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INTRODUCTION: The nursing management of intracranial hypertension in adult patients with severe brain injury is crucial for maintaining the stability of intracranial pressure, which ultimately improves patient outcomes. OBJECTIVES: This project aimed to implement evidence-based practices for the nursing management of intracranial hypertension in adult patients with severe brain injury. METHODS: This evidence implementation project was conducted in a neurosurgery intensive care unit in a large tertiary hospital in Guangzhou, China. The project was guided by the JBI Evidence Implementation Framework, which is an audit and feedback model with seven stages. The Ottawa Model of Research Use was used to identify barriers and facilitators to best practices and to develop improvement strategies. RESULTS: Thirty-three nurses and 50 patients with severe brain injury participated in the baseline and follow-up audits. After project implementation, follow-up audits revealed significantly improved compliance with best practices compared with baseline. Nurses' awareness of best practices increased (41% to 96%); nursing assessment, monitoring, and interventions related to intracranial hypertension rose significantly (from 82%, 75%, and 59% to 98%, 84%, and 87%, respectively); and patients' optic nerve sheath diameter was notably lower (6.002±0.677 mm to 5.698±0.730 mm). CONCLUSIONS: The systematic integration of consistent training and education, together with the refinement of care processes and the creation of relevant tools, led to a significant improvement in awareness and adherence to best practices. Further testing of this program in more hospitals is needed. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A243.
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BACKGROUND: Research on the co-production of multiple enzymes by Bacillus velezensis as a novel species is still a topic that needs to be studied. This study aimed to investigate the fermentation characteristics of B. velezensis D6 co-producing α-amylase and protease and to explore their enzymatic properties and applications in fermentation. RESULTS: The maximum co-production of α-amylase and protease reached 13.13 ± 0.72 and 2106.63 ± 64.42 U mL-1, respectively, under the optimal fermented conditions (nutrients: 20.0 g L-1 urea, 20.0 g L-1 glucose, 0.7 g L-1 MnCl2; incubation conditions: initial pH 7.0, temperature 41 °C, 8% inoculation size and 30% working volume). Moreover, the genetic co-expression of α-amylase and protease increased from 0 to 24 h and then decreased after 36 h at the transcriptional level, which coincided with the growth trend of B. velezensis D6. The optimal reaction temperature of α-amylase was 55-60 °C, while that of protease was 35-40 °C. The activities of α-amylase and protease were retained by over 80% after thermal treatment (90 °C, 1 h), which indicated that two enzymes co-produced by B. velezensis D6 demonstrated excellent thermal stability. Moreover, the two enzymes were stable over a wide pH range (pH 4.0-8.0 for α-amylase; pH 4.0-9.0 for protease). Finally, the degrees of hydrolysis of corn, rice, sorghum and soybeans by α-amylase from B. velezensis D6 reached 44.95 ± 2.95%, 57.16 ± 2.75%, 52.53 ± 4.01% and 20.53 ± 2.42%, respectively, suggesting an excellent hydrolysis effect on starchy raw materials. The hydrolysis degrees of mackerel heads and soybeans by protease were 43.93 ± 2.19% and 26.38 ± 1.72%, respectively, which suggested that the protease from B. velezensis D6 preferentially hydrolyzed animal-based protein. CONCLUSION: This is a systematic study on the co-production of α-amylase and protease by B. velezensis D6, which is crucial in widening the understanding of this species co-producing multi-enzymes and in exploring its potential application. © 2024 Society of Chemical Industry.
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There are complex and diverse substances in traditional vinegars, some of which have been identified as biologically active factors, but the variety of functional compounds is currently restricted. In this study, it was aimed to determine the bioactive compounds in 10 typical functional vinegars. The findings shown that total flavonoids (0.21-7.19 mg rutin equivalent/mL), total phenolics (0.36-3.20 mg gallic acid equivalent/mL), and antioxidant activities (DPPH: 3.17-47.63 mmol trolox equivalent/L, ABTS: 6.85-178.29 mmol trolox equivalent/L) varied among different functional vinegars. In addition, the concentrations of the polysaccharides (1.17-44.87 mg glucose equivalent/mL) and total saponins (0.67-12.46 mg oleanic acid equivalent/mL) were determined, which might play key role for the function of tested vinegars. A total of 8 organic acids, 7 polyphenol compounds and 124 volatile compounds were measured and tentatively identified. The protocatechuic acid (4.81-485.72 mg/L), chlorogenic acid (2.69-7.52 mg/L), and epicatechin (1.18-97.42 mg/L) were important polyphenol compounds in the functional vinegars. Redundancy analysis indicated that tartaric acid, oxalic acid and chlorogenic acid were significantly positively correlated with antioxidant capacity. Various physiologically active ingredients including cyclo (Pro-Leu), cyclo (Phe-Pro), cyclo (Phe-Val), cyclo (Pro-Val), 1-monopalmitin and 1-eicosanol were firstly detected in functional vinegars. Principle component analysis revealed that volatiles profile of bergamot Monascus aromatic vinegar and Hengshun honey vinegar exhibited distinctive differences from other eight vinegar samples. Moreover, the partial least squares regression analysis demonstrated that 11 volatile compounds were positively correlated with the antioxidant activity of vinegars, which suggested these compounds might be important functional substances in tested vinegars. This study explored several new functionally active compounds in different functional vinegars, which could widen the knowledge of bioactive factor in vinegars and provide new ideas for further development of functional vinegar beverages.
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Ácido Acético , Antioxidantes , Ácido Clorogênico , Ácido Gálico , PolifenóisRESUMO
IMPORTANCE: The fungal cell wall consists of glucans, mannoproteins, and chitin and is essential for cell viability, morphogenesis, and pathogenesis. The enzymes of the GH72 family are responsible for ß-(1,3)-glucan elongation and branching, which is crucial for the formation of the glucan-chitin polymer at the bud neck of yeast cells. In the human fungal pathogen Candida albicans, there are five GH72 enzyme-encoding genes: PHR1, PHR2, PHR3, PGA4, and PGA5. It is known that expression of PHR1 and PHR2 is controlled by the pH-responsive Rim101 pathway through the transcription factor Rim101. In this study, we have demonstrated that the transcription expression of PHR2 is also controlled by the transcription factor Crz1 through its binding motif in the promoter. Therefore, we have uncovered a dual-control mechanism by which PHR2 expression is negatively regulated via CaRim101 through the pH-responsive pathway and positively modulated by CaCrz1 through the calcium/calcineurin signaling pathway.
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Proteínas Fúngicas , Fatores de Transcrição , Humanos , Proteínas Fúngicas/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Sinalização do Cálcio , Candida albicans/metabolismo , Glucanos/metabolismo , Quitina/metabolismo , Regulação Fúngica da Expressão GênicaRESUMO
As one of the major components in the fungal cell wall, chitin is a polymer of ß-1,4-linked N-acetylglucosamine. Chitinases are hydrolytic enzymes that break down glycosidic bonds in the chitin. The human fungal pathogen Candida albicans has three chitinase-encoding genes, CaCHT1, CaCHT2 and CaCHT3. The CaCHT4 gene encodes a protein with the glycoside hydrolase family GH18 domain, Glyco_18, which suggests that CaCht4 might be a chitinase. In the present study, we have cloned, expressed and purified the N-terminally His6-tagged CaCht4 protein from bacterial cells. Further biochemical characterization has shown that this recombinant CaCht4 protein shows both exochitinase (chitobiosidase) and endochitinase activities, but has no N-acetylglucosaminase activity. The optimal temperature for the exochitinase activity of CaCht4 is 55 °C. Taken together, these data support that the CaCHT4 gene encodes a chitinase. Our finding provides a basis for us to understand the biological functions of the CaCHT4 gene in C. albicans.
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Candida albicans , Quitinases , Humanos , Candida albicans/genética , Quitinases/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Clonagem Molecular , Quitina/metabolismoRESUMO
Chitin is a polymer of ß-1,4-linked N-acetylglucosamine (GlcNAc) and plays a central role in the assembly of the fungal cell wall. Chitinases are hydrolytic enzymes that break down glycosidic bonds in the chitin. Chitinases are classified into three categories, endochitinases, exochitinases and N-acetylglucosaminases, according to the manner in which the enzyme cleaves the chitin polymer. Saccharomyces cerevisiae has two chitinase-encoding genes, CTS1 and CTS2. However, whether Cts2p shows a chitinase activity remains unknown. In this study, we have cloned, expressed and purified the recombinant Cts2p protein from bacterial cells. We have demonstrated that Cts2p has a higher chitobiosidase (exochitinase) activity than endochitinase activity, but no N-acetylglucosaminase activity. The optimal temperature for the chitobiosidase activity of Cts2p is 37 °C.
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Quitinases , Saccharomycetales , Saccharomycetales/genética , Quitinases/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Quitina/metabolismo , Clonagem MolecularRESUMO
The main challenge for the advancement of current high-speed automotives is aerodynamic heating. In this study, the application of lateral jet for thermal protection of the high-speed automotives is extensively studied. The simulation of the lateral coolant jet is done via Computational fluid dynamic at high-velocity condition. Finding optimum jet configuration for reduction of the aerodynamic heating is the main goal of this research. Two different coolant jets (Helium and Carbon dioxide) are investigated as coolant jet and flow study and fuel penetration mechanism are fully presented. In addition, the thermal load on the main body of nose cone is compared for different configurations. Our results specify that the injection of lateral jet near the tip of spike is effective for thermal protection of main body via deflection of bow shock. Also, Carbon dioxide jet with lower diffusivity is more effective for the protection of forebody with multi-row disk from sever aerodynamic heating.
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PURPOSE: Cancer testis antigens (CTAs) are optimal tumor diagnostic markers and involved in carcinogenesis. However, colorectal cancer (CRC) related CTAs are less reported with impressive diagnostic capability or relevance with tumor metabolism rewiring. Herein, we demonstrated CRC-related CTA, Protamine 1 (PRM1), as a promising diagnostic marker and involved in regulation of cellular growth under nutrient deficiency. METHODS: Transcriptomics of five paired CRC tissues was used to screen CRC-related CTAs. Capability of PRM1 to distinguish CRC was studied by detection of clinical samples through enzyme linked immunosorbent assay (ELISA). Cellular functions were investigated in CRC cell lines through in vivo and in vitro assays. RESULTS: By RNA-seq and detection in 824 clinical samples from two centers, PRM1 expression were upregulated in CRC tissues and patients` serum. Serum PRM1 showed impressive accuracy to diagnose CRC from healthy controls and benign gastrointestinal disease patients, particularly more sensitive for early-staged CRC. Furthermore, we reported that when cells were cultured in serum-reduced medium, PRM1 secretion was upregulated, and secreted PRM1 promoted CRC growth in culture and in mice. Additionally, G1/S phase transition of CRC cells was facilitated by PRM1 protein supplementation and overexpression via activation of PI3K/AKT/mTOR pathway in serum deficient medium. CONCLUSIONS: In general, our research presented PRM1 as a specific CRC antigen and illustrated the importance of PRM1 in CRC metabolism rewiring. The new vulnerability of CRC cells was also provided with the potential to be targeted in future. Diagnostic value and grow factor-like biofunction of PRM1 A represents the secretion process of PRM1 regulated by nutrient deficiency. B represents activation of PI3K/AKT/mTOR pathway of secreted PRM1.
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Proliferação de Células , Neoplasias Colorretais , Protaminas , Estresse Fisiológico , Animais , Humanos , Masculino , Camundongos , Antígenos de Neoplasias/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Nutrientes/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Protaminas/imunologia , Protaminas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fase S , Estresse Fisiológico/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
Physicochemical, proteomics, and bioinformatics analyses were conducted to investigate protein profiles in Trichiurus haumela under frozen (120 d) and chilled (6 d) storage. Springiness, chewiness, myofibrillar active sulfhydryl content, and Ca2+-ATPase activity significantly decreased, suggesting that cold stress altered muscle proteins. Compared with fresh hairtail (FH), 66 common differentially abundant proteins (DAPs) had lower abundances in chilled (3 d; CSH) and frozen (120 d; FSH) hairtail, including myosin binding proteins, filamins, actinin, troponin, and muscle-restricted coiled-coil protein. Gene Ontology (GO) annotation showed DAPs were mainly involved in cellular process, cellular anatomical entity, intracellular, and binding items. Eukaryotic orthologous group (KOG) analysis revealed that changes in cytoskeleton and energy production and conversion functions dominated during cold storage, degrading the myofibril and connective tissue structures and the physicochemical performance of muscle tissues. This study presents deep insights into the protein alternation mechanisms in hairtail muscle under cold stress.
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Chemical and liquid chromatography-mass spectrometry (LC-MS)-based lipidomics techniques were used to investigate the alternations of lipid profiles in hairtail (Trichiurus haumela) muscle after chilled storage for six days. The chemical results showed that the peroxide values (PVs) and thiobarbituric acid reactive species (TBARS) content in the muscle increased significantly, from 0.43 meq/kg of lipids and 0.86 mg malondialdehyde (MDA)/kg of muscle to 8.36 meq/kg and 10.69 mg MDA/kg, respectively, after six days of chilled storage. LC-MS-based lipidomics analyses detected 1446 lipids in hairtail muscle tissues assigned to 26 lipid categories, including 257 triglycerides (TGs), 232 phosphatidylcholines (PCs), 149 phosphatidylethanolamines (PEs), and 78 ceramides (Cers), among other classes. In total, 175 and 67 differentially abundant lipids (DALs) accumulating at low and high abundance levels, respectively, were detected in chilled stored hairtail (CSH) compared to fresh (FH) samples. Among the DALs, the PCs, PEs, and TGs/diglycerides (DGs) as predominant lipid components were more prone to oxidation/hydrolysis, likely owing to their highly unsaturated properties. The apparent alterations between the CSH and FH samples might result from lipid lipolysis, modifications of main- and side-chains, backbone cleavage, and/or the decomposition of lipids during chilled storage.
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Lipidômica , Perciformes , Animais , Cromatografia Líquida , Músculos , Espectrometria de Massas em Tandem/métodos , TriglicerídeosRESUMO
Chemical and LC/MS-based lipidomics strategies were performed to explore the alterations of lipid profiles in hairtail (Trichiurus haumela) muscle during 120 days of frozen storage. Chemical results indicated that the PV and TBARS values in hairtail muscle significantly increased during 120 days of frozen storage. Lipidomics results detected 1223 lipids in hairtail muscle assigned to 26 lipid categories, including 261 triglycerides (TGs), 251 phosphatidylcholines (PCs), 153 phosphatidylethanolamines (PEs), and 66 diglycerides (DGs). Totally, 153 and 67 differentially abundant lipids (DALs) accumulated at high and low levels, respectively, were detected in frozen hairtail (FSH) compared to in fresh (FH) samples. Among these, PEs, PCs, and TGs/DGs as predominant lipid components were vulnerable to oxidation/hydrolysis mainly due to their unsaturated properties. The apparent alterations between FSH and FH samples may result from lipid side-chain modifications, backbone cleavage, and/or decomposition of lipids during long-term storage. This study provides novel insight into the molecular mechanisms of lipid alternations in hairtail muscle during frozen storage.
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Lipidômica , Perciformes , Animais , Hormônio Foliculoestimulante , Lipídeos , MúsculosRESUMO
Ultrasound imaging has developed into an indispensable imaging technology in medical diagnosis and treatment applications due to its unique advantages, such as safety, affordability, and convenience. With the development of data information acquisition technology, ultrasound imaging is increasingly susceptible to speckle noise, which leads to defects, such as low resolution, poor contrast, spots, and shadows, which affect the accuracy of physician analysis and diagnosis. To solve this problem, we proposed a frequency division denoising algorithm combining transform domain and spatial domain. First, the ultrasound image was decomposed into a series of sub-modal images using 2D variational mode decomposition (2D-VMD), and adaptively determined 2D-VMD parameter K value based on visual information fidelity (VIF) criterion. Then, an anisotropic diffusion filter was used to denoise low-frequency sub-modal images, and a 3D block matching algorithm (BM3D) was used to reduce noise for high-frequency images with high noise. Finally, each sub-modal image was reconstructed after processing to obtain the denoised ultrasound image. In the comparative experiments of synthetic, simulation, and real images, the performance of this method was quantitatively evaluated. Various results show that the ability of this algorithm in denoising and maintaining structural details is significantly better than that of other algorithms.
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Processamento de Imagem Assistida por Computador/métodos , Ultrassonografia/métodos , Algoritmos , Anisotropia , Artefatos , Simulação por Computador , Humanos , Razão Sinal-Ruído , Tomografia Computadorizada por Raios X/métodosRESUMO
In Saccharomyces cerevisiae, the Rim101 pathway senses extracellular pH changes through a complex consisted of Rim8, Rim9 and Rim21 at the plasma membrane. Activation of this sensor complex induces a proteolytical complex composed of Rim13 and Rim20 and leads to the C-terminal processing and activation of the transcription factor Rim101. Deletion mutants for RIM8, RIM9, RIM13, RIM20, RIM21 and RIM101 causes yeast cells to be sensitive to calcium stress, but how they regulate calcium sensitivity remain unknown. Here we show that deletion mutations of these six Rim101 pathway components elevate the activation level of the calcium/calcineurin signaling and the transcriptional expression level of the vacuolar calcium pump gene PMC1, but lead to a reduction in transcriptional expression level of the ER/Golgi calcium pump gene PMR1 in yeast cells. Deletion of NRG1, encoding one of the repression targets of Rim101, rescues the transcriptional expression of PMR1 in all these mutants. Furthermore, ectopic expression of a constitutively active form of Rim101 or further deletion of NRG1 suppresses the calcium sensitivity of these six deletion mutants. Therefore, the pH-sensing Rim101 pathway positively regulates the transcriptional expression of PMR through its downstream target Nrg1 to affect the calcium sensitivity of yeast cells.
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ATPases Transportadoras de Cálcio/genética , Chaperonas Moleculares/genética , Proteínas Repressoras/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Cálcio/metabolismo , Sinalização do Cálcio/genética , Ciclosporina/farmacologia , Deleção de Genes , Regulação Fúngica da Expressão Gênica , Genes Fúngicos , Concentração de Íons de Hidrogênio , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Mutação , Proteínas Repressoras/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genéticaRESUMO
The antioxidative effects of κ-carrageenan oligosaccharides (CO) on the stability of proteins and lipids in mackerel fillets were determined during frozen storage. Electronic nose analysis indicated that CO treatments maintained the stability of the overall volatile flavor profiles in frozen mackerel. Protein oxidation analysis suggested that the incorporation of CO significantly retarded the rapid decrease of Ca2+-ATPase activity and active sulphydryl (A-SH) contents while also effectively inhibiting the increases in carbonyl content and surface hydrophobicity of myofibrillar proteins (MPs) compared to the control treatments. Lipid stability results showed that the peroxide values (PVs), conjugated diene (CD) content, anisidine values (AVs), and thiobarbituric acid index (TBA-i) values of the extracted lipids were also clearly reduced by CO treatments during frozen storage. Fatty acid composition determinations further confirmed that the permeated CO molecules stabilized the polyunsaturated C22:6n3 (DHA) in the lipids, most likely due to their efficient free radical scavenging activities.
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The budding yeast Saccharomyces cerevisiae remains a central position among biofuel-producing organisms. However, the gene expression regulatory networks behind the ethanol fermentation is still not fully understood. Using a static fermentation model, we have examined the ethanol yields on biomass of deletion mutants for all yeast nonessential genes encoding transcription factors and their related proteins in the yeast genome. A total of 20 (about 10%) transcription factors are identified to be regulators of ethanol production during fermentation. These transcription factors are mainly involved in cell cycling, chromatin remodeling, transcription, stress response, protein synthesis and lipid synthesis. Our data provides a basis for further understanding mechanisms regulating ethanol production in budding yeast.
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Montagem e Desmontagem da Cromatina , Etanol/metabolismo , Fermentação/genética , Saccharomyces cerevisiae/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Regulação Fúngica da Expressão Gênica , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Through a genome-wide screen we have identified calcium-tolerant deletion mutants for five genes in the budding yeast Saccharomyces cerevisiae. In addition to CNB1 and RCN1 that are known to play a role in the calcium signalling pathway, the protein kinase gene CMK2, the sphingolipid homeostasis-related gene ORM2 and the gene SIF2 encoding the WD40 repeat-containing subunit of Set3C histone deacetylase complex are involved in the calcium sensitivity of yeast cells to extracellular calcium. Cmk2 and the transcription factor Crz1 have opposite functions in the response of yeast cells to calcium stress. Deletion of CMK2 elevates the level of calcium/calcineurin signalling and increases the expression level of PMR1 and PMC1, which is dependent on Crz1. Effects of Cmk2 on calcium sensitivity and calcium/calcineurin signalling are dependent on its kinase activity. Therefore, Cmk2 is a negative feedback controller of the calcium/calcineurin signalling pathway. Furthermore, the cmk2 crz1 double deletion mutant is more resistant than the crz1 deletion mutant, suggesting that Cmk2 has an additional Crz1-independent role in promoting calcium tolerance.
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Calcineurina/metabolismo , Cálcio/metabolismo , Regulação Fúngica da Expressão Gênica , Genes Fúngicos , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Biocatálise , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , ATPases Transportadoras de Cálcio/genética , ATPases Transportadoras de Cálcio/metabolismo , Deleção de Genes , Modelos Biológicos , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Fenótipo , ATPases Transportadoras de Cálcio da Membrana Plasmática/genética , ATPases Transportadoras de Cálcio da Membrana Plasmática/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMO
Maf1 is a repressor of RNA polymerase (Pol) III transcription for tRNA. Nutrient deprivation and environmental stress repress Pol III transcription through Maf1 in Saccharomyces cerevisiae. The sole Candida albicans homolog CaMaf1 is a protein of 380 amino acids with conserved domains and motifs of the eukaryotic Maf1 family. Here, we show that C. albicans cells lacking CaMAF1 show elevated levels of tRNA. Deletion of CaMAF1 increases the sensitivity of C. albicans cells to lithium cation and SDS as well as tolerance to rapamycin and azole. In addition, deletion of CaMAF1 reduces the level of filamentation and alters the surface morphology of colonies. CaMaf1 is localized in the nucleus of log-phase growing cells. However, a dynamic change of subcellular localization of CaMaf1 exists during serum-induced morphological transition, with CaMaf1 being localized in the nuclei of cells with germ tubes and short filaments but outside of the nuclei of cells with long filaments. In addition, CaMaf1 is required for rapamycin-induced repression of CaERG20, encoding the farnesyl pyrophosphate synthetase involved in ergosterol biosynthesis. Therefore, CaMaf1 plays a role as a general repressor of Pol III transcription in C. albicans.
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Antifúngicos/farmacologia , Candida albicans/genética , Tolerância a Medicamentos/genética , Proteínas Fúngicas/metabolismo , RNA Polimerase III/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica , Sequência de Aminoácidos , Candida albicans/citologia , Candida albicans/efeitos dos fármacos , Candida albicans/metabolismo , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Deleção de Genes , Regulação Fúngica da Expressão Gênica , Geraniltranstransferase/genética , Testes de Sensibilidade Microbiana , RNA de Transferência/metabolismo , Proteínas Repressoras/química , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Fatores de Transcrição/química , Fatores de Transcrição/genéticaRESUMO
Purpose: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. In China, chronic hepatitis B virus (HBV) infection remains the major risk factor for HCC. In this study, we performed a genome-wide association study (GWAS) among Chinese populations to identify novel genetic loci contributing to susceptibility to HBV-related HCC.Experimental Design: GWAS scan is performed in a collection of 205 HBV-related HCC trios (each trio includes an affected proband and his/her both parents), and 355 chronic HBV carriers with HCC (cases) and 360 chronic HBV carriers without HCC (controls), followed by two rounds of replication studies totally consisting of 3,796 cases and 2,544 controls.Results: We identified a novel association signal within the CDK14 gene at 7q21.13 (index rs10272859, OR = 1.28, P = 9.46 × 10-10). Furthermore, we observed that the at-risk rs10272859[G] allele was significantly associated with higher mRNA expression levels of CDK14 in liver tissues. Chromosome conformation capture assays in liver cells confirmed that a physical interaction exists between the promoter region of CDK14 and the risk-associated SNPs in strong linkage disequilibrium with the index rs10272859 at 7q21.13. This index rs10272859 also showed significant association with the survival of HCC patients.Conclusions: Our findings highlight a novel locus at 7q21.13 conferring both susceptibility and prognosis to HBV-related HCC, and suggest the CDK14 gene to be the functional target of the 7q21.13 locus. Clin Cancer Res; 24(4); 906-15. ©2017 AACR.
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Carcinoma Hepatocelular/genética , Cromossomos Humanos Par 7/genética , Quinases Ciclina-Dependentes/genética , Estudo de Associação Genômica Ampla , Hepatite B Crônica/genética , Neoplasias Hepáticas/genética , Adulto , Povo Asiático/genética , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/etnologia , Estudos de Casos e Controles , China , Feminino , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/etnologia , Humanos , Desequilíbrio de Ligação , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/etnologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Análise de SobrevidaRESUMO
Hypertrophic scars (HS) area fibroproliferative disorder of the skin, which causes aesthetic and functional impairment. However, the molecular pathogenesis of this disease remains largely unknown and currently no efficient treatment exists. MicroRNAs (miRNAs) are involved in a variety of pathophysiological processes, however the role of miRNAs in HS development remains unclear. To investigate the miRNA expression signature of HS, microarray analysis was performed and 152 miRNAs were observed to be differentially expressed in HS tissue compared with normal skin tissues. Of the miRNAs identified, miRNA21 (miR21) was significantly increased in HS tissues and hypertrophic scar fibroblasts (HSFBs) as determined by reverse transcriptionquantitative polymerase chain reaction analysis. It was also observed that, when miR21 in HSFBs was blocked through use of an antagomir, the phenotype of fibrotic fibroblasts in vitro was reversed, as demonstrated by growth inhibition, induction of apoptosis and suppressed expression of fibrosisassociated genes collagen type I α 1 chain (COL1A1), COL1A2 and fibronectin. Furthermore, miR21 antagomir administration significantly reduced the severity of HS formation and decreased collagen deposition in a rabbit ear HS model. The total scar area and scar elevation index were calculated and were demonstrated to be significantly decreased in the treatment group compared with control rabbits. These results indicated that the miR21 antagomir has a therapeutic effect on HS and suggests that targeting miRNAs may be a successful and novel therapeutic strategy in the treatment of fibrotic diseases that are difficult to treat with existing methods.
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Antagomirs/genética , Cicatriz Hipertrófica/genética , MicroRNAs/genética , Transcriptoma , Adolescente , Adulto , Animais , Apoptose , Linhagem Celular , Cicatriz Hipertrófica/patologia , Cicatriz Hipertrófica/terapia , Análise por Conglomerados , Colágeno/genética , Colágeno/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Modelos Animais de Doenças , Fibrose , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Coelhos , Adulto JovemRESUMO
RATIONALE: Hepatic portal venous gas (HPVG) is a very rare radiological finding that occurs when gas enters the portal venous system. HGVG can be caused by various diseases, with the most common being intestinal ischemia or necrosis. While there are few reports of HPVG associated with colon cancer, we report a case of HPVG associated with advanced colon cancer. DIAGNOSIS: The diagnosis of this patient was HPVG caused by colon cancer. INTERVENTIONS: Left colon cancer resection, pancreatic tail resection, splenectomy, and transverse colostomy were performed. OUTCOMES: The patient recovered well, and postoperative paraffin pathology confirmed that the resected tumor was colon cancer. LESSONS: Abdominal computed tomography is an effective method for diagnosing and monitoring HPVG. Klebsiella pneumonia is a potential gas-producing microorganism associated with HPVG, which may be confirmed by Blood culture or drainage culture. The prognosis of HPVG is closely related to the underlying pathology. Surgery should be performed early when there are signs of intestinal ischemia, necrosis, or perforation.