Abstract:
:Many oncogenes are involved in the progression from low-grade squamous intraepithelial lesions (LSILs) to high-grade squamous intraepithelial lesions (HSILs); which greatly increases the risk of cervical cancer (CC). Thus, a reliable biomarker for risk classification of LSILs is urgently needed. The prolyl isomerase Pin1 is overexpressed in many cancers and contributes significantly to tumour initiation and progression. Therefore, it is important to assess the effects of cancer therapies that target Pin1. In our study, we demonstrated that Pin1 may serve as a biomarker for LSIL disease progression and may constitute a novel therapeutic target for CC. We used a the novel Pin1 inhibitor KPT-6566, which is able to covalently bind to Pin1 and selectively target it for degradation. The results of our investigation revealed that the downregulation of Pin1 by shRNA or KPT-6566 inhibited the growth of human cervical cancer cells (CCCs). We also discovered that the use of KPT-6566 is a novel approach to enhance the therapeutic efficacy of cisplatin (DDP) against CCCs in vitro and in vivo. We showed that KPT-6566-mediated inhibition of Pin1 blocked multiple cancer-driving pathways simultaneously in CCCs. Furthermore, targeted Pin1 treatment suppressed the metastasis and invasion of human CCCs, and downregulation of Pin1 reversed the epithelial-mesenchymal transition (EMT) of CCCs via the c-Jun/slug pathway. Collectively, we showed that Pin1 may be a marker for the risk of progression to HSIL and that inhibition of Pin1 has anticancer effects against CC.
journal_name
Aging Disjournal_title
Aging and diseaseauthors
Guo YT,Lu Y,Jia YY,Qu HN,Qi D,Wang XQ,Song PY,Jin XS,Xu WH,Dong Y,Liang YY,Quan CSdoi
10.14336/AD.2019.0415subject
Has Abstractpub_date
2020-02-01 00:00:00pages
44-59issue
1issn
2152-5250pii
ad-11-1-44journal_volume
11pub_type
杂志文章abstract::Aging, type 2 diabetes, and male gender are major risk factors leading to increased COVID-19 morbidity and mortality. Thymic production and the export of naïve T cells decrease with aging through the effects of androgens in males and in type 2 diabetes. Furthermore, with aging, recovery of naïve T-cell populations aft...
journal_title:Aging and disease
pub_type: 杂志文章
doi:10.14336/AD.2020.0619
更新日期:2020-07-23 00:00:00
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journal_title:Aging and disease
pub_type: 杂志文章
doi:
更新日期:2011-01-01 00:00:00
abstract::Healthcare-associated pneumonia (HCAP) is a new concept of pneumonia proposed by the American Thoracic Society/Infectious Diseases Society of America in 2005. This category is located between community-acquired pneumonia and hospital-acquired pneumonia with respect to the characteristics of the causative pathogens and...
journal_title:Aging and disease
pub_type: 杂志文章,评审
doi:10.14336/AD.2014.0127
更新日期:2014-02-08 00:00:00
abstract::Alzheimer's disease (AD) and vascular dementia (VAD) are the major forms of dementia affecting elderly people, in which the levels of many metabolites are altered in cerebrospinal fluid (CSF) and serum. These metabolites could be risk factors or potential biomarkers, but the significance of some of these are not clear...
journal_title:Aging and disease
pub_type: 杂志文章
doi:
更新日期:2013-03-07 00:00:00
abstract::Silence information regulator 1 (SIRT1), a member of the sirtuin family, targets histones and many non-histone proteins and participates in various physiological functions. The enzymatic activity of SIRT1 is decreased in patients with Parkinson's disease (PD), which may reduce their ability to resist neuronal damage c...
journal_title:Aging and disease
pub_type: 杂志文章,评审
doi:10.14336/AD.2020.0216
更新日期:2020-12-01 00:00:00
abstract::As one of the leading causes of death around the world, suicide is a global public health threat. In the Chinese population, suicides constitute one-fifth of all recorded suicides in the world. Despite the factual data on suicide rates, the understanding of various causal factors behind suicide, including risk and pro...
journal_title:Aging and disease
pub_type: 杂志文章,评审
doi:10.14336/AD.2014.0223
更新日期:2015-03-10 00:00:00
abstract::Cataract is a major cause of blindness worldwide, its complicated and unclear etiopathogenesis limit effective therapy. Here, we found that Yap, a downstream effector of the Hippo pathway, is specifically expressed in lens epithelial cells and Yap conditional knockout (cKO) in the lens leads to cataract. Histologicall...
journal_title:Aging and disease
pub_type: 杂志文章
doi:10.14336/AD.2018.0910
更新日期:2019-04-01 00:00:00
abstract::Declines in both physical and cognitive function are associated with increasing age. Understanding the physiological link between physical frailty and cognitive decline may allow us to develop interventions that prevent and treat both conditions. Although there is significant epidemiological evidence linking physical ...
journal_title:Aging and disease
pub_type: 杂志文章,评审
doi:10.14336/AD.2019.0521
更新日期:2020-03-09 00:00:00
abstract::With an increased life expectancy in humans and thus an increase in the number of the elderly population, the frequency of hip fractures will rise as well. Aside from a higher incidence, hip fractures in a geriatric population is a significant problem due to the possible onset of severe and in some cases dramatic comp...
journal_title:Aging and disease
pub_type: 杂志文章,评审
doi:10.14336/AD.2014.0500177
更新日期:2014-06-01 00:00:00
abstract::The immune system declines with aging, leading to an increased susceptibility to infections and higher incidence and progression of autoimmune phenomena and neoplasia. Down syndrome prematurely shows clinical manifestations that are normally seen with aging. This review provides a concise overview of abnormalities in ...
journal_title:Aging and disease
pub_type: 杂志文章
doi:
更新日期:2011-12-01 00:00:00
abstract::Alzheimer disease (AD) is the most common dementing illness. Metabolic defects in the brain with aging contribute to the pathogenesis of AD. These changes can be found systematically and thus can be used as potential biomarkers. Erythrocytes (RBCs) are passive "reporter cells" that are not well studied in AD. In the p...
journal_title:Aging and disease
pub_type: 杂志文章
doi:10.14336/AD.2013.0400244
更新日期:2013-10-01 00:00:00
abstract::A promising strategy for the prevention of Alzheimer's disease (AD) is the identification of age-related changes that place the brain at risk for the disease. Additionally, AD is associated with chronic dehydration, and one of the significant changes that are known to result in metabolic dysfunction is an increase in ...
journal_title:Aging and disease
pub_type: 杂志文章
doi:10.14336/AD.2016.0323
更新日期:2016-10-01 00:00:00
abstract::Age related bone loss predisposes adults to osteoporosis. This is especially true for individuals with spinal cord injury (SCI). The effects of decreased bone loading with older age and paralysis significantly contribute to decreased bone mass and increased risk for fragility fractures. Loading bone via volitional mus...
journal_title:Aging and disease
pub_type: 杂志文章
doi:
更新日期:2013-02-07 00:00:00
abstract::Cardiovascular disease is one of the most common causes of death worldwide and the most usual in the western populations. Although it affects both sexes, it is more frequent in males in whom it shortens the average life expectancy. This difference has been attributed to the negative effects of testosterone; however, r...
journal_title:Aging and disease
pub_type:
doi:10.14336/AD.2013.0400381
更新日期:2013-10-07 00:00:00
abstract::Cerebral microbleeds (CMBs), which indicate hemorrhage-prone disease, may associate with hemostatic abnormalities, but the association between CMBs and coagulation function is uncertain. We aimed to examine this possible association. The following coagulation function indicators were evaluated in 85 consecutive ischem...
journal_title:Aging and disease
pub_type: 杂志文章
doi:10.14336/AD.2016.0715
更新日期:2017-04-01 00:00:00
abstract::Microglial activation is an important contributor to the pathogenesis of Parkinson's disease (PD). Microglia are tightly and efficiently regulated by immune checkpoints, including CD200-CD200R1 and CX3CL1-CX3CR1. Understanding the involvement of these checkpoints in disease progression provides important insights into...
journal_title:Aging and disease
pub_type: 杂志文章
doi:10.14336/AD.2019.0615
更新日期:2020-03-09 00:00:00
abstract::Mammalian Sterile20-like (MST) kinases are located upstream in the mitogen-activated protein kinase pathway, and play an important role in cell proliferation, differentiation, renewal, polarization and migration. Generally, five MST kinases exist in mammalian signal transduction pathways, including MST1, MST2, MST3, M...
journal_title:Aging and disease
pub_type: 杂志文章,评审
doi:10.14336/AD.2017.0702
更新日期:2018-06-01 00:00:00
abstract::Melatonin is a pleiotropically acting regulator molecule, which influences numerous physiological functions. Its secretion by the pineal gland progressively declines by age. Strong reductions of circulating melatonin are also observed in numerous disorders and diseases, including Alzheimer's disease, various other neu...
journal_title:Aging and disease
pub_type: 杂志文章
doi:
更新日期:2012-04-01 00:00:00
abstract::Aging is associated with increased fat mass and elevated serum leptin levels (hyperleptinemia), causing proinflammation in the kidneys where it plays a primary role in the removal of endogenous leptin from the circulation. Lymphocyte-specific kinase (Lck) is a positive regulator of inflammatory signaling and a potenti...
journal_title:Aging and disease
pub_type: 杂志文章
doi:10.14336/AD.2019.0218
更新日期:2019-12-01 00:00:00
abstract::The serotonin receptor 2A gene polymorphism is associated with attentional processes in schizophrenia. However, the specificity of the underlying cognitive constructs affected within this domain requires further elucidation. We carried out the first investigation of whether the TC/CC genotype of the 5-HT2A T102C polym...
journal_title:Aging and disease
pub_type: 杂志文章
doi:
更新日期:2012-08-01 00:00:00
abstract::Aging is a common risk factor for the occurrence and development of many diseases, such as Parkinson's disease, Alzheimer's disease, diabetes, hypertension, atherosclerosis and coronary heart disease, and cancer, among others, and is a key problem threatening the health and life expectancy of the elderly. Oxidative da...
journal_title:Aging and disease
pub_type: 杂志文章,评审
doi:10.14336/AD.2019.1021
更新日期:2020-10-01 00:00:00
abstract::Sepsis is a severe disease frequently occurred in the Intenisive Care Unit (ICU), which has a very high morbidity and mortality, especially in patients aged over 65 years. Owing to the aging effect and the ensuing deterioration of body function, the elder patients may have atypical responses to sepsis. Diagnosis and p...
journal_title:Aging and disease
pub_type: 杂志文章
doi:10.14336/AD.2018.1027
更新日期:2019-08-01 00:00:00
abstract::Galectin-3 (Gal-3) is highly expressed in fibrotic tissue related to diverse etiologies. endothelial-to-mesenchymal transition (EndoMT), A less well studied phenomenon serves as a critical process in pulmonary vascular remodeling associated with the development of pulmonary arterial hypertension (PAH). EndoMT is hypot...
journal_title:Aging and disease
pub_type: 杂志文章
doi:10.14336/AD.2018.1001
更新日期:2019-08-01 00:00:00
abstract::Sleep duration and quality have been associated with poor physical function, but both the temporality of the association and the independence of sleep duration and quality are unclear. We examined the prospective association of sleep duration and quality with physical function impairment and disability in older adults...
journal_title:Aging and disease
pub_type: 杂志文章
doi:10.14336/AD.2018.0611
更新日期:2019-06-01 00:00:00
abstract::A temporal framework linking circadian rhythms and clocks to aging rates identifies a specific window of target of rapamycin (TOR) signaling associated with growth hormone (GH) and insulin-like growth factor (IGF-1) (largely exclusive of insulin) in early sleep. IGF-1 signaling is released by growth hormone secretory ...
journal_title:Aging and disease
pub_type: 杂志文章
doi:
更新日期:2010-10-01 00:00:00
abstract::There has been increasing interest and research into sarcopenia in community-dwelling older adults since the European Working Group on Sarcopenia in Older People (EWGSOP) agreed a consensus definition in 2010. Sarcopenia has been defined as loss of muscle mass with loss of muscle function (strength or physical perform...
journal_title:Aging and disease
pub_type: 杂志文章,评审
doi:10.14336/AD.2017.0315
更新日期:2018-02-01 00:00:00
abstract::The relationship between CYP17A1 genetic polymorphisms and essential hypertension (EH) remains unclear. The aim of this study was to investigate the association of CYP17A1 genetic polymorphisms with EH in Han and Uighur populations in China. A Han population including 558 people (270 EH patients and 288 controls) and ...
journal_title:Aging and disease
pub_type: 杂志文章
doi:10.14336/AD.2015.0505
更新日期:2015-11-17 00:00:00
abstract::Liver hypoxia/ischemia injury leads to acute liver injury, delayed graft dysfunction, and failure during liver transplantation. Previous studies showed that autophagy is involved in liver hypoxia/ischemia injury. Our and others' studies have found that the damage-regulated autophagy modulator (DRAM) could induce the a...
journal_title:Aging and disease
pub_type: 杂志文章
doi:10.14336/AD.2018.0210
更新日期:2019-02-01 00:00:00
abstract::Superoxide is a precursor of many free radicals and reactive oxygen species (ROS) in biological systems. It has been shown that superoxide regulates major epigenetic processes of DNA methylation, histone methylation, and histone acetylation. We suggested that superoxide, being a radical anion and a strong nucleophile,...
journal_title:Aging and disease
pub_type: 杂志文章,评审
doi:10.14336/AD.2014.0924
更新日期:2015-06-01 00:00:00
abstract::Oxidative stress and iron accumulation are tightly associated with neurodegenerative diseases. Mitochondrial ferritin (FtMt) is identified as an iron-storage protein located in the mitochondria, and its role in regulation of iron hemeostasis in neurodegenerative diseases has been reported. However, the role of FtMt in...
journal_title:Aging and disease
pub_type: 杂志文章
doi:10.14336/AD.2016.1108
更新日期:2017-07-21 00:00:00