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BACKGROUND The type of traumatic temporomandibular joint (TMJ) ankylosis depends on the degree of severity of TMJ trauma. Here, we performed comprehensive differential molecular profiling between TMJ fibrous and bony ankylosis. MATERIAL AND METHODS Six sheep were used and a bilateral different degree of TMJ trauma was performed to induce fibrous ankylosis in one side and bony ankylosis in the other side. The ankylosed calluses were harvested at days 14 and 28 postoperatively and analyzed by Affymetrix OviGene-1_0-ST microarrays. DAVID was used to perform the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis for the different expression genes (DEGs). The DEGs were also typed into protein-protein interaction (PPI) networks to get the interaction data. Ten DEGs, including 7 hub genes from PPI analysis, were confirmed by real-time PCR. RESULTS We found 90 and 323 DEGs at least 2-fold at days 14 and 28, respectively. At day 14, bony ankylosis showed upregulated DEGs, such as TLR8, SYK, NFKBIA, PTPRC, CD86, ITGAM, and ITGAL, indicating a stronger immune and inflammatory response and cell adhesion, while genes associated with anti-adhesion (PRG4) and inhibition of osteoblast differentiation (SFRP1) had higher expression in fibrous ankylosis. At day 28, bony ankylosis showed increased biological process related to new bone formation, while fibrous ankylosis was characterized by a prolonged immune and inflammatory reaction. CONCLUSIONS This study provides a differential gene expression profile between TMJ fibrous and bony ankylosis. Further study of these key genes may provide new ideas for future treatment of TMJ bony ankylosis.
Assuntos
Anquilose/genética , Fibrose/genética , Transtornos da Articulação Temporomandibular/genética , Traumatismos do Nervo Trigêmeo/genética , Animais , Anquilose/patologia , Modelos Animais de Doenças , Expressão Gênica/genética , Fraturas Mandibulares/genética , Análise em Microsséries , Ovinos/genética , Articulação Temporomandibular/metabolismo , Articulação Temporomandibular/patologia , Transtornos da Articulação Temporomandibular/patologia , Transcriptoma , Traumatismos do Nervo Trigêmeo/patologiaRESUMO
BACKGROUND: Traumatic haemarthrosis was hypothesized to be the etiology of temporomandibular (TMJ) ankylosis. Here, taking haematoma absorbance as a control, we aimed to reveal the molecular mechanisms involved in haematoma organizing into ankylosis using transcriptome microarray profiles. MATERIAL/METHODS: Disk removal was performed to building haematoma absorbance (HA) in one side of TMJ, while removal of disk and articular fibrous layers was performed to induced TMJ ankylosis through haematoma organization (HO) in the contralateral side in a sheep model. Haematoma tissues harvested at days 1, 4 and 7 postoperatively were examined by histology, and analyzed by Affymetrix OviGene-1_0-ST microarrays. The DAVID were recruited to perform the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis for the different expression genes (DEGs). The DEGs were also typed into protein-protein interaction (PPI) networks to get the interaction data. Six significant genes screened from PPI analysis, were confirmed by real-time PCR. RESULTS: We found 268, 223 and 17 DEGs at least twofold at days 1, 4 and 7, respectively. At day 1, genes promoting collagen ossification (POSTN, BGN, LUM, SPARC), cell proliferation (TGF-ß), and osteogenic differentiation of mesenchymal stem cells (BMP-2) were up-regulated in the HO side. At day 4, several genes involved in angiogenesis (KDR, FIT1, TEK) shower higher expression in the HO side. While HA was characterized by a continuous immune and inflammatory reaction. CONCLUSIONS: Our results provide a comprehensive understanding of the role of haematoma in the onset and progress of TMJ ankylosis. The study will contribute to explaining why few injured TMJs ankylose and most do not from the molecular level.
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Anquilose , Hemartrose , Animais , Anquilose/genética , Côndilo Mandibular , Análise em Microsséries , Osteogênese , Ovinos , Articulação TemporomandibularRESUMO
OBJECTIVES: To study the technical feasibility of contrast-enhanced ultrasound (CEUS) in evaluating femoral head perfusion in a rabbit model of steroid-induced femoral head osteonecrosis. METHODS: Twenty rabbits were divided randomly into a control group (n = 8) and an experimental group (n = 12). Rabbits in the experimental group were induced by lipopolysaccharide and methylprednisolone to build a model of steroid-induced femoral head osteonecrosis. Contrast-enhanced ultrasound examinations were performed at 3 and 5 weeks after induction. Then, pathologic examinations and microvessel density (MVD) calculations were performed on the excised rabbit femoral heads. RESULTS: The MVD of the experimental group decreased significantly 3 and 5 weeks after induction compared with that of the control group. According to the CEUS examination results, significant differences existed in the ascending slope, descending slope, mean transit time, and time to peak between the groups at 5 weeks (P < .05). A correlation analysis showed that the descending slope had a certain correlation with the MVD (correlation coefficient, 0.376). A receiver operating characteristic curve was used to analyze the capacity of the CEUS parameters to predict the occurrence of osteonecrosis. The areas under the curve for the ascending slope and descending slope were 0.758 and 0.760, respectively (P < .05). CONCLUSIONS: Contrast-enhanced ultrasound can visualize the microcirculation in steroid-induced osteonecrosis of the femoral head in rabbits and may be a useful imaging method for the early monitoring and prediction of femoral head osteonecrosis.
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Meios de Contraste , Cabeça do Fêmur/irrigação sanguínea , Cabeça do Fêmur/diagnóstico por imagem , Aumento da Imagem/métodos , Osteonecrose/diagnóstico por imagem , Ultrassonografia/métodos , Animais , Modelos Animais de Doenças , Estudos de Viabilidade , Feminino , Cabeça do Fêmur/patologia , Masculino , Metilprednisolona , Microvasos/diagnóstico por imagem , Osteonecrose/patologia , Coelhos , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To investigate the effect of Jiarong Tablets (JRT) on the testicular morphology and function of rats with late-onset hypogonadism (LOH). METHODS: LOH models were established in 8 eighteen-month-old male SD rats, treated intragastrically with distilled water (the model control group, n = 4) or JRT at 0.375 g/kg/d, qd (the JRT group, n = 4), and another 5 two-month-old normal male SD rats were also given distilled water by gavage (normal control group), all for 28 days. Then all the rats were weighed and sacrificed for measurement of the serum T level and pathological and electron microscopic examination of the testis tissue. RESULTS: Compared with the normal controls, the LOH models showed significantly decreased testis coefficient (P < 0.05) and serum T level (ï¼»3.40 ± 0.06ï¼½ vs ï¼»5.88 ± 0.46ï¼½ ng /ml, P < 0.05). No statistically significant differences were observed in the model control and JRT groups in the body weight and testis coefficient (P > 0.05), but the serum T level (ï¼»4.50 ± 0.78ï¼½ ng/ml) was remarkably decreased in the latter (P < 0.05). In comparison with the model controls, the rats treated with JRT exhibited increases in the sperm count in the seminiferous tubules and the amount of testicular interstitial cells. Electron microscopy revealed a markedly increased number of mitochondria in the JRT-treated animals, with some mitochondrial sheaths and cristae but no obvious mitochondrial edema. CONCLUSIONS: Jiarong Tablets can elevate the serum T level and improve the testicular morphology and ultrastructure of LOH rats.
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Medicamentos de Ervas Chinesas , Hipogonadismo , Testículo/efeitos dos fármacos , Animais , Medicamentos de Ervas Chinesas/farmacologia , Hipogonadismo/tratamento farmacológico , Masculino , Ratos , Ratos Sprague-Dawley , Contagem de Espermatozoides , Comprimidos , Testículo/anatomia & histologia , Testosterona/sangueRESUMO
To clone bHLH( basic helix-loop-helix) gene from Carthamus tinctorius,analyze the expression level in different plant tissues and construct the plant expression vector. The bHLH1 gene was cloned by RT-PCR techniques,and the protein characteristics were analyzed by bioinformatics,and phylogenetic tree was constructed. The expression of bHLH1 gene in different tissues and the roots after inoculated by Fusarium oxysporum were analyzed using real time-PCR,and the plant expression vector p BASTA-bHLH1 was constructed. The obtained ORF sequence of bHLH1 gene was 897 bp,encoded a protein of 298 amino acids. Sequence alignment and phylogenetic tree analyses showed that C. tinctorius bHLH1 had a certain homology with other species of amino acids,and was the most similar to the amino acid sequence of tobacco. Real-time PCR results showed significant differences,CtbHLH1 gene in red flower petals in different tissues and different flowering period had remarkable difference in expression level,its high amount expressed in petals,flowers third day after blossom expressed the highest quantity,at the end of the flowering the expression quantity is low. In addition,it is expressed in the root,and the expression in the stem and leaves is extremely low. The bHLH1 gene of C. tinctorius is successfully cloned,and the expression is analyzed. The plant expression vector p BASTA-bHLH is constructed.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Carthamus tinctorius/genética , Proteínas de Plantas/genética , Sequência de Aminoácidos , Clonagem Molecular , Flores/genética , Regulação da Expressão Gênica de Plantas , Vetores Genéticos , FilogeniaRESUMO
Etomidate (ETO) is a highly-efficient drug that can induce anesthesia with increasing doses, thus subject to strict regulation. However, an accurate and efficient method for ETO intake detection is currently lacking. Therefore, this study developed a straightforward sample preparation method using LC-MS/MS to analyze ETO and its primary metabolite, etomidate acid (ETA), in urine, liver, and kidney samples. Snap frozen pig liver and kidney samples were ground into a fine powder. Then, all the biological samples, including human urine, pig liver and kidney tissues, were deproteinized using acetonitrile and filtered for analysis. The separation was achieved in 9.01 min with gradient elution. The calibration curves ranged from 0.5 to 50 ng/mL for ETO in urine and 0.5 to 50 ng/g in liver and kidney, while the curves ranged from 1 to 100 ng/mL for ETA in urine and 1 to 100 ng/g in liver and kidney. The correlation coefficients (R2) were greater than 0.9957. The Limit of detection (LOD) and limit of quantitation (LOQ) for ETO were 0.2 and 0.5 ng/mL in urine samples and 0.2 and 0.5 ng/g in liver and kidney samples, respectively. For ETA, the LOD and LOQ were 0.5 and 1 ng/mL in urine samples and 0.5 and 1 ng/g in liver and kidney samples. This method was assessed by validation parameters, including selectivity, intra- and inter-day precision and accuracy, recovery, matrix effect, dilution integrity and stability. It was successfully applied to a practical case, revealing ETO and ETA concentrations in urine of 1.01 and 5.58 µg/mL, in liver samples of 12.30 and 1.13 µg/g, and in kidney samples of 6.95 and 4.23 µg/g. This suggests that the method is suitable for routine forensic detection of illicit ETO abuse.
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Etomidato , Humanos , Animais , Suínos , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massa com Cromatografia Líquida , Fígado , Rim , Reprodutibilidade dos TestesRESUMO
Objective: The Obturator Functioning Scale (OFS) is a scale without formal measures of validity in any language. This study aimed to translate and adapt the OFS from English to Chinese and check its reliability and validity in Chinese-speaking patients with obturator prostheses after cancer-related maxillectomy. Methods: The 15-item Chinese preversion of the OFS was completed by 133 patients in three tertiary stomatological hospitals. Of these, 41 completed it again one week after the first measurement. The patients also completed the Chinese version of the University of Washington quality of life scale (UW-QOL, Version 4). Results: Item 12 ("upper lip feels numb") was deleted to achieve a better statistical fit. The 14-item Chinese version of the OFS (OFS-Ch) demonstrated high internal consistency (Cronbach's alpha = 0.908). The test-retest reliability coefficients for most items exceeded 0.90, indicating substantial reproducibility. Confirmatory factor analysis found that the scale consisted of three correlated factors: 1) eating (four items), 2) speech (five items), and 3) other problems (five items). This explained 70.2 % of the total variance using exploratory factor analysis. The scale was significantly convergent and discriminant and could validly discriminate between patients with Brown I and IId maxillary defects. Conclusions: Our results showed that the OFS-Ch scale is a valid tool for evaluating oral dysfunction and satisfaction with appearance for patients with the obturator prosthesis and identifying those at risk of poor obturator function in clinical settings.
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Tilapia is an important freshwater aquaculture species worldwide. In recent years, streptococcal diseases have severely threatened development of tilapia aquaculture, while effective prevention and control methods have not yet been established. In order to understand the immunological response of tilapia to infection by Streptococcus agalactiae (S. agalactiae), this study employed Solexa/Illumina RNA-seq and digital gene expression (DGE) technology to investigate changes in the tilapia transcriptome before and after S. agalactiae infection. We obtained 82,799 unigenes (mean size: 618 bp) using de novo assembly. Unigenes were annotated by comparing against databases including Nr, Swissprot, cluster of orthologous groups of proteins, Kyoto encyclopedia of genes and genomes, and gene ontology. Combined with DGE technology, transcriptomic changes in tilapia before and after bacteria challenging were examined. A total of 774 significantly up-regulated and 625 significantly down-regulated unigenes were identified, among which 293 were mapped to 181 signaling pathways including 17 immune-related pathways involving 65 differentially expressed genes. We observed a change in the expression of six genes in the Toll-like receptor signaling pathway, and this was subsequently confirmed via quantitative real-time PCR. This comparative study of the tilapia transcriptome before and after S. agalactiae infection identified important differentially-expressed immune-related genes and signaling pathways that will provide useful insights for further analysis of the mechanisms of tilapia defense against S. agalactiae infection.
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Ciclídeos/genética , Ciclídeos/microbiologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Infecções Estreptocócicas/genética , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/fisiologia , Animais , Biblioteca Gênica , Ontologia Genética , Imunidade/genética , Anotação de Sequência Molecular , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/genética , Receptores Toll-Like/metabolismo , Transcriptoma , Regulação para Cima/genéticaRESUMO
OBJECTIVE: To investigate the correlation between plasmacytoid dendritic cell (pDC) dose in grafts and the occurrence of cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The clinical data of 80 children who received allo-HSCT in Children's Hospital of Soochow University from August 20, 2020 to June 11, 2021 were retrospectively analyzed. Proportions of DC subsets and T-cell subsets in grafts were detected by flow cytometry in order to calculate infused cell dose of each cell. Weekly monitoring of CMV-DNA copies in peripheral blood for each child were performed after transplantation. The last follow-up date was December 31, 2021. RESULTS: All the children gained hematopoietic reconstitution. CMV infection was observed in 51 children (63.8%±5.4%) within the first 100 days after transplantation, including 2 cases developing CMV disease. Univariate analysis indicated that infused doses of DC and pDC were significantly associated with CMV infection within 100 days after allo-HSCT (P <0.05). Multivariate analysis indicated that a high dose infusion of pDC was an independent protective factor for CMV infection within 100 days after allo-HSCT (P <0.05). By the end of follow-up, 7 children died of transplantation-related complications, including 2 deaths from CMV disease, 2 deaths from extensive chronic graft-versus-host disease, and 3 deaths from capillary leak syndrome. The overall survival rate was 91.2%. CONCLUSION: The pDC in grafts may be associated with early infection of CMV after allo-HSCT, while a high infused pDC dose may serve as a protective factor for CMV infection after transplantation.
Assuntos
Infecções por Citomegalovirus , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Criança , Humanos , Estudos Retrospectivos , Doença Enxerto-Hospedeiro/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Células DendríticasRESUMO
OBJECTIVE: To evaluate whether the pedicle submental island flap (SIF) can be safely used in the oral tongue squamous cell carcinoma (OTSCC) patients with pathologically node-positive (pN+) neck, especially pN+ at level I. METHODS: Retrospectively, 101 OTSCC patients with SIF reconstruction were enrolled. Oncological outcomes included the total locoregional recurrence, the SIF related locoregional recurrence (SRLR) which referred to the local recurrence at flap and ipsilateral neck recurrence at level I, recurrence free survival (RFS), overall survival (OS), and disease specific survival (DSS). RESULTS: Sixty-one patients were pathologically node-negative (pN0) and 40 were pN+. Thirteen patients experienced locoregional recurrence, of which 5 had a SRLR. The pN+ group had a significantly higher locoregional recurrence rate, lower 5-year RFS, OS and DSS than pN0 group (P < 0.05). Patients with pN0 had a significantly higher neck RFS when compared to those with pN+ either at level I (P = 0.005) or at other levels (P < 0.001). However, the neck RFS was similar between the two subgroups of pN+ (P = 0.550). Especially, patients with pN+ at level I had a significantly higher SRLR rate (P = 0.006) compared to those with pN0 at level I. Multivariate analysis showed that pN+ was an unfavorable factor for tumor recurrence and OS. CONCLUSION: Our data did not support the use of SIF in OTSCC patients with pN+ neck at level I due to an significantly increased SRLR rate compared to those with pN0 neck at level I.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Procedimentos de Cirurgia Plástica , Neoplasias da Língua , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Estudos Retrospectivos , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Neoplasias da Língua/cirurgia , Neoplasias da Língua/patologia , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/patologia , Retalhos Cirúrgicos/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgiaRESUMO
Largemouth bass ( Micropterus salmoides) is an economically important fish species in North America, Europe, and China. Various genetic improvement programs and domestication processes have modified its genome sequence through selective pressure, leaving nucleotide signals that can be detected at the genomic level. In this study, we sequenced 149 largemouth bass fish, including protospecies (imported from the US) and improved breeds (four domestic breeding populations from China). We detected genomic regions harboring certain genes associated with improved traits, which may be useful molecular markers for practical domestication, breeding, and selection. Subsequent analyses of genetic diversity and population structure revealed that the improved breeds have undergone more rigorous genetic changes. Through selective signal analysis, we identified hundreds of putative selective sweep regions in each largemouth bass line. Interestingly, we predicted 103 putative candidate genes potentially subjected to selection, including several associated with growth (p sst1 and grb10), early development ( klf9, sp4, and sp8), and immune traits ( pkn2, sept2, bcl6, and ripk2). These candidate genes represent potential genomic landmarks that could be used to improve important traits of biological and commercial interest. In summary, this study provides a genome-wide map of genetic variations and selection footprints in largemouth bass, which may benefit genetic studies and accelerate genetic improvement of this economically important fish.
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Bass , Animais , Bass/genética , Análise de Sequência de DNA/veterinária , Genoma , América do Norte , ChinaRESUMO
Lysozyme is an important molecule of innate immune system for the defense against bacterial infections. Three genes encoding chicken-type (c-type) lysozymes, C1-, C2-, C3-type, were obtained from tilapia Oreochromis aureus by RT-PCR and the RACE method. Catalytic and other conserved structure residues required for functionality were identified. The amino acid sequence identities between C1- and C2-type, C1- and C3-type, C2- and C3-type were 67.8%, 65.7% and 63.9%, respectively. Phylogenetic tree analyze indicated the three genes were firstly grouped to those of higher teleosteans, Pleuronectiformes and Tetraodontiformes fishes, and then clustered to those of lower teleosteans, Cypriniformes fishes. Bioinformatic analysis of mature peptide showed that the three genes possess typical sequence characteristics, secondary and tertiary structure of c-type lysozymes. The three tilapia c-type lysozymes mRNAs were mainly expressed in liver and muscle, and C1-type lysozyme also highly expressed in intestine. C1-type lysozyme mRNA was weakly expressed in stomach, C2- and C3-type mRNAs were weakly expressed in intestine. After bacterial challenge, up-regulation was obvious in kidney and spleen for C1-type lysozyme mRNA, while for C2- and C3-type lysozyme obvious increase were observed in stomach and liver, suggesting that C1-type lysozyme may mainly play roles in defense, while C2- and C3-type lysozyme mainly conduct digestive function against bacteria infection. All the three c-type recombinant lysozymes displayed lytic activity against Gram-negative and Gram-positive bacteria. These results indicated that three c-type lysozymes play important roles in the defense of O. aureus against bacteria infections.
Assuntos
Aeromonas hydrophila/imunologia , Ciclídeos/genética , Proteínas de Peixes/genética , Infecções por Bactérias Gram-Negativas/veterinária , Muramidase/genética , Animais , Ciclídeos/imunologia , Clonagem Molecular , DNA Complementar/análise , Escherichia coli/genética , Proteínas de Peixes/imunologia , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica , Infecções por Bactérias Gram-Negativas/imunologia , Dados de Sequência Molecular , Muramidase/metabolismo , Filogenia , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência/veterinária , Análise de Sequência de Proteína/veterinária , Distribuição TecidualRESUMO
BACKGROUND: Traditional radiography is limited in its ability to give reliable information on the number and morphology of root canals. The application of cone-beam computed tomography (CBCT) provides a non-invasive three-dimensional confirmatory diagnosis as a complement to conventional radiography. The aim of this study was to evaluate the root and canal morphology of mandibular premolars in a western Chinese population using CBCT scanning. METHODS: The sample included 149 CBCT images comprising 178 mandibular first premolars and 178 second premolars. The tooth position, number of roots and canals, and canal configuration according to Vertucci's classification were recorded. RESULTS: The results showed that 98% of mandibular first premolars had one root and 2% had two roots; 87.1% had one canal, 11.2% had two canals and 0.6% had three canals. The prevalence of C-shaped canals was 1.1%. All mandibular second premolars had one root; 97.2% had one canal and 2.2% had two canals. The prevalence of C-shaped canals was 0.6%. CONCLUSIONS: The prevalence of multiple canals in mandibular first premolars was mainly of Type V, and mandibular second premolars had a low rate of canal variation in this western Chinese population. Root canal bifurcation occurred at the middle or apical third in most bicanal mandibular premolars. CBCT scanning can be used in the management of mandibular premolars with complex canal morphology.
Assuntos
Dente Pré-Molar/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico/estatística & dados numéricos , Cavidade Pulpar/diagnóstico por imagem , Mandíbula/diagnóstico por imagem , Raiz Dentária/diagnóstico por imagem , China/epidemiologia , Humanos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: The purpose of this retrospective study was to compare the differences in quality of life (QOL) outcomes between the conventional obturator prostheses (COP) and the pedicled submental artery island flap (SAIF) in the reconstruction of Brown IIb maxillary defects. MATERIALS AND METHODS: The QOL of 116 eligible patients who had a lapse ≥ 12 months after the cancer-related maxilla ablation was evaluated by the University of Washington quality of life scale (UW-QOL), Performance Status Scale for Head and Neck (PSS-HN), and Obturator Functioning Scale (OFS). RESULTS: Patients in the SAIF group reported statistically and clinically significant higher overall QOL scores but lower chewing scores in the UW-QOL scale when compared with those in the COP group (P < 0.05). Clinically significantly higher scores were also observed in the recreation and anxiety domains in the UW-QOL scale for the SAIF group, but there was no statistical significances. The COP group reported more complaints about the nasal leakage when swallowing and the shape of the upper lip, and had a stronger willingness to avoid family or social events in the OFS (P < 0.05). CONCLUSIONS: For patients with Brown IIb defects, SAIF reconstruction can achieve reduced nasal leakage when swallowing, improved upper-lip contour, increased social activity, and superior overall QOL than COP. The inferior chewing function in the SAIF group indicated the need for dental rehabilitation with a conventional denture or osseointegrated implants.
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Neoplasias , Procedimentos de Cirurgia Plástica , Humanos , Maxila/cirurgia , Neoplasias/cirurgia , Obturadores Palatinos , Qualidade de Vida , Estudos Retrospectivos , Retalhos Cirúrgicos/cirurgiaRESUMO
BACKGROUND: Acute myeloid leukemia (AML) is a myeloid neoplasm makes up 7.6% of hematopoietic malignancies. Super-enhancers (SEs) represent a special group of enhancers, which have been reported in multiple cell types. In this study, we explored super-enhancer profiling through ChIP-Seq analysis of AML samples and AML cell lines, followed by functional analysis. METHODS: ChIP-seq analysis for H3K27ac was performed in 11 AML samples, 7 T-ALL samples, 8 B-ALL samples, and in NB4 cell line. Genes and pathways affected by GNE-987 treatment were identified by gene expression analysis using RNA-seq. One of the genes associated with super-enhancer and affected by GNE-987 treatment was LYL1 basic helix-loop-helix family member (LYL1). shRNA mediated gene interference was used to down-regulate the expression of LYL1 in AML cell lines, and knockdown efficiency was detected by RT-qPCR and western blotting. The effect of knockdown on the growth of AML cell lines was evaluated by CCK-8. Western blotting was used to detect PARP cleavage, and flow cytometry were used to determine the effect of knockdown on apoptosis of AML cells. RESULTS: We identified a total of 200 genes which were commonly associated with super-enhancers in â§10 AML samples, and were found enriched in regulation of transcription. Using the BRD4 inhibitor GNE-987, we assessed the dependence of AML cells on transcriptional activation for growth and found GNE-987 treatment predominantly inhibits cell growth in AML cells. Moreover, 20 candidate genes were selected by super-enhancer profile and gene expression profile and among which LYL1 was observed to promote cell growth and survival in human AML cells. CONCLUSIONS: In summary, we identified 200 common super-enhancer-associated genes in AML samples, and a series of those genes are cancer genes. We also found GNE-987 treatment downregulates the expression of super-enhancer-associated genes in AML cells, including the expression of LYL1. Further functional analysis indicated that LYL1 is required for AML cell growth and survival. These findings promote understanding of AML pathophysiology and elucidated an important role of LYL1 in AML progression.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos , Leucemia Mieloide Aguda , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteínas de Ciclo Celular , Criança , Humanos , Leucemia Mieloide Aguda/genética , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genéticaRESUMO
Transgenic technique provides a new way for fish breeding. Stable lines of growth hormone gene transfer carps, salmon and tilapia, as well as fluorescence protein gene transfer zebra fish and white cloud mountain minnow have been produced. The fast growth characteristic of GH gene transgenic fish will be of great importance to promote aquaculture production and economic efficiency. This paper summarized the progress in transgenic fish research and ecological assessments. Microinjection is still the most common used method, but often resulted in multi-site and multi-copies integration. Co-injection of transposon or meganuclease will greatly improve the efficiency of gene transfer and integration. "All fish" gene or "auto gene" should be considered to produce transgenic fish in order to eliminate misgiving on food safety and to benefit expression of the transferred gene. Environmental risk is the biggest obstacle for transgenic fish to be commercially applied. Data indicates that transgenic fish have inferior fitness compared with the traditional domestic fish. However, be-cause of the genotype-by-environment effects, it is difficult to extrapolate simple phenotypes to the complex ecological interactions that occur in nature based on the ecological consequences of the transgenic fish determined in the laboratory. It is critical to establish highly naturalized environments for acquiring reliable data that can be used to evaluate the environ-mental risk. Efficacious physical and biological containment strategies remain to be crucial approaches to ensure the safe application of transgenic fish technology.
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Animais Geneticamente Modificados/genética , Peixes/genética , Técnicas de Transferência de Genes , Animais , Elementos de DNA Transponíveis , Ecossistema , Hormônio do Crescimento/genética , MicroinjeçõesRESUMO
The aim of this study was to compare the functional characteristics of mesenchymal stromal cells (MSCs) from a sheep model of traumatic temporomandibular joint (TMJ) fibrous and bony ankylosis. A sheep model of bilateral TMJ trauma-induced fibrous ankylosis on one side and bony ankylosis on the contralateral side was used. MSCs from fibrous ankylosed callus (FA-MSCs) or bony ankylosed callus (BA-MSCs) at weeks 1, 2, 4, and 8 after surgery were isolated and cultured. MSCs derived from the bone marrow of the mandibular condyle (BM-MSCs) were used as controls. The MSCs from the different sources were characterized morphologically, phenotypically, and functionally. Adherence and trilineage differentiation potential were presented in the ovine MSCs. These cell populations highly positively expressed MSC-associated specific markers, namely CD29, CD44, and CD166, but lacked CD31 and CD45 expressions. The BA-MSCs had higher clonogenic and proliferative potentials than the FA-MSCs. The BA-MSCs also showed higher osteogenic and chondrogenic potentials, but lower adipogenic capacity than the FA-MSCs. In addition, the BA-MSCs demonstrated higher chondrogenic, but lower osteogenic capacity than the BM-MSCs. Our study suggests that inhibition of the osteogenic and chondrogenic differentiations of MSCs might be a promising strategy for preventing bony ankylosis in the future.
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Chemotherapy can effectively reduce the leukemic burden and restore immune cell production in most acute myeloid leukemia (AML) cases. Nevertheless, endogenous immunosurveillance usually fails to recover after chemotherapy, permitting relapse. The underlying mechanisms of this therapeutic failure have remained poorly understood. Here, we show that abnormal IL-36 production activated by NF-κB is an essential feature of mouse and human leukemic progenitor cells (LPs). Mechanistically, IL-36 directly activates inflammatory monocytes (IMs) in bone marrow, which then precludes clearance of leukemia mediated by CD8+ T cells and facilitates LP growth. While sparing IMs, common chemotherapeutic agents stimulate IL-36 production from residual LPs via caspase-1 activation, thereby enabling the persistence of this immunosuppressive IL-36IM axis after chemotherapy. Furthermore, IM depletion by trabectedin, with chemotherapy and PD-1 blockade, can synergistically restrict AML progression and relapse. Collectively, these results suggest inhibition of the IL-36IM axis as a potential strategy for improving AML treatment.
RESUMO
Screening of trait-associated molecular markers can be used to enhance the efficiency of selective breeding. Previously, we produced the first high-density genetic linkage map for the mandarin fish (Siniperca chuatsi) and identified 11 quantitative-trait loci significantly associated with growth, of which one is located within the growth hormone (GH) gene. To investigate the GH gene polymorphisms and their correlation with growth, the complete sequence was cloned and 32 single-nucleotide polymorphisms (SNPs) and one simple-sequence repeat (SSR) were identified. Of which, eight SNPs (G1-G8) and the SSR (GH-AG)were selected for genotyping and correlation analysis with growth traits in a random population. The results showed that the four novel polymorphicloci (G1, G2, G3 and GH-AG) were significantly correlated with growth traits of mandarin fish (P < 0.05). Of these, G1, G3 and GH-AG showed highly significant correlations with multiple growth traits (P < 0.01) and the combined SNP analysis showed that G1-G3 formed four effective diplotypes (D1-D4), among which D1 was highly significantly greater than D4 (P < 0.01) for some important growth traits. In conclusion, our results show that the four polymorphic loci G1-G3 and GH-AG within the mandarin fish GH gene are significantly correlated with growth traits and could be used as candidate molecular markers for selective breedingof superior varieties of mandarin fish.
Assuntos
Peixes/crescimento & desenvolvimento , Peixes/genética , Hormônio do Crescimento/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Alelos , Animais , Frequência do Gene , Genótipo , Desequilíbrio de Ligação , Locos de Características Quantitativas , Característica Quantitativa HerdávelRESUMO
High-throughput gene expression profiling has recently emerged as a promising technique that provides insight into cancer subtype classification and improved prediction of prognoses. Immune/inflammatory-related mRNAs may potentially enrich genes to allow researchers to better illustrate cancer microenvironments. Oral cavity squamous cell carcinoma (OC-SCC) exhibits high morbidity and poor prognosis compared to that of other types of head and neck squamous cell carcinoma (HNSCC), and these differences may be partially due to differences within the tumor microenvironments. Based on this, we designed an immune-related signature to improve the prognostic prediction of OC-SCC. A cohort of 314 OC-SCC samples possessing whole genome expression data that were sourced from The Cancer Genome Atlas (TCGA) database was included for discovery. The GSE41613 database was used for validation. A risk score was established using immune/inflammatory signatures acquired from the training dataset. Principal components analysis, GO analysis, and gene set enrichment analysis were used to explore the bioinformatic implications. When grouped by the dichotomized risk score based on the signature, this classifier could successfully discriminate patients with distinct prognoses within the training and validation cohorts (P < 0.05 in both cohorts) and within different clinicopathological subgroups. Similar somatic mutation patterns were observed between high and low risk score groups, and different copy number variation patterns were also identified. Further bioinformatic analyses suggested that the lower risk score group was significantly correlated with immune/inflammatory-related biological processes, while the higher risk score group was highly associated with cell cycle-related processes. The analysis indicated that the risk score was a robust predictor of patient survival, and its functional annotation was well established. Therefore, this bioinformatic-based immune-related signature suggested that the microenvironment of OC-SCC could distinguish among patients with different underlying biological processes and clinical outcomes, and the use of this signature may shed light on future OC-SCC classification and therapeutic design.