• 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).
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.
The Journal of Biomedical Research--2021, 35(5)
Original Article
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.
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.
Superficial esophageal squamous cell carcinoma (SESCC) is defined as carcinoma with mucosal or submucosal invasion, regardless of regional lymph node metastasis (LNM). The lymph node status is not only a key factor to determine the training strategy, but also the most important prognostic factor in esophageal cancer. In this study, we establish a clinical nomogram for predicting LNM in patients with SESCC. A predictive model was established based on the training cohort composed of 711 patients who underwent esophagectomy for SESCC from December 2009 to June 2018. A prospective cohort of 203 patients from June 2018 to January 2019 was used for validation. Favorable calibration and well-fitted decision curve analysis were conducted and good discrimination was observed (concordance index [C-index], 0.860; 95% confidence interval [CI], 0.825–0.894) through internal validation. The external validation cohort presented good discrimination (C-index, 0.916; 95% CI, 0.860–0.971). This model may facilitate the prediction of LNM in patients with SESCCs.
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.
Donation after circulatory-determined death (DCD) is an important part of renal transplantation. Therefore, DCD renal transplantation animal model should be established to study the mechanism of organ injury. Here, we established a stable DCD rat renal transplantation model and investigated the dynamic regulation of graft self-repairing and antioxidant capacities with different non-heart-beating times (NHBTs). Male Sprague-Dawley rats were randomly divided into four groups with the NHBT of the donors from 0 to 15, 30, and 45 minutes. Recipients in long NHBT groups had a significantly lower survival rate and poorer graft function than those in short NHBT groups. Grafts from the 15-minute and 30-minute NHBT groups showed light and severe injury respectively at an early stage after transplantation and recovered within 7 days after transplantation, whereas the self-repairing of the grafts in the 45-minute NHBT group was delayed. The expressions of proliferating cell nuclear antigen (PCNA) and von Willebrand factor (vWF) were dependent on NHBT. The expression of antioxidant proteins paralleled graft recovery. In conclusion, the recipients can up-regulate antioxidant capacity to enhance graft self-repairing in DCD renal transplantation. Prolonged NHBT can delay the self-repairing and antioxidation of grafts.
Brugada syndrome (BrS) is a complex genetic cardiac ion channel disease that causes a high predisposition to sudden cardiac death. Considering that its heterogeneity in clinical manifestations may result from genetic background, the application of patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) may help to reveal cell phenotype characteristics underlying different genetic variations. Here, to verify and compare the pathogenicity of mutations (SCN5A c.4213G>A and SCN1B c.590C>T) identified from two BrS patients, we generated two novel BrS iPS cell lines that carried missense mutations in SCN5A or SCN1B, compared their structures and electrophysiology, and evaluated the safety of quinidine in patient-specific iPSC-derived CMs. Compared to the control group, BrS-CMs showed a significant reduction in sodium current, prolonged action potential duration, and varying degrees of decreased Vmax, but no structural difference. After applying different concentrations of quinidine, drug-induced cardiotoxicity was not observed within 3-fold unbound effective therapeutic plasma concentration (ETPC). The data presented proved that iPSC-CMs with variants in SCN5A c.4213G>A or SCN1B c.590C>T are able to recapitulate single-cell phenotype features of BrS and respond appropriately to quinidine without increasing incidence of arrhythmic events.
Letter to the Editor
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
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
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
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](836)
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](741)
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](846)
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](820)
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](869)
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](741)
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](899)
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](1134)
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](784)
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](732)