Publications by authors named "Wenshu Li"

48 Publications

Genome wide association study of the whiteness and colour related traits of flour and dough sheets in common wheat.

Sci Rep 2021 Apr 22;11(1):8790. Epub 2021 Apr 22.

State Key Laboratory of Crop Biology, Key Laboratory of Crop Biology of Shandong Province, Group of Wheat Quality and Molecular Breeding, College of Agronomy, Shandong Agricultural University, Tai'an, 271000, Shandong, People's Republic of China.

Flour whiteness and colour are important factors that influence the quality of wheat flour and end-use products. In this study, a genome wide association study focusing on flour and dough sheet colour using a high density genetic map constructed with 90K single nucleotide polymorphism arrays in a panel of 205 elite winter wheat accessions was conducted in two different locations in 2 years. Eighty-six significant marker-trait associations (MTAs) were detected for flour whiteness and the brightness index (L* value), the redness index (a* value), and the yellowness index (b* value) of flour and dough sheets (P < 10) on homologous group 1, 2, 5 and 7, and chromosomes 3A, 3B, 4A, 6A and 6B. Four, three, eleven, eleven MTAs for the flour whiteness, L* value, a* value, b* value, and one MTA for the dough sheet L* value were identified in more than one environment. Based on MATs, some important new candidate genes were identified. Of these, two candidate genes, TraesCS5D01G004300 and Gsp-1D, for BS00000020_51 were found in wheat, relating to grain hardness. Other candidate genes were associated with proteins, the fatty acid biosynthetic process, the ketone body biosynthetic process, etc.
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http://dx.doi.org/10.1038/s41598-021-88241-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062544PMC
April 2021

[Enhanced epitope immunoreactivity of the dominant epitope of Toxoplasma gondii fused at the "N terminus" of HPV16L1].

Sheng Wu Gong Cheng Xue Bao 2021 Jan;37(1):290-300

Department of Microbiology and Immunology, Wenzhou Medical University, Wenzhou 325000, Zhejiang, China.

For improving epitope immunogenicity and achieving the co-immunization, late protein 1 (L1) of HPV type 16 (HPV16L1) was selected as the vector to carry the dominant epitope of Toxoplasma gondii because of the shared common population between Toxoplasma gondii and human papillomavirus (HPV). RSepitope-HPV16L1 (RSepitope fused at the "N-terminus" of HPV16L1) and HPV16L1-RSepitope (RSepitope fused at the "C-terminus" of HPV16L1) chimeras were constructed. After transfection of COS-7 cells with the recombinants, Western blot, RT-PCR, and immunofluorescence experiments confirmed that RSepitope-HPV16L1 could successfully express the corresponding mRNA and protein of RSepitope and HPV16L1, but the HPV16L1-RSepitope construct could not. A "prime-boost" immunization program was applied in mice to further evaluate the immune response elicited by the constructs, and the RSepitope-HPV16L1 immunization group produced the most significantly increased humoral and cellular immune responses (the highest RSepitope-specific IgG antibody level and the highest IFN-γ production, respectively), in which both elevated Th1 and Th2 immune responses were obtained. Moreover, the advantage of HPV16L1 as an epitope carrier was remarkable for RSepitope-HPV16L1, which induced a more prominent immunological response than RSepitope alone (without fusion with HPV16L1). Our research indicated that the N-terminus of HPV16L1 could be a better insertion site for enhancing target epitope immunogenicity, and our study offers a design for epitope vaccine of reasonable combination.
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http://dx.doi.org/10.13345/j.cjb.200210DOI Listing
January 2021

Nanoindentation and Hierarchy Structure of the Bovine Hoof Wall.

Materials (Basel) 2021 Jan 8;14(2). Epub 2021 Jan 8.

School of Materials Science and Engineering, Central South University, Changsha 410083, China.

The bovine hoof wall with an α-keratin structure protects the bovine foot from impact loads when the cattle are running. Reduced modulus, hardness and creep behavior of the bovine hoof wall have been investigated by a nanoindentation technique. The average reduced modulus of the Transverse Direction (TD) specimens from the outside to inside wall is 3.76 and 2.05 GPa, respectively, while the average reduced modulus of the Longitudinal Direction (LD) specimens from the outside to inside wall is 4.54 and 3.22 GPa, respectively. Obviously, the orientation and the position of the bovine hoof wall have a significant influence on its mechanical properties. The use of the generalized Voigt-Kelvin model can make a good prediction of creep stage. Mechanical properties of the LD specimens are stronger than those of the TD specimens. The bovine hoof wall has a layered structure, which can effectively absorb the energy released by the crack propagation and passivate the crack tip. Therefore, a kind of structural model was designed and fabricated by three-dimensional printing technology, which has a 55% performance improvement on fracture toughness. It is believed that the reported results can be useful in the design of new bionic structure materials which may be used in motorcycle helmets and athletes' protective equipment to achieve light weight and improved strength at the same time.
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http://dx.doi.org/10.3390/ma14020289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827064PMC
January 2021

Targeted biological effect of an affitoxin composed of an HPV16E7 affibody fused with granzyme B (ZHPV16E7-GrB) against cervical cancer in vitro and in vivo.

Curr Cancer Drug Targets 2020 Dec 7. Epub 2020 Dec 7.

Department of Microbiology and Immunology, Wenzhou Medical University, Wenzhou, Zhejiang Province. China.

Background: High risk type 16 of human papillomavirus (HPV16) is associated with 50% of cervical cancer, for which reliable targeted therapies are lacking. HPV early protein 7 (E7) is an oncoprotein responsible for cell malignant transformation. In our previous work, a highly specific affibody targeting HPV16E7 (ZHPV16E7) was developed.

Objective: In order to improve the targeted therapeutic effect, the present study prepared an affitoxin consisting of ZHPV16E7 fused with granzyme B (GrB), namely, ZHPV16E7-GrB, and evaluated its targeting action in vitro and in vivo.

Methods: The ZHPV16E7-GrB fusion protein was produced in a prokaryotic expression system. The targeted binding properties of the ZHPV16E7-GrB to the HPV16E7 were confirmed by immunofluorescence assay (IFA) in cervical cancer cell lines, by immunohistochemical assay (IHA) in cervical cancer tissue from clinical specimens and by near-infrared imaging in tumour-bearing mice. The anti-tumour effect on both cervical cancer cells in vitro and tumour-bearing mice in vivo were further evaluated.

Results: A 34-kDa ZHPV16E7-GrB fusion protein was produced in E. coli and displayed corresponding immunoreactivity. IFA revealed that ZHPV16E7-GrB bound specifically to HPV16-positive TC-1 and SiHa cells. IHA showed that ZHPV16E7-GrB also bound specifically to HPV16-positive clinical tissue specimens. In addition, the near-infrared imaging results showed that ZHPV16E7-GrB was enriched in tumour tissues. Moreover, both the ZHPV16E7-GrB affitoxin and ZHPV16E7 affibody (without GrB) significantly reduced the proliferation of cervical cancer cells in vitro and tumour-bearing mice in vivo, and the antiproliferative effect of ZHPV16E7-GrB was higher than that of the ZHPV16E7 affibody.

Conclusions: The affitoxin by coupling the affibody with GrB is a promising targeted therapeutic agent with the dual advantages of the targeted affibody and the GrB cytotoxin.
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http://dx.doi.org/10.2174/1568009620666201207145720DOI Listing
December 2020

Oroxylin A reverses hypoxia-induced cisplatin resistance through inhibiting HIF-1α mediated XPC transcription.

Oncogene 2020 11 25;39(45):6893-6905. Epub 2020 Sep 25.

State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.

Hypoxia is a key concern during the treatment of non-small cell lung cancer (NSCLC), and hypoxia-inducible factor 1 alpha (HIF-1α) has been associated with increased tumor resistance to therapeutic modalities such as cisplatin. Compensatory activation of nucleotide excision repair (NER) pathway is the major mechanism that accounts for cisplatin resistance. In the present study, we suggest a novel strategy to improve the treatment of NSCLC and overcome the hypoxia-induced cisplatin resistance by cotreatment with Oroxylin A, one of the main bioactive flavonoids of Scutellariae radix. Based on the preliminary screening, we found that xeroderma pigmentosum group C (XPC), an important DNA damage recognition protein involved in NER, dramatically increased in hypoxic condition and contributed to hypoxia-induced cisplatin resistance. Further data suggested that Oroxylin A significantly reversed the hypoxia-induced cisplatin resistance through directly binding to HIF-1α bHLH-PAS domain and blocking its binding to HRE3 transcription factor binding sites on XPC promoter which is important to hypoxia-induced XPC transcription. Taken together, our findings not only demonstrate a crucial role of XPC dependent NER in hypoxia-induced cisplatin resistance, but also suggest a previously unrecognized tumor suppressive mechanism of Oroxylin A in NSCLC which through sensitization of cisplatin-mediated growth inhibition and apoptosis under hypoxia.
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http://dx.doi.org/10.1038/s41388-020-01474-xDOI Listing
November 2020

New Insights of Emerging SARS-CoV-2: Epidemiology, Etiology, Clinical Features, Clinical Treatment, and Prevention.

Front Cell Dev Biol 2020 22;8:410. Epub 2020 May 22.

Department of Microbiology and Immunology, School of Basic Medical Sciences, Institute of Molecular Virology and Immunology, Institute of Tropical Medicine, Wenzhou Medical University, Wenzhou, China.

Since the first reports that the novel coronavirus was showing human-to-human transmission characteristics and asymptomatic cases, the number of patients with associated pneumonia has continued to rise and the epidemic has grown. It now threatens the health and lives of people across the world. The governments of many countries have attached great importance to the prevention of SARS-CoV-2, via research into the etiology and epidemiology of this newly emerged disease. Clinical signs, treatment, and prevention characteristics of the novel coronavirus pneumonia have been receiving attention worldwide, especially from medical personnel. However, owing to the different experimental methods, sample sizes, sample sources, and research perspectives of various studies, results have been inconsistent, or relate to an isolated aspect of the virus or the disease it causes. Currently, systematic summary data on the novel coronavirus are limited. This review combines experimental and clinical evidence into a systematic analysis and summary of the current progress of research into SARS-CoV-2, from multiple perspectives, with the aim of gaining a better overall understanding of the disease. Our report provides important information for current clinicians, for the prevention and treatment of COVID-19 pneumonia.
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http://dx.doi.org/10.3389/fcell.2020.00410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256189PMC
May 2020

Evidence of behaviour change during an Ebola virus disease outbreak, Sierra Leone.

Bull World Health Organ 2020 May 26;98(5):330-340B. Epub 2020 Mar 26.

Centers for Disease Control and Prevention, Atlanta, United States of America (USA).

Objective: To evaluate changes in Ebola-related knowledge, attitudes and prevention practices during the Sierra Leone outbreak between 2014 and 2015.

Methods: Four cluster surveys were conducted: two before the outbreak peak (3499 participants) and two after (7104 participants). We assessed the effect of temporal and geographical factors on 16 knowledge, attitude and practice outcomes.

Findings: Fourteen of 16 knowledge, attitude and prevention practice outcomes improved across all regions from before to after the outbreak peak. The proportion of respondents willing to: (i) welcome Ebola survivors back into the community increased from 60.0% to 89.4% (adjusted odds ratio, aOR: 6.0; 95% confidence interval, CI: 3.9-9.1); and (ii) wait for a burial team following a relative's death increased from 86.0% to 95.9% (aOR: 4.4; 95% CI: 3.2-6.0). The proportion avoiding unsafe traditional burials increased from 27.3% to 48.2% (aOR: 3.1; 95% CI: 2.4-4.2) and the proportion believing spiritual healers can treat Ebola decreased from 15.9% to 5.0% (aOR: 0.2; 95% CI: 0.1-0.3). The likelihood respondents would wait for burial teams increased more in high-transmission (aOR: 6.2; 95% CI: 4.2-9.1) than low-transmission (aOR: 2.3; 95% CI: 1.4-3.8) regions. Self-reported avoidance of physical contact with corpses increased in high but not low-transmission regions, aOR: 1.9 (95% CI: 1.4-2.5) and aOR: 0.8 (95% CI: 0.6-1.2), respectively.

Conclusion: Ebola knowledge, attitudes and prevention practices improved during the Sierra Leone outbreak, especially in high-transmission regions. Behaviourally-targeted community engagement should be prioritized early during outbreaks.
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http://dx.doi.org/10.2471/BLT.19.245803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265950PMC
May 2020

Synthetic NiO catalyst-assisted peroxymonosulfate for degradation of benzoic acid from aqueous solution.

Water Environ Res 2020 Sep 2;92(9):1388-1397. Epub 2020 May 2.

College of Architecture and Environment, Sichuan University, Chengdu, China.

A heterogeneous NiO catalyst was prepared by a precipitation process using nickel nitrate with oxalic acid and tested for heterogeneous oxidation of benzoic acid (BA) in the presence of peroxymonosulfate (PMS). It was found that the synthetic NiO is highly effective in heterogeneous activation of PMS to produce sulfate radicals ( ) and hydroxyl radicals ( OH), and also presents stable performance in the heterogeneous activation of PMS for BA degradation. Physicochemical properties of the NiO catalyst were characterized by several techniques, such as thermogravimetric analysis, Brunauer-Emmett-Teller, Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, and transmission electron microscopy. It was found that NiO and NiOOH were formed on the synthetic NiO catalyst and were stably distributed on the catalyst surface. Nearly 95% decomposition could be achieved in 30 min at the conditions of 500 ml 20 μM BA solution, 0.25 g catalyst, and [PMS]:[BA] = 30:1. The heterogeneous reactions, the effects of PMS concentration, and catalyst dosage on the BA degradation were investigated. The heterogeneous BA degradation reactions followed first-order kinetics. Additionally, quenching experiments proved that the dominant radical in the solution was OH. The experiments results also showed that this approach is effective for the degradation of many other pollutants (such as tetracycline hydrochloride, 2, 4-dichlorophenol, Acid orange 7, rhodamine B, and methyl red). PRACTITIONER POINTS: A novel NiO material was fabricated for degradation of benzoic acid. The synthetic NiO catalyst comprised active NiO and NiOOH. The main radical for benzoic acid removal rate was OH. A plausible mechanism for catalyzed degradation of the benzoic acid was proposed.
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http://dx.doi.org/10.1002/wer.1336DOI Listing
September 2020

Up-regulation of miR-145 may contribute to repeated implantation failure after IVF-embryo transfer by targeting PAI-1.

Reprod Biomed Online 2020 May 30;40(5):627-636. Epub 2020 Jan 30.

Reproductive Medicine Centre, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.

Research Question: Repeated implantation failure (RIF) is a major limiting factor in assisted reproductive technology. As miR-145 (also known as MIR145) is up-regulated in patients with RIF, this study asked, what is the molecular mechanism underlying the affect of miR-145 on embryo implantation in RIF?

Design: Ishikawa cells were infected with lentivirus containing miR-145 and miR-145 NC. Massive transcriptome data analyses and bioinformatics analysis were used to search for a potential candidate target of miR-145. The expression of the potential candidate target was detected using quantitative reverse transcription PCR (qRT-PCR) and western blotting in the Ishikawa cells infected with lentivirus containing miR-145 or miR-145 NC. Subsequently, a dual luciferase reporter assay was performed to verify whether the potential candidate target was a novel direct target of miR-145. In addition, expression of PAI-1 (plasminogen activator inhibitor 1, also known as SERPINE1) in endometrial tissue from women with RIF and in control endometrial tissue was examined using qRT-PCR and immunohistochemistry.

Results: Based on massive transcriptome data analyses and bioinformatics analysis, PAI-1 was regarded as a potential candidate target of miR-145. miR-145 overexpression was achieved in Ishikawa cells. PAI-1 was confirmed as a direct target of miR-145 by bioinformatic analysis, qRT-PCR, western blotting and dual luciferase reporter assay. Further, results from the clinical sample indicated that at both the mRNA and protein levels, PAI-1 expression was down-regulated in endometrial tissues from women with RIF compared with control group women, and this was negatively related to miR-145 expression.

Conclusions: The study results suggests that miR-145 may target and down-regulate PAI-1 expression and influence embryo implantation in women with RIF who are undergoing IVF.
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http://dx.doi.org/10.1016/j.rbmo.2020.01.018DOI Listing
May 2020

N, S-Doped porous carbons for persulfate activation to remove tetracycline: Nonradical mechanism.

J Hazard Mater 2020 06 28;391:122055. Epub 2020 Jan 28.

College of Architecture & Environment, Sichuan University, Chengdu 610065, PR China.

Nitrogen and sulfur-codoped porous carbons (SNCs) with porous structures and high surface areas were successfully synthesized employing coffee grounds, sodium bicarbonate and L-cysteine monohydrochloride as precursors. The SNCs were highly efficient for adsorption and exhibited outstanding catalytic performance for the oxidative degradation of tetracycline hydrochloride (TeC) solutions, especially at a calcined temperature of 700 °C (SNCs-700). The radical quenching, advanced in situ electron paramagnetic resonance (EPR) technology, PS decomposition rates and Linear Sweep Voltammetry (LSV) indicated that the excellent oxidative effectiveness of the PS/SNCs-700 system originated from the nonradical pathways (singlet oxygen (O) and electron transfer). It's supposed that N and S doping can effectively create point defects, which could generate O, while carbonyl groups were determined to be the main active sites contributing to the electron transfer. TeC degradation intermediates were also identified, three degradation pathways, revealing that the pre-adsorption significantly accelerated the nonradical oxidation pathways. This approach provides an innovative method for the large-scale production and application of high-quality catalysts in water treatment.
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http://dx.doi.org/10.1016/j.jhazmat.2020.122055DOI Listing
June 2020

Long non-coding RNA CCAT2 promotes oncogenesis in triple-negative breast cancer by regulating stemness of cancer cells.

Pharmacol Res 2020 02 3;152:104628. Epub 2020 Jan 3.

Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. Electronic address:

Triple-negative breast cancers (TNBC) are more aggressive due to lacking receptors for hormone therapy and maintaining stemness features in cancer cells. Herein we found long non-coding RNA CCAT2 overexpressed specially in TNBC, and in breast cancer stem cells (BCSC) as well. Enforced overexpression and targeted knockdown demonstrated the oncogenic function of CCAT2 both in vitro and in vivo. CCAT2 promoted the expression of stemness markers including OCT4, Nanog and KLF4, increased mammosphere formation and induced ALDH+ cancer stem cell population in TNBC. A chromosomally adjacent gene OCT4-PG1, as a pseudogene of OCT4, was upregulated by CCAT2, and positively regulated the stemness features of TNBC cells. miR-205 was identified as a target gene of CCAT2 in TNBC. Point-mutation in CCAT2 impaired the sponge inhibition of miR-205. Overexpression of miR-205 rescued the oncogenic phenotypes induced by CCAT2. In addition, Notch2, as a target gene of miR-205, was downregulated by miR-205 and upregulated by CCAT2 in TNBC. Collectively, the current study revealed a novel function of CCAT2 in promoting tumor initiation and progression in TNBC through upregulating OCT4-PG1 expression and activating Notch signaling. These findings not only demonstrated a lncRNA-based therapeutic strategy in treatment of TNBC, but also added a node to the regulatory network of CCAT2 that controls aggressiveness of breast cancer stem cells.
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http://dx.doi.org/10.1016/j.phrs.2020.104628DOI Listing
February 2020

Review of Dissolved Oxygen Detection Technology: From Laboratory Analysis to Online Intelligent Detection.

Sensors (Basel) 2019 Sep 16;19(18). Epub 2019 Sep 16.

College of Information and Electrical Engineering, China Agricultural University, Beijing 100083, China.

Dissolved oxygen is an important index to evaluate water quality, and its concentration is of great significance in industrial production, environmental monitoring, aquaculture, food production, and other fields. As its change is a continuous dynamic process, the dissolved oxygen concentration needs to be accurately measured in real time. In this paper, the principles, main applications, advantages, and disadvantages of iodometric titration, electrochemical detection, and optical detection, which are commonly used dissolved oxygen detection methods, are systematically analyzed and summarized. The detection mechanisms and materials of electrochemical and optical detection methods are examined and reviewed. Because external environmental factors readily cause interferences in dissolved oxygen detection, the traditional detection methods cannot adequately meet the accuracy, real-time, stability, and other measurement requirements; thus, it is urgent to use intelligent methods to make up for these deficiencies. This paper studies the application of intelligent technology in intelligent signal transfer processing, digital signal processing, and the real-time dynamic adaptive compensation and correction of dissolved oxygen sensors. The combined application of optical detection technology, new fluorescence-sensitive materials, and intelligent technology is the focus of future research on dissolved oxygen sensors.
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http://dx.doi.org/10.3390/s19183995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767127PMC
September 2019

Effective Neutralizing Antibody Produced in Mice Directly Immunized with Integrated Expressing HPV16L1 Protein.

Viral Immunol 2019 09 5;32(7):308-317. Epub 2019 Aug 5.

Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, Wenzhou Medical University, Wenzhou, China.

The human papillomavirus (HPV) vaccine has not been widely used in developing countries because of its high cost and multiple subtype restrictions. The present study aimed to develop an economical, convenient, and effective vaccine to produce neutralizing antibodies. Using (L1) from the HPV16 subtype as the target antigen (HPV16L1) and as the antigen release system, integrated . expressing HPV16L1 (named yeast-) was prepared and vaccinated directly into mice by subcutaneous multipoint injection. After immunization was performed thrice, high titers (greater than 1:40,960) of specific anti-HPV16L1 antibodies were obtained in immune serum and were observed to continuously rise over time. The indirect hemagglutination test and indirect hemagglutination inhibition test were used to detect neutralizing antibody activity and the results demonstrated the hemagglutination ability of the immune serum and the reduction in or loss of the hemagglutination ability if preneutralized antigen was added to the immune serum. The protection conferred by immune serum to tumor-bearing mice at the early stages was confirmed, but the neutralizing activity disappeared when the tumor reached a size of 1 mm. The neutralization activity of the immune serum was confirmed both and .
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http://dx.doi.org/10.1089/vim.2019.0055DOI Listing
September 2019

Mps1 regulates spindle morphology through MCRS1 to promote chromosome alignment.

Mol Biol Cell 2019 04 20;30(9):1060-1068. Epub 2019 Feb 20.

College of Arts and Science, New York University at Shanghai, Shanghai 200122, China.

Accurate partitioning of chromosomes during mitosis is essential for genetic stability and requires the assembly of the dynamic mitotic spindle and proper kinetochore-microtubule attachment. The spindle assembly checkpoint (SAC) monitors the incompleteness and errors in kinetochore-microtubule attachment and delays anaphase. The SAC kinase Mps1 regulates the recruitment of downstream effectors to unattached kinetochores. Mps1 also actively promotes chromosome alignment during metaphase, but the underlying mechanism is not completely understood. Here, we show that Mps1 regulates chromosome alignment through MCRS1, a spindle assembly factor that controls the dynamics of the minus end of kinetochore microtubules. Mps1 binds and phosphorylates MCRS1. This mechanism enables KIF2A localization to the minus end of spindle microtubules. Thus, our study reveals a novel role of Mps1 in regulating the dynamics of the minus end of microtubules and expands the functions of Mps1 in genome maintenance.
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http://dx.doi.org/10.1091/mbc.E18-09-0546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724509PMC
April 2019

Generation of reactive oxygen species by promoting the Cu(II)/Cu(I) redox cycle with reducing agents in aerobic aqueous solution.

Water Sci Technol 2018 Nov;78(5-6):1390-1399

College of Architecture & Environment, Sichuan University, Chengdu 610065, China E-mail:

This study investigated the generation of reactive oxygen species (ROS) (O •, HO, and HO•) by promoting the Cu(II)/Cu(I) redox cycle with certain reducing agents (RAs) in aerobic aqueous solution, and benzoic acid (BA) was employed as indicator for the hydroxyl radical (HO•). Hydroxylamine (HA) can reduce Cu(II) to Cu(I) to induce chain reactions of copper species resulting in the generation of the superoxide radical (O •) and hydrogen peroxide (HO), and the intermediate Cu(I) can further activate HO via a Fenton-like reaction to produce HO•, creating the remarkable BA degradation. O is indispensable, and unprotonated HA is the motive power in the O/Cu/HA system. Moreover, pH is a crucial factor of the O/Cu/HA system due to the protonated HA not being able to reduce Cu(II) into Cu(I). The oxidation of HA can be effectively induced by trace amounts of Cu(II), and both a higher HA dosage and a higher Cu(II) dosage can enhance HO generation and BA degradation. In addition, some other RAs that can reduce Cu(II) into Cu(I) could replace HA in the O/Cu/HA system to induce the generation of these ROS in aerobic aqueous solution.
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http://dx.doi.org/10.2166/wst.2018.416DOI Listing
November 2018

12(S)-hydroxyeicosatetraenoic acid impairs vascular endothelial permeability by altering adherens junction phosphorylation levels and affecting the binding and dissociation of its components in high glucose-induced vascular injury.

J Diabetes Investig 2019 May 24;10(3):639-649. Epub 2018 Oct 24.

Department of Cardiology, First Affiliated Hospital, College of Medicine, Zhengzhou University, Zhengzhou, China.

Aims/introduction: Diabetes is an important risk factor for atherosclerotic disease. The initiating factor of atherosclerosis is local endothelial cell injury. The arachidonic acid metabolite, 12(S)-hydroxyeicosatetraenoic acid (12[S]-HETE), might be involved in this process. In recent years, some studies have discussed the effect of 12(S)-HETE on vascular endothelial cell function. In the present study, we investigated the effect of 12(S)-HETE on vascular endothelial cell function in high-glucose conditions and the mechanisms involved.

Materials And Methods: Human umbilical vein endothelial cells were cultured in conventional M199 medium and high-glucose M199 medium. Human umbilical vein endothelial cells were stimulated with 12(S)-HETE and cinnamyl-3,4-dihydroxy-α-cyanocinnamate (a 12/15-lipoxygenases inhibitor). A type 1 diabetes mellitus model was established in C57BL/6 or 12/15-lipoxygenases knockout mice with streptozotocin. Aortic tissue was harvested for subsequent testing. The transmembrane transport of dextran and human acute monocytic leukaemia cell line (THP-1) cells was measured. The adherens junction protein, IkBα, nuclear factor kappa Bp65 (P65), intercellular adhesion molecule 1 and vascular cell adhesion protein 1 expression and phosphorylation, and the binding/dissociation of endothelial cell components were observed.

Results: Transendothelial migration of dextran and THP-1 cells was significantly increased by stimulation of human umbilical vein endothelial cell monolayers with high glucose and 12(S)-HETE (P < 0.05). High glucose and 12(S)-HETE altered the vascular endothelial cadherin and β-catenin phosphorylation level, and promoted the dissociation of β-catenin and vascular endothelial cadherin. Expression levels of P-Ikbα, P-P65, intercellular adhesion molecule 1 and vascular cell adhesion protein 1 were elevated in high glucose and 12(S)-HETE treated cells and diabetic mice compared with controls (P < 0.05).

Conclusions: The lipoxygenases metabolite, 12(S)-HETE, can impair vascular endothelial permeability by altering adherens junction phosphorylation levels, and affecting the binding and dissociation of its components in high-glucose conditions.
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http://dx.doi.org/10.1111/jdi.12941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497583PMC
May 2019

Bispecific affibody molecule targeting HPV16 and HPV18E7 oncoproteins for enhanced molecular imaging of cervical cancer.

Appl Microbiol Biotechnol 2018 Sep 25;102(17):7429-7439. Epub 2018 Jun 25.

Institute of Molecular Virology and Immunology, Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, People's Republic of China.

High-risk human papillomavirus (HPV16 and HPV18) are now widely recognized as responsible for cervical cancer, which remains to be the most common gynecologic malignancy in women worldwide. It is well known that viral oncoproteins E6/E7 play key roles in HPV-associated cervical carcinogenesis. Thus, in vivo detection of the two oncoproteins may provide important diagnostic information influencing patient management. More recently, affibody molecules have been demonstrated to be a promising candidate for development as molecular imaging probes. Based on the two monomeric affibody molecules (Z and Z) generated in our laboratory, here, we used a peptide linker (GlySer) to link Z and Z to develop a novel heterodimeric affibody Z-(GlySer)-Z Both biosensor and immunofluorescence assays have proved that the heterodimeric affibody molecule targeted simultaneously HPV16 and HPV18E7 proteins by binding to the viral oncoproteins. In vivo tumor-imaging experiments using the Dylight755-labeled heterodimeric affibody revealed that strongly high-contrast tumor retention of the heterodimers occurred in both HPV16- and HPV18-derived tumors of nude mice 0.5 h post-injection. The accumulation of Dylight755-labeled heterodimers in tumors was achieved over 48 h. Therefore, we believe that this novel heterodimeric affibody molecule has great potential utility in molecular imaging in vivo and diagnosis of HPV-associated cervical cancers.
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http://dx.doi.org/10.1007/s00253-018-9167-2DOI Listing
September 2018

Impact of Ebola experiences and risk perceptions on mental health in Sierra Leone, July 2015.

BMJ Glob Health 2018 17;3(2):e000471. Epub 2018 Mar 17.

Division of Global Health Protection, Centers for Global Health, US Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA.

Background: The mental health impact of the 2014-2016 Ebola epidemic has been described among survivors, family members and healthcare workers, but little is known about its impact on the general population of affected countries. We assessed symptoms of anxiety, depression and post-traumatic stress disorder (PTSD) in the general population in Sierra Leone after over a year of outbreak response.

Methods: We administered a cross-sectional survey in July 2015 to a national sample of 3564 consenting participants selected through multistaged cluster sampling. Symptoms of anxiety and depression were measured by Patient Health Questionnaire-4. PTSD symptoms were measured by six items from the Impact of Events Scale-revised. Relationships among Ebola experience, perceived Ebola threat and mental health symptoms were examined through binary logistic regression.

Results: Prevalence of any anxiety-depression symptom was 48% (95% CI 46.8% to 50.0%), and of any PTSD symptom 76% (95% CI 75.0% to 77.8%). In addition, 6% (95% CI 5.4% to 7.0%) met the clinical cut-off for anxiety-depression, 27% (95% CI 25.8% to 28.8%) met levels of clinical concern for PTSD and 16% (95% CI 14.7% to 17.1%) met levels of probable PTSD diagnosis. Factors associated with higher reporting of any symptoms in bivariate analysis included region of residence, experiences with Ebola and perceived Ebola threat. Knowing someone quarantined for Ebola was independently associated with anxiety-depression (adjusted OR (AOR) 2.3, 95% CI 1.7 to 2.9) and PTSD (AOR 2.095% CI 1.5 to 2.8) symptoms. Perceiving Ebola as a threat was independently associated with anxiety-depression (AOR 1.69 95% CI 1.44 to 1.98) and PTSD (AOR 1.86 95% CI 1.56 to 2.21) symptoms.

Conclusion: Symptoms of PTSD and anxiety-depression were common after one year of Ebola response; psychosocial support may be needed for people with Ebola-related experiences. Preventing, detecting, and responding to mental health conditions should be an important component of global health security efforts.
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http://dx.doi.org/10.1136/bmjgh-2017-000471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5873549PMC
March 2018

Risk Communication and Ebola-Specific Knowledge and Behavior during 2014-2015 Outbreak, Sierra Leone.

Emerg Infect Dis 2018 02;24(2):336-344

We assessed the effect of information sources on Ebola-specific knowledge and behavior during the 2014-2015 Ebola virus disease outbreak in Sierra Leone. We pooled data from 4 population-based knowledge, attitude, and practice surveys (August, October, and December 2014 and July 2015), with a total of 10,604 respondents. We created composite variables for exposures (information sources: electronic, print, new media, government, community) and outcomes (knowledge and misconceptions, protective and risk behavior) and tested associations by using logistic regression within multilevel modeling. Exposure to information sources was associated with higher knowledge and protective behaviors. However, apart from print media, exposure to information sources was also linked to misconceptions and risk behavior, but with weaker associations observed. Knowledge and protective behavior were associated with the outbreak level, most strongly after the peak, whereas risk behavior was seen at all levels of the outbreak. In future outbreaks, close attention should be paid to dissemination of information.
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http://dx.doi.org/10.3201/eid2402.171028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5782897PMC
February 2018

National survey of Ebola-related knowledge, attitudes and practices before the outbreak peak in Sierra Leone: August 2014.

BMJ Glob Health 2017 4;2(4):e000285. Epub 2017 Dec 4.

Division of Global Health Protection, Center for Global Health, US Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Background: The 2014-2015 Ebola epidemic in West Africa was the largest ever to occur. In the early phases, little was known about public knowledge, attitudes and practices (KAP) relating to Ebola virus disease (Ebola). Data were needed to develop evidence-driven strategies to address gaps in knowledge and practice.

Methods: In August 2014, we conducted interviews with 1413 randomly selected respondents from 9 out of 14 districts in Sierra Leone using multistage cluster sampling. Where suitable, Ebola-related KAP questions were adapted from other internationally validated questionnaires related to infectious diseases.

Results: All respondents were aware of Ebola. When asked unprompted, 60% of respondents could correctly cite fever, diarrhoea and vomiting as signs/symptoms of Ebola. A majority of respondents knew that avoiding infected blood and bodily fluids (87%) and contact with an infected corpse (85%) could prevent Ebola. However, there were also widespread misconceptions such as the belief that Ebola can be prevented by washing with salt and hot water (41%). Almost everyone interviewed (95%) expressed at least one discriminatory attitude towards Ebola survivors. Unprompted, self-reported actions taken to avoid Ebola infection included handwashing with soap (66%) and avoiding physical contact with patients with suspected Ebola (40%).

Conclusion: Three months into the 2014 Ebola outbreak in Sierra Leone, our findings suggest there was high awareness of the disease but misconceptions and discriminatory attitudes toward survivors remained common. These findings directly informed the development of a national social mobilisation strategy and demonstrated the importance of KAP assessment early in an epidemic.
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http://dx.doi.org/10.1136/bmjgh-2017-000285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728302PMC
December 2017

Investigation of the neuroprotective effects of Lycium barbarum water extract in apoptotic cells and Alzheimer's disease mice.

Mol Med Rep 2018 Mar 19;17(3):3599-3606. Epub 2017 Dec 19.

School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China.

Alzheimer's disease (AD) affects people worldwide and is caused by chronic and progressive damage to the central nervous system. Lycium barbarum (LB), a renowned functional food and medicinal plant in Southeast Asia, may possess protective effects against nerve injury. The present study aimed to investigate the neuroprotective effects of LB water extract in a differentiated (D)PC12 cellular apoptosis model induced by L‑glutamic acid (L‑Glu), and a mouse model of AD, induced by the combination of AlCl3 and D‑galactose. LB markedly increased DPC12 cell survival against L‑Glu induced damage by increasing cell viability, reducing the apoptosis rate and G1 phase arrest, suppressing intracellular reactive oxygen species accumulation, blocking Ca2+ overload and preventing mitochondrial membrane potential depolarization. LB additionally normalized the expression levels of apoptosis regulator Bcl‑2, apoptosis regulator BAX, and cleaved caspase‑3, ‑8 and ‑9 in L‑Glu exposed cells. In the AD mouse model, LB increased the amount of horizontal and vertical movement in the autonomic activity test, improved endurance time in the rotarod test and decreased escape latency time in the Morris water maze test. Additionally, the levels of acetylcholine and choline acetyltransferase were significantly increased in the serum and hypothalamus in the LB‑treated AD mice. These data suggested that LB may exert neuroprotective effects and may aid in preventing neurodegenerative disease.
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http://dx.doi.org/10.3892/mmr.2017.8310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802160PMC
March 2018

Degradation of 2,4-dichlorophenol by activating persulfate and peroxomonosulfate using micron or nanoscale zero-valent copper.

J Hazard Mater 2018 Feb 14;344:1209-1219. Epub 2017 Nov 14.

State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090, China.

The ability of persulfate (PS) and peroxymonosulfate (PMS) activated by micron or nanoscale zero-valent copper (ZVC or nZVC) to degrade 2,4-dichlorophenol (2,4-DCP) was quantified under various conditions. Mechanism investigation revealed that PS and PMS accelerated the corrosion of ZVC or nZVC to release Cu under acidic conditions. The in-situ generated Cu further decomposed PS or PMS to produce SO and OH, which then dramatically degraded 2,4-DCP. The k for 2,4-DCP removal followed pseudo-first-order kinetics, k of ZVC/PMS and nZVC/PMS systems were 10∼30 times greater than these in ZVC/PS and nZVC/PS systems. The nZVC/PMS system was most effective to remove 2,4-DCP which even did better than the nZVI/PMS system, with rate constant values ranging from 0.041 to 1.855min. At higher pH ZVC is ineffective, but nZVC can activate PS and PMS to significantly degrade 2,4-DCP at pH up to 7.3. The 2,4-DCP degradation pathway was found to involve dechloridation, dehydrogenation, hydroxylation, ring open and mineralization. 56.7% and 45.3% of TOC removals were respectively obtained in the ZVC/PMS and nZVC/PMS systems within 120min. This study helps to comprehend the application of zero-valent metals in reactive radicals-based oxidation processes and the reactivity of Cu as an activator of PS and PMS.
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http://dx.doi.org/10.1016/j.jhazmat.2017.11.023DOI Listing
February 2018

Contributions of the US Centers for Disease Control and Prevention in Implementing the Global Health Security Agenda in 17 Partner Countries.

Emerg Infect Dis 2017 12;23(13)

The Global Health Security Agenda (GHSA), a partnership of nations, international organizations, and civil society, was launched in 2014 with a mission to build countries' capacities to respond to infectious disease threats and to foster global compliance with the International Health Regulations (IHR 2005). The US Centers for Disease Control and Prevention (CDC) assists partner nations to improve IHR 2005 capacities and achieve GHSA targets. To assess progress through these CDC-supported efforts, we analyzed country activity reports dating from April 2015 through March 2017. Our analysis shows that CDC helped 17 Phase I countries achieve 675 major GHSA accomplishments, particularly in the cross-cutting areas of public health surveillance, laboratory systems, workforce development, and emergency response management. CDC's engagement has been critical to these accomplishments, but sustained support is needed until countries attain IHR 2005 capacities, thereby fostering national and regional health protection and ensuring a world safer and more secure from global health threats.
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http://dx.doi.org/10.3201/eid2313.170898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711326PMC
December 2017

Knowledge, Attitudes, and Practices Related to Ebola Virus Disease at the End of a National Epidemic - Guinea, August 2015.

MMWR Morb Mortal Wkly Rep 2017 Oct 20;66(41):1109-1115. Epub 2017 Oct 20.

Health communication and social mobilization efforts to improve the public's knowledge, attitudes, and practices (KAP) regarding Ebola virus disease (Ebola) were important in controlling the 2014-2016 Ebola epidemic in Guinea (1), which resulted in 3,814 reported Ebola cases and 2,544 deaths.* Most Ebola cases in Guinea resulted from the washing and touching of persons and corpses infected with Ebola without adequate infection control precautions at home, at funerals, and in health facilities (2,3). As the 18-month epidemic waned in August 2015, Ebola KAP were assessed in a survey among residents of Guinea recruited through multistage cluster sampling procedures in the nation's eight administrative regions (Boké, Conakry, Faranah, Kankan, Kindia, Labé, Mamou, and Nzérékoré). Nearly all participants (92%) were aware of Ebola prevention measures, but 27% believed that Ebola could be transmitted by ambient air, and 49% believed they could protect themselves from Ebola by avoiding mosquito bites. Of the participants, 95% reported taking actions to avoid getting Ebola, especially more frequent handwashing (93%). Nearly all participants (91%) indicated they would send relatives with suspected Ebola to Ebola treatment centers, and 89% said they would engage special Ebola burial teams to remove corpses with suspected Ebola from homes. Of the participants, 66% said they would prefer to observe an Ebola-affected corpse from a safe distance at burials rather than practice traditional funeral rites involving corpse contact. The findings were used to guide the ongoing epidemic response and recovery efforts, including health communication, social mobilization, and planning, to prevent and respond to future outbreaks or sporadic cases of Ebola.
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http://dx.doi.org/10.15585/mmwr.mm6641a4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689093PMC
October 2017

Ultrasound enhanced heterogeneous activation of peroxymonosulfate by a Co-NiOx catalyst.

Water Sci Technol 2017 Sep;76(5-6):1436-1446

College of Architecture and Environment, Sichuan University, Chengdu 610065, China E-mail:

Sulfate radical-based advanced oxidation processes have had considerable attention due to the highly oxidizing function of sulfate radicals (SO·) resulting in acceleration of organic pollutants degradation in aqueous environments. A Co-Ni mixed oxide nanocatalyst, which was prepared by the sol-gel method, was employed to activate peroxymonosulfate (PMS, HSO) to produce SO· with Acid Orange 7 (AO7) selected as a radical probe. The catalyst was characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR) and transmission electron microscopy (TEM). The characterization results indicated that the ingredient of the catalyst had been changed and the amount of surface hydroxyl increased significantly with the addition of Ni. Therefore, it proved that Co-NiOx catalyst was more effective than CoOx to activate PMS. Moreover, ultrasound (US) can increase the degradation rate of AO7 and US/Co-NiOx/PMS system. This study also focused on some synthesis parameters and the system reached the maximum efficiency under the condition when [PMS] = 0.4 mM, [catalyst] = 0.28 g/L, Pus = 200 W. The AO7 removal in these systems follows first order kinetics. Last but not least, quenching studies was conducted which indicated that the amount of hydroxyl radicals (·OH) increases with the increase of initial pH and SO· was the primary reactive oxidant for AO7 degradation.
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http://dx.doi.org/10.2166/wst.2017.316DOI Listing
September 2017

Attitudes about vaccines to prevent Ebola virus disease in Guinea at the end of a large Ebola epidemic: Results of a national household survey.

Vaccine 2017 12 15;35(49 Pt B):6915-6923. Epub 2017 Jul 15.

Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329, USA. Electronic address:

Introduction: In 2014-2016, an Ebola epidemic devastated Guinea; more than 3800 cases and 2500 deaths were reported to the World Health Organization. In August 2015, as the epidemic waned and clinical trials of an experimental, Ebola vaccine continued in Guinea and neighboring Sierra Leone, we conducted a national household survey about Ebola-related knowledge, attitudes, and practices (KAP) and opinions about "hypothetical" Ebola vaccines.

Methods: Using cluster-randomized sampling, we selected participants aged 15+ years old in Guinea's 8 administrative regions, which had varied cumulative case counts. The questionnaire assessed socio-demographic characteristics, experiences during the epidemic, Ebola-related KAP, and Ebola vaccine attitudes. To assess the potential for Ebola vaccine introduction in Guinea, we examined the association between vaccine attitudes and participants' characteristics using categorical and multivariable analyses.

Results: Of 6699 persons invited to participate, 94% responded to at least 1 Ebola vaccine question. Most agreed that vaccines were needed to fight the epidemic (85.8%) and that their family would accept safe, effective Ebola vaccines if they became available in Guinea (84.2%). These measures of interest and acceptability were significantly more common among participants who were male, wealthier, more educated, and lived with young children who had received routine vaccines. Interest and acceptability were also significantly higher among participants who understood Ebola transmission modes, had witnessed Ebola response teams, knew Ebola-affected persons, believed Ebola was not always fatal, and would access Ebola treatment centers. In multivariable analyses of the majority of participants living with young children, interest and acceptability were significantly higher among those living with vaccinated children than among those living with unvaccinated children.

Discussion: The high acceptability of hypothetical vaccines indicates strong potential for introducing Ebola vaccines across Guinea. Strategies to build public confidence in use of Ebola vaccines should highlight any similarities with safe, effective vaccines routinely used in Guinea.
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http://dx.doi.org/10.1016/j.vaccine.2017.06.026DOI Listing
December 2017

Induction of Humoral and Cellular Immune Responses in Mice by Multiepitope Vaccines Composing of Both T and B Lymphocyte Epitopes of MAGE-A3 which are Recombined into HBcAg.

Protein Pept Lett 2017 ;24(10):947-954

Department of Gastroenterological Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang. China.

Background: Melanoma-associated antigen-A3 (MAGE-A3) is a tumor specific antigen and a potential candidate for cancer immunotherapy. We had screened three immunodominant multiepitopes of MAGE-A3, and identified these multiepitope peptides had significantly higher reactivity to serum samples from gastric cancer patients. However, the immune responses of three multiepitope peptides carried by HBcAg in mice have not been investigated.

Objectives: The main objective of this study was to analyze the humoral and cellular immune responses in mice induced by these three multiepitope vaccines of MAGE-A3.

Methods: Three multiepitopes of MAGE-A3 (MAGE-A3(EPI-1, or -2, or -3)) were respectively inserted at HBcAg major immunodominant region (HBcAg(MIR)) of the pET21a(+)/HBcAg(MIR) recombinant plasmid. These recombinant chimeras were identified by PCR, and transfected respectively into E. Coli Ressotta strain. The expression products of rHBcAg(MIR)/MAGE-A3(EPI-1, or -2, or -3) were purified respectively by Ni2+ chelated affinity column, and then confirmed by SDS-PAGE and Western-blot analysis.Purified three rHBcAg(MIR)/MAGE-A3 multiepitopes were administrated respectively into BALB/c (H-2Kd) mice by intradermal injection. The production of rHBcAg(MIR)/MAGE-A3(EPI-1, or -2, or -3) specific IgG in serum from immunized mice were measured by ELISA. Spleen cells from all immunized mice were harvested after one week of last immunization for lymphocyte proliferation assay and cytotoxic T-lymphocyte assay.

Results: PCR and Sequencing analysis showed the presence of the required gene fragment in pET21a(+)/ HBcAg(MIR)/MAGE-A3(EPI-1, or -2, or -3) recombinant plasmid. Purified rHBcAg(MIR)/MAGE-A3(EPI-1, or -2, or -3) could be probed specifically by McAb of 6×his-tag. ELISA analysis indicated that serum from immunized mice with rHBcAg(MIR)/MAGE-A3(EPI-1, -2, or -3) proteins could be discerned specifically by complete MAGE-A3 protein, and high level of antibodies in immune serum were obtained, and all antibody titers could reach above 1:1600. The splenocytes from groups of rHBcAg(MIR)/MAGE-A3(EPI-1,-2, or -3), stimulated respectively with corresponding peptides showed the higher proliferative responses comparing with control groups of HBcAg(MIR) or PBS (p<0.05, respectively). Splenocytes from mice immunized with rHBcAg(MIR)/MAGE-A3 (EPI-1, or -2, or -3) could killed target cells effectively, and there were significant difference of CTL activities compared with control groups of HBcAg(MIR), or PBS (p<0.05, respectively) at any ratio of effector : target.

Conclusion: Our results indicated MIR in HBcAg presenting platform could present MAGE-A3 multiepitopes efficiently and induced significant humoral or cellular immunity. The immune strategy based on multiepitopeimmunization could have potential for preventing or controlling MAGE-A3 associated malignant disease.
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http://dx.doi.org/10.2174/0929866524666170621094921DOI Listing
January 2019

β-Catenin Is a Candidate Therapeutic Target for Myeloid Neoplasms with del(5q).

Cancer Res 2017 08 13;77(15):4116-4126. Epub 2017 Jun 13.

Department of Medicine, Division of Hematology/Oncology, University of Illinois at Chicago, Chicago, Illinois.

Deletion of the chromosome 5q [del(5q)] is one of the most common cytogenetic abnormalities observed in patients with myelodysplastic syndromes (MDS) and therapy-related MDS or acute myeloid leukemia (t-MDS/tAML). Emerging evidence indicates that activation of the Wnt/β-catenin pathway contributes to the development of myeloid neoplasms with del(5q). Whether β-catenin is a potential therapeutic target for myeloid neoplasms with del(5q) has yet to be evaluated. Here, we report that genetic deletion of a single allele of β-catenin rescues ineffective hematopoiesis in an haploinsufficient mouse model, which recapitulates several characteristic features of the preleukemic stage of myeloid neoplasms with a -5/del(5q). In addition, loss of a single allele of β-catenin reversed the defective self-renewal capacity of Apc-haploinsufficient hematopoietic stem cells and reduced the frequency of apoptosis induced by Apc haploinsufficiency. Suppression of β-catenin by indomethacin or β-catenin shRNA reduced proliferation and survival of human leukemia cell lines with del(5q) but not of control leukemia cell lines ; β-catenin inactivation also inhibited leukemia progression in xenograft mice reconstituted with del(5q) leukemia cell lines. Inhibition of β-catenin also stunted growth and colony-forming abilities of primary bone marrow cells from del(5q) AML patients Overall, our data support the idea that β-catenin could serve as a therapeutic target for the treatment of myeloid neoplasms with del(5q). .
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http://dx.doi.org/10.1158/0008-5472.CAN-17-0202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559383PMC
August 2017

Major Immunodominant Region of Hepatitis B Virus Core Antigen as a Delivery Vector to Improve the Immunogenicity of the Fusion Antigen ROP2-SAG1 Multiepitope from Toxoplasma gondii in Mice.

Viral Immunol 2017 09 24;30(7):508-515. Epub 2017 Apr 24.

Department of Microbiology and Immunology, Wenzhou Medical University , Wenzhou, China .

To prepare the dominant multiepitope fusion antigen ROP2-SAG1 (RSmultiepitope) from Toxoplasma gondii in a prokaryotic system, the major immunodominant region (MIR) of the human hepatitis B virus core antigen (HBcAg(MIR)) was used as a delivery vector. The gene encoding the RSmultiepitope was inserted into HBcAg(MIR), and rHBcAg(MIR)-RSmultiepitope was prepared, purified, and administered to BALB/c mice through intradermal injection. An indirect enzyme-linked immunosorbent assay analysis based on a multiepitope peptide facilitated the specific differentiation of sera obtained from mice immunized with the rHBcAg(MIR)-RSmultiepitope protein, and high titers (greater than 1:6,400) of specific anti-RSmultiepitope antibodies were obtained. Immunized splenocytes demonstrated enhanced IFN-γ production. Based on these results, the HBcAg(MIR) vector is easily applied in vitro for targeting the RSmultiepitope and efficiently presents this target epitope for the induction of significant humoral and cellular immune responses. This study offers a novel strategy for the design of a target epitope delivery system for a toxoplasmosis vaccine.
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http://dx.doi.org/10.1089/vim.2016.0135DOI Listing
September 2017

Assessments of Ebola knowledge, attitudes and practices in Forécariah, Guinea and Kambia, Sierra Leone, July-August 2015.

Philos Trans R Soc Lond B Biol Sci 2017 May;372(1721)

Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

The border region of Forécariah (Guinea) and Kambia (Sierra Leone) was of immense interest to the West Africa Ebola response. Cross-sectional household surveys with multi-stage cluster sampling procedure were used to collect random samples from Kambia ( = 635) in July 2015 and Forécariah ( = 502) in August 2015 to assess public knowledge, attitudes and practices related to Ebola. Knowledge of the disease was high in both places, and handwashing with soap and water was the most widespread prevention practice. Acceptance of safe alternatives to traditional burials was significantly lower in Forécariah compared with Kambia. In both locations, there was a minority who held discriminatory attitudes towards survivors. Radio was the predominant source of information in both locations, but those from Kambia were more likely to have received Ebola information from community sources (mosques/churches, community meetings or health workers) compared with those in Forécariah. These findings contextualize the utility of Ebola health messaging during the epidemic and suggest the importance of continued partnership with community leaders, including religious leaders, as a prominent part of future public health protection.This article is part of the themed issue 'The 2013-2016 West African Ebola epidemic: data, decision-making and disease control'.
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http://dx.doi.org/10.1098/rstb.2016.0304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394642PMC
May 2017
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