Publications by authors named "Xiaojing Meng"

41 Publications

NLRP3 induces the autocrine secretion of IL-1β to promote epithelial-mesenchymal transition and metastasis in breast cancer.

Biochem Biophys Res Commun 2021 Jun 8;560:72-79. Epub 2021 May 8.

Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China. Electronic address:

Tumor metastasis is a leading cause of mortality in patients with breast cancer (BC). As a predominant component of inflammasome, Nod-like receptor protein 3 (NLRP3) was found to be required for tumor progression, while the role of NLRP3 in BC metastasis remains largely undefined. In current study, we found that invasive BC had aberrant upregulation of NLRP3 expression, especially in the claudin-low subtype. And higher expression of NLRP3 predicted poor survival of BC patients. Further investigation suggested that NLRP3 promotes the migration and invasion, as well as the metastasis of BC cells. Moreover, we revealed that NLRP3 induces the autocrine secretion of IL-1β to promote epithelial-mesenchymal transition via a Caspase-1-dependent manner. Hence, this study suggested that upregulation of NLRP3 in BC induces the autocrine secretion of IL-1β and promotes EMT and metastasis of BC cells.
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http://dx.doi.org/10.1016/j.bbrc.2021.04.122DOI Listing
June 2021

Increased risk of multiple pregnancy complications following large-scale power outages during Hurricane Sandy in New York State.

Sci Total Environ 2021 May 24;770:145359. Epub 2021 Jan 24.

Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Rensselaer, NY 12144, USA; Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, State University of New York, Albany, NY 12144, USA. Electronic address:

Background: Large-scale power outages (PO) are increasing in the context of climate change. Although some research has been conducted into the adverse health impacts of POs, significant gaps remain regarding whether POs would affect the health of pregnant women. We investigated the association between ED visits due to pregnancy complications and the occurence, intensity, and duration of large-scale POs in eight Sandy-affected counties in New York State (NYS).

Methods: In this cross-sectional study, daily ED visits for pregnancy complications and large-scale PO data in eight counties in NYS from October to December in 2005-2014 were collected. Using time-series analysis, we estimated the relative increase in ED visits for pregnancy complications during POs compared with non-PO periods at lag 0-7 days. Short-term health impacts of PO intensity and PO duration were investigated. Estimations were also stratified by sociodemographic characteristics and disease subtypes including threatened or spontaneous abortion, threatened or early labor, hypertension complications, infections of genitourinary tract, renal diseases, gestational diabetes mellitus, mental illnesses, and cardiovascular diseases during pregnancy.

Results: From October to December in 2005-2014, there were 307,739 ED visits for pregnancy complications in the eight counties. We found significant increases in ED visits for overall pregnancy complications (16.6%, 95% confidence interval [CI]: 10.3%, 23.2%) during the Hurricane-PO period at lag 0-7 days. The ED visits increased by 8.8% per level increase in PO intensity and 1.4% per day increase in PO duration. Specifically, threatened/early delivery and gestational diabetes mellitus during the PO period increased by 26.7% (95% CI: 8.2%, 48.4%) and 111.8% (95% CI: 16.7%, 284.4%), respectively. Young adult, Black, Hispanic, and uninsured individuals were at higher risk of complications.

Conclusions: POs may adversely impact pregnancy, especially for certain pregnancy complications and among low sociodemographic women.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145359DOI Listing
May 2021

The interactive effects of ambient air pollutants-meteorological factors on confirmed cases of COVID-19 in 120 Chinese cities.

Environ Sci Pollut Res Int 2021 Jun 27;28(21):27056-27066. Epub 2021 Jan 27.

Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, People's Republic of China.

Emerging evidence has confirmed meteorological factors and air pollutants affect novel coronavirus disease 2019 (COVID-19). However, no studies to date have considered the impact of interactions between meteorological factors and air pollutants on COVID-19 transmission. This study explores the association between ambient air pollutants (PM, NO, SO, CO, and O), meteorological factors (average temperature, diurnal temperature range, relative humidity, wind velocity, air pressure, precipitation, and hours of sunshine), and their interaction on confirmed case counts of COVID-19 in 120 Chinese cities. We modeled total confirmed cases of COVID-19 as the dependent variable with meteorological factors, air pollutants, and their interactions as the independent variables. To account for potential migration effects, we included the migration scale index (MSI) from Wuhan to each of the 120 cities included in the model, using data from 15 Jan. to 18 Mar. 2020. As an important confounding factor, MSI was considered in a negative binomial regression analysis. Positive associations were found between the number of confirmed cases of COVID-19 and CO, PM, relative humidity, and O, with and without MSI-adjustment. Negative associations were also found for SO and wind velocity both with and without controlling for population migration. In addition, air pollutants and meteorological factors had interactive effects on COVID-19 after controlling for MSI. In conclusion, air pollutants, meteorological factors, and their interactions all affect COVID-19 cases.
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http://dx.doi.org/10.1007/s11356-021-12648-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837878PMC
June 2021

Genome-Wide Identification and Analysis of and Gene Families in Species and Response to Stress in .

Int J Mol Sci 2021 Jan 7;22(2). Epub 2021 Jan 7.

College of Agronomy and Biotechnology, Southwest University, Chongqing 400715, China.

Mitogen-activated protein kinase (MAPK) cascades are common and conserved signal transduction pathways and play important roles in various biotic and abiotic stress responses and growth and developmental processes in plants. With the advancement of sequencing technology, more systematic genetic information is being explored. The work presented here focuses on two protein families in species: MAPK kinases (MKKs) and their phosphorylation substrates MAPKs. Forty-seven MKKs and ninety-two MAPKs were identified and extensively analyzed from two tetraploid ( and ) and three diploid (, , and ) species. Phylogenetic relationships clearly distinguished both MKK and MAPK families into four groups, labeled A-D, which were also supported by gene structure and conserved protein motif analysis. Furthermore, their spatial and temporal expression patterns and response to stresses (cold, drought, heat, and shading) were analyzed, indicating that and transcript levels were generally modulated by growth, development, and stress signals. In addition, several protein interaction pairs between BnaMKKs and C group BnaMAPKs were detected by yeast two-hybrid assays, in which BnaMKK3 and BnaMKK9 showed strong interactions with BnaMAPK1/2/7, suggesting that interaction between BnaMKKs and C group BnaMAPKs play key roles in the crosstalk between growth and development processes and abiotic stresses. Taken together, our data provide a deeper foundation for the evolutionary and functional characterization of and gene families in species, paving the way for unraveling the biological roles of these important signaling molecules in plants.
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http://dx.doi.org/10.3390/ijms22020544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827818PMC
January 2021

Switching of delta opioid receptor subtypes in central amygdala microcircuits is associated with anxiety states in pain.

J Biol Chem 2021 Jan 8:100277. Epub 2021 Jan 8.

School of Basic Medical Sciences, Anhui Medical University, Meishan Road 81, Hefei 230022, China; Hefei National Laboratory for Physical Sciences at the Microscale, Department of Biophysics and Neurobiology, University of Science and Technology of China, Hefei 230027, PR China. Electronic address:

Anxiety is often comorbid with pain. Delta opioid receptors (DORs) are promising targets for the treatment of pain and mental disorders with little addictive potential. However, their roles in anxiety symptoms at different stages of pain are unclear. In the current study, mice with inflammatory pain at the 4th hour following complete Freund's adjuvant (CFA) injection displayed significant anxiety-like behavior, which disappeared at the 7th day. Combining electrophysiology, optogenetics, and pharmacology, we found that activation of delta opioid receptor 1 (DOR1) in the central nucleus amygdala (CeA) inhibited both the anxiolytic excitatory input from the basolateral amygdala (BLA) and the anxiogenic excitatory input from the parabrachial nucleus (PBN). In contrast, activation of delta opioid receptor 2 (DOR2) did not affect CeA excitatory synaptic transmission in normal and 4-hour CFA mice but inhibited the excitatory projection from the PBN rather than the BLA in 7-day CFA mice. Furthermore, the function of both DOR1 and DOR2 was downregulated to the point of not being detectable in the CeA of mice at the 21st day following CFA injection. Taken together, these results suggest that functional switching of DOR1 and DOR2 is associated with anxiety states at different stages of pain via modulating the activity of specific pathways (BLA-CeA and PBN-CeA).
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http://dx.doi.org/10.1016/j.jbc.2021.100277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948800PMC
January 2021

Effects of ecologically relevant concentrations of cadmium on locomotor activity and microbiota in zebrafish.

Chemosphere 2020 Oct 27;257:127220. Epub 2020 May 27.

Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China. Electronic address:

Cadmium (Cd) is widely spread in the aquatic environment, and its impact on humans and the ecosystem is an important issue in public health. However, its effects on zebrafish microbiota are still poorly understood. In this study, the potential developmental neurotoxicity and microbiota dysbiosis of ecologically relevant concentrations of Cd (0, 1.25, 2.5 and 5 μg/L) was evaluated by waterborne exposure for 7 days. The data showed that exposure to 5 μg/L of Cd significantly decreased survival rates and impaired locomotor activities. Uptake of Cd was enhanced with the increase of the concentration and duration of exposure. High-throughput sequencing analysis revealed a significant change in the richness and diversity of the microbiota of Cd-treated zebrafish. At the phylum level, the abundance of Proteobacteria increased, while that Firmicutes was significantly decreased after exposure to 5 μg/L Cd. At the genus level, there were significant changes in the abundances of several bacteria involved in the regulation of neurodegenerative diseases (Pseudomonas, Ruminococcaceae, Blautia, Bacteroides, Lactobacillus, Lachnospiraceae, and Phascolarctobacterium) in the Cd-treatment groups, as compared to the control group. In addition, the mRNA expression profiles of bdnf and genes involved in serotonin signaling and metabolism were changed in the Cd exposure groups. Together, these data suggest that Cd could be harmful to zebrafish health by inducing the microbiota changes, and the microbiota could serve as a potential target to protect against the adverse effects of Cd toxicity.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127220DOI Listing
October 2020

induces necrotizing enterocolitis by regulating NLRP3 inflammasome expression via TLR4.

J Med Microbiol 2020 May 25;69(5):748-758. Epub 2020 Mar 25.

Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, PR China.

Neonatal infection with can cause severe intestinal damage and necrotizing enterocolitis (NEC). The inflammasome and Toll-like receptors mediate intestinal damage caused by other intestinal pathogens causing NEC, but the exact mechanism is unclear. We evaluated the molecular mechanisms underlying -induced NEC. The effects of treatment on two cell lines and a Sprague-Dawley rat model of NEC were evaluated by a cell death assay, western blot and real-time PCR analyses of the NLRP3 inflammasome and downstream factors, and observation of cell and intestinal damage. caused cellular damage , as well as intestinal damage in an animal model. NLRP3, caspase-1, TLR4 and MyD88, as well as the downstream factor IL-1β, were upregulated in -infected J774A.1 and HT-29 cells. Western blotting showed that infected J774A.1 and HT-29 cells and the NEC rat model had higher expression levels of N-terminal gasdermin D (GSDMD) compared with those in the control groups. and its components promote NF-κB expression via the TLR4/MyD88 signalling pathway, thereby regulating the NLRP3 inflammasome and mediating GSDMD cleavage, resulting in pyroptosis-induced intestinal damage. We found that upregulates NF-κB via TLR4/MyD88 to promote activation of the NLRP3 inflammasome, leading to the up-regulation of downstream caspase-1, release of IL-1β, GSDMD-mediated pyroptosis and development of NEC. These findings clarify the mechanisms by which contributes to NEC.
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http://dx.doi.org/10.1099/jmm.0.001181DOI Listing
May 2020

A protective role of autophagy in Pb-induced developmental neurotoxicity in zebrafish.

Chemosphere 2019 Nov 1;235:1050-1058. Epub 2019 Jul 1.

Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China. Electronic address:

Lead (Pb) is one of the most toxic heavy metals and has aroused widespread concern as it can cause severe impairments in the developing nervous system. Autophagy has been proposed as an injury factor in Pb-induced neurotoxicity. In this study, we used zebrafish embryo as a model, measured the general toxic effects of Pb, and investigated the effect of Pb exposure on autophagy, and its role in Pb-induced developmental neurotoxicity. Zebrafish embryos were exposed to Pb at concentrations of 0, 0.1, 1 or 10 μM until 4 days post-fertilization. Our data showed that exposure to 10 μM Pb significantly reduced survival rates and impaired locomotor activity. Uptake of Pb was enhanced as the concentration and duration of exposure increased. Inhibition of lysosomal degradation with bafilomycin A1 treatment abolished the suppression of Lc3-II protein expression by Pb. Furthermore, autophagosome formation was inhibited by Pb in the brain. In addition, mRNA expression of beclin1, one of the critical genes in autophagy, were decreased in Pb exposure groups at 72 h post-fertilization. Whole-mount in situ hybridization assay showed that beclin1 gene expression in the brain was reduced by Pb. Rapamycin, an autophagy inducer, partly resolved developmental neurotoxicity induced by Pb exposure. Our results suggest that autophagy plays a protective role in the developmental neurotoxicity of Pb in zebrafish embryos and larvae.
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http://dx.doi.org/10.1016/j.chemosphere.2019.06.227DOI Listing
November 2019

Calcium-sensing stromal interaction molecule 2 upregulates nuclear factor of activated T cells 1 and transforming growth factor-β signaling to promote breast cancer metastasis.

Breast Cancer Res 2019 08 29;21(1):99. Epub 2019 Aug 29.

Department of Occupational Health and Occupational Medicine, School of Public Health, Southern Medical University, Guangzhou, 510515, Guangdong, China.

Background: Stromal interaction molecule (STIM) 2 is a key calcium-sensing molecule that regulates the stabilization of calcium ions (Ca) and therefore regulates downstream Ca-associated signaling and cellular events. We hypothesized that STIM2 regulates epithelial-mesenchymal transition (EMT) to promote breast cancer metastasis.

Methods: We determined the effects of gain, loss, and rescue of STIM2 on cellular motility, levels of EMT-related proteins, and secretion of transforming growth factor-β (TGF-β). We also conducted bioinformatics analyses and in vivo assessments of breast cancer growth and metastasis using xenograft models.

Results: We found a significant association between STIM2 overexpression and metastatic breast cancer. STIM2 overexpression activated the nuclear factor of activated T cells 1 (NFAT1) and TGF-β signaling. Knockdown of STIM2 inhibited the motility of breast cancer cells by inhibiting EMT via specific suppression of NFAT1 and inhibited mammary tumor metastasis in mice. In contrast, STIM2 overexpression promoted metastasis. These findings were validated in human tissue arrays of 340 breast cancer samples for STIM2.

Conclusion: Taken together, our results demonstrated that STIM2 specifically regulates NFAT1, which in turn regulates the expression and secretion of TGF-β1 to promote EMT in vitro and in vivo, leading to metastasis of breast cancer.
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http://dx.doi.org/10.1186/s13058-019-1185-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6716836PMC
August 2019

MRP4 sustains Wnt/β-catenin signaling for pregnancy, endometriosis and endometrial cancer.

Theranostics 2019 9;9(17):5049-5064. Epub 2019 Jul 9.

Deparment of Biomedical Engineering, Faculty of Engineering, the Hong Kong Polytechnic University.

: Abnormal Wnt/β-catenin signaling in the endometrium can lead to both embryo implantation failure and severe pathogenic changes of the endometrium such as endometrial cancer and endometriosis. However, how Wnt/β-catenin signaling is regulated in the endometrium remains elusive. We explored possible regulation of Wnt/β-catenin signaling by multi-drug resistance protein 4 (MRP4), a potential target in cancer chemotherapy, and investigated the mechanism. : Knockdown of MRP4 was performed in human endometrial cells or in a mouse embryo-implantation model . Immunoprecipitation, immunoblotting and immunofluorescence were used to assess protein interaction and stability. Wnt/β-catenin signaling was assessed by TOPflash reporter assay and quantitative PCR array. Normal and endometriotic human endometrial tissues were examined. Data from human microarray or RNAseq databases of more than 100 participants with endometriosis, endometrial cancer or IVF were analyzed. and tumorigenesis was performed. : MRP4-knockdown, but not its transporter-function-inhibition, accelerates β-catenin degradation in human endometrial cells. MRP4 and β-catenin are co-localized and co-immunoprecipitated in mouse and human endometrium. MRP4-knockdown in mouse uterus reduces β-catenin levels, downregulates a series of Wnt/β-catenin target genes and impairs embryo implantation, which are all reversed by blocking β-catenin degradation. Analysis of human endometrial biopsy samples and available databases reveals significant and positive correlations of MRP4 with β-catenin and Wnt/β-catenin target genes in the receptive endometrium in IVF, ectopic endometriotic lesions and endometrial cancers. Knockdown of MRP4 also inhibits and endometrial tumorigenesis. : A previously undefined role of MRP4 in stabilizing β-catenin to sustain Wnt/β-catenin signaling in endometrial cells is revealed for both embryo implantation and endometrial disorders, suggesting MRP4 as a theranostic target for endometrial diseases associated with Wnt/β-catenin signaling abnormality.
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http://dx.doi.org/10.7150/thno.32097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691374PMC
August 2020

Relationship between occupational noise exposure and hypertension: A cross-sectional study in steel factories.

Am J Ind Med 2019 11 12;62(11):961-968. Epub 2019 Aug 12.

Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China.

Background: Hazardous exposure to occupational noise may be associated with an increased risk of cardiovascular disease and hypertension. This study was performed to assess the relationship between noise exposure and hypertension prevalence in steelworkers.

Methods: A cross-sectional survey using self-reported noise exposure and audiometrically measured hearing loss was performed. One thousand eight hundred and seventy-four workers were interviewed. Multiple logistic regression was used to calculate odds ratios for hypertension by noise exposure. Linear regression analysis was used to test associations between noise exposure and systolic blood pressure (SBP) and diastolic blood pressure (DBP).

Results: Occupational noise-exposed subjects had significantly higher blood pressure levels than nonexposed subjects (SBP: 123.18 ± (standard deviation) 12.44 vs 119.80 ± 12.50 mm Hg; DBP: 77.86 ± 9.34 vs 75.49 ± 8.73 mmHg). The prevalence of hypertension was approximately 5% in the control group without noise exposure or hearing impairment and increased from 6% to 21% across the range of increasing degree of hearing loss and, separately, of cumulative exposure time. Noise exposure (any) was associated with an increase in the prevalence of hypertension (odds ratio, 2.03, 95% confidence interval [CI]: 1.15-3.58). Noise-induced hearing loss and cumulative noise exposure time were positively correlated with BP (hearing loss: SBP: β = .09, 95% CI: 0.04-0.15 mm Hg, DBP: β = .11, 95% CI: 0.06-0.17 mm Hg; cumulative exposure time: SBP: β = .10, 95% CI: 0.04-0.15 mm Hg, DBP: β = .09, 95% CI: 0.04-0.15 mm Hg).

Conclusions: Noise exposure measured in two different ways was strongly associated with the prevalence of hypertension in steelworkers. Reducing noise in the steel factory could be a way of decreasing the risk of hypertension in this population.
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http://dx.doi.org/10.1002/ajim.23034DOI Listing
November 2019

MeHg-induced autophagy via JNK/Vps34 complex pathway promotes autophagosome accumulation and neuronal cell death.

Cell Death Dis 2019 05 21;10(6):399. Epub 2019 May 21.

Department of Occupational Health and Occupational Medicine, School of Public Health, Southern Medical University, 510515, Guangzhou, Guangdong, China.

Methylmercury (MeHg), an environmental toxin, may specifically cause neurological disorders. Recent studies have reported that autophagy can be induced by metals and be involved in metal cytotoxicity. However, the role of autophagy in MeHg-induced neurotoxicity remains unknown. Here, we demonstrate that MeHg induces mTOR-independent autophagy through JNK/Vps34 complex pathway, which further promotes autophagosome accumulation and neuronal cell death. In addition to cell death, MeHg increased LC3-II expression in a concentration- and time-dependent manner in neuronal cells; furthermore, western blot analysis of LC3-II expression under baf A1-treated condition indicates that MeHg activates autophagy induction. However, we found lysosomal degradative function was impaired by MeHg. Under this condition, MeHg-activated autophagy induction would elicit autophagosome accumulation and cell death. Consistent with this inference, the autophagy inhibitor decreased the MeHg-induced autophagosome accumulation and neuronal cells death, whereas the autophagy inducers further augmented MeHg cytotoxicity. Then, the mechanism of autophagy induction is investigated. We show that MeHg-induced autophagy is mTOR-independent. Vacuolar protein sorting 34 (Vps34) complex is critical for mTOR-independent autophagy. MeHg induced the interaction between Beclin1 and Vps34 to form Vps34 complex. Importantly, knockdown of Vps34 inhibited autophagy induction by MeHg. Furthermore, we found that JNK, but not p38 or ERK, promoted the formation of Vps34 complex and autophagy induction. Finally, inhibition of JNK or downregulation of Vps34 decreased autophagosome accumulation and alleviated MeHg-induced neuronal cell death. The present study implies that inhibiting JNK/Vps34 complex autophagy induction pathway may be a novel therapeutic approach for the treatment of MeHg-induced neurotoxicity.
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http://dx.doi.org/10.1038/s41419-019-1632-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529499PMC
May 2019

The immediate and lasting impact of Hurricane Sandy on pregnancy complications in eight affected counties of New York State.

Sci Total Environ 2019 Aug 1;678:755-760. Epub 2019 May 1.

Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Rensselaer, NY, USA. Electronic address:

Background: The frequency and intensity of hurricane have increased greatly. However, whether hurricane exposure is associated with an increased risk of pregnancy complications is less known.

Objective: To assess the immediate impact and lasting impact of Hurricane Sandy (Sandy) on pregnancy complications.

Methods: Using time-series study, we estimated the relative risks (RRs) of emergency department (ED) visits for pregnancy complications in eight affected counties in New York State, based on data of 2005-2014. The immediate impact was estimated by comparing the ED visits of pregnancy complications during the Sandy period to the non-Sandy periods. For the lasting impact of Sandy, we estimated the RRs by contrasting the ED visits in the following 12 months after Sandy with the same months of other years.

Results: We found that ED visits for overall pregnancy complications increased 6.3% (95% confidence interval (CI): 2.2%, 10.5%) during the Sandy month. ED visits increased for threatened abortion (9.9%, 95% CI: 4.4%, 15.7%), threatened labor (10.1%, 95% CI: 1.9%, 18.9%), early onset of delivery (115.9%, 95% CI: 6.9%, 336.3%), renal disease (73.2%, 95% CI: 0.3%, 199.4%), and diabetes (42.3%, 95% CI: 15.0%, 76.0%). Gestational hypertension and renal disease were elevated 7-8 months after Sandy. The ED visits of mental illness increased gradually after Sandy and peaked eight months later with visits increasing 33.2%.

Conclusions: This study suggests that hurricanes may impact pregnancy health immediately and that some negative health may last for months thereafter.
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http://dx.doi.org/10.1016/j.scitotenv.2019.04.436DOI Listing
August 2019

Differential response to lead toxicity in rat primary microglia and astrocytes.

Toxicol Appl Pharmacol 2019 01 23;363:64-71. Epub 2018 Nov 23.

Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China. Electronic address:

Lead (Pb) is one of the most widely studied occupational and environmental toxins. Chronic exposure to Pb affects neural function in the central nervous system (CNS). Glial cells in the CNS, such as microglia and astrocytes, respond differently to Pb-induced toxicity. However, the underlying mechanism has not yet been identified. We measured the cell viability and intracellular Pb uptake in rat primary microglia and astrocytes using the CCK-8 assay and inductively coupled plasma mass spectrometry, and found that Pb decreased microglial viability at lower dosages than in astrocytes, while Pb uptake was greater in astrocytes. Pb-induced oxidative stress in microglia results in increased production of reactive oxygen species, down-regulation of glutathione, and enhanced Nrf2 protein expression, while there was no obvious change in astrocytes. The role of Nrf2 in Pb-induced oxidative stress has also been confirmed in primary microglia with the use of Nrf2 small interfering RNA and an Nrf2 agonist. These data indicate that primary microglia were more sensitive to Pb exposure than astrocytes, which is associated with an obvious oxidative stress response and up-regulation of Nrf2 might be involved in this process.
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http://dx.doi.org/10.1016/j.taap.2018.11.010DOI Listing
January 2019

Exosomes derived from breast cancer lung metastasis subpopulations promote tumor self-seeding.

Biochem Biophys Res Commun 2018 09 11;503(1):242-248. Epub 2018 Jun 11.

Department of Occupational Health and Occupational Medicine, School of Public Health, Southern Medical University, Guangzhou 510515, China. Electronic address:

Lung metastasis is a primary obstacle in the clinical treatment of metastatic breast cancer. Most patients with lung metastasis eventually die of recurrence. Recurrence may be related to self-seeding, which occurs when circulating tumor cells re-seed into the tumors they originated from (metastasis or carcinoma in situ). Tumor-derived exosomes have been intensively revealed to promote the progression of various cancers. However, whether tumor-derived exosomes play roles in tumor self-seeding has not yet been identified. By establishing a self-seeding nude mouse model, we found that exosomes derived from MDA231-LM2 cells (subpopulations of breast cancer lung metastasis) potentiate the growth of MDA-MB-231 xenografts. More importantly, laser confocal microscopy and flow cytometry results identified that MDA231-LM2-secreted exosomes promote the seeding of MDA231-LM2 cells into MDA-MB-231 xenografts. These findings suggest MDA231-LM2-secreted exosomes as a promising target to treat breast cancer lung metastasis.
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http://dx.doi.org/10.1016/j.bbrc.2018.06.009DOI Listing
September 2018

Targeting the NRF-2/RHOA/ROCK signaling pathway with a novel aziridonin, YD0514, to suppress breast cancer progression and lung metastasis.

Cancer Lett 2018 06 23;424:97-108. Epub 2018 Mar 23.

Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1013, Houston, TX, 77030, United States. Electronic address:

Metastasis is a major cause of breast cancer-associated mortality. Natural products extracted from herbs provide rich bioactive compounds with anticancer efficacy but may have limited or moderate potency and considerable toxicity. We developed a novel aziridonin, YD0514, by aziridinating oridonin, a natural product of the medicinal herb Rabdosia rubescens. In this study, we found that YD0514 significantly inhibited proliferation, motility, and adhesion of metastatic breast cancer cell lines MDA-MB-231, GI101, GILM2, and GILM3. YD0514 also decreased the protein expression of matrix metalloproteinases 2 and 9 (MMP2 and MMP9), focal adhesion kinase (FAK), and integrin family members. Importantly, YD0514 suppressed the growth of metastatic breast cancer xenograft tumors and significantly inhibited lung metastasis in vivo. Lastly, we showed that YD0514's anti-metastatic effect on highly aggressive breast cancer is mediated via regulating the NRF-2/RHOA/ROCK signaling pathway. These results demonstrate that YD0514, the first active analog based on an oridonin D-ring modification, has the potential to be developed as an anti-metastasis therapy for patients with metastatic cancers.
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http://dx.doi.org/10.1016/j.canlet.2018.03.029DOI Listing
June 2018

Weather variables and the El Niño Southern Oscillation may drive the epidemics of dengue in Guangdong Province, China.

Sci Total Environ 2018 May 27;624:926-934. Epub 2017 Dec 27.

Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 511430, China. Electronic address:

Objective: To investigate the periodicity of dengue and the relationship between weather variables, El Niño Southern Oscillation (ENSO) and dengue incidence in Guangdong Province, China.

Methods: Guangdong monthly dengue incidence and weather data and El Niño index information for 1988 to 2015 were collected. Wavelet analysis was used to investigate the periodicity of dengue, and the coherence and time-lag phases between dengue and weather variables and ENSO. The Generalized Additive Model (GAM) approach was further employed to explore the dose-response relationship of those variables on dengue. Finally, random forest analysis was applied to measure the relative importance of the climate predictors.

Results: Dengue in Guangdong has a dominant annual periodicity over the period 1988-2015. Mean minimum temperature, total precipitation, and mean relative humidity are positively related to dengue incidence for 2, 3, and 4months lag, respectively. ENSO in the previous 12months may have driven the dengue epidemics in 1995, 2002, 2006 and 2010 in Guangdong. GAM analysis indicates an approximate linear association for the temperature-dengue relationship, approximate logarithm curve for the humidity-dengue relationship, and an inverted U-shape association for the precipitation-dengue (the threshold of precipitation is 348mm per month) and ENSO-dengue relationships (the threshold of ENSO index is 0.6°C). The monthly mean minimum temperature in the previous two months was identified as the most important climate variable associated with dengue epidemics in Guangdong Province.

Conclusion: Our study suggests weather factors and ENSO are important predictors of dengue incidence. These findings provide useful evidence for early warning systems to help to respond to the global expansion of dengue fever.
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http://dx.doi.org/10.1016/j.scitotenv.2017.12.200DOI Listing
May 2018

Role of neurexin2a in lead-induced locomotor defect in developing zebrafish.

Aquat Toxicol 2018 Jan 22;194:167-175. Epub 2017 Nov 22.

Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China. Electronic address:

Low-dose chronic lead (Pb) exposure interferes with the development of the nervous system, which may lead to learning disabilities, behavioral abnormalities, and mental retardation. Neurexins (Nrxns) are synaptic cell-adhesion molecules associated with neurological disorders. We hypothesized that Pb can affect the expression of nrxns during synapse formation and alter the phenotype behavior. Here, apoptosis, nrxns mRNA expression, and alterations of locomotion were examined after exposure to Pb in zebrafish embryos/larvae. To confirm the function of nrxn2a, rescue experiments were performed using β-nrxn2a mRNA microinjection. Pb exposure increased apoptosis and altered locomotor behavior in zebrafish larvae. Quantitative PCR showed that among several synaptic adhesion molecules, only nrxn2a were affected by Pb exposure. Moreover, exposure to Pb at 10μmol/L upregulated mRNA expression of nrxn1a and nrxn3a at 24h post fertilization (hpf) and downregulated expression at 48 hpf, whereas the expression remained unchanged at 72 hpf. Only the two isoforms of nrxn2a were downregulated by Pb at 10μmol/L at all three time points. Rescue experiments showed that β-nrxn2a mRNA injection recovered the decreased locomotor activity and the increased apoptosis induced by Pb. In addition, overexpression of β-nrxn2a mRNA upregulated α-nrxn2a. These data indicated that Pb inhibited the expression of nrxn2a genes, which play a critical role in neural development, and further altered the behavior of zebrafish embryos/larvae.
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http://dx.doi.org/10.1016/j.aquatox.2017.11.011DOI Listing
January 2018

Mitochondrial calcium uniporter as a target of microRNA-340 and promoter of metastasis via enhancing the Warburg effect.

Oncotarget 2017 Oct 31;8(48):83831-83844. Epub 2017 Jul 31.

Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.

Background: A shift from oxygen phosphorylation to aerobic glycolysis was known as the Warburg effect and a characteristic of cancer cell metabolism facilitating metastasis. Mitochondrial calcium uniporter (MCU), a key ion channel that mediates Ca uptake into mitochondria, was found to promote cancer progression and metastasis. However, its explicit role in shifting metabolism of breast cancer cells has not been defined.

Methods: We evaluated MCU overexpression or knock-down on migration, invasion and glucose metabolismin breast cancer cells. Mitochondrial Ca dynamics were monitored with Rhod-2 fluorescence imaging. Luciferase reporter assay was used to confirm the interaction between miR-340 and 3'-untranslated region (3'-UTR) of gene. Mouse models of lung metastasis were used to determine whether gain-/loss-of-MCU impacts metastasis. MCU expression was assessed in 60 tumor samples from breast cancer patients by immunohistochemistry (IHC).

Results: Knockdown of MCU in MDA-MB-231 cells significantly reduced cell migration and invasion and lung metastasis ; whereas overexpression of MCU in MCF-7 cells significantly increased migration and invasion and lung metastasis . Overexpression of MCU promoted lung metastasis by enhancing glycolysis, whereas suppression of MCU abolished this effect. Moreover, a novel mechanism was identified that MCU was a direct target of microRNA-340, which suppressed breast cancer cell motility by inhibiting glycolysis. Consistently, significantly increased MCU protein was found in metastatic breast cancer patients.

Conclusions: We identified a novel mechanism that upregulated MCU promotes breast cancer metastasis via enhancing glycolysis, and that this process is posttranscriptionally and negatively regulated by microRNA-340.
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http://dx.doi.org/10.18632/oncotarget.19747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663558PMC
October 2017

MRP4 regulates ENaC-dependent CREB/COX-2/PGE signaling during embryo implantation.

Oncotarget 2017 Oct 28;8(45):78520-78529. Epub 2017 Jul 28.

Epithelial Cell Biology Research Centre, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.

Multi-drug resistance protein 4 (MRP4), a potential chemotherapeutic target as well as a transporter for endogenous signaling molecules (e.g. prostaglandins), is known to be expressed in the endometrium, although its possible role(s) in the physiology of the endometrium remains unknown. Here, we show that MRP4 is upregulated at implantation window and localized to the basolateral membrane of the endometrial epithelium, the interface between the epithelium and stroma in mice. In human endometrial epithelial cells, MRP4 expression is upregulated by ENaC activation and the inhibition of MRP4 blocks ENaC-dependent PGE release as well as phosphorylation of CREB. Intrauterine injection of MRP4 inhibitor in mice prior to implantation significantly downregulated implantation markers COX-2, Claudin4 and Lif, and reduced implantation rate. These results in together have revealed a previously undefined role of MRP4 in mediating ENaC-dependent CREB/COX-2/PGE signaling essential to embryo implantation with implication in cancer progression as well.
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http://dx.doi.org/10.18632/oncotarget.19676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5667979PMC
October 2017

Phosphorylation of dynamin-related protein 1 at Ser616 regulates mitochondrial fission and is involved in mitochondrial calcium uniporter-mediated neutrophil polarization and chemotaxis.

Mol Immunol 2017 07 4;87:23-32. Epub 2017 Apr 4.

Department of Occupational Health and Occupational Medicine, School of Public Health, Southern Medical University, Guangzhou, China. Electronic address:

During an inflammatory response, polarization of neutrophils is necessary for effective chemotaxis and bacterial endocytosis. Ca uptake into mitochondria through the mitochondrial calcium uniporter (MCU) is crucial for cell metabolism, signaling and survival; however, the physiological role of MCU in human neutrophils remains unclear. Here we show that MCU is vital for the polarization and chemotaxis of neutrophils. Activation of MCU by spermine promotes neutrophil polarization and chemotaxis, whereas inhibition of MCU by Ru360 blunts both processes. We also provide evidence that this role of the MCU in neutrophils may result from modulation of mitochondrial fission by increased levels of pDrp1 S616 via accumulation of Ca into the mitochondrial matrix. Thus, our study identifies the dependence of neutrophil polarization and chemotaxis on the MCU and highlights the importance of regulating mitochondrial fission during the anti-inflammatory cascade in human neutrophils.
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http://dx.doi.org/10.1016/j.molimm.2017.03.019DOI Listing
July 2017

Effects of cadmium, manganese, and lead on locomotor activity and neurexin 2a expression in zebrafish.

Environ Toxicol Chem 2017 08 23;36(8):2147-2154. Epub 2017 Feb 23.

Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China.

The synaptic adhesion protein Neurexin 2a (Nrxn2a) plays a key role in neuronal development and is associated with cognitive functioning and locomotor behavior. Although low-level metal exposure poses a potential risk to the human nervous system, especially during the developmental stages, little is known about the effects of metal exposures on nrxn2a expression during embryonic development. We therefore exposed wild-type zebrafish embryos/larvae to cadmium (CdCl ), manganese (MnCl ), and lead ([CH COO] Pb), to determine their effect on mortality, malformation, and hatching rate. Concentrations of these metals in zebrafish were detected by inductively coupled plasma mass spectrometry analysis. Locomotor activity of zebrafish larvae was analyzed using a video-track tracking system. Expression of nrxn2a was assessed by in situ hybridization and quantitative polymerase chain reaction. The results showed that mortality, malformation, and bioaccumulation increased as the exposure dosages and duration increased. Developmental exposure to these metals significantly reduced larval swim distance and velocity. The nrxn2aa and nrxn2ab genes were expressed in the central nervous system and downregulated by almost all of the 3 metals, especially Pb. These data demonstrate that exposure to metals downregulates nrxn2a in the zebrafish model system, and this is likely linked to concurrent developmental processes. Environ Toxicol Chem 2017;36:2147-2154. © 2017 SETAC.
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http://dx.doi.org/10.1002/etc.3748DOI Listing
August 2017

Effects of zinc incorporation on hierarchical ZSM-11 catalyst for methanol conversion.

Appl Petrochem Res 2016;6(1):41-47. Epub 2015 Jul 25.

Dagang Petrochemical Company, Tianjin, China.

Abstract: Hierarchical ZSM-11 and Zn-ZSM-11 catalysts were used in this study. The effects of two methods (direct synthesis and impregnation) of zinc incorporation on methanol conversion were investigated in a continuous-flow isotherm fixed-bed reactor. XRD, SEM, BET, FTIR, and XRF analytical results revealed that the introduction of zinc through direct synthesis generated new Brønsted acid sites that could tune the ratio of light olefins. The damage to the framework structure after zinc incorporation restrained the aromatization, dehydrogenation, and decomposition of methanol. The extent of this impact determined the degree of deactivation behaviors. Thus, the yield of propene and butene was enhanced through the direct synthesis method (2 % ZnZ11-C, 4 % ZnZ11-C), and the sample 4 % ZnZ11-C displayed a fast deactivation.

Graphical Abstract:
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http://dx.doi.org/10.1007/s13203-015-0120-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012370PMC
July 2015

Downregulation of ACE2/Ang-(1-7)/Mas axis promotes breast cancer metastasis by enhancing store-operated calcium entry.

Cancer Lett 2016 07 7;376(2):268-77. Epub 2016 Apr 7.

Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China. Electronic address:

The renin-angiotensin system (RAS) is an important component of the tumor microenvironment and plays a key role in promoting cancer cell proliferation, angiogenesis, metabolism, migration and invasion. Meanwhile, the arm of angiotensin-converting enzyme (ACE)2/angiotensin-(1-7) [Ang-(1-7)]/Mas axis in connection with RAS is associated with anti-proliferative, vasodilatory and anti-metastatic properties. Previous studies have shown that Ang-(1-7) reduces the proliferation of orthotopic human breast tumor growth by inhibiting cancer-associated fibroblasts. However, the role of ACE/Ang-(1-7)/Mas axis in the metastasis of breast cancer cells is still unknown. In the present study, we found that ACE2 protein level is negatively correlated with the metastatic ability of breast cancer cells and breast tumor grade. Upregulation of ACE2/Ang-(1-7)/Mas axis inhibits breast cancer cell migration and invasion in vivo and in vitro. Mechanistically, ACE2/Ang-(1-7)/Mas axis activation inhibits store-operated calcium entry (SOCE) and PAK1/NF-κB/Snail1 pathways, and induces E-cadherin expression. In summary, our results demonstrate that downregulation of ACE2/Ang-(1-7)/Mas axis stimulates breast cancer metastasis through the activation of SOCE and PAK1/NF-κB/Snail1 pathways. These results provide new mechanisms by which breast cancer develop metastasis and shed light on developing novel anti-metastasis therapeutics for metastatic breast cancer by modulating ACE2/Ang-(1-7)/Mas axis.
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http://dx.doi.org/10.1016/j.canlet.2016.04.006DOI Listing
July 2016

Store-operated Ca2+ entry plays a role in HMGB1-induced vascular endothelial cell hyperpermeability.

PLoS One 2015 17;10(4):e0123432. Epub 2015 Apr 17.

Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.

Aims: Endothelial dysfunction, including increased endothelial permeability, is considered an early marker for atherosclerosis. High-mobility group box 1 protein (HMGB1) and extracellular Ca2+ entry, primarily mediated through store-operated Ca2+ entry (SOCE), are known to be involved in increasing endothelial permeability. The aim of this study was to clarify how HMGB1 could lead to endothelia hyperpermeability.

Methods And Results: We have shown that human vascular endothelial cell permeability is increased, while transendothelial electrical resistance and VE-cadherin expression were reduced by HMGB1 treatment. Two SOCE inhibitors and knockdown of stromal interaction molecule 1 (STIM1), a Ca2+ sensor mediating SOCE, inhibited the HMGB1-induced influx of Ca2+ and Src activation followed by significant suppression of endothelial permeability. Moreover, knockdown of Orai1, an essential pore-subunit of SOCE channels, decreased HMGB1-induced endothelial hyperpermeability.

Conclusions: These data suggest that SOCE, acting via STIM1, might be the predominant mechanism of Ca2+ entry in the modulation of endothelial cell permeability. STIM1 may thus represent a possible new therapeutic target against atherosclerosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0123432PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401536PMC
January 2016

Mitochondrial Ca²⁺ uniporter is critical for store-operated Ca²⁺ entry-dependent breast cancer cell migration.

Biochem Biophys Res Commun 2015 Feb 29;458(1):186-93. Epub 2015 Jan 29.

Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China. Electronic address:

Metastasis of cancer cells is a complicated multistep process requiring extensive and continuous cytosolic calcium modulation. Mitochondrial Ca(2+) uniporter (MCU), a regulator of mitochondrial Ca(2+) uptake, has been implicated in energy metabolism and various cellular signaling processes. However, whether MCU contributes to cancer cell migration has not been established. Here we examined the expression of MCU mRNA in the Oncomine database and found that MCU is correlated to metastasis and invasive breast cancer. MCU inhibition by ruthenium red (RuR) or MCU silencing by siRNA abolished serum-induced migration in MDA-MB-231 breast cancer cells and reduced serum- or thapsigargin (TG)-induced store-operated Ca2+ entry (SOCE). Serum-induced migrations in MDA-MB-231 cells were blocked by SOCE inhibitors. Our results demonstrate that MCU plays a critical role in breast cancer cell migration by regulating SOCE.
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http://dx.doi.org/10.1016/j.bbrc.2015.01.092DOI Listing
February 2015

Role of the mitochondrial Ca²⁺ uniporter in Pb²⁺-induced oxidative stress in human neuroblastoma cells.

Brain Res 2014 Aug 2;1575:12-21. Epub 2014 Jun 2.

Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China. Electronic address:

Lead (Pb(2+)) has been shown to induce cellular oxidative stress, which is linked to changes in intracellular calcium (Ca(2+)) concentration. The mitochondrial Ca(2+) uniporter (MCU) participates in the maintenance of Ca(2+) homeostasis in neurons, but its role in Pb(2+)-induced oxidative stress is unclear. To address this question, oxidative stress was induced in human neuroblastoma SH-SY5Y cells and in newborn rats by Pb(2+) treatment. The results showed that the production of reactive oxygen species is increased in cells upon treatment with Pb(2+) in a dose-dependent manner, while glutathione and MCU expression were reduced. Moreover, neuronal nitric oxide synthase protein expression was elevated in rats exposed to Pb(2+) during gestation, while MCU expression was decreased. Application of the MCU activator spermine or MCU overexpression reversed Pb(2+)-induced oxidative stress and inhibition of mitochondrial Ca(2+) uptake, while the MCU inhibitor Ru360 and MCU knockdown potentiated the effects of Pb(2+). These results indicate that the MCU mediates the Pb(2+)-induced oxidative stress response in neurons through the regulation of mitochondrial Ca(2+) influx.
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http://dx.doi.org/10.1016/j.brainres.2014.05.032DOI Listing
August 2014

Store-operated Ca²⁺ entry mediated regulation of polarization in differentiated human neutrophil-like HL-60 cells under hypoxia.

Mol Med Rep 2014 Mar 13;9(3):819-24. Epub 2014 Jan 13.

Research Centre for High Altitude Medicine, Qinghai University Medical College, Qinghai University, Xining, Qinghai 810000, P.R. China.

The regulation of neutrophil polarization by calcium entry is critical for maintaining an effective host response. Hypoxia has a major effect on the apoptosis of neutrophils, however the role of store-operated Ca2+ entry (SOCE) in neutrophil polarization under hypoxia remains to be elucidated. In the present study, we examined the polarization of differentiated human neutrophil-like HL-60 (dHL-60) cells exposed to hypoxia (3% O2) and the results demonstrated that the percentage of polarized cells following exposure to an N-formyl-Met-Leu-Phe (fMLP) gradient in the Zigmond chamber was increased. We examined stromal interaction molecule 1 (STIM1) and Orai1 expression in dHL-60 cells during hypoxia, and it was observed that the expression of STIM1 and Orai1 was significantly reduced at day 2. However, no apparent change was observed on the first day, indicating that this effect is dependent on stimulation time. Fluo-4/acetoxymethyl (AM) ester imaging also demonstrated that SOCE was decreased in dHL-60 cells. The plasmid overexpression assay demonstrated that the response of polarization was returned to the control level. We demonstrated the inhibitory role of SOCE on the polarization of dHL-60 cells under hypoxic conditions, which may be the mechanism for the adaptation of neutrophils to hypoxia. SOCE is also suggested to be a key modulator of immune deficiency under hypoxic conditions and is potentially a therapeutic target.
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http://dx.doi.org/10.3892/mmr.2014.1894DOI Listing
March 2014

Association of X-ray repair cross complementing group 1 Arg399Gln polymorphisms with the risk of squamous cell carcinoma of the head and neck: evidence from an updated meta-analysis.

PLoS One 2013 30;8(10):e77898. Epub 2013 Oct 30.

Henan Center for Disease Control and Prevention, Zhengzhou, China ; Department of Occupational Health and Occupational Medicine, School of Public Health and Tropic Medicine, Southern Medical University, Guangzhou, China.

Background: Epidemiologic studies have reported the association of X-ray repair cross-complementary group 1 (XRCC1) Arg399Gln polymorphisms with susceptibility to squamous cell carcinoma of the head and neck (HNSCC). However, the results were conflictive rather than conclusive. The purpose of this study was to clarify the association of XRCC1 Arg399Gln variants with HNSCC risk.

Methods: Systematic searches were performed through the search engines of PubMed, Elsevier, Science Direct, CNKI and Chinese Biomedical Literature Database. Summary odds ratio (OR) with 95% confidence intervals (CI) was computed to estimate the strength association.

Results: Overall, we did not observe any association of XRCC1 Arg399Gln polymorphisms with HNSCC risk in total population (OR = 0.95, 95% CI: 0.76-1.19 for Gln/Gln vs. Arg/Arg, OR = 1.05, 95% CI: 0.92-1.20 for Arg/Gln vs. Arg/Arg, and OR = 1.03, 95% CI: 0.90-1.18 for Gln/Gln+Arg/Gln vs. Arg/Arg) based on 18 studies including 3917 cases and 4560 controls. In subgroup analyses, we observed an increased risk of XRCC1 399 Arg/Gln genotype for HNSCC in Caucasians (OR = 1.20, 95% CI: 1.00-1.44) and Gln/Gln genotype for larynx squamous cell carcinoma (OR = 1.63, 95% CI: 1.10-2.40). We did not observe any association between XRCC1 Arg399Gln variants and HNSCC risk in additional subgroup analyses.

Conclusion: The results from this present meta-analysis suggest that XRCC1 Arg399Gln variants may contribute to HNSCC risk among Caucasians and to the risk of larynx squamous cell carcinoma. Further, well-designed studies with larger sample sizes are required to verify our findings.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0077898PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3813759PMC
September 2014

Association of TGF-β1 -509C/T polymorphisms with breast cancer risk: evidence from an updated meta-analysis.

Tumour Biol 2014 Feb 28;35(2):935-42. Epub 2013 Aug 28.

Henan Center for Disease Control and Prevention, Zhengzhou, 450016, People's Republic of China.

Epidemiological studies have evaluated the association between transforming growth factor-β1 (TGF-β1) -509C/T polymorphisms and breast cancer risk. However, the results remain conflicting rather than conclusive. The aim of this study was to comprehensively clarify the association between TGF-β1 -509C/T polymorphisms and breast cancer risk. All relevant studies were searched in the electronic databases. The potential sources of heterogeneity were detected with the chi-square-based Q test. The strength of associations between TGF-β1 -509C/T polymorphisms and breast cancer risk was measured by odds ratio (OR) and 95 % confidence intervals (CI). Publication bias was tested by Begg's test and Egger's test. A total of 10 studies including 10,913 cases and 14,187 controls were included in the meta-analysis. Overall, there was no evidence of significant association of TGF-β1 -509C/T polymorphisms with breast cancer risk (TT vs. CC [OR = 0.97, 95 % CI = 0.83-1.14]; CT vs. CC [OR = 1.05, 95 % CI = 0.90-1.22]; TT + CT vs. CC [OR = 0.99, 95 % CI = 0.91-1.08]; T allele vs. C allele [OR = 0.99, 95 % CI = 0.93-1.06]). Similar results were also found in the subgroup analyses by ethnicity and source of control. When stratified by estrogen receptor (ER) status, TT genotype and T allele were associated with a decreased ER-positive breast cancer risk (OR = 0.66, 95 % CI = 0.49-0.90 and OR = 0.85, 95 % CI = 0.75-0.96, respectively). The present meta-analysis results suggest that TGF-β1 -509C/T variants may not contribute to the risk of breast cancer overall. However, T allele may be a potential protective factor for developing ER-positive breast cancer. Well-designed studies with larger sample size were required to verify our findings further.
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http://dx.doi.org/10.1007/s13277-013-1122-3DOI Listing
February 2014