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1.  Protective Effects of Astragaloside IV against Amyloid Beta1-42 Neurotoxicity by Inhibiting the Mitochondrial Permeability Transition Pore Opening 
PLoS ONE  2014;9(6):e98866.
Mitochondrial dysfunction caused by amyloid β-peptide (Aβ) plays an important role in the pathogenesis of Alzheimer disease (AD). Substantial evidence has indicated that the mitochondrial permeability transition pore (mPTP) opening is involved in Aβ-induced neuronal death and reactive oxygen species (ROS) generation. Astragaloside IV (AS-IV), one of the major active constituents of Astragalus membranaceus, has been reported as an effective anti-oxidant for treating neurodegenerative diseases. However, the molecular mechanisms still need to be clarified. In this study, we investigated whether AS-IV could prevent Aβ1-42-induced neurotoxicity in SK-N-SH cells via inhibiting the mPTP opening. The results showed that pretreatment of AS-IV significantly increased the viability of neuronal cells, reduced apoptosis, decreased the generation of intracellular reactive oxygen species (ROS) and decreased mitochondrial superoxide in the presence of Aβ1-42. In addition, pretreatment of AS-IV inhibited the mPTP opening, rescued mitochondrial membrane potential (ΔΨm), enhanced ATP generation, improved the activity of cytochrome c oxidase and blocked cytochrome c release from mitochondria in Aβ1-42 rich milieu. Moreover, pretreatment of AS-IV reduced the expression of Bax and cleaved caspase-3 and increased the expression of Bcl-2 in an Aβ1-42 rich environment. These data indicate that AS-IV prevents Aβ1-42-induced SK-N-SH cell apoptosis via inhibiting the mPTP opening and ROS generation. These results provide novel insights of AS-IV for the prevention and treatment of neurodegenerative disorders such as AD.
doi:10.1371/journal.pone.0098866
PMCID: PMC4048237  PMID: 24905226
2.  Report of Recombinant Norovirus GII.g/GII.12 in Beijing, China 
PLoS ONE  2014;9(2):e88210.
Background
Norovirus (NoV) has been recognized as the most important cause of nonbacterial acute gastroenteritis affecting all age group people in the world. Genetic recombination is a common occurance in RNA viruses and many recombinant NoV strains have been described since it was first reported in 1997. However, the knowledge of recombinant NoV in China is extremely limited.
Methods
A total of 685 stool specimens were tested for NoV infection from the acute gastroenteritis patients who visited one general hospital in Beijing from April 2009 to November 2011. The virus recombination was identified by constructing phylogenetic trees of two genes, further SimPlot and the maximum chi-square analysis.
Results
The overall positive rate was 9.6% (66/685). GII.4 New Orleans 2009 and GII.4 2006b variants were the dominant genotype. Four GII.g/GII.12 and one GII.12/GII.3 recombinant strains were confirmed, and all derived from adult outpatients. The predictive recombination point occurred at the open reading frame (ORF)1/ORF2 overlap.
Conclusions
The GII.g ORF1/GII.12ORF2 recombinant has been reported in several countries and it was the first report of this recombinant in China.
doi:10.1371/journal.pone.0088210
PMCID: PMC3914918  PMID: 24505432
3.  Up-regulated FHL1 Expression Maybe Involved in the Prognosis of Hirschsprung's Disease 
Background: In a subset of patients with Hirschsprung's disease (HSCR), gastrointestinal motor dysfunction persisted long after surgical correction. Gastrointestinal motility is achieved through the coordinated activity of the enteric nervous system, interstitial cells of Cajal, and smooth muscle (SMC) cells. Inhibition of four-and-a-half LIM protein-1 (Fhl1) expression by siRNA significantly decreases pulmonary artery SMCs migration and proliferation. Furthermore when up-expressing FHL1 in atrial myocytes, K (+) current density markedly increases, therefore changing myocytes' response to an electrical stimulus. However whether FHL1 in colon SMCs (the final effector organ) influences intestinal motility in HSCR patients has not been clarified. Methods: FHL1 mRNA and protein expressions were analyzed in 32 HSCR colons and 4 normal colons. Results: Smooth muscle layers were thicken and disorganized in HSCR. FHL1 was expressed in the ganglion cells of the myenteric plexus, submucosa, as well as in the longitudinal and circular muscle layer of the ganglionic colon. FHL1 mRNA relative expression level in aganglionic colons was 1.06±0.49 (ganglionic colon relative expression level was 1) (P=0.44). FHL1 protein gray level relative to GAPDH in normal colons was 0.83±0.09. FHL1 expression level in ganglionic colon (1.66±0.30) or aganglionic colon (1.81±0.35) was significantly higher than that in normal colons (P=0.045 and P=0.041, respectively). Meanwhile, we found FHL1 expression in aganglionic colon was slightly stronger than that in ganglionic colon (P=0.036). Conclusion: These data suggested that up-regulated FHL1 in smooth muscle in HSCR might be associated with intestinal wall remodeling in HSCR and might be one of the risk factors for gastrointestinal motor dysfunction.
doi:10.7150/ijms.7287
PMCID: PMC3917115  PMID: 24516350
FHL1; Hirschsprung's disease; expression; smooth muscle; prognosis
4.  Analysis of therapeutic effect and safety of target-dose metoprolol in the treatment of patients with diabetes mellitus with chronic heart failure 
Objective: To explore the therapeutic effect and safety of target-dose metoprolol in treating chronic heart failure (CHF) patients complicated with diabetes mellitus (DM).
Method s : One hundred and fifty-four elderly patients were randomly divided into an observation group and a control group (n=77), which were treated with target-dose metoprolol and conventional therapy, and routinely treated respectively. The New York Heart Association (NYHA) classification, left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), 6-min walking distance and medication safety of the two groups were compared.
Results: Compared with the results before treatment, the NYHA classification, LVESD, LVEDD, LVEF and 6-minutes walking distance of both groups were significantly improved (P<0.05), with significantly better results in the observation group than those in the control group after treatment (P<0.05). In the 6 months of follow-up, the incidence of cardiac events in the observation group (3.90%) was significantly lower than that of the control group (14.29%) (P<0.05). The levels of average fasting blood sugar and glycosylated hemoglobin in the groups showed no significant differences (P>0.05).
Conclusion: Treating CHF patients complicated with DM with target-dose metoprolol can obviously boost the cardiac function and exercise tolerance, leading to satisfactory clinical therapeutic effect, high security and moderate tolerance.
doi:10.12669/pjms.301.3908
PMCID: PMC3955532  PMID: 24639821
Chronic heart failure; Diabetes mellitus; Metoprolol; Therapeutic effect; Safety
5.  TRPP2 and TRPV4 Form an EGF-Activated Calcium Permeable Channel at the Apical Membrane of Renal Collecting Duct Cells 
PLoS ONE  2013;8(8):e73424.
Objective
Regulation of apical calcium entry is important for the function of principal cells of the collecting duct. However, the molecular identity and the regulators of the transporter/channel, which is responsible for apical calcium entry and what factors regulate the calcium conduction remain unclear.
Methods and Results
We report that endogenous TRPP2 and TRPV4 assemble to form a 23-pS divalent cation-permeable non-selective ion channel at the apical membrane of renal principal cells of the collecting duct. TRPP2\TRPV4 channel complex was identified by patch-clamp, immunofluorescence and co-immunprecipitation studies in both principal cells that either possess normal cilia (cilia (+)) or in which cilia are absent (cilia (-)). This channel has distinct biophysical and pharmacological and regulatory profiles compared to either TRPP2 or TRPV4 channels. The rate of occurrence detected by patch clamp was higher in cilia (-) compared to cilia (+) cells. In addition, shRNA knockdown of TRPP2 increased the prevalence of TRPV4 channel activity while knockdown of TRPV4 resulted in TRPP2 activity and knockdown of both proteins vastly decreased the 23-pS channel activity. Epidermal growth factor (EGF) stimulated TRPP2\TRPV4 channel through the EGF receptor (EGFR) tyrosine kinase-dependent signaling. With loss of cilia, apical EGF treatment resulted in 64-fold increase in channel activity in cilia (-) but not cilia (+) cells. In addition EGF increased cell proliferation in cilia (-) cell that was dependent upon TRPP2\TRPV4 channel mediated increase in intracellular calcium.
Conclusion
We conclude that in the absence of cilia, an EGF activated TRPP2\TRPV4 channel may play an important role in increased cell proliferation and cystogenesis.
doi:10.1371/journal.pone.0073424
PMCID: PMC3745395  PMID: 23977387
6.  MicroRNAs may solve the mystery of chronic hepatitis B virus infection 
Hepatitis B virus (HBV) infection is a global public health problem that causes persistent liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma. A large amount of people die annually from HBV infection. However, the pathogenesises of the HBV-related diseases are ill defined and the therapeutic strategies for the diseases are less than optimum. The recently discovered microRNAs (miRNAs) are tiny noncoding RNAs that regulate gene expression primarily at the post-transcriptional level by binding to mRNAs. miRNAs contribute to a variety of physiological and pathological processes. A number of miRNAs have been found to play a pivotal role in the host-virus interaction including host-HBV interaction. Numerous studies have indicated that HBV infection could change the cellular miRNA expression patterns and different stages of HBV associated disease have displayed distinctive miRNA profiles. Furthermore, the differential expressed miRNAs have been found involved in the progression of HBV-related diseases, for instance some miRNAs are involved in liver tumorigenesis and tumor metastasis. Studies have also shown that the circulating miRNA in serum or plasma might be a very useful biomarker for the diagnosis and prognosis of HBV-related diseases. In addition, miRNA-based therapy strategies have attracted increasing attention, indicating a promising future in the treatment of HBV-related diseases.
doi:10.3748/wjg.v19.i30.4867
PMCID: PMC3740416  PMID: 23946591
MicroRNA; Hepatitis B virus; Hepatitis B; Host-virus interaction; Biomarker; Therapy
7.  Altered Expression of 14-3-3ζ Protein in Spinal Cords of Rat Fetuses with Spina Bifida Aperta 
PLoS ONE  2013;8(8):e70457.
Background
A large number of studies have confirmed that excessive apoptosis is one of the reasons for deficient neuronal function in neural tube defects (NTDs). A previous study from our laboratory used 2-D gel electrophoresis to demonstrate that 14-3-3ζ expression was low in the spinal cords of rat fetuses with spina bifida aperta at embryonic day (E) 17. As a member of the 14-3-3 protein family, 14-3-3ζ plays a crucial role in the determination of cell fate and anti-apoptotic activity. However, neither the expression of 14-3-3ζ in defective spinal cords, nor the correlation between 14-3-3ζ and excessive apoptosis in NTDs has been fully confirmed.
Methodology/Principal Findings
We used immunoblotting and quantitative real-time PCR (qRT-PCR) to quantify the expression of 14-3-3ζ and double immunofluorescence to visualize 14-3-3ζ and apoptosis. We found that, compared with controls, 14-3-3ζ was down-regulated in spina bifida between E12 and E15. Excessive apoptotic cells and low expression of 14-3-3ζ were observed in the dorsal region of spinal cords with spina bifida during the same time period. To initially explore the molecular mechanisms of apoptosis in NTDs, we investigated the expression of microRNA-7 (miR-7), microRNA-375 (miR-375) and microRNA-451 (miR-451), which are known to down-regulate 14-3-3ζ in several different cell types. We also investigated the expression of p53, a molecule that is downstream of 14-3-3ζ and can be down-regulated by it. We discovered that, in contrast to the reduction of 14-3-3ζ expression, the expression of miR-451, miR-375 and p53 increased in spina bifida rat fetuses.
Conclusions/Significance
These data suggest that the reduced expression of 14-3-3ζ plays a role in the excessive apoptosis that occurs in spina bifida and may be partly regulated by the over-expression of miR-451 and miR-375, and the consequent up-regulation of p53 might further promote apoptosis in spina bifida.
doi:10.1371/journal.pone.0070457
PMCID: PMC3735597  PMID: 23936434
8.  Chronic caffeine treatment reverses memory impairment and the expression of brain BNDF and TrkB in the PS1/APP double transgenic mouse model of Alzheimer’s disease 
Molecular Medicine Reports  2013;8(3):737-740.
The objective of this study was to investigate the effects of varying doses of caffeine on memory impairment and the expression of brain neurotrophic derived factor (BNDF) and TrkB in PS1/APP double transgenic mouse models. PS1/APP double transgenic mice were administered 0.3 ml/day of saline, 1.5 mg/day of caffeine or 0.75 mg/day of caffeine for eight weeks. A water maze test and western blotting were used to determine the memory capability and expression of hippocampal BNDF and TrkB of the mice. The results demonstrated that 0.75 mg/day and 1.5 mg/day doses of caffeine significantly increased memory capability and the expression of hippocampal BDNF and TrkB in PS1/APP mice with a dose-response effect. The results suggested that chronic caffeine treatment may reverse memory impairment in PS1/APP transgenic mice, and BDNF and its receptor TrkB, may be involved in this process.
doi:10.3892/mmr.2013.1601
PMCID: PMC3782531  PMID: 23900282
caffeine; memory; brain neurotrophic derived factor; TrkB; Alzheimer’s disease
9.  PEP-1-CAT protects hypoxia/reoxygenation-induced cardiomyocyte apoptosis through multiple sigaling pathways 
Background
Catalase (CAT) breaks down H2O2 into H2O and O2 to protects cells from oxidative damage. However, its translational potential is limited because exogenous CAT cannot enter living cells automatically. This study is aimed to investigate if PEP-1-CAT fusion protein can effectively protect cardiomyocytes from oxidative stress due to hypoxia/reoxygenation (H/R)-induced injury.
Methods
H9c2 cardomyocytes were pretreated with catalase (CAT) or PEP-1-CAT fusion protein followed by culturing in a hypoxia and re-oxygenation condition. Cell apoptosis were measured by Annexin V and PI double staining and Flow cytometry. Intracellular superoxide anion level was determined, and mitochondrial membrane potential was measured. Expression of apoptosis-related proteins including Bcl-2, Bax, Caspase-3, PARP, p38 and phospho-p38 was analyzed by western blotting.
Results
PEP-1-CAT protected H9c2 from H/R-induced morphological alteration and reduced the release of lactate dehydrogenase (LDH) and malondialdehyde content. Superoxide anion production was also decreased. In addition, PEP-1-CAT inhibited H9c2 apoptosis and blocked the expression of apoptosis stimulator Bax while increased the expression of Bcl-2, leading to an increased mitochondrial membrane potential. Mechanistically, PEP-1-CAT inhibited p38 MAPK while activating PI3K/Akt and Erk1/2 signaling pathways, resulting in blockade of Bcl2/Bax/mitochondrial apoptotic pathway.
Conclusion
Our study has revealed a novel mechanism by which PEP-1-CAT protects cardiomyocyte from H/R-induced injury. PEP-1-CAT blocks Bcl2/Bax/mitochondrial apoptotic pathway by inhibiting p38 MAPK while activating PI3K/Akt and Erk1/2 signaling pathways.
doi:10.1186/1479-5876-11-113
PMCID: PMC3660214  PMID: 23642335
Cell-penetrating peptide; PEP-1; Catalase; Cardiomyocyte; Apoptosis; MAPK
10.  Manganese superoxide dismutase inhibits neointima formation through attenuation of migration and proliferation of vascular smooth muscle cells 
Free radical biology & medicine  2011;52(1):173-181.
Superoxide anion is elevated during neointima development and is essential for neointimal vascular smooth muscle cell (VSMC) proliferation. However, little is known about the role of manganese superoxide dismutase (MnSOD, SOD2) in the neointima formation following vascular injury. SOD2 in the mitochondria plays an important role in cellular defense against oxidative damage. Because of its subcellular localization, SOD2 is considered the first line of defense against oxidative stress and plays a central role in metabolizing superoxide. Because mitochondria are the most important sources of superoxide anion, we speculated that SOD2 may have therapeutic benefits in preventing vascular remodeling. In this study, we used a rat carotid artery balloon-injury model and an adenoviral gene delivery approach to test the hypothesis that SOD2 suppresses vascular lesion formation. SOD2 was activated along with the progression of neointima formation in balloon-injured rat carotid arteries. Depletion of SOD2 by RNA interference markedly promoted the lesion formation, whereas SOD2 overexpression suppressed the injury-induced neointima formation via attenuation of migration and proliferation of VSMCs. SOD2 exerts its inhibitory effect on VSMC migration induced by angiotensin II by scavenging superoxide anion and suppressing the phosphorylation of Akt. Our data indicate that SOD2 is a negative modulator of vascular lesion formation after injury. Therefore, SOD2 augmentation may be a promising therapeutic strategy for the prevention of lesion formation in proliferative vascular diseases such as restenosis.
doi:10.1016/j.freeradbiomed.2011.10.442
PMCID: PMC3356780  PMID: 22062629
Manganese superoxide dismutase; Oxidative stress; Neointima; Migration; Proliferation; Vascular smooth muscle cells; Signal transduction; Free radicals
11.  PEP-1-CAT-Transduced Mesenchymal Stem Cells Acquire an Enhanced Viability and Promote Ischemia-Induced Angiogenesis 
PLoS ONE  2012;7(12):e52537.
Objective
Poor survival of mesenchymal stem cells (MSC) compromised the efficacy of stem cell therapy for ischemic diseases. The aim of this study is to investigate the role of PEP-1-CAT transduction in MSC survival and its effect on ischemia-induced angiogenesis.
Methods
MSC apoptosis was evaluated by DAPI staining and quantified by Annexin V and PI double staining and Flow Cytometry. Malondialdehyde (MDA) content, lactate dehydrogenase (LDH) release, and Superoxide Dismutase (SOD) activities were simultaneously measured. MSC mitochondrial membrane potential was analyzed with JC-1 staining. MSC survival in rat muscles with gender-mismatched transplantation of the MSC after lower limb ischemia was assessed by detecting SRY expression. MSC apoptosis in ischemic area was determined by TUNEL assay. The effect of PEP-1-CAT-transduced MSC on angiogenesis in vivo was determined in the lower limb ischemia model.
Results
PEP-1-CAT transduction decreased MSC apoptosis rate while down-regulating MDA content and blocking LDH release as compared to the treatment with H2O2 or CAT. However, SOD activity was up-regulated in PEP-1-CAT-transduced cells. Consistent with its effect on MSC apoptosis, PEP-1-CAT restored H2O2-attenuated mitochondrial membrane potential. Mechanistically, PEP-1-CAT blocked H2O2-induced down-regulation of PI3K/Akt activity, an essential signaling pathway regulating MSC apoptosis. In vivo, the viability of MSC implanted into ischemic area in lower limb ischemia rat model was increased by four-fold when transduced with PEP-1-CAT. Importantly, PEP-1-CAT-transduced MSC significantly enhanced ischemia-induced angiogenesis by up-regulating VEGF expression.
Conclusions
PEP-1-CAT-transduction was able to increase MSC viability by regulating PI3K/Akt activity, which stimulated ischemia-induced angiogenesis.
doi:10.1371/journal.pone.0052537
PMCID: PMC3532064  PMID: 23285080
12.  Effects of Traditional Chinese Medicine Wei-Wei-Kang-Granule on the Expression of EGFR and NF-KB in Chronic Atrophic Gastritis Rats 
Wei-Wei-Kang-Granule(WWKG) is a traditional Chinese medicine (TCM) preparation for the treatment of chronic atrophic gastritis (CAG). We examined the pathologic change and the effects of Wei-Wei-Kang-Granule (WWKG) on the expression of EGFR (epiderminal growth factor receptors) and NF-kB (nuclear transcription factor KappaB) in rats with chronic atrophic gastritis (CAG), and evaluated the possible mechanisms. Ninety rats were randomly divided into control group and four experimental groups. CAG rat models were induced by repeated stimulating experiments in the experimental groups. After modeled rats were intragastrically injected (i.g.) with WWKG at 6000mg/kg (large dose WWKG group), WWKG at 3000mg/kg (small dose WWKG group), San-Jiu-Wei-Tai-Granule(SJWTG) at 1600mg/kg(SJWTG group), and normal saline(0.9%)at 20ml/kg (model group and control group), respectively, once a day for 30 days. After 30 days, all rats were sacrificed and samples were taken from the sinus ventriculi and body of stomach. The gastric specimens were prepared for microscopic view with hematoxylin and eosin (H-E). The immunohistochemistry method was used to observe the expression of protein of EGFR and NF-kB in gastric tissue. The data were analyzed in pre-and post-treatment by computer image automatic analysis system. Immunohistochemistry detection showed that the average optical density of EGFR and NF-kB in antrum was lower in large and small dose WWKG groups than the model group (P<0.01). CAG in rats was related with the damage of barrier in gastric mucosa and the misbalance of cell proliferation and apoptosis. One of the mechanisms is perhaps to reduce the expressing of EGFR and NF-Kb in gastric mucosa.
PMCID: PMC3744208  PMID: 23983313
Chronic atrophic gastritis(CAG); EGFR; NF-kB
13.  VEGF/SDF-1 promotes cardiac stem cell mobilization and myocardial repair in the infarcted heart 
Cardiovascular Research  2011;91(3):402-411.
Aims
The objective of this study was to investigate whether vascular endothelial growth factor (VEGF) secreted by mesenchymal stem cells (MSC) improves myocardial survival and the engraftment of implanted MSC in infarcted hearts and promotes recruitment of stem cells through paracrine release of myocardial stromal cell-derived factor-1α (SDF-1α).
Methods and results
VEGF-expressing MSC (VEGFMSC)-conditioned medium enhanced SDF-1α expression in heart slices and H9C2 cardiomyoblast cells via VEGF and the vascular endothelial growth factor receptor (VEGFR). The VEGFMSC-conditioned medium markedly promoted cardiac stem cell (CSC) migration at least in part via the SDF-1α/CXCR4 pathway and involved binding to VEGFR-1 and VEGFR-3. In vivo, VEGFMSC-stimulated SDF-1α expression in infarcted hearts resulted in massive mobilization and homing of bone marrow stem cells and CSC. Moreover, VEGF-induced SDF-1α guided the exogenously introduced CSC in the atrioventricular groove to migrate to the infarcted area, leading to a reduction in infarct size. Functional studies showed that VEGFMSC transplantation stimulated extensive angiomyogenesis in infarcted hearts as indicated by the expression of cardiac troponin T, CD31, and von Willebrand factor and improved the left ventricular performance, whereas blockade of SDF-1α or its receptor by RNAi or antagonist significantly diminished the beneficial effects of VEGFMSC.
Conclusion
Exogenously expressed VEGF promotes myocardial repair at least in part through SDF-1α/CXCR4-mediated recruitment of CSC.
doi:10.1093/cvr/cvr053
PMCID: PMC3139446  PMID: 21345805
Myocardial infarction; VEGF; SDF-1α; Cardiac stem cell; Migration
14.  Response Gene to Complement 32 Promotes Vascular Lesion Formation through Stimulation of Smooth Muscle Cell Proliferation and Migration 
Objective
The objectives of this study are to determine the role of response gene to complement 32 (RGC-32) in vascular lesion formation after experimental angioplasty and to explore the underlying mechanisms.
Methods and Results
Using a rat carotid artery balloon-injury model, we documented for the first time that neointima formation was closely associated with a significantly increased expression of RGC-32 protein. shRNA Knockdown of RGC-32 via adenovirus (Ad)-mediated gene delivery dramatically inhibited the lesion formation by 62% as compared to control groups 14 days after injury. Conversely, RGC-32 overexpression significantly promoted the neointima formation by 33%. Gain and loss of function studies in primary culture of rat aortic smooth muscle cells (RASMCs) indicated that RGC-32 is essential for both the proliferation and migration of RASMCs. RGC-32 induced RASMC proliferation by enhancing p34CDC2 activity. RGC-32 stimulated the migration of RASMC via inducing focal adhesion contact and stress fiber formation. These effects were caused by the enhanced ROKα activity due to RGC-32-induced downregulation of Rad GTPase.
Conclusions
RGC-32 plays an important role in vascular lesion formation following vascular injury. Increased RGC-32 expression in vascular injury appears to be a novel mechanism underlying the migration and proliferation of vascular SMCs. Therefore, targeting RGC-32 is a potential therapeutic strategy for the prevention of vascular remodeling in proliferative vascular diseases.
doi:10.1161/ATVBAHA.111.230706
PMCID: PMC3146015  PMID: 21636805
Response gene to complement 32; Restenosis; Vascular smooth muscle cells; Migration; Proliferation
15.  MEK1act/tubulin interaction is an important determinant of mitotic stability in cultured HT1080 human fibrosarcoma cells 
Cancer research  2010;70(14):6004-6014.
Activation of the MAPK pathway plays a major role in neoplastic cell transformation. Using a proteomics approach we identified α tubulin and β tubulin as proteins that interact with activated MEK1, a central MAPK regulatory kinase. Confocal analysis revealed spatio-temporal control of MEK1-tubulin co-localization that was most prominent in the mitotic spindle apparatus in variant HT1080 human fibrosarcoma cells. Peptide arrays identified the critical role of positively charged amino acids R108, R113, R160 and K157 on the surface of MEK1 for tubulin interaction. Overexpression of activated MEK1 caused defects in spindle arrangement, chromosome segregation and ploidy. In contrast, chromosome polyploidy was reduced in the presence of an activated MEK1 mutant (R108A, R113A) that disrupted interactions with tubulin. Our findings indicate the importance of signaling by activated MEK1-tubulin in spindle organization and chromosomal instability.
doi:10.1158/0008-5472.CAN-09-4490
PMCID: PMC2938962  PMID: 20570892
MEK1; tubulin; mitotic stability; fibrosarcoma
16.  Complete Genome Sequence of the Bacterium Ketogulonicigenium vulgare Y25 ▿  
Journal of Bacteriology  2010;193(1):315-316.
Ketogulonicigenium vulgare is characterized by the efficient production of 2KGA from l-sorbose. Ketogulonicigenium vulgare Y25 is known as a 2-keto-l-gulonic acid-producing strain in the vitamin C industry. Here we report the finished, annotated genome sequence of Ketogulonicigenium vulgare Y25.
doi:10.1128/JB.01189-10
PMCID: PMC3019938  PMID: 21037005
17.  The combined transduction of copper, zinc-superoxide dismutase and catalase mediated by cell-penetrating peptide, PEP-1, to protect myocardium from ischemia-reperfusion injury 
Background
Our previous studies indicate that either PEP-1-superoxide dismutase 1 (SOD1) or PEP-1-catalase (CAT) fusion proteins protects myocardium from ischemia-reperfusion-induced injury in rats. The aim of this study is to explore whether combined use of PEP-1-SOD1 and PEP-1-CAT enhances their protective effects.
Methods
SOD1, PEP-1-SOD1, CAT or PEP-1-CAT fusion proteins were prepared and purified by genetic engineering. In vitro and in vivo effects of these proteins on cell apoptosis and the protection of myocardium after ischemia-reperfusion injury were measured. Embryo cardiac myocyte H9c2 cells were used for the in vitro studies. In vitro cellular injury was determined by the expression of lactate dehydrogenase (LDH). Cell apoptosis was quantitatively assessed with Annexin V and PI double staining by Flow cytometry. In vivo, rat left anterior descending coronary artery (LAD) was ligated for one hour followed by two hours of reperfusion. Hemodynamics was then measured. Myocardial infarct size was evaluated by TTC staining. Serum levels of myocardial markers, creatine kinase-MB (CK-MB) and cTnT were quantified by ELISA. Bcl-2 and Bax expression in left ventricle myocardium were analyzed by western blot.
Results
In vitro, PEP-1-SOD1 or PEP-1-CAT inhibited LDH release and apoptosis rate of H9c2 cells. Combined transduction of PEP-1-SOD1 and PEP-1-CAT, however, further reduced the LDH level and apoptosis rate. In vivo, combined usage of PEP-1-SOD1 and PEP-1-CAT produced a greater effect than individual proteins on the reduction of CK-MB, cTnT, apoptosis rate, lipoxidation end product malondialdehyde, and the infarct size of myocardium. Functionally, the combination of these two proteins further increased left ventricle systolic pressure, but decreased left ventricle end-diastolic pressure.
Conclusion
This study provided a basis for the treatment or prevention of myocardial ischemia-reperfusion injury with the combined usage of PEP-1-SOD1 and PEP-1-CAT fusion proteins.
doi:10.1186/1479-5876-9-73
PMCID: PMC3120689  PMID: 21600015
18.  Identification of Norovirus as the Top Enteric Viruses Detected in Adult Cases with Acute Gastroenteritis 
To elucidate the importance of the norovirus and other enteric viruses, and the difference of the genetic relatedness on norovirus between the outbreak and sporadic cases, a total of 557 stool samples, consisting of 503 sporadic cases and 54 samples of 4 outbreaks were collected and tested for norovirus and other enteric viruses in Beijing, China, July 2007–June 2008. The data showed norovirus, rotavirus, astrovirus, and sapovirus, were detected in 26.6%, 6.1%, 1.8%, and 0.5%, respectively. Norovirus was detected almost throughout the surveillance period, norovirus co-infecting with rotavirus, astrovirus, and sapovirus, respectively, were identified both in outbreak and the sporadic cases. GII.4/2006 was identified as the predominant strain circulating both in outbreak and sporadic cases. The results showed that norovirus was rather the important agent than other enteric viruses affected adults with acute gastroenteritis; no significant genetic relatedness of the dominant strains was found between the outbreak and sporadic cases.
doi:10.4269/ajtmh.2010.09-0491
PMCID: PMC2844560  PMID: 20348525
19.  4-Bromo-2-[1-(4-eth­oxy­phen­yl)-1-methyl­eth­yl]-1-methyl­benzene 
In title compound, C18H21BrO, the dihedral angle between two rings is 85.72°. No classical hydrogen bonds are found and only van der Waals forces stabilize the crystal packing.
doi:10.1107/S1600536810049445
PMCID: PMC3050309  PMID: 21522710
20.  Effect of p27mt gene on apoptosis of the colorectal cancer cell line Lovo 
AIM: To construct p27mt recombinant adenovirus, transfect the colorectal cell line Lovo and observe the effects of p27mt on Lovo cell apoptosis and cell cycle inhibition.
METHODS: We constructed recombinant adenovirus containing p27mt by homologous recombination in bacteria. The colorectal cancer cell line Lovo was infected with recombinant replication-defective adenovirus Ad-p27mt, and expression of p27mt was determined by Western blotting; the inhibitory effect of p27mt on Lovo cells was detected by cytometry. Cell cycle was determined by flow cytometry. DNA fragment analysis identified the occurrence of apoptosis.
RESULTS: The recombinant adenovirus which already contained p27mt target gene was successfully constructed. When multiplicity of infection was ≥ 50, the infection efficiency was 100%. After transfection of Lovo cells with Ad-p27mt the cells had high p27 expression which was identified by immunoblotting assay. PI staining and flow cytometry showed that 77.96% of colorectal cancer cells were inhibited in phase G0/G1, while in the Ad-LacZ group and blank control group, 27.57% and 25.29% cells were inhibited in the same phase, respectively. DNA fragment analysis, flow cytometry and TUNEL assay demonstrated that p27mt is able to induce apoptosis in colorectal cancer cells.
CONCLUSION: p27mt has an obvious blocking effect on colorectal cancer cell cycle, and most cells were inhibited in phase G0/G1. Therefore, p27mt can induce apoptosis in colorectal cells.
doi:10.3748/wjg.15.2794
PMCID: PMC2695897  PMID: 19522032
Apoptosis; Cell cycle; Colorectal cancer; p27mt; Recombinant adenovirus
21.  Clinical characteristics of the autumn-winter type scrub typhus cases in south of Shandong province, northern China 
Background
Before 1986, scrub typhus was only found endemic in southern China. Because human infections typically occur in the summer, it is called "summer type". During the autumn-winter period of 1986, a new type of scrub typhus was identified in Shandong and northern Jiangsu province of northern China. This newly recognized scrub typhus was subsequently reported in many areas of northern China and was then called "autumn-winter type". However, clinical characteristics of associated cases have not been reported.
Methods
From 1995 to 2006, all suspected scrub typhus cases in five township hospitals of Feixian county, Shandong province were enrolled. Indirect immunofluorescent assay (IFA) was used as confirmatory serodiagnosis test. Polymerase chain reaction (PCR) connected with restriction fragment length polymorphism (RFLP) and sequence analyses were used for genotyping of O. tsutsugamushi DNAs. Clinical symptoms and demography of confirmed cases were analyzed.
Results
A total of 480 scrub typhus cases were confirmed. The cases occurred every year exclusively between September and December with a peak occurrence in October. The case numbers were relatively higher in 1995, 1996, 1997, and 2000 than in other years. 57.9% of cases were in the group aged 21–50. More cases occurred in male (56%) than in female (44%). The predominant occupational group of the cases was farmers (85.0%). Farm work was reported the primary exposure to infection in 67.7% of cases. Fever, rash, and eschar were observed in 100.0%, 90.4%, and 88.5% of cases, respectively. Eschars formed frequently on or around umbilicus, abdomen areas, and front and back of waist (34.1%) in both genders. Normal results were observed in 88.7% (WBC counts), 84.5% (PLT counts), and 89.7% (RBC counts) of cases, respectively. Observations from the five hospitals were compared and no significant differences were found.
Conclusion
The autumn-winter type scrub typhus in northern China occurred exclusively from September to December with a peak occurrence in October, which was different from the summer type in southern China. In comparison with the summer type, complications associated with autumn-winter type scrub typhus were less severe, and abnormalities of routine hematological parameters were less obvious.
doi:10.1186/1471-2334-9-82
PMCID: PMC2703643  PMID: 19493361

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