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1.
Resuscitation ; 157: 149-155, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33129913

RESUMO

BACKGROUND: Prompt identification and management of patients having clinical deterioration on wards is one of the key steps to reduce in-hospital cardiac arrests (IHCA). Our organization implemented a novel Automated Code Blue Alert and Activation (ACBAA) system since 1st March 2018. METHODS: We conducted a retrospective before-and-after ACBAA system implementation study in JurongHealth Campus (JHC) of National University Health system (NUHS), Singapore. In JHC, code blue can be activated by both manual activation and ACBAA system activation from 1st March 2018. The ACBAA system will be activated when any of the pre-defined peri-arrest criteria is met. The primary outcome of the study was the incidence of IHCA. The secondary outcome included return of spontaneous circulation (ROSC) of IHCA and in-hospital survival to home discharge of code blue activation. OUTCOMES: The incidence of IHCA per 1000 hospital admissions after-ACBAA system implementation was 14.6% lower than before-ACBAA system though not statistically significant [relative risk (RR): 0.86, 95% confidence interval (CI) 0.55-1.34, P > 0.05]. Compared to the before-ACBAA system period, the after-ACBAA system period had a trend for higher rate of survival to home discharge after IHCA (RR: 2.13, 95% CI 0.65-6.93, P > 0.05) with good neurological outcome. CONCLUSIONS: Implementation of a novel ACBAA system has shown a trend in reducing IHCA incidence. In the era of digitalised healthcare system, the ACBAA system is practical and advisable to implement in order to reduce IHCA. Further studies are required to validate the criteria for peri-arrest code blue activation.

2.
BJPsych Open ; 6(6): e116, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33028449

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to significant strain on front-line healthcare workers. AIMS: In this multicentre study, we compared the psychological outcomes during the COVID-19 pandemic in various countries in the Asia-Pacific region and identified factors associated with adverse psychological outcomes. METHOD: From 29 April to 4 June 2020, the study recruited healthcare workers from major healthcare institutions in five countries in the Asia-Pacific region. A self-administrated survey that collected information on prior medical conditions, presence of symptoms, and scores on the Depression Anxiety Stress Scales and the Impact of Events Scale-Revised were used. The prevalence of depression, anxiety, stress and post-traumatic stress disorder (PTSD) relating to COVID-19 was compared, and multivariable logistic regression identified independent factors associated with adverse psychological outcomes within each country. RESULTS: A total of 1146 participants from India, Indonesia, Singapore, Malaysia and Vietnam were studied. Despite having the lowest volume of cases, Vietnam displayed the highest prevalence of PTSD. In contrast, Singapore reported the highest case volume, but had a lower prevalence of depression and anxiety. In the multivariable analysis, we found that non-medically trained personnel, the presence of physical symptoms and presence of prior medical conditions were independent predictors across the participating countries. CONCLUSIONS: This study highlights that the varied prevalence of psychological adversity among healthcare workers is independent of the burden of COVID-19 cases within each country. Early psychological interventions may be beneficial for the vulnerable groups of healthcare workers with presence of physical symptoms, prior medical conditions and those who are not medically trained.

3.
PeerJ ; 8: e9822, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32999759

RESUMO

The differences in small noncoding RNAs (sncRNAs), including miRNAs, piRNAs, and tRNA-derived fragments (tsRNAs), between X and Y sperm of mammals remain unclear. Here, we employed high-throughput sequencing to systematically compare the sncRNA profiles of X and Y sperm from bulls (n = 3), which may have a wider implication for the whole mammalian class. For the comparison of miRNA profiles, we found that the abundance of bta-miR-652 and bta-miR-378 were significantly higher in X sperm, while nine miRNAs, including bta-miR-204 and bta-miR-3432a, had greater abundance in Y sperm (p < 0.05). qPCR was then used to further validate their abundances. Subsequent functional analysis revealed that their targeted genes in sperm were significantly involved in nucleosome binding and nucleosomal DNA binding. In contrast, their targeted genes in mature oocyte were significantly enriched in 11 catabolic processes, indicating that these differentially abundant miRNAs may trigger a series of catabolic processes for the catabolization of different X and Y sperm components during fertilization. Furthermore, we found that X and Y sperm showed differences in piRNA clusters distributed in the genome as well as piRNA and tsRNA abundance, two tsRNAs (tRNA-Ser-AGA and tRNA-Ser-TGA) had lower abundance in X sperm than Y sperm (p < 0.05). Overall, our work describes the different sncRNA profiles of X and Y sperm in cattle and enhances our understanding of their potential roles in the regulation of sex differences in sperm and early embryonic development.

4.
Braz J Biol ; 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32696850

RESUMO

Dengue is a viral disease which is serious health concern from last few decades and the infection transmitted through mosquito bite into human. This study was conducted to carry out prevalence of dengue fever in District Swabi. A total of 196 blood sample were collected from patients with age ranges (0-80 years) having dengue fever on the basis of physical symptoms from Bacha Khan Medical Complex Swabi during August to October 2017. Serological test were performed for detection of IgM, IgG and NS1 (Non structural protein antigen of virus) against dengue. Out of total 196 confirmed dengue cases the most prone gender was male 123(62%) while 73(38%) were female. Among the age groups; 21-30 years group 62 (31.6%) was found the most predominated age group. The higly affected areas in district Swabi were Topi (40.8%) followed by Main Swabi (27%), Maneri (8.2%), Marghuz (6%), Shawa Ada (5.1%), Shah Mansoor (5.1%), Gohati (4.1%), and Chota Lahore (3.6%). Therefore, the health department should take actions by educating the public about basic cleanliness of the environment. The community should be encouraged to participate in the control of such vector based diseases/infections.

7.
Biosci Rep ; 39(8)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31371630

RESUMO

Clustered Regularly Interspaced Short Palindromic Repeat activation-synergistic activation mediator system (CRISPRa-SAM) has been efficiently used to up-regulate the targeted genes in human and mouse. But it is not known whether the CRISPRa-SAM system can be used against porcine disease because its two important transcriptional activation domains (P65 and heat shock transcription factor 1 (HSF1)) are from mouse and human, respectively. Pig is one of the most important meat sources, porcine viral infectious diseases cause massive economic losses to the swine industry and threaten the public health. We aimed to investigate whether the CRISPRa-SAM system could increase porcine antiviral activity by mediating two pig-specific target genes (Mx2 and ß1,4 N-acetylgalactosaminyltransferase (B4galnt2)). First, we constructed PK-15 and IPEC-J2 cell lines expressing nuclease-deficient Cas9 (dCas9)-vp64 and MS2-P65-HSF1 stably. Next, in these two cell models, we activated Mx2 and B4galnt2 expression through CRISPRa-SAM system. Antiviral activity to PRV or H9N2 was improved in PK-15 cells where Mx2 or B4galnt2 was activated. Altogether, our results demonstrated the potential of CRISPRa-SAM system as a powerful tool for activating pig genes and improving porcine antiviral activity.

9.
Trials ; 20(1): 195, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30947740

RESUMO

BACKGROUND: Maintaining adequate oxygenation during rapid sequence intubation (RSI) is imperative to prevent peri-intubation adverse events that can lead to increased duration of hospital and intensive care unit stay, or a prolonged vegetative state requiring long-term institutionalisation. Despite employing current best practices during RSI, desaturation during intubation still occurs. High-flow nasal cannula (HFNC) oxygenation may potentially improve oxygenation during pre- and apnoeic oxygenation to allow a longer safe apnoeic time for RSI. OBJECTIVE: We aim to test the hypothesis that the use of humidified high-flow oxygenation via nasal cannula at 60 L/min maintains higher oxygen saturation compared with current usual care of non-rebreather mask and standard nasal cannula at an oxygen flow rate of 15 L/min for pre- and apnoeic oxygenation. METHODS: This is a multi-centre randomised controlled trial enrolling adult patients aged 21 years and older who require rapid sequence intubation due to medical, surgical, or traumatic conditions in the Emergency Departments (EDs) of the National University Hospital and the Ng Teng Fong General Hospital. Eligible patients will undergo randomisation at an equal ratio into intervention or control arms. The primary endpoint will be the lowest oxygen saturation achieved during the first intubation attempt from time of administration of paralytic agent until quantitative end-tidal carbon dioxide is detected if the first intubation attempt is successful, or until the start of the second attempt if it is not. DISCUSSION: Prolongation of safe apnoea time through maintenance of oxygen saturation above 90% using HFNC oxygenation during RSI could potentially change current clinical practice, improve standard of care, and translate to better outcomes for patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03396094 . Registered on 10 January 2018.


Assuntos
Apneia/fisiopatologia , Intubação Intratraqueal/métodos , Pulmão/fisiopatologia , Oxigenoterapia/métodos , Respiração Artificial , Cânula , Estado Terminal , Serviço Hospitalar de Emergência , Feminino , Humanos , Intubação Intratraqueal/efeitos adversos , Masculino , Estudos Multicêntricos como Assunto , Oxigenoterapia/efeitos adversos , Oxigenoterapia/instrumentação , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial/efeitos adversos , Singapura , Fatores de Tempo , Resultado do Tratamento
10.
J Environ Manage ; 237: 644-651, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30870683

RESUMO

Environmental variations resulting in biotic and abiotic stresses demand adaptive changes in the photosynthetic machinery. To cope with these challenges, plant scientists are constantly striving to enhance photosynthetic activity. The photorespiration pathway, which fixes O2 and releases CO2 in C3 plants, competes with photosynthesis. One method to increase yield would be to enhance photosynthesis by engineering the photorespiratory pathway. To date, three engineered photorespiratory pathways have been produced, of which two have been proven experimentally in the model plant, Arabidopsis thaliana. These approaches might be helpful in enhancing crop resilience to future environmental challenges. In partially photorespiratory suppressed plants, it is hypothesized that a gene cluster may have formed between bacterial glycolate dehydrogenase (GDH), glyoxylate carboligase (GCL), and tartronic semi aldehyde (TSR) genes with Arabidopsis allantoin degradation genes like Arabidopsis allantoinase (AtALN) to utilize S-allantoin as a source of nitrogen. Observations of the use of allantoin as an exclusive source of nitrogen or energy by Arabidopsis and Escherichia coli led us to propose a genetic switch control model between nitrogen assimilation and energy producing pathways in partially photorespiratory suppressed plants.


Assuntos
Arabidopsis , Fotossíntese , Alantoína , Escherichia coli , Nitrogênio
11.
Sci Rep ; 9(1): 1433, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30723263

RESUMO

Emergence of Dengue as one of the deadliest viral diseases prompts the need for development of effective therapeutic agents. Dengue virus (DV) exists in four different serotypes and infection caused by one serotype predisposes its host to another DV serotype heterotypic re-infection. We undertook virtual ligand screening (VLS) to filter compounds against DV that may inhibit inclusively all of its serotypes. Conserved non-structural DV protein targets such as NS1, NS3/NS2B and NS5, which play crucial role in viral replication, infection cycle and host interaction, were selected for screening of vital antiviral drug leads. A dataset of plant based natural antiviral derivatives was developed. Molecular docking was performed to estimate the spatial affinity of target compounds for the active sites of DV's NS1, NS3/NS2B and NS5 proteins. The drug likeliness of the screened compounds was followed by ADMET analysis whereas the binding behaviors were further elucidated through molecular dynamics (MD) simulation experiments. VLS screened three potential compounds including Canthin-6-one 9-O-beta-glucopyranoside, Kushenol W and Kushenol K which exhibited optimal binding with all the three conserved DV proteins. This study brings forth novel scaffolds against DV serotypes to serve as lead molecules for further optimization and drug development against all DV serotypes with equal effect against multiple disease causing DV proteins. We therefore anticipate that the insights given in the current study could be regarded valuable towards exploration and development of a broad-spectrum natural anti-dengue therapy.

12.
Curr Issues Mol Biol ; 26: 55-64, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28879856

RESUMO

Global crop production is highly threatened due to pathogen invasion. The huge quantity of pesticides application, although harmful to the environment and human health, is carried out to prevent the crop losses worldwide, every year. Therefore, understanding the molecular mechanisms of pathogenicity and plant resistance against pathogen is important. The resistance against pathogens is regulated by three important phytohormones viz. salicylic acid (SA), jasmonic acid (JA) and ethylene (ET). Here we review possible role of CRISPR technology to understand the plant pathogenicity by mutating genes responsible for pathogen invasion or up-regulating the phytohormones genes or resistant genes. Thus hormone biosynthesis genes, receptor and feeding genes of pathogens could be important targets for modifications using CRISPR/Cas9 following multiplexing tool box strategy in order to edit multiple genes simultaneously to produce super plants. Here we put forward our idea thatthe genes would be either mutated in case of plant receptor protein targets of pathogens or up-regulation of resistant genes or hormone biosynthesis genes will be better choice for resistance against pathogens.


Assuntos
Proteínas de Bactérias/genética , Sistemas CRISPR-Cas , Produtos Agrícolas/genética , Resistência à Doença/genética , Endonucleases/genética , Edição de Genes/métodos , Genoma de Planta , Animais , Bactérias/genética , Bactérias/metabolismo , Bactérias/patogenicidade , Proteínas de Bactérias/metabolismo , Proteína 9 Associada à CRISPR , Produtos Agrícolas/imunologia , Produtos Agrícolas/microbiologia , Produtos Agrícolas/parasitologia , Ciclopentanos/imunologia , Ciclopentanos/metabolismo , Endonucleases/metabolismo , Etilenos/biossíntese , Etilenos/imunologia , Fungos/genética , Fungos/metabolismo , Fungos/patogenicidade , Mutação , Nematoides/genética , Nematoides/metabolismo , Nematoides/patogenicidade , Oxilipinas/imunologia , Oxilipinas/metabolismo , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Doenças das Plantas/parasitologia , Reguladores de Crescimento de Planta/biossíntese , Reguladores de Crescimento de Planta/genética , Reguladores de Crescimento de Planta/imunologia , Proteínas de Plantas/genética , Proteínas de Plantas/imunologia , Ácido Salicílico/imunologia , Ácido Salicílico/metabolismo
13.
Curr Issues Mol Biol ; 26: 93-102, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28879859

RESUMO

Genome editing is unraveling its benefits in wide areas of scientific development and understanding. The advances of genome editing from ZFNs and TALLENs to CRISPRs defines it wide applicability. Reproduction is the fundamental process by which all organisms maintain their generations. CRISPR/Cas9, a new versatile genome editing tool is recently tamed to correct several disease causing genetic mutations spreading its arms to improve reproductive health. It not only edit harmful genetic mutations but is also applied to control the spread of parasitic diseases like malaria by introducing selfish genetic elements, propagated through generations and population via reproduction. These applications made us to review the recent developments of CRISPRs use in reproductive biology.


Assuntos
Proteínas de Bactérias/genética , Sistemas CRISPR-Cas , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Endonucleases/genética , Genoma , Controle Biológico de Vetores/métodos , RNA Guia/genética , Medicina Reprodutiva/métodos , Animais , Anopheles/genética , Anopheles/parasitologia , Proteínas de Bactérias/metabolismo , Proteína 9 Associada à CRISPR , Embrião de Mamíferos , Endonucleases/metabolismo , Feminino , Edição de Genes , Humanos , Malária Falciparum/parasitologia , Malária Falciparum/prevenção & controle , Malária Falciparum/transmissão , Plasmodium falciparum/genética , RNA Guia/metabolismo
14.
Oncotarget ; 8(35): 58430-58442, 2017 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-28938568

RESUMO

Germ cells develop in a sophisticated immune privileged microenvironment provided by specialized junctions contiguous the basement membrane of the adjacent Sertoli cells that constituted the blood-testis barrier (BTB) in seminiferous epithelium of testis in mammals. Deciphering the molecular regulatory machinery of BTB activity is central to improve male fertility and the role of post-translational modification including SUMOylation pathway is one of the key factors. Herein, we unveiled the mystery of the SUMO-2/3 specific protease SENP3 (Sentrin-specific protease 3) in BTB dynamics regulation. SENP3 is predominantly expressed in the nucleus of Sertoli and spermatocyte cells in adult mouse testis, and knockdown of SENP3 compromises tight junction in Sertoli cells by destructing the permeability function with a concomitant decline in trans-epithelial electrical resistance in primary Sertoli cells, which could attribute to the conspicuous dysfunction of tight junction (TJ) proteins (e.g., ZO-1, occludin) at the cell-cell interface due to the inactivation of STAT3. Moreover, SENP3 knockdown disrupts F-actin architecture in Sertoli cells through intervening Rac1/CDC42-N-WASP-Arp2/3 signaling pathway and Profilin-1 abundance. Our study pinpoints SENP3 might be a novel determinant of multiple pathways governing BTB dynamics in testis to support germ cells development in mammals.

15.
Oncotarget ; 8(33): 54416-54433, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28903352

RESUMO

The biology of sperm, its capability of fertilizing an egg and its role in sex ratio are the major biological questions in reproductive biology. To answer these question we integrated X and Y chromosome transcriptome across different species: Bos taurus and Sus scrofa and identified reproductive driver genes based on Weighted Gene Co-Expression Network Analysis (WGCNA) algorithm. Our strategy resulted in 11007 and 10445 unique genes consisting of 9 and 11 reproductive modules in Bos taurus and Sus scrofa, respectively. The consensus module calculation yields an overall 167 overlapped genes which were mapped to 846 DEGs in Bos taurus to finally get a list of 67 dual feature genes. We develop gene co-expression network of selected 67 genes that consists of 58 nodes (27 down-regulated and 31 up-regulated genes) enriched to 66 GO biological process (BP) including 6 GO annotations related to reproduction and two KEGG pathways. Moreover, we searched significantly related TF (ISRE, AP1FJ, RP58, CREL) and miRNAs (bta-miR-181a, bta-miR-17-5p, bta-miR-146b, bta-miR-146a) which targeted the genes in co-expression network. In addition we performed genetic analysis including phylogenetic, functional domain identification, epigenetic modifications, mutation analysis of the most important reproductive driver genes PRM1, PPP2R2B and PAFAH1B1 and finally performed a protein docking analysis to visualize their therapeutic and gene expression regulation ability.

16.
PLoS One ; 12(6): e0179343, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28622342

RESUMO

INTRODUCTION: In the past 20 years, our understanding of acute respiratory distress syndrome (ARDS) management has improved, but the worldwide incidence and current outcomes are unclear. The reported incidence is highly variable, and no studies specifically characterise ARDS epidemiology in Asia. This observation study aims to determine the incidence, mortality and management practices of ARDS in a high income South East Asian country. METHODS: We conducted a prospective, population based observational study in 6 public hospitals. During a one month period, we identified all ARDS patients admitted to public hospital intensive care units (ICU) in Singapore, according to the Berlin definition. Demographic information, clinical management data and ICU outcome data was collected. RESULTS: A total of 904 adult patients were admitted to ICU during the study period and 15 patients met ARDS criteria. The unadjusted incidence of ARDS was 4.5 cases per 100,000 population, accounting for 1.25% of all ICU patients. Most patients were male (75%), Chinese (62%), had pneumonia (73%), and were admitted to a Medical ICU (56%). Management strategies varied across all ICUs. In-hospital mortality was 40% and median length of ICU stay was 7 days. CONCLUSION: The incidence of ARDS in a developed S.E Asia country is comparable to reported rates in European studies.


Assuntos
Mortalidade Hospitalar , Tempo de Internação , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Síndrome do Desconforto Respiratório do Adulto/terapia , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores Sexuais , Singapura/epidemiologia
17.
Biochim Biophys Acta Mol Cell Res ; 1864(7): 1195-1206, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28315713

RESUMO

Understanding the mechanisms underlying abnormal egg production and pregnancy loss is significant for human fertility. SENP7, a SUMO poly-chain editing enzyme, has been regarded as a mitotic regulator of heterochromatin integrity and DNA repair. Herein, we report the roles of SENP7 in mammalian reproductive scenario. Mouse oocytes deficient in SENP7 experienced meiotic arrest at prophase I and metaphase I stages, causing a substantial decrease of mature eggs. Hyperaceylation and hypomethylation of histone H3 and up-regulation of Cdc14B/C accompanied by down-regulation of CyclinB1 and CyclinB2 were further recognized as contributors to defective M-phase entry and spindle assembly in oocytes. The spindle assembly checkpoint activated by defective spindle morphogenesis, which was also caused by mislocalization and ubiquitylation-mediated proteasomal degradation of γ-tubulin, blocked oocytes at meiosis I stage. SENP7-depleted embryos exhibited severely defective maternal-zygotic transition and progressive degeneration, resulting in nearly no blastocyst production. The disrupted epigenetic landscape on histone H3 restricted Rad51C loading onto DNA lesions due to elevated HP1α euchromatic deposition, and reduced DNA 5hmC challenged the permissive status for zygotic DNA repair, which induce embryo death. Our study pinpoints SENP7 as a novel determinant in epigenetic programming and major pathways that govern oocyte and embryo development programs in mammals.


Assuntos
Blastocisto/metabolismo , Endopeptidases/genética , Epigênese Genética , Herança Materna , Meiose , Animais , Células Cultivadas , Ciclina B1/metabolismo , Ciclina B2/metabolismo , Endopeptidases/metabolismo , Feminino , Histonas/metabolismo , Pontos de Checagem da Fase M do Ciclo Celular , Camundongos , Oócitos/metabolismo , Gravidez , Tubulina (Proteína)/metabolismo , Zigoto/metabolismo
18.
Curr Issues Mol Biol ; 21: 21-40, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27033743

RESUMO

Preventing pathogen transmission to a new host is of major interest to the immunologist and could benefit from a detailed investigation of pathogen immune evasion strategies. The first line of defense against pathogen invasion is provided by macrophages. When they sense pathogens, macrophages initiate signals to inflammatory and pro-inflammatory cytokines through pattern recognition receptors (PRRs) subsequently mediating phagocytosis and inflammation. The macrophage immune machinery classically includes two subsets: the activated M1 and the activated M2 that respond accordingly in diverse immune challenges. The lipid and glycogen metabolic pathways work together with the lysosome to help the mature phagosome to degrade and eliminate intracellular pathogens in macrophages. The viral evasion strategies are even more complex due to the interplay between autophagy and apoptosis. However, pathogens evolve several strategies to camouflage themselves against immune responses in order to ensure their survival, replication and transmission. These strategies include the muting of PRRs initiated inflammatory responses, attenuation of M1 and/or induction of M2 macrophages, suppression of autophago-lysosomal formation, interference with lipid and glycogen metabolism, and viral mediation of autophagy and apoptosis cross-talk to enhance viral replication. This review focuses on pathogen immune evasion methods and on the strategies used by the host against camouflaged pathogens.


Assuntos
Interações Hospedeiro-Patógeno/fisiologia , Evasão da Resposta Imune , Macrófagos/imunologia , Animais , Apoptose/fisiologia , Autofagia/fisiologia , Humanos , Macrófagos/microbiologia , Macrófagos/virologia , Fagossomos/fisiologia , Receptores de Reconhecimento de Padrão/imunologia , Receptores de Reconhecimento de Padrão/metabolismo
19.
In Vitro Cell Dev Biol Anim ; 53(3): 258-264, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27826797

RESUMO

Maintenance and timely termination of cohesion on chromosomes ensures accurate chromosome segregation to guard against aneuploidy in mammalian oocytes and subsequent chromosomally abnormal pregnancies. Sororin, a cohesion stabilizer whose relevance in antagonizing the anti-cohesive property of Wings-apart like protein (Wapl), has been characterized in mitosis; however, the role of Sororin remains unclear during mammalian oocyte meiosis. Here, we show that Sororin is required for DNA damage repair and cohesion maintenance on chromosomes, and consequently, for mouse oocyte meiotic program. Sororin is constantly expressed throughout meiosis and accumulates on chromatins at germinal vesicle (GV) stage/G2 phase. It localizes onto centromeres from germinal vesicle breakdown (GVBD) to metaphase II stage. Inactivation of Sororin compromises the GVBD and first polar body extrusion (PBE). Furthermore, Sororin inactivation induces DNA damage indicated by positive γH2AX foci in GV oocytes and precocious chromatin segregation in MII oocytes. Finally, our data indicate that PlK1 and MPF dissociate Sororin from chromosome arms without affecting its centromeric localization. Our results define Sororin as a determinant during mouse oocyte meiotic maturation by favoring DNA damage repair and chromosome separation, and thereby, maintaining the genome stability and generating haploid gametes.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Ciclo Celular/genética , Centrômero/genética , Meiose/genética , Oócitos/crescimento & desenvolvimento , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Animais , Proteínas de Ciclo Celular/biossíntese , Segregação de Cromossomos/genética , Dano ao DNA/genética , Reparo do DNA/genética , Feminino , Proteínas Ligadas por GPI/genética , Regulação da Expressão Gênica no Desenvolvimento , Histonas/genética , Camundongos , Corpos Polares/citologia , Proteínas Serina-Treonina Quinases/genética , Proteínas/genética , Proteínas Proto-Oncogênicas/genética
20.
Acta Histochem ; 119(1): 26-31, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27884396

RESUMO

This study was undertaken to determine if visfatin is involved in the inflammation or apoptosis introduced by LPS in rats. Forty 8-week old Wistar rats were divided into four groups (n=10 in each group) and injected with saline, visfatin, LPS and visfatin+LPS co-stimulated via caudal vein. The duodenum, jejunum and ileum were harvested from all the rats. Compared to the saline treated group, visfatin significantly increased the number of TUNEL-positive apoptotic cells and the expression of caspase-3 protein in intestinal mucosa. Similarly, ELISA and western blot analysis also showed the up-regulation of pro-caspase-3 and cleaved caspase-3 expression in the visfatin group compared to the control group. In contrast to LPS, visfatin down-regulated the expression of cleaved-caspase-3 in the visfatin+LPS co-stimulated group, resulting in a significant decrease in apoptosis in intestinal mucosal cells. We observed more pro-caspase-3 positive cells in the visfatin+LPS co-stimulated group. The results indicate that, in the presence of LPS, visfatin plays an important role in the regulation of cell apoptosis and inflammation.


Assuntos
Apoptose/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Imunidade nas Mucosas/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Nicotinamida Fosforribosiltransferase/farmacologia , Animais , Caspase 3/genética , Caspase 3/metabolismo , Combinação de Medicamentos , Duodeno/citologia , Duodeno/efeitos dos fármacos , Duodeno/imunologia , Células Epiteliais/citologia , Células Epiteliais/imunologia , Expressão Gênica , Íleo/citologia , Íleo/efeitos dos fármacos , Íleo/imunologia , Marcação In Situ das Extremidades Cortadas , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Jejuno/citologia , Jejuno/efeitos dos fármacos , Jejuno/imunologia , Ratos , Ratos Wistar
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