Rho-GTPase Effector ROCK Phosphorylates Cofilin in Actin-Meditated Cytokinesis During Mouse Oocyte Meiosis

Duan, Xing,Jun-Liu,Dai, Xiao-Xin,Liu, Hong-Lin,Cui, Xiang-Shun,Kim, Nam-Hyung,Wang, Zhen-Bo,Qiang-Wang,Sun, Shao-Chen Society for the Study of Reproduction [etc.] 2014 BIOLOGY OF REPRODUCTION Vol.90 No.2

During oocyte meiosis, a spindle forms in the central cytoplasm and migrates to the cortex. Subsequently, the oocyte extrudes a small body and forms a highly polarized egg; this process is regulated primarily by actin. ROCK is a Rho-GTPase effector that is involved in various cellular functions, such as stress fiber formation, cell migration, tumor cell invasion, and cell motility. In this study, we investigated possible roles for ROCK in mouse oocyte meiosis. ROCK was localized around spindles after germinal vesicle breakdown and was colocalized with cytoplasmic actin and mitochondria. Disrupting ROCK activity by RNAi or an inhibitor resulted in cell cycle progression and polar body extrusion failure. Time-lapse microscopy showed that this may have been due to spindle migration and cytokinesis defects, as chromosomes segregated but failed to extrude a polar body and then realigned. Actin expression at oocyte membranes and in cytoplasm was significantly decreased after these treatments. Actin caps were also disrupted, which was confirmed by a failure to form cortical granule-free domains. The mitochondrial distribution was also disrupted, which indicated that mitochondria were involved in the ROCK-mediated actin assembly. In addition, the phosphorylation levels of Cofilin, a downstream molecule of ROCK, decreased after disrupting ROCK activity. Thus, our results indicated that a ROCK-Cofilinactin pathway regulated meiotic spindle migration and cytokinesis during mouse oocyte maturation.

Chk2 Regulates Cell Cycle Progression during Mouse Oocyte Maturation and Early Embryo Development

Dai, Xiao-Xin,Duan, Xing,Liu, Hong-Lin,Cui, Xiang-Shun,Kim, Nam-Hyung,Sun, Shao-Chen Korean Society for Molecular and Cellular Biology 2014 Molecules and cells Vol.37 No.2

As a tumor suppressor homologue during mitosis, Chk2 is involved in replication checkpoints, DNA repair, and cell cycle arrest, although its functions during mouse oocyte meiosis and early embryo development remain uncertain. We investigated the functions of Chk2 during mouse oocyte maturation and early embryo development. Chk2 exhibited a dynamic localization pattern; Chk2 expression was restricted to germinal vesicles at the germinal vesicle (GV) stage, was associated with centromeres at pro-metaphase I (Pro-MI), and localized to spindle poles at metaphase I (MI). Disrupting Chk2 activity resulted in cell cycle progression defects. First, inhibitor-treated oocytes were arrested at the GV stage and failed to undergo germinal vesicle breakdown (GVBD); this could be rescued after Chk2 inhibition release. Second, Chk2 inhibition after oocyte GVBD caused MI arrest. Third, the first cleavage of early embryo development was disrupted by Chk2 inhibition. Additionally, in inhibitor-treated oocytes, checkpoint protein Bub3 expression was consistently localized at centromeres at the MI stage, which indicated that the spindle assembly checkpoint (SAC) was activated. Moreover, disrupting Chk2 activity in oocytes caused severe chromosome misalignments and spindle disruption. In inhibitor-treated oocytes, centrosome protein ${\gamma}$-tubulin and Polo-like kinase 1 (Plk1) were dissociated from spindle poles. These results indicated that Chk2 regulated cell cycle progression and spindle assembly during mouse oocyte maturation and early embryo development.

Phase II Study on Dose Escalating Schedule of Paclitaxel Concurrent with Radiotherapy in Treating Patients with Locally Advanced Non-small Cell Lung Cancer

Cui, Lin,Liu, Xing-Xiang,Jiang, Yong,Liu, Jian-Jun,Zhou, Xiang-Rong,He, Xue-Jun,Chen, Jue,Huang, Xin-En Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.4

Objective: To evaluate clinical efficacy of a dose escalating schedule of paclitaxel concurrent with radiotherapy in treating patients with locally advanced non-small cell lung (NSCLC). Methods: Patients with locally advanced NSCLC were treated with conventional fractionated radiotherapy or three dimensional conformal radiotherapy (3 DCRT), concurrently with a dose escalating schedule of paclitaxel. All patients were divided into three groups, A with paclitaxel $30mg/m^2$, B with paclitaxel $60mg/m^2$ and C with paclitaxel $90mg/m^2$. Paclitaxel was repeated every week for a total of 4 or 6 weeks. Results: Among 109 patients, response rates were 68.8%, 71.1% and 71.8% (p>0.05) for group A (n=32), B (n=38), and C (n=39) respectively. Accordingly, disease control rates were 81.3%, 81.6% and 82.1% (p>0.05). Progression-free survival time was $8.0{\pm}5.0$ months, $11.6{\pm}6.1$ months, and $14.8{\pm}7.9$ months (p<0.05), respectively. Overall survival time was $15.4{\pm}7.6$ months, $18.2{\pm}8.0$ months, and $22.0{\pm}7.6$ months (p<0.05), one-year survival rates were 62.5%, 73.1% and 90.0% (p>0.05) and two-year survival rates were 31.3%, 38.5% and 50.0% (p<0.05). Main side-effects were bone marrow suppression, radiation related esophagitis and gastrointestinal reaction. Conclusion: In treating patients with NSCLC, concurrent chemoradiotherapy with paclitaxel improves early response compared with conventional fractionated radiotherapy or 3 DCRT. The survival rate was improved with the addition of paclitaxel, but there was an increase in adverse reactions when the dose of paclitaxel was increased.

Comparative Study on Transcatheter Arterial Chemoembolization, Portal Vein Embolization and High Intensity Focused Ultrasound Sequential Therapy for Patients

Cui, Lin,Liu, Xing-Xiang,Jiang, Yong,Wu, Xing-Jun,Liu, Jian-Jun,Zhou, Xiang-Rong,He, Xue-Jun,Huang, Xin-En Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

Objective: To investigate the safety and efficacy of transcatheter arterial chemoembolization (TACE), combined with portal vein embolization (PVE), and high intensity focused ultrasound (HIFU) sequential therapy in treating patients with hepatocellular carcinoma (HCC). Methods: Patients with inoperative HCC were treated by two methods: in the study group with TACE first, then PVE a week later, and then TACE+PVE every two months as a cycle, after 2~3 cycles finally HIFU was given; in the control group only TACE+PVE was given. Response (CR+PR), and disease control rate (CR+PR+SD), side effects, overall survival and time to progress were calculated. Results: Main side effects of both groups were nausea and vomiting. No treatment related death occurred. In the study group, 32 patients received TACE for overall 67 times, PVE 64 times, and HIFU 99 times; on average 2.1, 2 and 3.1 times for each patient, respectively. In the control group, 36 patients were given TACE 78 times and PVE 74 times, averaging 2.2 and 2.1 times per patient. Effective rate: 25.0% in study group and 8.3% in control group (p>0.05). Disease control rates were 71.9% and 44.4%, respectively (p<0.05). In patients with portal vein tumor thrombus, the rate reduced over 1/2 after treatment was 69.2%(9/13) in the study and 21.4%(3/14) in the control group (p<0.05). Rate of AFP reversion or decrease over 1/2 was 66.7%(16/24) in study and 37%(10/27) (p<0.05) in control group. Median survival time: 16 months in study and 10 months in control group. PFS was 7months in study and 3 months in control group. Log-rank test suggested that statistically significant difference exists between two groups (p=0.024). 1-, 2- and 3-year survival rates were 56.3%, 18.8% and 9.3% in study, while 30.6%, 5.6% and 0 in control group, respectively, with statistically significant difference between two groups (by Log-rank, p = 0.014). Conclusions: The treatment of TACE+PVE+HIFU sequential therapy for HCC increases response rate, prolong survival, and could thus be a safe and effective treatment for advanced cases.

Prevalence of Spina Bifida Occulta and Its Relationship With Overactive Bladder in Middle-Aged and Elderly Chinese People

Jun Wei Wu,Yu Rong Xing,Yi Bo Wen,Tian Fang Li,Quan De Feng,Xiao Ping Shang,Yun Long Li,Jin Jin Feng,Xin Xin Wang,Rong Qun Zhai,Xiang Fei He,Tao Chen,Xin Jian Liu,Jian Guo Wen 대한배뇨장애요실금학회 2016 International Neurourology Journal Vol.20 No.2

Purpose: To investigate the prevalence of spina bifida occulta (SBO) and its relationship with the presence of overactive bladder (OAB) in middle-aged and elderly people in China. Methods: A cross-sectional community-based survey was carried out at 7 communities in Zhengzhou City, China from December 15, 2013 to June 10, 2014, where residents aged over 40 years were randomly selected to participate. All of the participants underwent lumbosacral radiographic analysis and relevant laboratory tests. A questionnaire including basic information, past medical history and present illness, and the OAB symptom score was filled out by all participants. Chi-square tests and logistic regression were used for data analysis with a P-value of <0.05 denoting statistical significance. Results: A total of 1,061 subjects were qualified for the final statistical analysis (58.8±11.7 years; male, 471 [44.4%]; female, 590 [55.6%]). The overall prevalence of SBO was 15.1% (160 of 1,061): 18.3% (86 of 471) in men and 12.5% (74 of 590) in women. Among these subjects, 13.7% (145 of 1,061) had OAB: 13.2% (62 of 471) in men and 14.1% (83 of 590) in women. The results of logistic regression showed that age, SBO, history of cerebral infarction (HCI), and constipation were risk factors for OAB (P<0.05), while sex, history of childhood enuresis (HCE), body mass index (BMI), and diabetes mellitus (DM) were not (P>0.05). In men, age, SBO, and constipation were risk factors for OAB (P<0.05), while HCE, BMI, DM, HCI, and benign prostate hyperplasia were not (P>0.05). In women, age, SBO, and HCI were risk factors for OAB (P<0.05), while HCE, BMI, DM, vaginal delivery, and constipation were not (P>0.05). Conclusions: The prevalence of SBO is high and it is related to OAB in middle-aged and elderly people in China.

Anatomical Study of the Accessory Tendon of the Extensor Hallucis Longus Muscle and Its Clinical Application

Yue Li,Jing-Ying Zhang,Xin-Yue Zhao,Li-Ya Pan,De-Hao Jin,He-Xing Xu,Hu-Zhe Cui,Yan-Qun Liu,Xiang-Zheng Qin,Qingyuan Li 대한정형외과학회 2021 Clinics in Orthopedic Surgery Vol.13 No.2

Background: The accessory tendon of the extensor hallucis longus (ATEHL) muscle is a common abnormal structure, and its clinical significance remains debatable. In this study, we provide the incidence of the ATEHL and characterize its morphological types in Asian cadavers and investigate its clinical applications. Methods: The tendons from 50 adult cadaveric feet, fixed in 10% formalin, were analyzed. We measured the length and width of both the ATEHL and the extensor hallucis brevis (EHB). Results: All dissected specimens had an ATEHL. The first metatarsophalangeal joint was surrounded by an accessory tendon that inserted onto the joint capsule and the dorsal base of the proximal phalanx. We classified the ATEHL into 3 types based on their directions. Differences in ATEHL type based on sex were not statistically significant. Conclusions: We found an ATEHL in all cadaveric specimens in this study. We surmise that the ATEHL acts as an antagonist with the EHB when the toe is extending, which might help prevent the occurrence of hallux valgus deformity.

LPL gene Pvu II polymorphism and hypertriglycer-idemia: a meta-analysis involving 1,640 subjects

( Yan-yan Li ),( Yan-hong Zhou ),( Ge Gong ),( Hong-yu Geng ),( Xin-xing Yang ),( Xiang-ming Wang ),( Chuan-wei Zhou ),( Jian Xu ),( Yun Qian ) 대한내과학회 2017 The Korean Journal of Internal Medicine Vol.32 No.6

Background/Aims: Although lipoprotein lipase (LPL) gene Pvu II polymorphism has been associated with an increased risk of hypertriglyceridemia (HT), there is no clear consensus within the scientific community. Methods: A meta-analysis of 1,640 subjects from six individual studies was conducted to better elucidate the potential relationship between the LPL gene Pvu II polymorphism and HT within the Chinese population. Pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were evaluated by using fixed effect models. Results: Our analysis indicated a significant association between LPL gene Pvu II polymorphism and HT within the Chinese population under allelic (OR, 1.550; 95% CI, 1.320 to 1.830; p = 1.158 × 10^-7), recessive (OR, 0.540; 95% CI, 0.390 to 0.750; p = 0.0002), dominant (OR, 1.889; 95% CI, 1.501 to 2.377; p = 5.960 × 10^-8), homozygous (OR, 2.167; 95% CI, 1.531 to 3.067; p = 1.242 × 10^-5), heterozygous (OR, 1.810; 95% CI, 1.419 to 2.309; p = 1.842 × 10^-6), and additive genetic models (OR, 1.553; 95% CI, 1.320 to 1.828; p = 1.158 × 10^-7). Conclusions: Because LPL gene Pvu II restriction fragment length polymorphism polymorphism was associated with an elevated risk of HT, the P+ allele carriers of the LPL gene might be predisposed to HT.

Inhibitory effects of piceatannol on human cytomegalovirus (hCMV) in vitro

Wang San-Ying,Zhang Jing,Xu Xiao-Gang,Su Hui-Li,Xing Wen-Min,Zhang Zhong-Shan,Jin Wei-Hua,Dai Ji-Huan,Wang Ya-Zhen,He Xin-Yue,Sun Chuan,Yan Jing,Mao Gen-Xiang 한국미생물학회 2020 The journal of microbiology Vol.58 No.8

Human cytomegalovirus (hCMV) is a ubiquitous herpesvirus, which results in the establishment of a latent infection that persists throughout the life of the host and can be reactivated when the immunity is low. Currently, there is no vaccine for hCMV infection, and the licensed antiviral drugs mainly target the viral enzymes and have obvious adverse reactions. Thus, it is important to search for compounds with antihCMV properties. The present study aimed to investigate the suppressive effects of piceatannol on hCMV Towne strain infection and the putative underlying mechanisms using human diploid fibroblast WI-38 cells. Piceatannol supplementation prevented the lytic changes induced by hCMV infection in WI-38 cells. Furthermore, piceatannol suppressed the expression of hCMV immediate-early (IE) and early (E) proteins as well as the replication of hCMV DNA in a dose-dependent manner. Moreover, hCMV-induced cellular senescence was suppressed by piceatannol, as shown by a decline in the senescence-associated β-galactosidase (SA-β-Gal) activity and decreased production of intracellular reactive oxygen species (ROS). p16INK4a, a major senescence-associated molecule, was dramatically elevated by current hCMV infection that was attenuated by pre-incubation with piceatannol in a dose-dependent manner. These results demonstrated that piceatannol suppressed the hCMV infection via inhibition of the activation of p16INK4a and cellular senescence induced by hCMV. Together, these findings indicate piceatannol as a novel and potent anti-hCMV agent with the potential to be developed as an effective treatment for chronic hCMV infection.

Role of Nucleation-Promoting Factors in Mouse Early Embryo Development

Wang, Qiao-Chu,Liu, Jun,Wang, Fei,Duan, Xing,Dai, Xiao-Xin,Wang, Teng,Liu, Hong-Lin,Cui, Xiang-Shun,Sun, Shao-Chen,Kim, Nam-Hyung Cambridge University Press 2013 Microscopy and microanalysis Vol.19 No.3

<B>Abstract</B><P>During mitosis nucleation-promoting factors (NPFs) bind to the Arp2/3 complex and activate actin assembly. JMY and WAVE2 are two critical members of the NPFs. Previous studies have demonstrated that NPFs promote multiple processes such as cell migration and cytokinesis. However, the role of NPFs in development of mammalian embryos is still unknown. Results of the present study show that the NPFs JMY and WAVE2 are critical for cytokinesis during development of mouse embryos. Both JMY and WAVE2 are expressed in mouse embryos. After injection of JMY or WAVE2 siRNA, all embryos failed to develop to the morula or blastocyst stages. Moreover, using fluorescence intensity analysis, we found that the expression of actin decreased, and multiple nuclei were observed within a single cell indicating that NPFs-induced actin reduction caused the failure of cell division. In addition, injection of JMY and WAVE2 siRNA also caused ARP2 degradation, indicating that involvement of NPFs in development of mouse embryos is mainly through regulation of ARP2/3-induced actin assembly. Taken together, these data suggested that WAVE2 and JMY are involved in development of mouse embryos, and their regulation may be through a NPFs-Arp2/3-actin pathway.</P>

Analysis of Relationships Between Prethrombotic States and Cervical Cancer

Sun, You-Hong,Cui, Lin,Chen, Jue,Wang, Min,Liu, Jian-Jun,Liu, Xing-Xiang,Huang, Xin-En Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.14

Objective: To analyze the relationship between a prethrombotic state and the occurrence of thrombosis, as well as survival time for patients with cervical cancer. Methods: Patients with first diagnosis of cervical cancer were subgrouped according to FIGO staging, and two D-dimer levels were assessed. According to the results, patients are divided into an observation group (abnormal) and control group (normal). Results: For 106 patients with cervical cancer, 38 with abnormal D-dimer, the abnormal rate is 35.9%, of which stage I accounted for 6.5%, stage II 38.5%, stage III 50%, and stage IV 61.1% (p=0.013); The level of D-dimers in stageI wass $0.87{\pm}0.68ug/ml$, while in stage II it was $1.50{\pm}1.35ug/ml$, stage III $2.60{\pm}1.86ug/ml$ and stage IV $18.6{\pm}53.4ug/ml$ (P=0.031); after follow-up of patients for 2-30 months, the mortality of observation group is 21.1%, while for control group it was 2.94% (p <0.01). In the observation group, survival time was $15.1{\pm}5.8$ months, while for control group it was $21.0{\pm}5.4$ months, the difference between two groups being highly significant (p=0.000). Conclusion: There is a direct correlation between prethrombotic state and the grade malignancy of cervical cancer. The level is positively correlated with clinical stage, and is inversely related to survival time, so that a prethrombotic state could be used to predict the prognosis for patients with cervical cancer.