Objective Nephrolithiasis is one of the most common disorders of the urinary tract. The aim of this study was to examine a possible relationship between DNase Ⅰ/Ⅱ activity and E3 SUMO-protein ligase NSE2 in the sera...Objective Nephrolithiasis is one of the most common disorders of the urinary tract. The aim of this study was to examine a possible relationship between DNase Ⅰ/Ⅱ activity and E3 SUMO-protein ligase NSE2 in the sera of nephrolithiasis patients to evaluate the possibility of a new biomarker for evaluating kidney damage. Methods Sixty nephrolithiasis patients and 50 control patients were enrolled in a case-control study. Their blood urea, creatinine, protein levels and DNase Ⅰ/Ⅱ activity levels were measured by spectrometry. Serum NSMCE2 levels were measured by ELISA. Blood was collected from patients of the government health clinics in Kuantan-Pahang and fulfilled the inclusion criteria. Results The result indicated that mean levels of sera NSMCE2 have a significantly increase（P〈0.01） in patients compared to control group. Compared with control subjects, activities and specific activities of serum DNase Ⅰ and Ⅱ were significantly elevated in nephrolithiasis patients（P〈0.01）. Conclusion This study suggests that an increase in serum concentrations of DNase Ⅰ/Ⅱ and E3 SUMO-protein ligase NSE2 level can be used as indicators for the diagnosis of kidney injury in patients with nephrolithiasis.展开更多
为了筛选靶向DNA连接酶Ⅳ的抑制剂以实现更有效的基因定点插入,采用分子对接技术筛选出与前期研究中靶向DNA连接酶Ⅳ的抑制剂SCR7作用类似的小分子化合物。筛选到与化合物库一致的nocodazole、Fisetin和Methylene blue 3个小分子化合物...为了筛选靶向DNA连接酶Ⅳ的抑制剂以实现更有效的基因定点插入,采用分子对接技术筛选出与前期研究中靶向DNA连接酶Ⅳ的抑制剂SCR7作用类似的小分子化合物。筛选到与化合物库一致的nocodazole、Fisetin和Methylene blue 3个小分子化合物,通过用MSTN基因T11位点序列截断的Firefly Luciferase荧光素酶报告载体结合CRISPR/Cas9-gRNA-T11载体共转细胞,并结合不同的小分子化合物处理。结果表明,没有用小分子化合物处理时,萤火虫荧光素酶被截断的位置发生NHEJ修复,不能得到大量有活性的萤火虫荧光素酶;经过小分子化合物处理,抑制了细胞内的NHEJ,提高了HDR效率,能得到大量有活性的萤火虫荧光素酶。使用nocodazole、Methylene blue和Fisetin处理后的萤火虫荧光素酶检测结果65256.3、53713和77058.3分别是SCR7处理后的萤火虫荧光素酶检测结果41905.3的1.6、1.3和1.8倍,是没有SCR7处理后的萤火虫荧光素酶检测结果10120的6.4、5.3和7.6倍。证明所用的筛选策略正确,所筛选出的小分子化合物是具有DNA ligaseⅣ抑制活性的抑制剂,为后续研究奠定了基础。展开更多
Ovarian cancer(OC)is the sixth most common cancer and the seventh cause of death from cancer in women.The etiology and the ovarian carcinogenesis still need clarification although ovulation may be determinant due to i...Ovarian cancer(OC)is the sixth most common cancer and the seventh cause of death from cancer in women.The etiology and the ovarian carcinogenesis still need clarification although ovulation may be determinant due to its carcinogenic role in ovarian surface epithelium.The link between ovarian carcinogenesis and DNA repair is well established and it became clear that alterations in DNA damage response may affect the risk to develop OC.Polymorphisms are variations in the DNA sequence that exist in normal individuals of a population and are capable to change,among other mechanisms,the balance between DNA damage and cellular response.Consequently,genetic variability of the host has a great role in the development,progression and consequent prognosis of the oncologic patient as well as in treatment response.Standard treatment for OC patients is based on cytoreductive surgery,followed by chemotherapy with a platinum agent and a taxane.Although 80%of the patients respond to the first-line therapy,the development of resistance is common although the mechanisms underlying therapy failure remain mostly unknown.Because of their role in oncology,enzymes involved in the DNA repair pathways,like DNA Ligase IV(LIG4),became attractive study targets.It has been reported that variations in LIG4 activity can lead to a hyper-sensitivity to DNA damage,deregulation of repair and apoptosis mechanisms,affecting the susceptibility to cancer development and therapy response.To overcome resistance mechanisms,several investigations have been made and the strategy to target crucial molecular pathways,such as DNA repair,became one of the important areas in clinical oncology.This review aims to elucidate the link between DNA repair and OC,namely which concerns the role of LIG4 enzyme,and how genetic polymorphisms in LIG4 gene can modulate the activity of the enzyme and affect the ovarian carcinogenesis and treatment response.Moreover,we try to understand how LIG4 inhibition can be a potential contributor for the development of new cancer treatment strategies.展开更多
Nonhomologous DNA end joining （NHEJ） is the primary pathway for repair of double-strand DNA breaks in human cells and in multicellular eukaryotes. The causes of double-strand breaks often fragment the DNA at the sit...Nonhomologous DNA end joining （NHEJ） is the primary pathway for repair of double-strand DNA breaks in human cells and in multicellular eukaryotes. The causes of double-strand breaks often fragment the DNA at the site of damage, resulting in the loss of information there. NHEJ does not restore the lost information and may resect additional nucleotides during the repair process. The ability to repair a wide range of overhang and damage configurations reflects the flexibility of the nuclease, polymerases, and ligase of NHEJ. The flexibility of the individual components also explains the large number of ways in which NHEJ can repair any given pair of DNA ends. The loss of information locally at sites of NHEJ repair may contribute to cancer and aging, but the action by NHEJ ensures that entire segments of chromosomes are not lost.展开更多
Cancer therapy with heavy ion bearns has now been progressed by America,Japan,Germany and some other countries.It becomes the most advanced and efficacious new cancer radiotherapy owing its high LET and RBE,low OER,es...Cancer therapy with heavy ion bearns has now been progressed by America,Japan,Germany and some other countries.It becomes the most advanced and efficacious new cancer radiotherapy owing its high LET and RBE,low OER,especialy forming Bragg peak at the end of the tracks of the charged particles.DNA展开更多
【目的】探明地方鸡种与引进鸡种遗传多态性特点,探讨COⅠ这一特定基因的特定区段作为DNA条形码在识别鸡种方面的可行性和有效性。【方法】以13个中国地方鸡种和2个国外引进品种为研究对象,利用DNA测序技术测定了线粒体细胞色素C氧化酶...【目的】探明地方鸡种与引进鸡种遗传多态性特点,探讨COⅠ这一特定基因的特定区段作为DNA条形码在识别鸡种方面的可行性和有效性。【方法】以13个中国地方鸡种和2个国外引进品种为研究对象,利用DNA测序技术测定了线粒体细胞色素C氧化酶亚基Ⅰ(cytochrome c oxidaseⅠ,COⅠ)基因部分序列。【结果】选择的这段COⅠ基因序列有38个突变位点,15个鸡种单倍型多样度平均为0.963,核苷酸多样度平均为0.00518,其中引进鸡种明显低于地方鸡种(除藏鸡外);15个鸡种品种间Kimura双参数遗传距离为0.056%—0.917%,种内遗传距离为0—0.346%,15个鸡种的DNA分类和形态学分类基本一致,引进鸡种与地方鸡种分歧较远。【结论】利用线粒体细胞色素C氧化酶Ⅰ(COⅠ)这一特定基因的特定区段来做DNA条形编码的基础,进行不同鸡品种鉴定,具有可行性和有效性。展开更多
基金supported by grants from the International Islamic University Malaysia,the research management centre(No.IIUM/504/5/29/1)
文摘Objective Nephrolithiasis is one of the most common disorders of the urinary tract. The aim of this study was to examine a possible relationship between DNase Ⅰ/Ⅱ activity and E3 SUMO-protein ligase NSE2 in the sera of nephrolithiasis patients to evaluate the possibility of a new biomarker for evaluating kidney damage. Methods Sixty nephrolithiasis patients and 50 control patients were enrolled in a case-control study. Their blood urea, creatinine, protein levels and DNase Ⅰ/Ⅱ activity levels were measured by spectrometry. Serum NSMCE2 levels were measured by ELISA. Blood was collected from patients of the government health clinics in Kuantan-Pahang and fulfilled the inclusion criteria. Results The result indicated that mean levels of sera NSMCE2 have a significantly increase（P〈0.01） in patients compared to control group. Compared with control subjects, activities and specific activities of serum DNase Ⅰ and Ⅱ were significantly elevated in nephrolithiasis patients（P〈0.01）. Conclusion This study suggests that an increase in serum concentrations of DNase Ⅰ/Ⅱ and E3 SUMO-protein ligase NSE2 level can be used as indicators for the diagnosis of kidney injury in patients with nephrolithiasis.
基金Supported by Research Department of Portuguese League against Cancer(NRNorte)and Minister of Health of Portugal(CFICS-45/2007)
文摘Ovarian cancer(OC)is the sixth most common cancer and the seventh cause of death from cancer in women.The etiology and the ovarian carcinogenesis still need clarification although ovulation may be determinant due to its carcinogenic role in ovarian surface epithelium.The link between ovarian carcinogenesis and DNA repair is well established and it became clear that alterations in DNA damage response may affect the risk to develop OC.Polymorphisms are variations in the DNA sequence that exist in normal individuals of a population and are capable to change,among other mechanisms,the balance between DNA damage and cellular response.Consequently,genetic variability of the host has a great role in the development,progression and consequent prognosis of the oncologic patient as well as in treatment response.Standard treatment for OC patients is based on cytoreductive surgery,followed by chemotherapy with a platinum agent and a taxane.Although 80%of the patients respond to the first-line therapy,the development of resistance is common although the mechanisms underlying therapy failure remain mostly unknown.Because of their role in oncology,enzymes involved in the DNA repair pathways,like DNA Ligase IV(LIG4),became attractive study targets.It has been reported that variations in LIG4 activity can lead to a hyper-sensitivity to DNA damage,deregulation of repair and apoptosis mechanisms,affecting the susceptibility to cancer development and therapy response.To overcome resistance mechanisms,several investigations have been made and the strategy to target crucial molecular pathways,such as DNA repair,became one of the important areas in clinical oncology.This review aims to elucidate the link between DNA repair and OC,namely which concerns the role of LIG4 enzyme,and how genetic polymorphisms in LIG4 gene can modulate the activity of the enzyme and affect the ovarian carcinogenesis and treatment response.Moreover,we try to understand how LIG4 inhibition can be a potential contributor for the development of new cancer treatment strategies.
文摘Nonhomologous DNA end joining （NHEJ） is the primary pathway for repair of double-strand DNA breaks in human cells and in multicellular eukaryotes. The causes of double-strand breaks often fragment the DNA at the site of damage, resulting in the loss of information there. NHEJ does not restore the lost information and may resect additional nucleotides during the repair process. The ability to repair a wide range of overhang and damage configurations reflects the flexibility of the nuclease, polymerases, and ligase of NHEJ. The flexibility of the individual components also explains the large number of ways in which NHEJ can repair any given pair of DNA ends. The loss of information locally at sites of NHEJ repair may contribute to cancer and aging, but the action by NHEJ ensures that entire segments of chromosomes are not lost.
文摘Cancer therapy with heavy ion bearns has now been progressed by America,Japan,Germany and some other countries.It becomes the most advanced and efficacious new cancer radiotherapy owing its high LET and RBE,low OER,especialy forming Bragg peak at the end of the tracks of the charged particles.DNA
文摘【目的】探明地方鸡种与引进鸡种遗传多态性特点,探讨COⅠ这一特定基因的特定区段作为DNA条形码在识别鸡种方面的可行性和有效性。【方法】以13个中国地方鸡种和2个国外引进品种为研究对象,利用DNA测序技术测定了线粒体细胞色素C氧化酶亚基Ⅰ(cytochrome c oxidaseⅠ,COⅠ)基因部分序列。【结果】选择的这段COⅠ基因序列有38个突变位点,15个鸡种单倍型多样度平均为0.963,核苷酸多样度平均为0.00518,其中引进鸡种明显低于地方鸡种(除藏鸡外);15个鸡种品种间Kimura双参数遗传距离为0.056%—0.917%,种内遗传距离为0—0.346%,15个鸡种的DNA分类和形态学分类基本一致,引进鸡种与地方鸡种分歧较远。【结论】利用线粒体细胞色素C氧化酶Ⅰ(COⅠ)这一特定基因的特定区段来做DNA条形编码的基础,进行不同鸡品种鉴定,具有可行性和有效性。
