of cell growth and migration, and tumorigenesis in lung cancer. Collectively, our results reveal a previously unappreciated pro-oncogenic role of OTUD3 in lung cancer and indicate that deubiquitylases could elicit tumor-suppressing or tumor-promoting activities in a cell- and tissue-dependent context.


Assuntos
Proteínas de Choque Térmico/metabolismo , Neoplasias Pulmonares/enzimologia , Proteases Específicas de Ubiquitina/metabolismo , Animais , Carcinogênese , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Proteínas de Choque Térmico/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Nus , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteases Específicas de Ubiquitina/genética
6.
Ultrasound Med Biol ; 45(9): 2427-2433, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31160122

RESUMO

Insufficiency of microbubbles in the vessel-obstructing thrombus significantly reduces the effectiveness of ultrasound thrombolysis. With catheter-directed thrombolysis (CDT), microbubbles can be delivered directly into the thrombus. In this study, we combined CDT with intra-clot microbubble-enhanced ultrasound thrombolysis (IMUT) to investigate its safety and efficiency in thrombolysis in patients with acute lower limb deep vein thrombosis (DVT). For IMUT, a 1-MHz air-backed transducer directed 100-µs-pulse-length and 100-Hz-pulse-repetition pressure at 1 MPa was used. Thirteen DVT patients in the study group were treated with CDT and IMUT. Forty-three DVT patients in the historical control group were treated with CDT alone. The results indicated that the average thrombolysis time of the study group was significantly shorter (5.23 ± 1.59 d) than that of the control (10.00 ± 2.69 d), and the overall urokinase dosage of the study group ([3.82 ± 1.68] × 106 IU) was lower than that of the control ([4.99 ± 2.26] × 106 IU). No procedure-related complications were noted in either group. Therefore, combining CDT with IMUT can improve thrombolysis safely and efficiently.

7.
Clin Chim Acta ; 495: 507-511, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31152696

RESUMO

BACKGROUND: The pneumatic tube system (PTS) is widely established in clinical laboratories. We aimed to evaluate the impacts of PTS on high-sensitivity cardiac troponin T (hs-cTnT) assays. METHODS: The hemolysis distribution of hs-cTnT PTS specimens from emergency department (ED) were determined by hemolysis index (HI). Grouped samples from 15 healthy volunteers were delivered to the laboratory via manual delivery (MD) or PTS. Interference studies were conducted to access the influence of different hemolysis degrees on hs-cTnT assays. RESULTS: 7.26% PTS specimens from ED were hemolyzed in clinic. Compared with MD samples, we found highly elevated free plasma hemoglobin (Hb) in PTS samples. Hs-cTnT was interfered negatively with free Hb (R = -0.625, P < .001), and it was also validated in interference studies (R ≥ -0.820, all P ≤ .001). Clinically significant bias occurred in each hs-cTnT concentration at 100 mg/dl free Hb (Bias≥ - 13.85%, all P < .05). Moreover, bias of hs-cTnT assays at 50 mg/dl free Hb was approaching 10%, especially at 30 ng/l hs-cTnT concentration (Bias: -11.72%, P < .001). CONCLUSIONS: PTS could increase the frequency of specimen hemolysis which might cause false decrease in hs-cTnT assays. Hence, clinicians should be aware of the increased measurement bias in hs-cTnT from hemolyzed PTS samples with free Hb ≥50 mg/dl.


Assuntos
Análise Química do Sangue/instrumentação , Limite de Detecção , Miocárdio/metabolismo , Troponina T/sangue , Reações Falso-Negativas , Feminino , Voluntários Saudáveis , Humanos , Masculino , Troponina T/metabolismo , Adulto Jovem
8.
Ther Clin Risk Manag ; 15: 683-688, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239690

RESUMO

Background: Endoscopic sinus surgery (ESS) has been the definitive treatment for chronic rhinosinusitis (CRS), but the complications caused perioperatively may affect patients' quality of life (QoL). This study aims to evaluate the effects of enhanced recovery after surgery (ERAS) on improving perioperative QoL in ESS. Materials and methods: Seventy-four patients with chronic rhinosinusitis with nasal polyps (CRSwNP) met the criteria for inclusion. Participants undergoing ESS were randomly divided into an ERAS group and a control group, and QoL assessment was performed using the Chinese version of the 22-item Sinonasal Outcomes Test (SNOT-22). Measurements were administered at baseline, and on postoperative day 1 (POD1), POD3 and POD6. Complications such as nausea/emesis, hemorrhage, aspiration and dizziness were also recorded. Results: The preoperative global SNOT-22 scores (mean ± SD) were 39.89±4.86 in the ERAS group and 40.52±3.61 in the control group (t=0.643, P=0.522). On POD1, the global SNOT-22 scores increased significantly to 51.77±5.59 and 62.02±3.86 (t=9.218, P<0.01), and on POD3 they increased to 48.22±6.22 and 51.11±5.14, respectively (t=2.179, P<0.05). However, the scores recovered to 39.39±4.73 and 40.13±3.31 in the respective groups on POD6, which were lower than but not statistically significant different from the baseline (t=0.786, P=0.434). There were statistically significant improvements across all subdomains of SNOT-22 for patients in the two groups only in POD1 (all P<0.05). The ERAS group did not have an increased incidence of complications such as nausea/emesis (χ 2=0.223, P>0.05), hemorrhage, aspiration and dizziness compared to the control group. Conclusion: ERAS could improve perioperative QoL in patients with CRSwNP undergoing ESS, and SNOT-22 can be used for ERAS evaluation as a patients' outcome report.

9.
Neurosci Bull ; 35(2): 253-266, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30721394

RESUMO

Alzheimer's disease (AD) is characterized by decreased neuronal activity and atrophy, while hyperactivity of neurons seems to make them resistant to aging and neurodegeneration, a phenomenon which we have paraphrased as 'use it or lose it'. Our hypothesis proposes that (1) during their functioning, neurons are damaged; (2) accumulation of damage that is not repaired is the basis of aging; (3) the vulnerability to AD is determined by the genetic background and the balance between the amount of damage and the efficiency of repair, and (4) by stimulating the brain, repair mechanisms are stimulated and cognitive reserve is increased, resulting in a decreased rate of aging and risk for AD. Environmental stimulating factors such as bilingualism/multilingualism, education, occupation, musical experience, physical exercise, and leisure activities have been reported to reduce the risk of dementia and decrease the rate of cognitive decline, although methodological problems are present.


Assuntos
Encéfalo/fisiopatologia , Demência/prevenção & controle , Demência/fisiopatologia , Animais , Encéfalo/patologia , Demência/genética , Demência/patologia , Humanos , Modelos Neurológicos
10.
Brain Pathol ; 29(4): 502-512, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30511454

RESUMO

Our previous studies showed that the transcription factor early growth response-1 (EGR1) may play a role in keeping the brain cholinergic function intact in the preclinical stages of Alzheimer's disease (AD). In order to elucidate the mechanisms involved, we first performed data mining on our previous microarray study on postmortem human prefrontal cortex (PFC) for the changes in the expression of EGR1 and acetylcholinesterase (AChE) and the relationship between them during the course of AD. The study contained 49 patients, ranging from non-demented controls (Braak stage 0) to late AD patients (Braak stage VI). We found EGR1-mRNA was high in early AD and decreased in late AD stages, while AChE-mRNA was stable in preclinical AD and slightly decreased in late AD stages. A significant positive correlation was found between the mRNA levels of these two molecules. In addition, we studied the relationship between EGR1 and AChE mRNA levels in the frontal cortex of 3-12-months old triple-transgenic AD (3xTg-AD) mice. EGR1- and AChE-mRNA were lower in 3xTg-AD mice compared with wild-type (WT) mice. A significant positive correlation between these two molecules was present in the entire group and in each age group of either WT or 3xTg-AD mice. Subsequently, AChE expression was determined following up- or down-regulating EGR1 in cell lines and the EGR1 levels were found to regulate AChE at both the mRNA and protein levels. Dual-luciferase assay and electrophoretic mobility shift assay in the EGR1-overexpressing cells were performed to determine the functionally effective binding sites of the EGR1 on the AChE gene promoter. We conclude that the EGR1 can upregulate AChE expression by a direct effect on its gene promoter, which may contribute significantly to the changes in cholinergic function in the course of AD. The 3xTg-AD mouse model only reflects later stage AD.

11.
Molecules ; 23(12)2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30518083

RESUMO

Owing to their ultra-low thermal conductivity, silica aerogels are promising thermal insulators; however, their extensive application is limited by their high production cost. Thus, scientists have started to explore low-cost and easy preparation processes of silica aerogels. In this work, a low-cost method was proposed to prepare silica aerogels with industrial silica hydrosol and a subsequent ambient pressure drying (APD) process. Various surfactants (cationic, amphoteric, or anionic) were added to avoid solvent exchange and surface modification during the APD process. The effects of various surfactants on the microstructure, thermal conductivity, and thermal stability of the silica aerogels were studied. The results showed that the silica aerogels prepared with a cationic or anionic surfactant have better thermal stability than that prepared with an amphoteric surfactant. After being heated at 600 °C, the silica aerogel prepared with a cationic surfactant showed the highest specific surface area of 131 m²âˆ™g-1 and the lowest thermal conductivity of 0.038 W∙m-1∙K-1. The obtained low-cost silica aerogel with low thermal conductivity could be widely applied as a thermal insulator for building and industrial energy-saving applications.


Assuntos
Géis/química , Dióxido de Silício/química , Tensoativos/química , Solventes/química , Condutividade Térmica
12.
Cancer Manag Res ; 10: 6757-6768, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30584369

RESUMO

Purpose: The research of long non-coding RNAs (lncRNAs) has become a new passion with the discovery of abundant new lncRNAs and extensive investigation of their roles in various diseases, especially in cancers. Metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) emerges as a hotspot, which has been reported to be involved in dysregulation of cell signaling and closely correlated with cancer development, progression, and response to therapy. This review is a brief update of the current knowledge related to the role of MALAT1 in cancer-associated molecular pathways and pathophysiology and possible determinants for MALAT1 to function as a biomarker, aiming to stimulate the basic investigation of lncRNA MALAT1 as well as its translation to clinical applications. Methods: We have selected vast literature from electronic databases including studies associated with its clinical significance and the pivotal functions in cancer processes such as cell proliferation, apoptosis, metastasis, immunity, angiogenesis, and drug resistance. Results: Studies have shown that aberrant expression of MALAT1 is related to cancer pathophysiology with the potential to be translated clinically and MALAT1 can regulate cancer processes by interacting with molecules, such as proteins, RNAs and DNAs, and further altering different signal pathways. Conclusion: MALAT1 lncRNA promises to be a potential biomarker for cancer diagnosis as well as prognosis. Additionally, it might be a therapeutic target for human cancers.

13.
Front Neurol ; 9: 838, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30344508

RESUMO

Purpose: The purpose of this study was to comprehensively evaluate alterations of resting-state spontaneous brain activity in patients with idiopathic generalized epilepsy (IGE) and its subgroups [juvenile myoclonic epilepsy (JME) and generalized tonic-clonic seizures (GTCS)]. Methods: Resting state functional magnetic resonance imaging (fMRI) data were acquired from 60 patients with IGE and 60 healthy controls (HCs). Amplitude of low frequency fluctuation (ALFF), global functional connectivity density (gFCD), local FCD (lFCD), and long range FCD (lrFCD) were used to evaluate spontaneous brain activity in the whole brain. Moreover, the coupling between ALFF and FCDs (gFCD, lFCD, and lrFCD) was analyzed on both voxel-wise and subject-wise levels. Two-sample t-tests were used to analyze the difference in ALFF, FCDs and coupling on a subject-wise level between the two groups. Nonparametric permutation tests were used to evaluate differences in coupling on a voxel-wise level. Key findings: Patients with IGE and its subgroups showed reduced ALFF, gFCD and lrFCD in posterior regions of the default mode network (DMN). In addition, decreased ALFF and increased coupling with FCD were found in the cerebellum, while decreased coupling was observed in the bilateral pre- and postcentral gyrus in IGE compared with the coupling in HCs. Similar findings were found in the analysis between each of the two subgroups of IGE (JME and GTCS) and HCs, and JME patients had increased coupling in the cerebellum and bilateral middle occipital gyrus compared with coupling in the GTCS patients. Significance: This study demonstrated a multifactor abnormality of the DMN in IGE and emphasized that the abnormality in the cerebellum was associated with dysfunctional motor symptoms during seizures and might participate in the regulation of GSWDs in IGE.

14.
Nat Commun ; 9(1): 2464, 2018 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-29942010

RESUMO

Most tumor cells take up more glucose than normal cells. Splicing dysregulation is one of the molecular hallmarks of cancer. However, the role of splicing factor in glucose metabolism and tumor development remains poorly defined. Here, we show that upon glucose intake, the splicing factor SRSF5 is specifically induced through Tip60-mediated acetylation on K125, which antagonizes Smurf1-mediated ubiquitylation. SRSF5 promotes the alternative splicing of CCAR1 to produce CCAR1S proteins, which promote tumor growth by enhancing glucose consumption and acetyl-CoA production. Conversely, upon glucose starvation, SRSF5 is deacetylated by HDAC1, and ubiquitylated by Smurf1 on the same lysine, resulting in proteasomal degradation of SRSF5. The CCAR1L proteins accumulate to promote apoptosis. Importantly, SRSF5 is hyperacetylated and upregulated in human lung cancers, which correlates with increased CCAR1S expression and tumor progression. Thus, SRSF5 responds to high glucose to promote cancer development, and SRSF5-CCAR1 axis may be valuable targets for cancer therapeutics.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Ciclo Celular/metabolismo , Transformação Celular Neoplásica/patologia , Glucose/metabolismo , Neoplasias Pulmonares/patologia , Fatores de Processamento de Serina-Arginina/metabolismo , Células A549 , Acetilcoenzima A/biossíntese , Acetilação , Processamento Alternativo/genética , Animais , Apoptose/genética , Proteínas Reguladoras de Apoptose/genética , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Células HEK293 , Células HeLa , Células Hep G2 , Histona Desacetilase 1/metabolismo , Humanos , Lisina Acetiltransferase 5/metabolismo , Células MCF-7 , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
15.
Biomed Res Int ; 2018: 4104691, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29854751

RESUMO

Aims: Recent epidemiological studies have indicated that the incidence of epilepsy peaks after 60 years old, and epilepsy has become increasingly prevalent in elderly populations. The aim of this study is to identify the aetiologic characteristics of epilepsy in the elderly. Methods: We retrospectively recruited elderly patients with newly diagnosed epilepsy identified in three epilepsy centres in western China; elderly patients were defined as individuals aged 60 years or older. Demographic characteristics, clinical epilepsy data, and the diagnosis and aetiology of epilepsy were recorded. Results: A total of 760 patients with newly diagnosed epilepsy were enrolled in our study. Of these patients, 25% had experienced one or more episodes of status epilepticus, and 62.4% were confirmed as symptomatic. Among the symptomatic cohort, stroke and traumatic brain injury (TBI) were the two most common causes of epilepsy, followed by cerebral tumour, dementia, hippocampal sclerosis (HS), and central nervous system (CNS) infection. When analysed by residence and age, ischaemic stroke was the most common cause of epilepsy in urban patients, whereas traumatic brain injury was the leading cause of epilepsy in rural patients. Conclusion: More than three-fifths of newly diagnosed epilepsy cases in elderly patients were confirmed as symptomatic, and stroke and traumatic brain injury were the primary aetiologies in elderly epileptic patients.


Assuntos
Lesões Encefálicas Traumáticas/fisiopatologia , Estado Epiléptico/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/uso terapêutico , Lesões Encefálicas Traumáticas/complicações , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , População Rural , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/epidemiologia , Estado Epiléptico/etiologia , Acidente Vascular Cerebral/complicações
16.
Onco Targets Ther ; 11: 3185-3194, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29881292

RESUMO

Cisplatin (CDDP) is one of the most commonly used chemotherapy drugs for the treatment of various cancers. Although platinum-based therapies are highly efficacious against rapidly proliferating malignant tumors, the development of CDDP resistance results in significant relapse as well as decreased overall survival rates, which is a significant obstacle in CDDP-based cancer therapy. Long non-coding RNAs (lncRNAs) are involved in cancer development and progression by the regulation of processes related to chromatin remodeling, transcription, and posttranscriptional processing. Emerging evidence has recently highlighted the roles of lncRNAs in the development of CDDP resistance. In this review, we discuss the roles and mechanisms of lncRNAs in CDDP chemoresistance, including changes in cellular uptake or efflux of a drug, intracellular detoxification, DNA repair, apoptosis, autophagy, cell stemness, and the related signaling pathways, aiming to provide potential lncRNA-targeted strategies for overcoming drug resistance in cancer therapy.

17.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 35(3): 389-392, 2018 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-29896738

RESUMO

OBJECTIVE: To report on two cases affected with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX). METHODS: Two unrelated Chinese infants affected with IPEX were investigated. Case 1 was a 4-month-old boy with neonatal diabetes and severe enteropathy. Case 2 was a 6-day newborn boy with neonatal diabetes and ketoacidosis. DNA samples of the two infants and their parents were sequenced for FOXP3 gene mutations. Suspected mutations were verified among 100 unrelated healthy controls. The function of mutations was predicted with bioinformatics software. RESULTS: Both infants had onset of the disease during neonatal period, and manifested insulin-dependent diabetes mellitus, persistent diarrhea, eczema and malnutrition. In case 1, a novel splice site mutation was identified in intron 9 (c.967+3A>T) of the FOXP3 gene, for which his mother was a carrier. For case 2, a missense mutation (c.1150G>A) was detected in exon 11 of the FOXP3 gene, for which his mother was also a carrier. The IVS9 c.967+3A mutation was not detected among the 100 healthy controls. As predicted with Human Splicing Finder software, the c.967+3A>T mutation may influence the splicing of mRNA and affect the function of protein. CONCLUSION: Both cases had typical clinical manifestation of the IPEX syndrome, among whom a novel splice site mutation (IVS9 c.967+3A>T) and a missense mutation (c.1150G>A) of the FOXP3 gene were identified. The clinical manifestation of the IPEX syndrome may be variable and the mortality is high. FOXP3 gene sequencing is recommended when insulin-dependent diabetes mellitus is diagnosed during the neonatal period.


Assuntos
Fatores de Transcrição Forkhead/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Enteropatias/genética , Sequência de Bases , Diabetes Mellitus Tipo 1/genética , Fatores de Transcrição Forkhead/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Humanos , Lactente , Recém-Nascido , Enteropatias/imunologia , Masculino , Dados de Sequência Molecular , Mutação
18.
Sci Adv ; 4(4): eaat1098, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29662956

RESUMO

Spin superfluid is a novel emerging quantum matter arising from the Bose-Einstein condensate (BEC) of spin-1 bosons. We demonstrate the spin superfluid ground state in canted antiferromagnetic Cr2O3 thin film at low temperatures via nonlocal spin transport. A large enhancement of the nonlocal spin signal is observed below ~20 K, and it saturates from ~5 down to 2 K. We show that the spins can propagate over very long distances (~20 µm) in such spin superfluid ground state and that the nonlocal spin signal decreases very slowly as the spacing increases with an inverse relationship, which is consistent with theoretical prediction. Furthermore, spin superfluidity has been investigated in the canted antiferromagnetic phase of the (11[Formula: see text]0)-oriented Cr2O3 film, where the magnetic field dependence of the associated critical temperature follows a 2/3 power law near the critical point. The experimental demonstration of the spin superfluid ground state in canted antiferromagnet will be extremely important for the fundamental physics on the BEC of spin-1 bosons and paves the way for future spin supercurrent devices, such as spin-Josephson junctions.

19.
FASEB J ; 32(9): 4627-4640, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29565736

RESUMO

Testosterone is essential for spermatogenesis and the maintenance of secondary sexual characteristics in males. An important transcription factor, LIM-homeobox gene 9 (Lhx9) is indispensable for testis development and testosterone production; however, post-translational modifications of Lhx9 are largely unknown. Here, for the first time to our knowledge, we demonstrate that the level of Lhx9 protein increases in human chorionic gonadotropin-exposed Leydig cells and can be polyubiquitylated. We found that Smad ubiquitylation regulatory factor 1 (Smurf1), an E3 ubiquitin ligase, targets Lhx9 for ubiquitin-mediated proteasome degradation, thereby negatively modulating its function. Increasing Smurf1 decreases the level of Lhx9 and inhibits the Lhx9 transactivation capacity of steroidogenic factor 1 [nuclear receptor subfamily 5, group A, member 1 (NR5A1)]. In contrast, the depletion of Smurf1 leads to increased expression of Lhx9 protein and enhances testosterone biosynthesis-related gene transcripts [NR5A1, steroidogenic acute regulatory protein, CYP17A1, hydroxy-δ-5-steroid dehydrogenase, hydroxy-δ-5-steroid dehydrogenase isomerase 6, and hydroxysteroid (17-ß) dehydrogenase 3] and testosterone production in Leydig cells. Furthermore, we found that Smurf1 knockout mice exhibit higher levels of Lhx9 protein and steroidogenesis, which leads to increased serum testosterone concentration. These findings reveal that Smurf1 promotes Lhx9 ubiquitylation and is involved in testosterone production in Leydig cells directly. Our results provide new insights into the molecular events that play a role in the homeostasis of testosterone levels and may provide a new target for testosterone regulation.-Hu, F., Zhu, Q., Sun, B., Cui, C., Li, C., Zhang, L. Smad ubiquitylation regulatory factor 1 promotes LIM-homeobox gene 9 degradation and represses testosterone production in Leydig cells.


Assuntos
Proteínas com Homeodomínio LIM/genética , Células Intersticiais do Testículo/metabolismo , Fatores de Transcrição/genética , Ubiquitina-Proteína Ligases/genética , Animais , Genes Homeobox/genética , Humanos , Masculino , Camundongos Knockout , Espermatogênese/efeitos dos fármacos , Espermatogênese/fisiologia , Testosterona/metabolismo , Testosterona/farmacologia , Fatores de Transcrição/metabolismo
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(1): 136-140, 2018 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-29397832

RESUMO

OBJECTIVE: To study the changes of T lymphocyte subsets and immunoglobulin in peripheral blood of patients with acute lymphoblastic leukemia (ALL) and non-acute lymphocytic leukemia (N-ALL) before and after treatment and their value for monitoring of disease and evaluation of prognosis. METHODS: One hundred and six cases of leukemia were selected in our hospital, including 48 cases of ALL (ALL group) and 58 cases of N-ALL (N-ALL group); 54 peoples of normal physical examination were selected as the normal control group in the same period. The IgA, IgG and IgM levels of peripheral blood were detected, and the absolute value of T lymphocyte subsets was determined by cell slide method. According to whether the patients' status was improved or not by treatment, the 106 patients were divided into the unimproved group (55 cases including 25 ALL, 30 N-ALL) and improved group (51 cases including 23 ALL, 28 N-ALL). RESULTS: The levels of IgA, IgG and IgM in 106 cases of leukemia were significantly lower than those in the control group (all P<0.05), and the CD3+ level, CD3+CD4+/CD3+CD8+ ratio and the absolute value of CD3+CD4+T cells in the peripheral blood were significantly lower than those in the control group(all P<0.05); the absolute value of CD3+CD8+T cells showed no significant difference in comparison with the control group (P >0.05). After treatment, IgA,IgG and IgM levels in the improved group were significantly higher than those before therapy (all P<0.05), while their levels were not significantly different from that in the control group (all P>0.05); the CD3+ level, CD3+CD4+/CD3+CD8+ ratio and the absolute value of CD3+CD4+T cells in the peripheral blood were significantly higher than those before therapy (all P<0.05), while those were not significantly different from the control group (all P>0.05). Compared with levels before treatment, the levels of above mentioned indicators in the unimproved group after treatment were not significantly different (all P>0.05); and the CD3+ level, CD3+CD4+/CD3+CD8+ ratio and the absolute value of CD3+CD4+T cells were significantly lower than those in the control group (all P<0.05), and the absolute value of CD3+CD8+T cells were higher than that in the control group (P<0.05). CONCLUSION: After the treatment, the T lymphocyte subsets (CD3+, CD3+CD4+T cells) and immunoglobulin (IgA, IgG, IgM) levels in peripheral blood of patients with ALL and N-ALL have been improved significantly, and the detection of these indexes is helpful for disease monitoring and prognosis evaluation.


Assuntos
Subpopulações de Linfócitos T , Relação CD4-CD8 , Humanos , Imunoglobulinas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Prognóstico
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