Publications by authors named "Qiong Feng"

58 Publications

Single Dose of SHR-1222, a Sclerostin Monoclonal Antibody, in Healthy Men and Postmenopausal Women With Low Bone Mass: A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation, Phase I Study.

Front Pharmacol 2021 20;12:770073. Epub 2021 Oct 20.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

SHR-1222 is a humanized monoclonal antibody targeting sclerostin and has the potential to promote bone formation and reduce bone resorption. This study was aimed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of SHR-1222 in healthy men and postmenopausal women with low bone mass (BMD). It was a randomized, double-blind, placebo-controlled, dose-escalation, phase I study. Subjects received SHR-1222 at 50, 100, 200, 300, and 400 mg sequentially or matching placebo subcutaneously. Totally, 50 subjects with low BMD were enrolled and randomly assigned; 10 received placebo and 40 received SHR-1222 (50 mg, n = 4; 100, 200, 300, or 400 mg, n = 9). The most common adverse events that occurred at least 10% higher in subjects with SHR-1222 treatment than those with placebo were decreased blood calcium, blood urine present, increased blood cholesterol, electrocardiogram T wave abnormal, urinary tract infection, increased blood pressure diastolic, and positive bacterial test. All the above adverse events were mild in severity and well resolved except one of increased blood cholesterol in a subject lost to follow-up. The serum SHR-1222 concentration increased in a dose-dependent manner. Administration of SHR-1222 upregulated the bone-formation markers N-terminal propeptide of type 1 procollagen, osteocalcin, and bone-specific alkaline phosphatase, while downregulated the bone-resorption marker β-C-telopeptide. The BMD at the lumbar spine notably rose after a single dose of SHR-1222. The largest increase occurred in the 400 mg cohort (3.8, 6.7, and 6.1% on day 29, 57, and 85, respectively; compared with 1.4, 0.8, and 1.0% in the placebo group). Although 10.0% of subjects receiving SHR-1222 tested positive for anti-SHR-1222 antibodies, no obvious effects of antibody formation were found on pharmacokinetics. Overall, SHR-1222 was well tolerated at doses from 50 to 400 mg and is a promising new remedy for osteoporosis. http://www.clinicaltrials.gov, NCT03870100.
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http://dx.doi.org/10.3389/fphar.2021.770073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564351PMC
October 2021

Blocking tumor necrosis factor-α delays progression of chronic obstructive pulmonary disease in rats through inhibiting MAPK signaling pathway and activating SOCS3/TRAF1.

Exp Ther Med 2021 Nov 16;22(5):1311. Epub 2021 Sep 16.

Department of Pulmonary and Critical Care Medicine, The Affiliated Hospital of Jianghan University, Wuhan, Hubei 430015, P.R. China.

The present study was conducted in order to study the detailed molecular mechanism of tumor necrosis factor (TNF)-α in chronic obstructive pulmonary disease (COPD). The rats were treated with cigarette smoke (CS) and lipopolysaccharide (LPS) to establish the COPD model. Next, the changes in lung injury in COPD rats with TNF-α knockdown was tested. Meanwhile, the regulation of TNF-α on MAPK pathway and its downstream molecules (SOCS3/TRAF1) was determined by western blotting. On this basis, the activation of MAPK and inhibition of SOCS3/TRAF1 was also examined. Subsequently, the lung function was tested with the plethysmograph, the cells of bronchoalveolar lavage fluid was counted and classified. Furthermore, lung tissue sections were stained with hematoxylin and eosin to verify whether the treatment of MAPK pathway and downstream molecules affected the effect of TNF-α knockdown on COPD. The present study showed that TNF-α knockdown could alleviate the decrease in the function and inflammatory injury of the lungs of rats with COPD. Western blot analysis verified that TNF-α knockdown could inhibit the activation of MAPK pathway and increase the expression of SOCS3/TRAF1. The following experimental results showed that the relief of lung injury caused by TNF-α knockdown could be deteriorated by activating MAPK pathway. It was also found that the symptom of COPD was decreased following transfection with sh-TNF-α but worsened by SOCS3/TRAF1 knockdown. Overall, TNF-α knockdown inhibited the activation of MAPK pathway and increased the expression of SOCS3/TRAF1, thus delaying the process of COPD.
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http://dx.doi.org/10.3892/etm.2021.10746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461615PMC
November 2021

MicroRNA-137 acts as a tumor suppressor in osteosarcoma by targeting enhancer of zeste homolog 2.

Exp Ther Med 2021 Oct 12;22(4):1168. Epub 2021 Aug 12.

[This retracts the article DOI: 10.3892/etm.2017.4435.].
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http://dx.doi.org/10.3892/etm.2021.10602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392873PMC
October 2021

Structure with thin SiO/SiN bilayer and Al electrodes for high-frequency, large-coupling, and low-cost surface acoustic wave devices.

Ultrasonics 2021 Aug 17;115:106460. Epub 2021 May 17.

Key Laboratory of Advanced Materials (MOE), School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China. Electronic address:

With the development of fifth-generation wireless systems, the Internet of Things, and health services, surface acoustic wave (SAW)-based filters and sensors have attracted considerable interest. This study presents a new structure for high-frequency, large-coupling, and low-cost SAW devices that helps implement high-frequency and wideband filters and enhances the sensitivity of sensors. The structure is based on 15°Y-X LiNbO, thin SiO/SiN bilayer overlay, and Al electrodes. Furthermore, a low-cost fabrication process for SAW devices based on this structure was designed. Simulation and experimental results show that the bilayer substantially weakens the leaky nature of shear-horizontal-type SAWs with a phase velocity higher than that of a slow-shear bulk wave in LiNbO. Thus, the limitation related to the velocity of 4029 m/s was overcome, and the phase velocity reached approximately 4500 m/s, which means an increase of 50% compared with that of conventional Cu/15°Y-X LiNbO devices. Consequently, the frequency dramatically increases, and the quality of the SAW response is ensured. Simultaneously, a large electromechanical coupling factor close to 20% can be achieved, which is still suitable for wideband filters and sensors with high energy transduction coefficients. This new structure is expected to become a major candidate for SAW devices in the future.
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http://dx.doi.org/10.1016/j.ultras.2021.106460DOI Listing
August 2021

Rationale and design for Lowering-hyperUricaemia treatment on cardiovascular outcoMes In peritoNeal diAlysis patients: a prospective, multicentre, double-blind, randomised controlled trial (LUMINA).

BMJ Open 2020 10 10;10(10):e037842. Epub 2020 Oct 10.

Department of Nephrology, Sun Yat-sen University First Affiliated Hospital,National Health Commission Key Laboratory of Nephrology (Sun Yat-sen University), Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, Guangdong, China

Introduction: The prevalence of hyperuricaemia in peritoneal dialysis patients is quite high. Studies have demonstrated a correlation between hyperuricaemia and cardiovascular disease and treatment of hyperuricaemia reportedly reduces cardiovascular risk in patients with chronic kidney disease. However, whether hyperuricaemia treatment benefits cardiovascular outcomes in continuous ambulatory peritoneal dialysis (CAPD) patients is not yet known.

Methods And Analyses: This prospective, multicentre, double-blind, randomised controlled trial was designed to evaluate the effects of hyperuricaemia treatment on cardiovascular event risk in CAPD patients. Based on a power of 80%, with type I error α=0.05, two-sided test and 1:1 parallel control study, considering a dropout rate of 20%, a total of 548 eligible patients are expected to be randomly assigned to either the hyperuricaemia treatment group (febuxostat) or control group (placebo).

Ethics And Dissemination: This study has been approved by the Medical Ethics Committee of the First Affiliated Hospital, Sun Yat-sen University and the ethics committees of other participating institutions. Written informed consent will be obtained from potential trial participants or authorised surrogates.The findings of the study will be disseminated through publications in peer-reviewed journals, and presentations at national and international conferences.

Trial Registration Number: NCT03200210. 25 June 2017. The trial was started on 13 July 2017, and is expected to end by 31 December 2022. Till 20 Jan 2020, a total of 548 patients have been recruited.

Protocol Version: The protocol version number and date are YLT-1604-V2.0 and 15 December 2016.
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http://dx.doi.org/10.1136/bmjopen-2020-037842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552848PMC
October 2020

RAB31 is targeted by miR-26b and serves a role in the promotion of osteosarcoma.

Oncol Lett 2020 Nov 15;20(5):244. Epub 2020 Sep 15.

Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.

Ras-related protein Rab-31 (RAB31), a small guanosine 5'-triphosphate-binding protein, is a member of the Rab family and has been demonstrated to serve an oncogenic role in several common types of human cancer. However, the function of RAB31 in osteosarcoma (OS) has not been previously studied. The present study identified that the expression levels of RAB31 were significantly higher in OS tissue samples compared with matched adjacent non-tumor tissue samples, and high RAB31 expression was associated with malignant progression and a poor prognosis for patients with OS. Furthermore, it was identified that the expression levels of RAB31 were increased in OS cell lines compared with normal osteoblast cells. Silencing of RAB31 expression significantly inhibited OS cell proliferation, cell cycle progression, migration and invasion, and significantly increased the rate of cell apoptosis. In addition, the present study used a luciferase reporter assay to demonstrate that RAB31 was a direct target gene of microRNA-26b (miR-26b), which is a known tumor suppressor in OS. The expression levels of RAB31 were negatively associated with miR-26b expression in OS cells. Finally, miR-26b was demonstrated to be significantly decreased in OS tissues compared with adjacent non-tumor tissues, and an inverse correlation was observed between the expression levels of RAB31 and miR-26b in OS tissues. In summary, to the best of our knowledge, the present study is the first to report that RAB31 is a target gene of miR-26b, and silencing of RAB31 may inhibit OS growth and progression.
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http://dx.doi.org/10.3892/ol.2020.12106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509508PMC
November 2020

Long-Noncoding RNA PCAT6 Aggravates Osteosarcoma Tumourigenesis via the MiR-143-3p/ZEB1 Axis.

Onco Targets Ther 2020 26;13:8705-8714. Epub 2020 Aug 26.

Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang 300006, People's Republic of China.

Introduction: The long-noncoding RNA PCAT6 plays an important regulatory role in the development of several cancers. However, the expression pattern and underlying mechanisms of PCAT6 in osteosarcoma (OS) are yet unknown.

Methods: We used real-time PCR to measure PCAT6 expression in 106 tumor pairs and corresponding non-tumor tissues from OS patients. Statistical analyses were applied to evaluate the prognostic value and associations of PCAT6 expression with clinical parameters. Furthermore, the PCAT6 was silenced with siRNA in OS cells. Moreover, phenotype of PCAT6 silenced OS cells was measured using colony formation, CCK-8, cell migration and invasion assay. Finally, the molecular mechanism of PCAT6/miR-143-3p/ZEB1 axis in OS progression was explored.

Results: The expression level of PCAT6 in OS tissues was significantly elevated as compared with that in the adjacent normal bone tissues and that high PCAT6 expression closely correlated with the malignant phenotype and poor survival among patients with OS. Multivariate analyses revealed PCAT6 overexpression as an independent prognostic factor for the poor outcome of patients with OS. Functional assay results demonstrated that the knockdown of PCAT6 expression notably suppressed the proliferation, migration, and invasion of OS cells. An elevated PCAT6 level aggravated the malignant phenotype of OS cells via ZEB1 expression upregulation. Mechanistic studies revealed that PCAT6 could sponge endogenous miR-143-3p and inhibit its activity, resulting in an increase in ZEB1 level. Finally, we demonstrated that the tumour-promoting role of PCAT6 in OS was dependent on the regulation of the miR-143-3p/ZEB1 axis.

Conclusion: These findings highlight the potential role of PCAT6, which could serve as a valuable prognostic indicator for patients with OS.
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http://dx.doi.org/10.2147/OTT.S258415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457841PMC
August 2020

Genetic Polymorphisms of / in Chronic Obstructive Pulmonary Disease.

COPD 2020 10 5;17(5):595-600. Epub 2020 Aug 5.

Department of General Practice, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.

Chronic obstructive pulmonary disease (COPD) is a high incidence in the elderly and significantly affects the quality of life. and play an important role in tobacco-related diseases and inflammatory reactions. Thus, we aim to investigate the association between / polymorphisms and the risk of COPD. In this study, a total of 821 subjects were recruited which include 313 COPD cases and 508 healthy controls. Seven SNPs of / were selected for genotyping. The odds ratios (ORs) and 95% confidence interval (95% CI) were calculated using logistic regression analysis to evaluate the association between COPD risk and / polymorphisms. Our study showed that A allele of rs9332220 in was associated with reducing COPD risk (OR = 0.64, 95% CI = 0.43-0.94,  = 0.021). And rs111853758 G allele carrier could significantly decrease 0.35-fold COPD risk compared with T allele carrier (OR = 0.65, 95% CI = 0.45-0.96,  = 0.027). Furthermore, sex-based stratification analysis showed that rs9332220 and rs111853758 polymorphisms were associated with the risk of COPD in males. This is the first study to investigate the association between and genetic polymorphisms and COPD risk, which may give a new perspective on the prevention and diagnosis of COPD.
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http://dx.doi.org/10.1080/15412555.2020.1780577DOI Listing
October 2020

The effect of CYP3A4 genetic variants on the susceptibility to chronic obstructive pulmonary disease in the Hainan Han population.

Genomics 2020 11 30;112(6):4399-4405. Epub 2020 Jul 30.

Department of General Practice, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, Hainan, China. Electronic address:

Purpose: Genetic polymorphisms act a crucial role in chronic obstructive pulmonary disease (COPD) progression. This study aimed to investigate the correlation between CYP3A4 variants and COPD risk.

Methods: We carried out a case-control study of 821 individuals (313 patients and 508 healthy subjects) to identify the correlation of CYP3A4 SNPs with COPD risk in the Hainan Han population. The association was evaluated by Odds ratios (OR) and 95% confidence intervals (CI).

Results: Our study showed that rs4646437 polymorphism was related to a significantly increased susceptibility to COPD (OR 1.45, 95% CI = 1.10-1.90, p = 0.008). Stratified analyses indicated that rs4646437 polymorphism was significantly related to an increased risk of COPD in males (OR 1.95, 95% CI = 1.19-3.20, p = 0.008). However, rs4646440 played a protective role in females (OR 0.54, 95% CI = 0.31-0.93, p = 0.024). Rs4646437 was found to significantly improve the risk of COPD in smokers (OR 1.67, 95% CI = 1.12-2.48, p = 0.011). While rs4646440 had a significantly lower susceptibility to COPD in non-smokers (OR 0.64, 95% CI = 0.45-0.90, p = 0.010). Haplotype analysis revealed that AT haplotype of CYP3A4 was found to increase the risk of COPD in non-smokers (OR 1.71, 95% CI = 1.04-2.82, p = 0.034).

Conclusion: Our result gives a new understanding of the association between CYP3A4 gene and COPD in the Hainan Han population.
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http://dx.doi.org/10.1016/j.ygeno.2020.07.043DOI Listing
November 2020

Hdc-expressing myeloid-derived suppressor cells promote basal-like transition and metastasis of breast cancer.

Int J Clin Exp Pathol 2020 1;13(6):1431-1443. Epub 2020 Jun 1.

Department of Pathology, The Fourth Affiliated Hospital of Nanchang University Nanchang, China.

Metastases are the greatest contributors to death from breast cancer. Here, we identified a distinct subpopulation of luminal breast cancer characterized by cytokeratin 14 (CK14) expression in secondary colonies rather than primary tumors. This entity possessed a poorer prognosis compared to their CK14 counterparts. Immunohistochemical analysis showed that myeloid-derived suppressor cells (MDSCs) were recruited into the tumor microenvironment and exhibited a close spatial relationship with CK14 cancer cells. We demonstrated that histidine decarboxylase (Hdc) is capable of labeling myeloid-biased hematopoietic stem cell/progenitor cell (HSC/HSPC) and immature myeloid cells infiltrating in tumor tissues. FACS data obtained from -CreER; eGFP; MMTV-PyVT female mice revealed an increased percentage of Hdc PMN-MDSCs in metastatic masses. Hdc PMN-MDSCs expressed high levels of canonical Wnts, including Wnt2, Wnt4, Wnt5a, and Wnt7b, to aberrantly activate Wnt/β-catenin signaling in CK14 malignant cells. β-catenin translocated from the membrane into the cytoplasm and nucleus. Targeted ablation of Hdc PMN-MDSCs-derived Wnts through and iDTR transgenic models hampered the metastatic cascade, making Hdc immature myeloid cells an attractive candidate for tailed immunotherapies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344006PMC
June 2020

The correlation between CYP4F2 variants and chronic obstructive pulmonary disease risk in Hainan Han population.

Respir Res 2020 Apr 15;21(1):86. Epub 2020 Apr 15.

Department of General Practice, Hainan General Hospital, Haikou, 570102, Hainan, China.

Background: Chronic obstructive pulmonary disease (COPD) is a complex pulmonary disease. Cytochrome P450 family 4 subfamily F member 2 (CYP4F2) belongs to cytochrome P450 superfamily of enzymes responsible for metabolism, its single nucleotide polymorphisms (SNPs) were reported to be involved in metabolism in the development of many diseases. The study aimed to assess the relation between CYP4F2 SNPs and COPD risk in the Hainan Han population.

Method: We genotyped five SNPs in CYP4F2 in 313 cases and 508 controls by Agena MassARRAY assay. The association between CYP4F2 SNPs and COPD risk were assessed by χ test and genetic models. Besides, logistic regression analysis was introduced into the calculation for odds ratio (OR) and 95% confidence intervals (CIs).

Results: Allele model analysis indicated that rs3093203 A was significantly correlated with an increased risk of COPD. Also, rs3093193 G and rs3093110 G were associated with a reduced COPD risk. In the genetic models, we found that rs3093203 was related to an increased COPD risk, while rs3093193 and rs3093110 were related to a reduced risk of COPD. After gender stratification, rs3093203, rs3093193 and rs3093110 showed the association with COPD risk in males. With smoking stratification, rs3093144 was significantly associated with an increased risk of COPD in smokers. CYP4F2 SNPs were significantly associated with COPD risk.

Conclusions: Our findings illustrated potential associations between CYP4F2 polymorphisms and COPD risk. However, large-scale and well-designed studies are needed to determine conclusively the association between the CYP4F2 SNPs and COPD risk.
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http://dx.doi.org/10.1186/s12931-020-01348-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161254PMC
April 2020

Influence of the CYP2J2 Gene Polymorphisms on Chronic Obstructive Pulmonary Disease Risk in the Chinese Han Population.

Arch Bronconeumol (Engl Ed) 2020 Nov 26;56(11):697-703. Epub 2020 Mar 26.

Department of General Practice, Hainan General Hospital, Haikou 570311, Hainan, China. Electronic address:

Introduction: Cytochrome P450 (CYP) 2J2 is a major enzyme that controls epoxyeicosatrienoic acids biosynthesis, which may play a role in chronic obstructive pulmonary disease (COPD) development. In this study, we aimed to assess the influence of CYP2J2 polymorphisms with COPD susceptibility.

Material And Methods: A case-control study enrolled 313 COPD cases and 508 controls was to investigate the association between CYP2J2 polymorphisms and COPD risk. Agena MassARRAY platform was used to genotype CYP2J2 polymorphisms. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the association between CYP2J2 polymorphisms and COPD risk.

Results: We observed rs11207535 (homozygote: OR=0.08, 95%CI=0.01-0.96, p=0.047; recessive: OR=0.08, 95%CI=0.01-0.94, p=0.044), rs10889159 (homozygote: OR=0.08, 95%CI=0.01-0.92, p=0.043; recessive: OR=0.08, 95%CI=0.01-0.90, p=0.040) and rs1155002 (heterozygote: OR=1.63, 95%CI=1.13-2.36, p=0.009; dominant: OR=1.64, 95%CI=1.15-2.35, p=0.006; additive: OR=1.45, 95%CI=1.09-1.92, p=0.011) were significantly associated with COPD risk. Allelic tests showed T allele of rs2280274 was related to a decreased risk of COPD and T allele of rs1155002 was associated with an increased COPD risk. Stratified analyses indicated the effects of CYP2J2 polymorphisms and COPD risk were dependent on gender and smoking status (p<0.05). Additionally, two haplotypes (ACT and ACC) significantly decreased COPD risk.

Conclusion: It suggested CYP2J2 polymorphisms were associated with COPD susceptibility in the Chinese Han population.
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http://dx.doi.org/10.1016/j.arbres.2019.11.026DOI Listing
November 2020

Hepatic insulin resistance induced by mitochondrial oxidative stress can be ameliorated by sphingosine 1-phosphate.

Mol Cell Endocrinol 2020 02 20;501:110660. Epub 2019 Nov 20.

Department of Endocrinology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China. Electronic address:

The bioactive lipid mediator sphingosine 1-phosphate (S1P) is considered to be involved in the development of insulin resistance (IR) via effects on oxidative stress; the mechanism however is not yet fully revealed. To this end, we investigated the role and mechanism of S1P on hepatic IR. We found that treatment of the normal human liver cell LO2 with 1000 nM insulin for 48 h reduced glucose uptake and increased serine phosphorylation of insulin receptor substrate-1, indicating a reduction in insulin receptor signaling. Moreover, the same concentration of insulin caused accumulation of reactive oxygen species (ROS) in the cytosol and mitochondria, and enhanced expression of the antioxidant transcription factor (Nrf2) and upregulated Nrf2 nuclear translocation. Using known inhibitors and donors of ROS (HO, ·O-, ·OH), the results demonstrated the differential roles for the specific ROS in regulating IR in LO2 cells, with HO having a more significant inhibitory role compared with ·O and ·OH. Cell treatment with S1P at 0.1-5.0 μM reversed the effects of high insulin concentrations on ROS generation, glucose uptake, and insulin signaling. HO also reversed the beneficial effects of S1P in alleviating IR. These results show that HO signaling plays a key determinant in hepatic IR induced by insulin. S1P can ameliorate hepatic IR by reducing mitochondrial ROS generation, and the possible anti-IR effect mechanism may be involved in HO signaling.
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http://dx.doi.org/10.1016/j.mce.2019.110660DOI Listing
February 2020

genetic polymorphisms influence chronic obstructive pulmonary disease susceptibility in the Hainan population.

Int J Chron Obstruct Pulmon Dis 2019 5;14:2103-2115. Epub 2019 Sep 5.

Department of Respiratory Intensive Care Unit (RICU), The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 45000, People's Republic of China.

Introduction: Chronic obstructive pulmonary disease (COPD) is a lung disease closely related to exposure to exogenous substances. can activate many exogenous substances, which in turn affect lung cells. The aim of this study was to assess the association of single-nucleotide polymorphisms (SNPs) in with COPD risk in a Chinese Han population.

Materials And Methods: Genotypes of the five candidate SNPs in were identified among 318 cases and 508 healthy controls with an Agena MassARRAY method. The association between polymorphisms and COPD risk was evaluated using genetic models and haplotype analyses.

Results: In allele model, we observed that rs4803420 G and rs1038376 A were related to COPD risk. And rs4803420 G/T and G/T-T/T were related to a decreased COPD risk compared to GG genotype in the co-dominant and dominant models, respectively. When comparing with the AA genotype, rs1038376 A/T and A/T-T/T were associated with an increased COPD risk in the co-dominant and dominant models, respectively. Further gender stratification co-dominant and dominant models analysis showed that genotype G/T and G/T-T/T of rs4803420, and genotype A/T and A/T-T/T of rs1038376 were significantly associated with COPD risk compared to the wide type in males and females, while allele C of rs12979270 was only associated with COPD risk in females. Smoking status stratification analysis showed that rs12979270 C was significantly associated with an increased COPD risk under the allele model compared with allele A in the smoking subgroup. Haplotype analysis showed that haplotype GTA and TAA were related to COPD risk.

Conclusion: Our data is the first to demonstrate that polymorphisms may exert effects on COPD susceptibility in the Chinese Han population.
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http://dx.doi.org/10.2147/COPD.S214961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733340PMC
April 2020

TERT gene polymorphisms are associated with chronic obstructive pulmonary disease risk in the Chinese Li population.

Mol Genet Genomic Med 2019 08 3;7(8):e773. Epub 2019 Jul 3.

Department of General Practice, Hainan General Hospital, Haikou, China.

Background: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide and is characterized by a partially reversible airflow limitation. Currently, many studies put forward that COPD is associated with both genetic and environmental factors. It has been reported that germline mutations in telomerase are risk factors for COPD susceptibility. In this study, we validated the association between TERT polymorphisms and COPD risk with a case-control study in the Chinese Li population.

Methods: A total of 279 COPD patients and 290 control individuals were recruited. We identified five single nucleotide polymorphisms (SNPs) in TERT that were associated with COPD. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in logistic regression models after adjusting for age and gender to assess the association.

Results: In the genetic model analysis, we found the "C/T-T/T" genotype of rs10069690 in TERT was associated with an increased COPD risk in the dominant model (p = 0.046); the rs2853677 in TERT was significantly associated with increased COPD risk based on the codominant model ("A/G" genotype, p = 0.033), dominant model (A/G-G/G genotype, p = 0.0091), and log-additive model (p = 0.023). The rs2853676 in TERT could increase the risk of COPD in the dominant model ("C/T-T/T" genotype, p = 0.026) and in the Log-additive model (p = 0.022).

Conclusion: Our data shed new light on the association between TERT SNPs and COPD susceptibility in the Chinese Li population.
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http://dx.doi.org/10.1002/mgg3.773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687861PMC
August 2019

MAPT/Tau accumulation represses autophagy flux by disrupting IST1-regulated ESCRT-III complex formation: a vicious cycle in Alzheimer neurodegeneration.

Autophagy 2020 04 28;16(4):641-658. Epub 2019 Jun 28.

Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China and Hubei Province for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Macroautophagy/autophagy deficit induces intracellular MAPT/tau accumulation, the hallmark pathology in Alzheimer disease (AD) and other tauopathies; however, the reverse role of MAPT accumulation in autophagy and neurodegeneration is not clear. Here, we found that overexpression of human wild-type full-length MAPT, which models MAPT pathologies as seen in sporadic AD patients, induced autophagy deficits repression of autophagosome-lysosome fusion leading to significantly increased LC3 (microtubule-associated protein 1 light chain 3)-II and SQSTM1/p62 (sequestosome 1) protein levels with autophagosome accumulation. At the molecular level, intracellular MAPT aggregation inhibited expression of IST1 (IST1 factor associated with ESCRT-III), a positive modulator for the formation of ESCRT (the Endosomal Sorting Complex Required for Transport) complex that is required for autophagosome-lysosome fusion. Upregulating in human MAPT transgenic mice attenuated autophagy deficit with reduced MAPT aggregation and ameliorated synaptic plasticity and cognitive functions, while downregulating induced autophagy deficit with impaired synapse and cognitive function in naïve mice. IST1 can facilitate association of CHMP2B (charged multivesicular body protein 2B) and CHMP4B/SNF7-2 to form ESCRT-III complex, while lack of IST1 impeded the complex formation. Finally, we demonstrate that MAPT accumulation suppresses transcription with the mechanisms involving the ANP32A-regulated mask of histone acetylation. Our findings suggest that the AD-like MAPT accumulation can repress autophagosome-lysosome fusion by deregulating ANP32A-INHAT-IST1-ESCRT-III pathway, which also reveals a vicious cycle of MAPT accumulation and autophagy deficit in the chronic course of AD neurodegeneration. AAV: adeno-associated virus; Aβ: β-amyloid; aCSF: artificial cerebrospinal fluid; AD: Alzheimer disease; ANP32A: acidic nuclear phosphoprotein 32 family member A; ATG: autophagy related; AVs: autophagic vacuoles; CEBPB: CCAAT enhancer binding protein beta; CHMP: charged multivesicular body protein; DMEM: Dulbecco's modified eagle's medium; EBSS: Earle's balanced salt solution; EGFR: epidermal growth factor receptor; ESCRT: endosomal sorting complex required for transport; fEPSPs: field excitatory postsynaptic potentials; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GSK3B: glycogen synthase kinase 3 beta; HAT: histone acetyl transferase; HDAC: histone deacetylase; INHAT: inhibitor of histone acetyl transferase; IST1: IST1 factor associated with ESCRT-III; LAMP2: lysosomal associated membrane protein 2; LTP: long-term potentiation; MAP1LC3: microtubule associated protein 1 light chain 3; MAPT/tau: microtubule associated protein tau; MVB: multivesicular bodies; MWM: Morris water maze; PBS: phosphate-buffered saline solution; RAB7: member RAS oncogene family; SNAREs: soluble N-ethylmaleimide-sensitive factor attachment protein receptors; SQSTM1/p62: sequestosome 1.
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http://dx.doi.org/10.1080/15548627.2019.1633862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138218PMC
April 2020

Tau accumulation triggers STAT1-dependent memory deficits by suppressing NMDA receptor expression.

EMBO Rep 2019 06 13;20(6). Epub 2019 May 13.

Key Laboratory of Ministry of Education of China and Hubei Province for Neurological Disorders, Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Intracellular tau accumulation forming neurofibrillary tangles is hallmark pathology of Alzheimer's disease (AD), but how tau accumulation induces synapse impairment is elusive. By overexpressing human full-length wild-type tau (termed hTau) to mimic tau abnormality as seen in the brain of sporadic AD patients, we find that hTau accumulation activates JAK2 to phosphorylate STAT1 (signal transducer and activator of transcription 1) at Tyr701 leading to STAT1 dimerization, nuclear translocation, and its activation. STAT1 activation suppresses expression of N-methyl-D-aspartate receptors (NMDARs) through direct binding to the specific GAS element of GluN1, GluN2A, and GluN2B promoters, while knockdown of STAT1 by AAV-Cre in STAT1 mice or expressing dominant negative Y701F-STAT1 efficiently rescues hTau-induced suppression of NMDAR expression with amelioration of synaptic functions and memory performance. These findings indicate that hTau accumulation impairs synaptic plasticity through JAK2/STAT1-induced suppression of NMDAR expression, revealing a novel mechanism for hTau-associated synapse and memory deficits.
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http://dx.doi.org/10.15252/embr.201847202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549025PMC
June 2019

Syphilis-attributable adverse pregnancy outcomes in China: a retrospective cohort analysis of 1187 pregnant women with different syphilis treatment.

BMC Infect Dis 2019 Mar 29;19(1):292. Epub 2019 Mar 29.

Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, China.

Background: Syphilis is responsible for a substantial burden of preventable adverse outcomes in pregnancy. The purpose of this study was to compare the frequency of adverse pregnancy outcomes among syphilis-seropositive women who received different treatment regimens at different times in Guangzhou, China.

Methods: Pregnant women with syphilis infection who received prenatal and delivery services in Guangzhou between January 2014 and December 2016 were included. Association between treatment status and the composite adverse outcomes (preterm birth, infant smaller than gestational age, stillbirth, and spontaneous abortion) was estimated.

Results: Of 1187 syphilis-seropositive pregnant women included in the analysis, 900 (75.8%) syphilis-seropositive pregnant women received treatment, and 287(24.2%) did not receive treatment. Adverse pregnancy outcomes were observed among 16.3% (147/900) of women with treatment and 33.8% (97/287) of women without treatment. Syphilis-seropositive pregnant women treated with one or two courses of penicillin had a similar risk of adverse pregnancy outcomes (adjusted RR = 1.36, 95% CI: 0.94-1.96). Adverse outcomes were more common among women whose non-treponemal serum test titer was >1:8 and received treatment after 28 weeks compared to before 28 weeks (adjusted RR = 2.34, 95% CI: 1.22-4.48).

Conclusions: Women who received one course of penicillin and women who received two courses of penicillin had a similar risk of adverse pregnancy outcomes. Syphilis treatment before 28 weeks of pregnancy is critical. Strategies to promote high-quality prenatal services are needed.
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http://dx.doi.org/10.1186/s12879-019-3896-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439997PMC
March 2019

Inflammation-dependent ISG15 upregulation mediates MIA-induced dendrite damages and depression by disrupting NEDD4/Rap2A signaling.

Biochim Biophys Acta Mol Basis Dis 2019 06 28;1865(6):1477-1489. Epub 2019 Feb 28.

Department of Pathophysiology, Key Laboratory of Ministry of Education of China for Neurological Disorders, School of Basic Medicine of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China. Electronic address:

Background: Maternal immune activation (MIA) is an independent risk factor for psychiatric disorders including depression spectrum in the offsprings, but the molecular mechanism is unclear. Recent studies show that interferon-stimulated gene-15 (ISG15) is involved in inflammation and neuronal dendrite development; here we studied the role of ISG15 in MIA-induced depression and the underlying mechanisms.

Methods: By vena caudalis injecting polyinosinic: polycytidylic acid (poly I:C) into the pregnant rats to mimic MIA, we used AAV or lentivirus to introduce or silence ISG15 expression. Synaptic plasticity was detected by confocal microscope and Golgi staining. Cognitive performances of the offspring were measured by Open field, Forced swimming and Sucrose preference test.

Results: We found that MIA induced depression-like behaviors with dendrite impairments in the offspring with ISG15 level increased in the offsprings' brain. Overexpressing ISG15 in the prefrontal cortex of neonatal cubs (P0) could mimic dendritic pathology and depressive like behaviors, while downregulating ISG15 rescued these abnormalities in the offsprings. Further studies demonstrated that MIA-induced upregulation of inflammatory cytokines promoted ISG15 expression in the offspring' brain which suppressed Rap2A ubiquitination via NEDD4 and thus induced Rap2A accumulation, while upregulating NEDD4 abolished ISG15-induced dendrite impairments.

Conclusions: These data reveal that MIA impedes offsprings' dendrite development and causes depressive like behaviors by upregulating ISG15 and suppressing NEDD4/Rap2A signaling. The current findings suggest that inhibiting ISG15 may be a promising intervention of MIA-induced psychiatric disorders in the offsprings.
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http://dx.doi.org/10.1016/j.bbadis.2019.02.020DOI Listing
June 2019

Identification of autoimmune type 1 diabetes and multiple organ-specific autoantibodies in adult-onset non-insulin-requiring diabetes in China: A population-based multicentre nationwide survey.

Diabetes Obes Metab 2019 04 25;21(4):893-902. Epub 2018 Dec 25.

Department of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University, Changsha, China.

Aims: To investigate the prevalence of adult-onset autoimmune diabetes (ADM) and predisposition to autoimmune diseases by quantifying serum organ-specific autoantibodies in people with phenotype of type 2 diabetes (T2D).

Materials And Methods: We included a nationally representative sample of 46 239 adults aged ≥20 years from 14 provinces, of whom 4671 had diabetes, plus 1000 control subjects with normal glucose tolerance (NGT). Participants were screened centrally for autoantibodies to glutamic acid decarboxylase (GAD), islet antigen 2 (IA2) and zinc transporter isoform-8 (Znt8) and were defined as having ADM where positive for these antibodies. We then assayed thyroid peroxidase (TPO), tissue transglutaminase (tTG) and 21-hydroxylase (21-OH) autoantibodies in randomly selected participants with ADM and in age-matched, sex-matched and non-ADM controls with T2D plus controls with NGT.

Results: Post-normalization, the standardized prevalence rate of ADM was 6.0% (95% confidence interval [CI] 5.3-6.8) in initially non-insulin-requiring participants with ADM, corresponding to six million adults in China, in whom adjusted antibody positivity was: TPO autoantibodies 16.3% (95% CI 10.8-21.8), tTG autoantibodies 2.1% (95% CI 0.0-4.2), and 21-OH autoantibodies 1.8% (95% CI -0.2 to 3.8). Those participants with ADM who were GAD autoantibody-positive had high risk of TPO autoantibody positivity (odds ratio [OR] 2.39, P = 0.0031) and tTG autoantibody positivity (OR 6.98, P = 0.027), while those positive for IA2 autoantibodies had a high risk of tTG autoantibody positivity (OR 19.05, P = 0.001).

Conclusions: A proportion of people with phenotype of T2D in China have ADM, with diabetes-associated autoantibodies, and may be at risk of developing other organ-specific autoimmune diseases; therefore, it may be clinically relevant to consider screening such Chinese populations.
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http://dx.doi.org/10.1111/dom.13595DOI Listing
April 2019

Cognitive deficits and Alzheimer-like neuropathological impairments during adolescence in a rat model of type 2 diabetes mellitus.

Neural Regen Res 2018 Nov;13(11):1995-2004

Department of Pathophysiology; Henan Key Laboratory of Degenerative Brain Disease, Henan Medical College, Zhengzhou, Henan Province, China.

Numerous studies have shown that many patients who suffer from type 2 diabetes mellitus exhibit cognitive dysfunction and neuronal synaptic impairments. Therefore, growing evidence suggests that type 2 diabetes mellitus has a close relationship with occurrence and progression of neurodegeneration and neural impairment in Alzheimer's disease. However, the relationship between metabolic disorders caused by type 2 diabetes mellitus and neurodegeneration and neural impairments in Alzheimer's disease is still not fully determined. Thus, in this study, we replicated a type 2 diabetic animal model by subcutaneous injection of newborn Sprague-Dawley rats with monosodium glutamate during the neonatal period. At 3 months old, the Barnes maze assay was performed to evaluate spatial memory function. Microelectrodes were used to measure electrophysiological function in the hippocampal CA1 region. Western blot assay was used to determine expression levels of glutamate ionotropic receptor NMDA type subunit 2A (GluN2A) and GluN2B in the hippocampus. Enzyme-linked immunosorbent assay was used to determine levels of interleukin-1β, tumor necrosis factor α, and interleukin-6 in the hippocampus and cerebral cortex, as well as hippocampal amyloid beta (Aβ) and Aβ levels. Our results showed that in the rat model of type 2 diabetes mellitus caused by monosodium glutamate exposure during the neonatal period, latency was prolonged and the number of errors increased in the Barnes maze. Further, latency was increased and time in the escape platform quadrant shortened. Number of times crossing the platform was also reduced in the Morris water maze. After high frequency stimulation of the hippocampus, synaptic transmission was inhibited, expression of GluN2A and GluN2B were decreased in the hippocampus, expression of interleukin 1β, interleukin 6, and tumor necrosis factor α was increased in the hippocampus and cortex, and levels of Aβ and Aβ were increased in the hippocampus. These findings confirm that type 2 diabetes mellitus induced by neonatal monosodium glutamate exposure results in Alzheimer-like neuropathological changes and further causes cognitive deficits and neurodegeneration in young adulthood.
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http://dx.doi.org/10.4103/1673-5374.239448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6183048PMC
November 2018

Monosodium glutamate exposure during the neonatal period leads to cognitive deficits in adult Sprague-Dawley rats.

Neurosci Lett 2018 08 6;682:39-44. Epub 2018 Jun 6.

Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, No. 13 Hangkong Road, Wuhan 430030, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, JS 226001, China. Electronic address:

Epidemiological surveys show that 70-80% of patients with Alzheimer's disease (AD) have type 2 diabetes mellitus (T2DM) or show an abnormality of blood glucose levels. Therefore, an increasing number of evidence has suggested that diabetic hyperglycemia is tightly linked with the pathogenesis and progression of AD. In the present study, we replicated T2DM animal model via subcutaneous injection of newborn Sprague-Dawley (SD) rats with monosodium glutamate (MSG) during the neonatal period to investigate the effects and underlying mechanisms of hyperglycemia on cognitive ability. We found that neonatal MSG exposure induced hyperglycemia as well as Alzheimer-like learning and memory deficits with decreased dendritic spine density and hippocampal synaptic-related protein expression and increased phosphorylated tau levels in ∼3-month-old SD rats. Our results suggested that hyperglycemia probably causes cognitive impairment and Alzheimer-like neuropathological changes, which provide the experimental data connecting T2DM and AD.
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http://dx.doi.org/10.1016/j.neulet.2018.06.008DOI Listing
August 2018

Inhibition of Histone Acetylation by ANP32A Induces Memory Deficits.

J Alzheimers Dis 2018 ;63(4):1537-1546

Department of Pathophysiology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.

There is accumulating evidence that decreased histone acetylation is involved in normal aging and neurodegenerative diseases. Recently, we found that ANP32A, a key component of INHAT (inhibitor of acetyltransferases) that suppresses histone acetylation, increased in aged and cognitively impaired C57 mice and expressing wild-type human full length tau (htau) transgenic mice. Downregulating ANP32A restored cognitive function and synaptic plasticity through upregulation of the expressions of synaptic-related proteins via increasing histone acetylation. However, there is no direct evidence that ANP32A can induce neurodegeneration and memory deficits. In the present study, we overexpressed ANP32A in the hippocampal CA3 region of C57 mice and found that ANP32A overexpression induced cognitive abilities and synaptic plasticity deficits, with decreased synaptic-related protein expression and histone acetylation. Combined with our recent studies, our findings reveal that upregulated ANP32A induced-suppressing histone acetylation may underlie the cognitive decline in neurodegenerative disease, and suppression of ANP32A may represent a promising therapeutic approach for neurodegenerative diseases including Alzheimer's disease.
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http://dx.doi.org/10.3233/JAD-180090DOI Listing
June 2019

MicroRNA-92b promotes cell proliferation and invasion in osteosarcoma by directly targeting Dickkopf-related protein 3.

Exp Ther Med 2018 Jan 23;15(1):173-181. Epub 2017 Oct 23.

Department of Immunology and Microbiology, Medical School of Jishou University, Jishou, Hunan 416000, P.R. China.

Deregulation of microRNA-92b (miR-92b) has been implicated in osteosarcoma. However, the underlying regulatory mechanism of miR-92b in osteosarcoma growth and metastasis remains largely unclear. In the present study, reverse transcription-quantitative polymerase chain reaction and western blotting were used to measure mRNA and protein expression. MTT and Transwell assays were conducted to determine cell proliferation and invasion, and a luciferase reporter assay was performed to confirm the association between miR-92b and Dickkopf3-related protein (DKK3). The results demonstrated that miR-92b was significantly upregulated in osteosarcoma tissues compared with matched adjacent non-tumor tissues. Additionally, high miR-92b levels were significantly associated with lung metastasis and advanced tumor, node, metastasis stage (P<0.05) but not with age, sex, tumor size, location, serum lactate dehydrogenase or serum alkaline phosphatase. miR-92b expression was also significantly upregulated in osteosarcoma cell lines compared with normal osteoblast cells. Knockdown of miR-92b significantly inhibited the proliferation and invasion of osteosarcoma U2OS cells (P<0.01). By contrast, overexpression of miR-92b significantly increased U2OS cell proliferation and invasion (P<0.01). DKK3 was identified as a target gene of miR-92b and it was demonstrated that DKK3 expression was negatively regulated by miR-92b in U2OS cells. Restoration of DKK3 expression abrogated the increased proliferation and invasion of U2OS cells induced by miR-92b overexpression. Notably, DKK3 was significantly downregulated in osteosarcoma tissues compared with adjacent non-tumor tissues and its expression was inversely correlated to miR-92b levels in osteosarcoma tissues. Taken together, these data indicate that miR-92b promotes cell proliferation and invasion in osteosarcoma by targeting DKK3. Therefore, miR-92b may become a potential therapeutic target for osteosarcoma.
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http://dx.doi.org/10.3892/etm.2017.5356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729699PMC
January 2018

Propoxur enhances MMP-2 expression and the corresponding invasion of human breast cancer cells via the ERK/Nrf2 signaling pathway.

Oncotarget 2017 Oct 7;8(50):87107-87123. Epub 2017 Jul 7.

Center of Hygiene Assessment and Research, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing 100071, China.

Propoxur is considered a prime etiological suspect of increasing tumor incidence, but the role is still undefined. In this study, two human breast cancer cells lines, MCF-7 and MDA-MB-231 cells, were used as cell models. Cells were respectively treated with 0, 0.01, 1, or 100 μM propoxur. PD98059, a MEK inhibitor, was administered to block the ERK/MAPK pathway. Migration and reactive oxygen species were measured by wound healing and Transwell assays, and flow cytometry. Protein expression and subcellular location were detected by western blotting and immunofluorescence staining, respectively. Results showed that propoxur treatment enhanced cell migration and invasion in a dose-dependent manner, while MMP-2 expression, but not MMP-9, was significantly increased in two cell lines. Meanwhile, the treatment increased intracellular reactive oxygen species, Nrf2 expression and nuclear translocation, and ERK1/2 phosphorylation. Inversely, inhibition of ERK1/2 activation with PD98059 significantly attenuated propoxur-induced Nrf2 expression and nuclear translocation. Moreover, PD98059 suppressed propoxur-induced cell migration and invasion, and MMP-2 overexpression. Collectively, these results indicate that propoxur can trigger reactive oxygen species overproduction, further promoting breast cancer cell migration and invasion by regulating the ERK/Nrf2 signaling pathways.
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http://dx.doi.org/10.18632/oncotarget.19081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675619PMC
October 2017

Effectiveness of a Kindergarten-Based Intervention for Preventing Childhood Obesity.

Pediatrics 2017 Dec 10;140(6). Epub 2017 Nov 10.

Division of Birth Cohort Study and

Background And Objectives: Interventions to prevent childhood obesity targeting school age children have mostly reported limited effectiveness, suggesting such prevention programs may need to start at an earlier age, but evidence has been scarce. We reported a pilot study aiming to demonstrate the feasibility of a multifaceted intervention for preschool children and to provide a preliminary assessment of the effectiveness.

Methods: This nonrandomized controlled trial recruited children aged 3 to 6 years from 6 kindergartens in Guangzhou, China. Based on the preference of the School and Parents Committees, 4 kindergartens (648 children) received a 3-component intervention (training of kindergarten staff, initiating healthy curriculum for children, and close collaboration between families and kindergartens) over 12 months, while the other 2 kindergartens (336 children), serving as controls, received routine health care provision. Outcome measures were the changes in BMI score between baseline and the end of 12 months, and the prevalence of postintervention children who were overweight or obese.

Results: By 12 months, children within the intervention group had a smaller BMI score increase (0.24) compared to the control (0.41), with a difference of -0.31 (95% CI -0.47 to -0.15). The prevalence of overweight or obesity was also lower among the intervention group at the end of the study (OR: 0.43, 95% CI 0.19 to 0.96), adjusted for baseline status.

Conclusions: Our results indicated a multicomponent health behavior intervention might be effective in reducing the prevalence of obesity, but the longer term effects will need confirmation from randomized controlled trials.
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http://dx.doi.org/10.1542/peds.2017-1221DOI Listing
December 2017

Metabolic effect of obesity on polycystic ovary syndrome in adolescents: a meta-analysis.

J Obstet Gynaecol 2017 Nov 28;37(8):1036-1047. Epub 2017 Jun 28.

a Department of Gynecology and Obstetrics , Guangzhou Women and Children's Medical Center, Guangzhou Medical University , Guangzhou , China.

This meta-analysis provides an updated and comprehensive estimate of the effects of obesity on metabolic disorders in adolescent polycystic ovary syndrome (PCOS). Relevant articles consistent with the search terms published up to 31 January 2014 were retrieved from PubMed, EMBASE, PsycINFO and CENTRAL. Thirteen articles (16 independent studies) conformed to the inclusion criteria. The evaluated outcomes were the metabolic parameters of obese adolescents with PCOS (case group) relative to normal-weight adolescents with PCOS, or obese adolescents without PCOS. Compared with normal-weight adolescents with PCOS, the case group had significantly lower sex hormone-binding globulin and high-density lipoprotein cholesterol, and significantly higher triglycerides, leptin, fasting insulin, low-density lipoprotein cholesterol and free testosterone levels. Relative to obese adolescents without PCOS, the case group had significantly higher fasting insulin, low-density lipoprotein cholesterol, free testosterone levels and 2-h glucose during the oral glucose tolerance test. These results indicate that metabolic disorders in adolescent PCOS are worsened by concomitant obesity. This study highlights the importance of preventing obesity during the management of adolescent PCOS. Impact statement What is already known about this subject: Obesity and PCOS share many of the same metabolic disorders, for example, hyperandrogenism and hyperinsulinemia with subsequent insulin resistance. Knowledge regarding metabolic features in obese adolescents with PCOS is limited, and there is concern whether obesity and PCOS are related. What do the results of this study add: Relative to PCOS adolescents of normal weight, obese adolescents with PCOS (the case group) had significantly lower SHBG and HDL-C, and significantly higher triglycerides, leptin, fasting insulin, LDL-C and free testosterone levels. The results indicate that metabolic disorders in adolescent PCOS are worsened by concomitant obesity. What are the implications of these findings for clinical practice and/or further research: Obesity, metabolic disorders and PCOS in adolescents are associated. Obesity exacerbates metabolic disorders in adolescent PCOS. This study highlights the importance of preventing obesity during the management of adolescent PCOS. Therapeutic intervention combined with lifestyle modification may provide better treatment for adolescent PCOS. The aetiologies of PCOS combined with obesity in adolescents require further investigation.
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http://dx.doi.org/10.1080/01443615.2017.1318840DOI Listing
November 2017

MicroRNA-137 acts as a tumor suppressor in osteosarcoma by targeting enhancer of zeste homolog 2.

Exp Ther Med 2017 Jun 5;13(6):3167-3174. Epub 2017 May 5.

Department of Immunology and Microbiology, Medical School of Jishou University, Jishou, Hunan 416000, P.R. China.

MicroRNA (miR) are short non-coding RNA that bind to the 3'-untranslational region of their target genes, inhibiting translation and causing mRNA degradation. miR deregulation has been implicated in human cancer; however, the detailed regulatory mechanism of miR-137 in osteosarcoma (OS) remains largely unknown. In the present study, miR-137 and enhancer of zeste homologue 2 (EZH2) mRNA and protein expression levels were analyzed using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. MTT and transwell assays were performed to evaluate cell viability and invasion capacities and a luciferase reporter gene assay was used to determine the targeting relationship. The results of the current study indicated that miR-137 expression was significantly downregulated in OS tissues and cell lines (P<0.01). Moreover, it was observed that low miR-137 expression levels were significantly associated with lung metastasis and advanced TMN stage (P<0.05), but not associated with age, gender, tumor size, location, serum lactate dehydrogenase or serum alkaline phosphatase. Increasing levels of miR-137 significantly inhibited U2OS cell viability and invasion (P<0.01). By contrast, knockdown of miR-137 markedly increased U2OS cell viability and invasion. EZH2 was identified as a direct target gene of miR-137 in U2OS cells by luciferase reporter assay and EZH2 expression was found to be significantly increased in OS tissues and cell lines (P<0.01). EZH2 was significantly downregulated following miR-137 overexpression (P<0.01), and was upregulated following miR-137 knockdown in U2OS cells. Furthermore, EZH2 overexpression significantly attenuated the suppressive effects of miR-137 on U2OS cell viability and invasion (P<0.01), suggesting that miR-137 inhibits the viability and invasion of OS cells by targeting EZH2. Therefore, the results of the current study suggest that the miR-137/EZH2 axis may be a potential target for novel potential therapeutic strategies to treat OS.
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http://dx.doi.org/10.3892/etm.2017.4435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450755PMC
June 2017
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