Publications by authors named "Ziliang Wang"

96 Publications

Differential methylation of genes in the human placenta associated with bisphenol A exposure.

Environ Res 2021 Jun 2;200:111389. Epub 2021 Jun 2.

Department of Epidemiology and Social Science, NHC Key Lab. of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai, China.

Prenatal exposure to bisphenol A (BPA) is associated with numerous adverse health outcomes among offspring. Although DNA methylation is considered one of the underlying causes of these associations, few studies have focused on the association between prenatal BPA exposure and DNA methylation in the human placenta. In this study, we examined the association between prenatal BPA exposure and DNA methylation in the placenta of 146 mother-infant pairs from the Shanghai-Minhang Birth Cohort Study. BPA concentrations in maternal urine samples were measured using high-performance liquid chromatography. Six placenta samples were selected for whole-genome methylation analysis using Infinium Human Methylation 450K Beadchip, followed by pyrosequencing-based methylation analysis of three selected genes in 146 placentas. Among 282 differentially methylated CpGs, representing 208 genes, 127 were hypermethylated, and 155 were hypomethylated in the BPA exposure group. Prenatal BPA exposure was associated with a higher methylation level of HLA-DRB6 in individuals as determined using pyrosequencing, which was consistent with the whole-genome methylation analysis results. Compared with that subjects with low BPA exposure, the methylation level (ln-transformed) of HLA-DRB6 in placentas from those with high BPA exposure increased by 0.29% (95% confidence interval[CI]: 0.02%, 0.56%) at the CpG2 site, and the average methylation level (ln-transformed) of the three CpG sites increased by 0.30% (95%CI: -0.03%, 0.63%). Our findings provide evidence that prenatal BPA exposure might alter DNA methylation levels in the placenta.
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http://dx.doi.org/10.1016/j.envres.2021.111389DOI Listing
June 2021

Programmed death ligand-1 regulates angiogenesis and metastasis by participating in the c-JUN/VEGFR2 signaling axis in ovarian cancer.

Cancer Commun (Lond) 2021 Jun 3;41(6):511-527. Epub 2021 May 3.

Department of Gynecological Oncology and Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.

Background: Although programmed cell death-ligand 1 (PD-L1) plays a well-known function in immune checkpoint response by interacting with programmed cell death-1 (PD-1), the cell-intrinsic role of PD-L1 in tumors is still unclear. Here, we explored the molecular regulatory mechanism of PD-L1 in the progression and metastasis of ovarian cancer.

Methods: Immunohistochemistry of benign tissues and ovarian cancer samples was performed, followed by migration, invasion, and angiogenesis assays in PD-L1-knockdown ovarian cancer cells. Immunoprecipitation, mass spectrometry, and chromatin immunoprecipitation were conducted along with zebrafish and mouse experiments to explore the specific functions and mechanisms of PD-L1 in ovarian cancer.

Results: Our results showed that PD-L1 induced angiogenesis, which further promoted cell migration and invasion in vitro and in vivo of ovarian cancer. Mechanistically, PD-L1 was identified to directly interact with vascular endothelial growth factor receptor-2 (VEGFR2) and then activated the FAK/AKT pathway, which further induced angiogenesis and tumor progression, leading to poor prognosis of ovarian cancer patients. Meanwhile, PD-L1 was found to be regulated by the oncogenic transcription factor c-JUN at the transcriptional level, which enhanced the expression of PD-L1 in ovarian cancer. Furthermore, we demonstrated that PD-L1 inhibitor durvalumab, combined with the antiangiogenic drug, apatinib, could enhance the effect of anti-angiogenesis and the inhibition of cell migration and invasion.

Conclusion: Our results demonstrated that PD-L1 promoted the angiogenesis and metastasis of ovarian cancer by participating in the c-JUN/VEGFR2 signaling axis, suggesting that the combination of PD-L1 inhibitor and antiangiogenic drugs may be considered as a potential therapeutic approach for ovarian cancer patients.
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http://dx.doi.org/10.1002/cac2.12157DOI Listing
June 2021

The lnc-CTSLP8 upregulates CTSL1 as a competitive endogenous RNA and promotes ovarian cancer metastasis.

J Exp Clin Cancer Res 2021 May 1;40(1):151. Epub 2021 May 1.

Department of Gynecology and Obstetrics, XinHua Hospital, Shanghai JiaoTong University School of Medicine, 1665 Kongjiang Rd, Yangpu District, Shanghai, 200092, China.

Background: Ovarian cancer is highly lethal and has a poor prognosis due to metastasis. Long non-coding RNAs (lncRNAs) are key regulators of tumor development, but their role in ovarian cancer metastasis remains unclear.

Methods: The expression of lnc-CTSLP8 in ovarian cancer was analyzed in public databases (TCGA and GEO) and validated via qRT-PCR. Lnc-CTSLP8 overexpression and knockout cell lines were constructed using a lentiviral vector and the CRISP/Cas9 system. Cell proliferation, colony formation, migration, and invasion were analyzed. An ovarian orthotopic tumor mouse model was used for the in vivo study. Changes in autophagosomes, autolysosomes, and mitochondria in ovarian cancer cells were observed via transmission electron microscopy. EMT markers were detected by immunoblotting and immunofluorescence assays. RNA immunoprecipitation, RNA pull-down, and dual luciferase reporter assays were performed to confirm the interaction between lnc-CTSLP8 and miR-199a-5p.

Results: A novel pseudogene, lnc-CTSLP8, was identified in ovarian cancer, with significantly elevated expression in metastatic tumor tissues compared to primary ovarian tumors. When overexpressed, lnc-CTSLP8 promoted ovarian cancer in vitro and in vivo by acting as a sponge for miR-199a-5p. Autophagy and EMT in ovarian cancer were also enhanced by lnc-CTSLP8. Mechanistically, lnc-CTSLP8 upregulated CTSL1 as a competitive endogenous RNA and exhibited oncogenic effects. Moreover, CTSL1 inhibitor treatment and miR-199a-5p overexpression abrogated the effects of lnc-CTSLP8 overexpression.

Conclusions: lnc-CTSLP8 acts as a ceRNA in ovarian cancer and represents a potential therapeutic target for metastatic ovarian cancer.
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http://dx.doi.org/10.1186/s13046-021-01957-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088648PMC
May 2021

Prenatal exposure to residential PM and its chemical constituents and weight in preschool children: A longitudinal study from Shanghai, China.

Environ Int 2021 Sep 24;154:106580. Epub 2021 Apr 24.

NHC Key Lab. Of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), School of Public Health, Fudan University, 779 Old Hu Min Road, Shanghai 200237, China.

Background: Studies have reported that prenatal exposure to fine particulate matter (PM) might be associated with adverse birth outcomes in offspring. However, evidence with regard to the effects of prenatal exposure to PM and, especially, its main chemical constituents on offspring's weight in childhood is limited and inconsistent.

Objectives: The present study aimed to examine associations of prenatal exposure to PM total mass and its chemical constituents in each trimester with children's weight from birth to 6 years of age using data from Shanghai-Minhang Birth Cohort Study.

Methods: A total of 1,084 mother-infant pairs were included with both PM exposure data and at least one measurement of weight and height. Weight-for-Length (WLZ), BMI-for-Age (BMIz), and Weight-for-Age (WAZ) z-scores were generated according to the World Health Organization guidelines. Exposure to PM total mass and its chemical constituents [organic carbon (OC), black carbon (BC), ammonium (NH), nitrate (NO), sulfate (SO), and soil dust (SOIL)] during pregnancy was estimated from a satellite based modelling framework. We used multiple informant model to estimate the associations of trimester-specific PM total mass and its specific constituents concentrations with WLZ/BMIz and WAZ of offspring at birth and 1, 4, and 6 years of age.

Results: In multiple informant model, we observed consistent patterns of associations between exposure to PM total mass, OC, BC, NH, NO, and SO during the 2 and 3 trimesters and decreased WLZ/BMIz and WAZ at 1, 4, and 6 years of age in boys. We observed associations between prenatal exposure to PM total mass, NH, and NO during the 1 and 2 trimesters and increased WLZ/BMIz and WAZ in girls at birth. However, there were null associations at 1 and 4 years of age and inverse associations at 6 years of age.

Conclusions: Prenatal exposure to PM total mass and its main chemical constituents was associated with decreased weight in boys from 1 to 6 years of age, with increased weight at birth and decreased weight at 6 years of age in girls. Our findings suggest that prenatal exposure to PM and its chemical constituents may have a lasting effect on offspring's weight in childhood.
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http://dx.doi.org/10.1016/j.envint.2021.106580DOI Listing
September 2021

Stanniocalcin-2 promotes cell EMT and glycolysis via activating ITGB2/FAK/SOX6 signaling pathway in nasopharyngeal carcinoma.

Cell Biol Toxicol 2021 Apr 2. Epub 2021 Apr 2.

Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Stanniocalcin-2 (STC2) has been proved to regulate a variety of signaling pathways including cell growth, metastasis, and therapeutic resistance. However, the role of STC2 in the regulation of nasopharyngeal carcinoma (NPC) remains poorly understood. In this study, we investigated the regulatory function of STC2 on epithelial-mesenchymal transition (EMT) and glycolysis traits in NPC and revealed the underlying molecular mechanisms. We found that STC2 was highly expressed in primary nasopharyngeal carcinoma tissues and lymph node metastatic tissues. Silencing of STC2 inhibited cell proliferation, invasion, and glycolysis. Further analyses for the clinical samples demonstrated that STC2 expression was associated with the poor clinical progression. Moreover, we demonstrated the interaction of ITGB2 with STC2 and its involvement in STC2-mediated ITGB2/FAK/SOX6 axis. Collectively, our results provide new insights into understanding the regulatory mechanism of STC2 and suggest that the STC2/ITGB2/FAK/SOX6 signaling axis may be a potential therapeutic target for NPC.
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http://dx.doi.org/10.1007/s10565-021-09600-5DOI Listing
April 2021

Prenatal exposure to bisphenol analogues and digit ratio in children at ages 4 and 6 years: A birth cohort study.

Environ Pollut 2021 Jun 25;278:116820. Epub 2021 Feb 25.

NHC Key Lab. of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Public Health School, Fudan University, 779 Old Humin Road, Shanghai, China. Electronic address:

Bisphenol analogues (BPs), including bisphenol A (BPA), have been shown to exhibit similar endocrine disrupting activities. However, epidemiological evidence on the reproductive and developmental toxicities of BPs other than BPA is scarce. The second to fourth digit ratio (2D:4D), an endocrine-sensitive endpoint, has been suggested to be a biomarker of prenatal sex steroid exposure and associated with reproductive outcomes in later life. Using the data of 545 mother-child pairs from the Shanghai-Minhang Birth Cohort Study, we prospectively assessed the effects of prenatal exposure to BPs on 2D:4D in children at ages 4 and 6 years. Single-spot urine samples were collected in the third trimester and analyzed for BPs. Digit lengths were measured using a vernier caliper in children at ages 4 and 6 years, and the 2D:4D values for both hands were calculated. A multivariable linear regression model was applied to examine associations between prenatal BPs exposure and 2D:4D digit ratios at each age separately. The generalized estimating equation (GEE) model was used to deal with repeated 2D:4D measures obtained at ages 4 and 6 years. We found that prenatal exposure to BPA alternatives including BPF, BPS, and BPAF was associated with higher digit ratio in boys and/or girls (feminizing), while TCBPA, a halogenated bisphenol, was associated with lower 2D:4D in boys (masculinizing). These associations were more pronounced at 4 years of age, and tended to remain after further considering the potential confounding from prenatal co-exposure to other BPs and childhood BPs exposure. Our study provides epidemiological evidence that BPs exposure during pregnancy may alter the digit development in children, indicative of disrupted reproductive development in later life. Given these new findings, further studies are needed to corroborate our results.
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http://dx.doi.org/10.1016/j.envpol.2021.116820DOI Listing
June 2021

Association between prenatal exposure to polybrominated diphenyl ethers and anogenital distance in girls at ages 0-4 years.

Int J Hyg Environ Health 2021 Apr 11;233:113706. Epub 2021 Feb 11.

NHC Key Lab. of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai, China. Electronic address:

Anogenital distance (AGD) is a sensitive marker for the effect of in utero hormonal disturbance. However, studies on the associations between prenatal exposure to polybrominated diphenyl ethers (PBDEs), a group of endocrine disruptors, and AGD are limited. We examined the associations between prenatal PBDE exposure and AGD in girls at ages 0-4 years in the Shanghai-Minhang Birth Cohort Study. We measured PBDE in cord plasma collected from 148 girls at birth. Of them, two AGD metrics (AGD: from the anterior surface of the clitoral hood to the center of the anus; AGD: from the posterior end of the fourchette to the center of the anus) were measured in 142, 114, 104 and 120 of girls at birth, 6, 12, and 48 months of age, respectively. Linear regression models and linear mixed models were used to evaluate the associations between PBDE exposure and AGD at ages 0-4 years. We found positive associations of PBDE exposure with AGD and AGD in linear regression models, although some associations only reached significance at 6 and 48 months of age. For AGD, the associations were statistically significant for BDE-47, -99, and -100 at 6 months of age (β = 2.34, 95% CI (0.21, 4.48) for BDE-47; β = 2.21, 95% CI (0.05, 4.36) for BDE-99; β = 2.12, 95% CI (0.01, 4.23) for BDE-100), and for BDE-99 and -100 at 48 months of age (β = 4.49, 95% CI (1.27, 7.71) for BDE-99; β = 5.04, 95% CI (1.87, 8.22) for BDE-100), while statistically significant associations with AGD were only observed for BDE-99, -100, -153, and ∑PBDEs at 48 months of age (β = 7.62, 95% CI (2.59, 12.64) for BDE-99; β = 7.04, 95% CI (2.01, 12.07) for BDE-100; β = 5.41, 95% CI (0.45, 10.38) for BDE-153; β = 5.05 mm, 95% CI (0.09, 10.01 for ∑PBDEs). A consistent pattern of positive associations between prenatal exposure to PBDEs and AGD was also observed in linear mixed models. The finding provided further insights into the adverse effects of PBDEs on reproductive development at low dose exposure.
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http://dx.doi.org/10.1016/j.ijheh.2021.113706DOI Listing
April 2021

Prenatal exposure to perfluoroalkyl substances and thyroid hormone concentrations in cord plasma in a Chinese birth cohort.

Environ Health 2020 11 26;19(1):127. Epub 2020 Nov 26.

Department of Social Medicine and Reproductive Epidemiology, National Health Commission Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, #779 Lao Hu Min Road, Shanghai, 200032, China.

Background: Evidence of associations between prenatal exposure to perfluoroalkyl substances (PFASs) and fetal thyroid hormones (THs) is controversial, and few studies have estimated the associations, while addressing the high correlations among multiple PFASs. We aimed to examine the associations between prenatal PFAS exposure and thyroid hormone concentrations in cord blood.

Methods: A total of 300 mother-infant pairs from the Shanghai-Minhang Birth Cohort Study were included. We measured the concentrations of eight PFASs in maternal plasma samples collected at 12-16 gestational weeks, as well as those of total thyroxine (T4), free T4 (FT4), total triiodothyronine (T3), free T3 (FT3), and thyroid stimulating hormone (TSH) in cord plasma. We estimated the associations between maternal PFAS concentrations and TH concentrations using linear regression and Bayesian kernel machine regression (BKMR) models.

Results: In BKMR models, higher PFAS mixture concentrations were associated with increased T3 concentrations, and there were suggestive associations with increased FT3 concentrations. For single-exposure effects in BKMR models, a change in PFDA, PFUdA, and PFOA concentrations from the 25th to 75th percentile was associated with a 0.04 (95%CrI: - 0.01, 0.09), 0.02 (95%CrI: - 0.03, 0.07), and 0.03 (95%CrI: - 0.001, 0.06) nmol/L increase in T3 concentrations, respectively. PFOA, PFNA, and PFDA were the predominant compounds in PFASs-FT3 associations, and the corresponding estimates were 0.11 (95% CrI: 0.02, 0.19), - 0.17 (95% CrI: - 0.28, - 0.07), and 0.12 (95% CrI: - 0.004, 0.24) pmol/L, respectively. A change in PFNA and PFOA concentrations from the 25th to 75th percentile was associated with a - 1.69 (95% CrI: - 2.98, - 0.41) μIU/mL decrease and a 1.51 (95% CrI: 0.48, 2.55) μIU/mL increase in TSH concentrations. The associations of PFOA and PFNA with T3/FT3 were more pronounced in boys, while those with TSH were more pronounced in girls.

Conclusion: Our results suggest that prenatal exposure to multiple PFASs was associated with thyroid hormones in cord blood. However, individual PFAS had varied effects-differing in magnitude and direction-on fetal thyroid hormones.
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http://dx.doi.org/10.1186/s12940-020-00679-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690128PMC
November 2020

Prenatal exposure to perfluoroalkyl substances and cord plasma lipid concentrations.

Environ Pollut 2021 Jan 21;268(Pt A):115426. Epub 2020 Aug 21.

NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, 779 Old Hu Min Road, Shanghai, 200237, China. Electronic address:

The effect of prenatal exposure to perfluoroalkyl substances (PFAS) on lipid concentrations in newborns is unknown. Using data from the Shanghai-Minhang Birth Cohort Study, we prospectively assessed the health effects of prenatal exposure to individual and multiple PFAS on cord lipid concentrations. Maternal plasma samples collected at 12-16 weeks of gestation were analyzed for eleven PFAS, and cord blood samples were analyzed for lipids: total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). We used multiple linear regression models to evaluate the associations of each individual PFAS with each lipid parameter, and used Bayesian Kernel Machine Regression (BKMR) models to assess the overall and single-exposure effects of eight PFAS with the detection rate above 80% on cord lipid concentrations. In multiple linear regression models, for each unit increase in ln-transformed maternal concentrations of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA), and perfluorotridecanoic acid (PFTrDA), ln-transformed TC concentration decreased by 0.15 mg/dL (95% confidence interval (CI): -0.25, -0.05), 0.12 mg/dL (95% CI: -0.19, -0.05), 0.12 mg/dL (95% CI: -0.19, -0.05), and 0.05 mg/dL (95% CI: -0.09, -0.01), respectively, and ln-transformed HDL-C concentration decreased by 0.17 mg/dL (95% CI: -0.29, -0.05), 0.12 mg/dL (95% CI: -0.20, -0.03), 0.12 mg/dL (95% CI: -0.20, -0.03), and 0.06 mg/dL (95% CI: -0.11, -0.00), respectively. Statistically significant inverse associations were also observed between ln-transformed concentrations of PFDA, PFUdA, or PFTrDA and ln-transformed cord concentrations of TG and LDL-C. In BKMR models, the mixture of eight PFAS showed suggestively inverse association with all ln-transformed lipid concentrations, such that ln-transformed TC concentration of exposure to the 75th percentile of the mixture was 0.11 units (95% credible interval, -0.21, -0.01) lower than the 25th percentile exposure. Our findings indicated that prenatal exposure to PFAS may disrupt lipid metabolism in newborns.
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http://dx.doi.org/10.1016/j.envpol.2020.115426DOI Listing
January 2021

Effects of prenatal exposure to polybrominated diphenyl ethers (PBDEs) on the second to fourth digit ratio in children aged 4 years.

Int J Hyg Environ Health 2021 Jan 29;231:113639. Epub 2020 Oct 29.

NHC Key Lab. of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), School of Public Health, Fudan University, China.

Background: The second to fourth digit ratio (2D:4D) is assumed to be a biomarker of prenatal sex steroid exposure, correlating negatively with prenatal testosterone and positively with prenatal estrogen. The ratio has been suggested to be influenced by endocrine disrupting chemicals (EDCs). However, evidence regarding effects of prenatal exposure to polybrominated diphenyl ethers (PBDEs) on 2D:4D of children was sparse.

Objectives: We investigated the associations between prenatal exposure to PBDEs and 2D:4D of children aged 4 years.

Methods: Participants were mother-child pairs from the Shanghai-Minhang Birth Cohort Study (S-MBCS) which enrolled pregnant women at 12-16 weeks of gestation from April to December 2012. Nine PBDE congeners in venous umbilical cord plasma of 340 children were measured. Digit lengths were measured using a vernier caliper in children aged 4 years and 2D:4D for left and right hands and average 2D:4D value of both hands were calculated. A total of 281 children (160 boys and 121 girls) who had data on both 2D:4D and PBDE concentrations were included in the final analysis. Associations between prenatal PBDE exposures and 2D:4D were investigated using multiple linear regression models.

Results: Among the nine congeners, BDE-47 had the highest detection rate of 86.12% with the highest median concentration of 0.20 ng/ml lipid. Five PBDE congeners with detection rates greater than or close to 50% (BDE-28, -47, -99, -100 and -153) and ΣPBDEs (the sum of them) were included in final analysis. For girls, a consistent pattern for the positive associations between prenatal PBDE exposures and 2D:4D of children was observed mainly for the left hand, where those in the highest exposure groups had higher 2D:4D compared to the lowest exposure groups (a feminizing effect), with statistically significant associations observed for BDE-47 (β = 0.0247, 95% confidence interval (CI): 0.0017, 0.0477), -100 (β = 0.0264, 95% CI: 0.0087, 0.0441) and ΣPBDEs (β = 0.0201, 95% CI: 0.0027, 0.0374). For boys, compared with the lowest exposure groups, statistically significantly higher (feminized) 2D:4D for both hands was observed in those with the highest exposure levels of BDE-100 (β = 0.0147, 95% CI: 0.0005, 0.0289 for the left hand; β = 0.0182, 95% CI: 0.0046, 0.0318 for the right hand) and those with the middle and the highest exposure levels of BDE-153 (middle vs. undetected, β = 0.0215, 95% CI: 0.0072, 0.0358 for the left hand; β = 0.0155, 95% CI: 0.0015, 0.0295 for the right hand; highest vs. undetected, β = 0.0162, 95% CI: 0.0017, 0.0307 for the left hand; β = 0.0152, 95% CI: 0.0011, 0.0294 for the right hand).

Conclusions: Our study provides preliminary evidence that prenatal exposure to PBDEs might be associated with higher 2D:4D in boys and girls.
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http://dx.doi.org/10.1016/j.ijheh.2020.113639DOI Listing
January 2021

Chronic social defeat stress mouse model: Current view on its behavioral deficits and modifications.

Behav Neurosci 2020 Oct 22. Epub 2020 Oct 22.

Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University.

Stress is the main cause of mood disorders such as depression and posttraumatic stress disorder. Individuals respond to stress differently, as some develop depressive symptoms, whereas others successfully cope with adversity, but it remains unclear what makes some particularly vulnerable to stress. The chronic social defeat stress (CSDS) mouse model, an ethologically valid rodent model that exhibits long-term physiological and behavioral phenotypes similar to depression and anxiety, can imitate individual differences in stress responses in humans. In this review, we not only summarize various behavioral deficits of the CSDS mouse model that were reported since its establishment but also concentrate on modified CSDS mouse models that have been developed in recent years, aiming at providing useful information for future research and application of this model. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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http://dx.doi.org/10.1037/bne0000418DOI Listing
October 2020

More stringent criteria are needed for diagnosing internet gaming disorder: Evidence from regional brain features and whole-brain functional connectivity multivariate pattern analyses.

J Behav Addict 2020 Oct 7;9(3):642-653. Epub 2020 Oct 7.

6Department of Psychiatry, Child Study Center, Yale University School of Medicine, New Haven, CT, USA.

Background: Internet gaming disorder (IGD) is included in the DSM-5 as a provisional diagnosis. Whether IGD should be regarded as a disorder and, if so, how it should be defined and thresholded have generated considerable debate.

Methods: In the current study, machine learning was used, based on regional and interregional brain features. Resting-state data from 374 subjects (including 148 IGD subjects with DSM-5 scores ≥5 and 93 IGD subjects with DSM-5 scores ≥6) were collected, and multivariate pattern analysis (MVPA) was employed to classify IGD from recreational game use (RGU) subjects based on regional brain features (ReHo) and communication between brain regions (functional connectivity; FC). Permutation tests were used to assess classifier performance.

Results: The results demonstrated that when using DSM-5 scores ≥5 as the inclusion criteria for IGD subjects, MVPA could not differentiate IGD subjects from RGU, whether based on ReHo or FC features or by using different templates. MVPA could differentiate IGD subjects from RGU better than expected by chance when using DSM-5 scores ≥6 with both ReHo and FC features. The brain regions involved in the default mode network and executive control network and the cerebellum exhibited high discriminative power during classification.

Discussion: The current findings challenge the current IGD diagnostic criteria thresholding proposed in the DSM-5, suggesting that more stringent criteria may be needed for diagnosing IGD. The findings suggest that brain regions involved in the default mode network and executive control network relate importantly to the core criteria for IGD.
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http://dx.doi.org/10.1556/2006.2020.00065DOI Listing
October 2020

Association between prenatal bisphenol a exposure and promoter hypermethylation of CAPS2, TNFRSF25, and HKR1 genes in cord blood.

Environ Res 2020 11 4;190:109996. Epub 2020 Aug 4.

Department of Epidemiology and Social Science, NHC Key Lab. of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai, China.

In utero exposure to bisphenol A (BPA) in early stages of development has been reported to exert adverse health effects on offspring later in life. Epigenetic alterations, particularly DNA methylation, may be one plausible biological mechanism involved. We examined the association between maternal BPA exposure and DNA methylation in cord blood. We randomly selected 96 paired samples of maternal urine and infant cord blood collected from the Shanghai-Minhang Birth Cohort. BPA levels in maternal urine were measured using high-performance liquid chromatography (HPLC). Three cord blood samples with maternal BPA levels >2.0 μg/g Cr and three samples with undetected BPA were randomly selected for genome-wide methylation analysis using methylated DNA binding domain sequencing (MBD-Seq). The genes with hypermethylated promoter regions were chosen for validation using quantitative methylation-specific polymerase chain reaction (Q-MSP). Based on MBD-seq results, we observed that maternal BPA exposure was primarily associated with hypermethylation of genes involved in signal transduction in the nervous system. Using Q-MSP, we further validated the association between maternal BPA exposure and promoter hypermethylation of three genes in multiple linear regression models: a log unit increase in BPA was associated with 12.63% (95%CI: 7.99, 17.26), 11.17%, (95%CI: 3.31, 19.02), and 16.57% (95% CI: 10.59, 22.56) increase in promoter of CAPS2, TNFRSF25, and HKR1 methylation, respectively. Our findings provide evidence that in utero exposure to BPA could alter the offspring's epigenome by altering DNA methylation pattern.
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http://dx.doi.org/10.1016/j.envres.2020.109996DOI Listing
November 2020

Males are more sensitive to reward and less sensitive to loss than females among people with internet gaming disorder: fMRI evidence from a card-guessing task.

BMC Psychiatry 2020 07 7;20(1):357. Epub 2020 Jul 7.

Center for Cognition and Brain Disorders, Institute of Psychological Research, Hangzhou Normal University, Hangzhou, 311121, Zhejiang Province, China.

Background: Many studies have found an interesting issue in the Internet gaming disorder (IGD): males are always observed to be the majority. However, there are little research to exploring the differences in the neural mechanisms between males and females in decision-making process among people with IGD. Therefore, explore the reward/loss processing between different gender with IGD could help in understanding the underlying neural mechanism of IGD.

Methods: Data from functional magnetic resonance imaging (fMRI) were collected from 111 subjects (IGD: 29 males, 25 females; recreational internet game user (RGU): 36 males, 21 females) while they were performing a card-guessing task. We collected and compared their brain features when facing the win and loss conditions in different groups.

Results: For winning conditions, IGD group showed hypoactivity in the lingual gyrus than RGU group, male players showed hyperactivity in the left caudate nucleus, bilateral cingulate gyrus, right middle frontal gyrus (MFG), right precuneus and inferior parietal lobule relative to the females. And significant sex-by-group interactions results showed higher brain activities in the thalamus, parahippocampal gyrus and lower brain activities in Inferior frontal gyrus (IFG) were observed in males with IGD than females. For losing conditions, IGD group showed hypoactivity in the left lingual gyrus, parahippocampal gyrus and right anterior cingulate cortex (ACC) compared to the RGU group, male players showed hyperactive left caudate nucleus and hypoactive right middle occipital gyrus relative to females. And significant sex-by-group interactions results showed that compared to females with IGD, males with IGD showed decreased brain activities in the IFG and lingual gyrus.

Conclusions: First, there appeared to be no difference in reward processing between the IGD and RGU group, but IGD showed less sensitivity to loss. Secondly, male players showed more sensitivity to rewards and less sensitivity to losses. Last but not least, males and females showed opposite activation patterns in IGD degree and rewards/losses processing. And male IGD subjects are more sensitive to reward and less sensitive to loss than females, which might be the reason for the gender different rates on IGD.
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http://dx.doi.org/10.1186/s12888-020-02771-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341652PMC
July 2020

Aurora-A/SOX8/FOXK1 signaling axis promotes chemoresistance via suppression of cell senescence and induction of glucose metabolism in ovarian cancer organoids and cells.

Theranostics 2020 25;10(15):6928-6945. Epub 2020 May 25.

Department of Gynecology and Obstetrics, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.

Cisplatin derivatives are first-line chemotherapeutic agents for epithelial ovarian cancer. However, chemoresistance remains a major hurdle for successful therapy and the underlying molecular mechanisms are poorly understood at present. RNA sequencing of organoids (PDO) established from cisplatin-sensitive and -resistant ovarian cancer tissue samples was performed. Glucose metabolism, cell senescence, and chemosensitivity properties were subsequently examined. Immunoprecipitation, mass spectrometry, Fӧrster resonance energy transfer-fluorescence lifetime imaging (FRET-FLIM), luciferase reporter assay, ChIP and animal experiments were conducted to gain insights into the specific functions and mechanisms of action of the serine/threonine kinase, Aurora-A, in ovarian cancer. Aurora-A levels were significantly enhanced in cisplatin-resistant PDO. Furthermore, Aurora-A promoted chemoresistance through suppression of cell senescence and induction of glucose metabolism in ovarian cancer organoids and cells. Mechanistically, Aurora-A bound directly to the transcription factor sex determining region Y-box 8 (SOX8) and phosphorylated the Ser327 site, in turn, regulating genes related to cell senescence and glycolysis, including hTERT, P16, LDHA and HK2, through enhancement of forkhead-box k1 (FOXK1) expression. Aurora-A regulates cell senescence and glucose metabolism to induce cisplatin resistance by participating in the SOX8/FOXK1 signaling axis in ovarian cancer. Our collective findings highlight a novel mechanism of cisplatin resistance and present potential therapeutic targets to overcome chemoresistance in ovarian cancer.
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http://dx.doi.org/10.7150/thno.43811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295065PMC
May 2021

Efficacy of albumin-bound paclitaxel in the treatment of advanced refractory breast cancer and its effect on serum resistin.

J BUON 2020 Mar-Apr;25(2):681-687

Department of Breast Surgery, Weihai Central Hospital, Weihai 264400, P.R. China.

Purpose: This study aimed to investigate the efficacy of albumin-bound paclitaxel (nab-paclitaxel) in the treatment of advanced refractory breast cancer (BC) and its effect on serum resistin.

Methods: A retrospective study was performed based on the clinical records of 95 patients with advanced refractory BC admitted to Weihai Central Hospital from March 2012 to May 2015. Thirty-four patients were treated with traditional paclitaxel and enrolled in the control group, while the other 61 patients were treated with nab-paclitaxel and enrolled in the study group. The efficacy, toxicity and side effects, quality of life, and serum resistin levels were compared between the two groups.

Results: The total response rate (RR) of the study group was much higher than that of the control group (p<0.05). The leukopenia level of the study group during the treatment was significantly lower than that of the control group (p<0.05). The level of serum resistin in the study group after treatment was significantly lower than in the control group (p<0.05). The improvement rate of quality of life in the study group was significantly higher than in the control group (p<0.05).

Conclusion: The results indicated that nab-paclitaxel is very effective in treating advanced refractory BC and reduces the level of serum resistin. It can improve the quality of life of patients and is worthy of clinical promotion.
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January 2021

Apigenin attenuates myocardial infarction-induced cardiomyocyte injury by modulating Parkin-mediated mitochondrial autophagy.

J Biosci 2020 ;45

State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

We aimedto detect whether the effect of apigenin (Apig) on themyocardial infarction-induced cardiomyocyte injury of mouse myocardial cells and acute myocardial infarction (AMI) mice was through regulating Parkin expression via miR-103-1-5p. The myocardial infarction cardiomyocyte model (Hypoxia/reoxygenation) was first constructed, then the mouse myocardial cells were treated with Apig, and the expression of miR-103-1-5p was decreased and the expression of Parkin was increased by qRT-PCR and Western blot. It was confirmed by miRNA pulldown and luciferase reporter system that miR-103-1-5p in mouse myocardial cells can bind to Parkin mRNA and inhibit Parkin expression.Next, a lentiviral vector silenced Parkin and overexpressingmiR-103-1-5pwas constructed and transfected into Apig-treated cells. Autophagy was detected by mitochondrial autophagy marker proteins [atypical protein kinase C (aPKC)-interacting protein (p62) and bcl-2/Adenovirus E1B 19-kd interacting protein 3 (BNIP3)] viaWestern blot, mitochondrial function was detected by JC-1 probe, and apoptosis was detected by flow cytometry. It was confirmed that Apig regulated mitochondria autophagy through miR-103-1-5p and Parkin, which ultimately affected cardiomyocyte death. Finally, an AMI mouse model was constructed, and then the mice were treated with Apig. The infarct size was detected by triphenyl tetrazolium chloride (TTC) staining, and the Apig relieved the myocardial infarction. The expression of miR-103-1-5p was decreased and the expression of Parkin was increased by qRT-PCR andWestern blot. The above results simplified that the cardio protection of Apig and miR-103-1-5p against injury of myocardial infarction cardiomyocyte by targeting Parkin. These results provided a novel treatment againstmyocardial infarction cardiomyocyte.
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April 2021

Short-form RON (sf-RON) enhances glucose metabolism to promote cell proliferation via activating β-catenin/SIX1 signaling pathway in gastric cancer.

Cell Biol Toxicol 2021 Feb 12;37(1):35-49. Epub 2020 May 12.

Department of Medical Oncology and Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.

Recepteur d'origine nantais (RON) has been implicated in cell proliferation, metastasis, and chemoresistance of various human malignancies. The short-form RON (sf-RON) encoded by RON transcripts was overexpressed in gastric cancer tissues, but its regulatory functions remain illustrated. Here, we found that sf-RON promoted gastric cancer cell proliferation by enhancing glucose metabolism. Furthermore, sf-RON was proved to induce the β-catenin expression level through the AKT1/GSK3β signaling pathway. Meanwhile, the binding sites of β-catenin were identified in the promoter region of SIX1 and it was also demonstrated that β-catenin positively regulated SIX1 expression. SIX1 enhanced the promoter activity of key proteins in glucose metabolism, such as GLUT1 and LDHA. Results indicated that sf-RON regulated the cell proliferation and glucose metabolism of gastric cancer by participating in a sf-RON/β-catenin/SIX1 signaling axis and had significant implications for choosing the therapeutic target of gastric cancer.
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http://dx.doi.org/10.1007/s10565-020-09525-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851020PMC
February 2021

IgA Nephropathy Concomitant With Karyomegalic Interstitial Nephritis.

Am J Med Sci 2020 09 17;360(3):287-292. Epub 2020 Apr 17.

Department of Renal Pathology, King Medical Diagnostics Center, Guangzhou, China.

Immunoglobulin A (IgA) nephropathy is one of the most common glomerulonephritis characterized by the deposition of IgA in glomerular mesangium. Karyomegalic interstitial nephritis (KIN) is a rare interstitial nephritis with potential hereditary factors. IgA nephropathy concomitant with KIN has not yet been reported. Herein, we describe the clinical course, ultrasonic images and gastrointestinal endoscopy findings of a 28-year-old-male patient with IgA nephropathy with KIN. The pathologic examination of the renal biopsy specimen demonstrated mild mesangial proliferative IgA nephropathy with KIN. Molecular genetic testing detected an abnormality in FAN1 gene. The heterozygous mutation was present on chromosome 15q13.3. However, IgA nephropathy with KIN is a rare disorder, and its pathogenesis is yet to be clarified.
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http://dx.doi.org/10.1016/j.amjms.2020.04.010DOI Listing
September 2020

Prenatal exposure to residential PM and anogenital distance in infants at birth: A birth cohort study from Shanghai, China.

Environ Pollut 2020 Sep 27;264:114684. Epub 2020 Apr 27.

School of Public Health, Fudan University, 130 Dong An Road, Shanghai, 200032, China.

Fine particulate matter (PM) is believed to be one of the most hazardous air pollution with a ubiquitous presence. Animal studies have reported the association between prenatal exposure to traffic pollutant (not exclusively including PM) and reproductive development in male offspring. However, the effects of prenatal exposure to PM on reproductive health in children are still unknown. The present study was based on the Shanghai-Minhang Birth Cohort Study (S-MBCS). A total of 876 pregnant women and their infants were included. Infants' anogenital distance (AGD, the distance from the anus to the genitals; AGDap [anus-penis] and AGDas [anus-scrotum] for boys, and AGDac [anus-clitoris] and AGDaf [anus-fourchette] for girls) were measured at birth. PM concentrations during pregnancy were estimated using satellite based modeling approach. Multiple linear regression analysis and multiple informant model were conducted to examine the associations between prenatal exposure to PM (pre μg/m) and offspring's AGDs (mm). In order to minimize the misclassification of exposure, a sensitivity analysis restricted to mothers being off work during pregnancy was performed. In multiple linear regression models, we found that prenatal exposure to PM during the 1 and 3 trimesters was associated with shorter AGDs. In multiple informant model, similar patterns were found, and statistically significant reductions were observed in AGDap (β=-0.278, 95%CI: -0.343∼-0.212), AGDac (β=-0.188, 95%CI: -0.247∼-0.130) and AGDaf (β= -0.163, 95%CI: -0.238∼-0.088) with PM exposure during the 1 trimester, and AGDap (β=-0.201, 95%CI: -0.247∼-0.155), AGDas (β=-0.158, 95%CI: -0.198∼-0.117), AGDac (β=-0.128, 95%CI: -0.167∼-0.089) and AGDaf (β = -0.144, 95%CI: -0.194∼-0.094) with PM exposure during the 3 trimester. The sensitivity analysis restricted to women being off work during pregnancy showed similar results. PM exposure during the 1 and 3 trimesters was associated with shortened AGDs in offspring at birth. Our findings provide preliminary evidence that prenatal exposure to PM might be associated with the reproductive development of offspring.
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http://dx.doi.org/10.1016/j.envpol.2020.114684DOI Listing
September 2020

Decreased effective connection from the parahippocampal gyrus to the prefrontal cortex in Internet gaming disorder: A MVPA and spDCM study.

J Behav Addict 2020 Apr 1;9(1):105-115. Epub 2020 Apr 1.

2 Center for Cognition and Brain Disorders, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang Province,PR China.

Objectives: Understanding the neural mechanisms underlying Internet gaming disorder (IGD) is essential for the condition's diagnosis and treatment. Nevertheless, the pathological mechanisms of IGD remain elusive at present. Hence, we employed multi-voxel pattern analysis (MVPA) and spectral dynamic causal modeling (spDCM) to explore this issue.

Methods: Resting-state fMRI data were collected from 103 IGD subjects (male = 57) and 99 well-matched recreational game users (RGUs, male = 51). Regional homogeneity was calculated as the feature for MVPA based on the support vector machine (SVM) with leave-one- out cross-validation. Mean time series data extracted from the brain regions in accordance with the MVPA results were used for further spDCM analysis.

Results: Results display a high accuracy of 82.67% (sensitivity of 83.50% and specificity of 81.82%) in the classification of the two groups. The most discriminative brain regions that contributed to the classification were the bilateral parahippocampal gyrus (PG), right anterior cingulate cortex (ACC), and middle frontal gyrus (MFG). Significant correlations were found between addiction severity (IAT and DSM scores) and the ReHo values of the brain regions that contributed to the classification. Moreover, the results of spDCM showed that compared with RGU, IGD showed decreased effective connectivity from the left PG to the right MFG and from the right PG to the ACC and decreased self-connection in the right PG.

Conclusions: These results show that the weakening of the PG and its connection with the prefrontal cortex, including the ACC and MFG, may be an underlying mechanism of IGD.
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http://dx.doi.org/10.1556/2006.2020.00012DOI Listing
April 2020

Disrupted prefrontal regulation of striatum-related craving in Internet gaming disorder revealed by dynamic causal modeling: results from a cue-reactivity task.

Psychol Med 2020 Feb 27:1-13. Epub 2020 Feb 27.

Connecticut Mental Health Center, New Haven, CT, USA.

Background: Studies of Internet gaming disorder (IGD) suggest an imbalanced relationship between cognitive control and reward processing in people with IGD. However, it remains unclear how these two systems interact with each other, and whether they could serve as neurobiological markers for IGD.

Methods: Fifty IGD subjects and matched individuals with recreational game use (RGU) were selected and compared when they were performing a cue-craving task. Regions of interests [anterior cingulate cortex (ACC), lentiform nucleus] were selected based on the comparison between brain responses to gaming-related cues and neutral cues. Directional connectivities among these brain regions were determined using Bayesian estimation. We additionally examined the posterior cingulate cortex (PCC) in a separate analysis based on data implicating the PCC in craving in addiction.

Results: During fixed-connectivity analyses, IGD subjects showed blunted ACC-to-lentiform and lentiform-to-ACC connectivity relative to RGU subjects, especially in the left hemisphere. When facing gaming cues, IGD subjects trended toward lower left-hemispheric modulatory effects in ACC-to-lentiform connectivity than RGU subjects. Self-reported cue-related craving prior to scanning correlated inversely with left-hemispheric modulatory effects in ACC-to-lentiform connectivity.

Conclusions: The results suggesting that prefrontal-to-lentiform connectivity is impaired in IGD provides a possible neurobiological mechanism for difficulties in controlling gaming-cue-elicited cravings. Reduced connectivity ACC-lentiform connectivity may be a useful neurobiological marker for IGD.
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http://dx.doi.org/10.1017/S003329172000032XDOI Listing
February 2020

Response to comments on "Circular RNAs and their emerging roles as diagnostic and prognostic biomarkers in ovarian cancer".

Cancer Lett 2020 04 20;476:183-184. Epub 2020 Feb 20.

Department of Obstetrics and Gynecology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. Electronic address:

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http://dx.doi.org/10.1016/j.canlet.2020.02.006DOI Listing
April 2020

Early stage neuroglobin level as a predictor of delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage.

Brain Behav 2020 03 5;10(3):e01547. Epub 2020 Feb 5.

Department of Neurosurgery, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, China.

Background: The neuroglobin (Ngb) is well recognized as a potential biomarker for the hypoxic-ischemic brain injury. However, connection between Ngb and delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) is still unclear.

Objective: To investigate the relationship between early stage Ngb level of aSAH patient and the occurrence of DCI.

Methods: We evaluated 126 aSAH patients who were enrolled into a prospective observational cohort study. Serum Ngb level on days 1, 2, 3, 5, and 7 after aSAH were determined using a commercial enzyme-linked immunosorbent assay kit. The relationship between Ngb level and DCI was analyzed.

Results: Forty-six (36.5%) aSAH patients experienced DCI. Patients with DCI had significantly higher Ngb levels than those without (p < .001). Multivariate model analysis revealed that day 3 Ngb level remained a significant factor after adjusting for World Federation of Neurosurgical Societies (WFNS) grade, modified Fisher grade, clipping and Ngb levels on days 1, 2, 5, and 7. Sensitivity, specificity, and Youden index of day 3 Ngb level for identifying DCI were derived as 73.9%, 72.5%, and 0.46, respectively, based on the best threshold of 8.4 ng/ml. Regardless in good-grade group or in poor-grade group, patients having day 3 Ngb level > 8.4 ng/ml has a significantly worse DCI survival rate than those having day 3 Ngb level <=8.4 ng/ml (p = .026 and .009, respectively).

Conclusions: Serum Ngb level was significantly elevated in DCI patients. Early stage aSAH Ngb level has the potential of being used as a novel DCI occurrence predictor, especially when Ngb level was combined with WFNS grade.
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http://dx.doi.org/10.1002/brb3.1547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066341PMC
March 2020

Circular RNAs and their emerging roles as diagnostic and prognostic biomarkers in ovarian cancer.

Cancer Lett 2020 03 2;473:139-147. Epub 2020 Jan 2.

Department of Obstetrics and Gynecology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. Electronic address:

Ovarian cancer (OC), one of the gynecologic malignancies with high invasive and metastatic potential, has a low survival rate in females. Although cytoreductive surgery combined with chemotherapy is the principal treatment for OC, the prognosis remains poor, and the recurrence rate of OC remains high. It is urgent to explore novel biomarkers for the diagnosis and prognosis of OC, as well as therapeutic targets. Circular RNAs (circRNAs) are a class of highly conserved, stable and abundant noncoding RNAs (ncRNAs). Recent studies have shown that circRNAs participate in OC progression by regulating various processes, including cell proliferation, migration, invasion and apoptosis. In addition, circRNAs are potential biomarkers for OC diagnosis and prognosis. This review provides an overview of recent findings on circRNAs in OC, including their functions and molecular mechanisms, and discusses their potential roles as diagnostic and prognostic biomarkers, as well as therapeutic targets for OC.
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http://dx.doi.org/10.1016/j.canlet.2019.12.043DOI Listing
March 2020

Erratum: Identification of lncRNA competitively regulated subpathways in myocardial infarction.

Exp Ther Med 2020 Jan 18;19(1):409. Epub 2019 Nov 18.

[This corrects the article DOI: 10.3892/etm.2019.7320.].
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http://dx.doi.org/10.3892/etm.2019.8210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923738PMC
January 2020

Recombinant Viral Capsid Protein L2 (rVL2) of HPV 16 Suppresses Cell Proliferation and Glucose Metabolism via ITGB7/C/EBPβ Signaling Pathway in Cervical Cancer Cell Lines.

Onco Targets Ther 2019 29;12:10415-10425. Epub 2019 Nov 29.

Department of Gynecology and Department of Radiology, Taizhou Municipal Hospital Affiliated to Taizhou University School of Medicine, Taizhou 318000, People's Republic of China.

Purpose: Capsid protein L2 is the minor capsid protein of human papillomavirus 16 (HPV16). Although L2-based vaccines were developed, the therapeutic effect of recombinant viral capsid protein L2 (rVL2) was still to be illustrated.

Methods: We used glucose uptake and lactate production assay to verify the inhibitory effect of rVL2 on the glucose metabolism in cervical cancer cells. Secondly, we performed gene-chip assay, RT-PCR, and Western blot to determine the role of ITGB7/C/EBPβ signaling pathway in rVL2-mediated glucose metabolism in vitro. Finally, we used an animal model to verify the function of rVL2 in cervical cancer.

Results: We found that rVL2 reduced glucose uptake and lactate production levels in cervical cancer cells, which caused the inhibition of cell proliferation. rVL2 decreased the expression levels of key metabolic enzymes, including GLUT1, LDHA, and ALDOA, to affect cell metabolism in cervical cancer cells by inhibiting ITGB7/C/EBPβ signaling pathway in vitro and in vivo.

Conclusion: These results demonstrated the vital role of rVL2 in the glycolysis-induced cell growth and proliferation via suppressing ITGB7/C/EBPβ signaling axis.
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http://dx.doi.org/10.2147/OTT.S228631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890187PMC
November 2019

Altered brain activities associated with cue reactivity during forced break in subjects with Internet gaming disorder.

Addict Behav 2020 03 9;102:106203. Epub 2019 Nov 9.

Department of Psychology, Zhejiang Normal University, 321004 Jinhua, Zhejiang Province, PR China; Institute of Psychological and Brain Sciences, Zhejiang Normal University, 321004 Jinhua, Zhejiang Province, PR China. Electronic address:

Background: Studies have proven that forced break can elicit strong psychological cravings for addictive behaviors. This phenomenon could create an excellent situation to study the neural underpinnings of addiction. The current study explores brain features during a cue-reactivity task in Internet gaming disorder (IGD) when participants were forced to stop their gaming behaviors.

Methods: Forty-nine IGD subjects and forty-nine matched recreational Internet game users (RGU) were asked to complete a cue-reactivity task when their ongoing gaming behaviors were forced to break. We compared their brain responses to gaming cues and tried to find specific features associated with IGD.

Results: Compared with RGU, the IGD subjects showed decreased activation in the anterior cingulate cortex (ACC), parahippocampal gyrus, and dorsolateral prefrontal cortex (DLPFC). Significant negative correlations were observed between self-reported gaming cravings and the baseline activation level (bate value) of the ACC, DLPFC, and parahippocampal gyrus.

Conclusions: IGD subjects were unable to suppress their gaming cravings after unexpectedly forced break. This result could also explain why RGU subjects are able to play online games without developing dependence.
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http://dx.doi.org/10.1016/j.addbeh.2019.106203DOI Listing
March 2020

Addiction severity modulates the precuneus involvement in internet gaming disorder: Functionality, morphology and effective connectivity.

Prog Neuropsychopharmacol Biol Psychiatry 2020 03 29;98:109829. Epub 2019 Nov 29.

Department of Psychiatry, Department of Neurobiology, and Child Study Center, Yale University School of Medicine, New Haven, CT, USA; Connecticut Council on Problem Gambling, Wethersfield, CT, USA; Connecticut Mental Health Center, New Haven, CT, USA. Electronic address:

Although higher precuneus activation has often been observed in subjects with addictions when facing addiction-relevant cues, the recruitment of the precuneus is not consistent across studies. Here, we examined the extent to which addiction severity may relate to precuneus involvement during cue reactivity in internet gaming disorder (IGD). We recruited 65 subjects with IGD, collected brain responses when exposed to gaming cues and assessed brain structure. We correlated IGD severity with brain responses during a cue-craving task, precuneus volume, and connectivity with respect to inputs/outputs to/from the precuneus. In the cue-craving task, IGD severity was positively correlated with precuneus activation when exposed to gaming cues. IGD severity was also positively correlated with the volume of precuneus and connectivity from the hippocampal gyrus to the precuneus. IGD severity was also negatively correlated with connectivity from the middle frontal gyrus to the precuneus. In IGD, IGD severity relates to precuneus involvement with respect to functionality, morphology, and connectivity. The precuneus may act as a platform for integrating potential contradictory information between executive control and sub-cortical cravings.
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http://dx.doi.org/10.1016/j.pnpbp.2019.109829DOI Listing
March 2020

Clinical significance of breast-conserving surgery for early breast cancer and its impact on patient life quality of life.

J BUON 2019 Sep-Oct;24(5):1898-1904

Department of Thyroid Breast Surgery, Weihai Central Hospital, Weihai 264400, P.R. China.

Purpose: To explore the clinical significance of breast-conserving surgery for early breast cancer and its impact on patient's life quality.

Methods: We retrospectively analyzed 156 patients with early breast cancer who were admitted to Weihai Municipal Hospital between August 2013 and January 2015. Among them, there were 82 cases of breast-conserving surgery (the experiment group) and 74 cases of conventional radical surgery (the control group). Hospitalization time, survival rate, metastasis rate, recurrence rate, complications, and life quality within two years were compared between the two groups.

Results: There were no significant differences in the survival rate, recurrence rate, and metastasis rate within 2 years between the two groups (p>0.05). However, the cosmetic effect, the amount of intraoperative blood loss average drainage flow volume, time of surgery, period of hospitalization, length of incision and incision infection rate after surgery were all lower in the experiment group. Patients in the experiment group had better life quality and a lower rate of anxiety.

Conclusions: The breast-conserving surgery had a positive impact on patients with early breast cancer. Patient who received this surgery had a lower rate of blood loss and smaller incision. The surgery duration was shorter and postoperative recovery time was shorter. Moreover, breast-conserving surgery had a better cosmetic effect. The Breast-conserving surgery is worthy of further application in the treatment of early breast cancer.
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May 2020