1.Effects of superoxide dismutase inhibition of AFP expression on the malignant biological behavior of PLC/PRF/5 liver cancer cells
Yi CHEN ; Baoying CHEN ; Yuli ZHOU ; Haixia XU ; Yu CAO ; Yue GU ; Mingyue ZHU ; Mengsen LI
China Pharmacy 2025;36(17):2120-2126
OBJECTIVE To explore the effect of superoxide dismutase (SOD) administration on the malignant behavior of PLC/PRF/5 liver cancer cells, and analyze the correlation between SOD and alpha-fetoprotein (AFP) expression, to provide new ideas for targeting AFP with SOD as a drug for hepatocellular carcinoma. METHODS Normal human liver cells L-02, AFP- negative human liver cancer cells HLE, and AFP-positive human liver cancer cells PLC/PRF/5 were used as experimental cells. Western blot assay and SOD activity detection kit were used to detect the expression of AFP, SOD and activity of SOD in cells before and after changing AFP expression; the effects of different concentrations of SOD [0 (control), 0.188, 0.375, 0.75, 1.5, 3 U/mL] administration on the migration and proliferation of PLC/PRF/5 cells were detected using cell scratch assay and CCK-8 assay. The effects of SOD overexpression on the expression of malignant biological behavior-related proteins AFP and sarcoma virus protein (Src) in PLC/PRF/5 cells were detected using Western blot. RESULTS Compared with L-02 group and HLE group, the expression levels of SOD1 and SOD2, and SOD activity in PLC/PRF/5 cells were significantly reduced (P<0.05). After down-regulating AFP expression in PLC/PRF/ 5 cells, compared with PLC/PRF/5 group, the expression levels of SOD1 and SOD2, as well as SOD activity, were significantly increased in the PLC/PRF/5-shAFP group (low-expression) (P<0.05). After 48 hours of SOD treatment, compared with control group, the scratch healing rates of PLC/PRF/5 cells in the 0.375, 0.75, 1.5 and 3 U/mL SOD groups were significantly reduced (P<0.05); after 72 hours of SOD treatment, compared with control group, the scratch healing rates of PLC/PRF/5 cells in the 0.375, 0.75, and 1.5 U/mL SOD groups were significantly reduced (P<0.05 or P<0.01). Compared with control group, proliferation rates of PLC/PRF/5 cells were significantly reduced in the 0.375, 0.75, 1.5 and 3 U/mL SOD groups (P<0.05 or P<0.01). Compared with the PLC/PRF/5 group before up-regulating SOD1 and SOD2 expression, the expression levels of AFP and Src in the PLC/PRF/5-oeSOD1 and PLC/PRF/5-oeSOD2 groups (over-expression) after up-regulating SOD1 and SOD2 expression were significantly reduced (P<0.05). CONCLUSIONS A certain concentration of SOD can inhibit malignant behavior such as migration and proliferation of PLC/PRF/5 cells, and the expression level and activity of SOD are negatively correlated with AFP.
2.A comprehensive guide to genome-wide DNA methylation research in neuropsychiatric disorders and its implications for deep-space environments.
Sheng XU ; Shishi MIN ; Haixia GU ; Xueying WANG ; Chao CHEN
Journal of Central South University(Medical Sciences) 2025;50(8):1320-1336
Neuropsychiatric disorders arise from complex interactions between genetic and environmental factors. DNA methylation, a reversible and environmentally responsive epigenetic regulatory mechanism, serves as a crucial bridge linking environmental exposure, gene expression regulation, and neurobehavioral outcomes. During long-duration deep-space missions, astronauts face multiple stressors-including microgravity, cosmic radiation, circadian rhythm disruption, and social isolation, which can induce alterations in DNA methylation and increase the risk of neuropsychiatric disorders. Genome-wide DNA methylation research can be divided into 3 major methodological stages: Study design, sample preparation and detection, and data analysis, each of which can be applied to astronaut neuropsychiatric health monitoring. Systematic comparison of the Illumina MethylationEPIC array and whole-genome bisulfite sequencing reveals their complementary strengths in terms of genomic coverage, resolution, cost, and application scenarios: the array method is cost-effective and suitable for large-scale population studies and longitudinal monitoring, whereas sequencing provides higher resolution and coverage and is more suitable for constructing detailed methylation maps and characterizing individual variation. Furthermore, emerging technologies such as single-cell methylation sequencing, nanopore long-read sequencing, and machine-learning-based multi-omics integration are expected to greatly enhance the precision and interpretability of epigenetic studies. These methodological advances provide key support for establishing DNA-methylation-based monitoring systems for neuropsychiatric risk in astronauts and lay an epigenetic foundation for safeguarding neuropsychiatric health during future long-term deep-space missions.
DNA Methylation
;
Humans
;
Space Flight
;
Mental Disorders/genetics*
;
Epigenesis, Genetic
;
Astronauts/psychology*
;
Weightlessness/adverse effects*
;
Epigenomics
3.Heavy metal pollution of soil and chronic diseases among residents around an abandoned rare earth ore in Jiangxi
Junwang GU ; Qi WANG ; Haixia JIN ; Yingying LIU ; Wei QIU
Shanghai Journal of Preventive Medicine 2023;35(5):494-499
ObjectiveTo understand the distribution characteristics of soil metal pollution around an abandoned rare earth ore in Jiangxi and the health impact on the surrounding residents. MethodsAccording to the distribution of abandoned rare earth ore, the village was divided into mining and non-mining areas. The prevalence of chronic diseases among residents over 15 years old in the village was collected through a self-designed questionnaire. Twenty-three soil samples were collected. The contents of rare earth metals (including lanthanum, cerium, praseodymium, and neodymium) and heavy metals (including arsenic (metalloids), cadmium, and lead) in the soil samples were determined by inductively coupled plasma mass spectrometry (ICP-MS). ResultsThe metal content showed a cumulative increasing trend. One of the23 sampling sites showed mild cadmium pollution. Compared with non-mining farmland, the metal content of farmland soil around the abandoned rare earth mine was relatively higher. The residents' top six self-reported chronic diseases were hypertension, chronic bronchitis, diabetes, stroke, hyperlipidemia, and cataract. The prevalence of hypertension in mining area was higher than non-mining area (χ2=4.141, P=0.042). The main related factors for hypertension in residents were the increase in age (OR=14.576, 95%CI: 2.773‒76.605) and body mass index (OR=3.147, 95%CI: 1.121‒8.835). ConclusionAbandoned rare earth ore may have a potential impact on the health of surrounding residents.
4.The impact of human umbilical cord-derived mesenchymal stem cells on the pancreatic function of type 2 diabetic mice and their regulatory role on NLRP3 inflammasomes
Jie WANG ; Yaqi YIN ; Yu CHENG ; Bing LI ; Wanlu SU ; Songyan YU ; Jing XUE ; Yulin GU ; Haixia ZHANG ; Linxi ZHANG ; Li ZANG ; Yiming MU
Chinese Journal of Internal Medicine 2023;62(9):1077-1084
Objective:To investigate the effect and regulation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on islets function and NOD-like receptor family, pyrin domain containing 3 (NLRP3) and autophagy in type 2 diabetic mellitus (T2DM) mice.Methods:Experimental study. Twenty, 8-week-old, male C57BL/6J mice were selected and divided into a normal control group ( n=5) and a high-fat feeding modeling group ( n=15). The model of T2DM was established by high-fat feeding combined with intraperitoneal injection of low-dose streptozotocin. After successful modeling, those mice were divided into a diabetes group ( n=7) and a UC-MSCs treatment group ( n=7). The UC-MSCs treatment group was given UC-MSCs (1×10 6/0.2 ml phosphate buffer solution) by tail vein infusion once a week for a total of 4 weeks; the diabetes group was injected with the same amount of normal saline, and the normal control group was not treated. One week after the treatment, mice underwent intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests, and then the mice were sacrificed to obtain pancreatic tissue to detect the expressions of interleukin-1β (IL-1β) and pancreatic and duodenal homeobox 1 (PDX-1) by immunofluorescence. The bone marrow-derived macrophages were stimulated with lipopolysaccharide and adenosine triphosphate (experimental group) in vitro, then co-cultured with UC-MSCs for 24 h (treatment group). After the culture, enzyme-linked immunosorbent assay was used to detect the secretion level of IL-1β in the supernatant, and immunofluorescence staining was used to detect the expression of NLRP3 inflammasome, and related autophagy proteins. Statistical analysis was performed using unpaired one-way analysis of variance, repeated measure analysis of variance. Results:In vivo experiments showed that compared with the diabetes group, the UC-MSCs treatment group partially repaired islet structure, improved glucose tolerance and insulin sensitivity (all P<0.05), and the expression of PDX-1 increased and IL-1β decreased in islets under confocal microscopy. In vitro experiments showed that compared with the experimental group, the level of IL-1β secreted by macrophages in the treatment group was decreased [(85.9±74.6) pg/ml vs. (883.4±446.2) pg/ml, P=0.001], the expression of NLRP3 inflammasome and autophagy-related protein P62 was decreased, and the expressions of microtubule-associated protein 1 light chain 3β (LC3) and autophagy effector Beclin-1 were increased under confocal microscopy. Conclusions:UC-MSCs can reduce the level of pancreatic inflammation in T2DM mice, preserving pancreatic function. This might be associated with the ability of UC-MSCs to inhibit the activity of NLRP3 inflammasomes in macrophages and enhance autophagy levels.
5.The association between RABL6 gene methylation in peripheral blood and early lung cancer in Chinese population
Haixia Huang ; Rong Qiao ; Mengxia Li ; Wanjian Gu ; Baohui Han ; Rongxi Yang
Acta Universitatis Medicinalis Anhui 2023;58(6):1030-1036
Objective :
To explore the relationship between the methylation level of RABL6 in peripheral blood and early lung cancer (LC) with a case-control study in the Chinese population.
Methods :
The methylation levels of 7 CpG sites in RABL6 gene in peripheral blood of samples from 275 LC patients (81.5% at stage I) ,and age- and gender-matched 185 benign lung nodule cases and 267 matched healthy controls were measured by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.Multinomial Logistic regression adjusted for covariates was used to analyze the association between the RABL6 methylation and LC.Mann-Whitney U test was applied for the comparisons of RABL6 methylation levels between clinical characteristics subgroups of LC.
Results :
Compared to the healthy controls,the methylation of RABL6 _CpG_ 17 was inversely associated with LC in females ( per - 10% methylation : OR = 2. 47,95% CI = 1. 19-5. 13,P = 0. 016) ,but positively associated with LC in males (per - 10% methylation : OR = 0. 52,95% CI = 0. 29-0. 94,P = 0. 030) .In addition,hypermethylation of RABL6_CpG _2 and RABL6_CpG_5 was significantly associated with LC in the subjects older than 55 years (for RABL6_CpG_ 2 : per -10% methylation : OR = 0. 77,95% CI = 0. 60-0. 99,P = 0. 038 ; for RABL6_CpG_5 : OR = 0. 58,95% CI = 0. 34-0. 97,P = 0. 038) .
Conclusion
The study reveals an association between peripheral blood-based RABL6 methylation levels and early LC,providing a new clue for developing peripheral blood-based DNA methylation as a potential marker for the evaluation of LC risk.
6.Multi-omics of Circular RNAs and Their Responses to Hormones in Moso Bamboo (Phyllostachys edulis).
Yongsheng WANG ; Huihui WANG ; Huiyuan WANG ; Ruifan ZHOU ; Ji WU ; Zekun ZHANG ; Yandong JIN ; Tao LI ; Markus V KOHNEN ; Xuqing LIU ; Wentao WEI ; Kai CHEN ; Yubang GAO ; Jiazhi DING ; Hangxiao ZHANG ; Bo LIU ; Chentao LIN ; Lianfeng GU
Genomics, Proteomics & Bioinformatics 2023;21(4):866-885
Circular RNAs (circRNAs) are endogenous non-coding RNAs with covalently closed structures, which have important functions in plants. However, their biogenesis, degradation, and function upon treatment with gibberellins (GAs) and auxins (1-naphthaleneacetic acid, NAA) remain unknown. Here, we systematically identified and characterized the expression patterns, evolutionary conservation, genomic features, and internal structures of circRNAs using RNase R-treated libraries from moso bamboo (Phyllostachys edulis) seedlings. Moreover, we investigated the biogenesis of circRNAs dependent on both cis- and trans-regulation. We explored the function of circRNAs, including their roles in regulating microRNA (miRNA)-related genes and modulating the alternative splicing of their linear counterparts. Importantly, we developed a customized degradome sequencing approach to detect miRNA-mediated cleavage of circRNAs. Finally, we presented a comprehensive view of the participation of circRNAs in the regulation of hormone metabolism upon treatment of bamboo seedlings with GA and NAA. Collectively, our study provides insights into the biogenesis, function, and miRNA-mediated degradation of circRNAs in moso bamboo.
RNA, Circular/metabolism*
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Multiomics
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Poaceae/metabolism*
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Seedlings/genetics*
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Hormones/metabolism*
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MicroRNAs/metabolism*
;
Gene Expression Regulation, Plant
7.Predictive value of biphasic CT air trapping sign and semi-quantitative score in predicting abnormal blood gas index and progression to severe disease in COVID-19 patients
Lijuan ZHOU ; Xiaoming LIN ; Haixia MAO ; Yaxing BAO ; Shiliang ZHANG ; Hongwei CHEN ; Quansheng GAO ; Lan GU ; Xiangming FANG
Chinese Journal of Radiology 2022;56(3):241-247
Objective:To explore the predictive value of low-dose biphasic (inspiratory and expiratory) CT air trapping sign and semi-quantitative score in predicting abnormal blood gas parameters and progression to severe disease in COVID-19 patients.Methods:Patients with non-severe COVID-19 who were diagnosed by nucleic acid testing and hospitalized in designated hospitals in Wuxi City from January 23 to February 29, 2020 were prospectively and consecutively recruited. All patients received low-dose biphasic CT examination on admission and repeated CT examination at regular intervals during the course. On the inspiratory phase admission of the bipolar CT, the scope of the lesion was evaluated by semi-quantitative score, and the air trapping sign on bipolar CT was assessed. The differences of semi-quantitative score, the presence of the air trapping sign and other clinical factors were compared between the patients with abnormal and the normal blood gas index, as well as between the cases progressed to severe disease and cases without disease progression using the independent sample t-test or χ 2 test. The area under the curve (AUC) of receiver operating characteristic (ROC) and the comprehensive discriminant improvement index (IDI) were used to evaluate the predictive effectiveness of the semi-quantitative scores, air trapping sign, and combination of two factors in differentiating cases with abnormal and normal blood gas indexes, as well as in differentiating cases with and without disease progression to severe COVID-19 cases. Results:In total 51 non-severe COVID-19 cases were included, with 16 cases showed air trapping sign during the first biphasic CT examination on admission. During the course of the disease, there were 13 patients with abnormal blood gas index, and 9 cases displaying air trapping sign (9/13). All 7 cases with progression to severe cases showed air trapping sign (7/7). Patients with advanced age, air trapping sign and higher semi-quantitative score were found more likely to have abnormal blood gas index ( t=3.10, χ 2=9.38, t=3.34, P<0.05); patients with advanced age, underlying diseases, air trapping sign and higher semi-quantitative score were more likely to develop into severe disease ( t=2.68, χ 2=6.65, χ 2=4.25, t=4.33, P<0.05). The AUC of semi-quantitative score, air trapping sign and combination of two factors in distinguishing abnormal blood gas index from normal blood gas index was 0.803, 0.754 and 0.794 respectively. The AUC of semi-quantitative score, air trapping sign and combination of two factors in distinguishing cases with progression to severe cases from non-progression was 0.881, 0.898 and 0.932, respectively. Air trapping sign combined with semi-quantitative score significantly improved the prediction effectiveness of disease progression, compared with semi-quantitative score or air trapping sign (IDI=0.271, 0.117). Conclusion:Air trapping sign and semi-quantitative score might be used as effective indicators to predict the progression of COVID-19 cases, and the combination of these two factors might be more helpful to predict the disease progression.
8.Serum C-type lectin-like receptor-2 combined with insulin resistance predicts the outcome of patients with acute ischemic stroke after intravenous thrombolysis
Haixia JI ; Han WANG ; Xiangyang ZHU ; Chenchen GU ; Xiaoyi YI
International Journal of Cerebrovascular Diseases 2021;29(9):659-665
Objective:To investigate the predictive value of serum C-type lectin-like receptor 2 (CLEC-2) combined with insulin resistance in the outcome of patients with acute ischemic stroke (AIS) after intravenous thrombolysis.Methods:Patients with AIS received alteplase intravenous thrombolytic therapy in the Department of Neurology, the Second Affiliated Hospital of Nantong University from October 2019 to March 2021 were enrolled retrospectively. According to the modified Rankin Scale score at 90 d after onset, they were divided into good outcome group (0-2) and poor outcome group (>2). Homeostasis model assessment of insulin resistance (HOMA-IR) was used to evaluate insulin resistance. Person correlation analysis was used to determine the correlation between CLEC-2 and HOMA-IR. Multivariate logistic regression analysis was used to determine the correlation between serum CELC-2, HOMA-IR and the outcome after intravenous thrombolysis. Receiver operating characteristic (ROC) curve was used to determine the predictive value of serum CLEC-2 combined with HOMA-IR for poor outcome after intravenous thrombolysis. Results:A total of 100 patients were enrolled (56 males, 56.0%; aged 70.6±10.86 years, range 49-83 years). The baseline National Institutes of Health Stroke Scale (NIHSS) score was 10.00±6.36. Senenty-four patients (74.0%) had a good outcome and 26 (26.0%) had a poor outcome. Person correlation analysis showed that there was a significant positive correlation between serum CLEC-2 and HOMA-IR ( r=0.523; P<0.001). Multivariate logistic regression analysis showed that after adjusting for confounding factors (C-reactive protein, baseline NIHSS score, onset-to-needle time), the highest quartile of serum CLEC-2 (compared with the lowest quartile: odds ratio [ OR] 4.836, 95% confidence interval [ CI] 1.105-21.169; P=0.036) and the highest quartile of HOMA-IR (compared with the quartile 1-3: OR 15, 95% CI 2.647-30.722; P=0.002) were the independent risk factors for the poor outcome in patients with AIS after intravenous thrombolysis. ROC curve analysis showed that the area under the curve for serum CLEC-2 combined with HOMA-IR to predict poor outcome was 0.785 (95% CI 0.688-0.883; P<0.001), the optimal cut-off value was 0.72, and the sensitivity and specificity were 76.0% and 95.0%, respectively. Conclusion:CLEC-2 combined with insulin resistance has a certain predictive value for the poor outcome of patients with AIS after intravenous thrombolysis.
9.Research progress on the study of the relationship between periodontitis and cancers of the digestive system
GU Wenjia ; LU Haixia ; ZHANG Yu ; FENG Xiping
Journal of Prevention and Treatment for Stomatological Diseases 2021;29(5):346-350
Periodontitis is closely related to many systemic diseases. Cancer of the digestive system is a common malignant tumor. Increasing evidence has shown that periodontitis is related to various digestive system cancers. This review summarizes the current research on the relationship between periodontitis and esophageal cancer, gastric cancer, and colorectal cancer and analyzes the possible mechanisms, including via microorganisms, immunity, inflammation, and genes. The content of periodontal pathogens and Helicobacter pylori in the mouth of patients with periodontitis is increased, with the secretion of many virulence factors and pathogenic enzymes and inhibition or evasion of the host’s non-specific immune function, making the digestive system organs connected to the oral cavity more vulnerable to cancer cell invasion. The plasma levels of interleukin-1β(IL-1β) , interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in patients with periodontitis and digestive system cancers are increased. These elevated factors promote the occurrence and development of cancer by activating endothelial cells, increasing the expression of adhesion molecules and inducing the production of matrix metalloproteinases. Additionally, formyl peptide receptors involved in the inflammatory response and NF-κB, as therapeutic targets of periodontitis, are associated with many cancers, but the mechanism is unclear. Periodontal health is considered a breakthrough point to provide a reference for the prevention and treatment of patients with these three common cancers of the digestive system.
10.Prolonged duration of positive virus-PCR results in patients with COVID-19 may be associated with diabetes mellitus
Xin GUAN ; Haixia GUAN ; Ye GU ; Luping LI ; Leishi WANG ; Yan WANG ; Haoge QIN ; Yunfei GAO ; Xiaomei WANG
Chinese Journal of Endocrinology and Metabolism 2020;36(8):661-666
Objective:To investigate the correlation between concomitant diabetes mellitus and clinical features in patients with COVID-19.Methods:Fifty patients with COVID-19 admitted to the Sixth People′s Hospital of Shenyang were divided into 2 groups with and without diabetes mellitus. Indexes such as hospitalization days, duration of positive virus-PCR result, secondary infection, duration of fever, rate of liver dysfunction, and rate of cardiac injury were compared between 2 groups.Results:The average hospitalization durations of diabetes group and control group were(24.0±6.8) and(18.4±5.9) days, respectively, and the duration of positive virus-PCR testing results were(16.0±4.5) and(12.3±4.4) days respectively, suggesting longer hospital stay and longer time for virus clearance in the diabetes group than those in the control group(both P<0.05). The rates of secondary infection, severe subtype, liver dysfunction and cardiac injury in the diabetes group increased, though without significant difference( P>0.05). Conclusion:Prolonged duration of positive virus-PCR result and average days of hospitalization in patients with COVID-19 may be associated with diabetes mellitus.


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