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1.
J Integr Plant Biol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961693

RESUMO

Dwarfing is a pivotal agronomic trait affecting both yield and quality. Citrus species exhibit substantial variation in plant height, among which internode length is a core element. However, the molecular mechanism governing internode elongation remains unclear. Here, we unveiled that the transcriptional cascade consisting of B-BOX DOMAIN PROTEIN 22 (BBX22) and ELONGATED HYPOCOTYL 5 (HY5) finely tunes plant height and internode elongation in citrus. Loss-of-function mutations of BBX22 in an early-flowering citrus (Citrus hindsii "SJG") promoted internode elongation and reduced pigment accumulation, whereas ectopic expression of BBX22 in SJG, sweet orange (C. sinensis), pomelo (C. maxima) or heterologous expression of BBX22 in tomato (Solanum lycopersicum) significantly decreased internode length. Furthermore, exogenous application of gibberellin A3 (GA3) rescued the shortened internode and dwarf phenotype caused by BBX22 overexpression. Additional experiments revealed that BBX22 played a dual role in regulation internode elongation and pigmentation in citrus. On the one hand, it directly bound to and activated the expression of HY5, GA metabolism gene (GA2 OXIDASE 8, GA2ox8), carotenoid biosynthesis gene (PHYTOENE SYNTHASE 1, PSY1) and anthocyanin regulatory gene (Ruby1, a MYB DOMAIN PROTEIN). On the other hand, it acted as a cofactor of HY5, enhancing the ability of HY5 to regulate target genes expression. Together, our results reveal the critical role of the transcriptional cascade consisting of BBX22 and HY5 in controlling internode elongation and pigment accumulation in citrus. Unraveling the crosstalk regulatory mechanism between internode elongation and fruit pigmentation provides key genes for breeding of novel types with both dwarf and health-beneficial fortification in citrus.

2.
Sci Rep ; 14(1): 10208, 2024 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702519

RESUMO

Serial casting as one of the applications to treat early-onset scoliosis has been reported efficiently to improve deformity, but no report has focused on the efficacy of braces in the treatment of congenital early-onset scoliosis and comparison with progressive idiopathic early-onset scoliosis. Patients with progressive EOS treated with braces in our institution with a minimum of 4 years follow-up were reviewed. Two groups according to the etiological diagnosis were analyzed and compared: the congenital scoliosis (CS) group and idiopathic scoliosis (IS) group. The success cases and the failure cases were also compared. 27 patients with an average main Cobb angle of 38.19° (20-55) underwent initial bracing at an average age of 55.7 months (24-108), the average follow-up time was 76.19 months (49-117). In IS group the main Cobb angle was corrected to 18.69 ± 12.06° (48.61%) following the first bracing; the final Cobb angle was 23.08 ± 22.15°(38.76%) after brace removal. In CS group the main Cobb angle was corrected to 33.93 ± 10.31°(17.1%) following the first bracing and 37.93 ± 14.74°(3.53%) after brace removal. Both coronal chest width and T1-T12 height increased dramatically from pre-bracing to the last follow-up. Patients diagnosed as IS tended to have a better result in main Cobb angle correction than that of CS (P = 0.049). By the time of last follow-up, 8 patients had undergone surgery, and the operation time was postponed by 68.88 ± 26.43 months. For patients with progressive early-onset scoliosis, bracing is an efficient nonsurgical alternative to casting, and some of them can be cured; if not, eventual surgical intervention can be delayed for a period of time without restrictions on the thoracic cavity.


Assuntos
Braquetes , Escoliose , Humanos , Escoliose/terapia , Feminino , Masculino , Criança , Pré-Escolar , Resultado do Tratamento , Progressão da Doença , Idade de Início , Seguimentos , Estudos Retrospectivos
3.
Proc Natl Acad Sci U S A ; 121(14): e2321615121, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38530892

RESUMO

Polymethoxyflavones (PMFs) are a class of abundant specialized metabolites with remarkable anticancer properties in citrus. Multiple methoxy groups in PMFs are derived from methylation modification catalyzed by a series of hydroxylases and O-methyltransferases (OMTs). However, the specific OMTs that catalyze the systematic O-methylation of hydroxyflavones remain largely unknown. Here, we report that PMFs are highly accumulated in wild mandarins and mandarin-derived accessions, while undetectable in early-diverging citrus species and related species. Our results demonstrated that three homologous genes, CreOMT3, CreOMT4, and CreOMT5, are crucial for PMF biosynthesis in citrus, and their encoded methyltransferases exhibit multisite O-methylation activities for hydroxyflavones, producing seven PMFs in vitro and in vivo. Comparative genomic and syntenic analyses indicated that the tandem CreOMT3, CreOMT4, and CreOMT5 may be duplicated from CreOMT6 and contributes to the genetic basis of PMF biosynthesis in the mandarin group through neofunctionalization. We also demonstrated that N17 in CreOMT4 is an essential amino acid residue for C3-, C5-, C6-, and C3'-O-methylation activity and provided a rationale for the functional deficiency of OMT6 to produce PMFs in early-diverging citrus and some domesticated citrus species. A 1,041-bp deletion in the CreOMT4 promoter, which is found in most modern cultivated mandarins, has reduced the PMF content relative to that in wild and early-admixture mandarins. This study provides a framework for reconstructing PMF biosynthetic pathways, which may facilitate the breeding of citrus fruits with enhanced health benefits.


Assuntos
Citrus , Citrus/química , Domesticação , Melhoramento Vegetal , Metilação , Metiltransferases/metabolismo
4.
Nat Commun ; 15(1): 1262, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341452

RESUMO

Replication fork reversal, a critical protective mechanism against replication stress in higher eukaryotic cells, is orchestrated via a series of coordinated enzymatic reactions. The Bloom syndrome gene product, BLM, a member of the highly conserved RecQ helicase family, is implicated in this process, yet its precise regulation and role remain poorly understood. In this study, we demonstrate that the GCFC domain-containing protein TFIP11 forms a complex with the BLM helicase. TFIP11 exhibits a preference for binding to DNA substrates that mimic the structure generated at stalled replication forks. Loss of either TFIP11 or BLM leads to the accumulation of the other protein at stalled forks. This abnormal accumulation, in turn, impairs RAD51-mediated fork reversal and slowing, sensitizes cells to replication stress-inducing agents, and enhances chromosomal instability. These findings reveal a previously unidentified regulatory mechanism that modulates the activities of BLM and RAD51 at stalled forks, thereby impacting genome integrity.


Assuntos
Tolerância ao Dano no DNA , Replicação do DNA , Humanos , RecQ Helicases/genética , RecQ Helicases/metabolismo , DNA/genética , DNA/metabolismo , Proteínas/metabolismo , Instabilidade Genômica , Rad51 Recombinase/genética , Rad51 Recombinase/metabolismo , Fatores de Processamento de RNA/metabolismo
5.
Int J Biol Macromol ; 258(Pt 1): 128883, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38141715

RESUMO

Multilayer nanocomposite film made of different materials has multifunctional properties and is applied in the field of flexible electronic devices. Herein, hydroxyethyl cellulose (HEC) and boron nitride nanosheets (BNNS) were used as the matrix and thermal conductivity material of the HEC/BNNS (HB) insulation layer and were combined with conductive blade structure graphene/silver nanowires (GA) film to prepare a three-layer HB/GA20/HB film. Using the high mechanical properties of the HEC based film, the tensile strength of the three-layer film is increased to 22.0 MPa, 633 % higher than that of the pure conductive film. The sensor prepared by multilayer film has good bending sensing performance (1500 cycles) and electromagnetic shielding performance (29.3 dB). The heating temperature of HB/GA20/HB film heater is up to 107.9 °C at 20 V. In the HB/GA20/HB film, the external HB layer provides insulation, thermal conductivity and physical support, and the internal GA layer with good conductive and sensing properties is combined to build a multi-functional sensor, which can be applied as a mobile sensor, heater and electromagnetic shielding material in the flexible wearable field.


Assuntos
Grafite , Nanofios , Prata , Celulose , Condutividade Elétrica
6.
Nat Chem Biol ; 19(5): 585-595, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36635566

RESUMO

The cell-cycle checkpoint kinase WEE1 is emerging as a therapeutic target for cancer treatment. However, how its catalytic activity is regulated remains poorly understood, and reliable biomarkers for predicting response to WEE1 inhibitor remain to be identified. Here we identify an evolutionarily conserved segment surrounding its Lys177 residue that inhibits WEE1 activity through an intermolecular interaction with the catalytic kinase domain. Upon DNA damage, CHK1-dependent phosphorylation of WEE1 at Ser642 primes GCN5-mediated acetylation at Lys177, resulting in dissociation of the inhibitory segment from the kinase domain and subsequent activation of WEE1 and cell-cycle checkpoints. Conversely, SIRT1 associates with and deacetylates WEE1, which maintains it in an inactive state. Consequently, SIRT1 deficiency induces WEE1 hyperacetylation and activation, rendering cancer cells resistant to WEE1 inhibition. These results suggest that SIRT1 expression level and abundance of WEE1 Lys177 acetylation in tumor cells can serve as useful biomarkers for predicting WEE1 inhibitor sensitivity or resistance.


Assuntos
Proteínas de Ciclo Celular , Neoplasias , Proteínas de Ciclo Celular/metabolismo , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Linhagem Celular Tumoral , Sirtuína 1/genética , Dano ao DNA , Biomarcadores , Neoplasias/tratamento farmacológico , Neoplasias/genética
8.
Ultrason Sonochem ; 92: 106244, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36508893

RESUMO

In this investigation, ultrasonic-assisted soldering at 260 °C in air produced high strength and high melting point Cu connections in 60 s using Ni foam reinforced Sn composite solder. Systematically examined were the microstructure, grain morphology, and shear strength of connections made with various porosities of Ni foam composite solders. Results shown that Ni foams as strengthening phases could reinforce Sn solder effectively. The addition of Ni foam accelerated the metallurgical reaction due to great amount of liquid/solid interfaces, and refined the intermetallic compounds (IMCs) grains by ultrasonic cavitation. The joints had different IMCs by using Ni foam with different porosity. Layered (Cu,Ni)6Sn5 and (Ni,Cu)3Sn4 phases both existed in Cu/Ni60-Sn/Cu joint while only (Cu,Ni)6Sn5 IMCs grew in Cu/Ni98-Sn/Cu joint. As ultrasonic time increasing, Ni skeletons were dissolved and the IMCs were peeled off from substrates and broken into small particles. And then, the IMCs gradually dissociated into refined particles and distributed homogeneously in the whole soldering seam under cavitation effects. Herein, the Cu/Ni60-Sn/Cu joint ultrasonically soldered for 60 s exhibited the highest shear strength of 86.9 MPa, as well as a high melting point about 800 â„ƒ for the solder seam composed of Ni skeletons and Ni-Cu-Sn IMCs. The characterization indicated that the shearing failure mainly occurred in the interlayer of the soldering seam. The homogeneous distributed granular IMCs and Ni skeletons hindered the crack propagation and improved the strength of Cu alloy joints.

9.
Bioact Mater ; 9: 491-507, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34820585

RESUMO

The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone, most likely resulted from the inability to replicate appropriate endogenous crosstalk between cells. Human umbilical vein endothelial cell-derived decellularized extracellular matrix (HdECM), which contains a collection of angiocrine biomolecules, has recently been demonstrated to mediate endothelial cells(ECs) - osteoprogenitors(OPs) crosstalk. We employed the HdECM to create a PCL (polycaprolactone)/fibrin/HdECM (PFE) hybrid scaffold. We hypothesized PFE scaffold could reconstitute a bio-instructive microenvironment that reintroduces the crosstalk, resulting in vascularized bone regeneration. Following implantation in a rat femoral bone defect, the PFE scaffold demonstrated early vascular infiltration and enhanced bone regeneration by microangiography (µ-AG) and micro-computational tomography (µ-CT). Based on the immunofluorescence studies, PFE mediated the endogenous angiogenesis and osteogenesis with a substantial number of type H vessels and osteoprogenitors. In addition, superior osseointegration was observed by a direct host bone-PCL interface, which was likely attributed to the formation of type H vessels. The bio-instructive microenvironment created by our innovative PFE scaffold made possible superior osseointegration and type H vessel-related bone regeneration. It could become an alternative solution of improving the osseointegration of bone substitutes with the help of induced type H vessels, which could compensate for the inherent biological inertness of synthetic polymers.

10.
Nat Cell Biol ; 22(9): 1056-1063, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32807901

RESUMO

p53 is the most intensively studied tumour suppressor1. The regulation of p53 homeostasis is essential for its tumour-suppressive function2,3. Although p53 is regulated by an array of post-translational modifications, both during normal homeostasis and in stress-induced responses2-4, how p53 maintains its homeostasis remains unclear. UFMylation is a recently identified ubiquitin-like modification with essential biological functions5-7. Deficiency in this modification leads to embryonic lethality in mice and disease in humans8-12. Here, we report that p53 can be covalently modified by UFM1 and that this modification stabilizes p53 by antagonizing its ubiquitination and proteasome degradation. Mechanistically, UFL1, the UFM1 ligase6, competes with MDM2 to bind to p53 for its stabilization. Depletion of UFL1 or DDRGK1, the critical regulator of UFMylation6,13, decreases p53 stability and in turn promotes cell growth and tumour formation in vivo. Clinically, UFL1 and DDRGK1 expression are downregulated and positively correlated with levels of p53 in a high percentage of renal cell carcinomas. Our results identify UFMylation as a crucial post-translational modification for maintenance of p53 stability and tumour-suppressive function, and point to UFMylation as a promising therapeutic target in cancer.


Assuntos
Proteína Supressora de Tumor p53/metabolismo , Ubiquitinação/fisiologia , Carcinoma de Células Renais/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Células HCT116 , Células HEK293 , Células HeLa , Humanos , Neoplasias Renais/metabolismo , Processamento de Proteína Pós-Traducional/fisiologia , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
11.
Cell J ; 22(3): 386-393, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31863665

RESUMO

OBJECTIVE: We aimed to explore potential molecular mechanisms of clear cell renal cell carcinoma (ccRCC) and provide candidate target genes for ccRCC gene therapy. MATERIALS AND METHODS: This is a bioinformatics-based study. Microarray datasets of GSE6344, GSE781 and GSE53000 were downloaded from Gene Expression Omnibus database. Using meta-analysis, differentially expressed genes (DEGs) were identified between ccRCC and normal samples, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) function analyses. Then, protein-protein interaction (PPI) networks and modules were investigated. Furthermore, miRNAs-target gene regulatory network was constructed. RESULTS: Total of 511 up-regulated and 444 down-regulated DEGs were determined in the present gene expression microarray data meta-analysis. These DEGs were enriched in functions like immune system process and pathways like Toll-like receptor signaling pathway. PPI network and eight modules were further constructed. A total of 10 outstanding DEGs including TYRO protein tyrosine kinase binding protein (TYROBP), interferon regulatory factor 7 (IRF7) and PPARG co-activator 1 alpha (PPARGC1A) were detected in PPI network. Furthermore, the miRNAs-target gene regulation analyses showed that miR-412 and miR-199b respectively targeted IRF7 and PPARGC1A to regulate the immune response in ccRCC. CONCLUSION: TYROBP, IRF7 and PPARGC1A might play important roles in ccRCC via taking part in the immune system process.

12.
Virology ; 516: 196-201, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29407377

RESUMO

We reviewed the epidemiological and clinical characteristics of 927 aseptic meningitis patients in Shandong in 2014, and the phylogeny of predominant enterovirus (EV) types causing this disease was analyzed. A total of 209 patients that were positive for EV were identified by both cell culture and a reverse transcription-seminested PCR in cerebrospinal fluid samples. The positive patients were most likely to be children within 15 years of age, had symptoms such as fever, vomiting and nausea (P< .05). The 209 EV sequences belonged to 11 types, and coxsackievirus B5, echovirus types 6 and 30 were predominant types. VP1 analysis exhibited multiple lineages were co-circulating. The significance of the study could come from the fact that surveillance is important to monitor the prevalence of EV types in population, which shows enterovirus meningitis maintains an important public health problem in China.


Assuntos
Infecções por Enterovirus/virologia , Enterovirus/isolamento & purificação , Enterovirus/fisiologia , Meningite Asséptica/virologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , China/epidemiologia , Surtos de Doenças , Enterovirus/classificação , Enterovirus/genética , Infecções por Enterovirus/epidemiologia , Feminino , Humanos , Lactente , Masculino , Meningite Asséptica/epidemiologia , Meningite Viral/epidemiologia , Meningite Viral/virologia , Pessoa de Meia-Idade , Filogenia , Estações do Ano , Adulto Jovem
13.
Sci Rep ; 7(1): 17982, 2017 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-29269776

RESUMO

The rubella vaccine has been included in the immunization program in Shandong province of China since 1995. Here we observed the rubella vaccine coverage, epidemiology, serosurvey, and virological surveillance data, in order to identify the challenges impeding the progress towards to its elimination following the implementation of rubella immunization over a 21-year period in Shandong province. We first noted that the annual increase in vaccination coverage resulted in decreased rate of rubella incidence, which was maintained at a low level. Second, the average age of rubella patients had shifted to the 15-29-year age group, making this group the main population affected by the rubella virus (RV). Third, more than 90% of the study population were immune to rubella. However, the positive rate of rubella IgG in some cities was relatively lower indicating that an insufficient proportion of individuals had been vaccinated. Finally, the transmission of the genotype 1E RV was gradually interrupted due to the implementation of rubella vaccination. Unfortunately, the endemicity of the imported genotype 2B RV was established due to the pockets with unvaccinated people. Therefore, comprehensive vaccination coverage of the population, combined with high quality monitoring of rubella, is necessary to achieve the rubella elimination goal.


Assuntos
Erradicação de Doenças , Vacina contra Rubéola/uso terapêutico , Rubéola (Sarampo Alemão)/prevenção & controle , Adolescente , Adulto , Anticorpos Antivirais/imunologia , Criança , Pré-Escolar , China/epidemiologia , Erradicação de Doenças/métodos , Erradicação de Doenças/estatística & dados numéricos , Feminino , Humanos , Programas de Imunização , Lactente , Recém-Nascido , Masculino , Filogenia , Reação em Cadeia da Polimerase em Tempo Real , Rubéola (Sarampo Alemão)/epidemiologia , Vírus da Rubéola/genética , Vírus da Rubéola/imunologia , Cobertura Vacinal/estatística & dados numéricos , Adulto Jovem
14.
Int J Infect Dis ; 61: 13-19, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28577994

RESUMO

BACKGROUND: Tremendous progress has been made in hepatitis B virus (HBV) prevention and control in the last 30 years in China, but it continues to be a major public health problem. The most recently reported population-based seroepidemiological survey on HBV in Shandong Province in China was published in 2006, and an updated baseline for HBV prevalence was badly needed in the province to identify the change in HBV epidemiology in the last decade. METHODS: Two population-based cross-sectional serosurveys were performed among the population aged 1-59 years in the same sample areas in Shandong Province, China in 2006 and 2014, respectively. Data on demographic characteristics were collected. A blood sample was obtained from each person and was tested for hepatitis B surface antigen (HBsAg), antibody against HBsAg (anti-HBs), and antibody against hepatitis B core antigen (anti-HBc). RESULTS: Overall, the prevalence rates of HBsAg, anti-HBs, and anti-HBc were 3.39% (95% confidence interval (CI) 2.51-4.26), 44.96% (95% CI 41.34-48.57), and 24.45% (95% CI 22.19-26.71), respectively, among the population aged 1-59 years in the 2006 serovsurvey; the corresponding prevalence rates were 2.49% (95% CI 1.81-3.17), 48.27% (95% CI 45.63-50.92), and 22.56% (95% CI 20.14-24.97), respectively, in 2014. The prevalence rates of HBsAg and anti-HBc were lower in 2014 than in 2006. Conversely, the prevalence of anti-HBs showed an increase. However, none of these differences were statistically significant (all p>0.05). The prevalence of HBsAg showed an increase among persons aged 20-24 years in 2014 (3.83%) compared with 2006 (2.98%) (t=0.45, p=0.67). Among all occupation groups, the prevalence of HBsAg was lower in 2014 than in 2006, while the prevalence of anti-HBc showed moderate increases in students and farmers (all p>0.05). The prevalence of HBsAg decreased more obviously in urban areas (65.49%) than rural areas (7.07%) from 2006 to 2014. CONCLUSIONS: The epidemiology of HBV infection has changed in Shandong Province, China over the last decade. More attention should be paid to HBV infection among students and farmers.


Assuntos
Hepatite B/epidemiologia , Adolescente , China/epidemiologia , Estudos Transversais , Feminino , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Humanos , Masculino , Prevalência , Estudos Soroepidemiológicos , Adulto Jovem
15.
J Control Release ; 255: 154-163, 2017 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-28385675

RESUMO

The development of new hetero-nanostructures for multifunctional applications in cancer therapy has attracted widespread attention. In this work, we put forward a facile approach to synthesize multifunctional hetero-nanostructures of cellulose nanocrystal (CNC)-gold nanoparticle hybrids wrapped with low-toxic hydroxyl-rich polycations to integrate versatile functions for effective cancer therapy. Biocompatible CNCs with the superior rod-like morphology for high cellular uptake were employed as substrates to flexibly load spherical gold nanoparticles (Au NPs) or gold nanorods (Au NRs) through gold-thiolate bonds, producing hetero-layered nanohybrids of CNC-Au NPs or CNC-Au NRs. Profound hydroxyl-rich cationic gene carrier, CD-PGEA (comprising ß-cyclodextrin cores and ethanolamine-functionalized poly(glycidyl methacrylate) arms), was then assembled onto the surface of CNC-Au nanohybrids through host-guest interaction and gold-thiolate bonds, where PEG was employed as the intermediate and spacer. The resultant CNC-Au-PGEA hetero-nanostructures exhibited excellent performances as gene carriers. Furthermore, CNC-Au NR-PGEA comprising Au NRs demonstrated favorable optical absorption properties and were validated for photoacoustic imaging and combined photothermal/gene therapy with considerable antitumor effects. The present work provided a flexible strategy for the construction of new multifunctional hetero-nanostructures with high antitumor efficacy.


Assuntos
DNA/administração & dosagem , Nanoestruturas/administração & dosagem , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Celulose/administração & dosagem , Celulose/química , Celulose/uso terapêutico , Terapia Combinada , DNA/uso terapêutico , Feminino , Ouro/administração & dosagem , Ouro/química , Ouro/uso terapêutico , Proteínas de Fluorescência Verde/genética , Radical Hidroxila/administração & dosagem , Radical Hidroxila/química , Radical Hidroxila/uso terapêutico , Metacrilatos/administração & dosagem , Metacrilatos/química , Metacrilatos/uso terapêutico , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Técnicas Fotoacústicas , Fototerapia , Poliaminas/administração & dosagem , Poliaminas/química , Poliaminas/uso terapêutico , Polieletrólitos , Ratos , Proteína Supressora de Tumor p53/genética , beta-Ciclodextrinas/administração & dosagem , beta-Ciclodextrinas/química , beta-Ciclodextrinas/uso terapêutico
16.
Nat Commun ; 8: 14186, 2017 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-28128204

RESUMO

Disturbance of endoplasmic reticulum (ER) homoeostasis induces ER stress and leads to activation of the unfolded protein response (UPR), which is an adaptive reaction that promotes cell survival or triggers apoptosis, when homoeostasis is not restored. DDRGK1 is an ER membrane protein and a critical component of the ubiquitin-fold modifier 1 (Ufm1) system. However, the functions and mechanisms of DDRGK1 in ER homoeostasis are largely unknown. Here, we show that depletion of DDRGK1 induces ER stress and enhances ER stress-induced apoptosis in both cancer cells and hematopoietic stem cells (HSCs). Depletion of DDRGK1 represses IRE1α-XBP1 signalling and activates the PERK-eIF2α-CHOP apoptotic pathway by targeting the ER-stress sensor IRE1α. We further demonstrate that DDRGK1 regulates IRE1α protein stability via its interaction with the kinase domain of IRE1α, which is dependent on its ufmylation modification. Altogether, our results provide evidence that DDRGK1 is essential for ER homoeostasis regulation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Proteínas de Transporte/fisiologia , Estresse do Retículo Endoplasmático/fisiologia , Retículo Endoplasmático/metabolismo , Endorribonucleases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Apoptose/fisiologia , Proteínas de Transporte/genética , Sobrevivência Celular/fisiologia , Técnicas de Silenciamento de Genes , Células HEK293 , Células Hep G2 , Humanos , Células MCF-7 , Camundongos , Domínios Proteicos/fisiologia , Estabilidade Proteica , Proteínas/metabolismo , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/fisiologia , Resposta a Proteínas não Dobradas/fisiologia , Proteína 1 de Ligação a X-Box/metabolismo
18.
Zhonghua Liu Xing Bing Xue Za Zhi ; 37(4): 460-3, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-27087206

RESUMO

OBJECTIVE: To examine the influence of three-booster-doses hepatitis B vaccines on children with normal and high antibody response to primary vaccination. METHODS: Antibody against hepatitis B surface antigen (anti-HBs) were detected after primary vaccination and children with normal or high response to hepatitis B primary vaccination at infancy, were identified. Children who were given three booster doses were selected to form the booster group and who were given no booster dose were 1∶1 matched with the same gender and residence to form the control group. Blood samples were obtained from all the participants and tested for anti-HBs and anti-HBc, 5 years after the primary vaccination. RESULTS: The positive rates of anti-HBs response to primary vaccination were 97.39% (224/230, 95% CI: 94.41%-99.04%) in the booster group and 53.91% (124/230, 95% CI: 47.24%-60.48%) in the control group (P<0.05), 5 years after the primary vaccination. Geometric mean concentration (GMC) of anti-HBs were 1 140.02 (887.46-1 464.46) mIU/ml in the booster group and 11.53 (8.73-15.23) mIU/ml in the control group (P<0.05). The prevalence rates of breakthrough HBV infection were 0.87% (2/230) in the booster group and 2.17%(5/230) in the control group (P>0.05). RESULTS from the multivariable analysis showed that the booster doses (OR=38.75, 95%CI: 16.23-92.54) and the level of anti-HBs after the primary vaccination (OR =3.06, 95%CI:1.51-6.17) were independently associated with the positive rates of anti-HBs, 5 years after the primary vaccination (P<0.05). CONCLUSION: Programs with three booster doses to children that showing normal and high antibody response to primary vaccination could improve the persistence of anti-HBs but possibly would not be able to prevent the HBV infection.


Assuntos
Anticorpos Anti-Hepatite B/imunologia , Vacinas contra Hepatite B/imunologia , Hepatite B/prevenção & controle , Imunização Secundária , Vacinação , Formação de Anticorpos , Estudos de Casos e Controles , Criança , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/administração & dosagem , Vírus da Hepatite B , Humanos , Lactente , Prevalência , Resultado do Tratamento
19.
Vaccine ; 34(51): 6553-6560, 2016 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-27013438

RESUMO

INTRODUCTION: Endemic measles persists in China, despite >95% reported coverage of two measles-containing vaccine doses and nationwide campaign that vaccinated more than 100 million children in 2010. We performed a case-control study in six Chinese provinces during January 2012 through June 2013 to identify risk factors for measles infection among children aged 0-7 months. METHODS: Children with laboratory-confirmed measles were neighborhood matched with three controls. We interviewed parents of case and control infants on potential risk factors for measles. Adjusted matched odds ratios (mOR) and 95% confidence intervals (CIs) were calculated by multivariable conditional logistic modeling. We calculated attributable fractions for risk factors that could be interpreted as causal. RESULTS: Eight hundred thirty cases and 2303 controls were enrolled. In multivariable analysis, male sex (mOR 1.6 [1.3, 2.0]), age 5-7 months (mOR 3.9 [3.0, 5.1]), migration between counties (mOR 2.3 [1.6, 3.4]), outpatient hospital visits (mOR 9.4 [6.6, 13.3]) and inpatient hospitalization (mOR 107.1 [48.8, 235.1]) were significant risk factors. The calculated attributable fractions for hospital visits was 43.1% (95% CI: 40.1, 47.5%) adjusted for age, sex and migration. CONCLUSIONS: Hospital visitation was the largest risk factor for measles infection in infants. Improved hospital infection control practices would accelerate measles elimination in China.


Assuntos
Sarampo/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Fatores de Risco
20.
Bing Du Xue Bao ; 32(4): 478-83, 2016 07.
Artigo em Chinês | MEDLINE | ID: mdl-29995371

RESUMO

To assess the significance of environmental surveillance in the control and prevention of viral gastroenteritis, we analyzed the molecular characteristics of norovirus (NoV), rotavirus(RV),and human astrovirus (HAstV), sequences detected in domestic sewage. Environmental sewage monitoring sites were set up in three cities in Shandong, China. RNA was extracted from seven sewage samples collected each year from 2009 to 2015.RT-PCR detection of norovirus, rotavirus, and human astrovirus was performed. Positive PCR segments were cloned into a T-vector, transformed and sequenced, and genotyping and phylogenic analysis performed. A total of 210 viral sequences belonging to 6NoV I,4NoV II,3RV G,3RV P and 4HAstV were obtained.GI.2,GII.4,G9,P[8],and HAstV-1were the most frequently detected types. Phylogenetic analysis revealed multiple transmission chains in the genotypes of GI.3,GI.6,GII.4,G9,P[8],HAstV-1,and HAstV-4.The results showed not only that sewage contains dramatic information regarding gastroenteritis viruses, but also that environmental surveillance is an important approach in monitoring the regional circulation of specific viruses.


Assuntos
Mamastrovirus/isolamento & purificação , Norovirus/isolamento & purificação , Rotavirus/isolamento & purificação , Esgotos/virologia , China , Genótipo , Humanos , Mamastrovirus/classificação , Mamastrovirus/genética , Norovirus/classificação , Norovirus/genética , Filogenia , RNA Viral/genética , Rotavirus/classificação , Rotavirus/genética
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