We have found that the expression of ring finger and WD repeat domain 3(RFWD3)is significantly higher in unpaired and paired hepatocellular carcinoma(HCC)tissues than in normal tissues.Moreover,this expression has a s...We have found that the expression of ring finger and WD repeat domain 3(RFWD3)is significantly higher in unpaired and paired hepatocellular carcinoma(HCC)tissues than in normal tissues.Moreover,this expression has a significant correlation with the infiltration level of 14 immune cell types and when the detected RFWD3 expression levels were grouped as high and low,a prominent difference was revealed for overall survival,disease-specific survival,and progression-free interval.Through statistical analysis(univariate Cox),we were also able to identify RFWD3 as an independent prognostic element for HCC,with RFWD3 having an ability to accurately predict HCC prognosis(area under the curve of 0.863).Finally,we have generated prognostic nomograms for probabilities of 1-,3-and 5-year overall survival in HCC via integrating the factors of age,pathologic stage,alpha-fetoprotein level,and RFWD3 expression.展开更多
目的观察肝豆灵片联合推拿手法治疗痰瘀互结型肝豆状核变性(WD)肌张力障碍的临床疗效。方法选取于2021年9月-2023年2月安徽中医药大学第一附属医院脑病科住院治疗的肌张力障碍的痰瘀互结型WD患者40例,随机分为对照组和观察组,每组各20...目的观察肝豆灵片联合推拿手法治疗痰瘀互结型肝豆状核变性(WD)肌张力障碍的临床疗效。方法选取于2021年9月-2023年2月安徽中医药大学第一附属医院脑病科住院治疗的肌张力障碍的痰瘀互结型WD患者40例,随机分为对照组和观察组,每组各20例。对照组采用二巯丙磺酸钠祛铜联合推拿手法治疗,观察组在对照组的基础上加用肝豆灵片治疗,8 d 1个疗程,共治疗4个疗程。治疗前后采用日常生活能力量表(ADL)、改良Ashworth肌张力分级评分、中医证候积分、有效率评价两组治疗效果。结果治疗后两组ADL量表评分均高于治疗前(P<0.01),改良Ashworth肌张力分级评分、中医证候积分均低于治疗前(P<0.01),观察组治疗后ADL量表评分高于对照组(P<0.01),Ashworth肌张力分级评分低于对照组(P<0.05),中医证候分低于对照组(P<0.01),观察组临床疗效高于对照组,差异无统计学意义(P>0.05)。结论肝豆灵片联合推拿手法可有效改善痰瘀互结型WD患者肌张力障碍,提高患者的生活质量,为临床治疗带来新思路。展开更多
今年初,西数(WD)更新了My Book台式硬盘产品线,推出My Book台式硬盘22TB版本,容量得到进一步提升,覆盖到更多用户群体。WD My Book 22TB版本仍旧采用单盘设计,具有小体积、大容量等特点,实际传输速度和综合体验怎样?消费电子编辑部拿到...今年初,西数(WD)更新了My Book台式硬盘产品线,推出My Book台式硬盘22TB版本,容量得到进一步提升,覆盖到更多用户群体。WD My Book 22TB版本仍旧采用单盘设计,具有小体积、大容量等特点,实际传输速度和综合体验怎样?消费电子编辑部拿到了这款产品,我们一起来了解下。展开更多
BACKGROUND Hepatocellular carcinoma(HCC)exhibits high invasiveness and mortality rates,and the molecular mechanisms of HCC have gained increasing research interest.The abnormal DNA damage response has long been recogn...BACKGROUND Hepatocellular carcinoma(HCC)exhibits high invasiveness and mortality rates,and the molecular mechanisms of HCC have gained increasing research interest.The abnormal DNA damage response has long been recognized as one of the important factors for tumor occurrence and development.Recent studies have shown the potential of the protein RING finger and WD repeat domain 3(RFWD3)that positively regulates p53 stability in response to DNA damage as a therapeutic target in cancers.AIM To investigate the relationship between HCC and RFWD3 in vitro and in vivo and explored the underlying molecular signalling transduction pathways.METHODS RFWD3 gene expression was analyzed in HCC tissues and adjacent normal tissues.Lentivirus was used to stably knockdown RFWD3 expression in HCC cell lines.After verifying the silencing efficiency,Celigo/cell cycle/apoptosis and MTT assays were used to evaluate cell proliferation and apoptosis.Subsequently,cell migration and invasion were assessed by wound healing and transwell assays.In addition,transduced cells were implanted subcutaneously and injected into the tail vein of nude mice to observe tumor growth and metastasis.Next,we used lentiviral-mediated rescue of RFWD3 shRNA to verify the phenotype.Finally,the microarray,ingenuity pathway analysis,and western blot analysis were used to analyze the regulatory network underlying HCC.RESULTS Compared with adjacent tissues,RFWD3 expression levels were significantly higher in clinical HCC tissues and correlated with tumor size and TNM stage(P<0.05),which indicated a poor prognosis state.RFWD3 silencing in BEL-7404 and HCC-LM3 cells increased apoptosis,decreased growth,and inhibited the migration in shRNAi cells compared with those in shCtrl cells(P<0.05).Furthermore,the in vitro results were supported by the findings of the in vivo experiments with the reduction of tumor cell invasion and migration.Moreover,the rescue of RFWD3 shRNAi resulted in the resumption of invasion and metastasis in HCC cell lines.Finally,gene expression profiling and subsequent experimental verification revealed that RFWD3 might influence the proliferation and metastasis of HCC via the Wnt/β-catenin signalling pathway.CONCLUSION We provide evidence for the expression and function of RFWD3 in HCC.RFWD3 affects the prognosis,proliferation,invasion,and metastasis of HCC by regulating the Wnt/β-catenin signalling pathway.展开更多
In this study, we isolated a WD40-repeat gene from Artemisia annua glandular trichomes. This gene shows 69.97% sequence similarity to Arabidopsis TTG1 at aminoacid level. Sub-cellular localization study shows that AaW...In this study, we isolated a WD40-repeat gene from Artemisia annua glandular trichomes. This gene shows 69.97% sequence similarity to Arabidopsis TTG1 at aminoacid level. Sub-cellular localization study shows that AaWD40 protein diffuses in both cell nucleus and cytosol. The correct nuclear localization of AaWD40 was observed when co-expressed with AabHLH, a putative A. thaliana AtTTG1 homologue cloned from Artemisia annua glandular trichomes. When AaWD40 gene was ectopically over expressed in Arabidopsis transparent testa glabrous1-1 (ttg1-1) mutants of A. thaliana, PAs production in seeds was restored, and the trichomeless phenotypes of mutant were rescued. Real-time PCR analysis results revealed that ETC1, CPC, TTG2 and BAN (the downstream targets of AtTTG1 depend on regulatory complex), which regulate the epidermal differentiation and anthocyanin biosynthesis were differentially expressed as a result of AaWD40 over expression. Furthermore, the CLV1, CLV2, CLV3 and WUS, which are required to maintain the stem-cell niche of Arabidopsis shoot apex, were also modulated by AaWD40 and Arabidopsis TTG1. The transcriptions of AP2/ERF, bHLH, MYB, WRKY and NACs family proteins, which are mostly involved in defense, stress response and development regulation, were remarkably modulated by AaWD40 over expression. We hypothesize that WD40 repeat proteins act as a crucial factor in regulating a wide variety of cellular functions in A. thaliana.展开更多
文摘We have found that the expression of ring finger and WD repeat domain 3(RFWD3)is significantly higher in unpaired and paired hepatocellular carcinoma(HCC)tissues than in normal tissues.Moreover,this expression has a significant correlation with the infiltration level of 14 immune cell types and when the detected RFWD3 expression levels were grouped as high and low,a prominent difference was revealed for overall survival,disease-specific survival,and progression-free interval.Through statistical analysis(univariate Cox),we were also able to identify RFWD3 as an independent prognostic element for HCC,with RFWD3 having an ability to accurately predict HCC prognosis(area under the curve of 0.863).Finally,we have generated prognostic nomograms for probabilities of 1-,3-and 5-year overall survival in HCC via integrating the factors of age,pathologic stage,alpha-fetoprotein level,and RFWD3 expression.
文摘目的观察肝豆灵片联合推拿手法治疗痰瘀互结型肝豆状核变性(WD)肌张力障碍的临床疗效。方法选取于2021年9月-2023年2月安徽中医药大学第一附属医院脑病科住院治疗的肌张力障碍的痰瘀互结型WD患者40例,随机分为对照组和观察组,每组各20例。对照组采用二巯丙磺酸钠祛铜联合推拿手法治疗,观察组在对照组的基础上加用肝豆灵片治疗,8 d 1个疗程,共治疗4个疗程。治疗前后采用日常生活能力量表(ADL)、改良Ashworth肌张力分级评分、中医证候积分、有效率评价两组治疗效果。结果治疗后两组ADL量表评分均高于治疗前(P<0.01),改良Ashworth肌张力分级评分、中医证候积分均低于治疗前(P<0.01),观察组治疗后ADL量表评分高于对照组(P<0.01),Ashworth肌张力分级评分低于对照组(P<0.05),中医证候分低于对照组(P<0.01),观察组临床疗效高于对照组,差异无统计学意义(P>0.05)。结论肝豆灵片联合推拿手法可有效改善痰瘀互结型WD患者肌张力障碍,提高患者的生活质量,为临床治疗带来新思路。
基金Supported by National Natural Science Foundation of China,No.82172944 and No.81900558Co-operation Research Plan of Medical Science and Technology of Henan Province,No.LHGJ20190149the Key Scientific Research Projects of Universities of Henan Province,No.21A320052。
文摘BACKGROUND Hepatocellular carcinoma(HCC)exhibits high invasiveness and mortality rates,and the molecular mechanisms of HCC have gained increasing research interest.The abnormal DNA damage response has long been recognized as one of the important factors for tumor occurrence and development.Recent studies have shown the potential of the protein RING finger and WD repeat domain 3(RFWD3)that positively regulates p53 stability in response to DNA damage as a therapeutic target in cancers.AIM To investigate the relationship between HCC and RFWD3 in vitro and in vivo and explored the underlying molecular signalling transduction pathways.METHODS RFWD3 gene expression was analyzed in HCC tissues and adjacent normal tissues.Lentivirus was used to stably knockdown RFWD3 expression in HCC cell lines.After verifying the silencing efficiency,Celigo/cell cycle/apoptosis and MTT assays were used to evaluate cell proliferation and apoptosis.Subsequently,cell migration and invasion were assessed by wound healing and transwell assays.In addition,transduced cells were implanted subcutaneously and injected into the tail vein of nude mice to observe tumor growth and metastasis.Next,we used lentiviral-mediated rescue of RFWD3 shRNA to verify the phenotype.Finally,the microarray,ingenuity pathway analysis,and western blot analysis were used to analyze the regulatory network underlying HCC.RESULTS Compared with adjacent tissues,RFWD3 expression levels were significantly higher in clinical HCC tissues and correlated with tumor size and TNM stage(P<0.05),which indicated a poor prognosis state.RFWD3 silencing in BEL-7404 and HCC-LM3 cells increased apoptosis,decreased growth,and inhibited the migration in shRNAi cells compared with those in shCtrl cells(P<0.05).Furthermore,the in vitro results were supported by the findings of the in vivo experiments with the reduction of tumor cell invasion and migration.Moreover,the rescue of RFWD3 shRNAi resulted in the resumption of invasion and metastasis in HCC cell lines.Finally,gene expression profiling and subsequent experimental verification revealed that RFWD3 might influence the proliferation and metastasis of HCC via the Wnt/β-catenin signalling pathway.CONCLUSION We provide evidence for the expression and function of RFWD3 in HCC.RFWD3 affects the prognosis,proliferation,invasion,and metastasis of HCC by regulating the Wnt/β-catenin signalling pathway.
文摘In this study, we isolated a WD40-repeat gene from Artemisia annua glandular trichomes. This gene shows 69.97% sequence similarity to Arabidopsis TTG1 at aminoacid level. Sub-cellular localization study shows that AaWD40 protein diffuses in both cell nucleus and cytosol. The correct nuclear localization of AaWD40 was observed when co-expressed with AabHLH, a putative A. thaliana AtTTG1 homologue cloned from Artemisia annua glandular trichomes. When AaWD40 gene was ectopically over expressed in Arabidopsis transparent testa glabrous1-1 (ttg1-1) mutants of A. thaliana, PAs production in seeds was restored, and the trichomeless phenotypes of mutant were rescued. Real-time PCR analysis results revealed that ETC1, CPC, TTG2 and BAN (the downstream targets of AtTTG1 depend on regulatory complex), which regulate the epidermal differentiation and anthocyanin biosynthesis were differentially expressed as a result of AaWD40 over expression. Furthermore, the CLV1, CLV2, CLV3 and WUS, which are required to maintain the stem-cell niche of Arabidopsis shoot apex, were also modulated by AaWD40 and Arabidopsis TTG1. The transcriptions of AP2/ERF, bHLH, MYB, WRKY and NACs family proteins, which are mostly involved in defense, stress response and development regulation, were remarkably modulated by AaWD40 over expression. We hypothesize that WD40 repeat proteins act as a crucial factor in regulating a wide variety of cellular functions in A. thaliana.
