TK

TK
  • 文章类型: Journal Article
    2014年,A2/A2B死亡供体肾脏移植的选择被纳入肾脏分配系统,以改善B血型候补名单候选人的获取。尽管报告的结果非常好,整个美国的中心使用率仍然很低。这里,我们研究了在单中心实施A2/A2B方案对B血型肾移植受者的影响,其中IgG的截止滴度≤1:8,IgM的截止滴度≤1:16.
    回顾性观察性研究。
    从2019年1月1日至2022年12月,在单个中心进行已故供体肾脏移植的B血型接受者。
    根据供血者血型,比较A2/A2B与血型的相容性,对已死亡供者肾移植的受者进行分析。
    患者一年生存率,死亡审查的同种异体移植功能,主要的非功能,延迟的移植物功能,使用血清肌酐水平和1年时估计的肾小球滤过率测量的同种异体移植功能,活检证实的排斥反应,并且需要血浆置换。
    使用分类变量的Fisher检验或χ2检验以及连续变量的非参数Wilcoxon秩和检验进行A2/A2B和相容组之间的比较。
    在研究期间,共有104名B型血患者在我们中心接受了已故供体肾脏移植,49人(47.1%)接受了A2/A2B移植。与血型兼容的受者相比,A2/A2B受者的等待时间更低(57.9个月比74.7个月,P=0.01)。A2/A2B受者在心脏死亡后更有可能接受供体(24.5%vs1.8%,P<0.05)和经历移植功能延迟(65.3%vs41.8%)。在1个月时,平均血清肌酐水平或估计的肾小球滤过率没有观察到差异,3个月,肾移植后1年,急性排斥反应,或主要不起作用。
    单中心研究。小队列规模限制结果分析。
    A2/A2B方案的实施使等待B血型患者的移植量增加了83.6%,并使移植等待时间减少了22.5%,移植结果相似。
    受血者的血型是等待死者肾移植的时间的主要决定因素之一。在美国,B型血患者的肾脏等待时间最长。少数族裔占B血型候补患者的很大比例,有助于观察到肾移植率的种族差异。在这项研究中,与接受血型相容的肾脏相比,接受A2/A2B不相容的肾脏导致接受肾脏移植几乎提前18个月.接受A2/A2B肾脏的结果没有差异。
    UNASSIGNED: The option for A2/A2B deceased donor kidney transplantation was integrated into the kidney allocation system in 2014 to improve access for B blood group waitlist candidates. Despite excellent reported outcomes, center uptake has remained low across the United States. Here, we examined the effect of implementing an A2/A2B protocol using a cutoff titer of ≤1:8 for IgG and ≤1:16 for IgM on blood group B kidney transplant recipients at a single center.
    UNASSIGNED: Retrospective observational study.
    UNASSIGNED: Blood group B recipients of deceased donor kidney transplants at a single center from January 1, 2019, to December 2022.
    UNASSIGNED: Recipients of deceased donor kidney transplants were analyzed based on donor blood type with comparisons of A2/A2B versus blood group compatible.
    UNASSIGNED: One-year patient survival, death-censored allograft function, primary nonfunction, delayed graft function, allograft function as measured using serum creatinine levels and estimated glomerular filtration rate at 1 year, biopsy-proven rejection, and need for plasmapheresis.
    UNASSIGNED: Comparison between the A2/A2B and compatible groups were performed using the Fisher test or the χ2 test for categorical variables and the nonparametric Wilcoxon rank-sum test for continuous variables.
    UNASSIGNED: A total of 104 blood type B patients received a deceased donor kidney transplant at our center during the study period, 49 (47.1%) of whom received an A2/A2B transplant. Waiting time was lower in A2/A2B recipients compared with blood group compatible recipients (57.9 months vs 74.7 months, P = 0.01). A2/A2B recipients were more likely to receive a donor after cardiac death (24.5% vs 1.8%, P < 0.05) and experience delayed graft function (65.3% vs 41.8%). There were no observed differences in the average serum creatinine level or estimated glomerular filtration rate at 1 month, 3 months, and 1 year post kidney transplantation, acute rejection, or primary nonfunction.
    UNASSIGNED: Single-center study. Small cohort size limiting outcome analysis.
    UNASSIGNED: Implementation of an A2/A2B protocol increased transplant volumes of blood group B waitlisted patients by 83.6% and decreased the waiting time for transplantation by 22.5% with similar transplant outcomes.
    Recipient blood type is one of the main determinants of waiting time to receive a deceased donor kidney transplant. Patients with blood type B have some of the longest waiting times for a kidney in the United States. Minorities comprise a large percentage of blood group B waitlist patients, contributing to observed racial differences in kidney transplantation rates. In this study, accepting an A2/A2B incompatible kidney resulted in receiving a kidney transplant almost 18 months earlier compared with receiving a blood group compatible kidney. No differences in outcomes were seen by accepting A2/A2B kidneys.
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  • 文章类型: Journal Article
    天瓜基里洛威格言。(TK)是葫芦科中的雌雄异株植物,其不同性别具有单独的药用用途。我们使用Illumina高通量测序技术对TK雄性和雌性花蕾的miRNA进行测序。我们进行了生物信息学分析,miRNA鉴定,和目标基因预测从测序获得的数据,并结合先前转录组测序研究的结果进行关联分析.因此,在雌性和雄性植物之间存在80种差异表达的miRNA(DES)(雌性植物中48种上调,32种下调)。此外,预测DES中的27个新miRNA具有282个靶基因,和51个已知的miRNA预测有3418个靶基因。通过在miRNAs和靶基因之间建立调控网络,筛选出12个核心基因,包括7个miRNA和5个靶基因。其中,tkmiR157a-5p,tkmiR156c,tkmiR156_2和tkmiR156k_2共同靶向调节tkSPL18和tkSPL13B。这两个靶基因在雄性和雌性植物中特异性表达,分别,参与BR的生物合成过程,这与TK的性别分化过程密切相关。这些miRNAs的鉴定将为TK性别分化机制的分析提供参考。
    Trichosanthes kirilowii Maxim. (TK) is a dioecious plant in the Cucurbitaceae family of which different sexes have separate medicinal uses. We used Illumina high-throughput sequencing technology to sequence miRNAs from male and female flower buds of TK. We performed bioinformatics analysis, miRNA identification, and target gene prediction on the data obtained from sequencing, and association analysis was performed in combination with the results of a previous transcriptome sequencing study. As a result, there were 80 differentially expressed miRNAs (DESs) between the female and male plants (48 upregulated and 32 downregulated in female plants). Moreover, 27 novel miRNAs in DESs were predicted to have 282 target genes, and 51 known miRNAs were predicted to have 3418 target genes. By establishing a regulatory network between miRNAs and target genes, 12 core genes were screened, including 7 miRNAs and 5 target genes. Among them, tkmiR157a-5p, tkmiR156c, tkmiR156_2, and tkmiR156k_2 jointly target the regulation of tkSPL18 and tkSPL13B. These two target genes are specifically expressed in male and female plants, respectively, and are involved in the biosynthesis process of BR, which is closely related to the sex differentiation process of TK. The identification of these miRNAs will provide a reference for the analysis of the sex differentiation mechanism of TK.
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  • 文章类型: Journal Article
    脱氧胸苷三磷酸(dTTP)是DNA的重要组成部分,与dTTP合成有关的酶的缺陷会导致神经退行性疾病。例如,DTYMK突变,编码胸苷酸激酶(TMPK)的基因,导致人类严重的小头畸形。然而,这背后的机制还没有得到很好的理解。在这里,我们使用斑马鱼模型,研究(I)TMPK,dTTP合成的从头和补救途径都需要的酶,和(ii)挽救途径的胸苷激酶(TK),以了解它们在神经病理学中的作用。
    我们的研究结果表明,母体储存的dNTPs仅足以满足6个细胞分裂周期,dNTP的水平与早期胚胎发生过程中的细胞周期长度成反比。TMPK和TK活性在胚胎的细胞质中突出,幼虫和成年鱼和大脑中含有最高的TMPK活性。在早期开发中,TMPK活性从6hpf开始逐渐增加,在72hpf时观察到明显增加,TMPK活性在96hpf时达到最大水平,并保持在高水平直到144hpf。dtymk编码的Dtymk蛋白的表达与其mRNA表达和神经元发育相关,但与检测到的TMPK活性无关。然而,尽管在开发的后期检测到高TMPK活性,Dtymk蛋白检测不到.此外,在后期检测到的TMPK酶显示出与Dtymk酶相似的生化特性,但未被Dtymk特异性抗体识别。
    我们的结果表明,在早期胚胎发生过程中,dNTP的活性合成是至关重要的,而Dtymk对于神经发育是必不可少的。这得到了最近一项关于dtymk基因敲除斑马鱼的研究的支持。此外,在发育的后期有一种新的TMPK样酶表达。
    Deoxythymidine triphosphate (dTTP) is an essential building block of DNA, and defects in enzymes involved in dTTP synthesis cause neurodegenerative disorders. For instance, mutations in DTYMK, the gene coding for thymidylate kinase (TMPK), cause severe microcephaly in human. However, the mechanism behind this is not well-understood. Here we used the zebrafish model and studied (i) TMPK, an enzyme required for both the de novo and the salvage pathways of dTTP synthesis, and (ii) thymidine kinases (TK) of the salvage pathway in order to understand their role in neuropathology.
    Our findings reveal that maternal-stored dNTPs are only sufficient for 6 cell division cycles, and the levels of dNTPs are inversely correlated to cell cycle length during early embryogenesis. TMPK and TK activities are prominent in the cytosol of embryos, larvae and adult fish and brain contains the highest TMPK activity. During early development, TMPK activity increased gradually from 6 hpf and a profound increase was observed at 72 hpf, and TMPK activity reached its maximal level at 96 hpf, and remained at high level until 144 hpf. The expression of dtymk encoded Dtymk protein correlated to its mRNA expression and neuronal development but not to the TMPK activity detected. However, despite the high TMPK activity detected at later stages of development, the Dtymk protein was undetectable. Furthermore, the TMPK enzyme detected at later stages showed similar biochemical properties as the Dtymk enzyme but was not recognized by the Dtymk specific antibody.
    Our results suggest that active dNTP synthesis in early embryogenesis is vital and that Dtymk is essential for neurodevelopment, which is supported by a recent study of dtymk knockout zebrafish with neurological disorder and lethal outcomes. Furthermore, there is a novel TMPK-like enzyme expressed at later stages of development.
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  • 文章类型: Journal Article
    马立克氏病(MD)是家鸡的一种普遍存在的疾病,其病原体是Gallidα疱疹病毒2(GaHV-2),也被称为马立克病病毒(MDV)。目前,MD是通过使用MDV的减毒活株进行疫苗接种来控制的(例如,CVI988/Rispens),MDV的非致病性血清型(GaHV-3),相关Melagrid甲疱疹病毒1(MeHV-1)的非致病性菌株。生产新疫苗株的一种有吸引力的策略是通过缺失主要病毒致癌基因meq而减毒的重组MDV。然而,meq缺失的MDV变体会导致母体抗体阴性鸡的法氏囊和胸腺萎缩,由此产生的免疫抑制使它们不合适。在这里,我们详细介绍了我们的尝试,以减轻由meq缺失的MDV引起的淋巴萎缩,通过病毒胸苷激酶(tk)基因的消融进一步减弱病毒。我们证明,从meq缺失的病毒rMd5B40/Δmeq中去除病毒tk导致病毒在体外复制时减毒,并使鸡免于体内淋巴器官的萎缩。当rMd5B40/Δmeq/Δtk/GFP用作疫苗时,它对vvMDV菌株686的攻击具有保护作用,但保护作用低于CVI988/Rispens疫苗提供的保护作用。
    Marek\'s disease (MD) is a ubiquitous disease of domesticated chickens and its etiologic agent is the Gallid alphaherpesvirus 2 (GaHV-2), also known as Marek\'s disease virus (MDV). MD is currently controlled by vaccination using live attenuated strains of MDV (e.g., CVI988/Rispens), non-pathogenic serotypes of MDV (GaHV-3), or non-pathogenic strains of the related Melagrid alphaherpesvirus 1 (MeHV-1). One attractive strategy for the production of new vaccine strains is a recombinant MDV attenuated by the deletion of the major viral oncogene meq. However, meq-deleted variants of MDV cause atrophy of the bursa and thymus in maternal antibody-negative chickens, and the resulting immunosuppression makes them unsuitable. Herein we detail our attempt to mitigate the lymphoid atrophy caused by meq-deleted MDV by further attenuation of the virus through ablation of the viral thymidine kinase (tk) gene. We demonstrate that ablation of the viral tk from the meq-deleted virus rMd5B40/Δmeq resulted in a virus attenuated for replication in vitro and which spared chickens from atrophy of the lymphoid organs in vivo. When the rMd5B40/Δmeq/Δtk/GFP was used as a vaccine it was protective against challenge with the vv+MDV strain 686, but the protection was less than that provided by the CVI988/Rispens vaccine.
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  • 文章类型: Journal Article
    UNASSIGNED: To evaluate the value of total keratometry (TK) to estimate corneal power in eyes that underwent SMILE for treatment of myopia or myopic astigmatism in subgroups of low and high astigmatism.
    UNASSIGNED: The difference between preoperative and postoperative measurements of corneal power (ΔTCRP, ΔTK) was compared with the surgically induced refractive change at the corneal plane (ΔSEco) by Pearson correlation. Vector analysis of TCRP- and TK-derived astigmatism was performed to evaluate the corneal astigmatism. Single-angle plots were generated with the AstigMATIC tool for standard astigmatism vector analysis.
    UNASSIGNED: Paired t-test revealed statistically significant differences in preoperative (p = .02) and postoperative (p = .0455) measurements between TK and TCRP in the group of high-level astigmatism and the postoperative low astigmatism group (p < .01). No significant differences were found in preoperative data in the group of low-level astigmatism (p = .60). The correlation of ΔSEco and TK (low astigmatism, R2 = 0.978; high astigmatism R2 = 0.980) was stronger than the correlation of TCRP 4.0 mm and ΔSEco (low astigmatism, R2 = 0.743; high astigmatism R2 = 0.959) in both astigmatic groups. The vector analysis demonstrated nearly identical results concerning the correction index (CI) for TK and TCRP. Comparing the difference vector (DV) between both parameters, TK-derived results were closer to the optimum.
    UNASSIGNED: The findings endorse TK as a reliable measure of corneal power after SMILE in patients with low and high astigmatism.
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  • 文章类型: Journal Article
    Cyanobacteria are one of the most promising microorganisms to produce biofuels and renewable chemicals due to their oxygenic autotrophic growth properties. However, to rely on photosynthesis, which is one of the main reasons for slow growth, low carbon assimlation rate and low production, is a bottleneck. To address this challenge, optimizing the Calvin-Benson-Bassham (CBB) cycle is one of the strategies since it is the main carbon fixation pathway. In a previous study, we showed that overexpression of either aldolase (FBA), transketolase (TK), or fructose-1,6/sedoheptulose-1,7-bisphosphatase (FBP/SBPase), enzymes responsible for RuBP regeneration and vital for controlling the CBB carbon flux, led to higher production rates and titers in ethanol producing strains of Synechocystis PCC 6803. In the present study, we investigated the combined effects of the above enzymes on ethanol production in Synechocystis PCC 6803. The ethanol production of the strains overexpressing two CBB enzymes (FBA ​+ ​TK, FBP/SBPase ​+ ​FBA or FBP/SBPase ​+ ​TK) was higher than the respective control strains, overexpressing either FBA or TK. The co-overexpression of FBA and TK led to more than 9 times higher ethanol production compared to the overexpression of FBA. Compared to TK the respective increase is 4 times more ethanol production. Overexpression of FBP/SBPase in combination with FBA showed 2.5 times higher ethanol production compared to FBA. Finally, co-overexpression of FBP/SBPase and TK reached about twice the production of ethanol compared to overexpression of only TK. This study clearly demonstrates that overexpression of two selected CBB enzymes leads to significantly increased ethanol production compared to overexpression of a single CBB enzyme.
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  • 文章类型: Journal Article
    OBJECTIVE: Malignant gliomas are aggressive spinal cord tumors. In this study, we hypothesized that combination therapy using an anti-angiogenic agent, bevacizumab, and hypoxia-inducible glioblastoma-specific suicide gene could reduce tumor growth.
    METHODS: In the present study, we evaluated the effect of combination therapy using bevacizumab and pEpo-NI2-SV-TK in reducing the proliferation of C6 cells and tumor growth in the spinal cord. Spinal cord tumor was generated by the injection of C6 cells into the T5 level of the spinal cord. Complexes of branched polyethylenimine (bPEI)/pEpo-NI2-SV-TK were injected into the spinal cord tumor. Bevacizumab was then administered by an intraperitoneal injection at a dose of 7 mg/kg. The anti-cancer effects of combination therapy were analyzed by histological analyses and magnetic resonance imaging (MRI). The Basso, Beattie and Bresnahan scale scores for all of the treatment groups were recorded every other day for 15 days to assess the rat hind-limb strength.
    RESULTS: The complexes of bPEI/pEpo-NI2-SV-TK inhibited the viability of C6 cells in the hypoxia condition at 5 days after treatment with ganciclovir. Bevacizumab was decreased in the cell viability of human umbilical vein endothelial cells. Combination therapy reduced the tumor size by histological analyses and MRI. The combination therapy group showed improved hind-limb function compared to the other groups that were administered pEpo-NI2-SV-TK alone or bevacizumab alone.
    CONCLUSIONS: This study suggests that combination therapy using bevacizumab with the pEpo-NI2-SV-TK therapeutic gene could be useful for increasing its therapeutic benefits for intramedullary spinal cord tumors.
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  • 文章类型: Journal Article
    To construct plasmids with Hre2.Grp78 chimeric promoter regulating fusion gene TK/VP3 and elaborate the effects of overexpressed TK/VP3 on nasopharyngeal carcinoma cells.
    Four plasmids were constructed, including pcDNA3.1-CMV-TK/VP3, pcDNA3.1-Hre2.TK/VP3, pcDNA3.1-Grp78.TK/VP3, and pcDNA3.1-Hre2.Grp78.TK/VP3. The human nasopharyngeal carcinoma cell line HNE1 cells were transfected with the 4 plasmids, respectively. Cell viabilities were evaluated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and apoptosis was conducted using flow cytometry analysis. The expression of TK, VP3, Grp78, and hypoxia-inducible factor 1α and apoptosis-related proteins was determined by real-time quantitative polymerase chain reaction and Western blotting.
    The recombinant plasmids that could steadily overexpress TK and VP3 were successfully constructed. Expression of TK and VP3 in cells transfected with pcDNA3.1-Hre2.TK/VP3 and pcDNA3.1-Grp78.TK/VP3 was significantly higher than pcDNA3.1-CMV-TK/VP3, and expression in cells transfected with pcDNA3.1-Hre2.Grp78.TK/VP3 was the highest. Under glucose deprivation or hypoxia condition, Grp78 or hypoxia-inducible factor 1α was overexpressed so that expression of TK and VP3 was significantly upregulated, which could further inhibit cell proliferation and enhance cell apoptosis.
    We successfully constructed 4 plasmids with Hre2.Grp78 chimeric promoter regulating fusion gene TK/VP3, which could significantly inhibit the proliferation as well as enhance the apoptosis of nasopharyngeal carcinoma cells under glucose deprivation or hypoxia condition.
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  • 文章类型: Journal Article
    The use of toxicokinetic (TK) data is becoming more prevalent in the evaluation of food ingredient safety as more TK information is being incorporated in safety data packages. Data demonstrating \"1) the extent of absorption, 2) tissue distribution, 3) pathways and rates of metabolism, and 4) rate(s) of elimination\" of food ingredients and their metabolites of intermediate and high toxicological potential may be useful for planning and designing toxicity studies, selecting doses for toxicity studies, addressing species differences, and understanding the potential modes of action to evaluate their safety. TK data reported in the literature or generated from mechanistic TK studies can be analyzed using mathematical methods, including compartment and noncompartment TK methods, whose predictions can enhance interpretation of observed effects. Because of recent advancements, several approaches have been developed to improve sensitivity of analyses of available TK data and reduce uncertainty for evaluating safety of food ingredients. An example of advanced TK methods is physiologically-based TK (PBTK) modeling that incorporates physiological/biochemical parameters into a TK framework to predict internal exposure. In this review, we discuss the utility of some TK methods and explore their relevance and potential value for food ingredient safety evaluation. We also describe the strengths and limitations of these TK methods and discuss current challenges and opportunities for expanding their application for evaluating safety of food ingredients. This review represents a state of science report, and not a guidance document, on the utility and relevance of TK methods for the safety evaluation of food ingredients.
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  • 文章类型: Journal Article
    The Calvin-Benson-Bassham (CBB) cycle is the main pathway to fix atmospheric CO2 and store energy in carbon bonds, forming the precursors of most primary and secondary metabolites necessary for life. Speeding up the CBB cycle theoretically has positive effects on the subsequent growth and/or the end metabolite(s) production. Four CBB cycle enzymes, ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), fructose-1,6/sedoheptulose-1,7-bisphosphatase (FBP/SBPase), transketolase (TK) and aldolase (FBA) were selected to be co-overexpressed with the ethanol synthesis enzymes pyruvate decarboxylase (PDC) and alcohol dehydrogenase (ADH) in the cyanobacterium Synechocystis PCC 6803. An inducible promoter, PnrsB, was used to drive PDC and ADH expression. When PnrsB was induced and cells were cultivated at 65 µmol photons m-2 s-1, the RuBisCO-, FBP/SBPase-, TK-, and FBA-expressing strains produced 55%, 67%, 37% and 69% more ethanol and 7.7%, 15.1%, 8.8% and 10.1% more total biomass (the sum of dry cell weight and ethanol), respectively, compared to the strain only expressing the ethanol biosynthesis pathway. The ethanol to total biomass ratio was also increased in CBB cycle enzymes overexpressing strains. This study experimentally demonstrates that using the cells with enhanced carbon fixation, when the product synthesis pathway is not the main bottleneck, can significantly increase the generation of a product (exemplified with ethanol), which acts as a carbon sink.
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