Publications by authors named "Xiuxiu Chen"

34 Publications

NDUFC1 Is Upregulated in Gastric Cancer and Regulates Cell Proliferation, Apoptosis, Cycle and Migration.

Front Oncol 2021 13;11:709044. Epub 2021 Dec 13.

Department of Pancreatic & Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Gastric cancer is one of the most common primary tumors of the digestive system. NADH: ubiquinone oxidoreductase subunit C1 (NDUFC1), which is an accessory subunit of the NADH dehydrogenase (complex I), is responsible for the transportation of electrons from NADH to the respiratory chain essential for the oxidative phosphorylation. However, little is known about the roles of NDUFC1 in carcinogenesis. In this study, NDUFC1 protein level in NSCLC tissues was tested by immunohistochemistry (IHC) staining. NDUFC1 mRNA level in gastric cancer cell lines was determined by qRT-PCR. MGC-803 and SGC-7901 cells were transfected with shNDUFC1 lentivirus designed to silence NDUFC1. MTT assay, CCK8 assay, wound healing assay and transwell migration assay were conducted. Cell cycle and apoptosis were detected by flow cytometry. experiments were performed using nude mice. The results indicated that overexpressed NDUFC1 in gastric cancer was related to more serious tumor infiltrates, a higher risk of lymphatic metastasis, a higher proportion of positive lymph nodes, and a more advanced tumor stage. Compared with shCtrl groups, MGC-803 and SGC-7901 of shNDUFC1 groups had lower abilities of proliferation and migration, higher levels of apoptosis. NDUFC1 knockdown also inhibited SGC-7901 cell growth and suppressed Ki67 expression in xenograft tumors. More importantly, we found that NDUFC1 downregulation made the levels of P-Akt, P-mTOR, CCND1, CDK6, PIK3CA, Bcl-2, Survivin, and XIAP decreased, and that PI3K/AKT signaling pathway agonist SC79 rescued the inhibitory effects on cell proliferation and migration, reversed the promoted effects on cell apoptosis caused by NDUFC1 knockdown. More importantly, compared with NDUFC1 knockdown group, the expression of P-Akt, Bcl-2, Survivin, and XIAP was raised in shNDUFC1 + SC79 group. Thus, our suspicion was that NDUFC1 exacerbates NSCLC progression PI3K/Akt pathway. Taken together, our study indicated that targeting NDUFC1 could open innovative perspectives for new multi-targeting approaches in the treatment of gastric cancer.
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http://dx.doi.org/10.3389/fonc.2021.709044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710466PMC
December 2021

Comparative analysis of physiological, agronomic and transcriptional responses to drought stress in wheat local varieties from Mongolia and Northern China.

Plant Physiol Biochem 2022 Jan 17;170:23-35. Epub 2021 Nov 17.

Key Laboratory of Plant Resources, Institute of Botany, Chinese Academy of Sciences, Beijing, 100093, China. Electronic address:

Drought is one of the major abiotic stresses that threaten wheat production worldwide, especially in the Mongolian Plateau and adjacent regions. This study aims to find local wheat varieties with high yields and drought resistance at various developmental stages based on agronomic traits and drought resistance indices analysis and explore the underlining molecular mechanisms by transcriptome analysis. Our results revealed that drought stress started at the seedling stage has a greater impact on crop yields. Four types of drought responses were found among the tested varieties. Type 1 and type 2 show low tolerance to drought stress despite high or low yield in control condition, type 3 exhibits high yield under control condition but dropped significantly after drought, and type 4 displays relatively high and stable yields under control and drought conditions. Transcriptome analysis performed with the representative varieties of the four types revealed GO terms and KEGG pathways enriched among drought-triggered differential expressed genes (DEGs). A network containing 18 modules was constructed using weighted gene co-expression analysis (WGCNA). Ten modules were significantly correlated to yield by module-trait correlation, and 3 modules showed Darkhan 144 specific gene expression patterns. C2H2 zinc finger factor-recognized motifs were identified from the promoters of genes in these modules. qRT-PCR confirmed several key DEGs with specific expression patterns and physiological measurements validated the relatively low oxidative damage and high antioxidant capacity in the drought tolerant variety Dankhan 144. These findings provide an important basis for local agriculture and breeding of drought-tolerant high yield wheat varieties.
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http://dx.doi.org/10.1016/j.plaphy.2021.11.026DOI Listing
January 2022

[Preparation of liquid crystal-based molecularly imprinted monolith and its molecular recognition thermodynamics].

Se Pu 2021 Nov;39(11):1171-1181

Tianjin Key Laboratory of Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.

Molecularly imprinted polymers (MIPs) incorporated with liquid crystalline monomers can imprint and recognize templates at a very low level of crosslinking, thus addressing challenges associated with conventional MIPs, such as the embedding of the imprinted sites, low binding capacity, and slow mass transfer due to the high degree of crosslinking. Compared with traditional MIPs, the prepared MIPs have a greater number of easily binding sites, which can effectively overcome the embedding and low utilization of imprinting sites. Simultaneously, with a decrease in the level of chemical crosslinking, the mass transfer of template molecules can be significantly improved. However, the imprinting effect of liquid crystalline MIPs is generally weaker than that of traditional MIPs due to the low degree of crosslinking. Therefore, to obtain liquid crystalline MIPs with a good imprinting effect, a series of low-crosslinked liquid crystalline molecularly imprinted monoliths were prepared by graft polymerization and evaluated by high performance liquid chromatography (HPLC) to systematically determine the relation between the polymerization parameters and the affinity of the resulting liquid crystalline MIPs. In this experiment, trimethylolpropane trimethacrylate (TRIM) was used to synthesize a monolithic column skeleton with toluene and dodecyl alcohol as porogens. ()-Naproxen was used as a template and liquid crystalline monomer 4-(4-cyanophenyl)-cyclohexyl ethylene (CPCE) was added for grafting to synthesize the liquid crystalline MIP monolith. The influence of the acetonitrile content and pH in the mobile phase on the chromatographic retention of the template molecule was investigated. The results showed that the main force of MIP recognizing naproxen changed from hydrogen bonding to hydrophobic interaction by the addition of the liquid crystalline monomer. Frontal analysis and adsorption isotherm fitting, including Langmuir, Freundlich, and Scatchard fitting, showed that when the crosslinking degree was 15%, the liquid crystalline MIPs exhibited the highest imprinting factor and heterogeneity, and the specific adsorption was stronger than non-specific adsorption. By analyzing the stoichiometric displacement model, the total affinity of the MIP monoliths for the template molecules (ln ) was determined to be 0.645, significantly higher than that of its analogues, indicating that the liquid crystalline imprinted monolith had a higher total affinity for the template molecule. The spatial matching degree () of the template molecule to the cavity structures of MIPs was also very high, and only inferior to that of ketoprofen. Nevertheless, the ln value of ketoprofen was only 0.242, which indicated that the spatial effect was not the key factor in determining the recognition ability of liquid crystalline imprinting systems. An analysis of the separation thermodynamics revealed that the separation of the liquid crystalline MIPs was an entropy-controlled process, while that of conventional liquid crystalline-free MIPs was an enthalpy-controlled process. Based on the above results, the addition of a liquid crystalline monomer may alter the recognition mechanism of MIPs, and an appropriately low crosslinking degree can significantly improve the recognition performance of liquid crystalline MIPs, paving the way for a new generation of MIPs.
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http://dx.doi.org/10.3724/SP.J.1123.2021.01017DOI Listing
November 2021

Application effects of targeted nursing model in patients undergoing thyroid surgery and its influence on patients' negative emotions.

Am J Transl Res 2021 15;13(4):2822-2830. Epub 2021 Apr 15.

Department of Surgery, Donghu Branch of The Second Affiliated Hospital of Hainan Medical University Haikou 570100, Hainan Province, China.

Objective: To explore the effectiveness of a targeted nursing model for patients undergoing thyroid surgery, and to analyse the influence of intervention on the negative emotions of patients.

Methods: Eighty patients who received thyroid surgery in our hospital were enrolled and divided into a study group (n=40, given targeted nursing) and a control group (n=40, given routine surgical nursing) according to the difference of intervention measures. The postoperative bed-leaving time, hospitalization time, medical expenses, drainage tube indwelling time and incidence of postoperative adverse reactions were compared between the two groups. The degree of pain, anxiety and depression was compared between the two groups at 1 d, 3 d, 5 d, and 7 d after surgery. The scales of voice handicap index (VHI-10) and standard swallowing assessment (SSA) were used to evaluate voice quality and swallowing function in the two groups.

Results: The postoperative bed-leaving time, hospitalization time, medical expenses, drainage tube indwelling time and incidence of postoperative adverse reactions of patients in the study group were lower than those in the control group (<0.05). The scores of visual analogue scale (VAS), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) in the study group at 3 d, 5 d and 7 d after surgery were lower than those in the control group (<0.05). The scores of VHI-10 and SSA in the study group were lower than those in the control group at 7 d and 30 d after surgery (<0.05).

Conclusion: Targeted nursing for patients undergoing thyroid surgery can help accelerate the improvement of postoperative clinical symptoms, relieve the unhealthy emotions and pain of patients, and help improve their voice quality and swallowing function, which also has a positive effect on reducing postoperative complications. Therefore, it is worthy of clinical popularization and application.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129208PMC
April 2021

Life cycle assessment of a long-term multifunctional winter wheat-summer maize rotation system on the North China Plain under sustainable P management.

Sci Total Environ 2021 Aug 17;783:147039. Epub 2021 Apr 17.

College of Resources and Environmental Science, National Academy of Agriculture Green Development, Key Laboratory of Plant-Soil Interactions, Ministry of Education, China Agricultural University, Beijing 100193, China. Electronic address:

In sustainable agriculture, sufficient crop yields and nutrients must be produced while maintaining environmental protection. Considering the role of phosphorus (P) fertilizer in influencing crops yield and environmental security, life cycle assessment was used to examine the environmental impacts of long-term P application on the grain yield and nutritional quality of winter wheat and summer maize. Thus, a long-term field experiment with six P application rates for winter wheat (0, 25, 50, 100, 200, and 400 kg P ha) and summer maize (0, 12.5, 25, 50, 100, and 200 kg P ha) was conducted on the North China Plain (NCP). The results showed that the cradle-to-farm gate eutrophication potential (EP), energy depletion (ED), and P depletion (PD) were significantly affected by the P application rate applied in winter wheat and summer maize production. The critical P rate required to ensure food security for wheat and maize was in line with the optimal rate for sustainable environmental development in terms of grain production and nutrient levels. On the NCP, the ED and PD of summer maize with optimized P management over 10 years were less than those of winter wheat regardless of using yield or nutrient level as the functional unit. However, the EP of the nutrient supply in winter wheat was less than that in summer maize under optimized P fertilization. The specific nutritional components that limited improvements in environment of wheat and maize production under the optimal P rate were energy (calories) and protein, respectively. In conclusion, in a multifunctional winter wheat-summer maize rotation system, optimized P fertilization (50 kg ha for winter wheat and 25 kg ha for summer maize) combined with the planting of high-yield wheat varieties and high-protein maize varieties showed great potential to reduce the environmental impacts of wheat and maize production.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147039DOI Listing
August 2021

Soil Microbial Composition and Gene Abundance Are Sensitive to Phosphorus Level in a Long-Term Wheat-Maize Crop System.

Front Microbiol 2020 14;11:605955. Epub 2021 Jan 14.

College of Resources and Environment, Academy of Agricultural Sciences, Southwest University, Chongqing, China.

Microbes associated with phosphorus (P) cycling are intrinsic to soil P transformation and availability for plant use but are also influenced by the application of P fertilizer. Nevertheless, the variability in soil P in the field means that integrative analyses of soil P cycling, microbial composition, and microbial functional genes related to P cycling remain very challenging. In the present study in the North China Plain, we subjected the bacterial and fungal communities to amplicon sequencing analysis and characterized the alkaline phosphatase ( encoding bacterial alkaline phosphatase in a long-term field experiment (10 years) with six mineral P fertilization rates up to 200 kg P ha. Long-term P fertilization increased soil available P, inorganic P, and total P, while soil organic P increased until the applied P rate reached 25 kg ha and then decreased. The fungal alpha-diversity decreased as P rate increased, while there were no significant effects on bacterial alpha-diversity. Community compositions of bacteria and fungi were significantly affected by P rates at order and family levels. The number of keystone taxa decreased from 10 to 3 OTUs under increasing P rates from 0 to 200 kg ha. The gene copy numbers of the biomarker of the alkaline phosphatase was higher at moderate P rates (25 and 50 kg ha) than at low (0 and 12.5 kg ha) and high (100 and 200 kg ha) rates of P fertilization, and was positively correlated with soil organic P concentration. One of the keystone taxa named BacOTU3771 belonging to Xanthomonadales was positively correlated with potential functional genes encoding enzymes such as glycerophosphoryl diester phosphodiesterase, acid phosphatase and negatively correlated with guinoprotein glucose dehydrogenase. Altogether, the results show the systematic effect of P gradient fertilization on P forms, the microbial community structure, keystone taxa, and functional genes associated with P cycling and highlight the potential of moderate rates of P fertilization to maintain microbial community composition, specific taxa, and levels of functional genes to achieve and sustain soil health.
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http://dx.doi.org/10.3389/fmicb.2020.605955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873961PMC
January 2021

CNOT7 modulates biological functions of ovarian cancer cells via AKT signaling pathway.

Life Sci 2021 Mar 4;268:118996. Epub 2021 Jan 4.

Department of Gynecology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, People's Republic of China; Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200126, People's Republic of China. Electronic address:

Aims: CNOT7 plays an important role in many biological processes, providing attractive opportunities for the treatment of malignant tumors. However, the functions and mechanism of CNOT7 in ovarian cancer (OC) have not been elucidated. The purpose of this study was to assess the role of CNOT7 in OC.

Materials And Methods: SKOV3 and A2780 cells were chosen as the cell lines for the experiments of this manuscript via the analysis of the expression of CNOT7 protein and the mRNA level in ovarian surface epithelium (OSE) cells, SKOV3, HO8910 and A2780 cells. The expression of CNOT7 was detected by western blot assays and RT-PCR in A2780 and SKOV3 cells. The MTT assays, colony formation assays and EdU assays were used to measure cell proliferation when CNOT7 was knocked down or overexpressed in A2780 and SKOV3 cells. Furthermore, cell migration and invasion ability were achieved from transwell assays. Cell cycle and apoptosis rate after small interference RNA-CNOT7 (siRNA-CNOT7) were detected by flow cytometry assays. Finally, the cell proliferation, migration and invasion ability were detected when A2780 and SKOV3 cells with CNOT7 overexpression were treated with LY294002.

Key Findings: The expression of CNOT7 protein in OC cells, including SKOV3, HO8910 and A2780 cells were significantly higher than that in OSE cells (P < 0.05). The mRNA level of CNOT7 in HO8910 and A2780 cells were significantly higher than that in OSE cells (P < 0.01). However, the mRNA level of CNOT7 in SKOV3 cells was no significant difference compared with OSE cells (P > 0.05). The results suggested that knockdown of CNOT7 could inhibit the cell proliferation, migration and invasion ability in A2780 and SKOV3 cells, and increase cell apoptosis and autophagy. The expression of apoptosis-related molecules (PARP, Caspase3 and Caspase9) and autophagy-related protein (LC3B) were up-regulated after CNOT7 knockdown, while the expression of cycle-related protein (CDK6) and the anti-apoptotic gene (Bcl2) were downregulated. Meanwhile, the opposite results were observed when CNOT7 was overexpressed in A2780 and SKOV3 cells. It is worth noting that the effect of CNOT7 overexpression in A2780 and SKOV3 cells could be partially or completely eliminated by treatment with AKT inhibitor LY294002.

Significance: CNOT7 has a carcinogenic effect in OC, and the carcinogenic effect may be achieved via the AKT signaling pathway.
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http://dx.doi.org/10.1016/j.lfs.2020.118996DOI Listing
March 2021

[Quorum sensing molecule N-3-oxodecanoyl-L-homoserine lactone (3-oxo-C-HSL) inhibits lipopolysaccharide-induced inflammatory responses of RAW264.7 macrophages].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2020 Sep;36(9):776-781

Central Laboratory, Sixth Medical Centre, Chinese People's Liberation Army General Hospital, Beijing 100048, China. *Corresponding author,

Objective To explore the regulatory effect of quorum sensing molecule N-3-oxodecanoyl-L-homoserine lactone (3-oxo-C-HSL) on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages. Methods RAW264.7 macrophages were divided into experimental group, control group and blank group. The experimental group was treated with different concentrations of 3-oxo-C-HSL and LPS; the control group was treated with DMSO and LPS; and the blank group was treated with DMSO and PBS. Cells and supernatants were collected after 12 hours of stimulation. The mRNA expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) were detected by real-time quantitative PCR, and the protein levels of IL-6 and TNF-α in supernatant were detected by ELSIA. Further, 25 μmol/L 3-oxo-C-HSL and 100 ng/mL LPS were used to stimulate the cells for 15, 30 and 60 minutes, and the phosphorylation of nuclear factor κBp65 (NF-κBp65) was detected by Western blot analysis. Results The 3-oxo-C-HSL could decrease the mRNA levels of IL-6, IL-1β, TNF-α, MCP-1 and the protein levels of IL-6 and TNF-α in LPS-treated RAW264.7 macrophages in a dose-dependent manner. In addition, 3-oxo-C-HSL could inhibit the phosphorylation of NF-κBp65 induced by LPS. Conclusion 3-oxo-C-HSL can alleviate LPS-induced inflammatory responses in RAW264.7 macrophages by inhibiting activation of NF-κB signaling pathway.
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September 2020

[Preparation of anti-lymphocyte activation gene 3 (LAG-3) fully human antibodies].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2020 May;36(5):451-456

Naval Clinical College, Anhui Medical University, Hefei 230032; Central Laboratory, Sixth Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100048, China. *Corresponding author, E-mail:

Objective Lymphocyte activation gene 3 (LAG-3) is a potential therapeutic target of tumor. This work aims to screen for anti-LAG-3 human scFvs from a human phage antibody library, and transform them into fully human antibodies. Methods The human phage antibody library was screened for anti-LAG-3 human scFvs. The specificity and affinity of phage scFvs were determined by ELISA and surface plasmon resonance (SPR), respectively. The anti-LAG-3 full human antibodies were obtained using eukaryotic expression system. Results Through 3 rounds of screening, we obtained 4 phage scFv clones that could bind to human LAG-3 recombinant protein. Affinity determination showed that the highest affinity reached 3.48×10. Then through the construction of whole human antibody expression vector, expression in eukaryotic cells, and purification, 3 clones of anti-LAG-3 full human antibodies were harvested finally. Conclusion Using a large-capacity human antibody phage display library, we obtained three anti-LAG-3 full human antibodies with high affinity.
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May 2020

Triphenyltin chloride reduces the development of rat adrenal cortex during puberty.

Food Chem Toxicol 2020 Sep 3;143:111479. Epub 2020 Jun 3.

Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People's Republic of China. Electronic address:

Triphenyltin has been classified as an endocrine disruptor. However, whether triphenyltin interferes with the adrenal glands during puberty remains unknown. Here, we reported the effects of triphenyltin on the adrenal glands in rats. Male Sprague Dawley rats (age of 35 days) were orally administered with 0, 0.5, 1, or 2 mg/kg/day triphenyltin for 18 days. Triphenyltin significantly lowered corticosterone levels at 1 and 2 mg/kg and adrenocorticotropic hormone at 2 mg/kg. The RNA-Seq analysis detected multiple differentially expressed genes. Four down-regulated genes were transcription factor genes (Nr4a1, Nr4a2, Nr4a3, and Ppard), which might be associated with the suppression of the adrenal cortex function. RNA-seq and qPCR showed that triphenyltin dose-dependently down-regulated the expression of the genes for cholesterol transport and biosynthesis, including Scarb1, Ldlr, Hmgcs1, Hmgcr, and Hsd17b7. Further Western blotting revealed that it lowered NR4A1, PPRAD, LDLR, and HMGCS1 protein levels. We treated H295R adrenal cells with 1-100 nM triphenyltin for 72 h. Triphenyltin induced significant higher ROS production at 100 nM and did not induce apoptosis at 10 and 100 nM. In conclusion, triphenyltin inhibits production of corticosterone via blocking the expression of cholesterol uptake transporters and cholesterol biosynthesis.
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http://dx.doi.org/10.1016/j.fct.2020.111479DOI Listing
September 2020

Effects of in utero exposure to diisodecyl phthalate on fetal testicular cells in rats.

Toxicol Lett 2020 May 6;330:23-29. Epub 2020 May 6.

Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. Electronic address:

Diisodecyl phthalate (DIDP) is one of synthetic phthalate plasticizers. It is widely used in plastic products and is a potential endocrine disruptor. However, the effects of DIDP on fetal testicular cell development remain unclear. The objective of the present study was to determine the effects of DIDP on fetal testis development in rats after in utero exposure. Sprague Dawley dams were randomly divided into 5 groups and were daily gavaged with DIDP (0, 10, 100, 500, and 1000 mg/kg body weight) from gestational day 14-21. Serum testosterone levels, fetal Leydig cell number and distribution, testicular gene and protein expression in male pups were examined. DIDP decreased serum testosterone levels at 1000 mg/kg (1.37 ± 0.40 ng/mL, mean ± SE) when compared to the control level (3.14 ± 0.60 ng/mL). DIDP did not affect numbers of Leydig and Sertoli cells. DIDP significantly induced abnormal aggregation of fetal Leydig cells and increased the incidence of multinucleated gonocytes at 1000 mg/kg. Furthermore, DIDP down-regulated expression of Star, Cyp11a1, Hsd17b3, and Insl3 in fetal Leydig cells at 1000 mg/kg and Sox9 in Sertoli cells at 1000 mg/kg. In conclusion, the current study indicates that in utero exposure to high-dose DIDP disrupts the development of fetal testicular cells, thus affecting the male reproductive system.
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http://dx.doi.org/10.1016/j.toxlet.2020.04.024DOI Listing
May 2020

Maternal exposure to zearalenone in masculinization window affects the fetal Leydig cell development in rat male fetus.

Environ Pollut 2020 Aug 13;263(Pt B):114357. Epub 2020 Mar 13.

Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China. Electronic address:

Zearalenone is a phenolic Fusarium mycotoxin, which is ubiquitous in human and animal feedstuff and often co-occurs with other mycotoxins. ZEA has been reported to disturb Leydig cell function and even cause the apoptosis to the Leydig cells. However, the effects of gestational exposure to zearalenone on fetal Leydig cells and the underlying mechanism remain unknown. Sprague Dawley dams were daily gavaged with 0, 2.5, 5, 10, and 20 mg/kg body weight ZEA from gestational day 14-21. On gestational day 21, rats were euthanized and serum testosterone levels were measured, and testes were collected for further evaluation of Leydig cell number, cell size, gene, and protein expression. Zearalenone significantly decreased anogenital distance and its index of male fetus, serum testosterone levels, Leydig cell proteins (SCARB1, STAR, CYP11A1, CYP17A1, and INSL3), and fetal Leydig cell number at 10 and/or 20 mg/kg by delaying the commitment of stem Leydig cells into the Leydig cell lineage and proliferation. Further study found that Notch signaling (RFNG, PSEN1, NOTCH1, and NOTCH3) was up-regulated by zearalenone. In conclusion, gestational exposure to high doses of zearalenone (10 and 20 mg/kg) blocks fetal Leydig cell development, thus possibly causing the anomalies of the male reproductive tract.
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http://dx.doi.org/10.1016/j.envpol.2020.114357DOI Listing
August 2020

Inhibition of steroid receptor coactivator-1 in the hippocampus impairs the consolidation and reconsolidation of contextual fear memory in mice.

Life Sci 2020 Mar 30;245:117386. Epub 2020 Jan 30.

Department of Military Psychology, College of Psychology, Army Medical University, Chongqing 400038, China. Electronic address:

Aims: Steroid receptor coactivator-1 (SRC-1) is a key coactivator for the efficient transcriptional activity of steroids in the regulation of hippocampal functions. However, the effect of SRC-1 on hippocampal memory processes remains unknown. Our aim was to investigate the roles of hippocampal SRC-1 in the consolidation and reconsolidation of contextual fear memory in mice.

Main Methods: Contextual fear conditioning paradigm was constructed in adult male C57BL/6 mice to examine the fear learning and memory processes. Adeno-associated virus (AAV) vector-mediated RNA interference (RNAi) was infused into hippocampus to block hippocampal SRC-1 level. Immunofluorescent staining was used to detect the efficiency of transfection. High plus maze and open field test were used to determine anxiety and locomotor activity. Western blot analyses were used to detect the expression of SRC-1 and synaptic proteins in the hippocampus.

Key Findings: We first showed that the expression of SRC-1 was regulated by fear conditioning training in a time-dependent manner, and knockdown of SRC-1 impaired contextual fear memory consolidation without affecting innate anxiety or locomotor activity. In addition, hippocampal SRC-1 was also regulated by the retrieval of contextual fear memory, and downregulation of SRC-1 disrupted fear memory reconsolidation. Moreover, knockdown of SRC-1 reversed the increased GluR1 and PSD-95 levels induced by contextual fear memory retrieval.

Significance: Our data indicate that hippocampal SRC-1 is required for the consolidation and reconsolidation of contextual fear memory, and SRC-1 may be a potential therapeutic target for mental disorders that are involved in hippocampal memory dysfunction.
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http://dx.doi.org/10.1016/j.lfs.2020.117386DOI Listing
March 2020

TERT rs10069690 polymorphism and cancers risk: A meta-analysis.

Mol Genet Genomic Med 2019 10 27;7(10):e00903. Epub 2019 Aug 27.

Department of Surgical Oncology, Second Affiliated Hospital of Hainan Medical College, Haikou, Hainan Province, China.

Background: Studies have identified that the telomerase reverse transcriptase (TERT) gene polymorphism rs10069690 (C>T) is associated with cancer risk, but the results remain inconclusive.

Methods: To provide a more precise estimation of the relationship, we performed a meta-analysis of 45 published studies including 329,035 cases and 730,940 controls. We conducted a search in PubMed, Google Scholar and Web of Science to select studies on the association between rs10069690 and cancer risk. Stratification by ethnicity, cancer type, cancers' classification, source of control, sample size, and genotype method was used to explore the source of heterogeneity. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were evaluated using random effects models. Sensitivity, publication bias, false-positive report probability (FPRP) and statistical power were also assessed.

Results: The result demonstrated that rs10069690 was significantly associated with an increased risk of cancer overall (OR = 1.09, 95% CI: 1.06-1.12, p < .001) under the allele model. Stratification analysis revealed an increased cancer risk in subgroups of breast cancer, ovarian cancer, lung cancer, thyroid cancer, and renal cell carcinoma (RCC). However, a significantly decreased association was observed in pancreatic cancer in the European population (OR = 0.93,95% CI: 0.87-0.99, p = .031). In the subgroup analysis based on cancer type, no significant association was found in prostate cancer, leukemia, colorectal cancer and glioma.

Conclusions: This meta-analysis suggested that the TERT rs10069690 polymorphism may be a risk factor for cancer, especially breast cancer, ovarian cancer, lung cancer, thyroid cancer, and RCC. Further functional studies are warranted to reveal the role of the polymorphism in carcinogenesis.
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http://dx.doi.org/10.1002/mgg3.903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785442PMC
October 2019

4-Bromodiphenyl Ether Causes Adrenal Gland Dysfunction in Rats during Puberty.

Chem Res Toxicol 2019 09 3;32(9):1772-1779. Epub 2019 Sep 3.

Department of Anesthesiology , the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou 325000 , China.

Polybrominated diphenyl ethers (PBDEs) are a group of flame retardants with two or more bromines attached. They are endocrine disruptors. PBDEs photodegrade into 4-bromodiphenyl ether (BDE3). Whether BDE3 impairs adrenal cortical cell function during postnatal development still remains unknown. The aim of the current study was to investigate the influence of BDE3 on adrenal cortical cell function. Sprague-Dawley rats (35 days of age, male) were orally administered with BDE3 (0, 50, 100, and 200 mg/kg/day body weight) for 21 days. BDE3 significantly increased serum aldosterone and corticosterone levels at 200 mg/kg without affecting adrenocorticotropic hormone level. Further study showed that BDE3 up-regulated at 100 and 200 mg/kg and , , , , and mRNA levels in the 200 mg/kg group. BDE3 also decreased the phosphorylation of AMP-activated protein kinase (AMPK) at 200 mg/kg and increased PGC-1α and phosphorylated cyclic AMP-responsive element-binding protein (CREB)/CREB at 200 mg/kg. Taken together, these findings demonstrate that BDE3 stimulates adrenal cell function likely through decreasing phosphorylation of AMPK and increasing phosphorylation of CREB.
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http://dx.doi.org/10.1021/acs.chemrestox.9b00123DOI Listing
September 2019

Human placental 3β-hydroxysteroid dehydrogenase/steroid Δ5,4-isomerase 1: Identity, regulation and environmental inhibitors.

Toxicology 2019 09 25;425:152253. Epub 2019 Jul 25.

Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Anesthesiology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address:

Human placental 3β-hydroxysteroid dehydrogenase/steroid Δ5, 4-isomerase 1 (HSD3B1), a high-affinity type I enzyme, uses pregnenolone to make progesterone, which is critical for maintenance of pregnancy. HSD3B1 is located in the mitochondrion and the smooth endoplasmic reticulum of placental cells and is encoded by HSD3B1 gene. HSD3B1 contains GATA and TEF-5 regulatory elements. Many endocrine disruptors, including phthalates, methoxychlor and its metabolite, organotins, and gossypol directly inhibit placental HSD3B1 thus blocking progesterone production. In this review, we discuss the placental HSD3B1, its gene regulation, biochemistry, subcellular location, and inhibitors from the environment.
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http://dx.doi.org/10.1016/j.tox.2019.152253DOI Listing
September 2019

Evaluation of GALNT16 polymorphisms to breast cancer risk in Chinese population.

Mol Genet Genomic Med 2019 08 8;7(8):e848. Epub 2019 Jul 8.

Surgical Oncology, The Second Affiliated Hospital of Hainan Medical College, Haikou, Hainan Province, China.

Background: Polypeptide N-acetylgalactosaminyltransferase 16 (GALNT16) is an N-acetylgalactosaminyltransferase gene that alters protein O-glycosylation, which plays a role in tumor development. This study aims to explore the association of eight GALNT16 polymorphisms with susceptibility to breast cancer (BC).

Methods: This case-control study included 563 BC patients and 552 age-matched healthy controls from the Chinese Han population. The genotypes of GALNT16 polymorphisms were detected using the Agena MassARRAY. The relationship between GALNT16 polymorphisms and BC risk was evaluated using a chi-squared test with an odds ratio (OR) and 95% confidence intervals (CI) under five genetic models.

Results: We observed that rs2105269 and rs72625676 were associated with higher BC risk in younger patients with age ≤51 (rs2105269, codominant: p = .006; recessive: p = .005 additive: p = .018; and allele: p = .012; rs72625676, codominant: p = .038; recessive: p = .037). For rs1275678 polymorphism, there was a significantly decreased risk of BC among elder patients (codominant: p = .017; dominant: p = .019; additive: p = .030; and allele: p = .029). Further analysis by clinical characteristics showed rs2105269 was associated with tumor size and lymph node metastasis.

Conclusion: Our study suggests that GALNT16 polymorphisms are associated with BC susceptibility in Chinese population.
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http://dx.doi.org/10.1002/mgg3.848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687646PMC
August 2019

Characterization of a novel anti-human lymphocyte activation gene 3 (LAG-3) antibody for cancer immunotherapy.

MAbs 2019 Aug/Sep;11(6):1139-1148. Epub 2019 Jun 26.

a Central Laboratory, Navy General Hospital of PLA , Beijing , China.

Lymphocyte activation gene 3 (LAG-3) is expressed on activated T cells, natural killer cells or B cells, and functions to negatively regulate homeostasis of these cells. Anti-LAG-3 antibodies might be useful for antitumor immunotherapy. In this study, we characterized a novel anti-LAG-3 antibody, LBL-007, which was isolated from a human antibody phage display library. LBL-007 was found to specifically bind to human LAG-3 antigen, but not to human CD4 or mouse LAG-3. LBL-007 bound activated T cells and promoted interleukin-2 secretion. LBL-007 internalization efficacy by endocytosis into different cells was better than that of another anti-LAG-3 antibody, relatlimab analog. Moreover, LBL-007 was able to block LAG-3 binding to MHC class II molecules and liver sinusoidal endothelial cell lectin, and block LAG-3-induced downstream signaling. In mice transplanted with colorectal cancer cells, treatment with either anti-PD-1 antibody or LBL-007 (10 mg/kg per mouse twice a week for three weeks) resulted in a significant delay in tumor growth compared with control IgG treatment, and their combination was even more effective. Serum LBL-007 levels were highly stable in monkeys after a single intravenous injection of LBL-007 at 3, 10, or 30 mg/kg. This study demonstrated that the combination of LBL-007 with an anti-PD-1 antibody is a promising antitumor regimen for immunotherapy of solid tumors in future that deserves further study.
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http://dx.doi.org/10.1080/19420862.2019.1629239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748621PMC
January 2020

Analysis of MIR155HG variants and colorectal cancer susceptibility in Han Chinese population.

Mol Genet Genomic Med 2019 08 22;7(8):e778. Epub 2019 Jun 22.

Surgical Oncology, The Second Affiliated Hospital of Hainan Medical College, Haikou, Hainan Province, China.

Background: MIR155HG plays an important role in malignant tumors, but it is rarely reported in the occurrence and development of colorectal cancer (CRC). This study investigated the effects of MIR155HG polymorphisms on CRC susceptibility from the perspective of molecular genetics.

Methods: Eight SNPs in MIR155HG were selected and genotyped among 514 CRC cases and 510 healthy controls using the Agena MassARRAY platform. The associations between these SNPs and the CRC risk were evaluated under genetic models using conditional logistic regression analysis. The HaploReg v4.1 database was used for SNPs functional prediction.

Results: The allele "C" of rs12482371 (p = 0.047), allele "C" of rs1893650 (p = 0.025), and the allele "A" of rs928883 (p = 0.037) in MIR155HG were significantly associated with CRC risk. Genetic model analysis revealed that rs12482371 and rs1893650 increased CRC risk; whereas rs928883 was associated with reduced CRC risk. Stratification analysis showed that rs9383938 was a protective factor in CRC patients under 60 years old. Rs12482371 and rs1893650 were associated with the CRC risk in females. Rs11911469 and rs34904192 may affect the clinical stage and lymph node metastasis. Moreover, the haplotypes CTT and GTC of LD block rs4143370|rs77218221|rs12482371, and the haplotypes CATGA and CACGG of LD block rs77699734|rs11911469|rs1893650|rs34904192|rs928883 were significantly associated with CRC risk.

Conclusion: This study revealed that MIR155HG SNPs were associated with CRC susceptibility and could be predictive biomarkers for CRC risk.
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http://dx.doi.org/10.1002/mgg3.778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687631PMC
August 2019

Fibroblast growth factor homologous factor 1 stimulates Leydig cell regeneration from stem cells in male rats.

J Cell Mol Med 2019 08 20;23(8):5618-5631. Epub 2019 Jun 20.

Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Fibroblast growth factor homologous factor 1 (FHF1) is an intracellular protein that does not bind to cell surface fibroblast growth factor receptor. Here, we report that FHF1 is abundantly present in Leydig cells with up-regulation during its development. Adult male Sprague Dawley rats were intraperitoneally injected with 75 mg/kg ethane dimethane sulphonate (EDS) to ablate Leydig cells to initiate their regeneration. Then, rats daily received intratesticular injection of FHF1 (0, 10 and 100 ng/testis) from post-EDS day 14 for 14 days. FHF1 increased serum testosterone levels without affecting the levels of luteinizing hormone and follicle-stimulating hormone. FHF1 increased the cell number staining with HSD11B1, a biomarker for Leydig cells at the advanced stage, without affecting the cell number staining with CYP11A1, a biomarker for all Leydig cells. FHF1 did not affect PCNA-labelling index in Leydig cells. FHF1 increased Leydig cell mRNA (Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, Insl3, Nr5a1 and Hsd11b1) and their protein levels in vivo. FHF1 increased preadipocyte biomarker Dlk1 mRNA level and decreased fully differentiated adipocyte biomarker (Fabp4 and Lpl) mRNA and their protein levels. In conclusion, FHF1 promotes Leydig cell regeneration from stem cells while inhibiting the differentiation of preadipocyte/stem cells into adipocytes in EDS-treated testis.
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http://dx.doi.org/10.1111/jcmm.14461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6653537PMC
August 2019

Aflatoxin B1 impairs leydig cells through inhibiting AMPK/mTOR-mediated autophagy flux pathway.

Chemosphere 2019 Oct 1;233:261-272. Epub 2019 Jun 1.

Center of Scientific Research, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; The Second Clinical Medical School of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address:

Aflatoxin B1 (AFB1), a potential endocrine disrupter, has been shown to induce hepatotoxicity in animal models, but the effects of AFB1 on Leydig cell function are unclear. In this study, in vivo exposure to AFB1 at 15 and 150 μg/kg/day lowered serum testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels, reduced Leydig cell number, and down-regulated the expression of testosterone biosynthesis-related genes. In vitro study showed that AFB1 (10 μM) significantly increased ROS levels, and decreased T production in Leydig cells by suppressing certain T-biosynthesis gene expressions. Moreover, AFB1 induced Leydig cell apoptosis through lowering pAMPK/AMPK ratio and increasing pmTOR/mTOR ratio, and then further up-regulating autophagy and apoptosis proteins, LC3, BECLIN 1, and BAX, as well as down-regulating autophagy flux protein P62 and anti-apoptosis protein BCL-2. AFB1-induced toxicity in Leydig cells was characterized by inhibiting T-biosynthesis gene expression, reducing Leydig cell number, promoting ROS production, and inducing cell apoptosis via suppressing AMPK/mTOR-mediated autophagy flux pathway.
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http://dx.doi.org/10.1016/j.chemosphere.2019.05.273DOI Listing
October 2019

Pubertal exposure to tebuconazole increases testosterone production via inhibiting testicular aromatase activity in rats.

Chemosphere 2019 Sep 15;230:519-526. Epub 2019 May 15.

Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China. Electronic address:

Tebuconazole is a triazole compound used agriculturally to treat plant pathogenic fungi. However, whether pubertal exposure to tebuconazole affects Leydig cell development remains unknown. Here, we exposed male Sprague-Dawley rats at 35 days of age to 0, 25, 50, or 100 mg kg day tebuconazole for 21 days. Tebuconazole exposure increased serum testosterone level but lowered estradiol level at a dose of 100 mg kg, without affecting serum luteinizing hormone and follicle-stimulating hormone concentrations. Tebuconazole up-regulated the expression of testicular Cyp11a1, Hsd11b1, and Fshr genes as well as their proteins at a dose of 100 mg kg. However, tebuconazole did not stimulate the proliferation of Leydig cells. Tebuconazole in vitro inhibits aromatase activity in primary rat Leydig cells with IC value of 40 μmol/L. In conclusion, tebuconazole exposure stimulates pubertal Leydig cell differentiation via inhibiting aromatase activity.
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http://dx.doi.org/10.1016/j.chemosphere.2019.05.122DOI Listing
September 2019

Mir-26b inhibits growth and resistance to paclitaxel chemotherapy by silencing the CDC6 gene in gastric cancer.

Arch Med Sci 2019 Mar 7;15(2):498-503. Epub 2018 Feb 7.

Department of Surgical Oncology, First Affiliated Hospital, China Medical University, Shenyang, China.

Introduction: Gastric cancer is one of the most common cancers of the digestive system and is associated with high morbidity and mortality. The aim of this study was to investigate whether miR-26b is involved in the proliferation and resistance to paclitaxel chemotherapy in gastric cancer cells.

Material And Methods: The expression of miR-26b in gastric cancer cell lines was determined by quantitative real-time PCR. Bioinformatics software was used to predict potential target genes of miR-26b. Luciferase assay was used to verify the interactions between target genes and miR-26b. CDC6 protein expression was measured by Western blot. The proliferation and chemotherapy resistance were analyzed by MTT assay. Cell invasion was evaluated by Transwell assay.

Results: MiR-26b was down-regulated in gastric cancer cell lines compared to normal control cells, and its expression in drug resistance cells was even lower ( < 0.05). CDC6 was identified as a potential target gene of miR-26b by using bioinformatics analysis software. The expression of CDC6 was inhibited by miR-26b both at RNA level, which was determined by luciferase assay, and at protein level, which was determined by Western blot ( < 0.05). Silencing CDC6 inhibited cell proliferation, invasion, and promoted apoptosis of gastric cancer cell lines, BGC823 and SGC7901 ( < 0.05). Moreover, CDC6 knockdown inhibited chemotherapy resistance to paclitaxel, IC50 to paclitaxel decreased from 153.17 ±0.49 μg/l to 39.81 ±0.28 μg/l ( < 0.05).

Conclusions: miR-26b inhibits growth and resistance to paclitaxel chemotherapy by silencing the CDC6 gene in the gastric cancer cell line SGC7901.
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http://dx.doi.org/10.5114/aoms.2018.73315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425209PMC
March 2019

Stem Leydig cell regeneration in the adult rat testis is inhibited after a short-term triphenyltin exposure.

Toxicol Lett 2019 May 15;306:80-89. Epub 2019 Feb 15.

Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. Electronic address:

Triphenyltin (TPT) is an organotin compound and may be an endocrine disruptor, impairing the male reproductive system. However, the effect of short-term TPT exposure on stem Leydig cell regeneration later on remains unknown. Here, we show that TPT affects stem Leydig cell regeneration in the adult rat testis. Adult male Sprague Dawley rats were gavaged with TPT (0, 0.5, 1.0, 2.0 mg/kg body weight/day) for 10 days, followed by a single intraperitoneal injection of ethane dimethane sulfonate (EDS, 75 mg/kg body weight) to eliminate Leydig cells. Testis parameters and hormone levels were investigated on post-EDS days 21, 35, and 56. TPT significantly reduced serum testosterone levels, decreased Leydig cell number and cell size, and down-regulated its specific gene and protein expression at 1.0 and 2.0 mg/kg even 56 days after cession of treatment. TPT lowered PCNA-labeling index of progenitor Leydig cells on post-EDS day 21. TPT also lowered AKT1 and AKT2, and ERK1/2 phosphorylation on post-EDS day 56. This study reveals that a short-term exposure to TPT blocks stem Leydig cell regeneration in the long term thus delaying spermatogenesis.
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http://dx.doi.org/10.1016/j.toxlet.2019.02.010DOI Listing
May 2019

In utero exposure to bisphenol A disrupts fetal testis development in rats.

Environ Pollut 2019 Mar 7;246:217-224. Epub 2018 Dec 7.

Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang, 325027, China. Electronic address:

Bisphenol A (BPA) is widely used in consumer products and is a potential endocrine disruptor linked with abnormal development of male reproductive tract. However, its action and its effects on the pathways in the development of male gonad are still unclear. Here we report that effects of BPA exposure during gestation on male gonad development. Sprague-Dawley rats were gavaged daily with BPA (0, 4, 40, and 400 mg/kg body weight) from gestational day 12 to day 21. BPA dose-dependently decreased serum testosterone levels (0.45 ± 0.08 ng/ml and 0.32 ± 0.08 ng/ml for 40 and 400 mg/kg BPA, respectively) versus the control level (1.11 ± 0.22 ng/ml, Mean ± SE). BPA lowered Leydig cell Insl3 and Hsd17b3 mRNA and their protein levels at doses of 40 and 400 mg/kg. BPA also lowered Leydig cell (Lhcgr, Cyp11a1, and Cyp17a1) and Sertoli cell (Amh) mRNA and their protein levels at 400 mg/kg. BPA decreased fetal Leydig cell number via inhibiting their proliferation, but it did not affect fetal Sertoli cell number. In conclusion, the current study shows that in utero exposure to BPA inhibits fetal Leydig and Sertoli cell differentiation, possibly disrupting the development of male reproductive tract.
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http://dx.doi.org/10.1016/j.envpol.2018.12.006DOI Listing
March 2019

Perfluorododecanoic Acid Blocks Rat Leydig Cell Development during Prepuberty.

Chem Res Toxicol 2019 01 24;32(1):146-155. Epub 2018 Dec 24.

Perfluorododecanoic acid (PFDoA) has been used as a surfactant and may have reproductive toxicity. However, whether PFDoA influences Leydig cell development during prepuberty remains unknown. In the present study, 21-day-old male Sprague-Dawley rats were gavaged 0, 5, or 10 mg/kg PFDoA from postnatal day 21 to 35. PFDoA decreased the serum concentrations of testosterone, luteinizing hormone, and follicle-stimulating hormone at doses of 5 and 10 mg/kg without influencing Leydig cell number and proliferation. However, PFDoA down-regulated the expression of Leydig cell genes ( Lhcgr, Scarb1, Star, Cyp11a1, Cyp17a1, and Hsd11b1) or their proteins. PFDoA dose-dependently reduced SIRT1 and PGC-1α levels. PFDoA did not affect AMPK and AKT2 levels but decreased their phosphorylation. We also treated primary progenitor Leydig cells purified from prepubertal rat testes with PFDoA for 24 h. It in vitro lowered viability and decreased mitochondrial membrane potential of progenitor Leydig cells, but it stimulated the generation of the intracellular reactive oxygen species and induced Leydig cell apoptosis at 10 μM. In conclusion, PFDoA blocks rat Leydig cell development during the prepubertal period possibly via targeting AMPK/SIRT1/PGC-1α and AKT2 signaling pathways.
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http://dx.doi.org/10.1021/acs.chemrestox.8b00241DOI Listing
January 2019

In utero exposure to triphenyltin disrupts rat fetal testis development.

Chemosphere 2018 Nov 8;211:1043-1053. Epub 2018 Aug 8.

Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China. Electronic address:

Triphenyltin is an organotin that is widely used as an anti-fouling agent and may have endocrine-disrupting effects. The objective of the current study was to investigate effects of triphenyltin on the development of rat fetal testis. Female pregnant Sprague Dawley dams were gavaged daily with triphenyltin (0, 0.5, 1, and 2 mg/kg body weight/day) from gestational day 12 to day 21. Triphenyltin dose-dependently decreased serum testosterone levels (0.971 ± 0.072 and 0.972 ± 0.231 ng/ml at 1 and 2 mg/kg, respectively) from control level (2.099 ± 0.351 ng/ml). Triphenyltin at 1 and 2 mg/kg doses also induced fetal Leydig cell aggregation, decreased fetal Leydig cell size and cytoplasmic size. Triphenyltin decreased the expression levels of Lhcgr, Scarb1, Star, Cyp11a1, Cyp17a1, Insl3, Fshr, Pdgfa, and Sox9 by 0.5 mg/kg dose and above. However, triphenyltin did not affect Leydig and Sertoli cell numbers. In conclusion, the current study indicated that in utero exposure of triphenyltin disrupted fetal Leydig and Sertoli cell development.
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http://dx.doi.org/10.1016/j.chemosphere.2018.08.016DOI Listing
November 2018

4-Bromodiphenyl ether delays pubertal Leydig cell development in rats.

Chemosphere 2018 Nov 8;211:986-997. Epub 2018 Aug 8.

Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. Electronic address:

Polybrominated diphenyl ethers are a class of brominated flame retardants that are potential endocrine disruptors. 4-Bromodiphenyl ether (BDE-3) is the most abundant photodegradation product of higher polybrominated diphenyl ethers. However, whether BDE-3 affects Leydig cell development during puberty is still unknown. The objective of this study was to explore effects of BDE-3 on the pubertal development of rat Leydig cells. Male Sprague Dawley rats (35 days of age) were gavaged daily with BDE-3 (0, 50, 100, and 200 mg/kg body weight/day) for 21 days. BDE-3 decreased serum testosterone levels (1.099 ± 0.412 ng/ml at a dose of 200 mg/kg BDE-3 when compared to the control level (2.402 ± 0.184 ng/ml, mean ± S.E.). BDE-3 decreased Leydig cell size and cytoplasmic size at a dose of 200 mg/kg, decreased Lhcgr, Star, Dhh, and Sox9 mRNA levels at ≥ 100 mg/kg and Scarb1, Cyp11a1, Hsd17b3, and Fshr at 200 mg/kg. BED-3 also decreased the phosphorylation of AKT1, AKT2, ERK1/2, and AMPK at 100 or 200 mg/kg. BDE-3 in vitro induced ROS generation, inhibited androgen production, down-regulated Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Srd5a1, and Akr1c14 expression in immature Leydig cells after 24-h treatment. In conclusion, the current study indicates that BDE-3 disrupts Leydig cell development via suppressing AKT, ERK1/2, and AMPK phosphorylation and inducing ROS generation.
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http://dx.doi.org/10.1016/j.chemosphere.2018.08.008DOI Listing
November 2018

Lambda-cyhalothrin delays pubertal Leydig cell development in rats.

Environ Pollut 2018 Nov 11;242(Pt A):709-717. Epub 2018 Jul 11.

The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang 325027, China. Electronic address:

Lambda-cyhalothrin (LCT) is a widely used broad-spectrum pyrethroid insecticide and is expected to cause deleterious effects on the male reproductive system. However, the effects of LCT on Leydig cell development during puberty are unclear. The current study addressed these effects. Twenty-eight-day-old male Sprague Dawley rats orally received LCT (0, 0.25, 0.5 or 1 mg/kg body weight/day) for 30 days. The levels of serum testosterone, luteinizing hormone, and follicle-stimulating hormone, Leydig cell number, and its specific gene and protein expression were determined. LCT exposure lowered serum testosterone levels at doses of 0.5 and 1 mg/kg and luteinizing hormone levels at a dose of 1 mg/kg, but increased follicle-stimulating hormone levels at doses of 0.5 and 1 mg/kg. LCT lowered Star and Hsd3b1 mRNA or their protein levels at a dose of 1 mg/kg. Immature Leydig cells were purified from pubertal rats and treated with different concentrations of LCT for 24 h and medium androgen levels, Leydig cell mRNA and protein levels, the mitochondrial membrane potential (△Ψm), and the apoptotic rate of immature Leydig cells were investigated. LCT inhibited androgen production at 5 μM and downregulated Scarb1 at 0.05 μM, Hsd3b1 and Hsd11b1 at 0.5 μM, and Cyp11a1 at 5 μM. LCT also decreased △Ψm at 0.5 and 50 μM. In conclusion, LCT can influence the function of Leydig cells.
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http://dx.doi.org/10.1016/j.envpol.2018.07.033DOI Listing
November 2018

Anatomical location of metastatic lymph nodes: an indispensable prognostic factor for gastric cancer patients who underwent curative resection.

Scand J Gastroenterol 2018 Feb 11;53(2):185-192. Epub 2017 Dec 11.

a Department of Surgical Oncology , First Affiliated Hospital of China Medical University , Shenyang , P.R. China.

Background: Although the numeric-based lymph node (LN) staging was widely used in the worldwide, it did not represent the anatomical location of metastatic lymph nodes (MLNs) and not reflect extent of LN dissection. Therefore, in the present study, we investigated whether the anatomical location of MLNs was still necessary to evaluate the prognosis of node-positive gastric cancer (GC) patients.

Methods: We reviewed 1451 GC patients who underwent radical gastrectomy in our institution between January 1986 and January 2008. All patients were reclassified into several groups according to the anatomical location of MLNs and the number of MLNs. The prognostic differences between different patient groups were compared and clinicopathologic features were analyzed.

Results: In the present study, both anatomical location of MLNs and the number of MLNs were identified as the independent prognostic factors (p < .01). The patients with extraperigastric LN involvement showed a poorer prognosis compared with the perigastric-only group (p < .001). For the N1-N2 stage patients, the prognostic discrepancy was still observed among them when the anatomical location of MLNs was considered (p < .05). For the N3-stage patients, although the anatomical location of MLNs had no significant effect on the prognosis of these patients, the higher number of MLNs in the extraperigastric area was correlated with the unfavorable prognosis (p < .05).

Conclusion: The anatomical location of MLNs was an important factor influencing the prognostic outcome of GC patients. To provide more accurate prognostic information for GC patients, the anatomical location of MLNs should not be ignored.
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http://dx.doi.org/10.1080/00365521.2017.1415371DOI Listing
February 2018
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