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1. chinaXiv:201605.01732 [pdf]

Quantitative combination of natural anti-oxidants prevents metabolic syndrome by reducing oxidative stress

Gao, Mingjing; Zhao, Zhen; Lv, Pengyu; Gao, Juntao; Zhang, Michael; Gao, Mingjing; Zhao, Zhen; Lv, Pengyu; Gao, Juntao; Zhang, Michael; Li, YuFang; Zhao, Baolu; Zhang, Michael; Gao, Mingjing
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology

Insulin resistance and abdominal obesity are present in the majority of people with the metabolic syndrome. Antioxidant therapy might be a useful strategy for type 2 diabetes and other insulin-resistant states. The combination of vitamin C (Vc) and vitamin E has synthetic scavenging effect on free radicals and inhibition effect on lipid peroxidation. However, there are few studies about how to define the best combination of more than three anti-oxidants as it is difficult or impossible to test the anti-oxidant effect of the combination of every concentration of each ingredient experimentally. Here we present a math model, which is based on the classical Hill equation to determine the best combination, called Fixed Dose Combination (FDC), of several natural anti-oxidants, including Vc, green tea polyphenols (GTP) and grape seed extract proanthocyanidin (GSEP). Then we investigated the effects of FDC on oxidative stress, blood glucose and serum lipid levels in cultured 3T3-L1 adipocytes, high fat diet (HFD)-fed rats which serve as obesity model, and KK-ay mice as diabetic model. The level of serum malondialdehyde (MDA) in the treated rats was studied and Hematoxylin-Eosin (HE) staining or Oil red slices of liver and adipose tissue in the rats were examined as well. FDC shows excellent antioxidant and anti-glycation activity by attenuating lipid peroxidation. FDC determined in this investigation can become a potential solution to reduce obesity, to improve insulin sensitivity and be beneficial for the treatment of fat and diabetic patients. It is the first time to use the math model to determine the best ratio of three anti-oxidants, which can save much more time and chemical materials than traditional experimental method. This quantitative method represents a potentially new and useful strategy to screen all possible combinations of many natural anti-oxidants, therefore may help develop novel therapeutics with the potential to ameliorate the worldwide metabolic abnormalities. (C) 2015 The Authors. Published by Elsevier B.V.

submitted time 2016-05-15 Hits11011Downloads1582 Comment 0

2. chinaXiv:201605.01730 [pdf]

Glycomic profiling of carcinoembryonic antigen isolated from human tumor tissue

Huang, Chuncui; Liu, Yaming; Li, Qianqian; Wu, Hongmei; Li, Yan; Zhan, Tiancheng; Ji, Dengbo
Subjects: Biology >> Biophysics

Background: Carcinoembryonic antigen (CEA) is a protein commonly found in human serum, with elevated CEA levels being linked to the progression of a wide range of tumors. It is currently used as a biomarker for malign tumors such as lung cancer and colorectal cancer [Urol Oncol: Semin Orig Invest 352: 644-648, 2013 and Lung Cancer 80: 45-49, 2013]. However, due to its low specificity in clinical applications, CEA can be used for monitoring only, rather than tumor diagnosis. The function of many glycoproteins is critically dependent on their glycosylation pattern, which in turn has the potential to serve in tumor detection. However, little is known about the detailed glycan patterns of CEA. Methods: To determine these patterns, we isolated and purified CEA proteins from human tumor tissues using immunoaffinity chromatography. The glycan patterns of CEA were then analyzed using a Matrix-Assisted Laser Desorption/Ionization-Time of Flight-Mass Spectrometry3 (MALDI-TOF-MS3) approach. Results: We identified 61 glycoforms in tumor tissue, where CEA is upregulated. These glycosylation entities were identified as bi-antennary, tri-antennary and tetra-antennary structures carrying sialic acid and fucose residues, and include a multitude of glycans previously not reported for CEA. Conclusion: Our findings should facilitate a more precise tumor prediction than currently possible, ultimately resulting in improved tumor diagnosis and treatment.

submitted time 2016-05-15 Hits2422Downloads1080 Comment 0

3. chinaXiv:201605.01534 [pdf]

Recent Progress and Challenges in High Throughput RNA Methylation Sequencing Data Analysis

Liu Lian; Zhang Shao-Wu; Chen Run-Sheng; Meng Jia; Chen Run-Sheng
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology

With the rapid development of high-throughput sequencing technologies, the emerging of methylated RNA immunoprecipitation sequencing (MeRIP-seq) technology makes it possible to detect RNA epigenetic modifications in a large scale, which allows transcriptome-wide profiling of RNA methylation. Mining the patterns of global mRNA methylation from these MeRIP-seq data can help reveal the potential functional roles of these mRNA methylations in regulating gene expression, splicing, RNA editing and RNA stability, effectively guiding the therapeutic intervention of cancer. Here, the principle of MeRIP-seq sequencing was first introduced. Then, the recent progress of the processing and analysis of MeRIP-seq data were comprehensively discussed. In the end, the computational problems and challenges faced in the process of MeRIP-seq data processing were also summarized.

submitted time 2016-05-12 Hits14268Downloads3289 Comment 0

4. chinaXiv:201605.01533 [pdf]

Broadening the versatility of lentiviral vectors as a tool in nucleic acid research via genetic code expansion

Zheng, Yongxiang; Yu, Fei; Wu, Yiming; Si, Longlong; Xu, Huan; Zhang, Chuanling; Xia, Qing; Xiao, Sulong; Wang, Qi; He, Qiuchen; Taira, Kazunari; Zhang, Lihe; Zhou, Demin; Wang, Qi; Chen, Peng; Wang, Jiangyun
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology

With the aim of broadening the versatility of lentiviral vectors as a tool in nucleic acid research, we expanded the genetic code in the propagation of lentiviral vectors for site-specific incorporation of chemical moieties with unique properties. Through systematic exploration of the structure-function relationship of lentiviral VSVg envelope by site-specific mutagenesis and incorporation of residues displaying azide- and diazirine-moieties, the modifiable sites on the vector surface were identified, with most at the PH domain that neither affects the expression of envelope protein nor propagation or infectivity of the progeny virus. Furthermore, via the incorporation of such chemical moieties, a variety of fluorescence probes, ligands, PEG and other functional molecules are conjugated, orthogonally and stoichiometrically, to the lentiviral vector. Using this methodology, a facile platform is established that is useful for tracking virus movement, targeting gene delivery and detecting virus-host interactions. This study may provide a new direction for rational design of lentiviral vectors, with significant impact on both basic research and therapeutic applications.

submitted time 2016-05-12 Hits11209Downloads1556 Comment 0

5. chinaXiv:201605.01527 [pdf]

Deficiency of CD40 Reveals an Important Role for LIGHT in Anti-Leishmania Immunity

Okwor, Ifeoma; Uzonna, Jude E.; Xu, Guilian; Tang, Haidong; Fu, Yang-Xin; Liang, Yong; Uzonna, Jude E.
Subjects: Biology >> Biophysics >> Immunology

We previously showed that LIGHT and its receptor herpes virus entry mediator (HVEM) are important for development of optimal CD4(+) Th1 cell immunity and resistance to primary Leishmania major infection in mice. In this study, we further characterized the contributions of this molecule in dendritic cell (DC) maturation, initiation, and maintenance of primary immunity and secondary anti-Leishmania immunity. Flow-cytometric studies showed that CD8 alpha(+) DC subset was mostly affected by HVEM-Ig and lymphotoxin beta receptor-Ig treatment. LIGHT signaling is required at both the priming and the maintenance stages of primary anti-Leishmania immunity but is completely dispensable during secondary immunity in wild type mice. However, LIGHT blockade led to impaired IL-12 and IFN-gamma responses and loss of resistance in healed CD40-deficient mice after L. major challenge. The protective effect of LIGHT was mediated primarily via its interaction with lymphotoxin beta receptor on CD8 alpha(+) DCs. Collectively, our results show that although LIGHT is critical for maintenance of primary Th1 response, it is dispensable during secondary anti-Leishmania immunity in the presence of functional CD40 signaling as seen in wild type mice.

submitted time 2016-05-12 Hits2583Downloads1430 Comment 0

6. chinaXiv:201605.01516 [pdf]

Circulating Peptidome to Indicate the Tumor-resident Proteolysis

Deng, Zaian; Zhang, Yaou; Cai, Guoping; Deng, Zaian; Li, Yaojun; Fan, Jia; Wang, Guohui; Shen, Haifa; Ferrari, Mauro; Hu, Tony Y.; Deng, Zaian; Zhang, Yaou; Cai, Guoping; Li, Yan; Shen, Haifa; Hu, Tony Y.; Ferrari, Mauro
Subjects: Biology >> Biophysics

Tumor-resident proteases (TRPs) are regarded as informative biomarkers for staging cancer progression and evaluating therapeutic efficacy. Currently in the clinic, measurement of TRP is dependent on invasive biopsies, limiting their usefulness as monitoring tools. Here we identified circulating peptides naturally produced by TRPs, and evaluated their potential to monitor the efficacy of anti-tumor treatments. We established a mouse model for ovarian cancer development and treatment by orthotopic implantation of the human drug-resistant ovarian cancer cell line HeyA8-MDR, followed by porous silicon particle-or multistage vector (MSV) -enabled EphA2 siRNA therapy. Immunohistochemistry staining of tumor tissue revealed decreased expression of matrix metallopeptidase 9 (MMP-9) in mice exhibiting positive responses to MSV-EphA2 siRNA treatment. We demonstrated, via an ex vivo proteolysis assay, that C3f peptides can act as substrates of MMP-9, which cleaves C3f at L-1311-L-1312 into two peptides (SSATTFRL and LWENGNLLR). Importantly, we showed that these two C3f-derived fragments detected in serum were primarily generated by tumor-resident, but not blood-circulating, MMP-9. Our results suggested that the presence of the circulating fragments specially derived from the localized cleavage in tumor microenvironment can be used to evaluate therapeutic efficacy of anti-cancer treatment, assessed through a relatively noninvasive and user-friendly proteomics approach.

submitted time 2016-05-12 Hits3054Downloads1065 Comment 0

7. chinaXiv:201605.01494 [pdf]

Identification of VEGFR2-Binding Peptides Using High Throughput Bacterial Display Methods and Functional Assessment

Pu, Kefeng; Yuan, Lihua; Chen, Lisha; Wang, Anxin; Zhou, Xuan; Zhu, Yimin; Pu, Kefeng; Chen, Lisha; Wang, Anxin; Pu, Kefeng; Chen, Lisha; Wang, Anxin; Zhang, Hailu
Subjects: Biology >> Biophysics >> Oncology

The signal transduction pathway initiated by vascular endothelial growth factor-vascular endothelial growth factor receptor 2 (VEGF-VEGFR2) plays an important role in the angiogenesis of tumors. The effective antagonists of VEGFR2 would behave as potent drugs for the treatment of malignant cancers. In our study, specific binding peptides with high affinity to VEGFR2 were obtained through bacterial display technology. Conserved motif (FF/YEXWGVK) among those peptide sequences was discovered. One of the selected peptides, VRBP1 (YDGNSFYEMWGVKPASES) was identified by screening the biased bacterial peptide library and its physiochemical feature was further characterized. The results of surface plasmon resonance (SPR) assay indicated that the dissociation constant (K-D) value of VRBP1 was 228.3 nM and this peptide competed with VEGF binding to VEGFR2. Particles conjugated with VRBP1 could recognize the human umbilical vein endothelial cells (HUVEC) which express VEGFR2 on the surface. Further therapeutic effect of VRBP1 was examined by in vivo experiments. VRBP1 could result in a significant decrease in tumor size of H460 xenografts. The results from the immunohistochemical assay showed that CD31 positive signals in VRBP1-treated group were fewer than those in the control ones. These data highlighted the potential of VEGFR2-binding peptides as effective molecules for cancer diagnosis and therapy.

submitted time 2016-05-12 Hits3917Downloads1666 Comment 0

8. chinaXiv:201605.01485 [pdf]

Synthetic Model of the Oxygen-Evolving Center: Photosystem II under the Spotlight

Hu, Cheng; Liu, Xiaohong; Wang, Jiangyun; Yu, Yang
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology

The oxygen-evolving center (OEC) in photosystem II catalyzes a water splitting reaction. Great efforts have already been made to artificially synthesize the OEC, in order to elucidate the structure-function relationship and the mechanism of the reaction. Now, a new synthetic model makes the best mimic yet of the OEC. This recent study opens up the possibility to study the mechanism of photosystem II and photosynthesis in general for applications in renewable energy and synthetic biology.

submitted time 2016-05-12 Hits1896Downloads1003 Comment 0

9. chinaXiv:201605.01478 [pdf]

Impaired maturation of large dense-core vesicles in muted-deficient adrenal chromaffin cells

Hao, Zhenhua; Feng, Yaqin; Ma, Jing; Li, Wei; Hao, Zhenhua; Wei, Lisi; Chen, Xiaowei; Zhou, Zhuan; Chen, Liangyi; Wei, Lisi; Chen, Xiaowei; Zhou, Zhuan; Chen, Liangyi; Feng, Yaqin; Du, Wen; Li, Wei
Subjects: Biology >> Biophysics >> Cell Biology

The large dense-core vesicle (LDCV), a type of lysosome-related organelle, is involved in the secretion of hormones and neuropeptides in specialized secretory cells. The granin family is a driving force in LDCV biogenesis, but the machinery for granin sorting to this biogenesis pathway is largely unknown. The mu mutant mouse, which carries a spontaneous null mutation on the Muted gene (also known as Bloc1s5), which encodes a subunit of the biogenesis of lysosome-related organelles complex-1 (BLOC-1), is a mouse model of Hermansky-Pudlak syndrome. Here, we found that LDCVs were enlarged in mu adrenal chromaffin cells. Chromogranin A (CgA, also known as CHGA) was increased in mu adrenals and muted-knockdown cells. The increased CgA in mu mice was likely due a failure to export this molecule out of immature LDCVs, which impairs LDCV maturation and docking. In mu chromaffin cells, the size of readily releasable pool and the vesicle release frequency were reduced. Our studies suggest that the muted protein is involved in the selective export of CgA during the biogenesis of LDCVs.

submitted time 2016-05-12 Hits2634Downloads1632 Comment 0

10. chinaXiv:201605.01472 [pdf]

Antigenic variation of the human influenza A (H3N2) virus during the 2014-2015 winter season

Hua Sha; Liu Mi; Wu AiPing; Jiang TaiJiao; Hua Sha; Liu Mi; Li XiYan; Cheng YanHui; Huang WeiJuan; Tan MinJu; Wei HeJiang; Guo JunFeng; Wang DaYan; Shu YueLong; Peng YouSong; Jiang TaiJiao; Wu AiPing; Jiang TaiJiao; Wu AiPing; Jiang TaiJiao
Subjects: Biology >> Biophysics >> Biology

The human influenza A (H3N2) virus dominated the 2014-2015 winter season in many countries and caused massive morbidity and mortality because of its antigenic variation. So far, very little is known about the antigenic patterns of the recent H3N2 virus. By systematically mapping the antigenic relationships of H3N2 strains isolated since 2010, we discovered that two groups with obvious antigenic divergence, named SW13 (A/Switzerland/9715293/2013-like strains) and HK14 (A/Hong Kong/5738/2014-like strains), co-circulated during the 2014-2015 winter season. HK14 group co-circulated with SW13 in Europe and the United States during this season, while there were few strains of HK14 in mainland China, where SW13 has dominated since 2012. Furthermore, we found that substitutions near the receptor-binding site on hemagglutinin played an important role in the antigenic variation of both the groups. These findings provide a comprehensive understanding of the recent antigenic evolution of H3N2 virus and will aid in the selection of vaccine strains.

submitted time 2016-05-12 Hits2413Downloads1446 Comment 0

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