Zhilian Wang

Olaparib Triggers Mitochondrial Fission Through the CDK5/Drp‐1 Signaling Pathway in Ovarian Cancer Cells

ABSTRACT Ovarian cancer (OC) is the leading cause of death from gynecological malignancies worldwide. Alterations in mitochondrial metabolism are considered defining characteristics and therapeutic targets of OC. Olaparib, an oral inhibitor of poly (ADP‐ribose) polymerase, has been approved for the treatment of OC. However, the precise mechanisms by which it exerts its effects remain unclear. In this study, we uncover a novel pharmacological function of Olaparib by demonstrating that it induces mitochondrial dysfunction in human SKOV3 ovarian cancer cells. Our findings revealed that Olaparib exposure induced mitochondrial oxidative stress by elevating mitochondrial ROS levels and diminishing GPx activity. Additionally, treatment with Olaparib led to mitochondrial dysfunction, as evidenced by decreased complex I and complex IV activity and reduced ATP production. We observed that Olaparib induced mitochondrial fission by decreasing the average length of mitochondria. Olaparib did not affect the levels of Mfn1, Mfn2, or the total expression of Drp‐1. Intriguingly, Olaparib increased the levels of phosphorylated Drp‐1 at Ser616. Further investigation revealed that Olaparib facilitated the activation of the CDK5 signaling pathway and induced Caspase 3 activation. Notably, inhibition of CDK5 signaling using roscovitine mitigated the effects of Olaparib on mitochondrial fission and dysfunction, indicating a role for CDK5 in this process. In summary, our research identifies that CDK5/Drp‐1‐mediated mitochondrial fission may represent a novel mechanism through which Olaparib exerts its anticancer effects in OC.

Prevalence and distribution of human papillomavirus genotypes in cervical intraepithelial neoplasia in China: a meta-analysis

Abstract Background and aim Data on type-specific human papillomavirus (HPV) are needed to investigate HPV-based screening tests and HPV vaccines. However, Chinese relevant data are insufficient. Therefore, this meta-analysis aimed to summarize and demonstrate the prevalence and distribution of HPV genotypes in cervical intraepithelial neoplasia (CIN) and compensate for the shortage of HPV vaccines in China. Methods The Medline, Embase, and the Cochrane Library databases, as well as references cited in the selected studies, were systematically searched for studies investigating the prevalence and distribution of HPV genotypes between January 2000 and April 2019 in China. Results A total of 8 studies were identified, which comprised 2950 patients with CIN1 and 5393 with CIN2/3. The overall HPV infection rate was 84.37%. The HPV infection rate was significantly higher in the CIN2/3 group (87.00%) than in the CIN1 group (79.56%) (χ2 = 80.095, P < 0.001). The most common HPV types in CIN1 in order of decreasing prevalence were as follows: HPV52 (20.31%), HPV16 (16.81%), HPV58 (14.44%), HPV18 (6.44%), and HPV53 (5.76%). However, in the CIN2/3 group, HPV16 (45.69%) was the predominant type, followed by HPV58 (15.50%), HPV52 (11.74%), HPV33 (9.35%), and HPV31 (4.34%). Conclusions This study suggested that HPV16, HPV52, and HPV58 were the top three types of CIN in China. The findings might provide a reference for future HPV-based cervical cancer screening tests, treatment of HPV infection, and application of HPV vaccines in China.

Prevalence, genotype distribution and risk factors of cervical HPV infection in Yangqu, China: a population-based survey of 10086 women

Human papillomavirus(HPV) infection is a necessary factor for the development of cervical cancer. The HPV vaccine is currently available, but there is still a lack of large-scale research on the distribution and risk factors of HPV. The aim of this study is to investigate the genotype distribution and risk factors of HPV infection in Yangqu which is located in North China. This study enrolled 10086 women aged <65 years from Yangqu County. HPV genotypes were identified via standard HPV DNA testing. The overall prevalence of HPV infection was 8.92%. The prevalence of high-risk HPV types was 8.80%, and it was 0.38% for low-risk HPV types. Single genotype infection accounted for 67.91% in HPV-positive cases. The most common HPV genotypes were HPV-16, -52, and -58. HPV-18 was only the 11th most common type in HPV-positive cases. Women ≥50 years of age had the highest prevalence rate of HPV, and women <30 years had the lowest prevalence rate. The distribution of HPV genotypes also varied among the three age groups: <30, 30-49, and ≥50 years. The risk factors that contributed to the rate of HPV infection included low educational level, low income, smoking, age at first sexual encounter <23 years old, and number of births ≥3 times. This large routine clinical practice report of HPV prevalence and genotype distribution revealed the characteristics of HPV infection-type distributions in Shanxi Province, which should be considered in formulating comprehensive prevention strategies including vaccination for cervical cancer in China.