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Thrombomodulin (TM) is a single-chain transmembrane glycoprotein that mainly exists in vascular endothelial cells, hematopoietic progenitor cells, monocytes and macrophages. TM is mainly composed of five structural regions: the N-terminal lectin-like domain which plays a role in anti-inflammatory, and the six epidermal growth factor-like repeats which function as coagulation and fibrinolysis as well as serine-rich threonine regions and transmembrane domains and cytoplasmic domains. TM exhibits anti-inflammatory and anticoagulant effects by binding to thrombin to activate protein C, and TM-thrombin complex can also activate fibrinolytic inhibitors to suppress fibrinolysis. Previous reports showed that inhibiting epithelial mesenchymal transformation, mitogen-activated protein kinase or activating protein C and fibrinolytic inhibitor are the major mechanisms by which TM exerts anti-tumor properties. In atherosclerosis, TM can prevent atherosclerosis by blocking the activation of thrombin-mediated PAR-1 and inhibiting autophagy and apoptosis of endothelial cells. TM lectin-like domains can also bind to thrombin to inhibit its activity and further inhibit pulmonary thrombosis, fibrosis and inflammation. Moreover, TM protein is also involved in the pathogenesis of diabetic nephropathy, preeclampsia and ischemia-reperfu-sion injury. At present, TM is only clinically used for the treatment of sepsis and disseminated intravascular coagulation. Its role and therapeutic potential in cardiovascular and cerebrovascular diseases, cancers and other diseases deserve further exploration.
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OBJECTIVE@#To provide clinical basis for the diagnosis and treatment of chronic neutrophilic leukemia (CNL) and to provide possible molecular targets for the treatment.@*METHODS@#By summarizing the clinical data of 14 patients with CNL, the clinical characteristics, gene mutation types and possible prognostic factors were analyzed.@*RESULTS@#Among the 14 patients with CNL, males (9 cases) were more than females (5 cases), with a median age of 57 years old. The detection rate of CSF3R mutation was 92.86% (13/14), including 12 cases (85.71%) with T318I mutation and 1 case of Y799X mutation, and only 1 case was not detected for mutation of CSF3R. The ASXL1 mutation was detected in 42.86% (6/14) of the patients, all of which were nonsense mutations, including 4 cases with R693X and 2 cases with E705X, and 14.29% (2/14) of the patients was detected for SETBP1 mutation, all of which were with D868N mutation. No patients with simultaneous ASXL1 and SETBP1 mutations were found, and JAK2 and CALR mutations were not detected. All of the patients had normal karyotypes. These patients' median survival time was 30 months (95%CI 13.19-46.80), and the influence of age over 60 years old was statistically significant (21.83 months vs 35.35 months) (P<0.05).@*CONCLUSION@#It is difficult to diagnose CNL. CSF3R T618I mutation is its specific mutation, and ASXL1 mutation and SETBP1 mutation have auxiliary diagnostic significance for CNL. The age>60 years old at diagnosis is a factor of unfavourable prognosis.
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Objective: To investigate the relationship between tumor-infiltrating lymphocytes (TILs) and the androgen receptor (AR) in human epidermal growth factor receptor 2 (HER-2)-positive breast cancer. Methods: Specimens of 448 patients with HER-2-positive breast cancer from the Tianjin Medical University Cancer Hospital between March 2018 and November 2018 were collected. TILs were pathologically evaluated. AR expression was immunohistochemically analyzed. The relationships among TILs, the AR, and clinicopathological parameters were determined. Results: There were 38.2% (171/448) patients with TILs non/low-infiltrated, 42.2% (189/448) with moderately infiltrated, and 19.6% (88/448) with high infiltration. AR was positive in 62.7%(281/448) of the patients. Spearman correlation analysis showed that TILs and the AR were negatively related (r=-0.140, P=0.003). TILs were significantly associated with the AR in estrogen receptor positive breast cancer (P=0.009). Conclusions: TILs and the AR were negatively related in HER-2-positive breast cancer, indicating that HER-2-positive breast cancer can be treated according to the different infiltration levels of TILs and AR expression.
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<p><b>OBJECTIVE</b>To examine one young female patient with hereditary FVII deficiency and her family members, to observe the gene mutation and clinical phenotype, and to investigate the molecular mechanism of the dysfunction.</p><p><b>METHODS</b>Prothrombin time (PT), activated partial thromoploastin time (APTT), fibrinogen (Fg) and FVII activity (FVII:C) and FVII antigen (FVII:Ag) were tested. The gene mutations were sought by DNA sequencing for all of the exons and flanks, 5' and 3' non-translation region of F7 gene. To confirm the role of the found gene mutation, the reverse sequence were determined with Chromas software. To infer the influence of the mutation on the synthesis and function of FVII protein, the FVII protein molecule model containing the found mutation was constructed and the function prediction was performed by the signal peptide prediction database.</p><p><b>RESULTS</b>Compared with the normal population, the proband's PT value was significantly prolonged, and the ratio % FVII:C and that of FVII:Ag were significantly decreased by 1.1% and 0.9%, respectively. The PT, APTT, FVII:C and FVII:Ag of the proband's parents were both normal. Heterozygous 556th nucleotide mutations T/G were found in the proband's and his father's exon lA of F7 gene, with codon CTG turning into CGG, corresponding leucine (L) into arginine (R), i.e Leu12Arg. Function prediction showed that L12R mutations affected the segmentation of different parts of the signal peptide and its corresponding function, which could result in the decline in the mature protein synthesis and its activity obviously. In addition, a spontaneous 3' untranslated region c11814-insAA heterozygous mutation was detected in the proband's F7 gene, while her parents didn't possess this mutation.</p><p><b>CONCLUSION</b>A new hererozygous mutation (L12R) located in signal peptide of F7 gene is the primary molecular basis of the case with hereditary FVII deficiency. At the same time, the proband's spontaneous 3' non-translation region c11814-insAA mutation may lead to the further reduetion of the FVII synthesis.</p>
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Femenino , Humanos , Factor VII , Deficiencia del Factor VII , Mutación , Linaje , Fenotipo , Señales de Clasificación de ProteínaRESUMEN
Hematopoietic stem cell (HSC) transplantation could be of therapeutic value for aplastic anemia (AA) patients, and immunosuppressants may facilitate the efficiency of the procedure. As anti-inflammatory cytokine interleukin-11 (IL-11) has a thrombopoietic effect, its use in cases of chronic bone marrow failure, such as AA, has been proposed to induce HSC function. However, the putative mechanisms that may support this process remain poorly defined. We found that decreased miR-204-5p levels were coincident with increased proliferation in mouse HSCs following exposure to IL-11 in vitro. Through inhibiting NF-кB activity, miR-204-5p repression was demonstrated to be a downstream effect of IL-11 signaling. miR-204-5p was shown to directly target thrombopoietin (TPO) via sequence-dependent 3′-UTR repression, indicating that this microRNA-dependent pathway could serve an essential role in supporting IL-11 functions in HSCs. Increased TPO expression in HSCs following IL-11 exposure could be mimicked or blocked by inhibiting or overexpressing miR-204-5p, respectively. Consistent with these in vitro findings, IL-11 promoted HSC engraftment in a mouse model of AA, an effect that was attenuated in cells overexpressing miR-204-5p. The reduction in miR-204-5p levels is an integral component of IL-11 signaling that may play an essential role in treating AA.
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<p><b>OBJECTIVE</b>To investigate the effects of artesunate (ART) on proliferation, cell cycle and apoptosis of SKM-1 cells in vitro and to explore the underlying mechanisms.</p><p><b>METHODS</b>After SKM-1 cells were treated with different concentrations of ART, the cell proliferation was determined by CCK-8 method. Apoptosis and distribution of cell cycle were detected by flow cytometry. Both DCFH-DA fluorescent probe and Fluo-3-Am fluorescent probe were used to detect the changes of intracellular reactive oxygen species (ROS) and calcium ion concentration. Western blot was used to measure the protein levels of BCL-2, BAX, BAD, P-BAD, survivin and XIAP.</p><p><b>RESULTS</b>ART obviously inhibited the growth of SKM-1 cells in time and dose-dependent manners (r = -0.841; r = 0.-786). The antioxidant trolox-pretreatment significantly decreased the growth inhibition effect of ART on SKM-1 cells. Caspase inhibitor Ac-DEVD-CHO partially reduced the growth inhibition effect of ART on SKM-1 cells. After treatment with ART for 24 hours, the apoptosis of SKM-1 cells was found, the cell cycle of SKM-1 was arrested in G0/G1 phase, ART could elevate the levels of calciumion and reactive orygen. ART could significantly down-regulate the protein expression levels of P-BAD and survivin in SKM-1 cells, and showed a highly negative correlation with ART dose (r = -0.909; r = -0.849). On the contrary, ART had no significant effect on expression levels of BAD and XIAP in SKM-1 cells, and after ART treatment, although BCL-2 protein expression was not significantly different when compared with control group, but the BCL-2/BAX ratio significantly decreased and highly negatively correlated with ART dose (r = -0.866).</p><p><b>CONCLUSION</b>The ART significantly suppresses the cell proliferation, induces the apoptosis and promoted cell cycle arrest at G0/G1 phase in SKM-1 cells. The mechanisms of ART anti-MDS is associated with the increase of intracellular calciumion concentration and ROS levels. In addition, the pro-apoptotic activity of ART may be involved in the regulation of BCL-2 /BAX ratio and the expressions of P-bad and survivin.</p>
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Humanos , Apoptosis , Artemisininas , Farmacología , Calcio , Metabolismo , Ciclo Celular , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo , Proteínas Inhibidoras de la Apoptosis , Metabolismo , Oligopéptidos , Farmacología , Especies Reactivas de Oxígeno , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To investigate the expression of high-molecular-weight keratins CK5/6, CK14, estrogen receptor (ER) and progesterone receptor (PR) in differential diagnosis of simple ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH) and low-grade ductal carcinoma in situ (low-grade DCIS) .</p><p><b>METHODS</b>The clinicopathological data of twenty cases of atypical ductal epithelial hyperplasia (ADH) with focal cancerization changed into low-grade DCIS diagnosed at Tianjin Medical University Cancer Institute and Hospital between January 2013 and February 2014 were reviewed and analyzed. The expressions of CK5/6, CK14, ER and PR were detected by immunohistochemistry.</p><p><b>RESULTS</b>Positive expressions of CK5/6 and CK14 were seen in UDH showing a mosaic pattern, while negative expression in ADH and low-grade DCIS. In addition, CK5/6 and CK14 were positively expressed in the myoepithelial cells of UDH, ADH and low-grade DCIS. Positive expressions of ER and PR were observed in UDH, ADH and low-grade DCIS. But they presented diffuse and homogeneous strong positive expression in ADH and variable positive expression in UDH.</p><p><b>CONCLUSION</b>In the intraductal proliferative lesions of the breast, the use of combined detection of the expression of CK5/6, CK14, ER and PR is of practical significance in the differential diagnosis of UDH, ADH and low-grade DCIS.</p>
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Femenino , Humanos , Mama , Metabolismo , Patología , Neoplasias de la Mama , Diagnóstico , Metabolismo , Carcinoma Ductal de Mama , Diagnóstico , Metabolismo , Carcinoma Intraductal no Infiltrante , Diagnóstico , Metabolismo , Diagnóstico Diferencial , Hiperplasia , Diagnóstico , Metabolismo , Inmunohistoquímica , Queratina-14 , Metabolismo , Queratina-5 , Metabolismo , Queratina-6 , Metabolismo , Receptores de Estrógenos , Metabolismo , Receptores de Progesterona , MetabolismoRESUMEN
To reveal the underlying mechanism of doxorubicin induced hepatotoxicity, an NMR-based metabolomic approach combined with multivariate statistical analysis was used to observe its metabolic alternations of rat liver. Sixteen differential metabolites between model rats and normal rats were characterized as potential pathological biomarkers related to doxorubicin induced hepatotoxicity. Six pathways, including phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, phenylalanine metabolism, glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, and tyrosine metabolism were regarded as the targeted metabolic pathways according to Metabolic Pathway Analysis (MetPA). The results suggested that the metabolic perturbations in rats with doxorubicin induced hepatotoxicity were mainly involved in amino acid metabolism, lipid pathways, purine metabolism, energy metabolism, dysfunction of biotransformation and oxidative stress. The investigation revealed the effects of doxorubicin on liver in a holistic metabolic way, which laid a foundation for further studies on its toxicity mechanism.
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Animales , Ratas , Biomarcadores , Metabolismo , Doxorrubicina , Toxicidad , Metabolismo Energético , Hígado , Metabolismo , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Redes y Vías Metabólicas , Metabolómica , Análisis Multivariante , Estrés OxidativoRESUMEN
<p><b>OBJECTIVE</b>To investigate the inhibitory effect of the copolymer of magnetic nanoparticles of Fe(3)O(4) (MNPs-Fe(3)O(4)) and artesunate (ART) on myelodysplastic syndromes (MDS) cell line SKM-1 cells and the potential mechanisms.</p><p><b>METHODS</b>The protein expression levels of BCL-2, BAX, Caspase-3, and Survivin in SKM-1 cells treated with or without the co-polymer were measured by Western blot. The co-polymer-induced apoptosis rate of SKM-1 cells was measured by flow cytometry.</p><p><b>RESULTS</b>The apoptosis rate of SKM-1 cells in the copolymer groups was higher than that in both MNPs-Fe(3)O(4) and artesunate groups alone. The MNPs-Fe(3)O(4) may enhance ART-induced cell apoptosis. Western blot assay showed that the expression of survivin and BCL-2 protein were down-regulated in the ART group, and this down-regulation was even more significant in the group of copolymer of ART with MNPs-Fe(3)O(4). The levels of BAX were increased both in ART group and the copolymer of ART with MNPs-Fe(3)O(4) group, as compared with control group and MNPs-Fe(3)O(4) group. The levels of active-caspase-3 were obviously up-regulated when the ART was combined with the MNPs-Fe(3)O(4). The copolymer of ART with MNPs-Fe(3)O(4) could trigger changes in the expression levels of apoptosis-related genes in SKM-1 cells, among which up-regulation of BAX and down-regulation of survivin and BCL-2 are the 2 major alterations.</p><p><b>CONCLUSION</b>Artesunate can induce the apoptosis of SKM-1 cells, and MNPs-Fe(3)O(4) may enhance the cell apoptosis induced by ART.</p>
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Humanos , Apoptosis , Artemisininas , Caspasa 3 , Línea Celular Tumoral , Regulación hacia Abajo , Compuestos Férricos , Proteínas Inhibidoras de la Apoptosis , Nanopartículas de Magnetita , Regulación hacia ArribaRESUMEN
As a highly conserved RNA binding protein, Lin28 is a specific post-transcriptional inhibitor of let-7 biogenesis and can inhibit the let-7 processing and synthesis. Lin28 is involved in the stem cell proliferation and promote the rapid growth of embryonic stem cells. Lin28 plays an important role in the formation of tumor stem cells. Overexpression of Lin28 promotes the tumor cell proliferation and is associated with advanced human cancers. Lin28 can promote tissue repair.
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Humanos , Proliferación Celular , Células Madre Embrionarias , Metabolismo , MicroARNs , Metabolismo , Neoplasias , Metabolismo , Células Madre Neoplásicas , Metabolismo , Proteínas de Unión al ARN , MetabolismoRESUMEN
The purpose of this study was to investigate the effect of bone marrow mesenchymal stem cells (BMMSC) from patients with chronic myeloid leukemia (CML) in blastic phase (Bp) on K562 cells and the primary CML-Bp cells, and to explore its potential mechanisms. K562 cells and primary CML-Bp cells were co-cultured with BMMSC of different groups; the cell proliferation was detected by MTT method, the cell apoptosis rate and mitochondrial membrane potential were measured by flow cytometry, the expression levels of Caspase-8, Caspase-9, and activated Caspase-3 in cells were measured by Western blot. The results showed that the CML-Bp BMMSC could enhance the survival rate of K562 cells treated with adviamycin (ADM) and display protective effect on K562 cells and primary CML-Bp mononuctear cells, inhibited ADM-induced leukimia cell apoptosis (P < 0.05); as compared with CML-chronic phase (CML-Cp) BMMSC and normal BMMSC, the CML-Bp BMMSC showed the highest protective effect on leukemic cells, the mitochondrial membrane potential of co-cultured cells slightly droped (P < 0.05). In the CML-Bp BMMSC cultured with K562 cells, the expression level of caspase-3 was more down-regulated than that in K562 alone plus ADM group, while the expression of caspase-9 significantly increased (P < 0.05). It is concluded that the CML-Bp BMMSC down-regulates ADM-induced leukemia cell appoptosis, its mechanism may relate with the inhibition of mitochondrial membrane potential drop, the stabilization of unactive expression of caspase-9 and down-regulation of caspase-3 expression.
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Humanos , Apoptosis , Médula Ósea , Caspasa 3 , Caspasa 8 , Caspasa 9 , Proliferación Celular , Células Cultivadas , Regulación hacia Abajo , Leucemia Mielógena Crónica BCR-ABL Positiva , Patología , Células Madre Mesenquimatosas , Biología Celular , MetabolismoRESUMEN
This study was purposed to investigate the expression and methylation status of TIG1 in acute leukemia (AL). The TIG1 expression of 53 cases of AL and 20 cases of normal control (NC) were measured by using real-time quantitative PCR (RT-QT-PCR) and methylation-specific PCR(MS-PCR). The leukemia KG-1a, U937 and K562 cells were treated with 5-Aza-CdR. The results indicated that TIG1 gene expressed at a high level in cases of NC, but expressed at a low level in patients with AL. TIG1 gene was unmethylated in NC, but frequently methylated in AL. Aberrant methylation rate of TIG1 in AL was 75% (40/53). The expression of TIG1 in unmethylated patients was higher than that in methylated patients. Hypermethylation of TIG1 promoter CpG islands was detected in all the cell lines. 5-Aza-CdR treatment led to the hypomethylation of TIG1 promoter CpG islands. After the treatment with 5-Aza-CdR of different concentration, the expression of TIG1 was restored, and the effect of 5-Aza-CdR displayed dose-dependency. It is concluded that the reduced expression of TIG1 may play an important role in the pathogenesis of AL, and methylation may be responsible for the decreased transcription of TIG1 gene.
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Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Estudios de Casos y Controles , Línea Celular Tumoral , Islas de CpG , Metilación de ADN , Regulación Leucémica de la Expresión Génica , Leucemia , Genética , Proteínas de la Membrana , Genética , Regiones Promotoras GenéticasRESUMEN
In order to enhance the understanding of thrombotic thrombocytopenic purpura (TTP), the clinical features, laboratory characteristics, treatment and outcome of 14 patients with TTP were retrospectively analyzed and investigated. The results showed that 7 out of 14 patients with TTP had predisposing factors, such as pregnancy in 4 cases, infection in 3 cases, systemic lupus erythematosus (SLE) in 1 case and hematopoietic stem cell transplantation (HSCT) in 1 case. Fourteen patients all had neuropsychological symptoms, hemolytic anemia with negative-Coombs test, and decreased platelet counts. Eight patients had irregular fever with different degree. There were 8 patients with kidney damage including proteinuria in 8 cases and renal function abnormalities in 4 cases. The von Willebrand factor-cleaving protease (VWF-CP, ADAMTS13) activity of 13 cases out of 14 patients significantly decreased (less than 10%). At same time, plasma ADAMTS13 inhibitors were detected in 12 cases out of these 13 patients with decreased ADAMTS13 activity. After treatment with plasma exchange, glucocorticoid and rituximab so on, 12 cases achieved complete remission, in which 8 cases relapsed in two years. Two patients died at last, in which one case was secondary to HSCT. It is concluded that TTP is a kind of thrombotic microangiopathy due to platelet microthrombosis involved in multiple systems and multiple organs dysfunction with dangerous clinical process. The mortality of TTP patients is very high. Early diagnosis and early treatment with plasma exchange as the main means can greatly improve the prognosis of patients with TTP.
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Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Embarazo , Adulto Joven , Proteínas ADAM , Sangre , Proteína ADAMTS13 , Intercambio Plasmático , Pronóstico , Púrpura Trombocitopénica Trombótica , Diagnóstico , Terapéutica , Estudios RetrospectivosRESUMEN
Objective:To study the clinico-pathologic characteristics, molecular phenotypes, and prognosis of young breast can-cer patients. Methods:Data from 133 low-age (age≤30 years) young breast cancer patients and 117 young (31 years≤age≤35 years) breast cancer patients who underwent surgery between January 2002 and December 2009 were reviewed. Cases of the middle and old-age elderly (age>35 years) breast cancer patients during the corresponding period were randomly selected as matched controls. The clinico-pathologic characteristics, molecular phenotypes, and prognosis were retrospectively analyzed. Results:The low-age young and young breast cancer patients significantly differed from the elderly patients in terms of tumor size, lymph node metastasis, histological grading, molecular phenotype, and relapse (P<0.05). The low-age young patients are more vulnerable to have triple-negative breast can-cer, recurrence, and distant metastasis (P<0.001). Moreover, the low-age young patients have lower overall survival and disease-free survival than the other groups (P<0.05). Conclusion:Young breast cancer patients have poor prognosis compared with the elderly. Ear-ly screening and prompt treatment are necessary for young breast cancer patients.
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The authors reviewed the new technologies used for Panax genus research, including molecular identification technologies (especially for DNA barcoding), modern biotechnologies (e. g. the first generation and second generation sequencing technologies), and gene cloning and identification in this paper. These technologies have been successfully applied to species identification, transcriptome analysis, secondary metabolite biosynthetic pathway and the key enzyme function identification, indicating that the application of modern biotechnologies provide guarantee for the molecular identification of Panax genus. The application of modern biotechnologies also reveals the genetic information of transcriptome and functional genomics, and promotes the design of Panax plants genomic map. In summary, the application of the new technologies lay the foundation for clarifying the molecular mechanisms of ginsenoside biosynthesis and enforcing the in vitro synthesis of important natural products and new drugs in future.
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Biotecnología , Métodos , Clonación Molecular , Dermatoglifia del ADN , Ginsenósidos , Panax , Genética , Metabolismo , Proyectos de InvestigaciónRESUMEN
Synthetic biology of traditional Chinese medicine (TCM) is a new and developing subject based on the research of secondary metabolite biosynthesis for nature products. The early development of synthetic biology focused on the screening and modification of parts or devices, and establishment of standardized device libraries. Panax notoginseng (Burk.) F.H.Chen is one of the most famous medicinal plants in Panax species. Triterpene saponins have important pharmacological activities in P. notoginseng. Squalene epoxidase (SE) has been considered as a key rate-limiting enzyme in biosynthetic pathways of triterpene saponins and phytosterols. SE acts as one of necessary devices for biosynthesis of triterpene saponins and phytosterols in vitro via synthetic biology approach. Here we cloned two genes encoding squalene epoxidase (PnSE1 and PnSE2) and analyzed the predict amino acid sequences by bioinformatic analysis. Further, we detected the gene expression profiling in different organs and the expression level of SEs in leaves elicited by methyl jasmonate (MeJA) treatment in 4-year-old P notoginseng using real-time quantitative PCR (real-time PCR). The study will provide a foundation for discovery and modification of devices in previous research by TCM synthetic biology. PnSE1 and PnSE2 encoded predicted proteins of 537 and 545 amino acids, respectively. Two amino acid sequences predicted from PnSEs shared strong similarity (79%), but were highly divergent in N-terminal regions (the first 70 amino acids). The genes expression profiling detected by real-time PCR, PnSE1 mRNA abundantly accumulated in all organs, especially in flower. PnSE2 was only weakly expressed and preferentially in flower. MeJA treatment enhanced the accumulation of PnSEI mRNA expression level in leaves, while there is no obvious enhancement of PnSE2 in same condition. Results indicated that the gene expressions of PnSE1 and PnSE2 were differently transcribed in four organs, and two PnSEs differently responded to MeJA stimuli. It was strongly suggested that PnSEs play different roles in secondary metabolite biosynthesis in P. notoginseng. PnSE1 might be involved in triterpenoid biosynthesis and PnSE2 might be involved in phytosterol biosynthesis.
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Acetatos , Farmacología , Secuencia de Aminoácidos , Clonación Molecular , Ciclopentanos , Farmacología , Flores , Metabolismo , Regulación Enzimológica de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Oxilipinas , Farmacología , Panax notoginseng , Genética , Metabolismo , Filogenia , Fitosteroles , Reguladores del Crecimiento de las Plantas , Farmacología , Hojas de la Planta , Metabolismo , Raíces de Plantas , Metabolismo , Tallos de la Planta , Metabolismo , Plantas Medicinales , Genética , Metabolismo , Saponinas , Escualeno-Monooxigenasa , Química , Genética , Biología Sintética , Triterpenos , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To investigate the expression of vacuole membrane protein 1 (Vmp1) and its prognostic value in invasive ductal carcinoma (IDC) and concomitant ductal carcinoma in situ (DCIS) of the breast.</p><p><b>METHODS</b>The expression and location of Vmp1 in the breast tissues from 102 patients with IDC and 32 concomitant DCIS were detected by immunohistochemical SP method, and the relationship with clinicopathologic parameters was analyzed.</p><p><b>RESULTS</b>Vmp1 expression was observed in the cytoplasm of the cancer cells in 57.8% (59/102) cases, and correlated with grade (χ(2) = 12.644, P = 0.002), pTNM stage (χ(2) = 11.987, P = 0.001), node status (χ(2) = 9.341, P = 0.002), tumor diameter (χ(2) = 7.630, P = 0.022) as well as Nottingham Prognostic Index (NPI;χ(2) = 15.561, P = 0.000). The expression of Vmp1 in concomitant DCIS was higher than that in IDC (81.3% vs 56.3%; χ(2) = 4.655, P = 0.031). In this cohort, the mean disease-free survival was 81.2 months; the 5-year overall survival rate was 90.2% (92/102) and the disease-free survival rate was 81.4% (83/102). Vmp1 expression had significant influence on disease-free survival time, with Vmp1-negative patients showing poor prognosis (χ(2) = 11.192, P = 0.001). COX's proportional hazards regression model revealed that Vmp1 was a protective factor, with relative risk < 1.</p><p><b>CONCLUSIONS</b>The detection of Vmp1 in IDC may be helpful for prognosis prediction; the patients with Vmp1 expression may have a better prognosis.</p>
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Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Adulto Joven , Neoplasias de la Mama , Metabolismo , Patología , Cirugía General , Carcinoma Ductal de Mama , Metabolismo , Patología , Cirugía General , Carcinoma Intraductal no Infiltrante , Metabolismo , Patología , Cirugía General , Supervivencia sin Enfermedad , Estudios de Seguimiento , Metástasis Linfática , Proteínas de la Membrana , Metabolismo , Clasificación del Tumor , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Tasa de SupervivenciaRESUMEN
After searching the transcriptome dataset of Panax notoginseng, one unique sequence Pn02086 encoding UDP-glucosyltransferase (UGT), which may be involved in triterpene saponin biosynthesis, was discovered. The open reading frame of the UGT gene, named as PnUGT1, was cloned by 5'-RACE and RT-PCR method from P. notoginseng. The GenBank accession number for this gene is JX018210. The bioinformatic analysis of this gene and its corresponding protein was performed. The PnUGT1 gene contains a 1488 bp open reading frame and encodes a predicted protein of 495 amino acids. The molecular weight is 55.453 kD and the protein is unstable. In the secondary structure, the percentage of alpha helix, beta turn, random coil were 36.16%, 11.31%, 52.53%, respectively. The PnUGT1 contains 7 conserved domains predicted by InterProScan, including PSPG-box which is a unique consensus sequence of glycosyltransferases involved in plant secondary metabolism. The PnUGT1 was most likely to be located in the cytoplasm, without signal peptide and transmembrane region. Sequence alignment and phylogenetic analysis demonstrated that PnUGT1 had relative close relationship to the triterpene UDP-glucosyltransferase of Medicago truncatula (AAW56092), with the 66% similarity of conserved domain PSPG-box. PnUGT1 was more abundant in P. notoginseng leaf than in flower, stem and root. Therefore, PnUGT1 gene may be involved in notoginsenoside biosynthesis.
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Secuencia de Aminoácidos , Clonación Molecular , Biología Computacional , ADN Complementario , Genética , ADN de Plantas , Genética , Regulación de la Expresión Génica de las Plantas , Glucosiltransferasas , Genética , Metabolismo , Medicago truncatula , Genética , Metabolismo , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Panax notoginseng , Genética , Filogenia , Hojas de la Planta , Plantas Medicinales , Genética , Estructura Secundaria de Proteína , Alineación de SecuenciaRESUMEN
Squalene synthase (SQS) is a key enzyme in plant terpenoid biosynthetic pathway. This study focused on cloning and analysis of Huperzia serrata SQS (HsSQS1) gene. After searching the transcriptome dataset of H serrata, one unique sequence encoding SQS was discovered. The primers were designed according to the transcript sequence of HsSQS1 from the H. serrata transcriptome dataset. The open reading frame of HsSQS1 was cloned using RT-PCR strategy. The bioinformatic analysis of this gene and its corresponding protein were performed. The cDNA (named as HsSQS1) contains a 1263 bp open reading frame and encodes a predicted protein of 420 amino acids. The GenBank accession number for this gene is JQ004938. HsSQS1 contains two transmembrane regions, without signal peptide. The conserved domain of squalene synthase was presented in HsSQS1. HsSQS1 was more abundant in H. serrata root than in leaf and stem. This study cloned and analyzed squalene synthase gene from H. serrata for the first time. The result will provide a foundation for exploring the mechanism ofterpenoid biosynthesis in H. serrata plants.
Asunto(s)
Secuencia de Aminoácidos , Vías Biosintéticas , Clonación Molecular , ADN Complementario , Genética , Etiquetas de Secuencia Expresada , Farnesil Difosfato Farnesil Transferasa , Genética , Metabolismo , Genes de Plantas , Genética , Huperzia , Genética , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Filogenia , Hojas de la Planta , Raíces de Plantas , Tallos de la Planta , Plantas Medicinales , Genética , Triterpenos , QuímicaRESUMEN
<p><b>OBJECTIVE</b>To improve the recognition of Fechtner syndrome.</p><p><b>METHODS</b>The clinical and laboratory data and family survey of a patient with Fechtner's syndrom was reported.</p><p><b>RESULTS AND CONCLUSION</b>Giant platelets, thrombocytopenia and characteristic granulocyte inclusion bodies (Döhle-like bodies) were found in both peripheral blood and bone marrow smears of the patient. Clinically the patient had renal damage, nervous deafness, and vitreous lesions. There was a family genetic tendency on family survey the diagnosis of Fechtner syndrome is established.</p>