• ISSN 1674-8301
  • CN 32-1810/R
Articles in press have been peer-reviewed and accepted, which are not yet assigned to volumes /issues, but are citable by Digital Object Identifier (DOI).
Posttranscriptional regulation of cancer gene expression programs plays a vital role in carcinogenesis; identifying the critical regulators of tumorigenesis and their molecular targets may provide novel strategies for cancer diagnosis and therapeutics. Highly conserved RNA-binding protein Pumilio-1 (PUM1) regulates mouse growth and cell proliferation, propelling us to examine its role in cancer. We found human PUM1 is highly expressed in a diverse group of cancer, including prostate cancer; enhanced PUM1 expression is also correlated with reduced survival among prostate cancer patients. Detailed expression analysis in twenty prostate cancer tissues showed enhanced expression of PUM1 at mRNA and protein levels. Knockdown of PUM1 reduced prostate cancer cell proliferation and colony formation, and subcutaneous injection of PUM1 knockdown cells led to reduced tumor size. Downregulation of PUM1 in prostate cancer cells consistently elevated cyclin-dependent kinase inhibitor 1B (CDKN1B) protein expression through increased translation but did not impact its mRNA level, while overexpression of PUM1 reduced CDKN1B protein level. Our finding established a critical role of PUM1 mediated translational control, particularly the PUM1-CDKN1B axis, in prostate cancer cell growth and tumorigenesis. We proposed that PUM1-CDKN1B regulatory axis may represent a novel mechanism for the loss of CDKN1B protein expression in diverse cancers and potential targets for therapeutics development.
This study aimed to investigate the metabolic profile of gestational diabetes mellitus (GDM) at both antepartum and postpartum periods. Seventy pregnant women were divided into three groups: the normal glucose-tolerant group (NGT, n=35), the abnormal glucose-tolerant groups without insulin therapy (A1GDM, n=24) or with insulin therapy (A2GDM, n=11). Metabolic profiles of the plasma were acquired by proton nuclear magnetic resonance (1H-NMR) spectroscopy and analyzed by multivariate statistical data analysis. The relationship between demographic parameters and the potential metabolite biomarkers was further explored. Group antepartum or postpartum showed similar metabolic trends. Compare with those of the NGT group, the levels of 2-hydroxybutyrate, lysine, acetate, glutamine, succinate, tyrosine, formate, and all three BCAAs (leucine, valine, isoleucine) in the A2GDM group were increased dramatically, and the levels of lysine, acetate, and formate in the A1GDM group were elevated significantly. The dramatically decreased levels of 3-methyl-2-oxovalerate and methanol were observed both in the A1GDM group and A2GDM group. Compare to the A1GDM group, the branched-chain amino acids (BCAAs) of leucine, valine, and isoleucine were increased dramatically in the A2GDM group. The levels of aromatic amino acids (AAAs), tyrosine and phenylalanine, were significantly increased in GDM women, consistent with the severity of GDM. Interference of amino acid metabolism and disturbance in energy metabolism occurred in women with different grades of GDM. Metabolic profiles could reflect the severity of GDM. Plasma BCAA concentrations showing strong positive correlations with weight and pre-delivery BMI. This study provides a new perspective to understand the pathogenesis and etiology of GDM, which may help the clinical management and treatment of GDM.
Atopic dermatitis (AD) is a common skin disorder difficult to be treated with medication. This study investigated the potential of ovalicin extracted from Cordyceps militaris for the treatment of AD using in vitro and in vivo models. We found that, in canine macrophage cell line DH82, lipopolysaccharide (LPS) upregulated the expression of genes associated with inflammation and pruritic responses through activating calcium and interleukin-31 (IL-31) signaling, and the upregulation could be suppressed by ovalicin, with an effect significantly stronger than dexamethasone. Ovalicin also reduced the expression of IL-31 downstream genes, including JAK2 (Janus kinase 2), TRPV1 (transient receptor potential vanilloid receptor-1), and HRH2 (histamine receptor H2). Ovalicin significantly alleviated the allergic symptoms in the AD mouse model. Histologically, the number of macrophages and mast cells infiltrated in the dermis was significantly reduced by ovalicin treatment. In the skin tissue of AD mice, reduction of IL-31 receptor was observed in the ovalicin treated group compared to the group without ovalicin treatment. To our knowledge, this is the first study to elucidate the anti-atopic mechanism of ovalicin, which could be an alternative to steroidal drugs commonly used for AD treatment.
Accurate targeting of vesicular acetylcholine transporter (VAChT) to synaptic vesicles (SVs) is indispensable for efficient cholinergic transmission. Previous studies have suggested that the dileucine motif within the C-terminus of the transporter is sufficient for its targeting to SVs. However, the cytosolic machinery underlying specific regulation of VAChT trafficking and targeting to SVs is still unclear. Here we used the C-terminus of VAChT as a bait in a yeast two-hybrid screen to identify sorting nexin 5 (SNX5) as its novel interacting protein. SNX5 was detected in the SVs enriched LP2 subcellular fraction of rat brain homogenate and showed strong colocalization with VAChT in both brain sections and PC12 cells. Binding assays suggested that the C-terminal domain of VAChT can interact with both BAR and PX domain of SNX5. Depletion of SNX5 enhanced the degradation of VAChT and the process was mediated through the lysosomal pathway. More importantly, we found that, in PC12 cells, the depletion of SNX5 expression significantly decreased the synaptic vesicle-like vesicles (SVLVs) localization of VAChT. Therefore, the results suggest that SNX5 is a novel regulator for both stability and SV targeting of VAChT.
The Journal of Biomedical Research--2021, 35(4)
Editorial Commentary
Review Article
Current cell-based biosensors have progressed substantially from mere alternatives to molecular bioreceptors into enabling tools for interfacing molecular machineries and gene circuits with microelectronics and for developing groundbreaking sensing and theragnostic platforms. The recent literature concerning whole-cell biosensors is reviewed with an emphasis on mammalian cells, and the challenges and breakthroughs brought along in biomedical analyses through novel biosensing concepts and the synthetic biology toolbox. These recent innovations allow development of cell-based biosensing platforms having tailored performances and capable to reach the levels of sensitivity, dynamic range, and stability suitable for high analytic/medical relevance. They also pave the way for the construction of flexible biosensing platforms with utility across biological research and clinical applications. The work is intended to stimulate interest in generation of cell-based biosensors and improve their acceptance and exploitation.
The ultimate goal of single-cell analyses is to obtain the biomolecular content for each cell in unicellular and multicellular organisms at different points of their life cycle under variable environmental conditions. These require an assessment of: a) the total number of cells, b) the total number of cell types, and c) the complete and quantitative single molecular detection and identification for all classes of biopolymers, and organic and inorganic compounds, in each individual cell. For proteins, glycans, lipids, and metabolites, whose sequences cannot be amplified by copying as in the case of nucleic acids, the detection limit by mass spectrometry is about 105 molecules. Therefore, proteomic, glycomic, lipidomic, and metabolomic analyses do not yet permit the assembly of the complete single-cell omes. The construction of novel nanoelectrophoretic arrays and nano in microarrays on a single 1-cm-diameter chip has shown proof of concept for a high throughput platform for parallel processing of thousands of individual cells. Combined with dynamic secondary ion mass spectrometry, with 3D scanning capability and lateral resolution of 50 nm, the sensitivity of single molecular quantification and identification for all classes of biomolecules could be reached. Further development and routine application of such technological and instrumentation solution would allow assembly of complete omes with a quantitative assessment of structural and functional cellular diversity at the molecular level.
Magnetic particle-based immunoassays are widely used in microbiology-related assays for both microbial capture, separation, analysis, and detection. Besides facilitating sample operation, the implementation of micro-to-nanometer scale magnetic beads as a solid support potentially shortens the incubation time (for magnetic immuno capture) from several hours to less than an hour. Analytical technologies based on magnetic beads offer a rapid, effective and inexpensive way to separate and concentrate the target analytes prior to detection. Magneto-immuno separation uses magnetic particles coated with specific antibodies to capture target microorganisms, bear the corresponding antigens, and subsequently separate them from the sample matrix in a magnetic field. The method has been proven effective in separating various types of pathogenic bacteria from environmental water samples and in eliminating background interferences. Magnetic particles are often used to capture target cells (pathogenic bacteria) from samples. In most commercially available assays, the actual identification and quantitation of the captured cells is then performed by classical microbiological assays. This review highlights the most sensitive analytic methods (i.e., long-range surface plasmon resonance and electrochemical impedance spectroscopy) to detect magnetically tagged bacteria in conjunction with magnetic actuation.
Mechanotransduction, a conversion of mechanical forces into biochemical signals, is essential for human development and physiology. It is observable at all levels ranging from the whole body, organs, tissues, organelles down to molecules. Dysregulation results in various diseases such as muscular dystrophies, hypertension-induced vascular and cardiac hypertrophy, altered bone repair and cell deaths. Since mechanotransduction occurs at nanoscale, nanosciences and applied nanotechnology are powerful for studying molecular mechanisms and pathways of mechanotransduction. Atomic force microscopy, magnetic and optical tweezers are commonly used for force measurement and manipulation at the single molecular level. Force is also used to control cells, topographically and mechanically by specific types of nano materials for tissue engineering. Mechanotransduction research will become increasingly important as a sub-discipline under nanomedicine. Here we review nanotechnology approaches using force measurements and manipulations at the molecular and cellular levels during mechanotransduction, which has been increasingly play important role in the advancement of nanomedicine.
This mini-review gives a brief account of the emergence of the electron paramagnetic resonance (EPR) spectroscopy in the second half of the 20th century and reports the continuous wave EPR spectroscopy studies on human and animal blood. The question posed by this review is whether the EPR spectroscopy in the form it appeared 70 years ago is still able to provide useful information about different pathological conditions in humans, particularly in the area of diagnosis.
Hybrid lipopolymer vesicles are membrane vesicles that can be self-assembled on both the micro- and nano-scale. On the nanoscale, they are potential novel smart materials for drug delivery systems that could combine the relative strengths of liposome and polymersome drug delivery systems without their respective weaknesses. However, little is known about their properties and how they could be tailored. Currently, most methods of investigation are limited to the microscale. Here we provide a brief review on hybrid vesicle systems with a specific focus on recent developments demonstrating that nanoscale hybrid vesicles have different properties from their macroscale counterparts.
Bacterial nanocellulose (BNC) is a homopolymer of β-1,4 linked glycose, which is synthesized by Acetobacter using simple culturing methods to allow inexpensive and environmentally friendly small- and large-scale production. Depending on the growth media and types of fermentation methods, ultra-pure cellulose can be obtained with different physio-chemical characteristics. Upon biosynthesis, bacterial cellulose is assembled in the medium into a nanostructured network of glucan polymers that are semitransparent, mechanically highly resistant, but soft and elastic, and with a high capacity to store water and exchange gasses. BNC, generally recognized as safe as well as one of the most biocompatible materials, has been found numerous medical applications in wound dressing, drug delivery systems, and implants of heart valves, blood vessels, tympanic membranes, bones, teeth, cartilages, cornea, and urinary tracts.
Immunosensing methods are biosensing techniques based on specific recognition of an antigen–antibody immunocomplex, which have become commonly used in safeguarding public health. Taking advantage of antibody-related biotechnological advances, the utilization of an antigen-binding fragment of a heavy-chain-only antibody termed as 'nanobody' holds significant biomedical potential. Compared with the conventional full-length antibody, a single-domain nanobody retaining cognate antigen specificity possesses remarkable physicochemical stability and structural adaptability, which enables a flexible and efficient molecular design of the immunosensing strategy. This minireview aims to summarize the recent progress in immunosensing methods using nanobody targeting tumor markers, environmental pollutants, and foodborne microbes.
Original Article
As a well-known anticancer drug, paclitaxel (PTX), a first-line chemotherapeutic agent, remains unsatisfactory for gastric cancer therapy. It is reported that triptolide (TPL) could enhance the anti-gastric cancer effect of PTX. Considering the poor solubility of both drugs, we developed a red blood cell membrane-biomimetic nanosystem, an emerging tool in drug delivery, to co-load paclitaxel and triptolide (red blood cell membrane coated PTX and TPL co-loaded poly(lactic-co-glycolic acid) [PLGA] nanoparticles, RP(P/T)). The successful preparation was confirmed in terms of particle size, morphology, and surface markers assays. This biomimetic system could prolong circulation and escape immune surveillance. And these properties were verified by stability, in vitro drug release, and cellular uptake assays. Moreover, the MTT and colony formation assays demonstrated the superior anti-proliferation effect of the RP(P/T) to free drugs. The enhanced antitumor effects of RP(P/T) on migration and invasion were also evaluated by wound-healing and transwell assays. Overall, the bionic co-delivery nanoplatform with improved efficacy in vitro is a promising therapy for gastric cancer.
Myocardin in biology and disease
Joseph M. Miano
2015, 29(1): 3-19.   doi: 10.7555/JBR. 29.20140151
+Abstract PDF 5076KB
GYY4137 protects against myocardial ischemia and reperfusion injury by attenuating oxidative stress and apoptosis in rats
Guoliang Meng, Jing Wang, Yujiao Xiao, Wenli Bai, Liping Xie, Liyang Shan, Philip K Moore, Yong Ji
2015, 29(3): 203-213.   doi: 10.7555/JBR.28.20140037
+Abstract PDF 2347KB
Exosomes and their role in the micro-/macro-environment: a comprehensive review
Naureen Javeed, Debabrata Mukhopadhyay
2017, 31(5): 386-394.   doi: 10.7555/JBR.30.20150162
+Abstract PDF 185KB
Immune checkpoint inhibitors in cancer therapy
Eika S. Webb, Peng Liu, Renato Baleeiro, Nicholas R. Lemoine, Ming Yuan, Yaohe Wang
2018, 32(5): 317-326.   doi: 10.7555/JBR.31.20160168
+Abstract PDF 275KB
Recent advances in targeting the autotaxin-lysophosphatidate-lipid phosphate phosphatase axis in vivo
Matthew G.K. Benesch, Xiaoyun Tang, Ganesh Venkatraman, Raie T. Bekele, David N. Brindley
2016, 30(4): 272-284.   doi: 10.7555/JBR.30.20150058
+Abstract PDF 462KB
Statistical analysis for genome-wide association study
Ping Zeng, Yang Zhao, Cheng Qian, Liwei Zhang, Ruyang Zhang, Jianwei Gou, Jin Liu, Liya Liu, Feng Chen
2015, 29(4): 285-297.   doi: 10.7555/JBR.29.20140007
+Abstract PDF 3937KB
Autoantibodies in Alzheimer's disease: potential biomarkers, pathogenic roles, and therapeutic implications
Jianming Wu, Ling Li
2016, 30(5): 361-372.   doi: 10.7555/JBR.30.20150131
+Abstract PDF 426KB
Deciphering the role of hedgehog signaling in pancreatic cancer
Dongsheng Gu, Kelly E Schlotman, Jingwu Xie
2016, 30(5): 353-360.   doi: 10.7555/JBR.30.20150107
+Abstract PDF 376KB
Translating transitions - how to decipher peripheral human B cell development
Mats Bemark
2015, 29(4): 264-284.   doi: 10.7555/JBR.29.20150035
+Abstract PDF 858KB
Platelets in hemostasis and thrombosis: Novel mechanisms of fibrinogen-independent platelet aggregation and fibronectinmediated protein wave of hemostasis
Yan Hou, Naadiya Carrim, Yiming Wang, Reid C. Gallant, Alexandra Marshall, Heyu Ni
2015, 29(6): 437-444.   doi: 10.7555/JBR.29.20150121
+Abstract PDF 610KB
Class A scavenger receptor activation inhibits endoplasmic reticulum stress-induced autophagy in macrophage
Hanpeng Huang, Xiaoyu Li, Yan Zhuang, Nan Li, Xudong Zhu, Jin Hu, Jingjing Ben, Qing Yang, Hui Bai, Qi Chen
2014, 28(3): 213-221.   doi: 10.7555/JBR.28.20130105
+Abstract [PDF 11939KB](827)
Dual therapy of rosiglitazone/pioglitazone with glimepiride on diabetic nephropathy in experimentally induced type 2 diabetes rats
Ravi Prakash Rao, Ansima Singh, Arun K Jain, Bhartu Parsharthi Srinivasan
2011, 25(6): 411-417.   doi: 10.1016/S1674-8301(11)60054-7
+Abstract [PDF 1947KB](734)
A clinical perspective on mucoadhesive buccal drug delivery systems
Ritu MGilhotra, Mohd Ikram, Sunny Srivastava, Neeraj Gilhotra
2014, 28(2): 81-97.   doi: 10.7555/JBR.27.20120136
+Abstract [PDF 2323KB](844)
AEG-1 expression correlates with CD133 and PPP6c levels in human glioma tissues
Jia Guo, Xin Chen, Ruxing Xi, Yuwei Chang, Xuanwei Zhang, Xiaozhi Zhang
2014, 28(5): 388-395.   doi: 10.7555/JBR.28.20140015
+Abstract [PDF 14254KB](813)
Lipoprotein metabolism in nonalcoholic fatty liver disease
Zhenghui Gordon Jiang, Simon C. Robson, Zemin Yao
2013, 27(1): 1-13.   doi: 10.7555/JBR.27.20120077
+Abstract [PDF 1247KB](857)
ApoB/apoA1 is an effective predictor of coronary heart disease risk in overweight and obesity
Min Lu, Qun Lu, Yong Zhang, Gang Tian
2011, 25(4): 266-273.   doi: 10.1016/S1674-8301(11)60036-5
+Abstract [PDF 4KB](737)
Development of Leishmania vaccines: predicting the future from past and present experience
Joshua Muli Mutiso, John Chege Macharia, Maria Ndunge Kiio, James Maina Ichagichu, Hitler Rikoi, Michael Muita Gicheru
2013, 27(2): 85-102.   doi: 10.7555/JBR.27.20120064
+Abstract [PDF 4KB](886)
Atrial fibrillation
Thomas M. Munger, Li-Qun Wu, Win K. Shen
2014, 28(1): 1-17.   doi: 10.7555/JBR.28.20130191
+Abstract [PDF 5352KB](1110)
Maternal risk factors for low birth weight for term births in a developed region in China: a hospital-based study of 55,633 pregnancies
Yihua Bian, Zhan Zhang, Qiao Liu, Di Wu, Shoulin Wang
2013, 27(1): 14-22.   doi: 10.7555/JBR.27.20120046
+Abstract [PDF 4KB](776)
Fracture resistance of posterior teeth restored with modern restorative materials
Ibrahim M. Hamouda, Salah H. Shehata
2011, 25(6): 418-424.   doi: 10.1016/S1674-8301(11)60055-9
+Abstract [PDF 763KB](721)