Publications by authors named "Xiaoyan Fu"

92 Publications

Predicting the postoperative blood coagulation state of children with congenital heart disease by machine learning based on real-world data.

Transl Pediatr 2021 Jan;10(1):33-43

Department of Transfusion Medicine, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Background: Postoperative blood coagulation assessment of children with congenital heart disease (CHD) has been developed using a conventional statistical approach. In this study, the machine learning (ML) was used to predict postoperative blood coagulation function of children with CHD, and assess an array of ML models.

Methods: This was a retrospective and data mining study. Based on the samples of 1,690 children with CHD, and screening data based on demographic characteristics, conventional coagulation tests (CCTs) and complete blood count (CBC), with a precise data selection process, and the support of data mining and ML algorithms including Decision tree, Naive Bayes, Support Vector Machine (SVM), Adaptive Boost (AdaBoost) and Random Forest model, and explored the best prediction models of postoperative blood coagulation function for children with CHD by models performance measured in the area under the receiver operating characteristic (ROC) curve (AUC), calibration or Lift curves, and further verified the reliability of the models with statistical tests.

Results: In primary objective prediction, as decision tree, Naive Bayes, SVM, the AUC of our prediction algorithm was 0.81, 0.82, 0.82, respectively. The accuracy rate of the overall forecast has reached more than 75%. Subsequently, we furtherly build improved models. Among them, the true positive rate of the AdaBoost, Random Forest and SVM prediction models reached more than 80% in the ROC curve. These overall accuracy rate indicated a good classification model. Combined calibration curves and Lift curves, the better fit is the SVM model, which predicted postoperative abnormal coagulation, Lift =2.2, postoperative normal coagulation, Lift =1.8. The statistical results furtherly proved the reliability of ML models. The age, sex, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood cell count (WBC) and platelet count (PLT) were the key features for predicting the postoperative blood coagulation state of children with CHD.

Conclusions: ML technology and data mining algorithms may be used for outcome prediction in children with CHD for postoperative blood coagulation state based on the bulk of clinical data, especially CBC indictors from the real world.
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http://dx.doi.org/10.21037/tp-20-238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882284PMC
January 2021

Pinoresinol diglucoside (PDG) attenuates cardiac hypertrophy via AKT/mTOR/NF-κB signaling in pressure overload-induced rats.

J Ethnopharmacol 2021 May 16;272:113920. Epub 2021 Feb 16.

School of Nursing, PR China. Electronic address:

Ethnopharmacological Relevance: Pinoresinol diglucoside (PDG), the active compound extracted from Eucommia ulmoides, Styrax sp. and Forsythia suspensa, plays the roles in regulating hypertension, inflammation and oxidative stress.

Aims: Considering that hypertension and inflammation has been proved to contribute to cardiac remodeling, we tested the effects of PDG on cardiac hypertrophy (CM).

Methods: Male Sprague Dawley (SD) rats were used to construct hypertrophic rats by partial abdominal aortic constriction (AAC)-surgery. PDG solution (2 mg/ml) was used to treat AAC-induced rats by intraperitoneal injection at low dose (L-PDG, 2.5 mg/kg per day), medium dose (M-PDG, 5 mg/kg per day), and high dose (H-PDG, 7.5 mg/kg per day) for 3 weeks post AAC-surgery. CM was evaluated by the ratio of left ventricular weight to body weight ratio (LVW/BW), left ventricular wall thickness by H&E staining, and collagen content deposit by Masson's staining. Further, isoproterenol (ISO) and phenylephrine (PE) were used to produce cellular models of CM in neonatal rat ventricular cardiomyocytes (NRVMs). PDG pre-treated NRVMs 2 h at low dose (L-PDG, 2.5 μg/ml), medium dose (M-PDG, 5 μg/ml), and high dose (H-PDG, 7.5 μg/ml) for 24 h with or without PE- and ISO-stimulation. CM was evaluated by the expressions of hypertrophic biomarkers. Next, the hypertrophic biomarkers and pro-inflammatory cytokines were measured using quantitative real-time PCR (qRT-PCR), the expressions of protein kinase B (AKT)/mammalian target of rapamycin (mTOR)/transcription factor nuclear factor-kappa B (NF-kB) signaling pathway were determined by Western blotting.

Results: PDG treatment prevented cardiac histomorphology damages, decreased upregulations of hypertrophic biomarkers, and prevented fibrosis and inflammation after pressure overload resulting from AAC-surgery. Consistently, PDG remarkably inhibited the changes of cardiomyocyte hypertrophic biomarkers and inflammatory responses in cellular models of CM. Interestingly, PDG administration inhibited the activation of AKT/mTOR/NF-kB signaling pathway both in vivo and in vitro.

Conclusions: PDG prevents AAC-induced CM in vivo, PE- and ISO-induced CM in vitro. The AKT/mTOR/NF-kB signaling pathway could be the potential therapeutic target involved in the protection of PDG. These findings provide novel evidence that PDG might be a promising therapeutic strategy for CM.
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http://dx.doi.org/10.1016/j.jep.2021.113920DOI Listing
May 2021

Licochalcone A Attenuates Chronic Neuropathic Pain in Rats by Inhibiting Microglia Activation and Inflammation.

Neurochem Res 2021 May 8;46(5):1112-1118. Epub 2021 Feb 8.

Department of Rehabilitation, the Second Hospital, Cheeloo College of Medicine, Shandong University, No. 247, Beiyuan Avenue, Jinan, 250033, Shandong, China.

Immune response plays a vital role in the pathogenesis of neuropathic pain. Immune response-targeted therapy becomes an effective strategy for treating neuropathic pain. Licochalcone A (Lic-A) possesses anti-inflammatory and neuroprotective effects. However, the potential of Lic-A to attenuate neuropathic pain has not been well explored. To investigate the protective effect and evaluate the underlying mechanism of Lic-A against neuropathic pain in a rat model. Chronic constriction injury (CCI) surgery was employed in rats to establish neuropathic pain model. Rats were intraperitoneally administrated with Lic-A (1.25, 2.50 and 5.00 mg/kg) twice daily. Mechanical withdrawal threshold and thermal withdrawal latency were used to evaluate neuropathic pain. After administration, the lumbar spinal cord enlargement of rats was collected for ELISA, Western blot and immunofluorescence analysis. Mechanical withdrawal threshold and thermal withdrawal latency results showed that Lic-A significantly attenuated CCI-evoked neuropathic pain in dose-dependent manner. Lic-A administration also effectively blocked microglia activation. Moreover, Lic-A suppressed p38 phosphorylation and the release of inflammatory factors such as tumor necrosis factor-α, interleukin-1 and interleukin-6. Our findings provide evidence that Lic-A may have the potential to attenuate CCI-evoked neuropathic pain in rats by inhibiting microglia activation and inflammatory response.
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http://dx.doi.org/10.1007/s11064-021-03244-xDOI Listing
May 2021

Neuroglobin alleviates arsenic-induced neuronal damage.

Environ Toxicol Pharmacol 2021 May 2;84:103604. Epub 2021 Feb 2.

Center for Endemic Disease Control, Harbin Medical University, Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin, 150081, China. Electronic address:

People who drink water contaminated with arsenic for a long time develop neuritis, cerebellar symptoms, and deficits in memory and intellectual function. Arsenic induces oxidative stress and promotes apoptosis through multiple signalling pathways in nerve cells. Neuroglobin (Ngb), as a key mediator, is considered to be protective against oxidative stress. In this study, we aimed to study the effects of Ngb knockdown in arsenite-treated rat neurons on levels of apoptosis markers and reactive oxygen species and serum Ngb levels of subjects from arsenic-endemic regions in China. We discovered that arsenic-induced apoptosis and reactive oxygen species production were enhanced in Ngb-knocked-down rat neurons. Silencing of Ngb aggravated the arsenic-induced decrease in the rate of Bcl-2/Bax and the levels of Bcl-2 protein following arsenite treatment. The results also showed that serum Ngb levels were independently negatively correlated with arsenic concentration in drinking water. Furthermore, the serum Ngb levels of four groups (245 individuals) according to different degree exposure to arsenic were 815.18 ± 89.52, 1247.97 ± 117.18, 774.79 ± 91.55, and 482.72 ± 49.30 pg/mL, respectively. Taken together, it can be deduced that Ngb has protective effects against arsenic-induced apoptosis by eliminating reactive oxygen species.
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http://dx.doi.org/10.1016/j.etap.2021.103604DOI Listing
May 2021

Long non-coding RNA MAFG-AS1 knockdown blocks malignant progression in breast cancer cells by inactivating JAK2/STAT3 signaling pathway via MAFG-AS1/miR-3196/TFAP2A axis.

Int J Clin Exp Pathol 2020 1;13(10):2455-2473. Epub 2020 Oct 1.

Department of Laboratory Animals Center, Jinhua Institute for Food and Drug Control Jinhua, Zhejiang, China.

Background: Breast cancer is still a leading threat to women's lives. Long non-coding RNAs (lncRNA) associated with cancer progression are getting attention. The objective of this study was to investigate the role of lncRNA MAFG-antisense 1 (MAFG-AS1) and mechanisms of action in breast cancer.

Methods: The expression of MAFG-AS1, microRNA-3196 (miR-3196) and transcription factor AP-2 alpha (TFAP2A) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The cell proliferation was assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The number of colonies was observed through colony formation assay. The protein levels of Cyclin D1, Ki67, Bcl-2 associated X protein (Bax), B-cell lymphoma2 (Bcl-2), Hexokinase II (HK2), lactate dehydrogenase A (LDHA), TFAP2A, Janus kinase 2 (JAK2), phosphorylated-JAK2 (p-JAK2), signal transducer and activator of transcription 3 (STAT3), and phosphorylated-STAT3 were quantified by western blot. The cell apoptosis was monitored using flow cytometry. The glycolysis progression was evaluated according to glucose consumption and lactate production. The relationship between miR-3196 and MAFG-AS1 or TFAP2A was predicted by the online tool starBase and verified by the dual-luciferase reporter assay. The role of MAFG-AS1 was determined by the tumor formation assay in nude mice.

Results: MAFG-AS1 was highly expressed in tumor tissues and cells. MAFG-AS1 knockdown restrained proliferation, colony formation, and glycolysis but promoted apoptosis of breast cancer cells. MiR-3196 was a target of MAFG-AS1, and its inhibition reversed the role of MAFG-AS1 knockdown. TFAP2A was a target of miR-3196, and its overexpression abolished the effects of miR-3196 reintroduction. MAFG-AS1 knockdown suppressed the activity of the JAK2/STAT3 signaling pathway. Moreover, MAFG-AS1 knockdown reduced tumor growth .

Conclusion: MAFG-AS1 knockdown attenuated breast cancer progression and through activation of the JAK2/STAT3 signaling pathway by the MAFG-AS1/miR-3196/TFAP2A regulatory axis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642707PMC
October 2020

CUMS Promotes the Development of Premature Ovarian Insufficiency Mediated by Nerve Growth Factor and Its Receptor in Rats.

Biomed Res Int 2020 30;2020:1946853. Epub 2020 Jun 30.

Medical Molecular Biology Laboratory, Medical College, Jinhua Polytechnic, Jinhua, Zhejiang Province, China.

This study aimed to investigate whether chronic unpredictable mild stress (CUMS) affects follicular development in ovaries through the nerve growth factor (NGF)/high affinity nerve growth factor receptor, the Tropomyosin-related kinase A (TrkA) receptor, mediated signaling pathway and to reveal the relationship between chronic stress and premature ovarian insufficiency (POI) development. In this experiment, a CUMS rat model was constructed. It was found that serum estradiol (E2), anti-Mullerian hormone (AMH), and gonadotropin-releasing hormone (GnRH) levels decreased, while follicle-stimulating hormone (FSH) levels increased. The expression of NGF, TrkA, p75, and FSHR in ovarian tissue decreased significantly. The expression levels of TrkA and p75 protein in ovarian stroma and small follicles were observed by an immunofluorescence assay. In addition, the numbers of small follicles were significantly reduced. The expression of TrkA, p75, and FSHR in CUMS ovarian tissue was upregulated by exogenous NGF . Furthermore, after treatment with NGF combined with FSH, E2 secretion in ovarian tissue culture supernatant of CUMS rats also increased significantly. Therefore, CUMS downregulates NGF and TrkA and promotes the occurrence of POI in rats. Exogenous NGF and FSH can upregulate the NGF receptor, E2, and AMH , and improve the rat ovarian function. Future studies may associate these results with female population.
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http://dx.doi.org/10.1155/2020/1946853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345596PMC
April 2021

X-ray recharged long afterglow luminescent nanoparticles MgGeO:Mn,Yb,Li in the first and second biological windows for long-term bioimaging.

Nanoscale 2020 Jul 24;12(26):14037-14046. Epub 2020 Jun 24.

Key Lab of Urban Pollutant Conversion, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, China.

In this paper, we have designed long afterglow luminescent MgGeO:Mn,Yb,Li (MGO) nanoparticles in the first (NIR-I) and second (NIR-II) biological windows. Yb ions served not only as the trap center to enhance the NIR-I long afterglow emission of Mn at 680 nm, but also as an emitting center to produce a NIR-II long afterglow emission at ∼1000 nm. Furthermore, we have found the addition of Li can greatly increase the NIR-II afterglow emission of Yb and the optimal amount of Mn, Yb and Li was found to be 0.1, 0.5 and 0.5 mol%, respectively. The MGO nanoparticles synthesized using sol-gel methods showed a uniform morphology with a diameter of 50-100 nm, which were suitable for applications in bioimaging. More importantly, we have found MGO nanoparticles can be effectively excited to produce long persistent NIR-I and II luminescence using soft X-rays, suggesting that low dosage soft X-rays can also serve as a more powerful and deep tissue excitation source to recharge MGO nanoparticles. Furthermore, the MGO nanoparticles can also be re-excited to produce photo-stimulated emission under the irradiation of 650 and 808 nm NIR lasers. The in vivo imaging results have shown that MGO nanoparticles modified with folic acid (FA) can effectively realize super long-term targeted in vivo imaging of inflammation with a high sensitivity via recharging using soft X-rays and NIR lasers, which can provide not only an accurate diagnosis of inflammation, but also long-term monitoring of possible changes in the focus of inflammation in real time.
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http://dx.doi.org/10.1039/c9nr10622gDOI Listing
July 2020

Erratum to "Tetrandrine Ameliorates Airway Remodeling of Chronic Asthma by Interfering TGF-1/Nrf-2/HO-1 Signaling Pathway-Mediated Oxidative Stress".

Can Respir J 2020 21;2020:6958283. Epub 2020 Feb 21.

Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China.

[This corrects the article DOI: 10.1155/2019/7930396.].
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http://dx.doi.org/10.1155/2020/6958283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150693PMC
February 2020

Pigment epithelium-derived factor (PEDF) ameliorates arsenic-induced vascular endothelial dysfunction in rats and toxicity in endothelial EA.hy926 cells.

Environ Res 2020 07 12;186:109506. Epub 2020 Apr 12.

Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin, 150081, China. Electronic address:

Although the harmful effects of arsenic exposure on the cardiovascular system have received great attention, there is still no effective treatment. Vascular endothelial dysfunction (VED) is the initial step of cardiovascular diseases, where pigment epithelium-derived factor (PEDF) plays an important role in maintaining endothelial function. Here, we explored the protective role of PEDF in VED induced by arsenic, and its underlying molecular mechanism, designing an in vivo rat model of arsenic exposure recovery and in vitro endothelial EA. hy926 cell-based assays. The edema of aortic endothelial cells in rats significantly improved during recovery from arsenite exposure compared with rats exposed to 10 and 50 mg/L arsenite continuously. In addition, serum levels of nitric oxide (NO), von Willebrand factor, and nitric oxide synthase (inducible and total activities) in rats, which were greatly affected by arsenite exposure, returned to levels similar to those in the control group after recovery with distilled water. The recovery from arsenite exposure was associated with increased levels of PEDF; decreased protein levels of Fas, FasL, P53, and phospho-p38; and inhibited apoptosis in aortic endothelial cells in vivo. Recombinant human PEDF treatment (100 nM) prevented the toxic effects of arsenite (50 μM) on endothelial cells in vitro by increasing NO content, decreasing reactive oxygen species (ROS) levels, and inhibiting apoptosis, as well as increasing cell viability and decreasing levels of P53 and phospho-p38. Our findings suggest that PEDF protects endothelial cells from arsenic-induced VED by increasing NO release and inhibiting apoptosis, where P53 and p38MAPK are its main targets.
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http://dx.doi.org/10.1016/j.envres.2020.109506DOI Listing
July 2020

Direct Electrochemical Ammonia Synthesis from Nitric Oxide.

Angew Chem Int Ed Engl 2020 Jun 6;59(24):9711-9718. Epub 2020 Apr 6.

State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Zhongshan Road 457, Dalian, 116023, P. R. China.

NO removal from exhausted gas is necessary owing to its damage to environment. Meanwhile, the electrochemical ammonia synthesis (EAS) from N suffers from low reaction rate and Faradaic efficiency (FE). Now, an alternative route for ammonia synthesis is proposed from exhaust NO via electrocatalysis. DFT calculations indicate electrochemical NO reduction (NORR) is more active than N reduction (NRR). Via a descriptor-based approach, Cu was screened out to be the most active transition metal catalyst for NORR to NH owing to its moderate reactivity. Kinetic barrier calculations reveal NH is the most preferred product relative to H , N O, and N on Cu. Experimentally, a record-high EAS rate of 517.1 μmol cm  h and FE of 93.5 % were achieved at -0.9 V vs. RHE using a Cu foam electrode, exhibiting stable electrocatalytic performances with a 100 h run. This work provides an alternative strategy to EAS from exhaust NO, coupled with NO removal.
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http://dx.doi.org/10.1002/anie.202002337DOI Listing
June 2020

Toward a comparative description between transition metal and zeolite catalysts for methanol conversion.

Phys Chem Chem Phys 2020 Mar;22(9):5293-5300

State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Zhongshan Road 457, Dalian 116023, China.

Transition metals and zeolites are extremely different catalysts used for methanol conversion. Zeolites are able to catalyze methanol conversion to hydrocarbons like gasoline and olefins, while transition metals show the selectivity of syngas. It is quite important to establish a general description from a catalysis point of view for a variety of catalysts. In this work, we have employed density functional theory calculations to correlate adsorption energies for all intermediates over a set of transition metals and zeolites. We have successfully unveiled the difference in chemical reactivity and catalytic activity for zeolites and transition metals; a comparative description has been finally established between the acidity (and porous effects) of zeolites and electronic (and geometrical) effects over transition metals. The hydrogen adsorption strength was suggested to be a general descriptor for both transition metal and zeolite catalysts. In addition, it was found that some zeolites with the same ammonia adsorption strength, which was always used to describe the acidity in experimental studies, are likely to have different theoretical acidity (hydrogen bonding strength). This eventually opens one more dimension for rational selection and design of zeolites for catalysis application.
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http://dx.doi.org/10.1039/d0cp00126kDOI Listing
March 2020

MTHFD1L-Mediated Redox Homeostasis Promotes Tumor Progression in Tongue Squamous Cell Carcinoma.

Front Oncol 2019 5;9:1278. Epub 2019 Dec 5.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

Routine changes in cell metabolism can drive tumor development, as the cellular program develops to promote glycolysis and redox homeostasis during tumor progression; however, the associated mechanisms in tongue squamous cell carcinoma (TSCC) remain unclear. We investigated methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) expression, its clinical relevance, redox modification, and molecular mechanisms using TSCC cells and tissues. The anti-tumor effects of MTHFD1L knockdown on TSCC tumorigenesis were evaluated and . Kaplan-Meier curves and the log-rank test were used to analyze disease-free survival and overall survival. TSCC patients with high expression levels of MTHFD1L had shorter overall survival ( < 0.05) and disease-free survival ( < 0.05). Knockdown of MTHFD1L reduced nicotinamide adenine dinucleotide phosphate (NADPH) levels and increased reactive oxygen species (ROS), which accelerated cell death under oxidative stress, such as hypoxia or glucose deprivation. Additionally, inhibition of MTHFD1L suppressed TSCC cell growth and delayed the cell cycle, including in xenograft experiments. MTHFD1L confers redox homeostasis and promotes TSCC cell growth, which provides a great opportunity to study tumor metabolism in head and neck cancer. The mTORC1-4EBP1-eIF4E axis may affect the expression of MTHFD1L in TSCC. Inhibition of the expression of MTHFD1L may be an actionable and effective therapeutic target in TSCC.
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http://dx.doi.org/10.3389/fonc.2019.01278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906156PMC
December 2019

Tetrandrine Ameliorates Airway Remodeling of Chronic Asthma by Interfering TGF-1/Nrf-2/HO-1 Signaling Pathway-Mediated Oxidative Stress.

Can Respir J 2019 3;2019:7930396. Epub 2019 Nov 3.

Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China.

Background: Imbalanced oxidative stress and antioxidant defense are involved in airway remodeling in asthma. It has been demonstrated that Tetrandrine has a potent role in antioxidant defense in rheumatoid arthritis and hypertension. However, the correlation between Tetrandrine and oxidative stress in asthma is utterly blurry. This study aimed to investigate the role of Tetrandrine on oxidative stress-mediated airway remolding.

Materials And Methods: Chronic asthma was established by ovalbumin (OVA) administration in male Wistar rats. Histopathology was determined by HE staining. Immunofluorescence was employed to detect the expression of -SMA and Nrf-2. Level of oxidative stress and matrix metalloproteinases were examined by ELISA kits. Cell viability and cell cycle of primary airway smooth muscle cells (ASMCs) were evaluated by CCK8 and flow cytometry, respectively. Signal molecules were detected using western blot.

Results: Tetrandrine effectively impairs OVA-induced airway inflammatory and airway remodeling by inhibiting the expression of CysLT1 and CysLTR1. The increase of oxidative stress and subsequent enhancement of MMP9 and TGF-1 expression were rescued by the administration of Tetrandrine in the rat model of asthma. In in vitro experiments, Tetrandrine markedly suppressed TGF-1-evoked cell viability and cell cycle promotion of ASMCs in a dose-dependent manner. Furthermore, Tetrandrine promoted Nrf-2 nuclear transcription and activated its downstream HO-1 in vivo and in vitro.

Conclusion: Tetrandrine attenuates airway inflammatory and airway remodeling in rat model of asthma and TGF-1-induced cell proliferation of ASMCs by regulating oxidative stress in primary ASMCs, suggesting that Tetrandrine possibly is an effective candidate therapy for asthma.
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http://dx.doi.org/10.1155/2019/7930396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875008PMC
May 2020

Butylphthalide ameliorates airway inflammation and mucus hypersecretion via NF-κB in a murine asthma model.

Int Immunopharmacol 2019 Nov 4;76:105873. Epub 2019 Sep 4.

School of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, China. Electronic address:

Butylphthalide (NBP) is a phthalide compound contained in Angelicae Sinensis Radix which is one of the most widely used traditional Chinese medicines. This study aims to explore the therapeutic effect of NBP on airway inflammation, mucus hypersecretion and their possible mechanism in asthma mice. BALB/c mice were sensitized and challenged with ovalbumin (OVA) for establishment of asthma model and then treated with NBP during day 22-77. The pulmonary function of the mice was determined, and the pathology of lung tissue and goblet cell hyperplasia were observed through analyzing inflammation scores and goblet cell percentage, respectively. Cytokine IL-4, IL-8, IL-13 and tumor necrosis factor-alpha (TNF-α) in bronchoalveolar lavage fluid (BALF) and total immunogloblin E (T-IgE) and OVA-specific IgE in serum were examined by enzyme-linked immunosorbent assay (ELISA). The expressions of Mucin 5AC (Muc5ac) and nuclear transcription factor-kappa B (NF-κB) in lung tissues were evaluated by immunohistochemistry, western blot and real-time polymerase chain reaction (RT-PCR). The results show that 50 mg/kg NBP significantly reduced OVA-induced increase in inflammation scoring, goblet cell percentage and mucus secretion of airway tissue, and improved the pulmonary function. NBP could also decrease IL-4, IL-8 IL-13, and TNF-α in BALF and T-IgE and OVA-specific IgE in serum. The expression of Muc5ac and NF-κB in lung tissue was significantly down-regulated after NBP treatment. This study suggested that NBP may effectively inhibit airway inflammation and mucus hypersecretion in asthma by modulating NF-κB activation.
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http://dx.doi.org/10.1016/j.intimp.2019.105873DOI Listing
November 2019

Umbilical Cord Mesenchymal Stem Cell Transplantation Prevents Chemotherapy-Induced Ovarian Failure via the NGF/TrkA Pathway in Rats.

Biomed Res Int 2019 23;2019:6539294. Epub 2019 May 23.

Medical Molecular Biology Laboratory, Medical College, Jinhua Polytechnic, Jinhua, Zhejiang Province, China.

Chemotherapy leads to a loss of fertility and reproductive endocrine function, thereby increasing the risk of premature ovarian failure (POF). Studies have suggested that the transplantation of mesenchymal stem cells could inhibit apoptosis in ovarian granulosa cells and improve follicular development. In the present study, the effects of human umbilical cord mesenchymal stem cell (UCMSC) transplantation on ovarian function after ovarian damage caused by chemotherapy and the mechanism underlying these effects were investigated. POF model rats were obtained by the intraperitoneal injection of cyclophosphamide, and cultured UCMSCs were transplanted by tail vein injection. Serum estrogen, follicle-stimulating hormone, gonadotropin releasing hormone, and anti-Mullerian hormone levels were detected by ELISA. Folliculogenesis was evaluated by histopathological examination. The expression levels of nerve growth factor (NGF), high affinity nerve growth factor receptor (TrkA), follicle-stimulating hormone receptor (FSHR), and caspase-3 were evaluated by western blotting and RT-qPCR. The natural reproductive capacity was assessed by pregnant rate and numbers of embryos. The results indicated that UCMSC transplantation recovered disturbed hormone secretion and folliculogenesis in POF rats. NGF and TrkA levels increased, while FSHR and caspase-3 decreased. The pregnancy rate of POF rats was improved. Therefore, UCMSCs could reduce ovarian failure due to premature senescence caused by chemotherapy, and the NGF/TrkA signaling pathway was involved in the amelioration of POF.
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http://dx.doi.org/10.1155/2019/6539294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556346PMC
December 2019

Overexpression of a trypanothione synthetase gene from Trypanosoma cruzi, TcTrys, confers enhanced tolerance to multiple abiotic stresses in rice.

Gene 2019 Aug 12;710:279-290. Epub 2019 Jun 12.

Shanghai Key Laboratory of Agricultural Genetics and Breeding, Agro-Biotechnology Research Institute, Shanghai Academy of Agricultural Sciences, 2901 Beidi Rd, Shanghai 201106, PR China. Electronic address:

Plants are frequently exposed to variable environmental stresses that adversely affect plant growth, development and agricultural production. In this study, a trypanothione synthetase gene from Trypanosoma cruzi, TcTryS, was chemically synthesized and its roles in tolerance to multiple abiotic stresses were functionally characterized by generating transgenic rice overexpressing TcTryS. Overexpression of TcTryS in rice endows transgenic plants with hypersensitivity to ABA, hyposensitivity to NaCl- and mannitol-induced osmotic stress at the seed germination stage. TcTryS overexpression results in enhanced tolerance to drought, salt, cadmium, and 2,4,6-trichlorophenol stresses in transgenic rice, simultaneously supported by improved physiological traits. The TcTryS-overexpression plants also accumulated greater amounts of proline, less malondialdehyde and more transcripts of stress-related genes than wild-type plants under drought and salt stress conditions. In addition, TcTryS might play a positive role in maintaining chlorophyll content under 2,4,6-trichlorophenol stress. Histochemical staining assay showed that TcTryS renders transgenic plants better ROS-scavenging capability. All of these results suggest that TcTryS could function as a key regulator in modulation of abiotic stress tolerance in plant, and may have applications in the engineering of economically important crops.
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http://dx.doi.org/10.1016/j.gene.2019.06.018DOI Listing
August 2019

Binding of the polysaccharide from Acanthopanax giraldii Harms to toll-like receptor 4 activates macrophages.

J Ethnopharmacol 2019 Sep 4;241:112011. Epub 2019 Jun 4.

School of Clinical Medicine, Weifang Medical University, No.7166 W. Baotong Rd, Weifang City, 261042, China. Electronic address:

Ethnopharmacological Relevance: The traditional Chinese medicine, Acanthopanax giraldii Harms, is commonly used to treat arthralgia due to wind, cold and dampness, as well as weakness in the feet and knees. Its other reported effects include eliminating flatulence, strengthening muscles and bones, and delaying aging. The polysaccharides in A. giraldii Harms are the major bioactive substances that confer the herb's antioxidant properties as well as anticancer and antiviral effects.

Aims Of The Study: To elucidate the underlying mechanism and signaling cascade involved in the homogeneous A. giraldii Harms polysaccharide II (AHP-II)-mediated immunomodulation of mice macrophages.

Materials And Methods: The phagocytosis of neutral red and the production of nitric oxide, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), were measured to determine AHP-II-induced macrophage activation. Confocal microscopy and flow cytometry were used to confirm the binding of AHP-II to macrophages. The involvement of Toll-like receptor (TLR) 4 in AHP-II-induced macrophage activation was demonstrated using antibody blocking and macrophages from C3H/HeJ TLR4-mutant mice. Western blotting was used to map AHP-II-induced downstream signaling pathways.

Results: AHP-II increased the phagocytosis of macrophages and the release of nitric oxide, IL-6 and TNF-α cytokines. Direct, saturable and reversible binding of AHP-II to macrophages was observed, while it can be inhibited by the anti-TLR4 antibody. In addition, the presence of the anti-TLR4 antibody inhibited AHP-II-induced macrophage IL-6 and TNF-α production in the peritoneal macrophages of C3H/HeJ mice. Moreover, AHP-II-TLR4-stimulated macrophages activate the downstream intracellular ERK and JNK/nuclear factor (NF)-κB signaling pathways. In addition, the AHP-II-mediated regulation of IL-6 and TNF-α production from macrophages was greatly affected by specific ERK, JNK and NF-κB inhibitors.

Conclusion: Our study elucidated the immunomodulatory mechanism of AHP-II in macrophage activation and identified TLR4 as the main receptor coordinating AHP-II binding. Our findings suggest AHP-II may be used as a novel immunopotentiator for medical purposes.
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http://dx.doi.org/10.1016/j.jep.2019.112011DOI Listing
September 2019

Evaluation of lentinan effects on cytochrome P450 activity in rats by a cocktail method.

Iran J Basic Med Sci 2019 Mar;22(3):296-301

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China.

Objectives: In this study, a cocktail of probe drugs was used to assess whether lentinan could influence the activities of rat enzymes CYP3A4, CYP2D6, CYP1A2, CYP2C19, and CYP2C9 in vivo.

Materials And Methods: Fourteen days after intraperitoneal injection of lentinan, rats were given an oral dose of a cocktail solution containing phenacetin, tolbutamide, omeprazole, metoprolol, and midazolam. Then, we obtained blood in specific durations for the determination of plasma concentration of the probe drugs using UPLC-MS/MS. We also evaluated the pharmacokinetic parameters using the DAS 2.0 software.

Results: We found that various concentrations of lentinan increased the activity of rat CYP1A2, CYP3A4, CYP2D6, and CYP2C19 but not CYP2C9.

Conclusion: These findings suggest that clinical application of lentinan combination with CYP3A4, CYP1A2, CYP2C19, or CYP2D6 should be given careful consideration as this may lead to herb-drug interactions and hence treatment failure.
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http://dx.doi.org/10.22038/ijbms.2019.31611.7611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528719PMC
March 2019

Safety and Efficacy of Anti-PD-1 Monoclonal Antibodies in Patients With Relapsed or Refractory Lymphoma: A Meta-Analysis of Prospective Clinic Trails.

Front Pharmacol 2019 1;10:387. Epub 2019 May 1.

Department of Hematology and Research Laboratory of Hematology, West China Hospital, Sichuan University, Chengdu, China.

Immune checkpoint inhibition therapy with monoclonal antibody against programmed cell death protein 1 (PD-1), including nivolumab and pembrolizumab, has demonstrated powerful clinical efficacy in the treatment of advanced cancers. However, there is no evidence-based systematic review on the safety and efficacy of anti-PD-1 antibody in treating lymphoma. To evaluate the safety and efficacy of nivolumab/pembrolizumab, we analyzed clinical trials from PUBMED, EMBASE, and The Cochrane Library. For safety analysis, the incidence and exhibition of any grade and grade ≥3 adverse events (AEs) were evaluated. Overall response rate (ORR), 6-month progression-free survival (PFS) and 6-month overall survival (OS) were calculated for efficacy analysis. Overall ten studies and 718 patients (114 non-Hodgkin lymphomas, 604 Hodgkin lymphomas) were enrolled, including 4 phase I studies and 6 phase II studies. The pooled incidences of any grade and grade ≥3 adverse events (AEs) were 74 and 24%, respectively. Drug-related deaths occurred in two patients. The most common any grade AEs were fatigue (14.91%), rash (14.8%), hypothyroidism (13.77%), platelet count decreased (13.54%), pyrexia (13%). The most common grade ≥3 AEs were neutropenia (4.79%), pneumonitis (3.58%), rash (3.38%), and leukopenia (3.31%). Fatigue ( = 0.0072) and rash ( = 0.0078) in any grade AEs were less observed in patients treated with pembrolizumab than nivolumab. The pooled ORR, PFS rate and OS rate were 58, 73, and 96%, respectively. The ORR in patients with Hodgkin lymphomas (HL) was higher than patients with non-Hodgkin lymphomas (NHL) (69.08 vs. 30.77%, < 0.0001). However, there was no significant difference of efficacy between nivolumab and pembrolizumab. Nivolumab and pembrolizumab have promising outcomes with tolerable AEs and drug-related deaths in patients with relapsed or refractory lymphoma. Pembrolizumab caused less any grade AEs like fatigue and rash than nivolumab. Patients with HL got better response than NHL.
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http://dx.doi.org/10.3389/fphar.2019.00387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504777PMC
May 2019

TFAP2B overexpression contributes to tumor growth and progression of thyroid cancer through the COX-2 signaling pathway.

Cell Death Dis 2019 05 21;10(6):397. Epub 2019 May 21.

Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, Guangdong, China.

Thyroid cancer is commonly seen in the clinic with a rapidly increasing incidence globally. COX-2 overexpression correlates with the pathologic type of thyroid carcinoma, and it has been suggested that COX-2 overexpression is associated with a poor prognosis. However, little is known about its upstream regulatory mechanism. Bioinformatics suggested that transcription factor AP-2 beta (TFAP2B) might specifically bind to the COX-2 promoter, which was confirmed by biotin-labeled COX-2 promoter pulldown and luciferase reporter assays. We performed western blot and immunohistochemical staining to detect the expression of TFAP2B/COX-2 in thyroid cancer tissues (T) and the matched adjacent noncarcinoma tissues (ANT), and investigated the relationship between TFAP2B/COX-2 expression and clinical pathological factors in thyroid cancer patients. Afterward, MTS, colony formation, cell-apoptosis assay, transwell-invasion and scratch assays were performed to examine the proliferation, apoptosis, invasion, and migration of thyroid cancer cells with TFAP2B knocked down or overexpressed. The mouse xenograft experiment was performed to study in vivo the proliferation of thyroid cancer cells with TFAP2B knocked down or overexpressed. We found that TFAP2B bound to the promoter of COX-2 to activate its expression. Western blot and immunohistochemistry showed that TFAP2B/COX-2 was highly expressed in thyroid cancer, and high TFAP2B and COX-2 expression was associated with aggressive clinicopathological features in thyroid cancer. TFAP2B mediated thyroid cancer cell proliferation, apoptosis, invasion, and migration via the COX-2 signaling pathway in vitro and in vivo. TFAP2B bound to the promoter of COX-2 to activate its expression, indicating that TFAP2B is a critical regulatory molecule in the COX-2 signaling pathway that promoted tumor progression in thyroid cancer.
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http://dx.doi.org/10.1038/s41419-019-1600-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529436PMC
May 2019

A Variant of the Histone-Binding Protein sNASP Contributes to Mouse Lupus.

Front Immunol 2019 2;10:637. Epub 2019 Apr 2.

Department of Immunology, Weifang Medical University, Weifang, China.

The () sublocus is derived from the mouse lupus susceptibility 2 () locus identified in the NZM2410 model. Our current study dissected the functional characters and the genetic basis of the locus relative to lupus when co-expressed with the Fas mutation, an established inducer of autoimmunity. The rec1c.lpr mice exhibited mild expansion of lymph nodes and had a normal T cell cellularity, but developed significantly kidney and lung inflammation, indicating that the amplifies -induced autoimmune pathogenesis. A variant of somatic nuclear autoantigenic sperm protein (sNASP) was identified from the interval as a substitution of two consecutive amino acid residues in the histone-binding domain, resulting in an increased binding affinity to histone H4 and H3.1/H4 tetramer. To determine the role of the allele in mouse lupus, a novel strain was generated by introducing the mutations into the B6 genome. In this transgenic model, the allele synergized with the mutation leading to moderate autoimmune phenotypes and aggravating inflammatory pathology alterations in kidney and lung that were similar to those observed in the rec1c.lpr mice. These results establish that the allele is a pathogenic genetic element in the sublocus, which not only promotes autoimmunity, but also exacerbates the inflammation reaction of end organs in mouse lupus pathogenesis. It also shows the complexity of the locus, initially mapped as the major locus associated with B1a cell expansion. In addition to , which regulates this expansion, we have now identified in the same locus a protective allele of , a variant of Skint6 associated with T cell activation, and now a variant of that amplifies autoimmunity and tissue damage.
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http://dx.doi.org/10.3389/fimmu.2019.00637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454087PMC
June 2020

Effects of curcumin on artery blood gas index of rats with pulmonary fibrosis caused by paraquat poisoning and the expression of Smad 4, Smurf 2, interleukin-4 and interferon-γ.

Exp Ther Med 2019 May 4;17(5):3664-3670. Epub 2019 Mar 4.

Department of Nursing, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.

Effects of curcumin on artery blood gas index of rats with pulmonary fibrosis caused by paraquat poisoning and the expression of Mothers against decapentaplegic homolog 4 (Smad4), Smad ubiquitination regulatory factor 2 (Smurf2), interleukin-4 (IL-4) and interferon-γ (IFN-γ) were explored. A total of 54 Wistar rats were randomly selected, of which 36 rats were selected for paraquat poisoning pulmonary fibrosis modeling, and 18 were used in the control group for normal feeding. Then, 18 rats were randomly selected from the modeled groups and injected with curcumin and classified as the curcumin group. The remaining 18 rats were not processed and 17 were successfully modeled as the paraquat group. The expression of SMAD4, Smurf2, IL-4 and INF-γ was detected by enzyme-linked immunosorbent assay. Abdominal aortic blood was taken for determination of pH, arterial partial pressure of oxygen (PaO) and arterial partial pressure of carbon dioxide (PaCO). The artery blood PaO and serum INF-γ of the curcumin and paraquat groups were significantly higher on day 1 than those on day 5 (P<0.05). The artery blood PaO and serum INF-γ in the curcumin group were higher than those in the paraquat group (P<0.05). The artery blood PaCO, serum Smad4, Smurf2 and IL-4 in the curcumin group were significantly lower on day 1 than those on day 5 (P<0.05). The artery blood PaCO, serum Smad4, Smurf2 and IL-4 in the paraquat group were significantly lower on day 1 than those on day 5 (P<0.05). The PaCO, serum Smad4, Smurf2 and IL-4 in the curcumin group were lower than those in the paraquat group (P<0.05). In conclusion, curcumin can effectively improve pulmonary fibrosis in rats after treatment with paraquat poisoning. The results show that it is expected to be an effective drug for the treatment of paraquat, and provide effective reference and guidance for clinical treatment.
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http://dx.doi.org/10.3892/etm.2019.7341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447781PMC
May 2019

Construction of an Escherichia coli strain to degrade phenol completely with two modified metabolic modules.

J Hazard Mater 2019 07 16;373:29-38. Epub 2019 Mar 16.

Shanghai Key laboratory of Agricultural Genetics and Breeding, Agro-Biotechnology Research Institute, Shanghai Academy of Agricultural Sciences, Shanghai, PR China. Electronic address:

Phenol is a common water pollutant because of its broad industrial applications. Biological method is a promising alternative to conventional physical and chemical methods for removing this toxic pollutant from the environment. In this study, two metabolic modules were introduced into Escherichia coli, the widely used host for various genetic manipulations, to elucidate the metabolic capacity of E. coli for phenol degradation. The first module catalysed the conversion of phenol to catechol, whereas the second module cleaved catechol into the three carboxylic acid circulating intermediates by the ortho-cleavage pathway. Phenol was completely degraded and imported into the tricarboxylic acid cycle by the engineered bacteria. Proteomics analysis showed that all genes in the phenol degradation pathway were over-expressed and affected cell division and energy metabolism of the host cells. Phenol in coking wastewater was degraded powerfully by BL-phe/cat. The engineered E. coli can improve the removal rate and shorten the processing time for phenol removal and has considerable potential in the treatment of toxic and harmful pollutants.
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http://dx.doi.org/10.1016/j.jhazmat.2019.03.055DOI Listing
July 2019

The role of PERK and IRE1 signaling pathways in excessive fluoride mediated impairment of lymphocytes in rats' spleen in vivo and in vitro.

Chemosphere 2019 May 8;223:1-11. Epub 2019 Feb 8.

Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, 150081, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin, Heilongjiang, 150081, China; Institution of Environmentally Related Diseases, Harbin Medical University, Harbin, Heilongjiang, 150081, China. Electronic address:

Fluoride is capable of inducing immunotoxicity, but its molecular mechanisms remain elusive. This study aimed to explore the roles of Protein kinase receptor-like ER kinase (PERK) and inositol requiring enzyme 1 (IRE1) signaling pathways in excessive fluoride-induced immunotoxicity, focusing on the regulatory roles of these two pathways in cell division and apoptosis. Firstly, we assessed the changes in cell division and apoptosis in rats exposed to 0, 50, or 100 mg/L fluoride, and detected the expression of PERK and IRE1 signaling-related proteins in spleen. Additionally, to validate the role of these two pathways, we evaluated the changes in cell division and apoptosis of primary lymphocytes from rat's spleen to 4 mM fluoride after knockdown of PERK and IRE1 in vitro. In vivo results confirmed that fluoride inhibited cell division, promoted the apoptosis and resulted in histological and ultrastructural abnormalities of rat spleen. In addition, fluoride induced activation of the PERK and IRE1 signalings and the associated apoptosis. Moreover, the in vitro results further verified the findings in vivo that fluoride activated these two signalings in B lymphocytes. Importantly, after knockdown of PERK and IRE1 in lymphocytes, the cell division ability was restored, and apoptosis decreased in fluoride-treated lymphocytes; the results correlated well with the expression of PERK and IRE1 signaling-related proteins, thus confirming the pivotal role of these pathways in immunosuppression by excessive fluoride. This study indicates that the mechanisms underlying the deleterious effects of fluoride on immune system are related to activation of the PERK and IRE1 signaling pathways.
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http://dx.doi.org/10.1016/j.chemosphere.2019.02.031DOI Listing
May 2019

Core needle biopsy promotes lung metastasis of breast cancer: An experimental study.

Mol Clin Oncol 2019 Feb 5;10(2):253-260. Epub 2018 Dec 5.

Department of Medical Sciences, Jinhua Polytechnic, Jinhua, Zhejiang 321007, P.R. China.

Core needle biopsy (CNB) may be used to diagnose early-stage breast cancer, but it may increase the risk of distant metastasis of tumor cells. The aim of the present study was to explore the effect of CNB on the distant metastasis of breast cancer. A total of 30 BALB/c mice were divided into two groups, namely biopsy and non-biopsy groups. The biopsy-related lung metastasis model (biopsy group) was established by the inoculation in the mammary fat pad of the mouse breast cancer cell line 4T1 combined with CNB. Flow cytometry, quantitative polymerase chain reaction analysis, morphological analysis, as well as other techniques, were used to evaluate the biological behavior of the tumors in the mouse model. A stable and reliable lung metastasis model of breast cancer was successfully established. The number of metastatic lung nodules in the biopsy group was significantly higher compared with that in the non-biopsy group (P<0.05). Compared with the non-biopsy group, the mRNA expression of transforming growth factor (TGF)-β1, SOX4 and Ezh2 in the biopsy group was significantly upregulated (P<0.05) and the number of natural killer (NK) cells detected by flow cytometry was increased, but the difference was not statistically significant (P>0.05). Therefore, CNB was found to promote the lung metastasis of breast cancer, and the underlying mechanism may be associated with epithelial-to-mesenchymal transition (EMT) mediated by the TGF-β1 signaling pathway.
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http://dx.doi.org/10.3892/mco.2018.1784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327225PMC
February 2019

Heterologous Expression and Characterization of a Laccase from in and .

J Microbiol Biotechnol 2018 Dec;28(12):2057-2063

Shanghai Key Laboratory of Agricultural Genetics and Breeding, Agro-Biotechnology Research Institute, Shanghai Academy of Agricultural Sciences, Shanghai 201106, P.R. China.

Laccases can oxidize a variety of phenolic and non-phenolic substrates including synthetic dyes. In this research, a laccase gene from was chemically synthesized and optimized to heterogeneous expression in and . The properties of recombinant laccase expressed by were investigated. The laccase activity was optimal at 3.6 pH and 40°C. It exhibited and values of 0.565 mmol l⁻¹ and 1.51 μmol l⁻¹ min⁻¹ for ABTS respectively. As compared with untransformed control plants, the laccase activity in crude extracts of transgenic lines exhibited a 5.4 to 12.4-fold increase. Both laccases expressed in transgenic or could decolorize crystal violet. These results indicated that laccase gene may be transgenically exploited in fungi or plants for dye decolorization.
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http://dx.doi.org/10.4014/jmb.1807.08042DOI Listing
December 2018

Selenocystine inhibits JEG-3 cell growth and by triggering oxidative damage-mediated S-phase arrest and apoptosis.

J Cancer Res Ther 2018 ;14(7):1540-1548

Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.

Background: Selenocystine (SeC) is a nutritionally available selenoamino acid presenting novel anticancer potential against human cancers. However, neither the effects nor mechanism of SeC against choriocarcinoma growth has been clarified yet. This study investigated the anticancer effects and mechanism of SeC against JEG-3 human choriocarcinoma growth in vitro and in vivo.

Materials And Methods: The in vitro anticancer efficiency was evaluated with cell viability, apoptosis, and oxidative stress. JEG-3 cell viability was determined with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Cell cycle distribution and apoptosis were examined by flow cytometric analysis. Oxidative damage was detected with immunofluorescence and western blotting. The in vivo anticancer efficiency was evaluated in immunodeficient mouse model of choriocarcinoma. The mechanism was also investigated.

Results: SeC dose and time dependently inhibited the viability of JEG-3 cells in vitro. The result of flow cytometry (FCM) analysis showed that obvious S-phase arrest and cell apoptosis were initiated by SeC in JEG-3 cells, which was further convinced by the decreased levels of cyclin A, poly-ADP-ribose polymerase cleavage, and activation of caspase-3,-7, and-9. In addition, SeC resulted in significant generation of reactive oxygen species (ROS) and superoxide anion, followed by the activation of DNA damage. However, SeC-induced oxidative damage and apoptosis were effectively blocked after ROS inhibition. Further investigation indicated that SeC effectively suppressed JEG-3 choriocarcinoma tumor xenograft growth in vivo. The mechanism may be the induction of cell apoptosis and oxidative damage through inhibiting cell proliferation (Ki-67) and angiogenesis (CD-31).

Conclusions: Our findings supported that human choriocarcinoma growth could be inhibited by SeC in vitro and in vivo through triggering oxidative damage-mediated S-phase arrest and apoptosis. Thus, SeC may be promising in the treatment of human choriocarcinoma.
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http://dx.doi.org/10.4103/jcrt.JCRT_864_17DOI Listing
February 2019

Induced lesion and inhibited Ihh-PTHrP signalling pathway activity in the articular cartilage of rats caused by T-2 toxin.

Toxicon 2019 Feb 11;158:104-108. Epub 2018 Dec 11.

Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health, Harbin, 150081, Heilongjiang, China. Electronic address:

This study aims to investigate the role of Ihh-PTHrP signalling pathway in the articular cartilage injury of rats caused by T-2 toxin. Sixty male Wistar rats were randomly divided into four groups: group A, normal diet; group B, normal diet plus the dissolvent (0.9% sodium chloride sterile aqueous solution containing ethanol); group C, normal diet plus low T-2 toxin (0.1 mg/kg BW/day) and group D, normal diet plus high T-2 toxin (0.2 mg/kg BW/day) by intragastric administration daily for 4 weeks. Histological changes in articular cartilage were assessed by HE staining and scanning electron microscopy. The expression of Ihh and PTHrP in cartilage was assessed by immunohistochemistry. There is a significant difference in average weight gain between group A and group D P < 0.01, groups A and D P < 0.001, respectively. The result of scanning electron microscopy and HE staining showed that the damage of articular cartilage was much severe with the increase of T-2 toxin. Immunohistochemical analysis indicated that the expression of Ihh in group A and group B was higher than that of group C and group D (P < 0.05, <0.01, respectively). However, the expression of PTHrP was lower in group A and group B than that of group C and group D (P < 0.001, <0.001, respectively). These results indicated that T-2 toxin can cause the damage to articular cartilage and weight loss in rats. The effect of T-2 toxin on articular cartilage of rat may be related to the Ihh-PTHrP pathway.
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http://dx.doi.org/10.1016/j.toxicon.2018.12.001DOI Listing
February 2019

Corrigendum to "Odd-skipped related transcription factor 1 (OSR1) suppresses tongue squamous cell carcinoma migration and invasion through inhibiting NF-κB pathway" [Eur. J. Pharmacol. 15 (2018) 33-39].

Eur J Pharmacol 2019 03 7;847:158. Epub 2018 Dec 7.

Department of Head and Neck, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, China. Electronic address:

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http://dx.doi.org/10.1016/j.ejphar.2018.11.042DOI Listing
March 2019

Role of Pigment Epithelium-Derived Factor in Arsenic-Induced Vascular Endothelial Dysfunction in a Rat Model.

Biol Trace Elem Res 2019 Aug 3;190(2):405-413. Epub 2018 Nov 3.

Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), 157 Baojian Road, Harbin, 150081, China.

Water-borne arsenicosis is caused by the consumption of excess levels of inorganic arsenic from drinking water and is a worldwide public health issue. Arsenic exposure has recently attracted extensive attention due to its damage to the cardiovascular system. Vascular endothelial dysfunction (VED) is recognized as an important cause of cardiovascular diseases. Pigment epithelium-derived factor (PEDF) plays an important role in maintaining endothelial function, and our previous studies suggested that PEDF may have role in arsenic-induced damage. In the present study, we established subchronic arsenic exposure (3 months) rat model from drinking water at doses of 0, 2 mg/L, 10 mg/L, and 50 mg/L, respectively. The results showed that the endothelial cells of the aortic arch were obviously damaged, the apoptosis rate increased, the vWF and iNOS levels increased, and the NO and TNOS levels significantly decreased in the arsenic exposure groups. Regardless of serum or aortic arch endothelium, PEDF levels in the arsenic exposure groups decreased compared to the control group. The oxidative stress level and key proteins associated with apoptosis such as Fas, FasL, P53, and p-p38 were then detected to explore the detailed mechanisms. The results showed that the P53 and p-p38 levels significantly increased in the 10 mg/L and 50 mg/L groups compared to the control group. The MDA content in the arsenic exposure groups increased markedly, whereas the SOD activity decreased significantly with the increased arsenic dose. Taken together, our study is the first to find that PEDF plays a protective role in arsenic-induced endothelial dysfunction through anti-oxidation and anti-apoptosis, and p38 and P53 may be promising target proteins.
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http://dx.doi.org/10.1007/s12011-018-1559-8DOI Listing
August 2019