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Objective: To summarize the clinical characteristics, prognostic factors and treatment outcomes of childhood aggressive mature B-cell lymphoma after liver transplantation. Methods: This retrospective study included 18 children with newly diagnosed aggressive mature B-cell lymphoma after liver transplantation and treated from June 2018 to June 2022 in the Department of Hematology and Oncology of Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine. Clinical characteristics, treatment and outcomes of patients at last evaluation were analyzed. Overall survival (OS) and event free survival (EFS) rates were calculated by Kaplan-Meier method and Log-Rank analysis was performed to find factors of poor prognosis. Results: Among all 18 patients, there were 6 males and 12 females, and the age of onset was 40 (35, 54) months. The interval from transplant to tumor diagnosis was 21 (17, 35) months and 5 patients had early onset disease (<1 year since transplant). Seventeen patients had abdominal lesions. Diarrhea, vomiting and abdominal masses were the main clinical manifestations. All patients were Epstein-Barr virus (EBV) related posttransplant lymphoproliferative disorders (PTLD). One patient received individualized therapy due to critical sick at diagnosis, and the remaining 17 patients received CP (cyclophosphamide, methylprednisolone plus rituximab) and (or) modified EPOCH (prednisone, etoposide, doxorubicin, vincristine, cyclophosphamide plus rituximab) regimens. Of all 18 patients, 15 cases got complete response, 2 cases got partial response, 1 patient died of severe infection. The 2-year OS and EFS rates of 18 patients were (94±5)% and (83±8)%, respectively. None of age, gender or early onset disease had effect on OS and EFS rates in univariate analysis (all P>0.05). Conclusions: The symptoms of PTLD were atypical. Close surveillance of EBV-DNA for patients after liver transplantation was crucial to early stage PTLD diagnosis. CP or modified EPOCH regimen was efficient for pediatric patients with aggressive mature B cell lymphoma after liver transplantation.
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Protocolos de Quimioterapia Combinada Antineoplásica , Trasplante de Hígado , Linfoma de Células B , Humanos , Trasplante de Hígado/efectos adversos , Femenino , Masculino , Estudios Retrospectivos , Preescolar , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Linfoma de Células B/etiología , Pronóstico , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/etiología , Vincristina/uso terapéutico , Tasa de Supervivencia , Doxorrubicina/uso terapéutico , Doxorrubicina/administración & dosificación , Resultado del Tratamiento , Prednisona/uso terapéutico , Prednisona/administración & dosificación , Herpesvirus Humano 4/aislamiento & purificación , Trastornos Linfoproliferativos/etiología , Lactante , AdolescenteRESUMEN
The global prevalence and incidence of autoimmune diseases are increasing year by year, and the autoimmune diseases have become a major threat to public health. In the progression of the diseases, persistent and complex abnormal immune responses often lead to long-term unhealed skin ulcers, which not only affect the life quality of patients, but also lead to the aggravation of primary diseases. Therefore, doctors in burn surgery and other wound repair surgeries should pay attention to the understanding of autoimmune diseases. In the treatment of autoimmune disease-related ulcers, it is recommended to formulate a unified treatment plan according to the law of occurrence and development of the diseases, and multidisciplinary cooperation is needed to accelerate wound healing and improve the quality of wound healing.
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Enfermedades Autoinmunes , Úlcera Cutánea , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/terapia , Humanos , Calidad de Vida , Úlcera Cutánea/diagnóstico , Úlcera Cutánea/etiología , Úlcera Cutánea/terapia , Úlcera , Cicatrización de HeridasRESUMEN
ß-Galactosidase is one of the most important enzymes used in dairy processing. It converts lactose into glucose and galactose, and also catalyzes galactose to form galactooligosaccharides (GOS), so-called prebiotics. However, most of the ß-galactosidases from the starter cultures have low transgalactosylation activities, the process that results in galactose accumulation in yogurt. Here, a site-directed mutation strategy was attempted, to genetically modify ß-galactosidase from Streptococcus thermophilus. Out of 28 Strep. thermophilus strains, a ß-galactosidase gene named bgaQ, encoded for high ß-galactosidase hydrolysis activity (BgaQ), was cloned from the strain Strep. thermophilus SDMCC050237. It was 3,081 bp in size, with 1,027 deduced amino acid residuals, which belonged to the GH2 family. After replacing the Tyr801 and Pro802 around the active sites of BgaQ with His801 and Gly802, the GOS synthesis of the generated mutant protein BgaQ-8012 increased from 20.5% to 26.7% at 5% lactose, and no hydrolysis activity altered obviously. Subsequently, the purified BgaQ or BgaQ-8012 was added to sterilized milk inoculated with 2 starters from Strep. thermophilus SDMCC050237 and Lactobacillus delbrueckii ssp. bulgaricus ATCC11842. The GOS yields with added BgaQ or BgaQ-8012 increased to 5.8 and 8.3 g/L, respectively, compared with a yield of 3.7 g/L without enzymes added. Meanwhile, the addition of the BgaQ or BgaQ-8012 reduced the lactose content by 49.3% and 54.4% in the fermented yogurt and shortened the curd time. Therefore, this study provided a site-directed mutation strategy for improvement of the transgalactosylation activity of ß-galactosidase from Strep. thermophilus for GOS-enriched yogurt making.
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Streptococcus thermophilus , Yogur , Animales , Fermentación , Mutación , Streptococcus thermophilus/genética , Streptococcus thermophilus/metabolismo , beta-Galactosidasa/genética , beta-Galactosidasa/metabolismoRESUMEN
The histone methyltransferase DOT1L methylates lysine 79 (K79) on histone H3 and is involved in Mixed Lineage Leukemia (MLL) fusion leukemogenesis; however, its role in prostate cancer (PCa) is undefined. Here we show that DOT1L is overexpressed in PCa and is associated with poor outcome. Genetic and chemical inhibition of DOT1L selectively impaired the viability of androgen receptor (AR)-positive PCa cells and organoids, including castration-resistant and enzalutamide-resistant cells. The sensitivity of AR-positive cells is due to a distal K79 methylation-marked enhancer in the MYC gene bound by AR and DOT1L not present in AR-negative cells. DOT1L inhibition leads to reduced MYC expression and upregulation of MYC-regulated E3 ubiquitin ligases HECTD4 and MYCBP2, which promote AR and MYC degradation. This leads to further repression of MYC in a negative feed forward manner. Thus DOT1L selectively regulates the tumorigenicity of AR-positive prostate cancer cells and is a promising therapeutic target for PCa.
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N-Metiltransferasa de Histona-Lisina/genética , Neoplasias de la Próstata/genética , Proteínas Proto-Oncogénicas c-myc/genética , Receptores Androgénicos/genética , Adenosina/análogos & derivados , Adenosina/farmacología , Animales , Línea Celular Tumoral , Supervivencia sin Enfermedad , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , N-Metiltransferasa de Histona-Lisina/antagonistas & inhibidores , N-Metiltransferasa de Histona-Lisina/metabolismo , Humanos , Masculino , Ratones Endogámicos NOD , Ratones Noqueados , Ratones SCID , Compuestos de Fenilurea/farmacología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/terapia , Estabilidad Proteica/efectos de los fármacos , Proteínas Proto-Oncogénicas c-myc/metabolismo , Interferencia de ARN , Tratamiento con ARN de Interferencia/métodos , Receptores Androgénicos/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto/métodosRESUMEN
First-principles calculation of diffusion coefficients between Mg and Al is investigated comprehensively using density functional theory (DFT). The effect of different uncertainty sources arising from first principles calculations has been investigated systematically. These sources include the diffusion model, energetic, entropic and attempt frequency calculations. Variation in self and impurity diffusion coefficients of Mg and Al in stable phases are quantified using different DFT settings and compared with the experiments. Using the optimal DFT settings, diffusion coefficients in metastable phases of Al and Mg are predicted. The dataset refers to "An integrated experimental and computational study of diffusion and atomic mobility of the aluminum-magnesium system" [1].
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The effects of biological soil crusts (BSC) on vascular plant growth can be positive, neutral or negative, and little information is available on the impacts of different BSC successional stages on vascular plant population dynamics. We analysed seedling emergence, survival, plant growth and reproduction in response to different BSC successional stages (i.e. habitats: bare soil, cyanobacteria, lichen and moss crusts) in natural populations of Echinops gmelinii Turcz. in the Tengger Desert of northwest China. The winter annual E. gmelinii is a dominant pioneer herb after sand stabilisation. During the early stages of BSC succession, the studied populations of E. gmelinii were characterised by high density, plant growth and fecundity. As the BSC succession proceeded beyond moss crusts, the fecundity decreased sharply, which limited seedling recruitment. Differences in seedling survival among the successional stages were not evident, indicating that BSC have little effect on survival in arid desert regions. Moreover, E. gmelinii biomass allocation exhibited low plasticity, and only reproductive allocation was sensitive to the various habitats. Our results further suggest that the negative effects of BSC succession on population dynamics are primarily driven by increasing topsoil water-holding capacity and decreasing rain water infiltration into deeper soil. We conclude that BSC succession drives population dynamics of E. gmelinii, primarily via its effect on soil moisture. The primary cause for E. gmelinii population decline during the moss-dominated stage of BSC succession is decreased fecundity of individual plants, with declining seed mass possibly reducing the success of seedling establishment.
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Asteraceae/metabolismo , Biomasa , Briófitas/metabolismo , China , Clima Desértico , Ecosistema , Dinámica PoblacionalRESUMEN
Objective: To explore the relationship between different types of female reproductive system dysplasia and age of visit, clinical manifestations, common types of combined malformations and endometriosis. Methods: The patient's medical records in the Second Hospital of Hebei Medical University from December 2002 to June 2016 were collected and retrospectively analyzed. Results: Among 924 cases of genital tract dysplasia, uterine dysplasia (65.3%, 824/1 261) was the most common, followed by vaginal dysplasia (28.3%, 357/1 261), hymen atresia and urogenital fistula (3.7%, 47/1 261), and cervical dysplasia (2.6%, 33/1 261). (1) The youngest age was in patients with hymen atresia and urogenital fistula, with a median of 14.5 years old, while the older age were in patients with uterine, vaginal and cervical dysplasia, with median age of 25.0, 24.0 and 23.0 years old, respectively. (2) The clinical manifestations were lack of specificity, mainly abnormal findings of physical examination or accessory examination, primary amenorrhea, lower abdominal pain, infertility, adverse pregnancy history. (3) About other systemic malformations, urological malformations were the most common (4.8%, 44/924), followed by spinal malformations (0.5%, 5/924), inguinal hernia (0.4%, 4/924), heart malformations (0.2%, 2/924), cleft lip and palate (0.2%, 2/924). Oblique vaginal septal syndrome and MRKH syndrome were the most likely to be associated with other system malformations. (4) About combination with endometriosis, there was no significant difference between obstructive genital tract malformations (2.3%, 9/385) and non obstructive genital tract malformations (1.7%, 9/539; P=0.469). Conclusions: Female reproductive system dysplasia is the most common in uterine dysplasia, followed by vaginal dysplasia, hymen atresia and urogenital fistula, and cervical dysplasia. The age of visit is generally older, often found by abnormal findings of physical examination or accessory examination, primary amenorrhea, lower abdominal pain, infertility, adverse pregnancy history;and could be combined with a variety of other system malformations, most seen by urinary system malformations,there is also the risk of endometriosis.
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Genitales Femeninos/anomalías , Anomalías Urogenitales , Adolescente , Femenino , Humanos , Himen/anomalías , Embarazo , Estudios Retrospectivos , Útero/anomalías , Útero/cirugía , Vagina/anomalíasRESUMEN
Objective: To analyze the characteristics of super-antigen (SAg) of group A Streptococcus pyogenes (GAS), isolated from patients with scarlet fever or pharyngeal infections in Beijing between 2015-2017. Methods: Throat swab specimens from patients with scarlet fever or pharyngeal infections were collected and tested for GAS. Eleven currently known SAg genes including SpeA, speC, speG, speH, speI, speJ, speK, speL, speM, smeZ and ssa were tested by real-time PCR while M protein genes (emm genes) were amplified and sequenced by PCR. Results: A total of 377 GAS were isolated from 6 801 throat swab specimens, with the positive rate as 5.5%. There were obvious changes noticed among speC, speG, speH and speK in three years. A total of 45 SAg genes profiles were observed, according to the SAgs inclusion. There were significant differences appeared in the frequencies among two of the highest SAg genes profiles between emm1 and emm12 strains (χ(2)=38.196, P<0.001; χ(2)=72.310, P<0.001). There also appeared significant differences in the frequencies of speA, speH, speI and speJ between emm1 and emm12 strains (χ(2)=146.154, P<0.001; χ(2)=52.31, P<0.001; χ(2)=58.43, P<0.001; χ(2)=144.70, P<0.001). Conclusions: Obvious changes were noticed among SAg genes including speC, speG, speH and speK from patients with scarlet fever or pharyngeal infections in Beijing between 2015-2017. SAg genes including speA, speH, speI and speJ appeared to be associated with the emm 1 and emm 12 strains. More kinds of SAg genes profiles were isolated form GAS but with no significant differences seen in the main SAg genes profiles, during the epidemic period.
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Antígenos Bacterianos/genética , Faringitis/diagnóstico , Complicaciones Infecciosas del Embarazo/microbiología , Escarlatina/diagnóstico , Streptococcus pyogenes/genética , Streptococcus pyogenes/aislamiento & purificación , Superantígenos/genética , Proteínas de la Membrana Bacteriana Externa , Proteínas Bacterianas , Beijing/epidemiología , China/epidemiología , Exotoxinas , Femenino , Humanos , Proteínas de la Membrana , Faringitis/epidemiología , Faringitis/microbiología , Faringe/microbiología , Embarazo , Reacción en Cadena en Tiempo Real de la Polimerasa , Escarlatina/genética , Escarlatina/microbiología , Infecciones Estreptocócicas , Streptococcus pyogenes/inmunologíaRESUMEN
Neuroendocrine prostate cancer (NEPC) has increasingly become a clinical challenge. The mechanisms by which neuroendocrine (NE) cells arises from prostate adenocarcinoma cells are poorly understood. FOXA1 is a transcription factor of the forkhead family that is required for prostate epithelial differentiation. In this study, we demonstrated that FOXA1 loss drives NE differentiation, demarcated by phenotypical changes and NEPC marker expressions. Mechanistically, this is mediated by FOXA1 binding to the promoter of interleukin 8 (IL-8), a chemokine previously shown elevated in NEPC, to directly inhibit its expression. Further, IL-8 upregulation activates the MAPK/ERK pathway, leading to ERK phosphorylation and enolase 2 (ENO2) expression. IL-8 knockdown or ERK inhibition, on the other hand, abolished FOXA1 loss-induced NE differentiation. Analysis of xenograft mouse models confirmed FOXA1 loss in NEPC tumors relative to its adenocarcinoma counterparts. Importantly, FOXA1 is downregulated in human NEPC tumors compared to primary and castration-resistant prostate cancers, and its expression is negatively correlated with that of ENO2. These findings indicate that FOXA1 transcriptionally suppresses IL-8, the expression of which would otherwise stimulate the MAPK/ERK pathway to promote NE differentiation of prostate cancer cells. Our data strongly suggest that FOXA1 loss may play a significant role in enabling prostate cancer progression to NEPC, whereas IL-8 and MAPK/ERK pathways may be promising targets for therapeutic intervention.
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Adenocarcinoma/genética , Diferenciación Celular/genética , Factor Nuclear 3-alfa del Hepatocito/fisiología , Células Neuroendocrinas/fisiología , Tumores Neuroendocrinos/genética , Neoplasias de la Próstata/genética , Adenocarcinoma/patología , Carcinoma Neuroendocrino/genética , Carcinoma Neuroendocrino/patología , Línea Celular Tumoral , Progresión de la Enfermedad , Regulación hacia Abajo/genética , Humanos , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Tumores Neuroendocrinos/patología , Neoplasias de la Próstata/patologíaRESUMEN
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies that can result in damage to multiple organs. It is well documented that B cells play a critical role in the development of the disease. We previously showed that protein kinase C associated kinase (PKK) is required for B1 cell development as well as for the survival of recirculating mature B cells and B-lymphoma cells. Here, we investigated the role of PKK in lupus development in a lupus mouse model. We demonstrate that the conditional deletion of PKK in B cells prevents lupus development in Sle1Sle3 mice. The loss of PKK in Sle mice resulted in the amelioration of multiple classical lupus-associated phenotypes and histologic features of lupus nephritis, including marked reduction in the levels of serum autoantibodies, proteinuria, spleen size, peritoneal B-1 cell population and the number of activated CD4 T cells. In addition, the abundance of autoreactive plasma cells normally seen in Sle lupus mice was also significantly decreased in the PKK-deficient Sle mice. Sle B cells deficient in PKK display defective proliferation responses to BCR and LPS stimulation. Consistently, B cell receptor-mediated NF-κB activation, which is required for the survival of activated B cells, was impaired in the PKK-deficient B cells. Taken together, our work uncovers a critical role of PKK in lupus development and suggests that targeting the PKK-mediated pathway may represent a promising therapeutic strategy for lupus treatment.
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Linfocitos B/fisiología , Lupus Eritematoso Sistémico/inmunología , Nefritis Lúpica/inmunología , Proteínas Serina-Treonina Quinasas/metabolismo , Células TH1/inmunología , Animales , Autoanticuerpos/metabolismo , Proliferación Celular , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Humanos , Lipopolisacáridos/inmunología , Activación de Linfocitos/genética , Ratones , Ratones Noqueados , Terapia Molecular Dirigida , FN-kappa B/metabolismo , Proteínas Serina-Treonina Quinasas/genéticaRESUMEN
Hormonal regulation of gene expression by androgen receptor (AR) is tightly controlled by many transcriptional cofactors, including pioneer factors FOXA1 and GATA2, which, however, exhibit distinct expression patterns and functional roles in prostate cancer. Here, we examined how FOXA1, GATA2 and AR crosstalk and regulate hormone-dependent gene expression in prostate cancer cells. Chromatin immunoprecipitation sequencing analysis revealed that FOXA1 reprograms both AR and GATA2 cistrome by preferably recruiting them to FKHD-containing genomic sites. By contrast, GATA2 is unable to shift AR or FOXA1 to GATA motifs. Rather, GATA2 co-occupancy enhances AR and FOXA1 binding to nearby ARE and FKHD sites, respectively. Similarly, AR increases, but not reprograms, GATA2 and FOXA1 cistromes. Concordantly, GATA2 and AR strongly enhance the transcriptional program of each other, whereas FOXA1 regulates GATA2- and AR-mediated gene expression in a context-dependent manner due to its reprogramming effects. Taken together, our data delineated for the first time the distinct mechanisms by which GATA2 and FOXA1 regulate AR cistrome and suggest that FOXA1 acts upstream of GATA2 and AR in determining hormone-dependent gene expression in prostate cancer.
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Factor de Transcripción GATA2/fisiología , Regulación Neoplásica de la Expresión Génica , Factor Nuclear 3-alfa del Hepatocito/fisiología , Neoplasias de la Próstata/genética , Receptores Androgénicos/fisiología , Línea Celular Tumoral , Humanos , Masculino , Transcripción GenéticaRESUMEN
Objective:To evaluate the clinical application of balloon dilation Eustachian tuboplasty (BET) in patients with Eustachian tube dysfunction (ETD). Method:Twenty-five patients who were diagnosed as ETD and reserved BET surgery were retrospectively analyzed in this study. Result:After 1-year's follow-up, among 25 ETD patients, the total cure rate was 55.9% and the effective rate was 85.3%. The cure rate and effective rate was 52.9% and 76.5% in the delayed opening of the ET group; 58.8% and 94.1% in the unopened group, which was higher than the other one. Conclusion:BET surgery is safe and effective in the treatment of BET patients.
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Trompa Auditiva/cirugía , Timpanoplastia , Dilatación , Enfermedades del Oído , Trompa Auditiva/fisiopatología , Humanos , Estudios RetrospectivosRESUMEN
Tamoxifen, an estrogen receptor (ER) antagonist, is the mainstay treatment of breast cancer and the development of resistance represents a major obstacle for a cure. Although long non-coding RNAs such as HOTAIR have been implicated in breast tumorigenesis, their roles in chemotherapy resistance remain largely unknown. In this study, we report that HOTAIR (HOX antisense intergenic RNA) is upregulated in tamoxifen-resistant breast cancer tissues compared to their primary counterparts. Mechanistically, HOTAIR is a direct target of ER-mediated transcriptional repression and is thus restored upon the blockade of ER signaling, either by hormone deprivation or by tamoxifen treatment. Interestingly, this elevated HOTAIR increases ER protein level and thus enhances ER occupancy on the chromatin and potentiates its downstream gene regulation. HOTAIR overexpression is sufficient to activate the ER transcriptional program even under hormone-deprived conditions. Functionally, we found that HOTAIR overexpression increases breast cancer cell proliferation, whereas its depletion significantly impairs cell survival and abolishes tamoxifen-resistant cell growth. In conclusion, the long non-coding RNA HOTAIR is directly repressed by ER and its upregulation promotes ligand-independent ER activities and contributes to tamoxifen resistance.
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Neoplasias de la Mama/tratamiento farmacológico , Antagonistas de Estrógenos/uso terapéutico , ARN Largo no Codificante/metabolismo , Receptores de Estrógenos/metabolismo , Tamoxifeno/farmacología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Resistencia a Antineoplásicos , Femenino , Humanos , ARN Largo no Codificante/genética , Receptores de Estrógenos/genética , Transducción de Señal/efectos de los fármacos , Activación Transcripcional , Regulación hacia ArribaRESUMEN
Objective:Nasopharyngeal carcinoma(NPC) is a common malignant tumor, in recent years,most of studies have found that micro RNA played an important role in the development of NPC.This study was to explore the expression level of MiR-148a and its effect on the biological functions of NPC cells.Method:The expression of MiR-148a in NPC cell line CNE2 was detected by Real-time PCR method.MTT,clone formation assay and flow cytometry were applied to detect cell proliferation and apoptosis. We predicted that EGFR was the downstream target genes of MiR-148a through the analysis of bioinformatics software. Then the expression change of EGFR was measured by Real-time PCR and Western blot.Result:Comparing with normal nasopharyngeal epithelial tissue cells,MiR-148a expression level was significantly reduced in NPC cell line CNE2.MTT,clone formation assay and flow cytometry test show that overexpression of MiR-148a can inhibit cell proliferation and promote cell apoptosis.Real-time PCR and Western blot test show that MiR 148a can reduce the expression of EGFR.Conclusion:MiR-148a can affect the proliferation and apoptosis of NPC cell,and it is likely to be involved in the development and progression of NPC.
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Carcinoma/metabolismo , Regulación Neoplásica de la Expresión Génica , MicroARNs/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Línea Celular Tumoral , Proliferación Celular , Humanos , Carcinoma NasofaríngeoRESUMEN
Knowledge of the spatial patterns of genetic variation in wild populations has significant implications for in situ conservation and the determination of conservation order. To study the levels of genetic diversity, spatial genetic structures, and genetic distances in Glycine soja, 11 natural populations in northern China were analyzed by estimating genetic coefficients using inter-simple sequence repeat (ISSR) fingerprints via mixed sampling strategies. Sixteen ISSR primers generated 98 reproducible polymorphic amplification banding patterns of 172 scored, accounting for 56.98% of the polymorphisms among the populations. The dendrogram based on Nei's genetic distance showed that distinct genetic differentiation occurred in G. soja. The Unweighted Pair-Group Method with Arithmetic Mean cluster analysis indicated two broad groups, and one contained all of the populations except three from Chengde, which formed the smaller second group. The spatial genetic structure evident in the wild soybean populations may be attributed to restricted seed dispersal and the dominant breeding system of this species. The detection of genetic structures in wild soybean populations could be a significant index for the effective conservation of many wild populations, and it could be exploited by soybean breeding programs to increase production.
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Fabaceae/genética , Polimorfismo Genético , China , FilogeniaRESUMEN
A high-efficiency combinatorial approach has been applied to rapidly build the database of composition-dependent elastic modulus and hardness of the Ti-Ta and Ti-Zr-Ta systems. A diffusion multiple of the Ti-Zr-Ta system was manufactured, then annealed at 1173K for 1800h, and water quenched to room temperature. Extensive interdiffusion among Ti, Zr and Ta has taken place. Combining nanoindentation and electron probe micro-analysis (EPMA), the elastic modulus, hardness as well as composition across the diffusion multiple were determined. The composition/elastic modulus/hardness relationship of the Ti-Ta and Ti-Zr-Ta alloys has been obtained. It was found that the elastic modulus and hardness depend strongly on the Ta and Zr content. The result can be used to accelerate the discovery/development of bio-titanium alloys for different components in implant prosthesis.
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Materiales Biocompatibles/química , Técnicas Químicas Combinatorias/métodos , Aleaciones/química , Módulo de Elasticidad , Microanálisis por Sonda Electrónica/métodos , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Nanoestructuras/química , Titanio/químicaRESUMEN
Chromosomal translocations that juxtapose the androgen-sensitive transmembrane protease, serine 2 (TMPRSS2) gene promoter to the oncogenic ETS-family transcription factor ERG result in excessive ERG overexpression in approximately 50% of prostate cancer (PCa) patients. Although numerous studies have investigated ERG-downstream genes, such studies have not attempted to examine miRNAs, which however are emerging to be important regulators of cancer. Through bioinformatics analysis of ChIP-Seq ERG data and miRNA expression profiling data we nominated miR-200c as a direct target of ERG. Experimentation of PCa cells with ERG overexpression or knockdown demonstrated that ERG directly repressed miR-200c expression by physically binding to the erythroblast transformation-specific (ETS) motif within its promoter. Consequently, miR-200c was downregulated in ERG-positive PCa, and miR-200c target gene expression was restored. In addition, the expression pattern of miR-200c target genes predicted ERG status in clinical PCa specimens. Furthermore, miR-200c was found to be important in modulating ZEB1 upregulation by ERG. Most importantly, miR-200c reconstitution fully reversed ERG-induced epithelial-to-mesenchymal transition (EMT), cell migration and invasion. Therefore, our study report miR-200c as the first miRNA target of ERG and a critical inhibitor of PCa cell motility. Therapeutic delivery of miR-200c may provide personalized treatment for patients with the molecular subtype of PCa that harbors TMPRSS2-ERG gene fusions.
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MicroARNs/genética , Proteínas de Fusión Oncogénica/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Línea Celular Tumoral , Movimiento Celular/genética , Transición Epitelial-Mesenquimal/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Humanos , Masculino , Proteínas de Fusión Oncogénica/genética , Regiones Promotoras Genéticas , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Homeobox 1 de Unión a la E-Box con Dedos de ZincRESUMEN
There is a great need to assess the harmful effects or toxicities of chemicals to which man is exposed. In the present paper, the simplified molecular input line entry specification (SMILES) representation-based string kernel, together with the state-of-the-art support vector machine (SVM) algorithm, were used to classify the toxicity of chemicals from the US Environmental Protection Agency Distributed Structure-Searchable Toxicity (DSSTox) database network. In this method, the molecular structure can be directly encoded by a series of SMILES substrings that represent the presence of some chemical elements and different kinds of chemical bonds (double, triple and stereochemistry) in the molecules. Thus, SMILES string kernel can accurately and directly measure the similarities of molecules by a series of local information hidden in the molecules. Two model validation approaches, five-fold cross-validation and independent validation set, were used for assessing the predictive capability of our developed models. The results obtained indicate that SVM based on the SMILES string kernel can be regarded as a very promising and alternative modelling approach for potential toxicity prediction of chemicals.
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Contaminantes Ambientales/química , Contaminantes Ambientales/toxicidad , Relación Estructura-Actividad Cuantitativa , Máquina de Vectores de Soporte , Fenómenos Químicos , Ecotoxicología/instrumentación , Estructura Molecular , Curva ROC , Reproducibilidad de los Resultados , Estados Unidos , United States Environmental Protection AgencyRESUMEN
Adult-to-adult living donor liver transplantation (A-A LDLT) is an effective therapeutic modality to treat patients with end-stage liver disease. The aims of this study were to identify recipient characteristics of A-A LDLT seeking to determine variables that affected patient survival. We retrospectively examined a cohort of 154 consecutive A-A LDLT recipients with end-stage liver disease in our center over 4 years. All donors volunteered to give their partial livers with written consent. There were no organs from prisoners and no prisoner subjects. The overall survivals at 1, 2, 3, 6, 12, 24, 36, and 48 months were 93.5%, 90.9%, 88.9%, 86.3%, 80%, 65.6%, 63.8%, and 63.8%, respectively. About 31 pre- and intraoperative factors were analyzed to identify correlations with posttransplant survival using the Cox proportional-hazards regression model. Recipient age, serum creatinine concentration, intraoperative blood loss, and graft-to-recipient weight ratio were significant predictors of survival after transplantation. The prognostic index model, which was calculated by combining these four prognostic values with their regression coefficients, showed a c-statistic of 0.706 (95% confidence interval [CI] = 0.621-0.792) compared with the Model for End-stage Liver Disease value of 0.546 (95% CI = 0.350-0.558). There was a significant difference between the predictions achieved with the two models (P = .012). In conclusion, selecting younger recipients, better pretransplant renal condition, reduced intraoperative blood loss, and graft-to-recipient size match appeared to be advantageous to achieve better survivals among patients undergoing A-A LDLT.
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Trasplante de Hígado , Donadores Vivos , Modelos Biológicos , Adulto , Enfermedad Hepática en Estado Terminal/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
OBJECTIVE: This study reports the preliminary experience of dual grafts living donor liver transplantation (LDLT) for patients with acute-on-chronic liver failure (AoCLF) caused by hepatitis B. METHODS: Two patients who demonstrated acute-on-chronic hepatitis B liver failure and portal hypertension with Model for End-Stage Liver Disease (MELD) scores of 42 and 37, respectively, underwent dual LDLT grafts including one right lobe without a middle hepatic vein and one left lobe because the graft-to-recipient body weight ratio of the right lobe grafts were 0.53% and 0.66%. The donors and the recipients have been followed for over 1 year. RESULTS: Mortality and operative complications were not observed in the donors or recipients. At present, the donors and recipients have returned to their daily routine. No prisoners or organs from prisoners were used to obtain these data. CONCLUSION: Dual LDLT grafts including one right lobe without the middle hepatic vein and one left lobe may be a possible therapeutic option for subjects with acute-on-chronic hepatitis B-induced liver failure.