Publications by authors named "Xiaoli Hou"

40 Publications

CDDO-Im exerts antidepressant-like effects via the Nrf2/ARE pathway in a rat model of post-stroke depression.

Brain Res Bull 2021 Aug 12;173:74-81. Epub 2021 May 12.

Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, China; Henan Key Lab of Biological Psychiatry, Henan International Joint Laboratory of Psychiatry and Neuroscience, Xinxiang Medical University, China. Electronic address:

Increasing evidence suggests that oxidative damage and neuroinflammation play a critical role in the pathogenesis of post-stroke depression (PSD). These pathologic processes are tightly regulated by the NF-E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway. The synthetic triterpenoid, 2-Cyano-3,12-dioxooleana-1,9-dien-28-imidazolide (CDDO-Im), is a potent Nrf2 activator. This study investigated whether CDDO-Im exhibited antidepressant-like activity and elucidated its protective mechanisms in a rat model of PSD, which was produced by middle cerebral artery occlusion (MCAO) followed by 28 days of chronic unpredictable mild stress (CUMS) in conjunction with solitary housing. The results demonstrated that CDDO-Im treatment markedly improved the depressive-like behaviors and reduced neuronal cell loss in the hippocampus, through decreasing the malondialdehyde (MDA) content (indicative of lipid peroxidation), superoxide dismutase (SOD), NF-kB activation, interleukin-6 (IL-6) and interleukin-1b (IL-1β) in PSD rats. CDDO-Im treatment alleviated the oxidative stress and inflammatory response in PSD rats by promoting Nrf2 nuclear import and increasing the protein levels of Nrf2 downstream target genes, including heme oxygenase-1(HOMX1) and, quinone oxidoreductase-1(NQO1).These findings suggested that CDDO-Im treatment exhibited antidepressant-like effects and protected PSD rats from oxidative and inflammatory injury via the Nrf2/ARE pathway. Therefore, CDDO-Im treatment is worthy of further study.
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http://dx.doi.org/10.1016/j.brainresbull.2021.05.008DOI Listing
August 2021

Effects of Fish Oil Supplementation on Cardiometabolic Risk Factors in Overweight or Obese Children and Adolescents: A Meta-Analysis of Randomized Controlled Trials.

Front Pediatr 2021 27;9:604469. Epub 2021 Apr 27.

Department of Critical Medicine, Hainan Maternal and Children's Medical Center, Haikou, China.

Influences of fish oil supplementation on body weight and other cardiometabolic factors in overweight or obese children and adolescents remain not fully understood. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the role of fish oil for these children. Relevant studies were obtained by search of PubMed, Embase, and Cochrane's Library databases. A random-effect model, which incorporates the potential heterogeneity of the included studies, was used to pool the results. Twelve RCTs including 1,028 overweight or obese children and adolescents were included. Compared to control, fish oil supplementation significantly reduced body mass index [BMI, mean difference (MD): -0.96 kg/m, 95% confidence interval (CI): -1.69 to -0.23, = 0.01] but did not significantly reduce body weight or waist circumference ( = 0.68 and 0.76). Moreover, fish oil supplementation significantly reduced serum triglyceride (MD: -0.24 mmol/L, 95% CI: -0.40 to -0.08, = 0.004) but did not significantly affect serum total cholesterol and high-density or low-density lipoprotein cholesterol ( = 0.83, 0.42, and 0.31, respectively). Additionally, fish oil supplementation significantly lowered systolic blood pressure (SBP, MD: -2.46 mmHg, 95% CI: -4.93 to -0.01, = 0.04) but did not significantly change diastolic blood pressure ( = 0.22). Supplementation with fish oil did not significantly affect fasting plasma glucose ( = 0.33). In overweight or obese children and adolescents, supplementation with fish oil could reduce BMI, decrease serum triglyceride, and lower SBP, while serum cholesterol and fasting glucose may not be significantly affected.
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http://dx.doi.org/10.3389/fped.2021.604469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110710PMC
April 2021

Chloroform extract from Sophora Tonkinensis Gagnep. inhibit proliferation, migration, invasion and promote apoptosis of nasopharyngeal carcinoma cells by silencing the PI3K/AKT/mTOR signaling pathway.

J Ethnopharmacol 2021 May 30;271:113879. Epub 2021 Jan 30.

National Engineering Laboratory of Southwest Endangered Medicinal Resources Development, Guangxi Botanical Garden of Medicinal Plants, Nanning, 530023, PR China. Electronic address:

Ethnopharmacological Relevance: Sophora Tonkinensis Gagnep. (STG) has been used as a folk medicine for the treatment of different cancers, especially for nasopharyngeal carcinoma, cervical cancer, liver cancer, stomach cancer, lung cancer and leukemia in China. However, the main chemical composition and anticancer mechanism of chloroform extract of STG (CESTG) were still not very clear.

Aim Of Study: This work was carried out to investigate the anticancer effects and mechanisms of chloroform extract of STG (CESTG) on NPC.

Methods: Cultured NPC CNE1, CNE2 and Np69 cells were treated with CESTG. Cells were subjected to cell proliferation, colony-forming, migration and invasion assays. Cell cycle and apoptosis were measured by flow cytometry. Western blotting and morphological analysis were also performed. Tumor xenografts and drug treatments were made in BALB/c nude mice. The main compounds of CESTG was separated by HPLC.

Results: CESTG inhibited cell viability, clonal growth and induced cell apoptosis in a dose-dependent manner by silencing the PI3K/AKT/mTOR signaling pathway, which is associated with upregulation of cleaved PARP, caspase 3/7/8/9, cleaved caspase 3/7/8/9, Bax and downregulation of PARP, P-PI3K, PI3K, P-AKT, AKT, P-mTOR, mTOR and Bcl-2. In addition, CESTG arrested cell cycle in the G1/S phase, correlating with decreased levels of cyclin D1/B1, CDK 4 and 6. CESTG decreased cell migration and invasion which correlated with decreased expression of β-catenin, vimentin and snail. CESTG significantly inhibited the tumor growth without toxicity.

Conclusion: The results presented here suggest that CESTG could be use as a potential source of NPC therapeutic drug.
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http://dx.doi.org/10.1016/j.jep.2021.113879DOI Listing
May 2021

Temperature and pH Dual Responsive Nanogels of Modified Sodium Alginate and NIPAM for Berberine Loading and Release.

ACS Omega 2021 Jan 4;6(2):1119-1128. Epub 2021 Jan 4.

Laboratory and Equipment Management, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.

pH- and temperature-sensitive nanogels (NGs) were prepared from sodium alginate (SA) and -isopropylacrylamide (NIPAM), as the sensitivity at pH 5.5 and 31 °C. SA was pH-modified with glutamic acid (Glu) and ethylenediamine (EDA). The products Glu-SA (Glu-modified SA) and EGSA (EDA- and Glu-modified SA) were characterized by ninhydrin color reaction, infrared spectroscopy, and zeta potential, and the best reactant ratio was selected. Moreover, temperature-sensitive, pH-sensitive EGSA-NGs possessing a semi-interpenetrating network structure were prepared by radical polymerization using -isopropylacrylamide. The morphology of EGSA-NGs was characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The cytotoxicity test shows the low cytotoxicity and high biocompatibility of the NGs. The newly prepared NGs were also subjected to pH-sensitive temperature-sensitive in vitro drug-loading and drug-release experiments. The pH-sensitive and temperature-sensitive experiments showed that the particle size of EGSA-NGs was reduced at pH 5.5 and above 31 °C. The drug-loading and drug-release experiments also confirmed this finding, indicating that the newly synthesized NGs could release the drug according to the environmental changes. Therefore, the material has potential application value in solid tumor targeted therapy.
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http://dx.doi.org/10.1021/acsomega.0c03965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818125PMC
January 2021

SCAP knockout in SM22α-Cre mice induces defective angiogenesis in the placental labyrinth.

Biomed Pharmacother 2021 Jan 20;133:111011. Epub 2020 Nov 20.

Centre for Lipid Research, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China; John Moorhead Research Laboratory, Centre for Nephrology, University College London Medical School, Royal Free Campus, University College London, London, United Kingdom. Electronic address:

The placental labyrinth is important for the exchange of nutrients and gases between the mother and the embryo in mice. This interface contains cells of both trophoblast and allantoic mesodermal origin that together produce maternal blood sinuses and placental blood vessels. However, the molecular mechanisms that take place during process of placental labyrinth development, especially concerning fetal capillaries, are not well understood. SREBP cleavage-activating protein (SCAP), a membrane protein, is required for the synthesis of fatty acids and cholesterol. Recently, when we crossed the offspring of the cross between smooth muscle 22 alpha (SM22α)- Cre recombinase (Cre) mice and SCAP mice to research the function of SCAP in vascular smooth muscle cells (VSMCs) during certain pathological processes, we found that there were no resultant SM22α-Cre-specific SCAP knockout (KO) pups (SM22α-CreSCAP; hereafter referred to as SCAP KO). Through anatomic studies of these embryos and placentas, we found that SCAP KO resulted in defective placental vessels and abnormal fetal morphology. Further immunohistochemical and immunocytochemical analyses suggested that SCAP is knocked out in the pericytes of the placental labyrinth. Compared to wildtype mice, SCAP KO placentas had abnormal vasculature in the labyrinth and lower levels of angiogenesis. By using RNA-seq and western blotting, we found that the expression of some genes and proteins in SCAP KO placentas was changed, including those related to pericyte/endothelial interactions genes and angiogenesis. Our results suggest that the proper organizational structure of the placental labyrinth depends on SCAP expression in pericytes.
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http://dx.doi.org/10.1016/j.biopha.2020.111011DOI Listing
January 2021

MicroRNA-185 reduces the expression of hepatitis B virus surface antigen by targeting PRKCH in HepG2 2.2.15 cells.

Acta Virol 2020 ;64(3):297-306

MicroRNAs (miRNAs) are single-stranded noncoding RNAs with 18 to 25 nucleotides and play critical roles in a wide spectrum of biological processes. We repored that miR-185 inhibited hepatitis B surface antigen (HBsAg) expression and hepatitis B virus (HBV) replication without affecting the proliferation of HepG2 2.2.15 cells, compared with the controls. We identified that protein kinase C eta (PRKCH) is a direct target gene of miR-185 that affects HBV replication and protein expression and that the miR-185 may suppress HBV replication. Our results provide more information for gene therapy in HBV infection. Keywords: miR-185; HBV; HBV surface antigen; viral replication; PRKCH.
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http://dx.doi.org/10.4149/av_2020_304DOI Listing
January 2021

Jieduquyuziyin Prescription Suppresses Inflammatory Activity of MRL/lpr Mice and Their Bone Marrow-Derived Macrophages Inhibiting Expression of IRAK1-NF-κB Signaling Pathway.

Front Pharmacol 2020 14;11:1049. Epub 2020 Jul 14.

School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.

Jieduquyuziyin prescription (JP) has been used to treat systemic lupus erythematosus (SLE). Although the effectiveness of JP in the treatment of SLE has been clinically proven, the underlying mechanisms have yet to be completely understood. We observed the therapeutic actions of JP in MRL/lpr mice and their bone marrow-derived macrophages (BMDMs) and the potential mechanism of their inhibition of inflammatory activity. To estimate the effect of JP on suppressing inflammatory activity, BMDMs of MRL/lpr and MRL/MP mice were treated with JP-treated serum, and MRL/lpr mice were treated by JP for 8 weeks. Among them, JP and its treated serum were subjected to quality control, and BMDMs were separated and identified. The results showed that in the JP group of BMDMs stimulated by Lipopolysaccharide (LPS) in MRL/lpr mice, the secretion of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) reduced, and the expressions of Interleukin-1 receptor-associated kinase 1 (IRAK1) and its downstream nuclear factor κB (NF-κB) pathway decreased. Meanwhile, the alleviation of renal pathological damage, the decrease of urinary protein and serum anti-dsDNA contents, the inhibition of TNF-α level, and then the suppression of the IRAK1-NF-κB inflammatory signaling in the spleen and kidney, confirmed that the therapeutic effect of JP. These results demonstrated that JP could inhibit the inflammatory activity of MRL/lpr mice and their BMDMs by suppressing the activation of IRAK1-NF-κB signaling and was supposed to be a good choice for the treatment of SLE.
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http://dx.doi.org/10.3389/fphar.2020.01049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372094PMC
July 2020

and Human Papillomavirus Infection in Women From Southern Hunan Province in China: A Large Observational Study.

Front Microbiol 2020 5;11:827. Epub 2020 May 5.

Institute of Pathogenic Biology, Hengyang Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China.

and human papillomavirus (HPV) are the most common pathogens of sexually transmitted infections (STIs), which can increase the risk of cervical cancer and infertility. The purpose of this study was to evaluate the prevalence, genotype and risk factors of and/or HPV infection in women attending the annual physical examination, assistant reproductive treatment and visiting the gynecology clinics from Southern Hunan province in China. Cervical-swab samples were collected from 5006 participants. We found that the overall prevalence of , HPV infection and /HPV coinfection was 4.7% (236/5006), 15.5% (778/5006) and 1.2% (59/5006), while the prevalence of asymptomatic infection of that was 3.8% (38/1006), 10.8% (109/1006) and 0.6% (6/1006), respectively. Furthermore, 25.0% (59/236) of infection and 7.6% (59/778) of HPV infection were attributable to and HPV coinfection. and HPV infection were more often observed in young women of less than 25 years (10.4% and 21.3%, respectively) and in the outpatients from gynecology clinics (5.2% and 18.0%, respectively). Of note, a higher prevalence of infection was observed in HPV-positive women (7.6%) than HPV- negative ones (4.2%), and vice versa. The top three genotypes were E (1.4%), F (1.1%) and J (0.8%), and the counterparts of HPV genotypes were HPV52 (4.2%), HPV16 (2.3%) and HPV58 (2.2%), respectively. Among the 151 outpatients with colposcopy data, HPV infection was associated with severe cervical lesions with OR of 15.86 (95% CI 3.14-80.0, < 0.001) while infection was more likely associated with a low grade colposcopy impression (OR = 3.25, 95% CI: 1.22-8.65, = 0.018). Our data highlight the high prevalence of asymptomatic and HPV infection, particularly among women of <25 years. The two pathogens may serve as mutual risk factors to increase the risk of infections and cervical lesions. Widespread implementation of HPV and screening programs, especially for young women, would be an effective strategy to relieve the burden of sexually transmitted infections.
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http://dx.doi.org/10.3389/fmicb.2020.00827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214719PMC
May 2020

Adipose-tissue derived porcine mesenchymal stem cells efficiently ameliorate CCl-induced acute liver failure in mice.

Cytotechnology 2020 Jun 25;72(3):327-341. Epub 2020 Apr 25.

Storr Liver Centre, Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Westmead, NSW, 2145, Australia.

Adipose tissue derived mesenchymal stem cells (ADMSCs) may be an attractive therapeutic source for acute liver injury because of their high accessibility and non-invasiveness. Here, we investigated the therapeutic potentials of porcine ADMSCs for acute liver failure (ALF). The morphology, differentiation potential, expression patterns of cell surface markers and liver-specific genes were compared between the ADMSCs derived from the pigs with or without ALF. For therapeutic studies, the expanded porcine ADMSCs from either ALF pig (ALF-ADMSCs) or healthy control pig (Nor-ADMSCs) of passage 3 were transplanted into CCl-induced ALF mice, and the liver histology and functional tests were performed at days 1, 7, 14, and 21 after cell transplantation. ALF-ADMSCs expressed higher mRNA level of hepatic growth factor (HGF) than the Nor-ADMSCs. Both ALF-ADMSCs and Nor-ADMSCs improved liver histology, functions, and mouse survival rate. Higher level of porcine hepatocyte-specific genes was seen in the livers of ALF-ADMSCs transplanted mice as compared to the Nor-ADMSCs transplanted mice. In particular, ALF-ADMSCs transplanted mice expressed significantly higher level of albumin and cytokeratin 18 in the liver tissues as compared to the Nor-ADMSCs transplanted mice. ALF-ADMSCs might be superior to Nor-ADMSCs in the treatment of ALF as the former possesses stronger hepatic differentiation potential.
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http://dx.doi.org/10.1007/s10616-020-00370-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225243PMC
June 2020

Jieduquyuziyin Prescription-Treated Rat Serum Suppresses Activation of Peritoneal Macrophages in MRL/Lpr Lupus Mice by Inhibiting IRAK1 Signaling Pathway.

Evid Based Complement Alternat Med 2019 3;2019:2357217. Epub 2019 Nov 3.

School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, and Jieduquyuziyin prescription (JP) is a traditional Chinese medicine (TCM) formula that has been testified to be effective for SLE treatment as an approved hospital prescription for many years in China. However, its mechanism of action in the treatment of this disease is largely unknown. The purpose of this study was to determine whether JP-treated rat serum can inhibit the activation of peritoneal macrophages in MRL/lpr mice by downregulating the IRAK1 signaling pathway, thereby achieving the effect of improving SLE. The JP-treated rat serum was prepared, and the peritoneal macrophages of MRL/lpr lupus mice were isolated in vitro, and the effect of JP on cell viability was detected by the CCK8 method. After LPS induction and shRNA lentiviral transfection, the effect of JP on the expression of IRAK1 in cells was detected by immunofluorescence staining. The content of TNF- and IL-6 in the cell supernatant was determined by ELISA. The expression of IRAK1, NF-B, TNF-, and IL-6 mRNA was detected by RT-PCR, and the expression levels of IRAK1, p-IRAK1, TRAF6, IKB, p-IKB, IKK + IKK, NF-B, and p-NF-B proteins was detected by western blot method. We investigated the role of JP in peritoneal macrophages of the MRL/lpr mouse and identified the possible mechanisms of action. The results showed that JP could reduce the phosphorylation of IRAK1 and its downstream proteins induced by LPS and inhibit the expression of inflammatory cytokines, including TNF- and IL-6. In addition, after the transfection of cells with shRNA lentiviral, the results of JP tended to be consistent. In conclusion, JP may inhibit the activation of peritoneal macrophages in MRL/lpr mice by downregulating the IRAK1-NF-B signaling pathway, and IRAK1 may be a potential target for JP treatment of SLE.
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http://dx.doi.org/10.1155/2019/2357217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875022PMC
November 2019

Integrated Metabolomics and Lipidomics Analyses Reveal Metabolic Reprogramming in Human Glioma with IDH1 Mutation.

J Proteome Res 2019 03 9;18(3):960-969. Epub 2019 Jan 9.

CAS Key Laboratory of Separation Science for Analytical Chemistry , Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023 , P. R. China.

Mutations in isocitrate dehydrogenase ( IDH) 1 are high-frequency events in low-grade glioma and secondary glioblastoma, and IDH1 mutant gliomas are vulnerable to interventions. Metabolic reprogramming is a hallmark of cancer. In this study, comprehensive metabolism investigation of clinical IDH1 mutant glioma specimens was performed to explore its specific metabolic reprogramming in real microenvironment. Massive metabolic alterations from glycolysis to lipid metabolism were identified in the IDH1 mutant glioma tissue when compared to IDH1 wild-type glioma. Of note, tricarboxylic acid (TCA) cycle intermediates were in similar levels in both groups, with more pyruvate found entering the TCA cycle in IDH1 mutant glioma. The pool of fatty acyl chains was also reduced, displayed as decreased triglycerides and sphingolipids, although membrane phosphatidyl lipids were not changed. The lower fatty acyl pool may be mediated by the lower protein expression levels of long-chain acyl-CoA synthetase 1 (ACSL1), ACSL4, and very long-chain acyl-CoA synthetase 3 (ACSVL3) in IDH1 mutant glioma. Lower ACSL1 was further found to contribute to the better survival of IDH1 mutant glioma patients based on the The Cancer Genome Atlas (TCGA) RNA sequencing data. Our research provides valuable insights into the tissue metabolism of human IDH1 mutant glioma and unravels new lipid-related targets.
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http://dx.doi.org/10.1021/acs.jproteome.8b00663DOI Listing
March 2019

Effect of Jieduquyuziyin prescription-treated rat serum on MeCP2 gene expression in Jurkat T cells.

In Vitro Cell Dev Biol Anim 2018 Dec 26;54(10):692-704. Epub 2018 Oct 26.

School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.

How genomic DNA methylation and methyl CpG-binding protein 2 (MeCP2) gene expression affect the pathogenesis of systemic lupus erythematosus (SLE) remains poorly understood. Traditional Chinese medicine has a unique effect in the treatment of SLE patients. This study aimed to investigate the effect of Jieduquyuziyin prescription (JP)-treated rat serum on the gene expression of MeCP2 in Jurkat T cells and its role in the pathogenesis of SLE. Jurkat T cells were harvested, and drug-containing serum was prepared. The ferulic acid and paeoniflorin content in the drug-containing serum were determined by liquid chromatography-mass spectrometry (LC-MS/MS). 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays were used to screen the optimal concentration of drug-containing serum. The DNA methylation level in Jurkat T cells was detected with a Methylamp™ Total DNA Methylation Kit. The methylation status of the MeCP2 promoter region was detected using bisulfite modification and methylation-specific PCR (MSP). Real-time PCR was used to measure MeCP2 mRNA expression. Western blotting and flow cytometry were done to detect MeCP2 protein expression in Jurkat cell nuclei. Paeoniflorin and ferulic acid were detected in the drug-containing serum of JP-treated rats. The results showed that cell growth was affected in the high serum-containing drug group. The experimental results showed that JP and prednisone acetate increased the level of genomic DNA methylation and MeCP2 gene promoter region methylation in Jurkat cells. MeCP2 mRNA and protein levels were also increased in the JP and prednisone acetate groups. Furthermore, flow cytometry revealed that the expression of MeCP2 protein in Jurkat T cell nuclei was higher in the drug group than the blank control group, and these results were consistent with the western blot analysis results. Our study found that there is a negative correlation between drug-containing serum and cell survival rate. JP upregulated the levels of DNA methylation, MeCP2 mRNA and protein as effectively as prednisone acetate and thus may activate the MeCP2 gene by increasing the methylation level, thereby inhibiting the pathogenesis of SLE. Therefore, JP may potentially be used to treat SLE patients. The Jurkat T lymphocyte in vitro experiments provided a foundation to study the effects of JP on the lupus mouse CD4 T cell methylation mechanism and to further explore the pathogenesis of SLE.
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http://dx.doi.org/10.1007/s11626-018-0295-xDOI Listing
December 2018

Paeoniflorin inhibits activation of the IRAK1-NF-κB signaling pathway in peritoneal macrophages from lupus-prone MRL/lpr mice.

Microb Pathog 2018 Nov 24;124:223-229. Epub 2018 Aug 24.

College of Basic Medical, Zhejiang Chinese Medical University, Hangzhou, 310053, China. Electronic address:

Systemic lupus erythematosus (SLE) is a chronic and multisystemic autoimmune disease. Interleukin-1 receptor-associated kinase 1 (IRAK1) is associated with the susceptibility of SLE in humans and paeoniflorin has recently been reported to exhibit immunosuppressive properties. The aim of this study was to determine the effect of paeoniflorin on lipopolysaccharide (LPS)-triggered macrophage activation and and its role in LPS-induced IRAK1-nuclear factor κB (NF-κB) signaling pathways. Peritoneal macrophages from lupus-prone MRL/lpr mice and ICR mice were isolated, prepared and cultured. Cells were treated with LPS alone or LPS with paeoniflorin, and macrophage proliferation was analyzed using the CCK8 assay. The expression of IRAK1 in cells was analyzed by immunofluorescence staining. The level of gene expression of IRAK1, NF-κB, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was measured by RT-PCR, and TNF-α, IL-6 levels in the cell supernatant were determined by ELISA. The protein expression of IRAK1 and downstream molecules tumor necrosis factor receptor-associated factor 6 (TRAF6), inhibitor of nuclear factor kappa-B kinase (IKK), NF-kappa-B inhibitor alpha (IKBα), and NF-κB was detected by Western-blot analysis. Paeoniflorin was found to decrease the phosphorylation of IRAK1 and its downstream proteins induced by LPS and inhibit the expression of TNF-α and IL-6. Taken together, the data obtained indicate that paeoniflorin inhibits LPS-induced cell activation by inhibiting the IRAK1-NF-κB pathway in MRL/lpr mouse macrophages. Therefore, paeoniflorin may be a potential therapy for SLE.
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http://dx.doi.org/10.1016/j.micpath.2018.08.051DOI Listing
November 2018

Development of a High Coverage Pseudotargeted Lipidomics Method Based on Ultra-High Performance Liquid Chromatography-Mass Spectrometry.

Anal Chem 2018 06 8;90(12):7608-7616. Epub 2018 Jun 8.

CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics , Chinese Academy of Sciences , Dalian , Liaoning , 116023 , China.

Lipid coverage is crucial in comprehensive lipidomics studies challenged by high diversity in lipid structures and wide dynamic range in lipid levels. Current state-of-the-art lipidomics technologies are mostly based on mass spectrometry (MS), including direct-infusion MS, chromatography-MS, and matrix-assisted laser desorption ionization (MALDI) imaging MS, each with its pros and cons. Due to the need or favorability for measurement of isomers and isobars, chromatography-MS is preferable for lipid profiling. The ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)-based nontargeted lipidomics approach and UHPLC-tandem MS (UHPLC-MS/MS)-based targeted approach are two representative methodological platforms for chromatography-MS. In the present study, we developed a high coverage pseudotargeted lipidomics method combining the advantages of nontargeted and targeted lipidomics approaches. The high coverage of lipids was achieved by integration of the detected lipids derived from nontargeted UHPLC-HRMS lipidomics analysis of multiple matrices (e.g., plasma, cell, and tissue) and the predicted lipids speculated on the basis of the structure and chromatographic retention behavior of the known lipids. A total of 3377 targeted lipid ion pairs with over 7000 lipid molecular structures were defined. The pseudotargeted lipidomics method was well validated with satisfactory analytical characteristics in terms of linearity, precision, reproducibility, and recovery for lipidomics profiling. Importantly, it showed better repeatability and higher coverage of lipids than the nontargeted lipidomics method. The applicability of the developed pseudotargeted lipidomics method was testified in defining differential lipids related to diabetes. We believe that comprehensive lipidomics studies will benefit from the developed high coverage pseudotargeted lipidomics approach.
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http://dx.doi.org/10.1021/acs.analchem.8b01331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242181PMC
June 2018

Comprehensive Strategy to Construct In-House Database for Accurate and Batch Identification of Small Molecular Metabolites.

Anal Chem 2018 06 8;90(12):7635-7643. Epub 2018 Jun 8.

CAS Key Laboratory of Separation Science for Analytical Chemistry , Dalian Institute of Chemical Physics, Chinese Academy of Science , Dalian 116023 , China.

Identification of the metabolites is an essential step in metabolomics study to interpret the regulatory mechanism of pathological and physiological processes. However, it is still difficult in LC-MS -based studies because of the complexity of mass spectrometry, chemical diversity of metabolites, and deficiency of standards database. In this work, a comprehensive strategy is developed for accurate and batch metabolite identification in nontargeted metabolomics studies. First, a well-defined procedure was applied to generate reliable and standard LC-MS data, including t, MS, and MS information at a standard operational procedure. An in-house database including about 2000 metabolites was constructed and used to identify the metabolites in nontargeted metabolic profiling by retention time calibration using internal standards, precursor ion alignment and ion fusion, auto-MS information extraction and selection, and database batch searching and scoring. As an application example, a pooled serum sample was analyzed to deliver the strategy, and 202 metabolites were identified in the positive ion mode. It shows our strategy is useful for LC-MS -based nontargeted metabolomics study.
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http://dx.doi.org/10.1021/acs.analchem.8b01482DOI Listing
June 2018

Prevalence of the integration status for human papillomavirus 16 in esophageal carcinoma samples.

Turk J Gastroenterol 2018 03;29(2):157-163

College of Life Science and Bio-engineering, Beijing University of Technology, Beijing, China.

Background/aims: To investigate the etiology of esophageal cancer (EC) related with human papillomavirus (HPV) infection.

Materials And Methods: Fresh surgically resected tissue samples and clinical information were obtained from 189 patients. Genomic DNA was extracted, and HPV was detected using polymerase chain reaction (PCR) with HPV L1 gene primers of MY09/11; HPV16 was detected using HPV16 E6 type-specific primer sets. Copies of HPV16 E2, E6, and the human housekeeping gene β-actin were tested using quantitative PCR to analyze the relationship between HPV16 integration and esophageal squamous cell carcinoma and the relationship between the HPV16 integration status and clinical information of patients.

Results: Of the 189 samples, 168 HPV-positive samples were detected, of which 76 were HPV16 positive. Among the HPV16 positive samples, 2 cases (E2/E6 ratio>1) were 2.6% (2/76) purely episomal, 65 (E2/E6 ratio between 0 and 1) were 85.6% (65/76) mixture of integrated and episomal, and 9 (E2/E6 ratio=0) were 11.8% (9/76) purely integrated. The results indicate that integration of HPV16 was more common in the host genome than in the episome genome. The prevalence rate of HPV16 integration is increasing with the pathological stage progression of esophageal carcinoma (EC).

Conclusion: A high prevalence of HPV16 suggested that HPV16 has an etiological effect on the progress of EC. Integration of HPV16 is more common than episome genome in the host cells, indicating that continuous HPV infection is the key to esophageal epithelial cell malignant conversion and canceration.
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http://dx.doi.org/10.5152/tjg.2018.17568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284706PMC
March 2018

Integration sites of human papillomavirus 18 in esophageal cancer samples.

Oncol Lett 2018 May 7;15(5):7438-7442. Epub 2018 Mar 7.

College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, P.R. China.

To investigate the association between human papillomavirus (HPV) infection and esophageal cancer, genomic DNA was isolated from 189 samples obtained from patients with esophageal carcinoma, and HPV DNA was identified using the polymerase chain reaction (PCR) with the following specific primers: My09/11 for HPV L1 and HPV18 E6 for HPV18. The HPV18 gene products were sequenced to identify the HPV genotype and the HPV18 integration site was verified using PCR amplification of papillomavirus oncogene transcripts. HPV18 oncogene transcript products were ligated into a pMD-18T plasmid vector and sequenced to confirm the physical location of HPV18 integration. Of the 189 samples, 168 were positive for HPV, of which 33 were positive for HPV18. The sequencing analysis identified two HPV18 E6-positive samples containing one mutation and two samples containing two mutations in the viral DNA. In total ~600 bp of the HPV18 oncogene transcript was detected in three esophageal cancer samples. Sequence analysis revealed that, in two patients, the HPV18 infection was integrated into human chromosome 5, whereas in the remaining sample the virus was integrated into human chromosome 2. The high prevalence of HPV18 infection suggested that HPV18 infection is a pathogenic factor in esophageal carcinoma progression. The integration of HPV18 DNA into the host cell genome suggests that persistent HPV infection has a role in esophageal epithelial cell malignant transformation and carcinogenesis.
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http://dx.doi.org/10.3892/ol.2018.8191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920840PMC
May 2018

Darzens reaction of thioisatins and sulfonium salts: approach to the synthesis of thiochromenone derivatives with anticancer potency.

Org Biomol Chem 2018 05;16(18):3487-3494

Tianjin Key Laboratory of Organic Solar Cells and Photochemical Conversion, School of Chemistry & Chemical Engineering, Tianjin University of Technology, Tianjin 300384, P. R. China.

A new Darzens reaction of thioisatins and sulfonium salts has, for the first time, been reported. This reaction allows efficient access to thiochromenone derivatives in good to excellent yields under mild reaction conditions. The substrate scope includes both electron-withdrawing and electron-donating groups on both the thioisatins and sulfonium salts. Moreover, some of the synthesized thiochromenone derivatives have been found to show potent anticancer activities against six different cancer cell lines using the methylthiazoltetrazolium (MTT) assay.
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http://dx.doi.org/10.1039/c8ob00402aDOI Listing
May 2018

Effect of liposome‑mediated HSP27 transfection on collagen synthesis in alveolar type II epithelial cells.

Mol Med Rep 2018 May 14;17(5):7319-7324. Epub 2018 Mar 14.

School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei 063210, P.R. China.

To investigate the effect of liposome Lipofectamine® 2000‑mediated HSP27 plasmid transfection in A549 human alveolar type II epithelial cell line on collagen synthesis during transforming growth factor‑β1 (TGF‑β1)‑induced type II epithelial cell transition to myofibroblasts. Cells were transfected with varying ratios of the Lipofectamine® 2000‑mediated heat shock protein 27 (HSP27) plasmid and the transfection efficiency was determined using flow cytometry. The maximum transfection efficacy was confirmed by laser confocal microscopy. HSP gene expression and the most efficient HSP27 plasmid were determined using reverse transcription‑quantitative polymerase chain reaction. Western blot analysis was used to examine HSP27 and collagen expression levels. With a transfection efficiency of 83%, the 8 µg:20 µl ratio of liposome: Plasmid had the highest transfection levels. Among the four different interference sequences in the HSP27 plasmid, the D sequence had the highest interference effect with 70% silencing of the HSP27 gene. The expression of type I and III collagen in TGF‑β1‑induced transition of A549 human alveolar type II epithelial cell line to myofibroblasts was significantly downregulated by the successful transfection with HSP27‑interfering plasmid. The expression of type I and III collagen in the TGF‑β1‑induced transition of A549 cells to myofibroblasts was significantly downregulated by transfection of A549 cells with HSP27 plasmid D‑interfering sequence and optimal ratio of Lipofectamine® 2000 and HSP27 plasmid.
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http://dx.doi.org/10.3892/mmr.2018.8744DOI Listing
May 2018

CDK6 inhibits white to beige fat transition by suppressing RUNX1.

Nat Commun 2018 03 9;9(1):1023. Epub 2018 Mar 9.

Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA, 02111, USA.

Whereas white adipose tissue depots contribute to the development of metabolic diseases, brown and beige adipose tissue has beneficial metabolic effects. Here we show that CDK6 regulates beige adipocyte formation. We demonstrate that mice lacking the CDK6 protein or its kinase domain (K43M) exhibit significant increases beige cell formation, enhanced energy expenditure, better glucose tolerance, and improved insulin sensitivity, and are more resistant to high-fat diet-induced obesity. Re-expression of CDK6 in Cdk6 mature or precursor cells, or ablation of RUNX1 in K43M mature or precursor cells, reverses these phenotypes. Furthermore, RUNX1 positively regulates the expression of Ucp-1 and Pgc1α by binding to proximal promoter regions. Our findings indicate that CDK6 kinase activity negatively regulates the conversion of fat-storing cells into fat-burning cells by suppressing RUNX1, and suggest that CDK6 may be a therapeutic target for the treatment of obesity and related metabolic diseases.
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http://dx.doi.org/10.1038/s41467-018-03451-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845007PMC
March 2018

RIP140/PGC-1α axis involved in vitamin A-induced neural differentiation by increasing mitochondrial function.

Artif Cells Nanomed Biotechnol 2018 7;46(sup1):806-816. Epub 2018 Mar 7.

a Department of Pediatric , Peking University People's Hospital , Beijing , China.

Vitamin A deficiency and mitochondrial dysfunction are both associated with neural differentiation-related disorders, such as Alzheimer's disease (AD) and Down syndrome (DS). The mechanism of vitamin A-induced neural differentiation and the notion that vitamin A can regulate the morphology and function of mitochondria in its induction of neural differentiation through the RIP140/PGC-1α axis are unclear. The aim of this study was to investigate the roles and underlying mechanisms of RIP140/PGC-1α axis in vitamin A-induced neural differentiation. Human neuroblastoma cells (SH-SY5Y) were used as a model of neural stem cells, which were incubated with DMSO, 9-cis-retinoic acid (9-cis-RA), 13-cis-retinoic acid (13-cis-RA) and all-trans-retinoic acid (at-RA). Neural differentiation of SH-SY5Y was evaluated by Sandquist calculation, combined with immunofluorescence and real-time polymerase chain reaction (PCR) of neural markers. Mitochondrial function was estimated by ultrastructure assay using transmission electron microscopy (TEM) combined with the expression of PGC-1α and NEMGs using real-time PCR. The participation of the RA signaling pathway was demonstrated by adding RA receptor antagonists. Vitamin A derivatives are able to regulate mitochondrial morphology and function, and furthermore to induce neural differentiation through the RA signaling pathway. The RIP140/PGC-1α axis is involved in the regulation of mitochondrial function in vitamin A derivative-induced neural differentiation.
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http://dx.doi.org/10.1080/21691401.2018.1436552DOI Listing
April 2019

Plasma lipidomics reveals potential lipid markers of major depressive disorder.

Anal Bioanal Chem 2016 Sep 25;408(23):6497-507. Epub 2016 Jul 25.

Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, Liaoning, 116023, China.

Major depressive disorder (MDD) is a grave debilitating mental disease with a high incidence and severely impairs quality of life. Therefore, its physiopathological basis study and diagnostic biomarker discovery are extremely valuable. In this study, a non-targeted lipidomics strategy using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to reveal differential lipids between MDD (n = 60) and healthy controls (HCs, n = 60). Validation of changed lipid species was performed in an independent batch including 75 MDD and 52 HC using the same lipidomic method. Pronouncedly changed lipid species in MDD were discovered, which mainly were lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), 1-O-alkyl-2-acyl-PE (PE O), 1-O-alkyl-2-acyl-PC (PC O), sphingomyelin (SM), diacylglycerol (DG), and triacylglycerol (TG). Among these lipid species, LPC, LPE, PC, PE, PI, TG, etc. remarkably increased in MDD and showed pronounced positive relationships with depression severity, while 1-O-alkyl-2-acyl-PE and SM with odd summed carbon number significantly decreased in MDD and demonstrated negative relationships with depression severity. A combinational lipid panel including LPE 20:4, PC 34:1, PI 40:4, SM 39:1, 2, and TG 44:2 was defined as potential diagnostic biomarker with a good sensitivity and specificity for distinguishing MDD from HCs. Our study brings insights into lipid metabolism disorder in MDD and provides a specific potential biomarker for MDD diagnose.
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http://dx.doi.org/10.1007/s00216-016-9768-5DOI Listing
September 2016

Adjuvant Treatment with Yupingfeng Formula for Recurrent Respiratory Tract Infections in Children: A Meta-analysis of Randomized Controlled Trials.

Phytother Res 2016 Jul 4;30(7):1095-103. Epub 2016 May 4.

Department of Pediatrics, Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, China.

This meta-analysis aimed to evaluate the immunomodulating function of Yupingfeng Formula (YPFF) in children with recurrent respiratory tract infections (RRTIs). The PubMed, EMBASE, Cochrane Library, CNKI and WanFang databases were searched for randomized controlled trials comparing with and without YPFF for RRTIs in children. Twelve trials with 1236 patients were identified. Adjuvant treatment with YPFF significantly increased serum levels of IgA (weighted mean difference [WMD] 0.33 mg/mL; 95% confidence interval [CI] 0.20 to 0.45), IgG (WMD 1.36 mg/mL; 95% CI 1.06 to 1.65), IgM (WMD 0.16 mg/mL; 95% CI 0.02 to 0.31), and CD3(+) T-lymphocytes (WMD 10.16%; 95% CI 4.62 to 15.69) but not CD4(+) T-lymphocytes (WMD 3.16%; 95% CI -0.27 to 6.59) and CD8(+) T-lymphocytes (WMD -0.84%; 95% CI -2.50 to 0.81). YPFF also reduced the frequency of RRTIs (WMD -3.80 times; 95% CI -4.86 to -2.74) and increased total effective rates of symptom improvement (risk ratio: 1.44; 95% CI 1.19 to 1.75). Adjuvant treatment with YPFF could improve total clinical effective rate and decrease the frequency of respiratory tract infections in children with RRTIs. The beneficial effects of YPFF may be correlated to its immunomodulating action. More well-designed trials with larger sample sizes are needed to evaluate its efficacy and safety. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/ptr.5628DOI Listing
July 2016

The protective effects of Ribes diacanthum Pall on cisplatin-induced nephrotoxicity in mice.

J Ethnopharmacol 2016 Feb 17;178:297-306. Epub 2015 Oct 17.

Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, Jiangsu 211198, China; Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing, Jiangsu 211198, China. Electronic address:

Ethnopharmacological Relevance: Ribes diacanthum Pall. (Saxifragaceae), a Mongolian folk medicinal plant, was used to treat urinary system diseases. The present work aims to investigate the protective effects of Ribes diacanthum Pall (RDP) against cisplatin-induced nephrotoxicity.

Methods: The renal injury was modeled by intraperitoneal injection of cisplatin for 5 consecutive days (5 mg/kg). Nephroprotection of RDP was investigated by oral administration of RDP aqueous extract at a daily dose of 40 mg/kg for 14 consecutive days, starting 7 days prior to cisplatin administration.

Results: We demonstrated that pretreatment with RDP aqueous extract protected the mice from death induced by cisplatin administration. RDP treatment also significantly reduced blood urea nitrogen (BUN) and serum creatinine (Cr) levels observed in cisplatin-administrated mice. Histopathological analysis demonstrated that RDP administration protected cisplatin-induced renal tubular cell apoptosis. Further western blotting analysis revealed that RDP significantly reversed cisplatin-increased expression levels of cleaved-Caspase-3, Bax and cisplatin-decreased expression level of Bcl-2 in renal tissue. Finally, RDP markedly enhanced enzyme activities of reduced superoxide dismutase (SOD), Heme oxygenase 1 (HO-1) and catalase (CAT), suppressed lipid peroxidation as well as reactive oxygen species (ROS) production.

Conclusion: We concluded that RDP displayed nephroprotective effects against cisplatin-induced renal tubular cell apoptosis, possibly associated with both enhanced antioxidase activity and suppressed ROS generation. Given the major nephrotoxicity of cisplatin cancer chemotherapy, RDP might be a potential candidate for neoadjuvant chemotherapy.
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http://dx.doi.org/10.1016/j.jep.2015.10.003DOI Listing
February 2016

Can We Stop Antibiotic Therapy When Signs and Symptoms Have Resolved in Diabetic Foot Infection Patients?

Int J Low Extrem Wounds 2015 Sep 6;14(3):277-83. Epub 2015 Aug 6.

Tianjin Medical University, Tianjin, China.

The study aimed to investigate whether we can stop antibiotic therapy when signs and symptoms have resolved in diabetic foot infection (DFI) patients with different grades of peripheral arterial disease (PAD) and those without PAD, and to determine whether the severity of PAD and infection has an effect on antibiotic therapy duration. A prospective randomized controlled trial of DFI patients was carried out. Patients were randomized into 2 groups when signs and symptoms had resolved: continuing antibiotics group (CAG) and discontinuing antibiotics group (DAG). The recurrence and clinical outcomes were recorded. The recurrence rate of mild infection with mild/moderate PAD was similar in the 2 groups. Compared with CAG, the recurrence rate of mild infection with severe PAD was higher in DAG (P = .030), also for moderate/severe infection with PAD (mild/moderate [P = .032]; severe [P = .008]). No difference was found in the 2 groups (either mild or moderate/severe) for those without PAD. The clinical outcomes of mild infection in patients were similar in the 2 groups. For moderate/severe infection, the healing rate was higher (73.3% vs 48.3%), and the rate of minor/major amputation and death was lower (23.8% vs 49.4%; 6.9% vs 20.7%; 2.0% vs 13.8%) in the CAG. When the clinical signs and symptoms of infection have resolved, it might be appropriate to stop antibiotics for DFI patients without PAD, and also for patients with mild infection with mild/moderate PAD. For patients with mild infection with severe PAD and moderate/severe infection with PAD, we should perhaps continue antibiotic treatment. Continuing antibiotic therapy could improve clinical outcomes for patients with moderate/severe infection.
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http://dx.doi.org/10.1177/1534734615596891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601082PMC
September 2015

Clinical improvement in psoriasis with specific targeting of interleukin-23.

Nature 2015 May 9;521(7551):222-6. Epub 2015 Mar 9.

Merck &Co., Inc., Whitehouse Station, New Jersey 08889, USA.

Psoriasis is a chronic inflammatory skin disorder that affects approximately 2-3% of the population worldwide and has severe effects on patients' physical and psychological well-being. The discovery that psoriasis is an immune-mediated disease has led to more targeted, effective therapies; recent advances have focused on the interleukin (IL)-12/23p40 subunit shared by IL-12 and IL-23. Evidence suggests that specific inhibition of IL-23 would result in improvement in psoriasis. Here we evaluate tildrakizumab, a monoclonal antibody that targets the IL-23p19 subunit, in a three-part, randomized, placebo-controlled, sequential, rising multiple-dose phase I study in patients with moderate-to-severe psoriasis to provide clinical proof that specific targeting of IL-23p19 results in symptomatic improvement of disease severity in human subjects. A 75% reduction in the psoriasis area and severity index (PASI) score (PASI75) was achieved by all subjects in parts 1 and 3 (pooled) in the 3 and 10 mg kg(-1) groups by day 196. In part 2, 10 out of 15 subjects in the 3 mg kg(-1) group and 13 out of 14 subjects in the 10 mg kg(-1) group achieved a PASI75 by day 112. Tildrakizumab demonstrated important clinical improvement in moderate-to-severe psoriasis patients as demonstrated by improvements in PASI scores and histological samples.
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http://dx.doi.org/10.1038/nature14175DOI Listing
May 2015

Downregulation of LRPPRC induces apoptosis in prostate cancer cells through the mitochondria-mediated pathway.

Cancer Biother Radiopharm 2014 Nov;29(9):345-50

Department of Urology, People's Hospital of Zhengzhou City , Zhengzhou, China .

Leucine-rich pentatricopeptide repeat motif-containing protein (LRPPRC) is a multifunctional protein involved in the mitochondrial gene expression and function, cell cycle progression, and tumorigenesis. However, the functional role of LRPPRC in prostate cancer (PCa) has not yet been elucidated. In this study, two PCa cell lines were examined to determine the effects of LRPPRC on cell proliferation, invasion, and apoptosis in vitro. Our results showed that the expression levels of LRPPRC were significantly decreased in the two PCa cell lines after transfection with small interfering RNA (siRNA)-LRPPRC. Knockdown of LRPPRC by siRNA significantly inhibited the invasion and promoted the apoptosis of PCa cells. In addition, downregulation of LRPPRC expression resulted in the reduced expression of Bcl-2, upregulation of Bax, and cleaved caspase-9 and caspase-3. Taken together, these results show that the downregulation of LRPRPC expression induces apoptosis through the mitochondria-mediated pathway in PCa cells. These experimental data seem to suggest that LRPPRC plays a critical role in the development of PCa, and its inhibition could present a potential molecular approach for the treatment of PCa.
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http://dx.doi.org/10.1089/cbr.2014.1661DOI Listing
November 2014

Pharmacokinetics and bioavailability study of polydatin in rat plasma by using a LC-MS/MS method.

Pak J Pharm Sci 2014 Nov;27(6):1931-7

Laboratory of Toxicology & Pharmacology, Faculty of Tropical Medicine and Public Health, The Second Military Medical University, Shanghai, China.

To investigate the pharmacokinetic and bioavailability of polydatin (PD) in rats after oral and intravenous administration, a simple, rapid and sensitive liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method was developed and validated for the determination of polydation. After precipitating the plasma proteins with methanol, the analytes were separated on a C18 column (3.5µm, 2.1×100 mm) with an isocratic mobile phase consisting of methanol-acetonitrile-0.1% formic acid (18: 15: 67, v/v/v) at a flow rate of 0.3mL/min. The Agilent G6410A triple quadrupole LC/MS system was operated under the multiple reaction monitoring (MRM) mode and the electrospray ionization technique was in negative mode. Linear responses were obtained for PD ranging from 1.0-5000.0 ng/mL (r= 0.9984) and the LLOQ was 1.0ng/ml and was sufficient for the pharmacokinetic studies. The intra-day and inter-day accuracy and precision of the assay were less than 8.0%. The method is capable of quantifying PD. The pharmacokinetic parameters of polydatin after intragastric administration of PD with different doses (50, 100 and 300 mg/kg) and intravenous administration at the dose of 20 mg/kg, were obtained, with t1/2 of 200.30 min, 210.30 min, 272.26 min, and 112.5 min, and AUC0-∞ of 125626.41 μg/L· min, 250433.47 μg/L·min, 693722.60 μg/L· min and 1723509.57μg/L· min, respectively. The absolute bioavailability of PD was somewhat low to 2.9%. The results were firsly reported, as far as we know, about bioavailability of PD and seem important for linking PD and other phenolic glycosides-related drugs administration to their medicinal effects.
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November 2014

Classification of Aurora B kinase inhibitors using computational models.

Comb Chem High Throughput Screen 2014 Feb;17(2):114-23

State Key Laboratory of Chemical Resource Engineering, Department of Pharmaceutical Engineering, P.O. Box 53, Beijing University of Chemical Technology, 15 BeiSanHuan East Road, Beijing 100029, P.R. China.

Using Self-Organizing Map (SOM) and Support Vector Machine (SVM), four classification models were built to predict whether a compound is an active or weakly active inhibitor of Aurora B kinase. A dataset of 679 Aurora B kinase inhibitors was collected, and randomly split into a training set (278 active and 204 weakly active inhibitors) and a test set (109 active and 88 weakly active inhibitors). Based on 19 selected ADRIANA.Code descriptors and 135 MACCS fingerprints, all the four models showed a good prediction accuracy of over 87% on the test set. It benefited from the advantages of two different types of molecular descriptors in encoding structure information of compounds and characterizing the diversity of different inhibitors. Some molecular properties, such as hydrogen-bonding interactions and atom charge related descriptors were found to be important to the bioactivity of Aurora B kinase inhibitors.
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http://dx.doi.org/10.2174/13862073113166660063DOI Listing
February 2014

Clinical, virological, and histopathological manifestations of fatal human infections by avian influenza A(H7N9) virus.

Clin Infect Dis 2013 Nov 13;57(10):1449-57. Epub 2013 Aug 13.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases.

Background: Systematic analysis of histopathological and serial virological changes of fatal influenza A(H7N9) cases is lacking.

Methods: Patients with A(H7N9) infection admitted to our intensive care unit during 10-23 April 2013 were included. Viral loads in the respiratory tract, as inferred from the cycle threshold (Ct) value of reverse transcription polymerase chain reaction (RT-PCR), and the serum hemagglutination inhibition (HAI) antibody titer, were analyzed. Postmortem biopsies of the lung, liver, kidney, spleen, bone marrow, and heart were examined.

Results: Twelve patients (6 deaths, 6 survivors) were included. Median viral load was higher in sputa than the nasopharyngeal swabs for fatal cases (median Ct, 23 vs 30.5; P = .08). RT-PCR for A(H7N9) was positive in stool samples (4/6 [67%]) of fatal cases and (2/6 [33%]) of survivors, but was negative in the cerebrospinal fluid, urine, or blood of all patients. Nosocomial bacterial infections were more common in patients who died than in survivors (83% vs 50%). HAI titers increased by ≥4-fold in those with convalescent sera. Postmortem biopsy for 3 patients showed acute diffuse alveolar damage. Patient 1, who died 8 days after symptom onset, had intra-alveolar hemorrhage. Patients 2 and 3, who died 11 days after symptom onset, had pulmonary fibroproliferative changes. Reactive hemophagocytosis in the bone marrow and lymphoid atrophy in splenic tissues were compatible with laboratory findings of leukopenia, lymphopenia, and thrombocytopenia. Hypoxic and fatty changes of kidney and liver tissues are compatible with impaired renal or liver function.

Conclusions: Fatal A(H7N9) infection was characterized by viral and secondary bacterial pneumonia with 67% having positive RT-PCR in stool.
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http://dx.doi.org/10.1093/cid/cit541DOI Listing
November 2013
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