Publications by authors named "Jing-Ying Zhang"

41 Publications

Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer.

EBioMedicine 2021 Nov 21;74:103714. Epub 2021 Nov 21.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China. Electronic address:

Background: Molecular features underlining the multistage progression of gastric lesions and development of early gastric cancer (GC) are poorly understood, restricting the ability to GC prevention and management.

Methods: We portrayed proteomic landscape and explored proteomic signatures associated with progression of gastric lesions and risk of early GC. Tissue proteomic profiling was conducted for a total of 324 subjects. A case-control study was performed in the discovery stage (n=169) based on populations from Linqu, a known high-risk area for GC in China. We then conducted two-stage validation, including a cohort study from Linqu (n = 56), with prospective follow-up for progression of gastric lesions (280-473 days), and an independent case-control study from Beijing (n = 99).

Findings: There was a clear distinction in proteomic features for precancerous gastric lesions and GC. We derived four molecular subtypes of gastric lesions and identified subtype-S4 with the highest progression risk. We found 104 positively-associated and 113 inversely-associated proteins for early GC, with APOA1BP, PGC, HPX and DDT associated with the risk of gastric lesion progression. Integrating these proteomic signatures, the ability to predict progression of gastric lesions was significantly strengthened (areas-under-the-curve=0.88 (95%CI: 0.78-0.99) vs. 0.56 (0.36-0.76), Delong's P = 0.002). Immunohistochemistry assays and examination at mRNA level validated the findings for four proteins.

Interpretation: We defined proteomic signatures for progression of gastric lesions and risk of early GC, which may have translational significance for identifying particularly high-risk population and detecting GC at an early stage, improving potential for targeted GC prevention.

Funding: The funders are listed in the Acknowledgement.
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http://dx.doi.org/10.1016/j.ebiom.2021.103714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617343PMC
November 2021

Characterization of the complete chloroplast genome of the L. cv. Shepody (Solanaceae).

Mitochondrial DNA B Resour 2021 14;6(8):2342-2344. Epub 2021 Jul 14.

College of Horticulture, Jilin Agricultural University, Changchun City, P.R. China.

Potato ( L.), a species of the family Solanaceae, is the fourth most important food crop worldwide. L. cv. Shepody is a long, smooth, white-skinned potato cultivar with medium green leaves. It has good specific gravity and boils and bakes well. To support more molecular data for breeding of S. tuberosum, the complete chloroplast (cp) genome sequence of L. cv. Shepody was determined using the next-generation sequencing. In leaves, the chloroplast genome accounts for 3.88% of the total genome. The entire cp genome was determined to be 155,296 bp in length. It contained large single-copy (LSC) and small single-copy (SSC) regions of 85,737 and 18,373 bp, respectively, which were separated by a pair of 25,593 bp inverted repeat (IR) regions. The genome contained 132 total genes, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The overall GC content of the genome is 37.9%. A phylogenetic tree reconstructed by 60 chloroplast genomes reveals that L. cv. Shepody was closely related to S. tuberosum L. cv. Desiree with bootstrap support values of 100%.
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http://dx.doi.org/10.1080/23802359.2021.1934135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284121PMC
July 2021

Inhibition of autophagy by YC-1 promotes gefitinib induced apoptosis by targeting FOXO1 in gefitinib-resistant NSCLC cells.

Eur J Pharmacol 2021 Oct 13;908:174346. Epub 2021 Jul 13.

School of Life Science Lanzhou University, Lanzhou, 730000, PR China; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Science, Lanzhou University, Lanzhou, 730000, PR China. Electronic address:

Non-small cell lung cancer (NSCLC) is the most common cancer in the world. Gefitinib, an inhibitor of EGFR tyrosine kinase, is highly effective in treating NSCLC patients with activating EGFR mutations (L858R or Ex19del). However, despite excellent disease control with gefitinib therapy, innate resistance and inevitable acquired resistance represent immense challenges in NSCLC therapy. Gefitinib potently induces cytoprotective autophagy, which has been implied to contribute to both innate and acquired resistance to gefitinib in NSCLC cells. Currently, abrogation of autophagy is considered a promising strategy for NSCLC therapy. In the present study, YC-1, an inhibitor of HIF-1α, was first found to significantly inhibit the autophagy induced by gefitinib by disrupting the fusion of autophagosomes and lysosomes and thereby enhancing the proapoptotic effect of gefitinib in gefitinib-resistant NSCLC cells. Furthermore, the combinational anti-autophagic and pro-apoptotic effect of gefitinib and YC-1 was demonstrated to be associated with an enhanced of forkhead box protein O1 (FOXO1) transcriptional activity which resulted from an increase in the p-FOXO1 protein level in gefitinib-resistant NSCLC cells. Our data suggest that inhibition of autophagy by targeting FOXO1 may be a feasible therapeutic strategy to overcome both innate and acquired resistance to EGFR-TKIs.
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http://dx.doi.org/10.1016/j.ejphar.2021.174346DOI Listing
October 2021

Anatomical Study of the Accessory Tendon of the Extensor Hallucis Longus Muscle and Its Clinical Application.

Clin Orthop Surg 2021 Jun 2;13(2):261-265. Epub 2021 Feb 2.

Department of Hand and Foot Surgery, Yanbian Hospital, Yanji, China.

Backgroud: The accessory tendon of the extensor hallucis longus (ATEHL) muscle is a common abnormal structure, and its clinical significance remains debatable. In this study, we provide the incidence of the ATEHL and characterize its morphological types in Asian cadavers and investigate its clinical applications.

Methods: The tendons from 50 adult cadaveric feet, fixed in 10% formalin, were analyzed. We measured the length and width of both the ATEHL and the extensor hallucis brevis (EHB).

Results: All dissected specimens had an ATEHL. The first metatarsophalangeal joint was surrounded by an accessory tendon that inserted onto the joint capsule and the dorsal base of the proximal phalanx. We classified the ATEHL into 3 types based on their directions. Differences in ATEHL type based on sex were not statistically significant.

Conclusions: We found an ATEHL in all cadaveric specimens in this study. We surmise that the ATEHL acts as an antagonist with the EHB when the toe is extending, which might help prevent the occurrence of hallux valgus deformity.
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http://dx.doi.org/10.4055/cios20054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173238PMC
June 2021

Clinical features and prognostic impact of TCF3-PBX1 in childhood acute lymphoblastic leukemia: A single-center retrospective study of 837 patients from China.

Curr Probl Cancer 2021 Dec 16;45(6):100758. Epub 2021 May 16.

Department of Hematology-oncology, Children's Hospital of Zhejiang University School of Medicine, the Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, National Clinical Research Center for Child Health, Zhejiang University, Hangzhou, China. Electronic address:

Objectives: Conflicting data have been published regarding the prognostic impact of the t(1;19)/TCF3-PBX1 translocation in childhood ALL. The objective of this study was to explore the correlation between the TCF3-PBX1 fusion gene and clinical outcome in Chinese children with newly diagnosed ALL.

Methods: In order to address this issue in our setting, we summarized and analyzed the data of 837 Chinese children with ALL diagnosed between 2010 and 2017. All the patients were treated with the National Protocol of Childhood Leukemia in China (NPCLC)-ALL-2008 protocol. Clinical characteristics and prognosis of pediatric ALL patients with or without TCF3-PBX1 rearrangement were analyzed and compared retrospectively.

Results: The TCF3-PBX1 fusion gene was identified in 48 (5.7%) of 837 children with ALL. Our results showed that TCF3-PBX1 positive patients had higher pretreatment white blood cell counts, higher PB blasts percentages and worse risk classification at diagnosis. No statistically significant differences in CR rates, response to prednisone and relapse rates were found between TCF3-PBX1-positive and -negative patients. The 5-year predicted EFS, RFS, and OS of the TCF3-PBX1 positive group compared with the control group were 86.2%±5.3% vs 85.4%±1.3% (P=0.657), 88.2%±5.1% vs 92.2%±1.0% (P=0.458) and 90.4%±4.6% vs 89.0%±1.1% (P=0.561), respectively. No differences were observed regarding clinical outcome between these two groups. When compared with standard risk, intermediate risk and high risk group patients, the long-term survival of TCF3/PBX1 positive group was approximately similar to that of the intermediate risk group under the same protocol in our single center.

Conclusion: In contrast to previous studies, childhood ALL patients with TCF3-PBX1 transcripts do not appear to show a better outcome than their negative counterparts. TCF3/PBX1 positive was a definitive intermediate risk factor with our NPCLC-ALL-2008 protocol.
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http://dx.doi.org/10.1016/j.currproblcancer.2021.100758DOI Listing
December 2021

Characterization of the complete chloroplast genome of the L. cv. Favorita (Solanaceae).

Mitochondrial DNA B Resour 2021 Mar 16;6(3):909-911. Epub 2021 Mar 16.

College of Horticulture, Jilin Agricultural University, Changchun, P.R. China.

Potato ( L.), a species of the family Solanaceae, is the fourth most important food crop worldwide. L. cv. Favorita is a long oval, smooth, yellowish-skinned potato variety with green and plump leaves. It has a dry matter content of 17.7% and starch content of 12.4-14.01% in the tuber. In order to support more genetic data for the taxonomy of , the complete chloroplast (cp) genome sequence of L. cv. Favorita was determined using next-generation sequencing. In leaves, the chloroplast genome accounts for 5.17% of the total genome. The entire cp genome was determined to be 155,296 bp in length. It contained large single-copy (LSC) and small single-copy (SSC) regions of 85,737 and 18,373 bp, respectively, which were separated by a pair of 25,593 bp inverted repeat (IR) regions. The genome contained 132 total genes, including 87 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The overall GC content of the genome is 37.9%. A phylogenetic tree reconstructed by 60 chloroplast genomes reveals that L. cv. Favorita is most closely related to L. cv. Desiree and L. cv. Atlantic.
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http://dx.doi.org/10.1080/23802359.2021.1886885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971314PMC
March 2021

Characterization of the complete chloroplast genome of the L. cv. Atlantic (Solanaceae).

Mitochondrial DNA B Resour 2021 Jan 8;6(1):73-75. Epub 2021 Jan 8.

College of Horticulture, Jilin Agricultural University, Changchun City, P.R. China.

Potato ( L.), a species of the family Solanaceae, is the fourth most important food crop worldwide. L. cv. Atlantic, a main fried special potato, has a dry matter content of 19%-23% and a starch content of 16.26% in the tuber. In order to support more molecular data for the taxony of , the complete chloroplast (cp) genome sequence of L. cv. Atlantic was determined using next-generation sequencing. In leaves, the chloroplast genome accounts for 5.49% of the total genome. The entire cp genome was determined to be 155,296 bp in length. It contained large single-copy (LSC) and small single-copy (SSC) regions of 85,737 and 18,373 bp, respectively, which were separated by a pair of 25,593 bp inverted repeat (IR) regions. The genome contained 132 genes, including 87 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The overall GC content of the genome is 37.9%. A phylogenetic tree reconstructed by 64 chloroplast genomes reveals that L. cv. Atlantic is most closely related to L. cv. Desiree.
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http://dx.doi.org/10.1080/23802359.2020.1845998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808395PMC
January 2021

Pediatric blastic plasmacytoid dendritic cell neoplasm: report of four cases and review of literature.

Int J Hematol 2021 May 4;113(5):751-759. Epub 2021 Jan 4.

Department of Hematology-Oncology, Children's Hospital, Zhejiang University School of Medicine, The Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province, National Clinical Research Center for Child Health, #57 Zhuganxiang Road, Yan-An Street, Hangzhou, 310003, People's Republic of China.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological malignancy with poor outcome. Four children with BPDCN treated at our hospital were enrolled. All the four cases presented with cutaneous lesions. Bone marrow and central nervous system was involved in 50% and 25% of patients, respectively. The whole exome sequencing analysis revealed that KMT2 family genes were the most frequently mutated (4/4, 100%), followed by IKZF2 (2/4, 50%). The point mutation p.D348N was found in three patients and one patient had p.C394Y mutation in the KMT2C gene. Translocation of KMT2A-MLLT3 was found in Case 2. Case 1 had complex karyotype, who was induced by acute myeloid leukemia-like regimens. Although he received allogeneic hematopoietic stem cell transplantation twice as well as CD123 chimeric antigen receptor T cell therapy, the disease still progressed and he died 37 months after diagnosis. The other three patients were treated with Interfant-99 protocol. They tolerated the therapy well without significant toxicities and now in complete remission so far with a median follow up time of 9 months. More studies are needed to address the question whether the complex karyotype and KMT2 family genes are the causes of the relapse and refractory in BPDCN.
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http://dx.doi.org/10.1007/s12185-020-03070-xDOI Listing
May 2021

Regulating Stem Cell-Related Genes Induces the Plastic Differentiation of Cancer Stem Cells to Treat Breast Cancer.

Mol Ther Oncolytics 2020 Sep 31;18:396-408. Epub 2020 Jul 31.

State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, and School of Pharmaceutical Sciences, Peking University, Beijing, China.

Relapse of cancer is associated with multidirectional differentiation and unrestricted proliferative replication potential of cancer stem cells. Herein, we propose the plastic differentiation strategy for irreversible differentiation of cancer stem cells; further, salinomycin and its newly constructed functional liposomes are used to implement this strategy. Whole gene, cancer stem cell-related RNA, and protein expression analyses reveal that salinomycin induces the cancer stem cells into normal cells, dormant cells, and mature cancer cells. Besides, the results indicate that the gatekeeper is related to the inhibition of the protein kinase C (PKC) α signaling pathway. The differentiated normal or dormant cells are incorporated into normal tissue, whereas the rest are killed by chemotherapy. The findings would offer the evidence for plastic differentiation of cancer stem cells and propose a novel strategy for cancer therapy.
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http://dx.doi.org/10.1016/j.omto.2020.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452009PMC
September 2020

Suppression of Helicobacter pylori infection by daily cranberry intake: A double-blind, randomized, placebo-controlled trial.

J Gastroenterol Hepatol 2021 Apr 23;36(4):927-935. Epub 2020 Aug 23.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China.

Background And Aim: Dietary strategies that contribute to reducing incidence of Helicobacter pylori infection without negative side effects are highly desirable owing to worldwide bacterial prevalence and carcinogenesis potential. The aim of this study was to determine dosage effect of daily cranberry consumption on H. pylori suppression over time in infected adults to assess the potential of this complementary management strategy in a region with high gastric cancer risk and high prevalence of H. pylori infection.

Methods: This double-blind, randomized, placebo-controlled trial on 522 H. pylori-positive adults evaluated dose-response effects of proanthocyanidin-standardized cranberry juice, cranberry powder, or their placebos on suppression of H. pylori at 2 and 8 weeks by C-urea breath testing and eradication at 45 days post-intervention.

Results: H. pylori-negative rates in placebo, low-proanthocyanidin, medium-proanthocyanidin, and high-proanthocyanidin cranberry juice groups at week 2 were 13.24%, 7.58%, 1.49%, and 13.85% and at week 8 were 7.35%, 7.58%, 4.48%, and 20.00%, respectively. Consumption of high-proanthocyanidin juice twice daily (44 mg proanthocyanidin/240-mL serving) for 8 weeks resulted in decreased H. pylori infection rate by 20% as compared with other dosages and placebo (P < 0.05). Percentage of H. pylori-negative participants increased from 2 to 8 weeks in subjects who consumed 44 mg proanthocyanidin/day juice once or twice daily, showing a statistically significant positive trend over time. Encapsulated cranberry powder doses were not significantly effective at either time point. Overall trial compliance was 94.25%. Cranberry juice and powder were well-tolerated.

Conclusions: Twice-daily consumption of proanthocyanidin-standardized cranberry juice may help potentiate suppression of H. pylori infection.

Trial Registration: ChiCTR1800017522, per WHO ICTRP.
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http://dx.doi.org/10.1111/jgh.15212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246812PMC
April 2021

Systematic Review and Meta-Analysis of the Efficacy of Appropriate Empiric Anti-Enterococcal Therapy for Intra-Abdominal Infection.

Surg Infect (Larchmt) 2021 Mar 1;22(2):131-143. Epub 2020 Jun 1.

Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Delayed treatment of seriously infected patients results in increased mortality. However, antimicrobial therapy for the initial 24 to 48 hours is mostly empirically provided, without evidence regarding the causative pathogen. Whether empiric anti-enterococcal therapy should be administered to treat intra-abdominal infection (IAI) before obtaining culture results remains unknown. We performed a meta-analysis to explore the effects of empiric enterococci covered antibiotic therapy in IAI and the risk factors for enterococcal infection in IAI. We searched multiple databases systematically and included 23 randomized controlled trials (RCTs) and 13 observational studies. The quality of included studies was assessed, and the reporting bias was evaluated. Meta-analysis was performed using random effects or fixed effects models according to the heterogeneity. The risk ratio (RR), odds ratio (OR), and 95% confidence interval (CI) were calculated. Enterococci-covered antibiotic regimens provided no improvement in treatment success compared with control regimens (RR, 0.99; 95% CI, 0.97-1.00; p = 0.15), with similar mortality and adverse effects in both arms. Basic characteristic analysis revealed that most of the enrolled patients with IAI in RCTs were young, lower risk community-acquired intra-abdominal infection (CA-IAI) patients with a relatively low APACHE II score. Interestingly, risk factor screening revealed that malignancy, corticosteroid use, operation, any antibiotic treatment, admission to intensive care unit (ICU), and indwelling urinary catheter could predispose the patients with IAI to a substantially higher risk of enterococcal infection. "Hospital acquired" itself was a risk factor (OR, 2.81; 95% CI, 2.34-3.39; p < 0.001). It is unnecessary to use additional agents empirically to specifically provide anti-enterococcal coverage for the management of CA-IAI in lower risk patients without evidence of causative pathogen, and risk factors can increase the risk of enterococcal infection. Thus, there is a rationale for providing empiric anti-enterococcal coverage for severely ill patients with CA-IAI with high risk factors and patients with hospital-acquired intra-abdominal infection (HA-IAI).
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http://dx.doi.org/10.1089/sur.2020.001DOI Listing
March 2021

Analysis of rice root bacterial microbiota of Nipponbare and IR24.

Yi Chuan 2020 May;42(5):506-518

State Key Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.

The root-associated bacterial microbiota is closely related to life activities of land plants, and its composition is affected by geographic locations and plant genotypes. However, the influence of plant genotypes on root microbiota in rice grown in northern China remains to be explained. In this study, we performed 16S rRNA gene amplicon sequencing to generate bacterial community profiles of two representative rice cultivars, Nipponbare and IR24. They are planted in Changping and Shangzhuang farms in Beijing and have reached the reproductive stage. We compared their root microbiota in details by Random Forest machine learning algorithm and network analysis. We found that the diversity of rice root microbiota was significantly affected by geographic locations and rice genotypes. Nipponbare and IR24 showed distinct taxonomic composition of the root microbiota and the interactions between different bacteria. Moreover, the root bacteria could be used as biomarkers to distinguish Nipponbare from IR24 across regions. Our study provides a theoretical basis for the in-depth understanding of rice root microbiota in Northern China and the improvement of rice breeding from the perspective of the interaction between root microorganisms and plants.
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http://dx.doi.org/10.16288/j.yczz.20-070DOI Listing
May 2020

YC-1 potentiates the antitumor activity of gefitinib by inhibiting HIF-1α and promoting the endocytic trafficking and degradation of EGFR in gefitinib-resistant non-small-cell lung cancer cells.

Eur J Pharmacol 2020 May 8;874:172961. Epub 2020 Feb 8.

Institute of Biochemistry and Molecular Biology, School of Life Science Lanzhou University, Lanzhou, 730000, PR China. Electronic address:

The tyrosine kinase inhibitor (TKI) gefitinib exerts good therapeutic effect on NSCLC patients with sensitive EGFR-activating mutations. However, most patients ultimately relapse due to the development of drug resistance after 6-12 months of treatment. Here, we showed that a HIF-1α inhibitor, YC-1, potentiated the antitumor efficacy of gefitinib by promoting EGFR degradation in a panel of human NSCLC cells with wild-type or mutant EGFRs. YC-1 alone had little effect on NSCLC cell survival but significantly enhanced the antigrowth and proapoptotic effects of gefitinib. In insensitive NSCLC cell lines, gefitinib efficiently inhibited the phosphorylation of EGFR but not the downstream signaling of ERK, AKT and STAT3; however, when combined with YC-1 treatment, these signaling pathways were strongly impaired. Gefitinib treatment induced EGFR arrest in the early endosome, and YC-1 treatment promoted delayed EGFR transport into the late endosome as well as receptor degradation. Moreover, the YC-1-induced reduction of HIF-1α protein was associated with the enhancement of EGFR degradation. HIF-1α knockdown promoted EGFR degradation, showing synergistic antigrowth and proapoptotic effects similar to those of the gefitinib and YC-1 combination treatment in NSCLC cells. Our findings provide a novel combination treatment strategy with gefitinib and YC-1 to extend the usage of gefitinib and overcome gefitinib resistance in NSCLC patients.
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http://dx.doi.org/10.1016/j.ejphar.2020.172961DOI Listing
May 2020

DOES IT WORK? -a randomized controlled trial to test the efficacy of HCV and HIV-related education on drug users in MMT, China.

BMC Infect Dis 2019 Sep 5;19(1):774. Epub 2019 Sep 5.

Collaborative Innovation Center for Brain Science, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 South Wanping Road, Shanghai, 200030, China.

Background: HCV (Hepatitis C virus) is a prevalent chronic disease with potentially deadly consequences, especially for drug users. However, there are no special HCV or HIV (human immunodeficiency virus)-related intervention programs that are tailored for drug users in China; to fill this gap, the purpose of this study was to explore HCV and HIV-related knowledge among drug users in MMT (methadone maintenance treatment) sites of China and to investigate the effectiveness of HCV and HIV-related education for improving the knowledge of IDUs (injection drug users) and their awareness of infection.

Methods: The study was a randomized cluster controlled trial that compared a usual care group to a usual care plus HCV/HIV-REP (HCV/HIV-Reduction Education Program) group with a 24-week follow-up. The self-designed questionnaires, the HCV- and HIV-related knowledge questionnaire and the HIV/HCV infection awareness questionnaire, were used to collect the data. Four MMT clinics were selected for this project; two MMT clinics were randomly assigned to the research group, with subjects receiving their usual care plus HCV/HIV-REP, and the remaining two MMT clinics were the control group, with subjects receiving their usual care over 12 weeks. Sixty patients were recruited from each MMT clinic. A total of 240 patients were recruited. Follow-up studies were conducted at the end of the 12th week and the 24th week after the intervention.

Results: At baseline, the mean score (out of 20 possible correct answers) for HCV knowledge among the patients in the group receiving the intervention was 6.51 (SD = 3.5), and it was 20.57 (SD = 6.54) for HIV knowledge (out of 45 correct answers) and 8.35 (SD = 2.8) for HIV/HCV infection awareness (out of 20 correct answers). At the 12-week and 24-week follow-up assessments, the research group showed a greater increase in HCV-/HIV-related knowledge (group × time effect, F = 37.444/11.281, P < 0.05) but no difference in their HIV/HCV infection awareness (group × time effect, F = 2.056, P > 0.05).

Conclusion: An MMT-based HCV/HIV intervention program could be used to improve patient knowledge of HCV and HIV prevention, but more effort should be devoted to HIV/HCV infection awareness.

Trial Registration: Protocols for this study were approved by institution review board (IRB) of Shanghai Mental Health Center (IRB:2009036), and registered in U.S national institutes of health (http://www.clinicaltrials.gov, NCT01647191 ). Registered 23 July 2012.
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http://dx.doi.org/10.1186/s12879-019-4421-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727322PMC
September 2019

Environmentally relevant concentrations of arsenite induces developmental toxicity and oxidative responses in the early life stage of zebrafish.

Environ Pollut 2019 Nov 6;254(Pt A):113022. Epub 2019 Aug 6.

College of Geography and Environmental Science, Zhejiang Normal University, Jinhua, Zhejiang 321004, China.

Arsenic (As) present in water is a nonignorable environmental issue, even at low concentrations (≤150 μg L). To evaluate the toxic effect of low concentrations of As, zebrafish at early life stage were exposed to 0, 25, 50, 75, or 150 μg L AsIII for 120 h. Our results indicated that low concentration of AsIII decreased zebrafish larvae's survival rate to 85%, 89% and 86% at 50, 75 and 150 μg L. Furthermore, low concentrations of AsIII exposure caused oxidative stress (elevated superoxide dismutase (SOD) activity and influenced the mRNA transcriptional levels of Cu/ZnSOD and MnSOD) and damage (increased malondialdehyde levels). Meanwhile, zebrafish larvae regulated the mRNA transcription of metallothionein and heat shock protein 70 to alleviate toxicity caused by AsIII. These results revealed lower concentrations (≤150 μg L) of AsIII had a detriment effect on the survival of fish at early life stage, moreover, oxidative stress caused by AsIII posed potential risk for the zebrafish. This study provides novel insight into low concentration AsIII-induced toxicity in zebrafish.
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http://dx.doi.org/10.1016/j.envpol.2019.113022DOI Listing
November 2019

Chronic exposure to dichloroacetamide induces biochemical and histopathological changes in the gills of zebrafish.

Environ Toxicol 2019 Jul 18;34(7):781-787. Epub 2019 Mar 18.

College of Geography and Environmental Science, Zhejiang Normal University, Zhejiang, China.

To evaluate the impact of DCAcAm on zebrafish gill, we measure the responses of antioxidant enzyme (superoxide dismutase, SOD), lipid peroxidation (malondialdehyde, MDA), ATPase (Na /K -ATPase and Ca /Mg -ATP) and histopathological changes of gill in adult zebrafish, after exposed to different concentrations of DCAcAm (0, 1, 10, 100, and 1000 μg L ) for 30 days. Results indicated that DCAcAm first increased and then decreased SOD activity, and DCAcAm also lowered the activities of Na /K -ATPase and Ca /Mg -ATPase. These results indicated that high affinity of DCAcAm probably be a main factor, which can damage the structures of enzymes, thereby inhibiting the SOD and ATPase activities. Besides, histopathological investigation results also manifested that chronic exposure to DCAcAm can damage the gill tissues, disrupting the normal function of gills. We conclude that chronic exposure to DCAcAm was harmful to organisms, not only influence gill function, but also further cause damage on the gill tissues.
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http://dx.doi.org/10.1002/tox.22744DOI Listing
July 2019

The toxicity of 2,6-dichlorobenzoquinone on the early life stage of zebrafish: A survey on the endpoints at developmental toxicity, oxidative stress, genotoxicity and cytotoxicity.

Environ Pollut 2019 Feb 22;245:719-724. Epub 2018 Nov 22.

College of Geography and Environmental Science, Zhejiang Normal University, Jinhua, Zhejiang, 321004, China. Electronic address:

2,6-dichlorobenzoquinone (2,6-DCBQ), an emerging disinfection by-production, frequently occurs in reclaimed water and drinking water. However, limited information was available regarding its toxicity. To evaluate its impact, zebrafish at early life stage were exposed to 0, 10, 30, 60, 90, or 120 μg L 2,6-BDCQ for 72 h. Our results indicated that 2,6-BDCQ decreased zebrafish's survival rate to 65% and 44% at 90 and 120 μg L treatments and increased its aberration rate to 11% and 26% at 90 μg L and 120 μg L treatments. Besides, 2,6-BDCQ had adverse effect on its oxidative stress (elevated superoxide dismutase activity), lipid peroxidation (increased malondialdehyde levels), DNA damage (increased 8-hydroxydeoxyguanosine contents) and apoptosis (increased caspase-3 activity). Although lower concentrations (≤60 μg L) of 2,6-BDCQ didn't exhibit significant effect on its survival development or lipid peroxidation of zebrafish, they induced obvious DNA damage and apoptosis occurrence. These results revealed 2,6-BDCQ caused genotoxicity and cytotoxicity to zebrafish. This study provides novel insight into 2,6-DCBQ-induced toxicity in zebrafish.
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http://dx.doi.org/10.1016/j.envpol.2018.11.051DOI Listing
February 2019

Nanostructured Dihydroartemisinin Plus Epirubicin Liposomes Enhance Treatment Efficacy of Breast Cancer by Inducing Autophagy and Apoptosis.

Nanomaterials (Basel) 2018 Oct 9;8(10). Epub 2018 Oct 9.

State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

The heterogeneity of breast cancer and the development of drug resistance are the relapse reasons of disease after chemotherapy. To address this issue, a combined therapeutic strategy was developed by building the nanostructured dihydroartemisinin plus epirubicin liposomes. Investigations were performed on human breast cancer cells in vitro and xenografts in nude mice. The results indicated that dihydroartemisinin could significantly enhance the efficacy of epirubicin in killing different breast cancer cells in vitro and in vivo. We found that the combined use of dihydroartemisinin with epirubicin could efficiently inhibit the activity of Bcl-2, facilitate release of Beclin 1, and further activate Bax. Besides, Bax activated apoptosis which led to the type I programmed death of breast cancer cells while Beclin 1 initiated the excessive autophagy that resulted in the type II programmed death of breast cancer cells. In addition, the nanostructured dihydroartemisinin plus epirubicin liposomes prolonged circulation of drugs, and were beneficial for simultaneously delivering drugs into breast cancer tissues. Hence, the nanostructured dihydroartemisinin plus epirubicin liposomes could provide a new therapeutic strategy for treatment of breast cancer.
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http://dx.doi.org/10.3390/nano8100804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215314PMC
October 2018

Feasibility of a Mobile Phone App to Support Recovery From Addiction in China: Secondary Analysis of a Pilot Study.

JMIR Mhealth Uhealth 2018 Feb 27;6(2):e46. Epub 2018 Feb 27.

Collaborative Innovation Center for Brain Science, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Xu Hui District, Shanghai, China.

Background: Mobile health technologies have been found to improve the self-management of chronic diseases. However, there is limited research regarding their feasibility in supporting recovery from substance use disorders (SUDs) in China.

Objective: The objective of this study was to examine the feasibility of a mobile phone-based ecological momentary assessment (EMA) app by testing the concordance of drug use assessed by the EMA, urine testing, and a life experience timeline (LET) assessment.

Methods: A total of 75 participants dependent on heroin or amphetamine-type stimulant (ATS) in Shanghai were recruited to participate in a 4-week pilot study. Of the participants, 50 (67% [50/75]) were randomly assigned to the experimental group and 25 (33% [25/75]) were assigned to the control group. The experimental group used mobile health (mHealth) based EMA technology to assess their daily drug use in natural environments and received 2 short health messages each day, whereas the control group only received 2 short health messages each day from the app. Urine tests and LET assessments were conducted each week and a post-intervention survey was administered to both groups. The correlations among the EMA, the LET assessment, and the urine test were investigated.

Results: The mean age of the participants was 41.6 (SD 8.0) years, and 71% (53/75) were male. During the 4 weeks of observation, 690 daily EMA survey data were recorded, with a response rate of 49.29% (690/1400). With respect to drug use, the percent of agreement between the EMA and the LET was 66.7%, 79.2%, 72.4%, and 85.8%, respectively, for each of the 4 weeks, whereas the percent of agreement between the EMA and the urine test was 51.2%, 65.1%, 61.9%, and 71.5%, respectively. The post-intervention survey indicated that 46% (32/70) of the participants preferred face-to-face interviews rather than the mHealth app.

Conclusions: This study demonstrated poor agreement between the EMA data and the LET and found that the acceptance of mHealth among individuals with SUDs in China was not positive. Hence, greater efforts are needed to improve the feasibility of mHealth in China.
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http://dx.doi.org/10.2196/mhealth.8388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849798PMC
February 2018

Fabrication of paclitaxel hybrid nanomicelles to treat resistant breast cancer via oral administration.

Int J Nanomedicine 2018 2;13:719-731. Epub 2018 Feb 2.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing.

Aim: Oral chemotherapy using anticancer drugs would improve the clinical practice and the life quality of patients. The aim of the present study was to develop paclitaxel hybrid nanomicelles for oral administration to treat resistant breast cancer.

Methods: Evaluations were performed on human breast cancer MCF-7 cells, drug-resistant breast cancer MCF-7/Adr cells, and in MCF-7/Adr-xenografted BALB/c nude mice. The nanomicelles were composed of the polymer soluplus, d-α-tocopheryl polyethyleneglycol 1000 succinate (TPGS), and dequalinium (DQA). The constructed paclitaxel hybrid nanomicelles were ~65 nm in size.

Results: The nanomicelles improved cellular uptake and anticancer efficacy in the resistant breast cancer cells and induced mitochondria-mediated apoptosis. The mechanism of the apoptosis-inducing effect was related to the co-localization of the nanomicelles with mitochondria; the activation of pro-apoptotic protein Bax, cytochrome C, and apoptotic enzymes caspase 9 and 3; and the inhibition of anti-apoptotic proteins Bcl-2 and Mcl-1. Oral administration of paclitaxel hybrid nanomicelles had the same anticancer efficacy as the intravenous injection of taxol in resistant breast cancer-bearing mice. The oral suitability of this formulation was associated with the nanostructure and the actions of TPGS and DQA.

Conclusion: The fabricated paclitaxel hybrid nanomicelles could provide a promising oral formulation to treat drug-resistant breast cancer.
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http://dx.doi.org/10.2147/IJN.S150140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5799853PMC
April 2018

Gene identification of rare B(A) blood group.

Transfus Apher Sci 2017 Dec 11;56(6):855-857. Epub 2017 Sep 11.

Hebei Medical University, 2014 Clinical Medicine, Shijiazhuang 050017, China.

Objective: To study serologic and gene characteristics of the B(A) blood group of blood donation volunteers in Jilin Province, China.

Methods: ABO subgroups were identified by standard serologic techniques in ABO typing discrepancy samples from all donors at the Jilin Blood Center (410,354 non-repeat donors). DNA (deoxyribonucleic acid) was collected from each sample and PCR (polymerase chain reaction) was used to sequence exons 6 and 7 and intron 6, part 5 from the ABO subgroup samples. PCR products were sequenced to identify ABO subgroups and the B(A) allele.

Results: Four cases of B(A) blood type were found after sequencing, including two different alleles: B(A)02 and B(A)04. Three of the four alleles were B(A)04.

Conclusion: Among blood donation volunteers in Jilin Province, China, B(A)04 is the most common B(A) blood group allele, followed by B(A)02. The B(A) blood group is associated with a complicated serologic phenotype and DNA detection is necessary for this atypical phenotype sample.
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http://dx.doi.org/10.1016/j.transci.2017.09.001DOI Listing
December 2017

Hook1 inhibits malignancy and epithelial-mesenchymal transition in hepatocellular carcinoma.

Tumour Biol 2017 Jul;39(7):1010428317711098

1 Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Hook1 is a member of the hook family of coiled-coil proteins, which is recently found to be associated with malignant tumors. However, its biological function in hepatocellular carcinoma is yet unknown. Here, we evaluated the Hook1 levels in human hepatocellular carcinoma samples and matched peritumoral tissues by real-time polymerase chain reaction. Small interfering RNA knockdown and a transforming growth factor-β-induced epithelial-mesenchymal transition model were employed to investigate the biological effects of Hook1 in hepatocellular carcinoma. Our results indicated that Hook1 levels were significantly lower in hepatocellular carcinoma tissues than in the peritumoral tissues. In addition, Hook1 expression was significantly associated with hepatocellular carcinoma malignancy. Hook1 was downregulated after transforming growth factor-β-induced epithelial-mesenchymal transition. Moreover, Hook1 knockdown promoted epithelial-mesenchymal transition and attenuated the sensitivity of hepatocellular carcinoma cells to doxorubicin. In summary, our results indicate that downregulation of Hook1 plays a pivotal role in hepatocellular carcinoma progression via epithelial-mesenchymal transition. Hook1 may be used as a novel marker and therapeutic molecular target in hepatocellular carcinoma.
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http://dx.doi.org/10.1177/1010428317711098DOI Listing
July 2017

The use of functional epirubicin liposomes to induce programmed death in refractory breast cancer.

Int J Nanomedicine 2017 1;12:4163-4176. Epub 2017 Jun 1.

Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.

Currently, chemotherapy is less efficient in controlling the continued development of breast cancer because it cannot eliminate extrinsic and intrinsic refractory cancers. In this study, mitochondria were modified by functional epirubicin liposomes to eliminate refractory cancers through initiation of an apoptosis cascade. The efficacy and mechanism of epirubicin liposomes were investigated on human breast cancer cells in vitro and in vivo using flow cytometry, confocal microscopy, high-content screening system, in vivo imaging system, and tumor inhibition in mice. Mechanistic studies revealed that the liposomes could target the mitochondria, activate the apoptotic enzymes caspase 8, 9, and 3, upregulate the proapoptotic protein Bax while downregulating the antiapoptotic protein Mcl-1, and induce the generation of reactive oxygen species (ROS) through an apoptosis cascade. In xenografted mice bearing breast cancer, the epirubicin liposomes demonstrated prolonged blood circulation, significantly increased accumulation in tumor tissue, and robust anticancer efficacy. This study demonstrated that functional epirubicin liposomes could significantly induce programmed death of refractory breast cancer by activating caspases and ROS-related apoptotic signaling pathways, in addition to the direct killing effect of the anticancer drug itself. Thus, we present a simple nanomedicine strategy to treat refractory breast cancer.
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http://dx.doi.org/10.2147/IJN.S133194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459983PMC
October 2017

Lipid vesicles containing transferrin receptor binding peptide TfR-T and octa-arginine conjugate stearyl-R efficiently treat brain glioma along with glioma stem cells.

Sci Rep 2017 06 14;7(1):3487. Epub 2017 Jun 14.

Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, and School of Pharmaceutical Sciences, Peking University, Beijing, China.

Surgery and radiotherapy cannot fully remove brain glioma; thus, chemotherapy continues to play an important role in treatment of this illness. However, because of the restriction of the blood-brain barrier (BBB) and the regeneration of glioma stem cells, post-chemotherapy relapse usually occurs. Here, we report a potential solution to these issues that involves a type of novel multifunctional vinblastine liposomes equipped with transferrin receptor binding peptide TfR-T and octa-arginine conjugate stearyl-R. Studies were performed on brain glioma and glioma stem cells in vitro and were verified in brain glioma-bearing mice. The liposomes were transported across the BBB, killing brain glioma and glioma stem cells via the induction of necrosis, apoptosis and autophagy. Furthermore, we reveal the molecular mechanisms for treating brain glioma and glioma stem cells via functionalized drug lipid vesicles.
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http://dx.doi.org/10.1038/s41598-017-03805-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471209PMC
June 2017

Dual-functional drug liposomes in treatment of resistant cancers.

Adv Drug Deliv Rev 2017 06 20;115:46-56. Epub 2017 Apr 20.

Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address:

Efficacy of regular chemotherapy is significantly hampered by multidrug resistance (MDR) and severe systemic toxicity. The reduced toxicity has been evidenced after administration of drug liposomes, consisting of the first generation of regular drug liposomes, the second generation of long-circulation drug liposomes, and the third generation of targeting drug liposomes. However, MDR of cancers remains as an unsolved issue. The objective of this article is to review the dual-functional drug liposomes, which demonstrate the potential in overcoming MDR. Herein, dual-functional drug liposomes are referring to the drug-containing phospholipid bilayer vesicles that possess a dual-function of providing the basic efficacy of drug and the extended effect of the drug carrier. They exhibit unique roles in treatment of resistant cancer via circumventing drug efflux caused by adenosine triphosphate binding cassette (ABC) transporters, eliminating cancer stem cells, destroying mitochondria, initiating apoptosis, regulating autophagy, destroying supply channels, utilizing microenvironment, and silencing genes of the resistant cancer. As the prospect of an estimation, dual-functional drug liposomes would exhibit more strength in their extended function, hence deserving further investigation for clinical validation.
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http://dx.doi.org/10.1016/j.addr.2017.04.006DOI Listing
June 2017

C-type natriuretic peptide-modified lipid vesicles: fabrication and use for the treatment of brain glioma.

Oncotarget 2017 Jun;8(25):40906-40921

State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

Chemotherapy of brain glioma faces a major obstacle owing to the inability of drug transport across the blood-brain barrier (BBB). Besides, neovasculatures in brain glioma site result in a rapid infiltration, making complete surgical removal virtually impossible. Herein, we reported a novel kind of C-type natriuretic peptide (CNP) modified vinorelbine lipid vesicles for transferring drug across the BBB, and for treating brain glioma along with disrupting neovasculatures. The studies were performed on brain glioma U87-MG cells in vitro and on glioma-bearing nude mice in vivo. The results showed that the CNP-modified vinorelbine lipid vesicles could transport vinorelbine across the BBB, kill the brain glioma, and destroy neovasculatures effectively. The above mechanisms could be associated with the following aspects, namely, long circulation in the blood; drug transport across the BBB via natriuretic peptide receptor B (NPRB)-mediated transcytosis; elimination of brain glioma cells and disruption of neovasculatures by targeting uptake and cytotoxic injury. Besides, CNP-modified vinorelbine lipid vesicles could induce apoptosis of the glioma cells. The mechanisms could be related to the activations of caspase 8, caspase 3, p53, and reactive oxygen species (ROS), and inhibition of survivin. Hence, CNP-modified lipid vesicles could be used as a carrier material for treating brain glioma and disabling glioma neovasculatures.
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http://dx.doi.org/10.18632/oncotarget.16641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522305PMC
June 2017

ETS-related gene is a novel prognostic factor in childhood acute lymphoblastic leukemia.

Oncol Lett 2017 Jan 18;13(1):455-462. Epub 2016 Nov 18.

Division of Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, Key Laboratory of Reproductive Genetics, Zhejiang University, Ministry of Education, Hangzhou, Zhejiang 310003, P.R. China.

The ETS-related gene (ERG) has been demonstrated to be associated with overall survival in cytogenetically normal acute myeloid leukemia and acute T cell-lymphoblastic leukemia (T-ALL) in adult patients. However, there are no data available regarding the impact of ERG expression on childhood ALL. In the present study, ERG expression levels were analyzed in bone marrow samples from 119 ALL pediatric patients. ALL patients demonstrated higher ERG expression compared with the controls (P<0.0001). In addition, low ERG expression identified a group of patients with higher white blood cell counts (P=0.011), higher percentages of T-ALL immunophenotype (P=0.027), and higher relapse rates (P=0.009). Survival analyses demonstrated that low ERG expression was associated with inferior relapse-free survival (RFS) in childhood ALL (P=0.036) and was an independent prognostic factor in multivariable analyses for RFS. In conclusion, low ERG expression is associated with poor outcomes and may be used to serve as a molecular prognostic marker to identify patients with a high risk of relapse in childhood ALL.
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http://dx.doi.org/10.3892/ol.2016.5397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5245103PMC
January 2017

A new in-frame deletion in ribosomal protein S19 in a Chinese infant with Diamond-Blackfan anemia.

Blood Cells Mol Dis 2016 11 31;62:1-5. Epub 2016 Aug 31.

Division of Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Hangzhou 310003, PR China. Electronic address:

Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia that usually presents as macrocytic anemia during infancy. Ribosomal protein S19 (RPS19) is identified as the first gene associated with DBA. RPS19 is mutated in 25% of DBA patients, but its role in DBA pathogenesis remains to be elucidated. We have identified a novel heterozygous frameshift mutation in RPS19 gene in a DBA child presenting with profound anemia after birth. A single nucleotide heterozygous deletion (C.251delG) results in frameshift in RPS19 gene in exon 4 at codon 84 with possible premature stop codon (p.Arg84LysfsX21). The mutant allele was not detected in her parents, indicating de novo mutation. Both alleles were expressed at the same level. Using an immunofluorescence technique, the mutated-type RPS19 expressions were mostly localized to entire nuclei with little staining for nucleoli and its intracellular localization significantly differed from the wild-type RPS19, which was localized to both nuclei and nucleoli. This type of a mutation could be very helpful in further understanding the role of the RPS19 protein in DBA pathogenesis.
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http://dx.doi.org/10.1016/j.bcmd.2016.08.003DOI Listing
November 2016

LB-100 sensitizes hepatocellular carcinoma cells to the effects of sorafenib during hypoxia by activation of Smad3 phosphorylation.

Tumour Biol 2016 Jun 14;37(6):7277-86. Epub 2015 Dec 14.

Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88 Jiefang Road, Hangzhou, 310009, China.

Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis. The multikinase inhibitor sorafenib is the only clinically proved systematic treatment for HCC. However, few patients respond to sorafenib. Hypoxic microenvironments contribute to sorafenib resistance. LB-100, a serine/threonine protein phosphatase 2A (PP2A) inhibitor was previously found to be a chemosensitizer in HCC. Here, we tested whether LB-100 could sensitize HCC to the effects of sorafenib. Intriguingly, LB-100 enhanced the effects of sorafenib in HCC cells only during hypoxic environments. LB-100 dramatically increased intracellular p-Smad3 level, which was responsible for the effect of LB-100 as a sensitizer. LB-100 downregulated Bcl-2 expression and enhanced sorafenib-induced apoptosis in HCC cells. We further proved that PP2A mediated LB-100-induced p-Smad3 overexpression. In addition, p38 mitogen-activated protein kinase pathway was activated in hypoxic conditions, and enhanced p-Smad3-dependent Bcl-2 inhibition and consequent apoptosis. In conclusion, LB-100 sensitized HCC cells to sorafenib in hypoxic environments. This effect was mediated by inactivation of PP2A, resulting in enhanced level of p-Smad3. Increased p-Smad3 downregulated Bcl-2, causing increased apoptosis of HCC cells.
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http://dx.doi.org/10.1007/s13277-015-4560-2DOI Listing
June 2016

High expression of Midkine (MK) indicates poor prognosis in childhood acute lymphoblastic leukemia.

Hematology 2016 Mar 9;21(2):69-77. Epub 2015 Sep 9.

a Division of Hematology-Oncology , Children's Hospital of Zhejiang University School of Medicine, Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education , Hangzhou 310003 , PR China.

Objectives: Midkine (MK) expression has been reported to be correlated with the poor prognosis of patients with various tumors. However, there are no data available about the prognostic value of MK expression in childhood acute lymphoblastic leukemia (ALL).

Methods: In this study, MK mRNA expression was determined by real-time polymerase chain reaction in 120 childhood ALL and 30 healthy volunteers. Patients were dichotomized at the median value and divided into two groups: MK(low) group and MK(high) group.

Results: MK(high) patients had higher white blood cell counts, higher peripheral blood blasts percentages, and higher minimal residual disease levels than MK(low) patients. Moreover, the MK gene was expressed significantly higher in patients with relapsed ALL than in patients who maintained complete remission or at diagnosis. MK(high) patients harbored inferior relapse-free survival (RFS, P = 0.047) and overall survival (OS, P = 0.022) than MK(low) patients, and high expression of MK was found to be independently predictive of inferior OS (P = 0.032) but not RFS (P = 0.077) in the overall cohort.

Conclusion And Discussion: MK high expression is an independent adverse prognostic factor in childhood ALL. Its level may be incorporated into an improved risk classification system for ALL and suggest the need of alternative regimens.
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http://dx.doi.org/10.1179/1607845415Y.0000000050DOI Listing
March 2016
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