• 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).
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.
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.
The Journal of Biomedical Research--2019, 33(5)
Original Article
Previous research has shown that smooth muscle of the stomach undergoes developmental changes in the intracellular regulatory mechanism responsible for the contractile process. Whether these developmental changes relate to differences in the expression and/or activity of the key enzymes regulating smooth muscle contraction has not been previously evaluated. Therefore, we aimed to examine the expression and activation of the small monomeric G protein "RhoA" and Rho kinase (ROCK) as well as their correlation with the contraction of gastric smooth muscle cells (GSMCs) in newborn vs. adult rats. Freshly isolated single GSMCs from Sprague-Dawley rats at 1 week (newborn) and 3 months (adult) of age were used in the study. Protein and mRNA expression levels of both ROCK2 and total RhoA were higher in adult compared to newborn rats. Moreover, acetylcholine (ACh)-induced contractions of GSMCs in adult rats were significantly higher than that in newborn animals. Meanwhile, ROCK and Rho activation was higher in adult stomach cells compared to newborn ones. Pretreatment of GSMCs with Y-27632, the ROCK inhibitor, significantly reduced ACh-induced contraction in both groups of cells and greatly abolished contractile differences. In conclusion, our results indicate that RhoA/ROCK pathway and contraction of stomach muscle cells are under developmental regulation.
As one of the most common tumors in women, breast cancer has drawn considerable interest from investigators and clinicians in recent years. Despite early diagnosis and best therapeutic regimens available, the prognosis of malignant or metastatic breast cancer patients is still not optimistic. Hedgehog signaling, a classical pathway indispensable to embryonic development, participates in the growth of a variety of tumors. In the present study, the effect of Sonic Hedgehog (Shh) on breast cancer cells was investigated. We identified that Shh signal stimulated the migration of MCF-7 breast cancer cells. Smo and Gli1 were involved in Shh-stimulated migration of MCF-7 cells. Activating Smo and Gli1 induced cell migration, which was blocked by their specific antagonists. The effect of Shh signaling on MCF-7 cells was independent of Wnt5a, Dvl2 and Rab35, but directly dependent on Rac1. In conclusion, our study suggested that Shh promotes breast cancer cell migration via Rac1 independently of the non-canonical Wnt signaling pathway, which may represent a rational molecular target for combination medication in breast cancer.
Long noncoding RNA (lncRNA) HOTAIR and MALAT1 are implicated in the development of multiple cancers. Genetic variants within HOTAIR and MALAT1 may affect the gene expression, thereby modifying genetic susceptibility to cervical cancer. A case-control study was designed, including 1 486 cervical cancer patients and 1 536 healthy controls. Based on RegulomeDB database, 11 SNPs were selected and genotyped by using Sequenom's Mass ARRAY. Univariate and multivariate logistic regression models were used to calculate the odds ratio (OR) and 95% confidence interval (CI). We found that the A allele of rs35643724 in HOTAIR was associated with increased risk of cervical cancer, while the C allele of rs1787666 in MALAT1 was associated with decreased risk. Compared to individuals with 0–1 unfavorable allele, those with 3–4 unfavorable alleles showed 18% increased odds of having cervical cancer. Our findings suggest that HOTAIR rs35643724 and MALAT1 rs1787666 might represent potential biomarkers for cervical cancer susceptibility.
Overexpression of heat shock protein 27(HSP27) in gastric cancer is correlated with poor clinical prognosis. Melatonin, an endogenous hormone, shows promise in gastric cancer therapy. However, there is limited study on the biological activity of HSP27 in response to melatonin treatment. In this study, we show an anti-proliferative action of melatonin on human gastric cancer cell lines BGC-823 and MGC-803. Biochemically, the inhibitory effect of melatonin is accompanied by the upregulation of HSP27 phosphorylation level. Transfection of gastric cancer cells with HSP27-specific siRNA effectively reduces HSP27 phosphorylation and potentiated melatonin-induced inhibitory effect on cell proliferation. The reduction of cyclin D1 in melatonin-treated cells is also aggravated by HSP27 depletion. Moreover, melatonin stimulation increases p38 phosphorylation. Pretreatment with p38 inhibitor SB203580 not only remarkably suppresses melatonin-induced HSP27 phosphorylation, but also augment the inhibitory effect of melatonin on cyclin D1 expression as well as cell proliferation. Taken together, our study indicates the protective pathway of p38/HSP27 against melatonin-induced inhibitory effect on gastric cancer cell proliferation, suggesting that combined with p38/HSP27 pathway inhibitor, the therapeutic efficacy of melatonin on gastric cancer may be improved.
The actual incidence of human H7N9 infection is supposed to be much higher than the documented laboratory-confirmed cases. In this study, we estimated the number of the actual H7N9 cases in Jiangsu, China using a probabilistic multiplier model. Then, disability adjusted life years (DALYs), direct and indirect economic loss caused by this disease were calculated and analyzed. Till September 2017, the estimated total number of H7N9 cases was 2 952 [median, 90% probability range (PR): 1 487−22 094], which was 11.8 times (5.9−88.4) as large as the reported number. The median morbidity was estimated to be 4 (90% PR: 2−29) per 100 000 population. The total DALYs loss was 16 548 years, and the total economic loss (direct and indirect) was estimated to be RMB 1 044 618 758 (US$ 16.7 M). The average economic loss for per case and for per year was RMB 353 868 (US$ 56 440) and RMB 232 137 502 (US$ 37.0 M), respectively. The actual burden of human H7N9 infections was much heavier than what was documented. Our study provided an approach to estimate actual burden of infectious diseases using laboratory-confirmation.
The aim of this study was to identify the most frequent yeasts in the oral cavity of adult individuals without immune disorders and to associate the presence of these oral yeasts with different characteristics of each individual. Oral rinse samples were obtained from 96 healthy adults and cultured in Sabouraud dextrose agar media and CHROMagar. Yeasts were identified by sequencing the D1/D2 region of the 28S rRNA gene. Probable association among the socio-demographic characteristics, body mass index, family and personal medical history, oral hygiene, tobacco and/or alcohol consumption habits and presence of oral fungi was analyzed. Contingency tables and logistic regression were employed to evaluate possible relationships between the presence of oral fungi and mixed colonization with these variables. 57.3% of the healthy individuals had oral yeasts and 21.8% had mixed colonization. The most prevalent yeasts were Candida albicans (52%), C. parapsilosis (17.9%), and C. dubliniensis (7.57%). Yeasts with most frequently mixed colonization were C. albicans and C. parapsilosis. No relationships were found among the variables analyzed. However, the presence of mixed colonization was related to the presence of dental prostheses (P<0.006), dental apparatuses (P=0.016) and O'Leary index (P=0.012). This is the first study that characterized oral yeasts in Colombian healthy individuals, determined the most prevalent oral yeasts C. albicans, C. parapsilosis and C. dublinensis and an association of mixed colonization with the use of dental prostheses and aparatology and poor hygiene.
Natural volatile organic compounds (VOCs) extracted from conifers such as P. koraiensis and L. kaempferi have long been studied for their anti-oxidant, anti-proliferative, and anti-inflammatory effects. To evaluate the anti-inflammatory effects of VOCs from P. koraiensis and L. kaempferi, lipopolysaccharide (LPS) was administered to generate a mouse model for inflammation by the nasal route to the lungs and intraperitoneally to the whole body. VOCs of P. koraiensis and L. kaempferi were exposed to the mice by standardized wood panels with closed system. Increased levels of serum IgE and PGE2 were observed after exposure to dexamethasone and VOCs. We further determined the expression levels of inflammatory cytokine mRNA in the LPS-induced inflammation model by the reverse transcription quantitative polymerase chain reaction. Furthermore, the levels of cyclooxygenase-2, tumor necrosis factor-α, interleukin-1β, and interleukin-13 were determined in peripheral blood mononuclear cells. Those inflammatory cytokines and the key enzyme for inflammation cyclooxygenase-2 expression in PBMCs were strongly reversed by dexamethasone and VOCs. Lung tissues after nasal LPS exposure showed increased cytokine mRNA expressions which were suppressed by treatment with dexamethasone and VOCs. Furthermore, the damage induced by LPS was attenuated by dexamethasone and VOCs. In conclusion, the results from the present study indicate that VOCs of P. koraiensis and L. kaempferi have a therapeutic potential in the treatment or prevention of local and systemic inflammation due to their immunosuppressive effects.
Mesh hernia repair is one of the commonest open techniques of inguinal hernia repair. The main limiting factor in the use of new meshes is the cost. We carried out a prospective randomized double blind study and comprising of a hundred patients with 100 inguinal hernias admitted consecutively for elective surgery, divided into the polypropylene mesh (PPM) group and the mosquito net mesh (MNM) group each containing fifty patients. All cases were completed successfully and results revealed no difference in two groups. The results of the present study, in consistent with the published literature, reveal that the cheap indigenous mosquito mesh, which has similar properties of an imported mesh, can be safely used for tension-free inguinal hernia repair in adults. Further trials with a larger number of patients and longer follow-ups are justified and recommended.
Thoracic endovascular aortic repair (TEVAR) has been considered as a first-choice treatment for type B aortic dissection (TBAD). However, some patients that is lack of optimal landing zones (<15 mm in dissected Z2, Z3 or the presence of a lusorian artery) still pose significant challenges for TEVAR. We utilized a surgical stent-graft implantation in the descending aorta combined with supra-aortic vessels transposition through median sternotomy for these special TBAD patients. The short- and mid-term results showed that our procedure is a good and alternative therapy for such kind patients.
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](24)
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](27)
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](29)
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](32)
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](25)
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](30)
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](23)
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](27)
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](25)
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](29)