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71.
Using benzo(a)pyrene (BaP) as a probe for aryl hydrocarbon hydroxylase (AHH) activity, differences in mixed-function oxidase (MFO) activity were observed using microspectrofluorimetry in single living cells during long term treatment with 3-methylcholanthrene (3-MC) or carbaryl. Although these two compounds differ in chemical structure, similar effects were observed in 3T3 cell populations. The results suggest that the two compounds activate the same enzymatic system and that individual cells of a supposed homogeneous cell population are not equally sensitive to xenobiotics, i.e. subpopulations were observed which have differences in AHH activity.  相似文献   
72.
When Ehrlich ascites tumour cells are induced to proliferate by serum stimulation, the ornithine decarboxylase (ODC) activity increases rapidly and reaches two to three peaks during the first 24 h. Inhibition of the first peak in ODC activity (occurring at 4 h) by adding alpha-difluoromethylornithine (DFMO) within 2 h of serum stimulation, results in maximal growth inhibition. Under these conditions, similar degrees of polyamine depletion are achieved. When DFMO is added 3 h after seeding, however, enough polyamines have already accumulated during the initial burst in ODC activity to reduce the antiproliferative effect of the drug. The antiproliferative effect is further reduced when DFMO is added 6 h after seeding. When DFMO is added 23 h after seeding, i.e. after maximal accumulation of polyamines, there is no inhibition of cell proliferation. These findings are important to consider both when designing experimental as well as clinical regimens for this drug.  相似文献   
73.
Several RNA-cleaving deoxyribozymes (DNAzymes) have been reported for efficient cleavage of purine-containing junctions, but none is able to efficiently cleave pyrimidine-pyrimidine (Pyr-Pyr) junctions. We hypothesize that a stronger Pyr-Pyr cleavage activity requires larger DNAzymes with complex structures that are difficult to isolate directly from a DNA library; one possible way to obtain such DNAzymes is to optimize DNA sequences with weak activities. To test this, we carried out an in vitro selection study to derive DNAzymes capable of cleaving an rC-T junction in a chimeric DNA/RNA substrate from DNA libraries constructed through chemical mutagenesis of five previous DNAzymes with a kobs of ∼ 0.001 min− 1 for the rC-T junction. After several rounds of selective amplification, DNAzyme descendants with a kobs of ∼ 0.1 min− 1 were obtained from a DNAzyme pool. The most efficient motif, denoted “CT10-3.29,” was found to have a catalytic core of ∼ 50 nt, larger than other known RNA-cleaving DNAzymes, and its secondary structure contains five short duplexes confined by a four-way junction. Several variants of CT10-3.29 exhibit a kobs of 0.3-1.4 min− 1 against the rC-T junction. CT10-3.29 also shows strong activity (kobs  > 0.1 min− 1) for rU-A and rU-T junctions, medium activity (> 0.01 min− 1) for rC-A and rA-T junctions, and weak activity (> 0.001 min− 1) for rA-A, rG-T, and rG-A junctions. Interestingly, a single-point mutation within the catalytic core of CT10-3.29 altered the pattern of junction specificity with a significantly decreased ability to cleave rC-T and rC-A junctions and a substantially increased ability to cleave rA-A, rA-T, rG-A, rG-T, rU-A, and rU-T junctions. This observation illustrates the intricacy and plasticity of this RNA-cleaving DNAzyme in dinucleotide junction selectivity. The current study shows that it is feasible to derive efficient DNAzymes for a difficult chemical task and reveals that DNAzymes require more complex structural solutions for such a task.  相似文献   
74.
The investigation of Encelia canescens afforded, in addition to several known compounds, four new dimeric p-hydroxyacetophenone derivatives, two epimeric chromene dimers and two epimeric mixed dimers of euparin and encecalin. Furthermore, derivatives of tremetone and of encecalin were present. The structures were elucidated hy high field 1H NMR spectroscopy.  相似文献   
75.
Indol-3yl-acetic acid was identified in extracts of sterile roots of Zeamays seedlings by means of TLC, chromogenic reactions, GLC and GC-MS.  相似文献   
76.
《Current biology : CB》2021,31(22):5037-5045.e3
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77.
目的 研究严重急性呼吸综合征冠状病毒2(SARS-CoV-2)膜蛋白对宿主细胞mRNA前体(pre-mRNA)3"非翻译区(UTR)加工的影响。方法 本研究以人肺上皮细胞系A549为模型,利用瞬时转染在细胞内过表达SARS-CoV-2膜蛋白;利用RNA-Seq测序技术及生物信息学分析方法,系统性描绘宿主细胞选择性多聚腺苷酸化(alternative polyadenylation,APA)事件;Metascape数据库对发生显著APA变化的基因进行功能富集分析;RT-qPCR验证靶基因3"UTR长度变化;蛋白质免疫印迹(Western blot)检测目的蛋白表达水平。结果 SARS-CoV-2膜蛋白外源表达后宿主细胞内共813个基因发生显著APA变化。GO和KEGG分析显示,差异APA基因广泛参与有丝分裂细胞周期、调节细胞应激等生物过程,涉及病毒感染和蛋白质加工等。从中进一步筛选出AKT1基因,在IGV软件中显示3"UTR延长;RT-qPCR验证AKT1基因的3"UTR长度变化趋势;Western blot结果显示AKT1蛋白磷酸化水平增加。结论 SARS-CoV-2膜蛋白潜在影响宿主pre-mRNA的3"UTR加工,其中参与多种病毒性生物过程的AKT1基因 3"UTR延长,且其编码的蛋白质功能在细胞内被激活。  相似文献   
78.
The liver is more prone to infections that cause fibrosis, such as steatosis, non-alcoholic steatohepatitis, hepatotoxicity, cirrhosis, and hepatocellular carcinoma. Also, Viral hepatitis is a common condition worldwide it worsens into chronic inflammation of the liver. One of the healthiest fruits is the pomegranate for the body and health, as it contains a high nutritional value of minerals, vitamins, antioxidants, so we worked on this investigation to magnify the therapeutic applications of pomegranate fruits (POF) and peel (POP) in carbon tetrachloride-injected rats (Ccl4). The experiment was carried out in a caged animal. All rats were fed a basal diet for one week before the study, and they were divided into seven groups, each with six rats. As a control negative group (C–ve), the first group sample was fed only the basal diet for 28 days. The remaining rats (n = 36) were injected with carbon tetrachloride (Ccl4). Five groups were fed varying concentrations of (5 %, 10 %, 15 % POF, 5 %, and 10 % pomegranate peel (POP)), whereas one group was diagnosed with the illness and disease, and didn't even feed the experimental diet. The results revealed significant increases in T.BIL, D.BIL, and BIL in the serum of rats injected by CC14 to induce hepatopathy compared to the healthy group (normal rats). Also, the best treatment considering the serum D.BIL was recorded for the 5 % POF.  相似文献   
79.
Osteosarcoma (OS) is a type of malignant primary bone cancer, which is highly aggressive and occurs more commonly in children and adolescents. Thus, novel potential drugs and therapeutic methods are urgently needed. In the present study, we aimed to elucidate the effects and mechanism of melatonin on OS cells to provide a potential treatment strategy for OS. The cell survival rate, cell viability, proliferation, migration, invasion and metastasis were examined by trypan blue assay, MTT, colony formation, wound healing, transwell invasion and attachment/detachment assay, respectively. The expression of relevant lncRNAs in OS cells was determined by real-time qPCR analysis. The functional roles of lncRNA JPX in OS cells were further examined by gain and loss of function assays. The protein expression was measured by western blot assay. Melatonin inhibited the cell viability, proliferation, migration, invasion and metastasis of OS cells (Saos-2, MG63 and U2OS) in a dose-dependent manner. Melatonin treatment significantly downregulated the expression of lncRNA JPX in Saos-2, MG63 and U2OS cells. Overexpression of lncRNA JPX into OS cell lines elevated the cell viability and proliferation, which was accompanied by the increased metastasis. We also found that melatonin inhibited the OS progression by suppressing the expression of lncRNA JPX via regulating the Wnt/β-catenin pathway. Our results suggested that melatonin inhibited the biological functions of OS cells by repressing the expression of lncRNA JPX through regulating the Wnt/β-catenin signalling pathway, which indicated that melatonin might be applied as a potentially useful and effective natural agent in the treatment of OS.  相似文献   
80.
Apical sodium-dependent bile acid transporter (ASBT) catalyses uphill transport of bile acids using the electrochemical gradient of Na+ as the driving force. The crystal structures of two bacterial homologues ASBTNM and ASBTYf have previously been determined, with the former showing an inward-facing conformation, and the latter adopting an outward-facing conformation accomplished by the substitution of the critical Na+-binding residue glutamate-254 with an alanine residue. While the two crystal structures suggested an elevator-like movement to afford alternating access to the substrate binding site, the mechanistic role of Na+ and substrate in the conformational isomerization remains unclear. In this study, we utilized site-directed alkylation monitored by in-gel fluorescence (SDAF) to probe the solvent accessibility of the residues lining the substrate permeation pathway of ASBTNM under different Na+ and substrate conditions, and interpreted the conformational states inferred from the crystal structures. Unexpectedly, the crosslinking experiments demonstrated that ASBTNM is a monomer protein, unlike the other elevator-type transporters, usually forming a homodimer or a homotrimer. The conformational dynamics observed by the biochemical experiments were further validated using DEER measuring the distance between the spin-labelled pairs. Our results revealed that Na+ ions shift the conformational equilibrium of ASBTNM toward the inward-facing state thereby facilitating cytoplasmic uptake of substrate. The current findings provide a novel perspective on the conformational equilibrium of secondary active transporters.  相似文献   
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