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1.
Pestic Biochem Physiol ; 197: 105647, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38072522

ABSTRACT

Paraquat (PQ) is a highly effective and highly toxic herbicide that is highly toxic to both humans and animals. Pulmonary fibrosis is the primary cause of fatality in patients with PQ poisoning, there is no effective drug treatment yet. 2-Methoxyestradiol (2ME) is a natural metabolite of estradiol with anti-tumor, anti-angiogenesis, and anti-proliferative effects. Whether 2ME has the potential to inhibit pulmonary fibrosis induced by PQ is unclear. This study aims to investigate the potential effects and mechanism of 2ME on PQ-induced pulmonary fibrosis. C57BL/6 mice and A549 cells were exposed to PQ to establish pulmonary fibrosis model. In vivo, Hematoxylin and eosin (H&E) staining was utilized to assess the pathological characteristics. Masson's trichrome staining was employed to evaluate the collagen deposition. Western blot and immunohistochemistry were conducted to determine the expressions of fibrosis markers. In vitro, the expressions of epithelial-mesenchymal transition (EMT) markers were detected using western blot and immunofluorescence to evaluated the potential inhibition of PQ-induced EMT by 2ME. And proteins associated with the TGF-ß1/Smad2/3 signaling pathway were measured by western blot in vivo and in vitro. The result found that 2ME can ameliorated PQ-induced pulmonary fibrosis and inhibit the activation of TGF-ß1/Smad2/3 signaling pathway. These findings suggest that 2ME may serve as a potential therapeutic agent for treating PQ-induced pulmonary fibrosis.


Subject(s)
Paraquat , Pulmonary Fibrosis , Humans , Mice , Animals , Paraquat/toxicity , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/metabolism , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/pharmacology , Transforming Growth Factor beta1/therapeutic use , 2-Methoxyestradiol/pharmacology , 2-Methoxyestradiol/therapeutic use , Mice, Inbred C57BL , Signal Transduction
2.
Int J Ment Health Addict ; : 1-15, 2023 Jan 09.
Article in English | MEDLINE | ID: mdl-36688112

ABSTRACT

The onset age of anxiety is decreasing worldwide, yet the majority of the study conducted on anxiety were focused on adult populations. This study aimed to investigate the mediating effect of psychological capital and coping style tendency on the relationship between emotional intelligence and anxiety in Chinese adolescents and provide empirical evidence for research and prevention. A cross-sectional study recruited 5747 participants from 5 randomly selected middle schools in the northeast China. Study results showed that high emotional intelligence (P < 0.05), high level of psychological capital (P < 0.05), and positive coping style tendency (P < 0.05) were correlated to lower level of anxiety symptoms in adolescents. Psychological capital and coping style tendency performed partial and serial mediating effect on the relationship between emotional intelligence and anxiety. Teaching adolescents how to regulate emotions can strengthens their positive mentalities, promotes the use of positive coping strategies, and then attenuates the severity of anxiety symptoms in a nonadditive manner.

3.
Clin Nurs Res ; 32(3): 580-588, 2023 03.
Article in English | MEDLINE | ID: mdl-36633212

ABSTRACT

This study aimed to explore the relationships between modifiable and non-modifiable factors that influence sleep quality in hospitalized patients with cardiovascular disease in China. This study design was cross-sectional and descriptive. This study involved a convenience sample of 242 patients hospitalized for cardiovascular issues. Hierarchical regression model and qualitative comparative analysis model were performed. Regression revealed that age and depression both had statistically significant effects on sleep quality. The combination of conditions with strongest predictive effect on sleep quality was male of younger age, high level of depression, high level of anxiety, and low level of social support. Other combinations with predictive power on sleep quality are as follows: (1) younger male patients (aged 47-63 years) with high level of anxiety, high level of social support, and low level of depression; (2) older male patients (aged 63-79 years) with high level of depression, high level of social support, and low levels of anxiety; and (3) older male patients with high level of anxiety and low level of social support. Nurses may promote primary and secondary prevention of cardiovascular health prior to hospitalization, through routine screening for depressive and anxious symptoms and assessment of the patient's social support network. It is unknown whether these findings are unique to hospitalized patients. Therefore, future work should assess the fit of the model to other more diverse groups of hospitalized patients.


Subject(s)
Cardiovascular Diseases , Sleep Quality , Humans , Male , Depression , Cross-Sectional Studies , Anxiety , Sleep
4.
Clin Nurs Res ; 32(3): 549-559, 2023 03.
Article in English | MEDLINE | ID: mdl-36633263

ABSTRACT

Health-related quality of life (HRQOL) is the result of complex interactions between many different factors. But few studies to date have explored the structure of HRQOL. This study aimed to investigate the complex inter-relationship between HRQOL and influencing factors using network analysis. In all, 624 Chinese pregnant women in third trimester were recruited through recruiting sampling. We used regularized network analysis to create a complex network. The relationship with mother-in-law was the most central node followed by relationship with partner. We found the comorbidity of anxiety and depressive symptoms using network analysis. Physical- and mental-related quality of life were a "bridge node" connecting psychological factors with physiologic factors. The present network analysis highlights the strong link between relationship with mother-in-law or partner and HRQOL, which is also a unique phenomenon under Chinese culture. This analysis provides key variables for future intervention or improvement of pregnant women' HRQOL.


Subject(s)
Pregnant Women , Quality of Life , Humans , Female , Pregnancy , Pregnant Women/psychology , Quality of Life/psychology , Pregnancy Trimester, Third , East Asian People , Asian People , Depression/psychology
5.
Psychol Health Med ; 28(5): 1358-1367, 2023 06.
Article in English | MEDLINE | ID: mdl-35016579

ABSTRACT

Previous studies have reported high rates of poor mental health among nursing students, but few studies focused on the internal pathway of mental health. This cross-sectional study was conducted at a vocational medical school and investigated 384 nursing students. Symptom Check List-90, Index of Well-Being Scale and Cynical Attitudes Toward College Scale were used to test mental health, subjective well-being (SWB) and cynicism of nursing students, respectively. Academic cynicism, social cynicism and institutional cynicism were negatively related to mental health. SWB not only directly had positive effect on mental health, but had an indirect effect on mental health through academic cynicism, social cynicism and institutional cynicism.


Subject(s)
Mental Health , Students, Nursing , Humans , Students, Nursing/psychology , Cross-Sectional Studies , Surveys and Questionnaires
6.
J Affect Disord ; 320: 284-290, 2023 01 01.
Article in English | MEDLINE | ID: mdl-36179782

ABSTRACT

BACKGROUND: Using the data from a large-scale Chinese national survey, this study aimed to explore the underlying mechanisms between Chinese adults' self-assessments of family social status in childhood and depression. METHODS: The research data was from the China Family Panel Studies (CFPS) in 2020. We selected 13,430 Chinese adults aged 16-60 as participants, and used the PROCESS macro program to conduct moderated mediation analysis. RESULTS: Chinese adults' self-assessments of family social status in childhood had a statistically significant negative predictive effect on depression. The sharing frequency of WeChat Moments played a partial mediating role in the relationship between self-assessment of family social status in childhood and depression. Furthermore, social trust moderated the direct effect of mediation model. Age moderated the second half of the mediation model, and the effect was statistically significant in the younger population (young people), but not in the older population (middle-aged people). LIMITATIONS: This was a cross-sectional study and no causal conclusions could be drawn. CONCLUSIONS: Chinese adults' self-assessment of family social status in childhood could affect depression in adulthood through sharing frequency of WeChat Moments. People with higher social trust can effectively buffer the adverse effect of self-assessed low family social status in childhood on depression. Age moderated the relationship between sharing frequency of WeChat Moments and depression, but this moderating effect was only significant in the younger population.


Subject(s)
Depression , Self-Assessment , Humans , Middle Aged , Adult , Adolescent , Depression/epidemiology , Depression/etiology , Cross-Sectional Studies , Social Status , China
7.
Psychol Health Med ; : 1-14, 2022 Dec 18.
Article in English | MEDLINE | ID: mdl-36529913

ABSTRACT

The COVID-19 pandemic is a major public health emergency and a significant stressor to most people. The objective of this study was to examine the mental health status and social support level of participants from 2019 to 2020. The study aimed to investigate the changes in people's psychological capital state due to the COVID-19 pandemic. A longitudinal study was performed to study the psychosocial predictors of mental health among a sample of 2,999 Chinese employees in 2019, and the follow-up survey was conducted one year later. Regression coefficients were visualized in a heatmap. Path analysis was performed base on the structural equation model (SEM) to measure the associations between study variables. The status of mental health, resilience, and optimism changed significantly during the pandemic (P < 0.05). The level of employee's social support in 2019 could significantly and positively predicted the level of employee's psychological capital in 2020, and the level of employee mental health in 2019 significantly and negatively predicted the level of employee psychological capital in 2020. The mental health of employees played an intermediary role between social support and psychological capital. These results highlight that the COVID-19 pandemic has a strong impact on the psychological capital of company employees. While demanding performance, corporations should ensure timely intervention in the mental health of their employees.

8.
Pathol Res Pract ; 239: 154064, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36274378

ABSTRACT

Colorectal cancer (CRC) features high prevalence and mortality. Long non-coding RNAs (lncRNAs) exert nonnegligible roles in human cancer development. Nevertheless, the functions of most lncRNAs still remain unexplored. We currently focused on detecting the influence of SPINT1 antisense RNA 1 (SPINT1-AS1) on CRC development and investigating into the potential regulatory mechanism. RT-qPCR analysis first confirmed that SPINT1-AS1 exhibited high expression in KRAS-mutant (KRASMUT) CRC cells. Through series of functional experiments, we observed that knockdown of SPINT1-AS1 weakened KRASMUT CRC cell proliferation, migration and invasion. Afterwards, the implementation of mechanism assays help to verify that SPINT1-AS1 sequestered microRNA-433-3p (miR-433-3p) to regulate the expression of E2F transcription factor 3 (E2F3). Besides, E2F3 was validated to activate the transcription of SPINT1-AS1 in turn. Rescue experiments confirmed the functional influence of SPINT1-AS1/miR-433-3p/E2F3 on CRC cells. In summary, the molecular axis of SPINT1-AS1/miR-433-3p/E2F3 forms a positive loop which might become a potential biomarker in CRC.


Subject(s)
Colorectal Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Neoplasm Invasiveness/genetics , Feedback , Cell Movement/genetics , Cell Proliferation/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic/genetics , Proteinase Inhibitory Proteins, Secretory/genetics , Proteinase Inhibitory Proteins, Secretory/metabolism , E2F3 Transcription Factor
9.
Arch Psychiatr Nurs ; 40: 8-14, 2022 10.
Article in English | MEDLINE | ID: mdl-36064250

ABSTRACT

COVID-19 has caused major changes in people's mental health and behavior. This study aimed to investigate whether boredom proneness and fear of missing out acted as mediators between psychological distress and Internet addiction (IA). A cross-sectional survey was conducted in 2020, including 552 youths aged 17-28 years. The recruited participants were asked to complete a series of self-reported questionnaires regarding psychological distress, fear of missing out, boredom proneness and IA. The results indicate that during the COVID-19 pandemic, the reporting rate of IA in young adults was 28.1%, and fear of missing out and boredom proneness played multiple mediation roles in the relationship between psychological distress and IA. Governments and education departments should focus on young people with psychological deficits to prevent them from succumbing to IA.


Subject(s)
COVID-19 , Psychological Distress , Adolescent , Boredom , Cross-Sectional Studies , Disease Outbreaks , Fear , Humans , Internet , Internet Addiction Disorder/epidemiology , Pandemics , Young Adult
10.
Front Pharmacol ; 13: 811372, 2022.
Article in English | MEDLINE | ID: mdl-35645808

ABSTRACT

This study explored the role of metformin (MET) in regulating the polarization of alveolar macrophages to protect against acute lung injury (ALI) in rats caused by paraquat (PQ) poisoning. The in vivo studies showed that the 35 mg/kg dose of MET increased the survival rate of rats, alleviated pathological damages to the lungs and their systemic inflammation, promoted the reduction of the pro-inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels, and increased the anti-inflammatory factor IL-10 levels in the rat serum. At the same time, the MET intervention decreased the expression of M1 macrophage marker iNOS in the lungs of the PQ-poisoned rats while increasing the M2 macrophage marker, Arg1, expression. In vitro, the concentration of MET > 10 mmol/L affected NR8383 viability adversely and was concentration-dependent; however, no adverse impact on NR8383 viability was observed at MET ≤ 10 mmol/L concentration, resisting the reducing effect of PQ on NR8383 vitality. The PQ-induced NR8383 model with MET intervention showed significantly reduced secretions of IL-6 and TNF-α in NR8383, and lowered expressions of M1 macrophage markers iNOS and CD86. Additionally, MET increased IL-10 secretion and the M2 macrophage markers, Arg1 and Mrcl, expressions. Therefore, we speculate that MET could regulate alveolar macrophage polarization to protect against PQ-poisoning caused ALI.

11.
Int J Ment Health Nurs ; 31(5): 1239-1248, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35727700

ABSTRACT

This study aimed to explore the combination of different conditional variables that led to depressive symptoms among frontline nurses who were fought against COVID-19 during the outbreak in Wuhan City, Hubei Province of China. The study was conducted in August 2020, which included 331 frontline clinical nurses who supported Wuhan's fight against COVID-19. The age range was 21-57 years and included 315 female nurses and 16 male nurses. This study used the fuzzy-set qualitative comparative analysis research method to explore the path of depression among frontline nurses. This study generated nine different configurations for the path of depression among frontline nurses, and had a detailed demonstration for each configuration. Each configuration distinguishes the different effects of influencing factors. For example, in the first configuration, gender, sleep disorder and PTSD exist as core conditions, while social support exists as a core condition lack. This study was presented results which was different what linear regression model reports. It takes into consideration the combined effect of each conditional variable on the development of depression. Nurse managers should pay attention to the combination of multiple influencing factors, instead of focus on single factors.


Subject(s)
COVID-19 , Nurses , Adult , China/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Depression/etiology , Female , Humans , Male , Middle Aged , Pandemics , SARS-CoV-2 , Young Adult
12.
Front Public Health ; 10: 825176, 2022.
Article in English | MEDLINE | ID: mdl-35392470

ABSTRACT

The study was to compare the performance of the regression models and fuzzy set qualitative comparative analysis (fsQCA) models in analyzing the possible effects of sociodemographic variables (age and sex) and lifestyle behaviors (physical activity, sedentary time, sleep duration, physical education class and screen time) on depressive symptoms in adolescents. This cross-sectional surgery was conducted among 726 adolescents in Jilin Province of China, selected by random cluster sampling. The regression model showed that age, physical education (PE) class and sleep duration were associated with depressive symptoms. Meanwhile, the fsQCA models showed that shorter physical activity, PE class and sleep duration as well as longer sedentary and screen time were related to higher levels of depressive symptoms. Both regression and fsQCA models indicated that promoting lifestyle behaviors could affect depressive symptoms. Considering the differences between the two methods, they are not superior to the other method, but complementary and should be used in other studies at the same time.


Subject(s)
Depression , Life Style , Adolescent , China/epidemiology , Cross-Sectional Studies , Depression/diagnosis , Depression/epidemiology , Humans , Sedentary Behavior
13.
Front Psychol ; 13: 742381, 2022.
Article in English | MEDLINE | ID: mdl-35345636

ABSTRACT

This study examined the correlation between depressive symptoms, interpersonal sensitivity, and social support before and during the COVID-19 pandemic and verified causal relationships among them. The study used Social Support Scale and Symptom Self-Rating Scale to investigate relevant variables. A total of 1,414 employees from company were recruited for this longitudinal study, which a follow up study was conducted on the same group of participants 1 year later. Paired sample t-test results showed that significant differences were only found in social support, not in depressive symptoms or interpersonal sensitivity. The results of correlation analysis showed that social support, depressive symptoms, and interpersonal sensitivity were significantly correlated between wave 1 and wave 2. The cross-lag autoregressive pathway showed that employees' social support level, depressive symptoms, and interpersonal sensitivity all showed moderate stability. Crossing paths showed that wave 1 social support could significantly predict wave 2 depressive symptoms (ß = -0.21, p < 0.001) and wave 2 interpersonal sensitivity (ß = -0.21, p < 0.001). Wave 1 depressive symptoms (ß = -0.10, p < 0.01) could significantly predict wave 2 social support, while wave 1 interpersonal sensitivity (ß = 0.07, p = 0.10) could not predict wave 2 social support. Social support can be considered as a protective factor against mental health problems.

14.
J Affect Disord ; 303: 264-272, 2022 04 15.
Article in English | MEDLINE | ID: mdl-35176341

ABSTRACT

OBJECTIVE: The purpose of this study was to construct a cross-sectional study to predict the risk of bullying victimization among adolescents. METHODS: The study recruited 17,365 Chinese adolescents using stratified random cluster sampling method. The classical regression methods (logistic regression and Lasso regression) and machine learning model were combined to identify the most significant predictors of bullying victimization. Nomogram was built based on multivariable logistic regression model. The discrimination, calibration and generalization of nomogram were evaluated by the receiver operating characteristic curves (ROC), the calibration curve and a high-quality external validation. RESULTS: Grade, gender, peer violence, family violence, body mass index, family structure, depressive symptoms and Internet addiction, recognized as the best combination, were included in the multivariable regression. The nomogram established based on the non-overfitting multivariable model was verified by internal validation (Area Under Curve: 0.749) and external validation (Area Under Curve: 0.755), showing decent prediction of discrimination, calibration and generalization. CONCLUSION: Comprehensive nomogram constructed in this study was a useful and convenient tool to evaluate the risk of bullying victimization of adolescents. It is helpful for health-care professionals to assess the risk of bullying victimization among adolescents, and to identify high-risk groups and take more effective preventive measures.


Subject(s)
Bullying , Crime Victims , Adolescent , Cross-Sectional Studies , Humans , Nomograms , Violence
15.
Clin Nurs Res ; 31(1): 115-121, 2022 01.
Article in English | MEDLINE | ID: mdl-34259087

ABSTRACT

This study explores the association between life satisfaction and depression among patients with cardiovascular diseases and whether this association is mediated by self-esteem. A cross-sectional study was conducted in a third-grade hospital. We examined 300 patients with cardiovascular diseases with a mean age of 62.00 years (females, 133). Life satisfaction was associated with depression. Adding self-esteem to the model weakened the strength of the association between the two. Moreover, 34.2% of the effect of life satisfaction on depression could be explained by self-esteem. We found that self-esteem could totally explain the effect of life satisfaction on depression among patients with cardiovascular diseases.


Subject(s)
Cardiovascular Diseases , Personal Satisfaction , Cross-Sectional Studies , Depression , Female , Humans , Middle Aged , Patient Satisfaction , Self Concept
16.
Sleep Biol Rhythms ; 20(3): 381-390, 2022 Jul.
Article in English | MEDLINE | ID: mdl-38469420

ABSTRACT

This study aimed to explore effects of night sleep duration and its relationships with health lifestyle, depressive symptoms and Internet addiction among high school students. In this study, we used multistage stratified random cluster sampling method. A total of 2149 adolescents aged 14-18 years old were recruited in the study. Associations among sleep duration and demographic characteristics, health lifestyle, depressive symptoms and Internet addiction among Chinese students were analyzed by univariate analysis and binary logistic regression analysis. Then, the structural equation model (SEM) was used to study the relationships between sleep duration and other variables. The mean sleep duration was (6.56 ± 1.15) hours. Approximately 16.0% of all participants had short sleep duration, and 20.5% had long sleep duration. Binary logistic regression analysis revealed that having more high sugar drinks and fried foods were positively associated with short sleep duration. Depressive symptoms not only directly had a negatively impact on sleep duration, but also had an indirect effect on sleep duration through Internet addiction. Sleep problems are common within the population of adolescents. Depressive symptoms was an important factor in the prevention of abnormal sleep duration, and interventions that target Internet addiction is key to reduce inadequate sleep.

17.
Front Public Health ; 9: 666460, 2021.
Article in English | MEDLINE | ID: mdl-34395359

ABSTRACT

Objective: The study aimed to examine the relationship between perceived stress and post-traumatic stress disorder (PTSD) among frontline medical staff during the lockdown in Wuhan city, China, due to the COVID-19 outbreak. Methods: The study was conducted in August 2020, which included 516 medical staff between 21 to 65 years. The PTSD Checklist-Civilian, Perceived Stress Scale, Insomnia Severity Index, and Compassion Fatigue Short Scale were used. Results: The results indicated that 10.5% of the medical staff experienced PTSD symptoms, and insomnia severity mediated the effect of perceived stress on PTSD. In addition, compassion fatigue moderated the association between perceived stress and PTSD. Conclusion: The study elucidated the mechanisms underlying the association between perceived stress and PTSD. Moreover, it emphasized the importance of long-term monitoring of the mental health status of frontline medical staff who supported Wuhan. The results can serve as reference for relevant medical and health departments to formulate active interventions and preventive measures against PTSD for unsung heroes who put their lives on the line during difficult times.


Subject(s)
COVID-19 , Epidemics , Stress Disorders, Post-Traumatic , Communicable Disease Control , Humans , Medical Staff , SARS-CoV-2 , Stress Disorders, Post-Traumatic/epidemiology , Stress, Psychological/epidemiology
18.
Ecotoxicol Environ Saf ; 223: 112571, 2021 Oct 15.
Article in English | MEDLINE | ID: mdl-34352584

ABSTRACT

The present study investigates whether paraquat (PQ) regulates polarization of alveolar macrophages through glycolysis and promotes the occurrence of acute lung injury in rats. In vivo, the PQ intraperitoneal injection was used to construct a model of acute lung injury in rats. In vitro, the study measured the effect of different concentrations of PQ on the viability of the alveolar macrophages, and explored the polarization and glycolysis metabolism of alveolar macrophages at different time points after PQ intervention. Compared with the normal control (NC) group, the lung pathological damage in rats increased gradually after PQ poisoning, reaching a significant degree at 48 h after poisoning. The PQ-poisoned rat serum showed increased expressions of interleukin-6 (IL-6), tumor necrosis factor- α (TNF-α), and M1 macrophage marker, iNOS, while the expression of interleukin-10 (IL-10) and M2 macrophage marker, Arg1, decreased. The toxic effect of PQ on alveolar macrophages was dose- and time-dependent. Compared with the NC group, IL-6 and TNF-α in the cell supernatant gradually increased after PQ intervention, while the IL-10 content gradually decreased. The PQ intervention in alveolar macrophages increased the expression of intracellular glycolysis rate-limiting enzyme pyruvate kinase isozymes M1/M2 (PKM1/M2), lactate, lactate/pyruvate ratio, and the polarization of alveolar macrophage towards M1. Inhibition of cellular glycolysis significantly reduced the PQ-induced alveolar macrophage polarization to M1 type. Thus, PQ induced increased polarization of lung macrophages toward M1 and decreased polarization toward M2, promoting acute lung injury. Therefore, it can be concluded that PQ regulates the polarization of alveolar macrophages through glycolysis.


Subject(s)
Acute Lung Injury , Paraquat , Acute Lung Injury/chemically induced , Animals , Glycolysis , Lung/metabolism , Macrophages, Alveolar/metabolism , Paraquat/toxicity , Rats , Tumor Necrosis Factor-alpha/metabolism
19.
Int J Clin Exp Pathol ; 8(8): 9032-41, 2015.
Article in English | MEDLINE | ID: mdl-26464645

ABSTRACT

OBJECTIVE: This study aimed to investigate the radiosensitivity of bortezomib to cervical cancer and the possible underlying mechanism. METHODS: HeLa and SiHa cell lines with or without hypoxia treatment were divided into control, radiation alone, bortezomib alone, and radiotherapy plus bortezomib groups. CCK8 assay, clone formation assay, flow cytometry, and immunofluorescence test were used to measure cell proliferation, colony formation, apoptosis, and DNA double-strand break (DSB). Western blot analysis was performed to detect the expression of HIF-1α, PARP-1, and caspase-3, -8, and -9. RESULT: Statistical analysis of data revealed that bortezomib at nanomolar level exerted a radiosensitization effect on both cervical cancer cell lines in normoxia or hypoxia. Western blot analysis showed that the drug could inhibit hypoxia-related HIF-1α expression to increase apoptosis-related caspase-3, -8, and -9 activation and DNA DSB-related PARP-1 cleavage. CONCLUSIONS: Radiotherapy sensitization of bortezomib on cervical cancer cell lines had a drug-dose relation, and sensitization in hypoxia was more remarkable than in normoxia. Bortezomib may be a potential radiotherapy sensitization drug for cervical cancer.


Subject(s)
Bortezomib/pharmacology , Gene Expression/drug effects , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia/metabolism , Radiation-Sensitizing Agents/pharmacology , Uterine Cervical Neoplasms/metabolism , Apoptosis/drug effects , Caspase 3/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Female , HeLa Cells , Humans , Hypoxia/pathology , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/radiotherapy
20.
Sci Rep ; 5: 9476, 2015 Mar 30.
Article in English | MEDLINE | ID: mdl-25820571

ABSTRACT

Radioresistance has been an important factor in restricting efficacy of radiotherapy for non-small cell lung cancer (NSCLC) patients and new approaches to inhibit cancer growth and sensitize irradiation were warranted. Despite the important role of ubiquitin/proteasome system (UPS) during cancer progression and treatment, the expression and biological role of ubiquitin (Ub) in human NSCLC has not been characterized. In this study, we found that ubiquitin was significantly overexpressed in 75 NSCLC tissues, compared to their respective benign tissues by immunohistochemistry (P < 0.0001). Knock-down of ubiquitin by mixed shRNAs targeting its coding genes ubiquitin B (UBB) and ubiquitin C (UBC) suppressed the growth and increased the radiosensitivity in NSCLC H1299 cells. Apoptosis and γ H2AX foci induced by X-ray irradiation were enhanced by knock-down of ubiquitin. Western blot and immunostaining showed that knock-down of ubiquitin decreased the expression and translocation of NF-κB to the nucleus by reduced phospho-IκBα after irradiation. Suppression of ubiquitin decreased the proliferation and radioresistance of H1299 transplanted xenografts in nude mice by promoting apoptosis. Taken together, our results demonstrate the critical role of ubiquitin in NSCLC proliferation and radiosensitivity. Targeting ubiquitin may serve as a potentially important and novel approach for NSCLC prevention and therapy.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Cell Proliferation/genetics , Ubiquitin/biosynthesis , Animals , Apoptosis/radiation effects , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/radiotherapy , Cell Line, Tumor , Gene Expression Regulation, Neoplastic/radiation effects , Humans , Mice , NF-kappa B/biosynthesis , NF-kappa B/genetics , Radiation Tolerance/genetics , Ubiquitin/genetics , X-Rays , Xenograft Model Antitumor Assays
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