• ISSN 16748301
  • 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).
Hydrogen sulfide (H2S) is an important messenger for its strong anti-inflammatory effects, which may be involved in multiple cardiovascular diseases. In our previous study, we revealed that H2S attenuates diabetes-accelerated atherosclerosis through suppressing oxidative stress. Here we report that GYY4137, a H2S donor, reduced the plaque formation of aortic roots and the levels of both intercellular cell adhesion molecule 1 (ICAM1) and vascular cell adhesion molecule 1 (VCAM1) in diabetes-accelerated atherosclerotic cells and mouse models. The inflammatory factors of TNF-α, IL-1β, IL-6, and MCP1 were also significantly reduced by GYY4137. Mechanically, GYY4137 suppressed the activation of pyrin domain containing protein 3 (NLRP3) inflammasome in diabetes-accelerated atherosclerosis conditions. Upon knockdown of NLRP3, the increase of ICAM1 and VCAM1 caused by high glucose and oxLDL could be reversed, indicating that H2S protected the endothelium by inhibiting the activity of NLRP3 inflammasome. In conclusion, our study indicates that GYY4137 effectively protects against the development of diabetes-accelerated atherosclerosis by inhibiting inflammasome activation.
Complete congenital achromatopsia is a devastating hereditary visual disorder. Mutations in the CNGB3 gene account for more than 50% of all known cases of achromatopsia. This work investigated the efficiency of subretinal (SR) delivered AAV8 (Y447, 733F) vector containing a human PR2.1 promoter and a human CNGB3 cDNA in Cngb3−/−/Nrl−/− mice. The Cngb3−/−/Nrl−/− mouse was a cone-dominant model with Cngb3 channel deficiency, which partially mimicked the all-cone foveal structure of human achromatopsia with CNGB3 mutations. Following SR delivery of the vector, AAV-mediated CNGB3 expression restored cone function which was assessed by restoration of the cone mediated electroretinogram (ERG) and immunohistochemistry. This therapeutic rescue resulted in long-term improvement of retinal function with restoration of cone ERG amplitude. This study demonstrated an AAV-mediated gene therapy in a cone-dominant mouse model using a human gene construct and provided a potential to be utilized in clinical trials.
This study aimed to investigate the bile salt-stimulated lipase (BSSL) concentration in the milk of Chinese women and its correlation with maternal body mass index (BMI), gestational diabetes mellitus (GDM) and gestational hypertensive disorder (GHD). The BSSL levels in the milk samples were measured by enzyme-linked immunosorbent assay (ELISA). BSSL level in colostrum milk of mothers with full-term infants was positively correlated with pregnancy week and negatively correlated with maternal pre-pregnancy BMI and BMI late in pregnancy. Moreover, the BSSL concentration in mature milk was positively correlated with BMI gain during pregnancy. The BSSL concentration in colostrum milk was lower in GDM mothers than in normal mothers. The BSSL helps infants digest fat in early life and its level was associated with lactation. The changes in BSSL characteristics with maternal BMI and GDM in this study may have clinical implications regarding the effects of pregnancy weight and metabolism on the nutrition and health of the offspring.
The Journal of Biomedical Research--2020, 34(1)
Review Article
Phosphatidylcholine (PC) and phosphatidylethanolamine (PE), which make up the bulk of mammalian cell membrane phospholipids, are recognized for their importance in metabolic health. Perturbations in the ratio of PC:PE can affect membrane integrity and function, which thus have serious health consequences. Imbalance in the hepatic PC and PE membrane content can be linked to metabolic disturbances such as ER stress, fatty liver and insulin resistance. Given that impaired insulin sensitivity underlies the pathology of many metabolic disorders and skeletal muscle is a significant regulator of energy metabolism, it is likely that aberrant phospholipid metabolism in skeletal muscle affects whole-body insulin sensitivity. Sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) activity and mitochondrial function respond to alterations in PC:PE ratio and are associated with glucose homeostasis. Moreover, PC and PE content within the mitochondrial membrane influence mitochondrial respiration and biogenesis and thus, metabolic function. As skeletal muscle phospholipids respond to stimuli such as diet and exercise, understanding the implications of imbalances in PC:PE ratio is of great importance in the face of the rising epidemic of obesity related diseases. This review will summarize the current state of knowledge signifying the links between skeletal muscle PC:PE ratio and insulin sensitivity with respects to PC and PE metabolism, SERCA activity, mitochondrial function and exercise.
Original Article
Apolipoprotein A-Ⅱ (APOA-Ⅱ) is the second most abundant apolipoprotein of high-density lipoprotein (HDL) synthesized mainly by the liver and to a much lesser extent by the intestine. Transgenic mice overexpressing human APOA-Ⅱ present abnormal lipoprotein composition and are prone to atherosclerosis, though in humans the role for APOA-Ⅱ in coronary heart disease remains controversial. Here, we investigated the effects of overexpressed APOA-Ⅱ on HDL structure and function, adipose tissue metabolic activity, glucose tolerance and insulin sensitivity. C57BL/6 mice were infected with an adenovirus expressing human APOA-Ⅱ or a control adenovirus AdGFP, and five days post-infection blood and tissue samples were isolated. APOA-Ⅱ expression resulted in distinct changes in HDL apoproteome that correlated with increased antioxidant and anti-inflammatory activities. No effects on cholesterol efflux from RAW 264.7 macrophages were observed. Molecular analyses in white adipose tissue (WAT) indicated a stimulation of oxidative phosphorylation coupled with respiration for ATP production in mice overexpressing APOA-Ⅱ. Finally, overexpressed APOA-Ⅱ improved glucose tolerance of mice but had no effect on the response to exogenously administered insulin. In summary, expression of APOA-Ⅱ in C57BL/6 mice results in pleiotropic effects with respect to HDL functionality, adipose tissue metabolism and glucose utilization, many of which are beneficial to health.
Cardiac fibrosis is a common pathological change of many cardiovascular diseases. β-catenin has been shown to promote fibrosis. However, the precise role of its homolog γ-catenin in the process of fibrosis remains largely unclear. In this study, we found that the expression of γ-catenin was significantly decreased in angiotensin Ⅱ (Ang Ⅱ)-induced cardiac fibrosis model, contrary to most reports of β-catenin. Overexpression of γ-catenin in cardiac fibroblasts (CFs) significantly inhibited the expression of α-smooth muscle actin (α-SMA), whereas knocking down the expression of γ-catenin with siRNA promoted the occurrence of cardiac fibrosis. Mechanistically, γ-catenin could bind to GSK-3β to inhibit the phosphorylation of GSK-3β, therefore preventing cardiac fibrosis. Our study shows that γ-catenin is an important protective factor in cardiac fibrosis, which provides a new potential target for the treatment of cardiac fibrosis.
The objective of this study is to investigate the immune-enhancing ability of viable and heat-killed Weissella cibaria JW15 (JW15) isolated from Kimchi in RAW 264.7 macrophages. The immune effects were evaluated by measuring the production of NO, cytokines, inflammatory enzyme, and activation of NF-κB. Viable JW15 executed higher activity on stimulating the release of TNF-α as well as activating NF-κB compared to that of heat-killed JW15. Additionally, viable and heat-killed JW15 significantly increased the production of NO, IL-6 and TNF-α more than that of Lactobacillus rhamnosus GG (LGG). Furthermore, viable JW15 induced higher production of iNOS compared with that of viable LGG. Collectively, our finding indicates that viable JW15 had similar, if not more, immune-enhancing activities as heat-killed JW15. In addition, viable JW15 had higher immune-enhancing activity than commercial strain LGG. Therefore, viable JW15 has the potential to be used as a functional food to improve the host immune response.
The generation of a high-quality egg for reproduction requires faithful segregation of chromosome during oocyte meiosis. Here, we report that echinoderm microtubule-associated protein like 6 (EML6) is highly expressed in oocytes, and responsible for accurate segregation of homologous chromosomes in mice. Quantitative real-time RT-PCR and immunohistochemistry analyses revealed that EML6 was predominantly expressed by oocytes in the ovaries. Whole mount immunofluorescent staining showed that EML6 was colocalized with spindle microtubules in oocytes at various stages after meiotic resumption. This specialized localization was disrupted by nocodazole, the microtubule destabilizer, while enhanced by Taxol, a microtubule stabilizing reagent. In vivo knockdown of Eml6 expression by the specific siRNA resulted in chromosome misalignment and alteration in spindle dimension at both metaphase Ⅰ and Ⅱ stages, as well as the increased aneuploidy in the mature oocytes. Thus, these data suggest that EML family proteins participate in the control of oocyte meiotic division.
The aim of this study was to prepare camel serum albumin (CSA) nanoparticles using a self-assembly strategy to co-immobilize curcumin (CCM) and doxorubicin (Dox) which was in favor of combined chemotherapy and biomedical applications of bactrian (Camelus bactrianus) CSA. The constructed CSA nanoparticles (CSA-NPs) with the size around 200 nm displayed a high degree of polydispersity and further encapsulation of CCM and Dox caused no apparent morphological changes to the nanocomposite (CCM/Dox CSA-NPs). The synergistic cytotoxic effect of CCM and Dox on cancer cell A549 was observed with the calculated combination index less than 1.0. Moreover, the release kinetic profile of encapsulated drugs showed a concentration dependence of glutathione (GSH) originating from the GSH used in nanoparticle formation to break the intramolecular disulfide bonds. In vitro cytotoxicity evaluations also revealed that CCM/Dox CSA-NPs showed higher cytotoxicity than that of single drug loaded CSA-NPs, which was also validated by high content screen assay. Taken together, the CCM/Dox CSA-NPs with redox-responsive attributes provided an integrated protein-based combinational drug-delivery matrix to exert synergistic effects.
Choroidal neovascularization (CNV) is a leading cause of visual loss in age-related macular degeneration (AMD). However, the molecular mechanism for CNV progression is still unclear. This study aimed to identify CNV-related circular RNAs (circRNAs), a novel class of non-coding RNAs with diverse functions. A total of 117 circRNAs were differentially expressed in the murine CNV model by microarrays. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to identify the functions of selected circRNAs. The host genes of these circRNAs were predicted to be targeted to neurogenesis (ontology: biological process), proteinaceous extracellular matrix (ECM) (ontology: cellular component), and binding (ontology: molecular function). Differentially expressed circRNAs-mediated regulatory networks were enriched in ECM receptor interaction. Most of the dysregulated circRNAs could potentially bind to five different miRNAs by TargetScan and miRanda. Specifically, circ_15752 was identified in this circRNAs pool which may facilitate vascular endothelial cell proliferation, migration, and tube formation, suggesting a critical role in endothelial angiogenesis. Our work suggests that dysregulated circRNAs may be involved in CNV pathogenesis and serve as potential biomarkers for CNV.
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 11938KB](55)
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 1946KB](57)
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 2322KB](60)
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](63)
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](57)
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 1143KB](61)
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 1050KB](53)
Atrial fibrillation
Thomas M. Munger, Li-Qun Wu, Win K. Shen
2014, 28(1): 1-17.   doi: 10.7555/JBR.28.20130191
+Abstract [PDF 5351KB](58)
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 1263KB](53)
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 762KB](59)