Publications by authors named "Yuqin Shi"

27 Publications

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Efficacy and safety of postural intervention on prevention of deep venous thrombosis of lower extremity in postpartum women with pregnancy-induced hypertension: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Mar;100(12):e24959

Department of International Medical Services, Gansu Provincial Maternity and Child-Care Hospital, Lanzhou, Gansu Province, China.

Background: Deep venous thrombosis (DVT) is a relatively serious complication commonly seen in pregnant women, especially parturients with pregnancy-induced hypertension (PIH), whose incidence of DVT is higher. Because it can lead to pulmonary embolism (PE) and endanger the lives of patients, it has been paid much attention in clinic. Nursing plays an important role in the prevention and treatment of DVT. Early posture intervention can prevent postpartum DVT in hypertensive pregnant women, which has certain clinical value, but there is no evidence of evidence-based medicine. This study aims to systematically study the effectiveness and safety of postural intervention on prevention of deep venous thrombosis of lower extremity in postpartum women with PIH.

Methods: Use the computer to retrieve the English databases (PubMed, Embase, Web of Science, the Cochrane Library) and the Chinese databases (China Knowledge Network, Wanfang, Weipu, China Biomedical Database), in addition to the manual retrieval of Baidu academic, Google academic, from the construction of database to December 2020, for randomized controlled clinical studies of postural intervention on prevention of deep venous thrombosis of lower extremity in postpartum women with PIH. Two researchers independently extracted the data and evaluated the quality of the included research, and used RevMan5.3 software to do meta-analyze of the included literature.

Results: This study assessed the efficacy and safety of potential intervention on prevention of deep venous thrombosis of lower extremities with lower extremity hypertension by mean velocity of femoral venous flow in the lower extremities, lower extremity skin status, swelling level, and pain condition, lower extremity deep venous thrombosis rate, and incidence of pulmonary embolism.

Conclusion: This study will provide reliable evidence-based evidence for the clinical application of postural intervention on prevention of deep venous of lower extremity in Postpartum women with PIH.

Osf Registration Number: DOI 10.17605/OSF.IO/4NPKW.
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http://dx.doi.org/10.1097/MD.0000000000024959DOI Listing
March 2021

Early-life exposure to submicron particulate air pollution in relation to asthma development in Chinese preschool children.

J Allergy Clin Immunol 2021 Mar 5. Epub 2021 Mar 5.

Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, Wuhan 430065, China; Department of Environmental Hygiene and Occupational Medicine, School of Public Health, Wuhan University of Science and Technology, Wuhan 430065, China. Electronic address:

Background: Emerging research suggested an association of early-life particulate air pollution exposure with development of asthma in childhood. However, the potentially differential effects of submicron particulate matter (PM) remain largely unknown.

Objective: This study primarily aimed to investigate associations of childhood asthma and wheezing with in-utero and first-year exposures to size-specific particles.

Methods: We conducted a large cross-sectional survey among 5788 preschool children aged 3-5 years in central China. In-utero and first-year exposures to ambient PM, PM and PM at 1×1 km-resolution were assessed using machine learning based spatiotemporal models. A time-to-event analysis was performed to examine associations between residential PM exposures and childhood onset of asthma and wheezing.

Results: Early-life size-specific PM exposures, particularly during pregnancy, were significantly associated with increased risk of asthma, while no evident PM-wheezing associations were observed. Each 10 μg/m increase of in-utero and first-year PM exposure was accordingly associated with an asthma's hazard ratio (HR) in childhood of 1.618 (95% confidence interval: 1.159-2.258, p=0.005) and 1.543 (0.822-2.896, p=0.177). Subgroup analyses suggest that short breastfeeding duration may aggravate PM-associated risk of childhood asthma. Each 10 μg/m increase of in utero exposure to PM, for instance, was associated with a HR of 2.260 (1.393-3.666) among children with 0-5 months' breastfeeding and 1.156 (0.721-1.853) among those longer breastfed.

Conclusion: Our study added comparative evidence for increased risk of childhood asthma in relation to early-life PM exposures, highlighting stronger associations with ambient PM than PM and PM.
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http://dx.doi.org/10.1016/j.jaci.2021.02.030DOI Listing
March 2021

Global transcriptomic analysis of functional oligosaccharide metabolism in Pediococcus pentosaceus.

Appl Microbiol Biotechnol 2021 Feb 29;105(4):1601-1614. Epub 2021 Jan 29.

Key Laboratory of Food Bioengineering (China National Light Industry), College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.

Lactic acid bacteria (LAB) are important in food fermentation and may enhance overall host health. Previous studies to explore LAB metabolism mainly focused on the genera Lacticaseibacillus and Lactococcus. Pediococcus pentosaceus, historically recognized as an important food fermentation bacterial strain, can produce bacteriocins and occasionally demonstrated probiotic functionalities. This study thoroughly surveyed the growth kinetic of three P. pentosaceus isolates in various culture formulations, especially in fructooligosaccharide (FOS), xylooligosaccharide (XOS), or konjac mannooligosaccharide (KMOS) conditions. Results showed that P. pentosaceus effectively metabolized KMOS, the culture of which led to 23.6-fold population increase. However, FOS and XOS were less metabolized by P. pentosaceus. On functional oligosaccharide cultures, P. pentosaceus could result in higher population proliferation, more acidified fermentation environment, and higher glycoside hydrolysis activities in the culture. RNA-Seq analysis classified 1572 out of 1708 putative genes as mRNA-coding genes. The dataset also revealed that the three functional oligosaccharides led to extensive global functional gene regulations. Phosphate conservation and utilization efficiency enhancement may serve as a leading transcriptional regulation direction in functional oligosaccharide metabolisms. In summary, these discovered metabolic characteristics could be employed to support future studies. KEY POINTS: • Konjac mannooligosaccharides effectively promoted P. pentosaceus proliferation. • Functional genes were highly regulated in functional oligosaccharide utilization. • Phosphate conservation was an important transcriptional regulation direction.
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http://dx.doi.org/10.1007/s00253-021-11120-5DOI Listing
February 2021

Posttraumatic stress disorder symptoms in healthcare workers after the peak of the COVID-19 outbreak: A survey of a large tertiary care hospital in Wuhan.

Psychiatry Res 2020 12 25;294:113541. Epub 2020 Oct 25.

Department of Neurology, The Central Hospital of Wuhan, Wuhan 430030, China; Tongji Medical College and Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

This study examined the prevalence of posttraumatic stress disorder (PTSD) symptoms and assessed mental illness via an online survey among healthcare workers (HCWs) at the Central Hospital of Wuhan after the peak of the COVID-19 outbreak. PTSD symptoms were measured using the PTSD Checklist Civilian Version (PCL-C), with a cutoff score of 50. Among the 642 HCWs, the prevalence of probable PTSD was 20.87%. Additionally, 88.88%, 82.09%, 100%, and 95.52% of HCWs with probable PTSD reported varying degrees of anxiety, depression, somatic symptoms, and insomnia, respectively. HCWs with probable PTSD scored higher on the Hospital Anxiety and Depression Scale (HADS), Patient Health questionnaire-15 (PHQ-15), and Insomnia Severity Index (ISI) than non-PTSD HCWs (all p < 0.05). Multivariate regression analysis revealed that HCWs with negative COVID-19 tests (OR, 0.35; 95% CI, 0.21-0.58; p < 0.00), those with high Social Support Self-Rating Scale (SSRS) scores (OR, 0.30; 95% CI, 0.17-0.52; p < 0.00), and HCWs whose family members tested negative (OR, 0.64; 95% CI, 0.42-0.96; p = 0.03) were less likely to have probable PTSD. This study found a high prevalence of probable PTSD and severe mental illness among local HCWs. Our finding emphasizes the need to provide mental health support for HCWs.
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http://dx.doi.org/10.1016/j.psychres.2020.113541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585629PMC
December 2020

Carbon black nanoparticles induce HDAC6-mediated inflammatory responses in 16HBE cells.

Toxicol Ind Health 2020 Oct 12;36(10):759-768. Epub 2020 Aug 12.

Department of Occupational and Environmental Health, School of Public Health, Medical College, 481115Wuhan University of Science and Technology, Wuhan, Hubei, China.

Long-term inhalation of carbon black nanoparticles (CBNPs) leads to pulmonary inflammatory diseases. Histone deacetylase 6 (HDAC6) has been identified as an important regulator in the development of inflammatory disorders. However, the direct involvement of HDAC6 in CBNPs-induced pulmonary inflammatory responses remains unclear. To explore whether HDAC6 participates in CBNPs-induced pulmonary inflammation, human bronchial epithelial cell line (16HBE cells) was transfected with HDAC6 small interference RNA (siRNA) and then exposed to CBNPs at concentrations of 0, 25, and 50 µg/ml for 24 h. Intracellular HDAC6 and intraflagellar transport protein 88 (IFT88) mRNA and protein were determined by real-time polymerase chain reaction and Western blot, respectively. The secretions of inflammatory cytokines including interleukin (IL)-8, tumor necrosis factor (TNF)-α, IL-6, and IL-1β were measured by enzyme-linked immunosorbent assay. CBNPs induced a significant increase in the expressions of IL-8 and IL-6, accompanied by a high level of intracellular HDAC6 mRNA when compared with a blank control group ( < 0.05). However, there were no significant changes in the levels of TNF-α secretion, intracellular HDAC6 and IFT88 protein induced by CBNPs ( > 0.05). The HDAC6 mRNA expression was significantly suppressed in HDAC6 siRNA-transfected cells ( < 0.05). The secretions of IL-8, TNF-α, and IL-6 were significantly less in HDAC6 siRNA-transfected cells than that in normal 16HBE cells with exposure to 25 or 50 µg/ml of CBNPs, but intracellular IFT88 mRNA expression was markedly increased in HDAC6 siRNA-transfected cells when compared with normal 16HBE cells exposed to 50 µg/ml of CBNPs (all < 0.05). Downregulation of the HDAC6 gene inhibits CBNPs-induced inflammatory responses in bronchial epithelial cells, partially through regulating IFT88 expression. It is suggested that CBNPs may trigger inflammatory responses in bronchial epithelial cells by an HDAC6/IFT88-dependent pathway.
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http://dx.doi.org/10.1177/0748233720947214DOI Listing
October 2020

The role of STAT3/p53 and PI3K-Akt-mTOR signaling pathway on DEHP-induced reproductive toxicity in pubertal male rat.

Toxicol Appl Pharmacol 2020 10 22;404:115151. Epub 2020 Jul 22.

School of Resource and Environmental Engineer, Wuhan University of Science and Technology, PR China; School of Public Health, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology, PR China. Electronic address:

Di (2-ethylhexyl) phthalate (DEHP) is a known environmental endocrine disruptor that impairs development of testis and spermatogenesis. This study aims to explore the effects of STAT3/p53 and PI3K-Akt-mTOR signaling pathway on DEHP-induced reproductive toxicity in pubertal male rat. 24 6-week-old male Sprague-Dawley rats were randomly divided into 4 groups (Control, low-dose, middle-dose and high-dose group) and were treated with increasing concentration of DEHP (0, 250, 500, 1000 mg/kg/day) respectively for 28 consecutive days by intragastric administration. Our results showed that DEHP exposure induced obvious morphological changes of testis, decreased organ coefficient of testis and sperm count, and increased testicular cell apoptosis in the 500 and 1000 mg/kg/day DEHP groups (p < .05). The serum testosterone decreased in a dose-dependent manner after treatment with DEHP. Furthermore, the exposure of DEHP elevated the levels of oxidative stress accompanied by upregulated expression of p53 and reduced expression of STAT3. In addition, compared with the control group, the expression of PI3K, p-Akt and p-mTOR proteins significantly decreased, whereas the downstream autophagy-related proteins phosphorylated ULK1, Beclin-1, Atg7, LC3-II obviously increased in the 250 mg/kg/day DEHP group (p < .05). The expression of p62 was reduced in DEHP-treated groups. Our data indicated that autophagy could be activated to protect testes from DEHP-induced reproductive damage by inhibiting PI3K-Akt-mTOR signaling pathway in the 250 mg/kg/day DEHP group. STAT3/p53-mediated mitochondrial apoptosis pathway might play a major role to cause testis injury and reproductive dysfunction in the 500 and 1000 mg/kg/day DEHP groups.
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http://dx.doi.org/10.1016/j.taap.2020.115151DOI Listing
October 2020

Influence of silica particles on mucociliary structure and MUC5B expression in airways of C57BL/6 mice.

Exp Lung Res 2020 09 6;46(7):217-225. Epub 2020 May 6.

Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Public Health, Medical College, Wuhan University of Science and Technology, Wuhan, Hubei, China.

Impaired mucociliary clearance is an initial characteristic of recurrent cough, respiratory infection and chronic respiratory diseases. It has been demonstrated that prolonged inhalation of respirable silica particles results in a variety of pulmonary diseases, but whether the mucociliary system is involved in this process is unclear. This study aims to evaluate the effects of silica particles on mucociliary structure and MUC5B production in respiratory tract. C57BL/6 mice were administered with 2.5 mg silica particles through a single intratracheal instillation. The changes of mucociliary structure and MUC5B expression in trachea was evaluated by HE and AB-PAS staining, transmission electron microscopy and immunohistochemistry on days 1, 7, 28 and 84 post-exposure. The mucociliary structure of airway epithelium was obviously impaired by silica particles, showing disordered, shortened or partially lost cilia on the surface, increased mucus in mucous layer and submucosal glands from day 7 to day 84. A variety of ultrastructural abnormalities were discovered in silica-exposed airway cilia, including absence of central pair microtubules, disorganized microtubules and clusters of axoneme on day 1 and 7. The numbers of ciliary axonemes and basal bodies in ciliated epithelial cells were significantly decreased, whereas the proportion of abnormal axonemes was gradually increased with exposure to silica particles ( < 0.05). In addition, silica particles significantly decreased MUC5B expression on the surface of airway epithelium on day 28 and 84, but obviously increased its production in submucosal glands from day 1 to day 84 ( < 0.01). Silica particles could lead to ultrastructural defects in airway cilia, mucus hypersecretion and altered MUC5B expression in trachea, indicating that impaired mucociliary structure and altered MUC5B production might participate in the development of silica-related respiratory diseases.
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http://dx.doi.org/10.1080/01902148.2020.1762804DOI Listing
September 2020

Mouse spermatogenesis-associated protein 1 (SPATA1), an IFT20 binding partner, is an acrosomal protein.

Dev Dyn 2020 04 2;249(4):543-555. Epub 2020 Jan 2.

Department of Physiology, Wayne State University, Detroit, Michigan.

Background: Intraflagellar transport is a motor-driven trafficking system that is required for the formation of cilia. Intraflagellar transport protein 20 (IFT20) is a master regulator for the control of spermatogenesis and male fertility in mice. However, the mechanism of how IFT20 regulates spermatogenesis is unknown.

Results: Spermatogenesis associated 1 (SPATA1) was identified to be a major potential binding partner of IFT20 by a yeast two-hybrid screening. The interaction between SPATA1 and IFT20 was examined by direct yeast two-hybrid, co-localization, and co-immunoprecipitation assays. SPATA1 is highly abundant in the mouse testis, and is also expressed in the heart and kidney. During the first wave of spermatogenesis, SPATA1 is detectable at postnatal day 24 and its expression is increased at day 30 and 35. Immunofluorescence staining of mouse testis sections and epididymal sperm demonstrated that SPATA1 is localized mainly in the acrosome of developing spermatids but not in epididymal sperm. IFT20 is also present in the acrosome area of round spermatids. In conditional Ift20 knockout mice, testicular expression level and acrosomal localization of SPATA1 are not changed.

Conclusions: SPATA1 is an IFT20 binding protein and may provide a docking site for IFT20 complex binding to the acrosome area.
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http://dx.doi.org/10.1002/dvdy.141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536633PMC
April 2020

CRISPR/Cas9-Mediated Multiplex Genome Editing of JAGGED Gene in L.

Biomolecules 2019 11 12;9(11). Epub 2019 Nov 12.

Oil Crops Research Institute of Chinese Academy of Agricultural Sciences, Key Laboratory for Biology and Genetic Improvement of Oil Crops, Ministry of Agriculture and Rural Affairs, No. 2 Xudong 2nd Road, Wuhan 430062, China.

Pod shattering resistance is an essential component to achieving a high yield, which is a substantial objective in polyploid rapeseed cultivation. Previous studies have suggested that the JAGGED (JAG) gene is a key factor implicated in the regulatory web of dehiscence fruit. However, its role in controlling pod shattering resistance in oilseed rape is still unknown. In this study, multiplex genome editing was carried out by the CRISPR/Cas9 system on five homoeologs (BnJAG.A02, BnJAG.C02, BnJAG.C06, BnJAG.A07, and BnJAG.A08) of the JAG gene. Knockout mutagenesis of all homoeologs drastically affected the development of the lateral organs in organizing pod shape and size. The cylindrical body of the pod comprised a number of undifferentiated cells like a callus, without distinctive valves, replum, septum, and valve margins. Pseudoseeds were produced, which were divided into two halves with an incomplete layer of cells (probably septum) that separated the undifferentiated cells. These mutants were not capable of generating any productive seeds for further generations. However, one mutant line was identified in which only a BnJAG.A08-NUB-Like paralog of the JAG gene was mutated. Knockout mutagenesis in BnJAG.A08-NUB gene caused significant changes in the pod dehiscence zone. The replum region of the mutant was increased to a great extent, resulting in enlarged cell size, bumpy fruit, and reduced length compared with the wild type. A higher replum-valve joint area may have increased the resistance to pod shattering by ~2-fold in JAG mutants compared with wild type. Our results offer a basis for understanding variations in fruit by mutating JAG genes and providing a way forward for other Brassicaceae species.
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http://dx.doi.org/10.3390/biom9110725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921047PMC
November 2019

Abnormal fertility, acrosome formation, IFT20 expression and localization in conditional knockout mice.

Am J Physiol Cell Physiol 2020 01 2;318(1):C174-C190. Epub 2019 Oct 2.

Department of Physiology, Wayne State University, Detroit, Michigan.

GMAP210 (TRIP11) is a cis-Golgi network-associated protein and a Golgi membrane receptor for IFT20, an intraflagellar transport component essential for male fertility and spermiogenesis in mice. To investigate the role of GMAP210 in male fertility and spermatogenesis, floxed mice were bred with mice so that the gene is disrupted in spermatocytes and spermatids in this study. The mutant mice showed no gross abnormalities and survived to adulthood. In adult males, testis and body weights showed no difference between controls and mutant mice. Low-magnification histological examination of the testes revealed normal seminiferous tubule structure, but sperm counts and fertility were significantly reduced in mutant mice compared with controls. Higher resolution examination of the mutant seminiferous epithelium showed that nearly all sperm had more oblong, abnormally shaped heads, while the sperm tails appeared to have normal morphology. Electron microscopy also revealed abnormally shaped sperm heads but normal axoneme core structure; some sperm showed membrane defects in the midpiece. In mutant mice, expression levels of IFT20 and other selective acrosomal proteins were significantly reduced, and their localization was also affected. Peanut-lectin, an acrosome maker, was almost absent in the spermatids and epididymal sperm. Mitochondrion staining was highly concentrated in the heads of sperm, suggesting that the midpieces were coiling around or aggregating near the heads. Defects in acrosome biogenesis were further confirmed by electron microscopy. Collectively, our findings suggest that GMAP210 is essential for acrosome biogenesis, normal mitochondrial sheath formation, and male fertility, and it determines expression levels and acrosomal localization of IFT20 and other acrosomal proteins.
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http://dx.doi.org/10.1152/ajpcell.00517.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985835PMC
January 2020

The Role of CTGF in Inflammatory Responses Induced by Silica Particles in Human Bronchial Epithelial Cells.

Lung 2019 12 13;197(6):783-791. Epub 2019 Sep 13.

Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China.

Background: Prolonged exposure to crystalline silica leads to persistent pulmonary inflammation and progressive fibrosis. Connective tissue growth factor (CTGF) has emerged as a potent proinflammatory and profibrotic regulator to participate in a variety of chronic inflammatory diseases. However, the role of CTGF in silica-induced pulmonary inflammation remains poorly understood.

Methods: To explore the effect of CTGF on inflammatory responses caused by silica particles, human bronchial epithelial cells (16HBE) were transfected with CTGF siRNA and exposed to silica particles at concentrations of 0, 12.5, 25, 50, 100 μg/ml for 48 h. Intracellular CTGF mRNA and protein expressions were determined by RT-PCR and Western blotting, respectively. The levels of inflammatory cytokines including IL-8, TNF-α, IL-6, IL-1β, IL-17A and TGF-β were measured by ELISA kits.

Results: Silica particles induce significantly elevated intracellular CTGF mRNA expression in 16HBE cells in a dose-dependent manner when compared with blank control group (P < 0.05). The secretions of IL-8, TNF-α, IL-6 and IL-17A were also significantly increased by silica particles (P < 0.05). After exposure to 25 or 50 μg/ml silica particles, the expression of intracellular CTGF mRNA was significantly inhibited in 16HBE cells when transfected with CTGF siRNA (P < 0.05). The secreted levels of IL-8, TNF-α, IL-6 and IL-17A induced by silica particles were also significantly lower from CTGF siRNA-transfected cells than that from normal 16HBE cells (P < 0.05).

Conclusion: Inhibition of CTGF gene attenuates silica-induced inflammatory responses in bronchial epithelial cells, suggesting that CTGF could be a pivotal regulator in the development of silica-induced inflammation.
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http://dx.doi.org/10.1007/s00408-019-00272-xDOI Listing
December 2019

Let-7 inhibits the migration and invasion of extravillous trophoblast cell via targeting MDM4.

Mol Cell Probes 2019 06 10;45:48-56. Epub 2019 May 10.

Department of OCbstetrics, Gansu Maternal and Child Health Care Hospital, China. Electronic address:

Aims: Extravillous trophoblast (EVT) cells migration and invasion are important causes to preeclampsia (PE). Studies have shown that let-7 was involved in inhibiting proliferation and invasion of several cancer cells, however, its effect on EVT cells migration and invasion has hardly been reported. This study aimed to explore the relation between let-7 and EVT cell migration and invasion.

Methods: MicroRNA (miRNA) and genes expression levels were measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot (WB). Cell proliferation, migration and invasion were detected by cell counting kit-8 (CCK-8) assay, wound-healing assay and transwell assay. The binding site between let-7 and murine double minute 4 (MDM4) was identified using TargetScan. The targeting relation between let-7 and MDM4 was verified using dual luciferase reporter assay.

Results: The results revealed that in placental tissues of PE patients, let-7, matrix metalloproteinase-2 (MMP-2) and MMP-9 were lowly expressed and tissue inhibitors of metalloproteinase-1 (TIMP-1) and TIMP-2 were highly expressed. Let-7 silencing promoted the proliferation, migration, invasion of HTR8/SVneo cells and the expression levels of MMP-2 and MMP-9, however, it inhibited TIMP-1 and TIMP-2 expression levels, while overexpression of let-7 produced the opposite results. Furthermore, MDM4 is a target gene of let-7. Rescue experiments suggested that MDM4 siRNA partially reversed the effects of let-7 silencing on cells.

Conclusions: Let-7 silencing promoted proliferation, migration and invasion in EVT cells through the up-regulation of MDM4. Our study provided new insights into the molecular mechanism of PE.
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http://dx.doi.org/10.1016/j.mcp.2019.05.002DOI Listing
June 2019

Mutual promotion of apoptosis and autophagy in prepubertal rat testes induced by joint exposure of bisphenol A and nonylphenol.

Environ Pollut 2018 Dec 11;243(Pt A):693-702. Epub 2018 Sep 11.

MOE (Ministry of Education) Key Lab of Environment and Health, Department of Occupational and Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

BPA and NP are both typical endocrine disruptors, the exposed populations are widespread, and the health risks mustn't be ignored. However, the interactions between them on spermatogenesis are rarely mentioned. And the underlying mechanism is unclear yet. In the present study, prepubertal SD rats were exposed to different low doses of BPA and NP separately or jointly for 4 weeks. The results indicate that the joint exposure induced excessive apoptosis and autophagy in the testes, as proved by a series of characteristics such as chromatin condensation and autophagosomes formation. Besides, endocrine disorders and oxidative stress were also caused by the exposure. Apoptosis was mediated by the mitochondrial apoptosis pathway, since the Bax and Caspase-3 gene expressions significantly increased with a prominent decrease of Bcl-2. While autophagy was caused by the inhibition of the Akt/mTOR pathway, as the expressions of the downstream genes Beclin-1, Atg5, Atg12 and the split of LC3 protein increased altogether. Worse yet, autophagy and apoptosis might reinforce each other and make the situation more severe in the joint group. What's more, remarkable histopathological changes such as spermatogenic epithelium atrophy, germ cell loss, and various ultrastructural modifications were strongly related to the apoptosis and autophagy. In aggregate, this study shows the enormous risk on male reproductive system brought by the interactions between BPA and NP. The findings provide a broader vision to understand the roles of apoptosis and autophagy induced by the joint exposure in the aggravation of spermatogenesis impairment, which could be a reference for the situation of complex EDCs exposure-induced male reproductive toxicity, and possibly inspire us to find new ideas for preventive and therapeutic treatments.
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http://dx.doi.org/10.1016/j.envpol.2018.09.030DOI Listing
December 2018

Determinants of Health Care-Seeking Delay among Tuberculosis Patients in Rural Area of Central China.

Int J Environ Res Public Health 2018 09 13;15(9). Epub 2018 Sep 13.

Institute of Infectious Diseases, Hubei Center for Disease Control and Prevention, Wuhan 430079, China.

The prevalence of tuberculosis (TB) in low and middle-income countries is a significant public health and social concern. TB is a common infectious disease caused by the infection, which has a widespread infection rate. Health care-seeking delay maybe one of the most important neglected risk factors for the spread of TB. The aim of this study was to understand the situation of health care-seeking delay among rural tuberculosis patients in Hubei Province, and explore its risk factors. A total of 1408 rural tuberculosis patients were surveyed using a standard structured questionnaire in three cities of Hubei Province during the past two years. For the 1408cases of pulmonary tuberculosis, 39.70% of them were health care-seeking delayed. Logistic regressions indicate that the Han nationality, farming careers, the over 45 min walk to the township's hospital, and awareness of the national TB free treatment policy, were significantly associated with higher odds of a delay in care seeking. The prevalence of health care-seeking delay among tuberculosis patients was high in rural areas. It is essential to take comprehensive targeted interventions to reduce care-seeking delay.
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http://dx.doi.org/10.3390/ijerph15091998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164791PMC
September 2018

In vitro digestibility and prebiotic potential of curdlan (1 → 3)-β-d-glucan oligosaccharides in Lactobacillus species.

Carbohydr Polym 2018 May 31;188:17-26. Epub 2018 Jan 31.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, No.17 Qinghua Donglu, Haidian District, Beijing 100083, China. Electronic address:

Prebiotic effects of curdlan (1 → 3)-β-d-glucan oligosaccharides (GOS) were examined. GOS was tolerant against simulated gastrointestinal digestion, as well as low pH, thermal, and Maillard reaction conditions likely occurred during food processing. Growth of tested Lactobacillus (L.) strains was improved by GOS except L. brevis NRRL B-4527. E. coli did not grow on GOS as the only carbon source. In vitro batch fermentation using human faecal microbiota showed that GOS significantly increased the population of Lactobacillus sp. followed by Bifidobacterium sp. and Bacteroides sp. Growth of L. strains on GOS produced lactic acid, acetic, and propionic acid with decreased culture medium pH. Utilization pattern of GOS by representative L. strains was strain dependent. GOS with degree of polymerization (DP) of 2 and 3 were readily consumed. Findings here indicated that curdlan GOS (DP = 2 and 3) are promising physiologically active prebiotics for improvement of human intestinal health.
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http://dx.doi.org/10.1016/j.carbpol.2018.01.085DOI Listing
May 2018

4-Nonylphenol induces autophagy and attenuates mTOR-p70S6K/4EBP1 signaling by modulating AMPK activation in Sertoli cells.

Toxicol Lett 2017 Feb 29;267:21-31. Epub 2016 Dec 29.

MOE (Ministry of Education) Key Lab of Environment and Health, Department of Occupational and Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

The estrogenic chemical 4-nonylphenol (NP) is known to impair testicular devolopment and spermatogenesis in rodents. The objective of this study was to explore the effects of NP on autophagy induction and AMPK-mTOR signaling pathway in Sertoli cells (SCs), which are the "nursemaid cells" for meiosis of spermatocytes. In this study we exposed 7-week-old male rats to NP by intra-peritoneal injection at 0, 20, 50 or 100mg/kg body weight/2days for 20 consecutive days. Our results showed that exposure to NP dose-dependently induces the formation of autophagosomes in SCs, increases the expression of Beclin-1, the conversion of LC3-I to LC3-II and the mRNA expression of Atg3, Atg5, Atg7 and Atg12 in testis, and these effects are concomitant with the activation of AMPK, and the suppression of TSC2-mTOR-p70S6K/4EBP1 signaling cascade in testis. Furthermore, 10μM Compound C or AMPKα1 siRNA pre-treatment effectively attenuated autophagy and reversed AMPK-mTOR-p70S6K/4EBP1 signaling in NP-treated SCs. Co-treatment with 1mM AICAR remarkably strengthened NP-induced autophagy and mTOR inhibition in SCs. Together, these data suggest that NP stimulates Sertoli cell autophagy and inhibits mTOR-p70S6K/4EBP1 activity through AMPK activation, which is the potential mechanism responsible for the regulation of testis function and differentiation following NP exposure.
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http://dx.doi.org/10.1016/j.toxlet.2016.12.015DOI Listing
February 2017

Di(2-ethylhexyl) phthalate induces apoptosis through mitochondrial pathway in GC-2spd cells.

Environ Toxicol 2017 Mar 14;32(3):1055-1064. Epub 2016 Jul 14.

Department of Epidemiology and Health Statistics, School of Public Health, Medical College, Wuhan University of Science and Technology, 947 Heping Avenue, Wuhan, 430081, People's Republic of China.

Di(2-ethylhexyl) phthalate (DEHP), a plasticizer of synthetic polymers, is a well-known endocrine disrupting chemical (EDC) and reproductive toxicant. Addressing the unclear mechanism of DEHP-induced reproductive dysfunction, this study used GC-2spd cells to investigate the molecular mechanism involved in the DEHP-induced toxicity in the male reproductive system. The results indicated that the apoptotic cell death was significantly induced by DEHP exposure over 100 μM. Furthermore, DEHP treatment could induce oxidative stress in GC-2spd cells involving in the decrease of superoxide dismutase (SOD) activity (200 μM) and glutathione peroxidase (GSH-Px) activity (50 and 100 μM). In addition, DEHP induction also caused the elevated ratios of Bax/Bcl-2, release of cytochrome c and decomposition of procaspase-3 and procaspase-9 in GC-2spd cells. Taken together, our work provided the evidence that DEHP exposure might induce apoptosis of GC-2spd cells via mitochondria pathway mediated by oxidative stress. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1055-1064, 2017.
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http://dx.doi.org/10.1002/tox.22304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673478PMC
March 2017

Effects of 4-nonylphenol on spermatogenesis and induction of testicular apoptosis through oxidative stress-related pathways.

Reprod Toxicol 2016 07 22;62:27-38. Epub 2016 Apr 22.

MOE (Ministry of Education) Key Lab of Environment and Health, Department of Occupational and Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

This study tested the hypothesis that prepubertal exposure to 4-nonylphenol (NP) affects reproductive function in male rats. Twenty-four rats at five-weeks-old were randomly divided into four groups and treated with NP at varying concentrations (0, 5, 20, and 60mg/kg/2d) for thirty days by intra-peritoneal injection. 60mg/kg NP induced spermatogenic degeneration and pronounced deficits in epididymal sperm count, motility and function, whereas potentially stimulatory effects were observed at 5 NPmg/kg. Moreover, 60mg/kg NP resulted in a significant reduction in fructose, FSH and LH; induced apoptosis related to oxidative stress; inhibited mRNA and protein levels of Bcl-2 and PCNA; as well as the additional up-regulation of p53, Bax, Apaf-1, cytochrome c, cleaved-caspase-3, Fas and FasL expression. Our data suggest potentially hormetic effects of NP on spermatogenic function. High-dose NP impairs testicular development and function by reducing cell proliferation and inducing apoptosis involving oxidative stress-related p53-Bcl-2/Bax and -Fas/FasL pathways.
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http://dx.doi.org/10.1016/j.reprotox.2016.04.016DOI Listing
July 2016

4-Nonylphenol induces disruption of spermatogenesis associated with oxidative stress-related apoptosis by targeting p53-Bcl-2/Bax-Fas/FasL signaling.

Environ Toxicol 2017 Mar 18;32(3):739-753. Epub 2016 Apr 18.

MOE (Ministry of Education) Key Lab of Environment and Health, Department of Occupational and Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

4-Nonylphenol (NP) is a ubiquitous environmental chemical with estrogenic activity. Our aim was to test the hypothesis that pubertal exposure to NP leads to testicular dysfunction. Herein, 24 7-week-old rats were randomly divided into four groups and treated with NP (0, 25, 50, or 100 mg/kg body weight every 2 days for 20 consecutive days) by intraperitoneal injection. Compared to untreated controls, the parameters of sperm activation rate, curvilinear velocity, average path velocity, and swimming velocity were significantly lower at doses of 100 mg/kg, while sperm morphological abnormalities were higher, indicating functional disruption and reduced fertilization potential. High exposure to NP (100 mg/kg) resulted in disordered arrangement of spermatoblasts and reduction of spermatocytes in seminiferous tubules, while tissues exhibited a marked decline in testicular fructose content and serum FSH, LH, and testosterone levels. Oxidative stress was induced by NP (50 or 100 mg/kg) as evidenced by elevated MDA, decreased SOD and GSH-Px, and inhibited antioxidant gene expression (CAT, GPx, SOD1, and CYP1B1). In addition, NP treatment decreased proportions of Ki-67-positive cells and increased apoptosis in a dose-dependent manner. Rats treated with 100 mg/kg NP exhibited significantly increased mRNA expression of caspase-1, -2, -9, and -11, decreased caspase-8 and PCNA1 mRNA expression, downregulation of Bcl-2/Bax ratios and upregulation of Fas, FasL, and p53 at the protein and mRNA levels. Taken together, NP-induced apoptosis, hormonal deficiencies, and depletion of fructose potentially impairs spermatogenesis and sperm function. p53-independent Fas/FasL-Bax/Bcl-2 pathways may be involved in NP-induced oxidative stress-related apoptosis. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 739-753, 2017.
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http://dx.doi.org/10.1002/tox.22274DOI Listing
March 2017

Di-(2-ethylhexyl) phthalate induces apoptosis of GC-2spd cells via TR4/Bcl-2 pathway.

Environ Toxicol Pharmacol 2016 Jun 8;44:18-24. Epub 2016 Apr 8.

School of Public Health, Medical College, Wuhan University of Science and Technology, 947Heping Avenue, Wuhan 430081, PR China. Electronic address:

Di-(2-ethylhexyl) phthalate (DEHP) is a widely used environmental endocrine disruptor. Many studies have reported that DEHP exposure causes reproductive toxicity and cells apoptosis. However, the mechanism by which DEHP exposure causes male reproductive toxicity remains unknown. This study investigated the role of the testicular orphan nuclear receptor4 (TR4)/Bcl-2 pathway in apoptosis induced by DEHP, which resulted in reproductive damage. To elucidate the mechanism underpinning the male reproductive toxicity of DEHP, we sought to investigate apoptotic effects, expression levels of TR4/Bcl-2 pathway in GC-2spd cells, including TR4, Bcl-2 and caspase-3. GC-2spd cells were exposed to various concentrations of DEHP (0, 50, 100, or 200μM). The results indicated that, with the increase of the concentrations of DEHP, the survival rate of cell decreased gradually. DEHP exposure at over 100μM significantly induced apoptotic cell death. DEHP decreased SOD and GSH-Px activity in 200μM group. Compared to the control group, the mRNA levels of caspase-3 increased significantly, however, Bcl-2 mRNA decreased (P<0.05). In addition, there was a significant reduction in TR4, Bcl-2 and procaspase-3 protein levels. Taken together, these results lead us to speculate that in vitro exposure to DEHP might induce apoptosis in GC-2spd cells through the TR4/Bcl-2 pathway.
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http://dx.doi.org/10.1016/j.etap.2016.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491968PMC
June 2016

4-Nonylphenol induces apoptosis, autophagy and necrosis in Sertoli cells: Involvement of ROS-mediated AMPK/AKT-mTOR and JNK pathways.

Toxicology 2016 Feb 19;341-343:28-40. Epub 2016 Jan 19.

MOE (Ministry of Education) Key Lab of Environment and Health, Department of Occupational and Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

The xenoestrogen 4-nonylphenol (NP) induces reproductive dysfunction of male rats, but the fundamental mechanism of this phenomenon is largely unexplored. Sertoli cells (SCs) are pivotal for spermatogenesis and male fertility. The involvement of autophagy in NP-induced apoptotic and necrotic death of SCs was investigated. In this study, 24-h exposure of SCs to 20-30μM NP decreased cell viability, caused G2/M arrest, triggered ΔΨm loss, increased ROS production and induced caspase-dependent apoptosis, necrosis as well as autophagosome formation. NP-induced autophagy was confirmed by monodansylcadaverine-staining and LC3-I/LC3-II conversion. Furthermore, NP up-regulated the (Thr172)p-AMPK/AMPK and (Thr183/185)p-JNK/JNK ratios. This was followed by the down-regulation of (Ser473)p-Akt/Akt, (Thr1462)p-TSC2/TSC2, (Ser2448)p-mTOR/mTOR, (Thr389)p-p70S6K/p70S6K and (Thr37/45)p-4EBP1/4EBP1. Intriguingly, NP-induced apoptosis, autophagy and necrosis could be inhibited through blocking ROS generation by N-acetylcysteine. Autophagy inhibitor 3-MA enhanced NP-induced apoptosis and necrosis. Moreover, The activation of AMPK/mTOR/p70s6k/4EBP1 and JNK signalling pathways induced by NP could be efficiently reversed by pretreatment of N-acetylcysteine or 3-MA. Collectively, our findings provide the first evidence that NP promotes apoptosis, autophagy and necrosis simultaneously in SCs and that this process may involve ROS-dependent JNK- and Akt/AMPK/mTOR pathways. Modulation of autophagy induced by NP may serve as a survival mechanism against apoptosis and necrosis.
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http://dx.doi.org/10.1016/j.tox.2016.01.004DOI Listing
February 2016

RC/BTB2 is essential for formation of primary cilia in mammalian cells.

Cytoskeleton (Hoboken) 2015 Apr 29;72(4):171-81. Epub 2015 Apr 29.

School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei, China.

RC/BTB2 is a binding partner of sperm associated antigen 16S (SPAG16S), which is a regulator of spermiogenesis in mice, a process during which sperm flagella are formed. The expression of Rc/btb2 is also regulated by multicilin, a protein that controls ciliogenesis. Given that mouse Rc/btb2 mRNA is not only expressed in tissues bearing motile cilia, but also in tissues without motile cilia, we investigated whether RC/BTB2 plays a role in the general process of ciliogenesis by studying two cell lines that have primary cilia, NIH3T3, and IMCD3. We discovered that the subcellular localization of RC/BTB2 in the NIH3T3 and IMCD3 cells encompasses the pathway for ciliogenesis. RC/BTB2 was found in the Golgi bodies and centrosomes, two key structures essential for normal ciliogenesis. Knockdown of Rc/btb2 gene expression in these cell lines disrupted ciliogenesis. The percentage of cells with primary cilia was significantly reduced in stable cell lines transduced with specific Rc/btb2 shRNA viruses as compared to the control cells. When cilia were formed in the knockdown cells, they were significantly shorter than those in the control cells. Knockdown of Rc/btb2 expression did not affect cell proliferation and the cell cycle. Exogenous expression of RC/BTB2 in these stable knockdown cells restored ciliogenesis. These findings suggest that RC/BTB2 is a necessary component of the process of formation of primary cilia in somatic cells, perhaps through the transportation of cargos from Golgi bodies to centrosomes for cilia assembling.
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http://dx.doi.org/10.1002/cm.21214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758837PMC
April 2015

p,p'-DDE damages spermatogenesis via phospholipid hydroperoxide glutathione peroxidase depletion and mitochondria apoptosis pathway.

Environ Toxicol 2016 May 20;31(5):593-600. Epub 2014 Nov 20.

Department of Occupational and Environmental Health, MOE Key Lab of Environment and Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

One, 1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE), the major metabolite of 2,2-bis(4-chlorophenyl)-1,1,1-trichloroethane (DDT), is a known persistent organic pollutant (POPs) and male reproductive toxicant. However, the mechanism by which p,p'-DDE exposure causes male reproductive toxicity remains unknown. The objective of this study was to elucidate some mechanisms involved in this process, including the mitochondria apoptosis pathway and the role of phospholipid hydroperoxide glutathione peroxidase (PHGPx). Puberty male SD rats were given different doses of p,p'-DDE (0, 20, 60, 100 mg/kg body weight), after the treatment, the semen quality was evaluated. Western blotting was used to detect the PHGPx protein expression. Furthermore, real-time PCR was used to analyze the genetic expression of PHGPx, Bax, Cytochrom C (Cyt C), Apaf-1, and caspase-3 in the testis. Results indicated that after the exposure, sperm malformation rate showed a significant rise compared with the control group, and meanwhile, the sperm density and sperm motility parameters were reduced to some extent in different treated groups. The mitochondria apoptosis pathway was activated. And remarkably, the expression of PHGPx protein was greatly reduced by the exposure. We conclude that p,p'-DDE can damage spermatogenesis via PHGPx depletion and mitochondria apoptosis pathway.
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http://dx.doi.org/10.1002/tox.22072DOI Listing
May 2016

Effects of p,p'-DDE on the mRNA and protein expressions of vimentin, N-cadherin and FSHR in rats testes: an in vivo and in vitro study.

Environ Toxicol Pharmacol 2013 May 19;35(3):486-94. Epub 2013 Feb 19.

MOE Key Lab of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, Hubei, PR China.

To elucidate the mechanism underlying the testicular effects of 1,1-dichloro-2,2bis(p-chlorophenyl)ethylene (p,p'-DDE), the expressions of vimentin, neural cadherin and follicle-stimulating hormone receptor mRNA and proteins were measured in vivo and in vitro. Sprague-Dawley rats were dosed with p,p'-DDE at 0, 20, 60 and 100 mg/kg every other day by intraperitoneal injection for 10 days, and Sertoli cells were treated with p,p'-DDE (0, 10, 30, and 50 μM) for 24 h. Results indicated that the survival rate of Sertoli cells was decreased with increasing doses of p,p'-DDE. In vitro and in vivo studies, p,p'-DDE could increase the expression of neural cadherin, follicle-stimulating hormone receptor mRNA, while decrease the levels of vimentin, neural cadherin and follicle-stimulating hormone receptor proteins. Moreover, immunohistochemistry analysis revealed that the protein expressions of vimentin, neural cadherin and follicle-stimulating hormone receptor in pubertal rat testes were disrupted by treatment with p,p'-DDE. Taken together, these results suggested that p,p'-DDE exposure could induce testicular toxicity through the changes of the mRNA and protein expressions of vimentin, neural cadherin and follicle-stimulating hormone receptor in vitro and in vivo.
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http://dx.doi.org/10.1016/j.etap.2013.02.008DOI Listing
May 2013

p,p'-Dichlorodiphenoxydichloroethylene induced apoptosis of Sertoli cells through oxidative stress-mediated p38 MAPK and mitochondrial pathway.

Toxicol Lett 2011 Apr 28;202(1):55-60. Epub 2011 Jan 28.

MOE Key Lab of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, Hubei, PRChina.

p,p'-DDE, the major metabolite of dichlorodiphenoxytrichloroethane (DDT), is a known persistent organic pollutant and male reproductive toxicant. However, the mechanism underlying its male reproductive toxicity remains limited. Our previous studies have demonstrated that p,p'-DDE could induce mitochondria-mediated apoptosis of cultured rat Sertoli cells. In the present study, we investigated mitogen-activated protein kinase pathways as well as other mitochondria-related molecules including Bax family members and cytochrome c. Results showed that p,p'-DDE could induce oxidative stress-mediated p38 and JNK phosphorylation. In addition, elevated mRNA levels of cytochrome c and ratios of bax/bcl-w and bak/bcl-w were induced by p,p'-DDE treatment, which could be inhibited by RNA synthesis inhibitor (actinomycin D). p,p'-DDE-induced apoptosis was blocked by NAC (N-acetyl-L-cystein) preincubation and attenuated by pretreatment with p38 inhibitor (SB202190) or actinomycin D, but not with JNK inhibitor (SP600125). All of the findings suggested that oxidative stress-mediated p38 MAPK pathway and the balance between pro- and anti-apoptotic bax-gene family might play critical roles in p,p'-DDE-induced apoptosis.
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http://dx.doi.org/10.1016/j.toxlet.2011.01.020DOI Listing
April 2011

β-Benzene hexachloride induces apoptosis of rat Sertoli cells through generation of reactive oxygen species and activation of JNKs and FasL.

Environ Toxicol 2011 Apr;26(2):124-35

MOE Key Laboratory of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.

β-benzene hexachloride (β-BHC), the major metabolite of benzene-hexachloride (BHC), is a weak estrogen-like chemical. It is a known persistent organic pollutant and male reproductive toxicant. However, the mechanism by which β-BHC exposure causes male reproductive toxicity remains unknown. In the present study, rat Sertoli cells were used to investigate the molecular mechanism involved in β-BHC-induced toxicity in male reproductive system. The results indicated that β-BHC exposure at over 30 μM showed the induction of apoptotic cell death. β-BHC could induce elevation in reactive oxygen species (ROS) generation, increase in the leakage rate of LDH and MDA level, and decrease in SOD activity. In addition, there was an increase in the cellular levels of phospho-JNKs and FasL in the β-BHC-induced apoptosis; and a significant reduction of procaspase-3 and -8 was observed over 30-μM β-BHC treatment. The translocation of NF-κB enhanced with the increase of concentration of β-BHC. Furthermore, NAC administration, a scavenger of ROS, reversed β-BHC-induced apoptosis effects via inhibition of JNKs activation, FasL expression, and NF-κB translocation. These results lead us to speculate that ROS generation may play a critical role in the initiation of β-BHC-induced apoptosis by activation of the JNKs, translocation of NF-κB, expression of FasL, and further activation of caspase cascade.
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http://dx.doi.org/10.1002/tox.20536DOI Listing
April 2011

p,p'-DDE induces apoptosis of rat Sertoli cells via a FasL-dependent pathway.

J Biomed Biotechnol 2009 22;2009:181282. Epub 2009 Jul 22.

MOE Key Lab of Environment and Health, Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.

One,1-dichloro-2,2 bis(p-chlorophenyl) ethylene (p,p'-DDE), the major metabolite of 2,2-bis(4-Chlorophenyl)-1,1,1-trichloroethane (DDT), is a known persistent organic pollutant and male reproductive toxicant. It has antiandrogenic effect. However, the mechanism by which p,p'-DDE exposure causes male reproductive toxicity remains unknown. In the present study, rat Sertoli cells were used to investigate the molecular mechanism involved in p,p'-DDE-induced toxicity in male reproductive system. The results indicated that p,p'-DDE exposure at over 30 muM showed the induction of apoptotic cell death. p,p'-DDE could induce increases in FasL mRNA and protein, which could be blocked by an antioxidant agent, N-acetyl-l-cysteine (NAC). In addition, caspase-3 and -8 were activated by p,p'-DDE treatment in these cells. The activation of NF-kappaB was enhanced with the increase of p,p'-DDE dose. Taken together, these results suggested that exposure to p,p'-DDE might induce apoptosis of rat Sertoli cells through a FasL-dependent pathway.
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http://dx.doi.org/10.1155/2009/181282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717566PMC
October 2009