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1.
Artigo em Inglês | MEDLINE | ID: mdl-33388997

RESUMO

Previously we reported that administration of IgG could inhibit tumor progression in mouse models. At the same time, we also found that some IgGs have glycosylation modifications on their Fab fragments, which may have different biological functions than non-glycosylated IgG. In this study, we employed mouse tumor models to explore the roles of two different forms of IgG, i.e. Fab-glycosylated and Fab-non-glycosylated IgG, in tumor progression. The two types of IgGs were separated with ConA absorption which could react with glycan on the Fab arm but could not access glycan on the Fc fragment. In addition, we performed cytokine array, ELISA, western blotting, immunocytochemistry and other techniques to investigate the possible mechanisms of the actions of Fab-glycosylated IgG in the models. We found that Fab-glycosylated IgG, unlike Fab-non-glycosylated IgG, did not inhibit tumor growth and metastasis in the model. On the contrary, Fab-glycosylated IgG may bind to antigen-bound IgG molecules and macrophages through the glycosidic chain on the Fab fragment to affect antigen-antibody binding and macrophage polarization, which are likely to help tumor cells to evade the immune surveillance. A new mechanism of immune evasion with Fab-glycosylated IgG playing a significant role was proposed.

2.
Zhongguo Gu Shang ; 33(12): 1166-70, 2020 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-33369326

RESUMO

OBJECTIVE: To evaluate the clinical outcome of tibiotalocalcaneal fusion using cannulated screw and humeral proximal locking plate inverted fixation through a lateral transfibular approach. METHODS: From June 2015 to December 2018, 15 patients underwent a tibiotalocalcaneal fusion operation using cannulated screw and inverted proximal humerus locking plate through a transfibular approach. There were 10 males and 5 females with the age ranging from 45 to 72 (58.9±6.1) years, and the course of disease ranged from 2 to 35 (11.9±7.9)years. Preoperative diagnosis included 8 cases of post traumatic arthritis, 2 cases of Charcot arthritis, 2 cases of Charcot-Marie -Tooth (CMT), 1 case of ankle tuberculosis, 1 case of talar necrosis, and 1 case of pigmented villonnodular synovitis. Among them, 8 patients were combined with simple varus deformity, 4 patients with simple valgus deformity, 2 patients with equinovarus deformity, 1 patient with equinovarus deformity, 2 patients with adduction and internal rotation of middle and forefoot. American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot score and the visual analogue scale (VAS) score were used to evaluate the clinical outcome at the last follow up. RESULTS: One lost follow up and remaining fourteen patients were followed up. The follow up time ranged from 10 to 25(16.6±4.3) months. All the 15 patients had primary healing. Fusion time ranged from 15 to 24 (16.8 ± 2.4) weeks after operation. One patient with diabetes experienced delayed union and was successfully treated with secondary bone grafting combined with Platelet-Rich Plasma (PRP) injection. The AOFAS score increased from 38.7±3.3 to 84.5±2.6 (P<0.05), and the VAS score decreased from 7.5±1.6 to 1.9±0.3(P<0.05). CONCLUSION: Tibiotalocalcaneal fusion used cannulated screw and humeral proximal locking plate inverted fixation through a lateral transfibular approach has the advantages of relatively simple technique, high fusion rate, especially for patients with posterior foot deformity, which has satisfactory short term effects.


Assuntos
Placas Ósseas , Parafusos Ósseos , Articulação do Tornozelo , Artrodese , Feminino , Humanos , Úmero , Masculino , Estudos Retrospectivos , Resultado do Tratamento
3.
PLoS One ; 15(10): e0240223, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33052930

RESUMO

The Aedes aegypti mosquito plays an important role in the spread of diseases, including epidemic ones, such as dengue fever, Zika virus disease, yellow fever, and chikungunya disease. To control the population of Ae.aegypti, we transferred an HR3 RNAi fragment into the microalgae Chlamydomonas, which serves as food for Ae.aegypti larvae. Results showed that the HR3 RNAi transgenic algal strains were lethal to Ae.aegypti. The integumentary system of larvae fed with HR3 RNAi transgenic algal strains was severely damaged. Muscles of the larvae were unevenly distributed and disordered, and their midgut showed disintegration of the intestinal cavity. RNA-Seq results demonstrated that on the 4th day of inoculation with the transgenic algae, the abundance of early expressed genes in the 20E signal transduction pathway of larvae fed with the HR3 RNAi transgenic algal strain significantly reduced. These genes include E74, E75, E93, and 20E receptor complex EcR/USP and FTZ-F1 gene regulated by HR3. In later experiments, a scale test of 300 Ae.aegypti eggs per group was carried out for 30 days, and the survival rate of Ae.aegypti fed with the HR3 RNAi transgenic strain was only 1.3%. These results indicate that the HR3 RNAi transgenic strain exerts obvious insecticidal effect.

4.
Ann Hum Genet ; 84(3): 259-270, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31789429

RESUMO

The fatty acid amide hydrolase (FAAH) gene was involved in the modulation of reward and addiction pathophysiology of illicit drugs abuse, and its polymorphisms might be associated with risk of methamphetamine (METH) dependence. This study aimed to investigate the FAAH mRNA levels in peripheral blood mononuclear cells and plasma protein levels and to analyze the 385C/A polymorphism (rs324420) between METH-dependent patients and controls. The levels of FAAH mRNA in METH dependence were significantly lower than in controls (P < 0.001), however, its plasma protein underwent a significant ∼2-fold increase (P < 0.001). The A allele of the 385C/A polymorphism significantly increased the METH dependence risk (P < 0.001, odds ratio [OR] = 1.646, 95% confidence interval [CI] = 1.332-2.034). The carried A genotypes (AA, AC, and AA/AC) of 385C/A polymorphism also increased METH-dependence risks under a different genetic model (AA vs. CC: P = 0.017, OR = 2.454, 95%CI = 1.171-2.143; AC vs. CC: P < 0.001, OR = 1.818, 95%CI = 1.404-2.353; AC/AA vs. CC: P < 0.001, OR = 1.858, 95%CI = 1.444-2.319). The similar results were obtained after adjusting for age and sex. Unfortunately, we failed to find that any genotype of 385C/A polymorphism affected the mRNA or plasma protein levels in controls, respectively (P > 0.05). These data indicate that the FAAH may play an important role in the pathophysiological process of METH dependence, and the 385C/A polymorphism may be associated with METH dependence susceptibility in a Chinese Han population.

5.
Genomics ; 112(3): 2203-2212, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31881265

RESUMO

The roles of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in embryonic development remain unclear. We performed a comprehensive analysis of lncRNA and circRNA profiles in rabbit embryos at different stages by whole transcriptome sequencing. We identified 719 lncRNAs and 744 circRNAs that were differentially expressed between stages S1, S2 and S3. A total of 241 differentially expressed lncRNAs and 166 differentially expressed circRNAs were significantly involved in embryonic morphogenesis and development. An RNA network was established and of the embryonic development-associated RNAs, the lncRNAs TCONS_00009253 and TCONS_00010436 were persistently downregulated, while circRNA_07129, circRNA_15209, and circRNA_12526 were persistently upregulated, and their co-expressed mRNAs TBX1, WNT3 and FGFR2 were persistently downregulated during embryonic development. These candidate RNAs were mainly involved in the Wnt, PI3K-Akt, and calcium signaling pathways. This study reports candidate lncRNAs and circRNAs that may be indispensable for the morphogenesis and development of rabbit embryos.

6.
Front Plant Sci ; 10: 1147, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695707

RESUMO

Calcium-dependent protein kinases (CDPKs) are recognized as important calcium (Ca2+) sensors in signal transduction and play multiple roles in plant growth and developmental processes, as well as in response to various environmental stresses. However, little information is available about the CDPK family in the green microalga Chlamydomonas reinhardtii. In this study, 15 CrCDPK genes were identified in C. reinhardtii genome, and their functions in nitrogen (N) deficiency-induced oil accumulation were analyzed. Our results showed that all CrCDPK proteins harbored the typical elongation factor (EF)-hand Ca2+-binding and protein kinase domains. Phylogenetic analysis revealed that these CrCDPKs were clustered into one group together with a subclade of several CPKs from Arabidopsis and rice, clearly separating from the remaining AtCPKs and OsCPKs. These genes were located in 10 chromosomes and one scaffold of C. reinhardtii and contained 6-17 exons. RNA sequencing and quantitative reverse transcription (qRT)-PCR assays indicated that most of these CrCDPKs were significantly induced by N deficiency and salt stress. Lanthanum chloride (LaCl3), a plasma membrane Ca2+ channel blocker, limited oil accumulation in C. reinhardtii under N-deficient conditions, suggesting that Ca2+ was involved in N deficiency-induced oil accumulation. Furthermore, RNA interference (RNAi) silencing analyses demonstrated that six CrCDPKs played positive roles and three CrCDPKs played negative roles in N deficiency-induced oil accumulation in C. reinhardtii.

7.
Iran J Allergy Asthma Immunol ; 18(3): 251-261, 2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31522432

RESUMO

Growing evidence indicated conflicting results that Interleukin-18 (IL-18) promoter polymorphisms rs1946518 (A-607C), rs187238 (G-137C) and rs549908 (A-105C) were associated with asthma risk. The aim of this study is to comprehensively evaluate the IL-18 polymorphisms and asthma by a systematic review and meta-analysis. A total of 12 studies testing the association between these polymorphisms and asthma were examined (8 studies for A-607C, 8 studies for G-137C, and 4 studies for A-105C) in the update meta-analysis, up to Dec 30, 2017. Summary odds ratios (ORs) and 95% confidence intervals (CI) were used to estimate the strength of association between each polymorphism and asthma using fixed- and random-effects models when appropriate. Heterogeneity and publication bias were evaluated. The meta-analysis results indicated that any allele frequencies of the IL-18 polymorphisms (A-607C, G-137C and A-105C) was not associated with asthma risk (p>0.05). And no statistically significant association was observed between genotype frequencies of these polymorphisms and asthma under different genetic models (p>0.05). Subgroup analysis results were similar to the main analysis by ethnicity, sample size, genotyping methods, matching criteria and quality score. There was no evidence of publication bias. The present meta-analysis suggests that IL-18 polymorphisms (A-607C, G-137C and A-105C) were unlikely to be associated with asthma risk.


Assuntos
Asma/genética , Predisposição Genética para Doença , Interleucina-18/genética , Polimorfismo de Nucleotídeo Único , Alelos , Frequência do Gene , Estudos de Associação Genética , Heterogeneidade Genética , Genótipo , Humanos , Viés de Publicação , Medição de Risco , Fatores de Risco
8.
Cancer Manag Res ; 11: 2073-2085, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30881131

RESUMO

Background: Previous accidental findings showed that administration of immunoglobulin G (IgG) in treating autoimmune diseases was able to inhibit cancers that happened to grow in these patients. However, such treatment has not been used to treat cancer patients clinically. The mechanism and optimal dosages of this treatment have not been established. Subsequent animal experiments confirmed this effect, but all previous studies in animal models used human IgG which was heterogeneous to the animal hosts and therefore could adversely interfere with the results. Materials and methods: We tested different dosages of mouse IgG in treating and preventing three syngeneic cancer types (melanoma, colon cancer, and breast cancer) in three immune potent mouse models. The expression of Ki67, CD34, VEGF, MMPs, and cytokines in tumor tissues were examined with immunohistochemistry or quantitative real-time PCR to evaluate tumor proliferation, vascularization, metastasis, and proinflammatory response in the tumor microenvironment. Results: We found that low-dose IgG could effectively inhibit cancer progression, regulate tumor vessel normalization, and prolong survival. Administration of IgG before cancer cell inoculation could also prevent the development of cancer. In addition, IgG caused changes in a number of cytokines and skewed macrophage polarization toward M1-like phenotype, characterized by proinflammatory activity and inhibition of proliferation of cancer cells. Conclusion: Our findings suggest that nonspecific IgG at low dosages could be a promising candidate for cancer prevention and treatment.

9.
Plant Biotechnol J ; 17(7): 1394-1407, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30578709

RESUMO

Tetraploids have been reported to exhibit increased stress tolerance, but the underlying molecular and physiological mechanisms remain poorly understood. In this study, autotetraploid plants were identified by screening natural seedlings of trifoliate orange (Poncirus trifoliata). The tetraploids exhibited different morphology and displayed significantly enhanced drought and dehydration tolerance in comparison with the diploid progenitor. Transcriptome analysis indicated that a number of stress-responsive genes and pathways were differentially influenced and enriched in the tetraploids, in particular those coding for enzymes related to antioxidant process and sugar metabolism. Transcript levels and activities of antioxidant enzymes (peroxidase and superoxide dismutase) and sucrose-hydrolysing enzyme (vacuolar invertase) were increased in the tetraploids upon exposure to the drought, concomitant with greater levels of glucose but lower level of reactive oxygen species (ROS). These data indicate that the tetraploids might undergo extensive transcriptome reprogramming of genes involved in ROS scavenging and sugar metabolism, which contributes, synergistically or independently, to the enhanced stress tolerance of the tetraploid. Our results reveal that the tetraploids take priority over the diploid for stress tolerance by maintaining a more robust system of ROS detoxification and osmotic adjustment via elevating antioxidant capacity and sugar accumulation in comparison with the diploid counterpart.


Assuntos
Secas , Poncirus/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico , Açúcares/metabolismo , Tetraploidia , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Plantas Geneticamente Modificadas
11.
BMC Geriatr ; 18(1): 49, 2018 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-29454316

RESUMO

BACKGROUND: This study introduces the conceptual basis and operational measure, of BioPyschoSocial (BPS) health and related risk to better understand how well older people are managing and to screen for risk status. The BPS Risk Screener is constructed to detect vulnerability at older ages, and seeks to measure dynamic processes that place equal emphasis on Psycho-emotional and Socio-interpersonal risks, as Bio-functional ones. We validate the proposed measure and describe its application to programming. METHODS: We undertook a quantitative cross-sectional, psychometric study with n = 1325 older Singaporeans, aged 60 and over. We adapted the EASYCare 2010 and Lubben Social Network Scale questionnaires to help determine the BPS domains using factor analysis from which we derive the BPS Risk Screener items. We then confirm its structure, and test the scoring system. The score is initially validated against self-reported general health then modelled against: number of falls; cognitive impairment; longstanding diseases; and further tested against service utilization (linked administrative data). RESULTS: Three B, P and S clusters are defined and identified and a BPS managing score ('doing' well, or 'some', 'many', and 'overwhelming problems') calculated such that the risk of problematic additive BPS effects, what we term health 'loads', are accounted for. Thirty-five items (factor loadings over 0.5) clustered into three distinct B, P, S domains and were found to be independently associated with self-reported health: B: 1.99 (1.64 to 2.41), P: 1.59 (1.28 to 1.98), S: 1.33 (1.10 to 1.60). The fit improved when combined into the managing score 2.33 (1.92 to 2.83, < 0.01). The score was associated with mounting risk for all outcomes. CONCLUSIONS: BPS domain structures, and the novel scoring system capturing dynamic BPS additive effects, which can combine to engender vulnerability, are validated through this analysis. The resulting tool helps render clients' risk status and related intervention needs transparent. Given its explicit and empirically supported attention to P and S risks, which have the potential to be more malleable than B ones, especially in the older old, this tool is designed to be change sensitive.


Assuntos
Intervenção Médica Precoce/métodos , Nível de Saúde , Inquéritos Epidemiológicos/métodos , Seguridade Social , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Fatores de Risco , Singapura/epidemiologia , Inquéritos e Questionários
12.
J Eukaryot Microbiol ; 65(1): 117-126, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28703942

RESUMO

acyl-CoA:Diacylglycerol acyltransferases (DGAT) catalyse the final step of the triacylglycerol biosynthesis. Two major gene families have been shown to encode DGATs, DGAT1, and DGAT2. Abiotic factors such as low temperatures, nitrogen, or phosphorus deficiency was reported to play important roles in the growth and development in green algae. Whether DGATs are induced by low temperatures or phosphorus deficiency, and the corresponding promoter elements are not reported yet. In this study, we found DGTT3 to have a significant response to low temperatures, phosphorus deficiency, and other stresses, such as high concentrations of NaCl, 20 µM GA, and 20 µM abscisic acid. The promoter element of DGTT3 was then studied by deletion and scanning mutagenesis method. Results revealed that the - 319/- 247 region is essential for low-temperature and phosphate-deficiency-mediated induction of DGTT3 expression. The sequence from - 312 to - 299 of the CAATAGACTGCTGCT was the core sequence of the cold responsive element, which facilitated the promoter response to cold induction. Meanwhile, the sequence from - 319 to - 275 was critical to phosphate-deficiency regulation. Furthermore, the relationship between DNA methylation and transgenic silence in -N condition was analyzed, and results showed that the DNA methylation rate of the transformed insertion region was high. This phenomenon was responsible for the decrease in ARS gene expression in the transgenic algal strain under -N conditions.


Assuntos
Proteínas de Algas/genética , Chlamydomonas reinhardtii/genética , Temperatura Baixa , Regulação da Expressão Gênica , Fosfatos/deficiência , Proteínas de Algas/metabolismo , Metilação de DNA , Inativação Gênica , Transgenes
13.
J Forensic Leg Med ; 49: 15-19, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28486142

RESUMO

The age-related capacity decline of DNA damage repair in human peripheral blood has been demonstrated. Excision repair cross-complementation group1 (ERCC1) and Xeroderma pigmentosum complementation group F (XPF) were rate-limiting enzyme in nucleotide excision repair (NER) which was known as the most important DNA damage repair system. Consequently, we hypothesized that the expression and/or activity of ERCC1 and XPF may be associated with age. However, little was known about the quantitative relationship of ERCC1 and XPF expression levels with age. The aim of the present study was to analyze the correlation of ERCC1 and XPF expression levels with age by detecting the ERCC1 and XPF mRNA levels in peripheral blood mononuclear cells(PBMCs) and protein levels in plasma in healthy ethnic Han Chinese individuals, and finally find new molecular markers for forensic age estimation by establishing the mathematical model between ERCC1 and XPF expression levels and age. The results showed that the ERCC1 and XPF mRNA relative expression levels in PBMCs declined in an age-dependent manner (r = -0.578/-0.844, respectively, P < 0.01). The formula for age estimation based on the ERCC1 and XPF mRNA relative expression levels decline in PBMCs were Y = 3.3E-5x2-0.0261x+1.9175 (R2 = 0.3244, P < 0.01) and Y = 0.0003x2-0.0459x+2.0439 (R2 = 0.729, P < 0.01), respectively. There were no significant differences of the ERCC1 or XPF protein expression levels in plasma between age groups (P > 0.05). Furthermore, there were no significant differences of the ERCC1 or XPF mRNA and/or protein expression levels between males and females(P > 0.05). It suggested that the ERCC1 and XPF mRNA expression levels could be considered as valuable additional tool in individual age estimation, especially in cases where traditional morphologic method was inefficient or absent in forensic practice.


Assuntos
Envelhecimento/metabolismo , Proteínas de Ligação a DNA/metabolismo , Endonucleases/metabolismo , Leucócitos Mononucleares/metabolismo , RNA Mensageiro/metabolismo , Xeroderma Pigmentoso/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Criança , Pré-Escolar , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Ensaio de Imunoadsorção Enzimática , Grupos Étnicos/genética , Feminino , Marcadores Genéticos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Reação em Cadeia da Polimerase em Tempo Real , Análise de Regressão , Xeroderma Pigmentoso/genética , Adulto Jovem
14.
BMC Biochem ; 18(1): 6, 2017 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-28511672

RESUMO

BACKGROUND: Under iron-deficient conditions, Chlamydomonas exhibits high affinity for iron absorption. Nevertheless, the response, transmission, and regulation of downstream gene expression in algae cells have not to be investigated. Considering that the MAPK pathway is essential for abiotic stress responses, we determined whether this pathway is involved in iron deficiency signal transduction in Chlamydomonas. RESULTS: Arabidopsis MAPK gene sequences were used as entry data to search for homologous genes in Chlamydomonas reinhardtii genome database to investigate the functions of mitogen-activated protein kinase (MAPK) gene family in C. reinhardtii under iron-free conditions. Results revealed 16 C. reinhardtii MAPK genes labeled CrMAPK2-CrMAPK17 with TXY conserved domains and low homology to MAPK in yeast, Arabidopsis, and humans. The expression levels of these genes were then analyzed through qRT-PCR and exposure to high salt (150 mM NaCl), low nitrogen, or iron-free conditions. The expression levels of these genes were also subjected to adverse stress conditions. The mRNA levels of CrMAPK2, CrMAPK3, CrMAPK4, CrMAPK5, CrMAPK6, CrMAPK8, CrMAPK9, and CrMAPK11 were remarkably upregulated under iron-deficient stress. The increase in CrMAPK3 expression was 43-fold greater than that in the control. An RNA interference vector was constructed and transformed into C. reinhardtii 2A38, an algal strain with an exogenous FOX1:ARS chimeric gene, to silence CrMAPK3. After this gene was silenced, the mRNA levels and ARS activities of FOX1:ARS chimeric gene and endogenous CrFOX1 were decreased. The mRNA levels of iron-responsive genes, such as CrNRAMP2, CrATX1, CrFTR1, and CrFEA1, were also remarkably reduced. CONCLUSION: CrMAPK3 regulates the expression of iron-deficiency-responsive genes in C. reinhardtii.


Assuntos
Chlamydomonas reinhardtii/genética , Regulação da Expressão Gênica de Plantas , Ferro/deficiência , Proteína Quinase 3 Ativada por Mitógeno/fisiologia , Inativação Gênica/fisiologia , Genes de Plantas , Proteína Quinase 3 Ativada por Mitógeno/genética , RNA Mensageiro/análise , Transdução de Sinais , Estresse Fisiológico
15.
Biochim Biophys Acta Gen Subj ; 1861(1 Pt A): 3345-3354, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27569901

RESUMO

BACKGROUND: Iron deficiency related gene, Femu2, encodes protein homologous to a C2H2-type zinc finger protein, which participates in the regulation of FOX1 gene induced by iron (Fe) deficiency in Chlamydomonas reinhardtii. In this study, we investigate the gene function of Femu2 in response to salt stress in C. reinhardtii. METHODS: Femu2-overexpressing and Femu2-silencing transgenic cells were analyzed under salt stress. Several physiological indices were measured, and global changes in gene expression were investigated via RNA-seq. RESULTS: Compared with that of the non-treated control, the transcript levels of Femu2 were dramatically induced by iron deficiency and can also be significantly induced after algal cell exposure to Tris-acetate-phosphate (TAP) medium with 100 and 150mM NaCl. The promoter also responded to NaCl induction. Femu2-overexpressing transgenic algal cells exhibited significantly enhanced tolerance to salt stress. Conversely, Femu2-silencing cells showed higher sensitivity to salt stress than the control. Physiological analyses revealed that the overexpression of Femu2 increased the contents of proline and soluble sugars in transgenic cells under high salinity and that silencing Femu2 resulted in increased malondialdehyde level and decreased superoxide dismutase activity. RNA-seq results showed that a total of 248 genes have opposite expression profiles and that 5508 and 2120 genes were distinctly up-regulated or down-regulated in Femu2-overexpressing and Femu2-silencing transgenic cells under salt stress, respectively. CONCLUSION: Femu2 may play an important positive role in protecting C. reinhardtii against salt stress. GENERAL SIGNIFICANCE: The results of this study indicated that Femu2 may be useful in improving plant salt tolerance.


Assuntos
Chlamydomonas reinhardtii/genética , Chlamydomonas reinhardtii/fisiologia , Genes de Plantas , Ferro/deficiência , Proteínas de Plantas/genética , Cloreto de Sódio/farmacologia , Estresse Fisiológico/genética , Ácido Abscísico/farmacologia , Chlamydomonas reinhardtii/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Ontologia Genética , Inativação Gênica/efeitos dos fármacos , Manitol/farmacologia , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas/genética , Reação em Cadeia da Polimerase em Tempo Real , Tolerância ao Sal/efeitos dos fármacos , Tolerância ao Sal/genética , Estresse Fisiológico/efeitos dos fármacos
16.
Oncotarget ; 7(21): 31166-76, 2016 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-27145274

RESUMO

Concanavalin A (ConA) chromatography has been extensively used to separate asymmetric Immunoglobulin G (IgG), which possesses oligosaccharide attached to one of the two F(ab')2 arms, from symmetric IgG with no glycan attached to Fab fragments. In this study, applying affinity chromatography, silver stain, Western blot and lectin stain techniques, N- linked oligosaccharide attached to Fab fragment was demonstrated to be exposed on the surface of the protein and be accessible by ConA. In contrast, N- linked oligosaccharide attached to asparagine (Asn) 297 of IgG Fc was located in the inside of the natural protein and was inaccessible by ConA. In addition to asymmetric IgG, there are also detectable level of IgG with both F(ab')2 arms glycosylated that has not been reported previously. The discoveries of new basic molecular structure of IgG would have implications in understanding the function and properties of this important immune molecule with clinical applications.


Assuntos
Concanavalina A/química , Fragmentos Fab das Imunoglobulinas/química , Imunoglobulina G/química , Fracionamento Químico , Cromatografia/métodos , Glicosilação , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/isolamento & purificação
17.
BMC Med Res Methodol ; 16: 40, 2016 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-27059020

RESUMO

BACKGROUND: Regular and timely monitoring of blood glucose (BG) levels in hospitalized patients with diabetes mellitus is crucial to optimizing inpatient glycaemic control. However, methods to quantify timeliness as a measurement of quality of care are lacking. We propose an analytical approach that utilizes BG measurements from electronic records to assess adherence to an inpatient BG monitoring protocol in hospital wards. METHODS: We applied our proposed analytical approach to electronic records obtained from 24 non-critical care wards in November and December 2013 from a tertiary care hospital in Singapore. We applied distributional analytics to evaluate daily adherence to BG monitoring timings. A one-sample Kolmogorov-Smirnov (1S-KS) test was performed to test daily BG timings against non-adherence represented by the uniform distribution. This test was performed among wards with high power, determined through simulation. The 1S-KS test was coupled with visualization via the cumulative distribution function (cdf) plot and a two-sample Kolmogorov-Smirnov (2S-KS) test, enabling comparison of the BG timing distributions between two consecutive days. We also applied mixture modelling to identify the key features in daily BG timings. RESULTS: We found that 11 out of the 24 wards had high power. Among these wards, 1S-KS test with cdf plots indicated adherence to BG monitoring protocols. Integrating both 1S-KS and 2S-KS information within a moving window consisting of two consecutive days did not suggest frequent potential change from or towards non-adherence to protocol. From mixture modelling among wards with high power, we consistently identified four components with high concentration of BG measurements taken before mealtimes and around bedtime. This agnostic analysis provided additional evidence that the wards were adherent to BG monitoring protocols. CONCLUSIONS: We demonstrated the utility of our proposed analytical approach as a monitoring tool. It provided information to healthcare providers regarding the timeliness of daily BG measurements. From the real data application, there were empirical evidences suggesting adherence of BG timings to protocol among wards with adequate power for assessing timeliness. Our approach is extendable to other areas of healthcare where timeliness of patient care processes is important.


Assuntos
Glicemia/análise , Diabetes Mellitus/sangue , Registros Eletrônicos de Saúde/estatística & dados numéricos , Pacientes Internados/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde , Diabetes Mellitus/fisiopatologia , Feminino , Unidades Hospitalares , Humanos , Masculino , Modelos Estatísticos , Monitorização Fisiológica/métodos , Singapura , Centros de Atenção Terciária , Fatores de Tempo
18.
J Mol Neurosci ; 59(1): 168-76, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26888738

RESUMO

UNLABELLED: The xeroderma pigmentosum group F (XPF) gene participates in the pathophysiological process of ischemic stroke, and XPF polymorphisms might be associated with ischemic stroke susceptibility. This study aimed to investigate XPF messenger RNA (mRNA) levels in peripheral blood mononuclear cells and protein levels in plasma and to analyze the 30028T/C polymorphism (rs1799801) in ischemic stroke patients and controls. Levels of both mRNA and protein in ischemic stroke patients were significantly lower than in controls (P < 0.05). The C allele of the 30028T/C polymorphism significantly increased the risk of ischemic stroke (OR = 1.512, 95 % CI = 1.219-1.875). The CT and CC/CT genotypes of 30028T/C were observed significantly more frequently in ischemic stroke patients than in controls (CT: OR = 1.916, 95 % CI = 1.446-2.539; CC/CT: OR = 1.877, 95 % CI = 1.427-2.468). Similar results were obtained after adjusting for age, gender, and smoking status. Additionally, XPF plasma protein levels were significantly decreased in the CC/CT genotype compared with the TT genotype (P = 0.025). These data indicate that XPF might play an important role in the pathophysiological process of ischemic stroke, and the 30028T/C polymorphism might be associated with ischemic stroke susceptibility in a Chinese Han population.


Assuntos
Isquemia Encefálica/genética , Proteínas de Ligação a DNA/genética , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , Idoso , Isquemia Encefálica/sangue , Estudos de Casos e Controles , Proteínas de Ligação a DNA/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/patologia
20.
Bioorg Med Chem ; 23(18): 6173-84, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26314925

RESUMO

Sphingomyelin synthase (SMS) has been proved to be a potential drug target for the treatment of atherosclerosis. However, few SMS inhibitors have been reported. In this paper, structure-based virtual screening was performed on hSMS1. SAPA 1a was discovered as a novel SMS1 inhibitor with an IC50 value of 5.2 µM in enzymatic assay. A series of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) were synthesized and their biological activities toward SMS1 were evaluated. Among them, SAPA 1j was found to be the most potent SMS1 inhibitor with an IC50 value of 2.1 µM in in vitro assay. The molecular docking studies suggested the interaction modes of SMS1 inhibitors and PC with the active site of SMS1. Site-directed mutagenesis validated the involvement of residues Arg342 and Tyr338 in enzymatic sphingomyelin production. The discovery of SAPA derivatives as a novel class of SMS1 inhibitors would advance the development of more effective SMS1 inhibitors.


Assuntos
Acetamidas/química , Inibidores Enzimáticos/síntese química , Proteínas de Membrana/antagonistas & inibidores , Proteínas do Tecido Nervoso/antagonistas & inibidores , Transferases (Outros Grupos de Fosfato Substituídos)/antagonistas & inibidores , Acetamidas/síntese química , Acetamidas/metabolismo , Sítios de Ligação , Domínio Catalítico , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Células HeLa , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Simulação de Acoplamento Molecular , Mutagênese Sítio-Dirigida , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Relação Estrutura-Atividade , Transferases (Outros Grupos de Fosfato Substituídos)/genética , Transferases (Outros Grupos de Fosfato Substituídos)/metabolismo
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