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1.
Plant Cell ; 36(9): 3709-3728, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-38922302

RESUMO

Variation in gene expression levels is pervasive among individuals and races or varieties, and has substantial agronomic consequences, for example, by contributing to hybrid vigor. Gene expression level variation results from mutations in regulatory sequences (cis) and/or transcription factor (TF) activity (trans), but the mechanisms underlying cis- and/or trans-regulatory variation of complex phenotypes remain largely unknown. Here, we investigated gene expression variation mechanisms underlying the differential accumulation of the insecticidal compounds maysin and chlorogenic acid in silks of widely used maize (Zea mays) inbreds, B73 and A632. By combining transcriptomics and cistromics, we identified 1,338 silk direct targets of the maize R2R3-MYB TF Pericarp color1 (P1), consistent with it being a regulator of maysin and chlorogenic acid biosynthesis. Among these P1 targets, 464 showed allele-specific expression (ASE) between B73 and A632 silks. Allelic DNA-affinity purification sequencing identified 34 examples in which P1 allelic specific binding (ASB) correlated with cis-expression variation. From previous yeast one-hybrid studies, we identified 9 TFs potentially implicated in the control of P1 targets, with ASB to 83 out of 464 ASE genes (cis) and differential expression of 4 out of 9 TFs between B73 and A632 silks (trans). These results provide a molecular framework for understanding universal mechanisms underlying natural variation of gene expression levels, and how the regulation of metabolic diversity is established.


Assuntos
Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Zea mays , Zea mays/genética , Zea mays/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Alelos , Ácido Clorogênico/metabolismo , Fenótipo , Variação Genética
2.
Proc Natl Acad Sci U S A ; 120(19): e2219469120, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37126718

RESUMO

Basic helix-loop-helix (bHLH) proteins are one of the largest families of transcription factor (TF) in eukaryotes, and ~30% of all flowering plants' bHLH TFs contain the aspartate kinase, chorismate mutase, and TyrA (ACT)-like domain at variable distances C-terminal from the bHLH. However, the evolutionary history and functional consequences of the bHLH/ACT-like domain association remain unknown. Here, we show that this domain association is unique to the plantae kingdom with green algae (chlorophytes) harboring a small number of bHLH genes with variable frequency of ACT-like domain's presence. bHLH-associated ACT-like domains form a monophyletic group, indicating a common origin. Indeed, phylogenetic analysis results suggest that the association of ACT-like and bHLH domains occurred early in Plantae by recruitment of an ACT-like domain in a common ancestor with widely distributed ACT DOMAIN REPEAT (ACR) genes by an ancestral bHLH gene. We determined the functional significance of this association by showing that Chlamydomonas reinhardtii ACT-like domains mediate homodimer formation and negatively affect DNA binding of the associated bHLH domains. We show that, while ACT-like domains have experienced faster selection than the associated bHLH domain, their rates of evolution are strongly and positively correlated, suggesting that the evolution of the ACT-like domains was constrained by the bHLH domains. This study proposes an evolutionary trajectory for the association of ACT-like and bHLH domains with the experimental characterization of the functional consequence in the regulation of plant-specific processes, highlighting the impacts of functional domain coevolution.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Plantas , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Filogenia , Plantas/genética , Fatores de Transcrição/metabolismo , Sequências Hélice-Alça-Hélice
3.
Plant Cell ; 34(2): 867-888, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-34865154

RESUMO

Plants respond to wounding stress by changing gene expression patterns and inducing the production of hormones including jasmonic acid. This wounding transcriptional response activates specialized metabolism pathways such as the glucosinolate pathways in Arabidopsis thaliana. While the regulatory factors and sequences controlling a subset of wound-response genes are known, it remains unclear how wound response is regulated globally. Here, we how these responses are regulated by incorporating putative cis-regulatory elements, known transcription factor binding sites, in vitro DNA affinity purification sequencing, and DNase I hypersensitive sites to predict genes with different wound-response patterns using machine learning. We observed that regulatory sites and regions of open chromatin differed between genes upregulated at early and late wounding time-points as well as between genes induced by jasmonic acid and those not induced. Expanding on what we currently know, we identified cis-elements that improved model predictions of expression clusters over known binding sites. Using a combination of genome editing, in vitro DNA-binding assays, and transient expression assays using native and mutated cis-regulatory elements, we experimentally validated four of the predicted elements, three of which were not previously known to function in wound-response regulation. Our study provides a global model predictive of wound response and identifies new regulatory sequences important for wounding without requiring prior knowledge of the transcriptional regulators.


Assuntos
Arabidopsis/fisiologia , Regulação da Expressão Gênica de Plantas , Reguladores de Crescimento de Plantas/fisiologia , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Ciclopentanos/farmacologia , Redes e Vias Metabólicas , Modelos Biológicos , Oxilipinas/farmacologia , Reguladores de Crescimento de Plantas/farmacologia , Plantas Geneticamente Modificadas , Sequências Reguladoras de Ácido Nucleico , Reprodutibilidade dos Testes , Fatores de Transcrição/genética
4.
J Clin Microbiol ; 62(7): e0052424, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38934589

RESUMO

This study compared the performance of two commercial molecular assays, the STANDARD M10 Clostridioides difficile assay (M10) and the Xpert C. difficile assay (Xpert), for detecting toxigenic C. difficile in stool specimens. A total of 487 consecutive stool specimens submitted for routine C. difficile testing between June and November 2023 were included. Following routine testing using C. DIFF QUIK CHEK COMPLETE (QCC), M10 and Xpert were tested in parallel, alongside toxigenic culture (reference standard). Additionally, two-step algorithms, using QCC on the first step and either M10 or Xpert on the second step, were assessed. Both M10 and Xpert demonstrated a sensitivity and negative predictive value (NPV) of 100%. M10 exhibited significantly higher specificity and positive predictive value (PPV; 91.9% and 64.2%, respectively) than Xpert (90.3% and 59.8%, respectively). Both two-step algorithms showed a sensitivity and NPV of 98.4% and 99.8%, respectively. The specificity and PPV of the two-step algorithm using M10 (95.2% and 75.0%, respectively) were slightly higher than those of the one using Xpert (94.8% and 73.2%, respectively), without statistical significance. Receiver operating characteristic curve analysis, assessing the predictive ability of cycle threshold (Ct) values for the detection of free toxin, exhibited an area under the curve of 0.825 for M10 and 0.843 for Xpert. This indicates the utility of Ct values as predictors for the detection of free toxin in both assays. In conclusion, M10 proves to be an effective diagnostic tool with performance comparable to Xpert, whether utilized independently or as part of a two-step algorithm.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Fezes , Técnicas de Diagnóstico Molecular , Sensibilidade e Especificidade , Humanos , Clostridioides difficile/isolamento & purificação , Clostridioides difficile/genética , Fezes/microbiologia , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/microbiologia , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , Algoritmos , Toxinas Bacterianas/análise , Toxinas Bacterianas/genética , Valor Preditivo dos Testes
5.
FASEB J ; 37(5): e22900, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37039823

RESUMO

Ubiquitin-specific protease 4 (USP4) is highly overexpressed in colon cancer and acts as a potent protooncogenic protein by deubiquitinating ß-catenin. However, its prominent roles in tumor formation and migration in cancer cells are not fully understood by its deubiquitinating enzyme (DUB) activity on ß-catenin. Thus, we investigated an additional role of USP4 in cancer. In this study, we identified cortactin (CTTN), an actin-binding protein involved in the regulation of cytoskeleton dynamics and a potential prognostic marker for cancers, as a new cellular interacting partner of USP4 from proximal labeling of HCT116 cells. Additionally, the role of USP4 in CTTN activation and promotion of cell dynamics and migration was investigated in HCT116 cells. We confirmed that interacting of USP4 with CTTN increased cell movement. This finding was supported by the fact that USP4 overexpression in HCT116 cells with reduced expression of CTTN was insufficient to promote cell migration. Additionally, we observed that USP4 overexpression led to a significant increase in CTTN phosphorylation, which is a requisite mechanism for cell migration, by regulating Src/focal adhesion kinase (FAK) binding to CTTN and its activation. Our results suggest that USP4 plays a dual role in cancer progression, including stabilization of ß-catenin as a DUB and interaction with CTTN to promote cell dynamics by inducing CTTN phosphorylation. Therefore, this study demonstrates that USP4 is important for cancer progression and is a good target for treating or preventing cancer.


Assuntos
Neoplasias do Colo , beta Catenina , Humanos , Células HCT116 , beta Catenina/metabolismo , Cortactina/metabolismo , Movimento Celular/fisiologia , Proteases Específicas de Ubiquitina/metabolismo
6.
BMC Nurs ; 23(1): 396, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862941

RESUMO

BACKGROUND: Gender sensitivity, which is the capacity to recognize and address issues of gender discrimination and inequality, is initiated with an awareness of gender differences. This is particularly crucial in nursing, where care is tailored to the holistic needs of individuals. Given the sensitive nature of nursing to gender variances, it is essential that the influences of nurses' own experiences and perceptions on their gender sensitivity are explored. This study is aimed at assessing the effects of childhood experiences of domestic violence and perceptions of sexism among healthcare providers on their gender sensitivity. Additionally, it seeks to provide empirical data to support the enhancement of gender-sensitive practices within nursing environments, thereby fostering a culture of gender equality, and helping to promote the practical application of gender equality within nursing organizations. METHODS: A cross-sectional survey was employed to gather data from 146 nurses aged 24 and above residing in Daegu. The general characteristics of these nurses, their childhood experiences of domestic violence, their perceptions of sexism, and their level of gender sensitivity were measured. The data were then subjected to a series of statistical analyses, including t-tests, one-way analysis of variance, Pearson's correlation coefficients, and hierarchical regression analysis, to identify the factors influencing gender sensitivity. RESULTS: It was revealed by the analysis that nurses' gender sensitivity was not significantly associated with their childhood experiences of domestic violence. However, a negative correlation was found between gender sensitivity and their perceptions of sexism (r = -0.46, p < 0.001). Additionally, age and perception of sexism were emerged as significant predictors of gender sensitivity, accounting for 42.7% of the variance in the regression model. CONCLUSION: This study identifies age and sexism perceptions as key predictors of gender sensitivity among nurses, accounting for 42.7% of the variance. It highlights the importance of recognizing generational cultural differences and implementing flexible practices in nursing organizations. Leaders should enhance cultural awareness and address sexism. Further research is needed on the role of societal and cultural norms in recognizing domestic violence. These findings emphasize the need for targeted interventions to improve gender sensitivity and support high-quality nursing care.

7.
Plant J ; 110(2): 589-606, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35064997

RESUMO

Camelina (Camelina sativa) is an annual oilseed plant that is gaining momentum as a biofuel cover crop. Understanding gene regulatory networks is essential to deciphering plant metabolic pathways, including lipid metabolism. Here, we take advantage of a growing collection of gene expression datasets to predict transcription factors (TFs) associated with the control of Camelina lipid metabolism. We identified approximately 350 TFs highly co-expressed with lipid-related genes (LRGs). These TFs are highly represented in the MYB, AP2/ERF, bZIP, and bHLH families, including a significant number of homologs of well-known Arabidopsis lipid and seed developmental regulators. After prioritizing the top 22 TFs for further validation, we identified DNA-binding sites and predicted target genes for 16 out of the 22 TFs tested using DNA affinity purification followed by sequencing (DAP-seq). Enrichment analyses of targets supported the co-expression prediction for most TF candidates, and the comparison to Arabidopsis revealed some common themes, but also aspects unique to Camelina. Within the top potential lipid regulators, we identified CsaMYB1, CsaABI3AVP1-2, CsaHB1, CsaNAC2, CsaMYB3, and CsaNAC1 as likely involved in the control of seed fatty acid elongation and CsaABI3AVP1-2 and CsabZIP1 as potential regulators of the synthesis and degradation of triacylglycerols (TAGs), respectively. Altogether, the integration of co-expression data and DNA-binding assays permitted us to generate a high-confidence and short list of Camelina TFs involved in the control of lipid metabolism during seed development.


Assuntos
Arabidopsis , Brassicaceae , Arabidopsis/genética , Brassicaceae/genética , Humanos , Metabolismo dos Lipídeos/genética , Sementes/metabolismo , Triglicerídeos/metabolismo
8.
BJOG ; 130(4): 415-423, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35445798

RESUMO

OBJECTIVE: To investigate the epidemiological changes in extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) vaginal colonisation in pregnant women deemed at high risk, and to identify independent risk factors. Further, the differences in perinatal outcomes according to maternal ESBL-E vaginal colonisation were analysed. DESIGN: Cross-sectional study. SETTING: Republic of Korea. POPULATION: A cohort of 1460 women admitted to our high-risk pregnancy unit between 14+0 and 36+6  weeks of gestation. METHODS: The trend of changes in the association of ESBL-E vaginal colonisation from January 2010 to December 2020 was analysed. The main outcomes were analysed over the study period and ESBL-E vaginal colonisation. MAIN OUTCOME MEASURES: Rate of ESBL-E vaginal colonisation, risk factors for ESBL-E vaginal colonisation and perinatal outcomes. RESULTS: The ESBL-E vaginal colonisation rate has tended to increase over the past 11 years, which was attributed to a significantly higher proportion of ESBL-producing Escherichia coli. Cerclage (RR 3.7, 95% CI 2.19-6.40) and prior antibiotic treatment (RR 4.0, 95% CI 2.44-6.54) were found as independent risk factors for ESBL-E vaginal colonisation. Earlier gestational age at delivery and higher proven early-onset neonatal sepsis (EONS) rate were observed in the ESBL-E-positive group. CONCLUSIONS: The ESBL-E vaginal colonisation rate in pregnant patients at high risk has increased over the past decade, and the independent risk factors for colonisation are cerclage and prior antibiotic treatment. Additionally, maternal ESBL-E vaginal colonisation is associated with higher rates of proven EONS.


Assuntos
Infecções por Enterobacteriaceae , Recém-Nascido , Humanos , Feminino , Gravidez , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Gravidez de Alto Risco , Estudos Transversais , beta-Lactamases , Enterobacteriaceae , Antibacterianos/uso terapêutico , Fatores de Risco
9.
J Clin Pediatr Dent ; 47(3): 89-95, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37143426

RESUMO

Bisphenol A (BPA) from dental materials may be linked to children's health issues. This study aimed to assess the release of BPA from commercially available 3-dimensional (3D)-printed resin materials and evaluate BPA-related apoptotic effects on human periodontal ligament cells and gingival fibroblasts. Commercially available 3D-printed resin materials for prosthodontic use were selected as follows: NextDent C&B MFH (3D Systems, Rock Hill, SC, USA), DIOnavi-P. MAX (Dio Co., Busan, Korea), and DIOnavi-Denture02 (Dio Co., Busan, Korea). Identical cuboidal samples (1 cm × 1 cm × 0.5 cm) were printed from the materials and cured. BPA release was assessed using liquid chromatography/mass spectrometry (LC/MS). In addition, human gingival fibroblasts and periodontal ligament cells were exposed to various BPA solutions based on the LC/MS results. Cell Counting kit-8 (CCK-8) and real-time polymerase chain reaction analyses were performed to evaluate BPA-related apoptotic effects. The LC/MS analysis confirmed that none of the 3D-printed resin materials released BPA after curing. Both human gingival fibroblasts and periodontal ligament cells showed lower viability after BPA exposure. Regarding apoptosis-related gene expression, Caspase10 (CASP10) expression in periodontal ligament cells was significantly different in the BPA solutions (p < 0.05). The expression of BAX and Capspase8 (CASP8) in gingival fibroblasts was significantly increased by BPA in a dose-dependent manner (p < 0.05). Within the limitations of this study, the 3D-printed resin materials were not found to release BPA. This finding implies that 3D-printed resin materials are not associated with potential BPA-related risks in children.


Assuntos
Materiais Dentários , Fenóis , Criança , Humanos , Materiais Dentários/química , Fenóis/farmacologia , Fenóis/análise , Fenóis/química , Compostos Benzidrílicos/toxicidade , Compostos Benzidrílicos/análise , Compostos Benzidrílicos/química , Apoptose , Teste de Materiais , Resinas Compostas/química
10.
J Biol Chem ; 296: 100708, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33901489

RESUMO

About a third of the plant basic helix-loop-helix (bHLH) transcription factors harbor a C-terminal aspartate kinase, chorismate mutase, and TyrA (ACT)-like domain, which was originally identified in the maize R regulator of anthocyanin biosynthesis, where it modulates the ability of the bHLH to dimerize and bind DNA. Characterization of other bHLH ACT-like domains, such as the one in the Arabidopsis R ortholog, GL3, has not definitively confirmed dimerization, raising the question of the overall role of this potential regulatory domain. To learn more, we compared the dimerization of the ACT-like domains of R (RACT) and GL3 (GL3ACT). We show that RACT dimerizes with a dissociation constant around 100 nM, over an order of magnitude stronger than GL3ACT. Structural predictions combined with mutational analyses demonstrated that V568, located in a hydrophobic pocket in RACT, is important: when mutated to the Ser residue present in GL3ACT, dimerization affinity dropped by almost an order of magnitude. The converse S595V mutation in GL3ACT significantly increased the dimerization strength. We cloned and assayed dimerization for all identified maize ACT-like domains and determined that 12 of 42 formed heterodimers in yeast two-hybrid assays, irrespective of whether they harbored V568, which was often replaced by other aliphatic amino acids. Moreover, we determined that the presence of polar residues at that position occurs only in a small subset of anthocyanin regulators. The combined results provide new insights into possibly regulatory mechanisms and suggest that many of the other plant ACT-like domains associate to modulate fundamental cellular processes.


Assuntos
Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/química , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Multimerização Proteica , Arabidopsis , Modelos Moleculares , Domínios Proteicos , Estabilidade Proteica , Estrutura Quaternária de Proteína
11.
Cerebrovasc Dis ; 51(3): 331-337, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34638120

RESUMO

BACKGROUND: Clinical-diffusion mismatch (CDM) and perfusion-diffusion mismatch (PDM) are used to select patients for endovascular thrombectomy (EVT) in the late-window period. As CDM well reflects true penumbra, we hypothesized that patients with CDM and PDM would respond better to EVT than those with PDM only at the late-window period. METHODS: Acute ischemic stroke patients who received EVT 6-24 h after stroke onset were included. PDM (perfusion-/diffusion-weighted image (DWI) lesion volume >1.8) was used to select candidates for EVT in this time-period in our center. CDM was defined according to the DAWN trial criteria. Response to EVT was compared between patients with and without CDM. Early neurological improvement (ENI) was defined as improvement >4 points on National Institutes of Health Stroke Scale (NIHSS) score 1 day after EVT. Multivariable analysis was performed to investigate independent factors associated with ENI. The correlation between DWI lesion volume and NIHSS score was investigated in those with and without CDM. RESULTS: Among 94 patients enrolled, all patients had PDM and 44 (46.3%) had CDM. Forty-eight patients (51.1%) showed ENI. The prevalence of hypertension, initial NIHSS score, improvement in NIHSS score after EVT, and prevalence of ENI were greater in patients with CDM than those without. ENI was independently associated with onset-to-door time (odds ratio [95% confidence interval]: 0.998 [0.997-1.000]; p = 0.042), complete recanalization (23.912 [2.238-255.489]; p = 0.009), initial NIHSS score (1.180 [1.012-1.377]; p = 0.034), and the presence of CDM (5.160 [1.448-18.386]; p = 0.011). The correlation between DWI lesion volume and initial NIHSS score was strong in patients without CDM (r = 0.731) but only moderate in patients with CDM (r = 0.355). CONCLUSION: Patients with both CDM and PDM had a better response to late-window EVT than those with PDM only.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Imagem de Difusão por Ressonância Magnética , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Trombectomia/efeitos adversos , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/métodos , Resultado do Tratamento
12.
Sensors (Basel) ; 22(3)2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35161611

RESUMO

Threats of eavesdropping and information leakages have increased sharply owing to advancements in wireless communication technology. In particular, the Internet of Things (IoT) has become vulnerable to sniffing or jamming attacks because broadcast communication is usually conducted in open-network environments. Although improved security protocols have been proposed to overcome the limitations of wireless-communication technology and to secure safe communication channels, they are difficult to apply to mobile communication networks and IoT because complex hardware is required. Hence, a novel security model with a lighter weight and greater mobility is needed. In this paper, we propose a security model applying cooperative friendly jamming using artificial noise and drone mobility, which are autonomous moving objects, and we demonstrate the prevention of eavesdropping and improved security through simulations and field tests. The Cooperative Friendly Jamming Techniques for Drone-based Mobile Secure Zone (CFJ-DMZ) can set a secure zone in a target area to support a safe wireless mobile communication network through friendly jamming, which can effectively reduce eavesdropping threats. According to the experimental results, the average information leakage rate of the eavesdroppers in CFJ-DMZ-applied scenarios was less than or equal to 3%, an average improvement of 92% over conventional methods.

13.
BMC Oral Health ; 22(1): 550, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36456927

RESUMO

BACKGROUND: In clinical settings, tooth preparation for prefabricated zirconia crowns (PZCs) in the primary dentition varies widely. However, knowledge about the biomechanical behavior of PZCs in various clinical settings is limited. This study was conducted to evaluate the biomechanical behavior of PZCs in different clinical settings using 3-dimensional finite element analysis. METHODS: 3-dimensional models of the PZC, cement, and tooth with six different conditions were simulated in primary molar teeth, incorporating cement thickness (100, 500, and 1000 µm) and cement type (resin-modified glass ionomer cement and resin cement). A total of 200 N of occlusal force was applied to the models, both vertically and obliquely as representative cases. A general linear model univariate analysis with partial eta-squared (ηp2) was performed to evaluate the relative effects of the variables. RESULTS: The overall stress of tooth was increased as the cement space increases under oblique loading. The von Mises stress values of the resin cements were significantly higher than those of the resin-modified glass ionomer cements for all cement thicknesses (p < .05). The effect size of the cement type (ηp2 = .519) was more dominant than the cement thickness (ηp2 = .132) in the cement layer. CONCLUSIONS: Within the limits of this study, cement type has a greater influence on the biomechanical behavior of PZCs than cement thickness.


Assuntos
Cimentos Dentários , Preparo do Dente , Humanos , Criança , Análise de Elementos Finitos , Cimentos de Ionômeros de Vidro , Materiais Dentários , Cimentos de Resina , Coroas
14.
Environ Monit Assess ; 194(9): 606, 2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35867162

RESUMO

Climate change has become one of the highlighted issues of the world, resulting in vulnerability and adverse effects on livelihoods. It leads to an undeniable challenge for policymakers, the government, and other respective associations to formulate effective strategies; however, before formulating any coping, adaptation, or mitigation strategies, understanding the reality and perception of local people is crucial. This study investigated whether local farmers inhabiting Lower Mustang are aware of climatic change. The study comprised various methodologies, such as household surveys, field visits and focus group discussions (FGD). The farmers' responses were consistent with the actual temperature and precipitation data recorded between 1973 and 2018 at meteorological stations situated near the aforementioned regions. The finding shows that the average annual temperature of this region has risen by 0.021 °C/year over the last 45 years. Similarly, the annual precipitation increased 1.83 mm/year on average, which was also acknowledged by local farmers. From the field visit, it was also noticed that the vulnerability of climate change is considerably high and has insufficient capacity to cope with climate change. Thus, the government, and other stakeholders should assist in building the adaptive capacity of this Himalayan region.


Assuntos
Mudança Climática , Fazendeiros , Agricultura/métodos , Monitoramento Ambiental , Humanos , Nepal
15.
Mol Vis ; 27: 283-287, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34012230

RESUMO

Purpose: Granular corneal dystrophy type 2 (GCD2) is an autosomal dominant disorder and is associated with the arginine to histidine substitution at codon 124 (p.R124H) of the TGFBI gene. Although TGFBI p.R124H is known to be the most common corneal dystrophy-related pathogenic variant, there are few data on the frequency of this variant in the South Korean population. Methods: In total, 2,060 anonymous DNA samples from a public umbilical cord blood bank were tested for the TFGBI p.R124H variant using real-time PCR. Results: Six of the 2,060 samples [0.29%; 95% confidence interval (CI), 0.12-0.67%] were heterozygous for the TGFBI p.R124H variant. The prevalence of the GCD2-related TGFBI p.R124H variant in this population was estimated to be 291.3 per 100,000 [95% confidence interval (CI), 118.5-667.0]. Conclusions: To our knowledge, this is the largest study that has estimated the prevalence of the GCD2-related TGFBI p.R124H variant in South Korea.


Assuntos
Distrofias Hereditárias da Córnea/epidemiologia , Distrofias Hereditárias da Córnea/genética , Proteínas da Matriz Extracelular/genética , Fator de Crescimento Transformador beta/genética , Povo Asiático , Proteínas da Matriz Extracelular/sangue , Sangue Fetal , Humanos , Mutação , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , República da Coreia/epidemiologia , Fator de Crescimento Transformador beta/sangue
16.
BMC Cancer ; 21(1): 1097, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34641806

RESUMO

BACKGROUND: Pancreatic cancer has highly aggressive features, such as local recurrence that leads to significantly high morbidity and mortality and recurrence after successful tumour resection. Intraoperative radiation therapy (IORT), which delivers targeted radiation to a tumour bed, is known to reduce local recurrence by directly killing tumour cells and modifying the tumour microenvironment. METHODS: Among 30 patients diagnosed with pancreatic cancer, 17 patients received IORT immediately after surgical resection. We investigated changes in the immune response induced by IORT by analysing the peritoneal fluid (PF) and blood of patients with and without IORT treatment after pancreatic cancer surgery. Further, we treated three pancreatic cell lines with PF to observe proliferation and activity changes. RESULTS: Levels of cytokines involved in the PI3K/SMAD pathway were increased in the PF of IORT-treated patients. Moreover, IORT-treated PF inhibited the growth, migration, and invasiveness of pancreatic cancer cells. Changes in lymphocyte populations in the blood of IORT-treated patients indicated an increased immune response. CONCLUSIONS: Based on the characterisation and quantification of immune cells in the blood and cytokine levels in the PF, we conclude that IORT induced an anti-tumour effect by activating the immune response, which may prevent pancreatic cancer recurrence. CLINICAL TRIAL REGISTRATION: NCT03273374 .


Assuntos
Imunidade Celular/efeitos da radiação , Cuidados Intraoperatórios , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/cirurgia , Líquido Ascítico/química , Líquido Ascítico/metabolismo , Líquido Ascítico/efeitos da radiação , Linhagem Celular Tumoral , Movimento Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Citocinas/análise , Humanos , Linfócitos/citologia , Invasividade Neoplásica , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/imunologia , Fosfatidilinositol 3-Quinase/metabolismo , Estudos Prospectivos , Proteínas Smad/metabolismo , Microambiente Tumoral/efeitos da radiação
17.
J Clin Lab Anal ; 35(1): e23585, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32969071

RESUMO

BACKGROUND: The Automated Fluorescent Immunoassay System ROTA (AFIAS-Rota) and NORO (AFIAS-Noro) assays (Boditech Med Inc.) are newly developed diagnostic tests for rotavirus and norovirus infections. METHODS: Performance of AFIAS-Rota/Noro assays was evaluated in comparison with RIDASCREEN® Rotavirus and Norovirus ELISA kits (R-Biopharm) using clinical stool samples submitted from November 2018 to January 2019. Multiplex real-time reverse transcription-polymerase chain reaction was used as reference method. RESULTS: A total of 256 clinical specimens were analyzed. AFIAS-Rota and RIDASCREEN Rotavirus had almost perfect agreement (Kappa value = 0.95), and substantial agreement was observed between AFIAS-Noro and RIDASCREEN Norovirus (Kappa value = 0.80). For detection of rotavirus, AFIAS and RIDASCREEN assays showed satisfactory diagnostic sensitivity (100% and 97.8%, respectively) and specificity (99.5% and 99.1%). For detection of norovirus, the RIDASCREEN assay showed significantly higher sensitivity than the AFIAS-Noro (86.0% and 66.0%, respectively; P = .002). Analytic specificity of AFIAS-Rota/Noro assays showed no cross-reactivity against any other bacteria (14 strains) or viruses (2 strains). Hands-on time (6 minutes) and turnaround time (26 minutes) required to perform AFIAS assays were much shorter than those required for RIDASCREEN assays (20 and 150 minutes, respectively). CONCLUSION: The AFIAS-Rota/Noro assays showed overall excellent agreement with the RIDASCREEN assays. Although the AFIAS-Noro assay exhibited lower sensitivity than the RIDASCREEN Norovirus assay for detection of norovirus, the AFIAS-Rota/Noro assays could be useful as a rapid initial screening test in clinical laboratories due to its convenience and rapid turnaround time.


Assuntos
Infecções por Caliciviridae/diagnóstico , Imunofluorescência , Norovirus/isolamento & purificação , Infecções por Rotavirus/diagnóstico , Rotavirus/isolamento & purificação , Fezes/virologia , Imunofluorescência/métodos , Imunofluorescência/normas , Imunofluorescência/estatística & dados numéricos , Humanos , Norovirus/genética , Norovirus/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Rotavirus/genética , Rotavirus/imunologia , Sensibilidade e Especificidade , Virologia
18.
J Shoulder Elbow Surg ; 30(8): 1881-1890, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33271322

RESUMO

HYPOTHESIS AND BACKGROUND: Whether learning curve could affect the surgical outcome after arthroscopic rotator cuff repair is still unknown. The purpose of this study was to evaluate surgical learning curve for clinical outcome and retear rate after arthroscopic rotator cuff repairs that were performed by the beginner shoulder surgeon. We hypothesized that clinical outcome and retear rate would improve over time with the accumulation of a surgeon's experience. METHODS: This retrospective study consisted of 200 consecutive patients who had arthroscopic rotator cuff repairs, performed by a single surgeon between 2011 and 2018. We included symptomatic rotator cuff tears involving the supraspinatus/infraspinatus and/or subscapularis tendon and follow-up magnetic resonance imaging evaluations of repair integrity 6 months after surgery. Surgeon's learning was evaluated with calculation of cumulative retear rate and cumulative summation (CUSUM) analysis. Clinical outcomes and the retear rates were compared between group A (the first-half 100 patients) and group B (the latter-half of 100 patients). RESULTS: The mean follow-up period was 21 months (range, 12-55). The overall retear rate was 13% (26 patients). The CUSUM analysis showed that after patient number 97, the curve was maintained below the level of acceptable failure rate, suggesting the competency was obtained consistently. Comparing between groups, retear rate showed significant decrease from 18% in group A to 8% in group B (P = .036). Notably, retear rate in small to medium-sized tears (<3 cm) significantly decreased from 26% (12 of 46 patients) in group A to 2% (1 of 49 patients) in group B (P = .001). However, analysis in large to massive tears (≥3 cm) failed to show difference between groups (30%, 6 of 20, in group A and 25%, 6 of 24, in group B; P = .711). In multivariate analysis, higher fatty infiltration of the supraspinatus muscle (P = .008), more severe muscle atrophy of the teres minor (P = .010), and belonging to group A (P = .011) were associated with retear. CONCLUSION: Clinical outcomes and retear rate after arthroscopic rotator cuff repairs significantly improved during the learning curve period of a beginner shoulder surgeon.


Assuntos
Lesões do Manguito Rotador , Cirurgiões , Artroscopia , Humanos , Curva de Aprendizado , Imageamento por Ressonância Magnética , Amplitude de Movimento Articular , Estudos Retrospectivos , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/cirurgia , Resultado do Tratamento
19.
Molecules ; 26(20)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34684783

RESUMO

Signal transducer and activator of transcription 3 (STAT3) plays a critical role in the formation and growth of human cancer. Therefore, STAT3 is a therapeutic target for cancer drug discovery. Acacetin, a flavone present in various plants, inhibits constitutive and inducible STAT3 activation in STAT3-activated DU145 prostate cancer cells. Acacetin inhibits STAT3 activity by directly binding to STAT3, which we confirmed by a pull-down assay with a biotinylated compound and two level-free methods, namely, a drug affinity responsive target stability (DARTS) experiment and a cellular thermal shift assay (CETSA). Acacetin inhibits STAT3 phosphorylation at the tyrosine 705 residue and nuclear translocation in DU145 cells, which leads to the downregulation of STAT3 target genes. Acacetin then induces apoptosis in a time-dependent manner. Interestingly, acacetin induces the production of reactive oxygen species (ROS) that are not involved in the acacetin-induced inhibition of STAT3 activation because the suppressed p-STAT3 level is not rescued by treatment with GSH or NAC, which are general ROS inhibitors. We also found that acacetin inhibits tumor growth in xenografted nude mice. These results suggest that acacetin, as a STAT3 inhibitor, could be a possible drug candidate for targeting STAT3 for the treatment of cancer in humans.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Flavonas/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Fator de Transcrição STAT3/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Modelos Moleculares , Fosforilação/efeitos dos fármacos , Neoplasias da Próstata/patologia , Ligação Proteica , Proteínas Tirosina Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
BMC Oral Health ; 21(1): 419, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34445966

RESUMO

BACKGROUND: The aim of this study was to report a rare case of nasopalatine duct cyst with sebaceous differentiation. Further, a systematic search of the literature was performed to identify studies reporting patients with intraosseous jaw cysts with sebaceous differentiation. CASE PRESENTATION: A 55-year-old Korean man was referred to our hospital because of a cystic lesion of the anterior maxilla. Radiologic examination revealed a well-circumscribed radiolucent lesion in the anterior maxilla. Histology showed a respiratory columnar and cuboidal epithelium-lined cyst. Transition from the ciliated columnar epithelium to stratified squamous epithelium with sebaceous differentiation was observed. Based on these findings, the final diagnosis was nasopalatine duct cyst with sebaceous differentiation. A systematic search of the literature was performed to identify studies reporting patients with intraosseous jaw cysts with sebaceous differentiation. There were 24 cases of sebaceous differentiation in the epithelium of the cysts including 2 odontogenic keratocysts, 8 orthokeratinized odontogenic cysts, 8 dentigerous cysts, 1 radicular cyst, and 2 glandular odontogenic cysts. However, no case reports describing the occurrence of nasopalatine duct cysts with sebaceous differentiation have been reported. CONCLUSION: This first case report of nasopalatine duct cysts with sebaceous differentiation could provide insight into the diagnostic process of cystic lesions with sebaceous differentiation.


Assuntos
Cistos Maxilomandibulares , Cistos Odontogênicos , Tumores Odontogênicos , Cisto Radicular , Epitélio , Humanos , Masculino , Pessoa de Meia-Idade , Cistos Odontogênicos/diagnóstico por imagem
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