• 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).
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.
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.
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.
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.
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.
Increased expression of matrix metalloproteinase-1 (MMP-1) has been observed in the lesions of atherosclerosis and aneurysms; however, it is not fully understood whether macrophage-derived MMP-1 affects these diseases. To investigate whether macrophage-derived MMP-1 participates in the development of vascular diseases, we generated transgenic (Tg) rabbits expressing human MMP-1 in the monocyte/macrophage lineage under the control of the human scavenger receptor enhancer/promoter. Tg rabbits exhibited no visible abnormalities throughout their bodies. Western blotting analysis revealed that the amount of MMP-1 proteins in the conditioned media secreted from peritoneal macrophages of Tg rabbits was up to 3-fold higher than that in non-Tg rabbits. For the first experiment, Tg and non-Tg rabbits were fed a cholesterol diet for 16 weeks, and aortic and coronary atherosclerosis were evaluated. The gross lesion area of aortic atherosclerosis in Tg rabbits was not significantly different from that in non-Tg rabbits, but Tg rabbits had marked destruction of the medial elastic lamina of the aortic lesions on microscopic examination. For the second experiment, we generated aortic aneurysms by incubating with elastase. Compared with non-Tg rabbits, Tg rabbits exhibited a significantly greater aortic dilation. Increased macrophage-derived MMP-1 led to increased medial destruction in both aortic atherosclerosis and aneurysms. These results demonstrate that MMP-1 plays a different role in the pathogenesis of atherosclerosis and aneurysms.
Hepatic ischemic-reperfusion injury is a major cause of liver transplant failure, and is of increasing significance due to increased use of expanded criteria livers for transplantation. This review summarizes the mechanisms and protective strategies for hepatic ischemic-reperfusion injury in the context of liver transplantation. Pharmacological therapies, the use of pre-and post-conditioning and machine perfusion are discussed as protective strategies. The use of machine perfusion offers significant potential in the reconditioning of liver grafts and the prevention of hepatic ischemic-reperfusion injury, and is an exciting and active area of research, which needs more study clinically.
Postprandial glucose level is an independent risk factor for cardiovascular disease that exerts effects greater than glucose levels at fasting state, whereas increase in serum triglyceride level, under both fasting and postprandial conditions, contributes to the development of arteriosclerosis. Insulin resistance is a prevailing cause of abnormalities in postabsorptive excursion of blood glucose and postprandial lipid profile. Excess fat deposition renders a vicious cycle of hyperglycemia and hypertriglyceridemia in the postprandial state, and both of which are contributors to atherosclerotic change of vessels especially in patients with type 2 diabetes mellitus. Several therapeutic approaches for ameliorating each of these abnormalities have been attempted, including various antidiabetic agents or new compounds targeting lipid metabolism.
Nutrition status is very important for child growth. We aim to analyze the prevalence of undernutrition and associated factors among children under 5 years of age in Lhaviyani Atoll, Maldives.A total of 800 children (under 5 years) and their mothers were selected for this study. Data was collected by a pretested questionnaire and anthropometric measurements from the record book. Chi-square tests and multivariate logistic regression were used to find the association of nutritional status with determinants. The distribution of height for age and weight for age in studied children in Maldives was skewed to the left compared with the WHO standard. The prevalence of undernutrition based on underweight (10.75%), stunting (13.5%), and wasting (9.60%) was estimated to be 23.85% among children. Child age, gender and mother's education were significantly associated with undernutrition (P<0.05). Our survey highlighted that better nutritional interventions are needed to improve child health in this region.
Studies of the associations between maternal exposure to particulate matter (PM) and risk of adverse effects on fetal growth are inconsistent and inconclusive. Birth cohort studies are the best available study designed to answer this question, but so far the evidence from such studies has not been combined. We sought to assess the association between maternal exposure to PM and low birthweight (LBW) across 14 studies from 11 centers, and to explore the influence of trimester and exposure assessment methods on between-center heterogeneity in this association. Data were derived from PubMed, Embase, Google Scholar, CNKI, and WanFang database, references from relevant articles, and results from published studies until March 2017. A random-effects meta-analysis was used to combine the coefficient and odds ratios (OR) of individual studies conducted among 14 birth cohort studies. Results from random-effect meta-analysis suggested that a 17% and 6% increase in risk of LBW was associated with a 10 mg/m3 increase in PM2.5 and PM10 exposure concentrations at 3rd trimester (pooled odds ratios (OR), 1.17 and 1.06; 95% confidence interval (CI), 0.94–1.46 and 0.97-1.15, respectively), but our 95% CI included the null value. Our results showed a positive association between exposure to PM2.5 and PM10 during pregnancy and LBW based on birth cohort studies. However, neither reached formal statistical significance. This suggested that maternal exposure to PM may have adverse effects on birth outcomes. Additional mechanistic studies are necessary to confirm the relationship between PM pollution and LBW.
Volatile anesthetic preconditioning has been shown to be a potent way to provide myocardium protection against ischemia/reperfusion (I/R) injury; however, this cardioprotection is lost in senescent animal models and elderly patients. NFkB-regulated genes have been linked to myocardial I/R injury and anesthetic preconditioning. Here, we investigated NFkB activation related to anesthetic preconditioning in aging rat myocardium. Isolated, Langendorff perfused rat hearts from Fischer 344 male rats, 24 months old, were randomly assigned to one of the three groups. The hearts of the control group were perfused with physiologic solution without any intervention. The hearts in the I/R group were subjected to 25 minutes ischemia and followed by 60 minutes reperfusion. The hearts in the treatment group were subjected to 10 minutes 2.5% sevoflurane, followed by 20 minutes washout and by 25 minutes ischemia and 60 minutes of reperfusion, respectively. Left ventricular developed pressure (LVDP) and left ventricular end-diastolic pressure (LVEDP) were measured. Western blot analysis was used to measure inhibitor of kB (IkB) and anti-apoptotic genes: A1, ILP, c-IAP-2, Bcl-2, caspase 8 and caspase 9. Ischemia and reperfusion significantly decreased LVDP and increased LVEDP in aged rat hearts. Anesthetic preconditioning with sevoflurane did not change the effects I/R on LVDP and LVEDP, despite the fact that after treatment with anesthetic preconditioning, the levels of IκB, A1, ILP, caspase 8 and caspase 9 were significantly different compared to those of the control hearts. In conclusion, anesthetic preconditioning with sevoflurane does not improve myocardial systolic and diastolic functions. Our results suggest that the activation of NFkB regulated genes is different in the senescent myocardium and could account for loss of cardioprotection with aging.
Clinical xenotransplantations have been hampered by human preformed antibody-mediated damage of the xenografts. To overcome biological incompatibility between pigs and humans, one strategy is to remove the major antigens [Gal, Neu5Gc, and Sd(a)] present on pig cells and tissues. Triple gene (GGTA1, CMAH, and β4GalNT2) knockout (TKO) pigs were produced in our laboratory by CRISPR-Cas9 targeting. To investigate the antigenicity reduction in the TKO pigs, the expression levels of these three xenoantigens in the cornea, heart, liver, spleen, lung, kidney, and pancreas tissues were examined. The level of human IgG/IgM binding to those tissues was also investigated, with wildtype pig tissues as control. The results showed that αGal, Neu5Gc, and Sd(a) were markedly positive in all the examined tissues in wildtype pigs but barely detected in TKO pigs. Compared to wildtype pigs, the liver, spleen, and pancreas of TKO pigs showed comparable levels of human IgG and IgM binding, whereas corneas, heart, lung, and kidney of TKO pigs exhibited significantly reduced human IgG and IgM binding. These results indicate that the antigenicity of TKO pig is significantly reduced and the remaining xenoantigens on porcine tissues can be eliminated via a gene targeting approach.
Congestive heart failure (CHF) is defined as a cardiac dysfunction leading to low cardiac output and inadequate tissue perfusion. Intravenous positive inotropes are used to increase myocardial contractility in hospitalized patients with advanced heart failure. Milrinone is a phosphodiesterase Ⅲ inhibitor and used most commonly for inotropic effect. The well-known PROMISE study investigated the effects of milrinone on mortality in patients with severe CHF, and concluded that long-term therapy with milrinone increased morbidity and mortality among patients with advanced CHF. Previous studies have suggested that phosphodiesterase inhibitors can have potential effects on inflammatory pathways. Hence, we hypothesized that milrinone may alter inflammatory gene expressions in cardiomyocytes, thus leading to adverse clinical outcomes. We used rat cardiomyocyte cell line H9C2 and studied the impact of exposing cardiomyocytes to milrinone (10 mmol/L) for 24 hours on inflammatory gene expressions. RNA extracted from cultured cardiomyocytes was used for whole rat genome gene expression assay (41,000 genes). The following changes in inflammatory response-related gene expressions were discovered. Genes with increased expressions included:THBS2 (+ 9.98), MMP2 (+ 3.47), DDIT3 (+ 2.39), and ADORA3 (+ 3.5). Genes with decreased expressions were:SPP1 (- 5.28) and CD14 (- 2.05). We found that the above mentioned gene expression changes seem to indicate that milrinone may hinder the inflammatory process which may potentially lead to adverse clinical outcomes. However, further in vivo and clinical investigations will be needed to illustrate the clinical relevance of these gene expression changes induced by milrinone.
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.
The prevalence of cardiovascular diseases (CVDs) is increasing at a rapid pace in developed countries, and CVDs are the leading cause of morbidity and mortality. Natural products and ethnomedicine have been shown to reduce the risk of CVDs. Schizonepeta (S.) tenuifolia is a medicinal plant widely used in China, Korea, and Japan and is known to exhibit anti-inflammatory, antioxidant, and immunomodulatory activities. We hypothesized that given herbal plant exhibit pharmacological activities against CVDs, we specifically explored its effects on platelet function. Platelet aggregation was evaluated using standard light transmission aggregometry. Intracellular calcium mobilization was assessed using Fura-2/AM, and granule secretion (ATP release) was measured in a luminometer. Fibrinogen binding to integrin αⅡbβ3, was assessed using flow cytometry. Phosphorylation of mitogen-activated protein kinase (MAPK) signaling molecules and activation of the protein kinase B (Akt) was assessed using Western blot assays. S. tenuifolia, extract potently and significantly inhibited platelet aggregation, calcium mobilization, granule secretion, and fibrinogen binding to integrin αⅡbβ3. Moreover, all extracts significantly inhibited MAPK and Akt phosphorylation. S. tenuifolia extract inhibited platelet aggregation and granule secretion, and attenuated collagen mediated GPVI downstream signaling, indicating the potential therapeutic effects of these plant extracts on the cardiovascular system and platelet function. We suggest that S. tenuifolia extract may be a potent candidate to treat platelet-related CVDs and to be used as an antiplatelet and antithrombotic agent.
To evaluate the effect of methotrexate on collagen-induced arthritis, micro-computed tomography (micro-CT) and histopathological analyses were used in male Wistar rats. Rats were divided randomly into three groups. Group 1 was treated with 0.9% saline, and groups 2 and 3 were boosted with type Ⅱ collagen. From day 21 to 42, groups 1 and 2 were orally treated with 0.9% saline and group 3 was orally treated with 1.5 mg/kg methotrexate. All rats were sacrificed at day 42 after the first collagen treatment. Micro-CT analyses showed bony parameters, such as bone volume and trabecular number, were decreased in group 2 compared to group 1, and these parameters were recovered in group 3. Histopathological examination and pathological parameter scoring showed that the knee joints of rats in group 2 had severe joint destruction, showing cartilage and bone erosion, enlarged cavities with inflammatory cell infiltration and activation of synovial fibroblasts. By contrast, these changes were reduced in group 3. Taken together, methotrexate treatment showed therapeutic potential in male rat collagen-induced arthritis model, and micro-CT analysis and histopathological tools could be integrated to assess the quantification/qualification of arthritic lesions.
Contrary to freezing preservation and formalin embalming, Thiel embalmed cadaver presents soft texture and color very close to that of living organism, and many applications based on Thiel embalmed cadavers have been reported. However, Thiel embalmed cadavers cannot be used as reliable evaluation model for radiofrequency ablation (RFA) due to dramatic changes of electrical conductivity in the embalmed tissue. To address this issue, we investigated various modifications of the original Thiel embalming solution. By altering the chemicals' species and concentration we figured out a formula that can greatly reduce the embalming fluid's electrical conductivity without significantly compromising the 18-day embalmed kidney samples' suppleness and color. We also investigated a two-stage embalming technique by first submerging the kidney sample into original Thiel's tank fluid for 28 days, then the sample was withdrawn from the tank fluid and placed into modified dilution fluids for additional two weeks. Stiffening and discoloration occurred in these diluted samples implying the reversibility of Thiel-embalmed tissues' suppleness and color with the removal of the strong electrolytes. This study presents a modified embalming method which could be used for RFA evaluation and also helps our understanding of the mechanism of embalmment process.
Gastric cancer (GC)is one of the most common malignant gastrointestinal tumors, and its morbidity and mortality account for the second and third place respectively in malignant tumors in China. As a major 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-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 andcorresponding normal tissues from 42 pairs of GC samples. The lower expression of NFIA-AS1 wassignificantly associated with larger tumor size, lower histologicalgrade, and advanced TNM stage. Kaplan-meier analysisshowed that NFIA-AS1 expression couldbe used as anindependent predictor of overall survival.We alsodemonstrated that overexpression of NFIA-AS1significantly 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 asa biomarker for prognosis or progression of gastric cancer.
The interleukin-11(IL-11) and the IL-11 receptor subunit αhave been demonstrated to regulate the invasion and proliferation of tumor cells. This study was initiated to evaluate an noninvasive imaging of IL-11Rαexpression in breast tumors using near-infrared (NIR) fluorescent dye Cy7-labeled IL-11 mimic CGRRAGGSC. This work evaluated the IL-11Rα expression of breast tumor cells and the binding status of CGRRAGGSC peptide to IL-11Rα in vitro and in vivo by using western blots, immunofluorescence staining and near-infrared fluorescence imaging. Western blot and immunohistochemistry analysis showed that IL-11Rα was overexpressed in breast tumor cells (MCF-7). The cell-binding assay demonstrated specific binding of c(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 c(CGRRAGGSC) is suitable for IL-11Rα expression imaging study in vivo.
The Journal of Biomedical Research--2019, 33(3)
Review Article
The breakthrough discovery of cardiac natriuretic peptides provided the first direct demonstration of the connection between the heart and the kidneys for the maintenance of sodium and volume homeostasis in health and disease. Yet, little is still known about how the heart and other organs cross-talk. Here, we review three physiological mechanisms of communication linking the heart to other organs through: ⅰ) cardiac natriuretic peptides, ⅱ) the microRNA-208a/ mediator complex subunit-13 axis and ⅲ) the matrix metalloproteinase-2 (MMP-2)/C-C motif chemokine ligand-7/ cardiac secreted phospholipase A2 (sPLA2) axis – a pathway which likely applies to the many cytokines, which are cleaved and regulated by MMP-2. We also suggest experimental strategies to answer still open questions on the latter pathway. In short, we review evidence showing how the cardiac secretome influences the metabolic and inflammatory status of non-cardiac organs as well as the heart.
Original Article
Fasudil, a selective rho kinase (ROCK) inhibitor, has been reported to play a beneficial role in systemic inflammation in acute lung injury, but its mechanism for ameliorating pulmonary edema and inflammation remains unclear. Using hematoxylin-and-eosin (H&E) staining, immunohistochemistry, enzyme-linked immunosorbent assay, quantitative real time PCR and Western blotting, we found that fasudil attenuated LPS-induced lung injury, decreased lung edema, and suppressed inflammatory responses including leukocyte infiltration and IL-6 production. Further, fasudil upregulated LPS-induced aquaporin 5 reduction and inhibited NF-kB activation in the lungs of mice. Our results suggest that fasudil could restore the expression of aquaporin 5 to eliminate LPS-induced lung edema and prevent LPS-induced pulmonary inflammation by blocking the inflammatory pathway. Collectively, blockade of the ROCK pathway by fasudil may be a potential strategy for the treatment of acute lung injury.
Tumor necrosis factor alpha (TNF-α) is a cytokine that can potently stimulate the synthesis of a range of proinflammatory mediators in macrophages. The underlying epigenetic mechanism, however, is underexplored. Here we report that the transcriptional modulator megakaryocytic leukemia 1 (MKL1) is associated with a histone H3K4 methyltransferase activity. Re-ChIP assay suggests that MKL1 interacts with and recruits WDR5, a component of the COMPASS complex responsible for H3K4 methylation, to the promoter regions of pro-inflammatory genes in macrophages treated with TNF-α. WDR5 enhances the ability of MKL1 to stimulate the promoter activities of proinflammatory genes. In contrast, silencing of WDR5 attenuates TNF-α induced production of pro-inflammatory mediators and erases the H3K4 methylation from the gene promoters. Of interest, the chromatin remodeling protein BRG1 also plays an essential role in maintaining H3K4 methylation on MKL1 target promoters by interacting with WDR5. MKL1 knockdown disrupts the interaction between BRG1 and WDR5. Together, our data illustrate a role for MKL1 in moderating the crosstalk between BRG1 and WDR5 to activate TNF-α induced pro-inflammatory transcription in macrophages.
Caspase-8 (CASP8) is one key regulator of apoptosis of T lymphocytes and is encoded by the CASP8 gene. It has been reported that the six-nucleotide deletion polymorphism (-652 6N del) of the CASP8 gene had effect on some cancer risk. Few studies explored the association between CASP8 gene polymorphism and digestive tract cancer risk. To evaluate the association between the CASP8 -652 6N del polymorphism and the risk of digestive tract cancer, we conducted this meta-analysis. We found that CASP8-652 6N del polymorphism was associated with a significantly reduced risk of digestive tract cancer in the co-dominant model (del/del vs. ins/ins: OR = 0.82, 95%CI = 0.72–0.95; del/ins vs. ins/ins: OR = 0.92, 95%CI = 0.87–0.97; dominant model (del/ins + del/del vs. ins/ins: OR = 0.91, 95%CI = 0.87–0.96, recessive model: del/del vs. del/ins + ins/ins: OR = 0.85, 95%CI = 0.75–0.97). In the stratified analysis by cancer types, we found that all genetic models had protective effect on gastric cancer. Similar results were observed for colorectal cancer under heterozygote comparison and dominant model, but not under homozygote comparison or recessive model. In addition, a significantly decreased risk was found on esophageal cancer for most genetic models, except heterozygote comparison. When stratified by ethnicity and source of control, an evidently decreased risk was identified in the Asian populations and population-based studies. In conclusion, there exists an association between the CASP8 -652 6N del polymorphism and reduced digestive cancer risk, especially among Asians and populationbased studies.
Acrylamide, a potential carcinogen, exists in carbohydrate-rich foods cooked at a high temperature. It has been reported that acrylamide can cause DNA damage and cytotoxicity. The present study aimed to investigate the potential mechanism of human hepatocarcinoma HepG2 cell proliferation induced by acrylamide and to explore the antagonistic effects of a natural polyphenol curcumin against acrylamide via miR-21. The results indicated that acrylamide (≤100 μmol/L) significantly increased HepG2 cell proliferation and miR-21 expression. In addition, acrylamide reduced the PTEN expression in protein level, while induced the expressions of p-AKT, EGFR and cyclin D1. The PI3K/AKT inhibitor decreased p-AKT protein expression and inhibited the proliferation of HepG2 cells. In addition, curcumin effectively reduced acrylamide-induced HepG2 cell proliferation and induced apoptosis through the expression of miR-21. In conclusion, the results showed that acrylamide increased HepG2 cell proliferation via upregulating miR-21 expression, which may be a new target for the treatment and prevention of cancer.
Over the recent years, it has been found that microglia pseudopodia contact synapses, detect sick ones and prune them, even in adult animals. Myelinated nerves also carry out plasticity in which microglia remove myelin debris by phagocytosis. However, it remains unknown whether microglia explore structures on nerve fibers, such as Ranvier's node (RN) or myelin sheath, before they become debris. By double or triple staining RNs or myelin sheathes and microglia in healthy rat corpus callosum, this study unveiled direct contacts of microglia pseudopodia with RNs and with para- and inter-nodal myelin sheathes, which was then verified by electron microscopic observations. Our data indicated that microglia also explore unmyelinated nerve fibers. Furthermore, we used the animals with matured white matter; therefore, microglia may be actively involved in plasticity of matured white matter tracts as it does for synapse pruning, instead of only passively phagocytize myelin debris.
Nephrotic syndrome is one of the most common childhood kidney diseases. It is mostly found in the age group of 2 to 8 years. Around 10%–15% of nephrotic syndrome cases are non-responders of steroid treatment (SRNS). Angiotensin converting enzyme (ACE) (I/D) gene association studies are important for detecting kidney disease and herein we assessed the association of ACE (I/D) polymorphism with nephrotic syndrome in South Indian children. We recruited 260 nephrotic syndrome (162 boys and 98 girls) and 218 (140 boys and 78 girls) control subjects. ACE I/D polymorphism was analyzed by PCR using genotype allele specific primers. In ACE (I/D), we did not find significant association for the ungrouped data of nephrotic syndrome children and the control subjects. Kidney biopsies were done in 86 nephrotic syndrome cases (minimal change disease, n = 51; focal segmental glomerulosclerosis, n = 27; diffuse mesangial proliferation, n = 8). We segregated them into the minimal change disease / focal segmental glomerulosclerosis groups and observed that the ACE 'D' allele was identified with borderline significance in cases of focal segmental glomerulosclerosis and the 'Ⅰ' allele was assessed as having very weak association in cases of minimal change disease. 'Ⅱ' genotype was weakly associated with minimal change disease. Gender specific analysis revealed weak association of 'ID' genotype with female nephrotic syndrome in females. Dominant expression of DD genotype was observed in males with nephrotic syndrome. Our finding indicated that ACE (I/D) has moderate association with focal segmental glomerulosclerosis. However, due to the limited number of biopsy proven focal segmental glomerulosclerosis subjects enrolled, further studies are required to confirm these results.
In this study, we sought to assess the safety and accuracy of sacropelvic fixation performed with image-guided sacroiliac screw placement using postoperative computed tomography and X-rays. The sacroiliac screws were placed with navigation in five patients. Intact specimens were mounted onto a six-degrees-of-freedom spine motion simulator. Long lumbosacral constructs using bilateral sacroiliac screws and bilateral S1 pedicle and iliac screws were tested in seven cadaveric spines. Nine sacroiliac screws were well-placed under an image guidance system (IGS); one was placed poorly without IGS with no symptoms. Both fixation techniques significantly reduced range of motion (P < 0.05) at L5–S1. The research concluded that rigid lumbosacral fixation can be achieved with sacroiliac screws, and image guidance improves its safety and accuracy. This new technique of image-guided sacroiliac screw insertion should prove useful in many types of fusion to the sacrum, particularly for patients with poor bone quality, complicated anatomy, infection, previous failed fusion and iliac harvesting.
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](0)
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](0)
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](0)
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](0)
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](0)
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](0)
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](0)
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](0)
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](0)
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](0)