• 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).
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 (ontology: cellular component), and binding (ontology: molecular function). Differentially expressed circRNAs-mediated regulatory networks were enriched in extracellular matrix (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 suggested that dysregulated circRNAs may be involved in CNV pathogenesis and m serve as potential biomarkers for CNV.
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 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 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 screening 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.
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 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.
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.
The Journal of Biomedical Research--2019, 33(6)
Review Article
Cell death in the living system plays a vital role in maintaining the homeostasis and balancing the cell count in the body. Programmed cell death (PCD) is a crucial component of several development and defense mechanisms. PCD is also important in terms of aging which avoids the accumulation of cellular damage by maintaining cell division. Depending on the execution of cell death and its role in destruction, PCD is categorized into several subtypes. The major different forms of PCD in animals are apoptosis, autophagy and necrosis, which can be distinct in morphological terms. More intense investigations of cell death have given close insight showing other important types of cellular destruction and their pivotal roles in treating disease conditions like cancer. Flavonoids have been acquired a great interest for disease therapies and chemoprevention through activation of several PCD mechanisms. The significant potential of natural flavonoids in the induction of distinct signaling cascades is being a massive approach for targeting uncontrolled cell growth. For these reasons, understanding PCD mechanisms is a promising approach for the interventions in treating cancer. Thus, it is intriguing that understanding the different forms of PCD mechanism induced by flavonoids with more accurate descriptions on the biochemical and cellular processes are gaining more significance in cancer research. Here, we provide a brief overview on the different types of PCD and aim to discuss the functional role of flavonoids in promoting different types of cell death as well as an extensive brief review on their mechanism of action has been highlighted.
Original Article
Gastric cancer is one of the most common malignant gastrointestinal tumors whose morbidity and mortality account for the second and third place respectively in malignant tumors in China. As an important participant in tumor biology, the abnormal expression of long non-coding RNA (lncRNAs) in cancer cells is closely related to the occurrence and development of tumors and plays the role of oncogenes or tumor suppressor genes. In this study, we identified a novel lncRNA NFIA antisense RNA 1 (NFIA-AS1) and explored its role and clinical significance in gastric cancer. Real-time quantitative PCR was performed to detect the expression of NFIA-AS1 in tumor tissues and corresponding normal tissues from 42 pairs of gastric cancer samples. The lower expression of NFIA-AS1 was significantly associated with larger tumor size, lower histological grade, and advanced TNM stage. Kaplan-meier analysis showed that NFIA-AS1 expression could be used as an independent predictor of overall survival. We also demonstrated that overexpression of NFIA-AS1 significantly inhibited the proliferation of gastric cancer cells through affecting p16 levels. In conclusion, our results suggest that the lncRNA NFIA-AS1 may play the role of tumor suppressor gene, and serve as a biomarker for prognosis or progression of gastric cancer.
Many evidences showed that drug resistance of gastric cancer cells could be regulated by the abnormal expression of microRNAs (miRNAs), a post-transcriptional regulator of gene expression. Thus, we investigated the role of miR-3622b-5p in the development of cisplatin (DDP) resistance in human gastric cancer cell lines. A set of biochemical assays were used to elucidate the mechanism by which miR-3622b-5p regulates drug resistance in cancer cells. The expression of miR-3622b-5p was measured by quantitative real-time PCR and showed that miR-3622b-5p was significantly downregulated in the plasma of patients with acquired drug resistance to platinum-based chemotherapy for gastric cancer. miR-3622b-5p was also found significantly downregulated in DDP-resistant gastric cancer cell line SGC7901/DDP, compared with the parental SGC7901 cells. An in vitro drug sensitivity assay showed that overexpression of miR-3622b-5p sensitized SGC7901/DDP cells to DDP. The luciferase activity of reporters constructed by BIRC5 3′-untranslated regions in SGC7901/DDP cells suggested that BIRC5 was target gene of miR-3622b-5p. Ecpotic miR-3622b-5p expression in SGC7901/DDP cells significantly repressed the expression of the BIRC5 and sensitized the cells to DDP-induced apoptosis. By contrast, treatment with miR-3622b-5p inhibitor increased the protein expression of BIRC5 and led to a lower proportion of apoptotic cells in the SGC7901 cells. In conclusion, our findings suggest that miR-3622b-5p regulates DDP resistance of human gastric cancer cells at least in part by repressing the expression of BIRC5. Altering miR-3622b-5p expression may be a potential therapeutic strategy for the treatment of chemoresistance in gastric cancer in the future.
The interleukin-11 (IL-11) and the IL-11 receptor α-subunit (IL-11Rα) have been demonstrated to regulate the invasion and proliferation of tumor cells. Our study intends to evaluate a noninvasive imaging of IL-11Rα expression in breast tumors using near-infrared (NIR) fluorescent dye Cy7-labeled IL-11 mimic peptide CGRRAGGSC. This work evaluated the IL-11Rα expression of breast tumor cells and the binding status of this peptide to IL-11Rα in vitro and in vivo by using Western blotting, immunofluorescence staining and near-infrared fluorescence imaging. Our biochemical study showed that IL-11Rα was overexpressed in breast tumor cells (MCF-7). The cell-binding assay demonstrated specific binding of peptide CGRRAGGSC to MCF-7 cells in vitro. In vivo imaging results showed that NIR fluorescent signals of Cy7-CGRRAGGSC were selectively accumulated in tumor and metabolic organs. While in the blocking experiment, free CGRRAGGSC obviously blocked the concentration of the Cy7-CGRRAGGSC in the tumors. These results suggested that IL-11Rα may be used as a potential target for noninvasive imaging in IL-11Rα overexpressed tumors. Furthermore, the imaging agent of near-infrared fluorescent dye Cy7-labeled CGRRAGGSC is suitable for IL-11Rα expression imaging study in vivo.
Influenza-like illness (ILI) is an acute respiratory infection caused by various pathogens. However, the epidemiologic characteristics of ILI pathogens in Jiangsu province are unclear. To better understand the ILI etiology, the characteristics of the pathogens from nasopharyngeal swab samples of patients with ILI collected from 2012 to 2016 in 6 hospitals in Jiangsu province were studied. The pathogens, including influenza virus, respiratory syncytial virus (RSV), rhinovirus (HRV), adenovirus (ADV), herpes simplex virus (HSV), human coronavirus (hCoV), Streptococcus pneumoniae and Haemophilus influenzae, were detected by real-time PCR. At least one pathogen was identified in 1 334 of the patients (40.23%). Among viruses, HRV, influenza A virus (Flu A), ADV and RSV were the most frequently detected. ADV was the only pathogen that was distributed evenly in different years and regions (P>0.05). The etiological distribution varied in different age groups. Streptococcus pneumoniae was the most common pathogen in co-infections with a co-detection rate of 64.57% (319/494). The spectrum of etiologies could help to estimate disease burden and provide guidance for vaccination.
This survey was designed to assess the sanitation status of hospitals and the compliance of hospital staff to disinfection strategies within the past 11 years. A total of 199 provincial affiliated tertiary or secondary public hospitals from 2007 to 2017 were investigated and seven critical categories, namely indoor air, work surface, hand hygiene, ultraviolet (UV) irradiation intensity, use of disinfectants, sterilization of medical items, and effects of steam sterilizer, were monitored. The average qualified rates were (94.74±3.54)% (810/855), (97.25±1.65)% (1 876/1 929), (87.57±4.60)% (2 508/2 864), (95.00±4.50)% (1 196/1 259), and (98.76±1.14)% (1 599/1 619) for indoor air, work surface, hand hygiene, UV irradiation intensity, and sterilization of medical items, respectively. In terms of other categories, a few samples were not qualified: 3/1 575 for use of disinfectants and 1/243 for effects of steam sterilizer. The hospital disinfection monitoring and supervision program effectively improved the effectiveness of disinfection. Routine monitoring and supervision must be conducted to ensure a safe hospital treatment environment.
Airborne particulate matter (PM), especially PM2.5, can be easily adsorbed by human respiratory system. Their roles in carrying pathogens for spreading epidemic diseases has attracted great concern. Herein, we developed a novel gelatin filter-based and culture-independent method for investigation of the microbial diversity in PM samples during a haze episode in Tianjin, China. This method involves particle capture by gelatin filters, filter dissolution for DNA extraction, and high-throughput sequencing for analysis of the microbial diversity. A total of 584 operational taxonomic units (OTUs) of bacteria and 370 OTUs of fungi at the genus level were identified during hazy days. The results showed that both bacterial and fungal diversities could be evaluated by this method. This study provides a convenient strategy for investigation of microbial biodiversity in haze, facilitating accurate evaluation of airborne epidemic diseases.
The extent to which factors affect the probability of clinical pregnancy in the first fresh embryo transfer after assisted conception is unknown. In order to examine the predictors of clinical pregnancy, a retrospective cohort study was launched between January 1, 2013 and December 31, 2016 in four infertility clinics including 19 837 in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) fresh cycles with known outcomes and relevant records. A multivariable logistic regression was used to select the most significant predictors in the final nomogram for predicting clinical pregnancy. Furthermore, the model was validated by an independent validation set and the performance of the model was evaluated by the receiver operating characteristic (ROC) curves along with the area under the ROC curve (AUC) and calibration plots. In a training set including 17 854 participants, we identified that female age, tubal factor, number of embryos transferred, endometrial thickness and number of good-quality embryos were independent predictors for clinical pregnancy. We developed a nomogram using these five factors and the predictive ability was 0.66 for AUC (95% CI 0.64–0.68), which was independently validated in the validation set (AUC=0.66, 95% CI 0.65–0.68). Our results show that some specific factors can be used to provide infertile couples with an accurate assessment of clinical pregnancy following assisted conception and facilitate to guide couples and clinicians.
Brief Report
Conjunctive use of anesthetic agents results in drug interactions which can alter or influence multiple patient outcomes such as anesthesia depth, and cardiorespiratory parameters which can also be altered by patient conditions and surgical procedures. Using artificial intelligence technology to continuously gather data of drug infusion and patient outcomes, we can generate reliable computer models individualized for a patient during specific stages of particular surgical procedures. This data can then be used to extend the current anesthesia monitoring functions to include future impact prediction, drug administration planning, and anesthesia decisions.
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](38)
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](41)
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](44)
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](46)
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](39)
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](44)
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](36)
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](42)
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](39)
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](43)