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Find video protocols related to scientific articles indexed in Pubmed.
Association of Indoxyl Sulfate with Heart Failure among Patients on Hemodialysis.
Clin J Am Soc Nephrol
PUBLISHED: 10-22-2014
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Indoxyl sulfate, a protein-bound uremic toxin, may be associated with cardiovascular events and mortality in patients with CKD. This study aimed to investigate the relationship between indoxyl sulfate and heart failure in patients on hemodialysis.
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Effect of radio frequency fields on the radical pair magnetoreception model.
Phys Rev E Stat Nonlin Soft Matter Phys
PUBLISHED: 10-13-2014
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Although the radical pair (RP) model is widely accepted for birds' orientation, the physical mechanism of it is still not fully understood. In this paper we consider the RP model in the total angular-momentum representation and clearly show a detailed mechanism for orientation. When only the vertical hyperfine (HF) coupling component is considered, analytical expressions of singlet yield angular profiles are obtained with and without considering the radio frequency field, and when the horizontal HF coupling components are considered, a numerical calculation of the singlet yield is given. Based on these analytical and numerical results we present a detailed account of the following issues: how the HF coupling induces the singlet-triplet conversion; why the vertical radio frequency field can disorient the birds, while the parallel one cannot; and why the birds are able to "train" to different field strengths. Finally, we consider a multinuclei RP model.
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[Regulation of syringin, chlorogenic acid and 1,5-dicaffeoylquinic acid biosynthesis in cell suspension cultures of Saussurea involucrata].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 09-24-2014
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Syringin, chlorogenic acid and 1,5-dicaffeoylquinic acid are three main bioactive ingredients in herbs of Saussurea involucrata with various pharmacological properties, while their contents are very low. In this study, the biosynthesis of syringin, chlorogenic acid and 1,5-dicaffeoylquinic acid in the cell suspension cultures of S. involucrata were regulated by feeding carbon sources and precursors, which resulted in a great increase of the contents and yields of the above three bioactive ingredients. After 16 days of fermentation, the yields of syringin, chlorogenic acid and 1,5-dicaffeoylquinic acid reached 339.0, 225.3, 512.7 mg x L(-1), respectively. Meanwhile, their contents increased up to 67.9, 1.9, 10.6 times of wild medicinal material, respectively. The results provided a solid basis for further studies on application of cell suspension cultures of S. involucrata for large-scale production of bioactive compounds syringin, chlorogenic acid and 1,5-dicaffeoylquinic acid.
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Meroterpenoids and isoberkedienolactone from endophytic fungus Penicillium sp. associated with Dysosma versipellis.
Yao Xue Xue Bao
PUBLISHED: 09-13-2014
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Seven meroterpenoids and five small-molecular precursors were isolated from Penicillium sp., an endophytic fungus from Dysosma versipellis. The structures of new compounds, 11beta-acetoxyisoaustinone (1) and isoberkedienolactone (2) were elucidated based on analysis of the spectral data, and the absolute configuration of 2 was established by TDDFT ECD calculation with satisfactory match to its experimental ECD data. Meroterpenoids originated tetraketide and pentaketide precursors, resepectively, were found to be simultaneously produced in specific fungus of Penicillium species. These compounds showed weak cytotoxicity in vitro against HCT-116, HepG2, BGC-823, NCI-H1650, and A2780 cell lines with IC 50 > 10 micromol x L(-1).
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Inappropriately elevated endothelin-1 plays a role in the pathogenesis of intradialytic hypertension.
Hemodial Int
PUBLISHED: 09-02-2014
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The aim of this study is to investigate the effects of endogenous vasoactive substances on the occurrence of intradialytic hypertension (IDH) in patients during maintenance hemodialysis. Thirty-four maintenance hemodialysis patients were enrolled in this trial, and 17 of them were diagnosed with IDH (defined as an increase in blood pressure of at least 10?mmHg during or immediately after a hemodialysis session), while 17 age-matched and sex-matched controls without IDH were selected for a retrospective comparison. We collected patients' blood samples before and after a dialysis session and measured the plasma levels of N-terminal fragment brain natriuretic peptide, renin, angiotensin-II, aldosterone (ALD), angiotensin-converting enzyme (ACE), endothelin-1 (ET-1), nitric oxide (NO), norepinephrine (NOR), and adrenomedullin. The post-dialysis serum ET-1 concentrations were significantly higher (4.09?±?2.06 vs. 2.75?±?1.34?pg/mL, P?
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3.0T MRI arterial spin labeling and magnetic resonance spectroscopy technology in the application of Alzheimer's disease.
Exp. Gerontol.
PUBLISHED: 07-31-2014
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The purpose of this study was to investigate the changes in the cerebral blood flow (CBF) and spectrum variables in the posterior cingulate region of patients with AD under the detection of arterial spin labeling (ASL) and magnetic resonance spectroscopy (MRS). A total of 20 AD patients (8 males and 12 females; mean age, 64.84±8.82years) and 20 healthy controls (9 males and 11 females; mean age, 64.94±7.93years) were included in this study for analysis. All images were obtained using a 3.0-T MR imager and an 8-channel head array receiving coil. MRS measurements were conducted exploring variables of metabolite ratios. Statistical analyses were conducted with the SPSS 11.0 statistical software package. Findings in the present study revealed a significant difference in the mean MMSE scores between the AD group and the healthy control group (16.21±4.01 vs. 27.35±1.01, P<0.01). Compared with the healthy control group, CBF in the bilateral frontal region showed a significant decrease in the AD group (right frontal: 83.5±7.2 vs. 110±11.5, P<0.05; left frontal: 85.6±8.1 vs. 108.7±12.2, P<0.05, respectively), and a similar association was also observed in the TL, TPJ, parietal, and hippocampal regions (all P<0.05). MRS imaging in the posterior cingulate region showed a significant reduction in the NAA/Cr ratio in the AD group (1.43±0.1 vs. 1.49±0.0, P<0.05). Additionally, we found that the MI/Cr and Cho/Cr ratios were higher than normal controls in patients with AD (all P<0.05). Our results suggested that 3D ASL detection combined with MRS in studying AD could show the regional hypo-perfusion with the decrease of CBF and the abnormal metabolic changes of the posterior cingulate cortex.
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miR-26a and miR-214 down-regulate expression of the PTEN gene in chronic lymphocytic leukemia, but not PTEN mutation or promoter methylation.
Oncotarget
PUBLISHED: 07-28-2014
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We previous found the expression level of PTEN was low in the chronic lymphocytic leukemia (CLL) patients. To assess the pathogenic contribution of the low expression of PTEN, we determined PTEN-regulating miRNA interference, PTEN promoter methylation and PTEN gene mutation condition in CLL. One hundred and fifty-four previously untreated CLL patients and 200 cases of healthy controls were sequenced in exons 5-9 of PTEN. None of single nucleotide polymorphism site or mutation was detected in the coding sequences of those exons. Methylation of PTEN promoter was found in one (1.33%) of the 75 patients with CLL, but none of the 25 age-matched control subjects. We found that PTEN was a potential target of miR-26a and miR-214, which had been confirmed following dual-luciferase reporter assays, reverse transcription polymerase chain reaction and Western blotting. High expression of miR-26a was associated with advanced Binet stage (P=0.012), p53 aberrations (P=0.014) and inferior time to first treatment (P=0.038), and high expression of miR-214 was only associated with p53 aberrations (P=0.041). Inhibition of miR-26a or miR-214 could induce more apoptosis in primary cultured CLL cells. These findings support miR-26a and miR-214 down-regulate expression of PTEN in CLL, but not PTEN mutation or promoter methylation.
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SLC41A1 knockdown inhibits angiotensin II-induced cardiac fibrosis by preventing Mg(2+) efflux and Ca(2+) signaling in cardiac fibroblasts.
Arch. Biochem. Biophys.
PUBLISHED: 07-11-2014
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Na(+)/Mg(2+) exchanger plays an important role in cardiovascular system, but the molecular mechanisms still largely remain unknown. The Solute Carrier family 41A1 (SLC41A1), a novel Mg(2+) transporter, recently was found to function as Na(+)/Mg(2+) exchanger, which mainly regulates the intracellular Mg(2+) ([Mg(2+)]i) homeostasis. Our present studies were designed to investigate whether SLC41A1 impacts on the fibrogenesis of cardiac fibroblasts under Ang II stimulation. Our results showed that quinidine, a prototypical inhibitor of Na(+)/Mg(2+) exchanger, inhibited Ang II-induced cardiac fibrosis via attenuating the overexpression of vital biomarkers of fibrosis, including connective tissue growth factor (CTGF), fibronectin (FN) and ?-smooth muscle actin (?-SMA). In addition, quinidine also decreased the Ang II-mediated elevation of concentration of intracellular Ca(2+) ([Ca(2+)]i) and extrusion of intracellular Mg(2+). Meanwhile, silencing SLC41A1 by RNA interference also impaired the elevation of [Ca(2+)]i, [Mg(2+)]i efflux and the upregulation of CTGF, FN and ?-SMA provoked by Ang II. Furthermore, we found that Ang II-mediated activation of NFATc4 translocation decreased in SLC41A1-siRNA cells. These results support the notion that rapid extrusion of intracellular Mg(2+) is mediated by SLC41A1 and provide the evidence that the intracellular free Ca(2+) concentration is influenced by extrusion of intracellular Mg(2+) which facilitates fibrosis reaction in cardiac fibroblasts.
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Glucocorticoid Receptor ? Acts as a Co-activator of T-Cell Factor 4 and Enhances Glioma Cell Proliferation.
Mol. Neurobiol.
PUBLISHED: 07-07-2014
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We previously reported that glucocorticoid receptor ? (GR?) regulates injury-mediated astrocyte activation and contributes to glioma pathogenesis via modulation of ?-catenin/T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional activity. The aim of this study was to characterize the mechanism behind cross-talk between GR? and ?-catenin/TCF in the progression of glioma. Here, we reported that GR? knockdown reduced U118 and Shg44 glioma cell proliferation in vitro and in vivo. Mechanistically, we found that GR? knockdown decreased TCF/LEF transcriptional activity without affecting ?-catenin/TCF complex. Both GR? and GR? directly interact with TCF-4, while only GR? is required for sustaining TCF/LEF activity under hormone-free condition. GR? bound to the N-terminus domain of TCF-4 its influence on Wnt signaling required both ligand- and DNA-binding domains (LBD and DBD, respectively). GR? and TCF-4 interaction is enough to maintain the TCF/LEF activity at a high level in the absence of ?-catenin stabilization. Taken together, these results suggest a novel cross-talk between GR? and TCF-4 which regulates Wnt signaling and the proliferation in gliomas.
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Expert consensus for postmarketing Chinese medicine intensive hospital safety monitoring.
Chin J Integr Med
PUBLISHED: 07-04-2014
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It is of vital significance to conduct active postmarketing surveillance of Chinese medicine, as an active response to laws, rules and guidelines issued by the China Food and Drug Administration. These will provide technological support in evaluating adverse drug reactions (ADRs) or adverse drug events (ADEs). The expert consensus for postmarketing surveillance focuses on two surveillance designs; one is a large sample registry study to explore general population ADR/ADE characteristics, the other is a nested case-control study to explore the characteristic and mechanisms of ADRs.
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[A case report of a secondary tonsil follicular dendritic sarcoma after non-Hodgkin's lymphoma].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 06-26-2014
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Follicular dendritic sarcoma is a rare and low-grade malignant soft tissue tumors , often occurs in the lymph nodes, we report a case of tonsil follicular dendritic sarcoma which occured after Non-Hodgkin's lymphoma had be cured. The chief complaint was oropharyngeal foreign body sensation with hemoptysis three years, found in the left neck mass increased with more than 4 months. The left side of the pharyngeal wall thickening and disappearance of parapharyngeal space with the surrounding lymph nodes extremely enlarged and integrated was demonstrated by the contrast-enhanced CT of neck. Finally,the pathological diagnosis was tonsil follicular dendritic sarcoma.
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Association of TNF-?, TGF-?1, IL-10, IL-6, and IFN-? gene polymorphism with acute rejection and infection in lung transplant recipients.
Clin Transplant
PUBLISHED: 06-23-2014
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Infection and rejection are common complications faced by lung transplant recipients (LTRs) and have become major impediments to long-term survival. Cytokines may play an important role in the development of these complications. In this study, we explored the correlation between TNF-? (-308 A/G), TGF-?1 (+869 T/C, +915 G/C), IL-10 (-592 C/A, -819 T/C, -1082 G/A), IL-6 (-174 G/C), and IFN-? (+874 T/A) gene polymorphisms and the incidence of acute rejection and infection. Transplant outcomes were reviewed in a retrospective cohort of 113 LTRs from a single center between December 2004 and November 2012. Cytokine polymorphisms were measured using sequence-specific primer-based PCR. HLA typing was performed for the donors and recipients. We found that the LTRs with the IL-10 -819 CC and -592 CC genotypes had a significantly decreased risk of infection (p = 0.017, OR = 0.177, 95% CI = 0.04-0.85). However, we found no significant association between cytokine polymorphisms and acute rejection. Furthermore, the data revealed that the occurrence of acute rejection was strongly associated with infection episodes (?(2)  = 8.5256, p < 0.01). These results suggest that LTRs possessing the IL-10 -819 CC and -592 CC genotype may be protected from the occurrence of infection. Our results demonstrated that infection is an important cause of acute rejection for LTRs.
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Association of leptin receptor Lys109Arg and Gln223Arg polymorphisms with increased risk of clear cell renal cell carcinoma.
Asian Pac. J. Cancer Prev.
PUBLISHED: 06-18-2014
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Although roles of genetic polymorphisms of leptin receptor (LEPR) gene in several cancers have been documented, the association between polymorphisms of LEPR and clear cell renal cell carcinoma (CC-RCC) remains unknown. The aim of this study was to explore any relation.
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The significance of single nucleotide polymorphism rs2070770 in CD20 gene in Chinese patients with diffuse large B-cell lymphoma.
Leuk. Lymphoma
PUBLISHED: 06-06-2014
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The purpose of this study was to investigate the significance of polymorphisms in the CD20 gene in patients with diffuse large B-cell lymphoma (DLBCL). We sequenced exons 3-8 in 160 patients with de novo DLBCL and detected the expression of CD20 via immunohistochemistry. We found two single nucleotide polymorphisms (SNPs): rs17155019 in the 5' untranslated region and rs2070770 (ILE72/ILE72) in exon 4. There was no significant difference in genotype frequencies of SNPs between patients and controls (p = 0.855 and 0.251, respectively). In patients who received rituximab-containing chemotherapies, the T allele of rs2070770 was significantly associated with superior overall survival (OS) (p = 0.029) and progression-free survival (p = 0.045). Analogously, in patients who did not receive rituximab, the T allele of rs2070770 (p = 0.047) was also significantly associated with longer OS. In conclusion, SNPs of CD20 were not high risk factors of DLBCL, but the T allele of rs2070770 was a potential indicator of superior survival.
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Transforming growth factor-?1 (TGF-?1) induces mouse precartilaginous stem cell proliferation through TGF-? receptor II (TGFRII)-Akt-?-catenin signaling.
Int J Mol Sci
PUBLISHED: 05-24-2014
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Precartilaginous stem cells (PSCs) could self-renew or differentiate into chondrocytes to promote bone growth. In the current study, we aim to understand the role of transforming growth factor-?1 (TGF-?1) in precartilaginous stem cell (PSC) proliferation, and to study the underlying mechanisms. We successfully purified and primary-cultured PSCs from the neonate mice' perichondrial mesenchyme, and their phenotype was confirmed by the PSC marker fibroblast growth factor receptor-3 (FGFR-3) overexpression. We found that TGF-?1 induced Akt-glycogen synthase kinase-3? (GSK3?) phosphorylation and ?-catenin nuclear translocation in the mouse PSCs, which was almost blocked by TGF-? receptor-II (TGFRII) shRNA knockdown. Further, perifosine and MK-2206, two Akt-specific inhibitors, suppressed TGF-?1-induced GSK3? phosphorylation and ?-catenin nuclear translocation. Akt inhibitors, as well as ?-catenin shRNA knockdown largely inhibited TGF-?1-stimulated cyclin D1/c-myc gene transcription and mouse PSC proliferation. Based on these results, we suggest that TGF-?1 induces Akt activation to promote ?-catenin nuclear accumulation, which then regulates cyclin D1/c-myc gene transcription to eventually promote mouse PSC proliferation.
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Quantum coherence rather than quantum correlations reflect the effects of a reservoir on a system's work capability.
Phys Rev E Stat Nonlin Soft Matter Phys
PUBLISHED: 05-20-2014
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We consider a model of an optical cavity with a nonequilibrium reservoir consisting of a beam of identical two-level atom pairs (TLAPs) in the general X state. We find that coherence of multiparticle nonequilibrium reservoir plays a central role on the potential work capability of the cavity. We show that no matter whether there are quantum correlations in each TLAP (including quantum entanglement and quantum discord) or not, the coherence of the TLAPs has an effect on the work capability of the cavity. Additionally, constructive and destructive interferences could be induced to influence the work capability of the cavity by adjusting only the relative phase, with which quantum correlations have nothing to do. In this paper, the coherence of the reservoir, rather than the quantum correlations, effectively reflecting the effects of the reservoir on the system's work capability is demonstrated clearly.
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[Foreign body in parotid gland: a case report].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 05-08-2014
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A 44-year-old male complained recurrent swelling and pain in the left pre-auricular mass over 4 years, which aggravated for 4 months. Ultrasonography revealed a mixed mass echo in the left parotid gland. Computed tomography showed an enlarged parotid gland and a 1.5 cm x 0.9 cm low density shadow in the superficial lobe area with strip high-density shadow in the edge. Although the facial nerves of the patient were found adhered to the foreign body during the operation, the foreign body in parotid gland was removed surgically without any injure to them due to facial nerves protection. In conclusion, facial nerves dissection is necessary to avoid the postsurgical facial paralysis in the surgical removal of foreign bodies in parotid gland.
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Self-assembly and horizontal orientation growth of VO2 nanowires.
Sci Rep
PUBLISHED: 05-07-2014
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Single-crystalline vanadium dioxide (VO2) nanostructures have attracted an intense research interest recently because of their unique single-domain metal-insulator phase transition property. Synthesis of these nanostructures in the past was limited in density, alignment, or single-crystallinity. The assembly of VO2 nanowires (NWs) is desirable for a "bottom-up" approach to the engineering of intricate structures using nanoscale building blocks. Here, we report the successful synthesis of horizontally aligned VO2 NWs with a dense growth mode in the [1-100]quartz direction of a polished x-cut quartz surface using a simple vapor transport method. Our strategy of controlled growth of VO2 NWs promisingly paves the way for designing novel metal-insulator transition devices based on VO2 NWs.
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(R)-[(R)-3-Benzyl-2-oxooxazolidin-4-yl][4-(methyl-sulfon-yl)phen-yl]methyl acetate.
Acta Crystallogr Sect E Struct Rep Online
PUBLISHED: 05-01-2014
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The structure of the title compound, C20H21NO6S, is of inter-est with respect to its anti-bacterial properties. The oxazolidine ring makes dihedral angles of 79.63?(14) and 56.16?(12)° with the phenyl and benzene rings, respectively, while the phenyl and benzene rings make a dihedral angle of 64.37?(13)°. In the crystal, non-classical C-H?O hydrogen bonds link adjacent mol-ecules along the c axis.
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A semicircular controlled cortical impact produces long-term motor and cognitive dysfunction that correlates well with damage to both the sensorimotor cortex and hippocampus.
Brain Res.
PUBLISHED: 04-22-2014
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Animal models of traumatic brain injury (TBI) are essential for testing novel hypotheses and therapeutic interventions. Unfortunately, due to the broad heterogeneity of TBI in humans, no single model has been able to reproduce the entire spectrum of these injuries. The controlled cortical impact (CCI) model is one of the most commonly used models of contusion TBI. However, behavioral evaluations have revealed transient impairment in motor function after CCI in rats and mice. Here we report a new semicircular CCI (S-CCI) model by increasing the impact tip area to cover both the motor cortex and hippocampal regions in adult mice. Mice were subjected to S-CCI or CCI using an electromagnetic impactor (Impactor One, MyNeuroLab; semicircular tip: 3mm radius; CCI tip diameter: 3mm). We showed that S-CCI, at two injury severities, significantly decreased the neuroscore and produced deficits in performance on a rotarod device for the entire duration of the study. In contrast, the CCI induced motor deficits only at early stages after the injury, suggesting that the S-CCI model produces long-lasting motor deficits. Morris water maze test showed that both CCI and S-CCI produced persisting memory deficits. Furthermore, adhesive removal test showed significant somatosensory and motor deficits only in the S-CCI groups. Histological analysis showed a large extent of cortical contusion lesions, including both the sensory and motor cortex, and hippocampal damage in the S-CCI. These findings collectively suggest that the current model may offer sensitive, reliable, and clinically relevant outcomes for assessments of therapeutic strategies for TBI.
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The p65 subunit of NF-?B involves in RIP140-mediated inflammatory and metabolic dysregulation in cardiomyocytes.
Arch. Biochem. Biophys.
PUBLISHED: 04-13-2014
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The transcription factor NF-?B regulates expression of many genes that are involved in inflammation, fatty acid and glucose metabolism, and plays a crucial role in cardiac pathological processes. RIP140 is a corepressor that down-regulates expression of genes involved in the cellular substrate uptake and mitochondrial ?-oxidation. In addition to this, RIP140 also acts as a coactivator for p65-NF-?B, potentiating the secretion of proinflammatory cytokines in macrophages, but the effects in cardiomyocytes are still unknown. In this study, overexpression of RIP140 induced proinflammatory gene expression and cytokine release in neonatal rat cardiomyocytes, which could be reversed by p65-NF-?B inhibition. Furthermore, RIP140-mediated repression of metabolic-related genes, mitochondrial biogenesis and metabolic function were weakened after knocking down of p65-NF-?B. These findings suggest that p65-NF-?B plays an important role in RIP140-mediated proinflammatory response and energy metabolism in cardiomyocytes, and provide evidence for the crosstalk between proinflammatory processes and metabolic dysregulation in the heart.
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[Dual plating fixation for distal fibular comminuted fractures].
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
PUBLISHED: 04-04-2014
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To evaluate the technique and effectiveness of dual plating fixation for distal fibular comminuted fractures.
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Glucosylceramide synthase promotes Bcl-2 expression via the ERK signaling pathway in the K562/A02 leukemia drug-resistant cell line.
Int. J. Hematol.
PUBLISHED: 04-02-2014
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Multidrug resistance (MDR) to chemotherapeutic agents is a major obstacle to curative treatment of cancer. In various types of cancers, overexpression of glucosylceramide synthase (GCS) has been observed to be associated with MDR, thus making GCS a target for reversal of resistance. Our previous work demonstrated that GCS and Bcl-2 are co-overexpressed in the K562/A02 leukemia multidrug-resistant cell line compared with its sensitive counterpart, K562. In the present study, we investigated the effects of GCS on apoptosis in K562/A02 and the associated molecular mechanisms. Our results indicate that the inhibition of GCS caused downregulation of Bcl-2 as well as apoptosis enhancement in response to ADM via the ERK pathway, while JNK or p38 MAPK signaling appeared to play less significant roles in the regulation of apoptosis and MDR in K562/A02 cells. Targeting GCS by siRNA also enhanced ceramide accumulation, which is involved in GCS knockdown-induced inhibition of ERK activation and Bcl-2 expression levels.
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Fish consumption and risk of gastrointestinal cancers: A meta-analysis of cohort studies.
World J. Gastroenterol.
PUBLISHED: 03-16-2014
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To assess quantitatively the relationship between fish intake and the incidence of gastrointestinal cancers in a meta-analysis of cohort studies.
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C/EBP? knockdown protects cardiomyocytes from hypertrophy via inhibition of p65-NF?B.
Mol. Cell. Endocrinol.
PUBLISHED: 03-11-2014
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C/EBP?, a member of the bHLH gene family of DNA-binding transcription factors, has been indicated as a central signal in physiologic hypertrophy. However, the role of C/EBP? in pathological cardiac hypertrophy remains to be elucidated. In this study, we revealed that C/EBP? is involved in cardiac hypertrophy, the expression of C/EBP? were significantly increased in response to hypertrophic stimulation in vitro and in vivo. C/EBP? knockdown inhibited PE-induced cardiac hypertrophy, and diminished the nuclear translocation and DNA binding activity of p65-NF?B. These results suggested that C/EBP? knockdown protected cardiomyocytes from hypertrophy, which may be attributed to inhibition of NF?B-dependent transcriptional activity. These findings shed new light on the understanding of C/EBP?-related cardiomyopathy, and suggest the potential application of C/EBP? inhibitors in cardiac hypertrophy.
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Rapamycin attenuated cardiac hypertrophy induced by isoproterenol and maintained energy homeostasis via inhibiting NF-?B activation.
Mediators Inflamm.
PUBLISHED: 03-10-2014
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Rapamycin, also known as sirolimus, is an immunosuppressant drug used to prevent rejection organ (especially kidney) transplantation. However, little is known about the role of Rapa in cardiac hypertrophy induced by isoproterenol and its underlying mechanism. In this study, Rapa was administrated intraperitoneally for one week after the rat model of cardiac hypertrophy induced by isoproterenol established. Rapa was demonstrated to attenuate isoproterenol-induced cardiac hypertrophy, maintain the structure integrity and functional performance of mitochondria, and upregulate genes related to fatty acid metabolism in hypertrophied hearts. To further study the implication of NF-?B in the protective role of Rapa, cardiomyocytes were pretreated with TNF-? or transfected with siRNA against NF-?B/p65 subunit. It was revealed that the upregulation of extracellular circulating proinflammatory cytokines induced by isoproterenol was able to be reversed by Rapa, which was dependent on NF-?B pathway. Furthermore, the regression of cardiac hypertrophy and maintaining energy homeostasis by Rapa in cardiomyocytes may be attributed to the inactivation of NF-?B. Our results shed new light on mechanisms underlying the protective role of Rapa against cardiac hypertrophy induced by isoproterenol, suggesting that blocking proinflammatory response by Rapa might contribute to the maintenance of energy homeostasis during the progression of cardiac hypertrophy.
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Epidermal growth factor receptor inhibitor ameliorates excessive astrogliosis and improves the regeneration microenvironment and functional recovery in adult rats following spinal cord injury.
J Neuroinflammation
PUBLISHED: 03-09-2014
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Astrogliosis is a common phenomenon after spinal cord injury (SCI). Although this process exerts positive effects on axonal regeneration, excessive astrogliosis imparts negative effects on neuronal repair and recovery. Epidermal growth factor receptor (EGFR) pathway is critical to the regulation of reactive astrogliosis, and therefore is a potential target of therapeutics to better control the response. In this report, we aim to investigate whether blocking EGFR signaling using an EGFR tyrosine kinase specific inhibitor can attenuate reactive astrogliosis and promote functional recovery after a traumatic SCI.
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?1-adrenergic regulation of rapid component of delayed rectifier K+ currents in guinea-pig cardiac myocytes.
Mol Med Rep
PUBLISHED: 02-21-2014
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Human ether-à-go-go-related gene (hERG) potassium channels conduct the rapid component of the delayed rectifier potassium current (IKr), which is crucial for repolarization of cardiac action potential. Patients with hERG?associated long QT syndrome usually develop tachyarrhythmias during physical and/or emotional stress, both known to stimulate adrenergic receptors. The present study aimed to investigate a putative functional link between ?1-adrenergic stimulation and IKr in guinea-pig left ventricular myocytes and to analyze how IKr is regulated following activation of the ?1-adrenergic signaling pathway. The IKr current was measured using a whole-cell patch-clamp technique. A selective ?1-adrenergic receptor agonist, xamoterol, at concentrations of 0.01-100 µM decreased IKr in a concentration-dependent manner. The 10 µM xamoterol-induced inhibition of IKr was attenuated by the protein kinase A (PKA) inhibitor KT5720, the protein kinase C (PKC) inhibitor chelerythrine, and the phospholipase (PLC) inhibitor U73122, indicating involvement of PKA, PKC and PLC in ?1-adrenergic inhibition of IKr. The results of the present study indicate an association between IKr and the ?1-adrenergic receptor in arrhythmogenesis, involving the activation of PKA, PKC and PLC.
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A positive Babinski reflex predicts delayed neuropsychiatric sequelae in Chinese patients with carbon monoxide poisoning.
Biomed Res Int
PUBLISHED: 02-19-2014
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As the human population increased in China, the carbon monoxide is a serious environmental toxin in public health. However, predicting the delayed neuropsychiatric sequelae (DNS) of carbon monoxide poisoning (COP) has not been well studied. We investigated the independent predictors of DNS in patients with COP. This study was conducted at four hospitals in China. Data were retrospectively collected from 258 patients with COP between November 1990 and October 2011. DNS was the primary endpoint. A positive Babinski reflex was the independent predictor for DNS: sensitivity = 53.8% (95% confidence interval [CI]: 26.1-79.6), specificity = 88.6% (95% CI: 83.7-92.1), positive predictive value (PPV) = 20.0% (95% CI: 9.1-37.5), and negative predictive value (NPV) = 97.3% (95% CI: 94.0-98.9). The area under the receiver operating characteristic curve = 0.712 (95% CI: 0.544-0.880). A positive Babinski reflex was very memorable, immediately available, and applicable in clinical practice. Even when the sensitivity and PPV of a positive Babinski reflex were unsatisfactory, it had a good specificity and NPV for excluding the risk of DNS. In patients without a positive Babinski reflex, the risk for DNS was only 2.7%. This finding may help physicians make decisions about dispositions for patients with COP.
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Periconianone A, a new 6/6/6 carbocyclic sesquiterpenoid from endophytic fungus Periconia sp. with neural anti-inflammatory activity.
Org. Lett.
PUBLISHED: 02-19-2014
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Periconianone A (1), a polyoxygenated sesquiterpenoid with a new 6/6/6 tricarbocyclic skeleton, and periconianone B (2) were isolated from the endophytic fungus Periconia sp. Their structures and absolute configurations were elucidated by extensive spectroscopic analyses, calculated ECD, and single-crystal X-ray diffraction (Cu K?). The biosynthesis of the unusual six-membered carbonic ring of 1 was postulated to be formed through intramolecular aldol condensation. Compounds 1 and 2 showed significant neural anti-inflammatory activity.
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Establishment and maintenance of a standardized glioma tissue bank: Huashan experience.
Cell Tissue Bank
PUBLISHED: 02-14-2014
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Cerebral glioma is the most common brain tumor as well as one of the top ten malignant tumors in human beings. In spite of the great progress on chemotherapy and radiotherapy as well as the surgery strategies during the past decades, the mortality and morbidity are still high. One of the major challenges is to explore the pathogenesis and invasion of glioma at various "omics" levels (such as proteomics or genomics) and the clinical implications of biomarkers for diagnosis, prognosis or treatment of glioma patients. Establishment of a standardized tissue bank with high quality biospecimens annotated with clinical information is pivotal to the solution of these questions as well as the drug development process and translational research on glioma. Therefore, based on previous experience of tissue banks, standardized protocols for sample collection and storage were developed. We also developed two systems for glioma patient and sample management, a local database for medical records and a local image database for medical images. For future set-up of a regional biobank network in Shanghai, we also founded a centralized database for medical records. Hence we established a standardized glioma tissue bank with sufficient clinical data and medical images in Huashan Hospital. By September, 2013, tissues samples from 1,326 cases were collected. Histological diagnosis revealed that 73 % were astrocytic tumors, 17 % were oligodendroglial tumors, 2 % were oligoastrocytic tumors, 4 % were ependymal tumors and 4 % were other central nervous system neoplasms.
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[NF-? B mediates the effect of glucosylceramide synthase on P-glycoprotein modulation in a drug-resistance leukemia cell line].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 02-11-2014
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To investigate whether transcription factor-kappaB (NF-? B) is involved in the modulation of P-glycoprotein (P-gp) by glucosylceramide synthase (GCS) in a multidrug resistance leukemia cell line K562/A02 and to explore the relationship between NF-? B and extracelluar signal-regulated kinase (ERK).
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CES1A -816C as a genetic marker to predict greater platelet clopidogrel response in patients with percutaneous coronary intervention.
J. Cardiovasc. Pharmacol.
PUBLISHED: 02-11-2014
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This study was designed to determine whether CES1A -816A/C polymorphism could be associated with altered clopidogrel response. Recruited patients were pretreated with 300 mg clopidogrel loading dose before undergoing percutaneous coronary intervention for stenting and genotyped with CYP2C19 *2, *3, or *17, and CES1A -816A/C, respectively. Adenosine diphosphate-induced maximum platelet aggregation (MPA) was determined on day 3 after initiation of daily clopidogrel maintenance doses. The clinical primary end point was the 1-year incidence of definite stent thrombosis (ST). Multivariable linear regression revealed that the CES1A -816A/C polymorphism was independently associated with MPA measures with an absolute ? value of 6.76. Of 617 patients, a subcohort of 249 patients not carrying CYP2C19 *2, *3, or *17 were categorized into 3 groups based on the -816A/C genotype. The median MPA value was lower in 125 carriers of the -816C variant than in 124 noncarriers (21.5% vs. 31.7%, P = 0.001). The 1-year definite ST occurred in 7 patients in that subcohort, and only 1 ST case was one of carriers of the -816 A/A that was associated with higher MPA values. The CES1A -816C would be used to predict greater platelet response to clopidogrel than the CES1A -816A in percutaneous coronary intervention-treated patients not carrying CYP2C19 variants.
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Salvianolic acid B protects cardiomyocytes from angiotensin II-induced hypertrophy via inhibition of PARP-1.
Biochem. Biophys. Res. Commun.
PUBLISHED: 01-03-2014
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Salvianolic acid B (SalB), one of the major bioactive components in Salviamiltiorrhiza, has plenty of cardioprotective effects. The present study was designed to investigate the effect of SalB on angiotensin II (AngII)-induced hypertrophy in neonatal rat cardiomyocytes, and to find out whether or not this effect is attributed to inhibition of poly (ADP-ribose) polymerase-1 (PARP-1), which plays a key role in cardiac hypertrophy. Our results showed that SalB prevented the cardiomyocytes from AngII-induced hypertrophy, associated with attenuation of the mRNA expressions of atrial natriuretic factor and brain natriuretic peptide, and reduction in the cell surface area. SalB inhibited the activity of PARP-1. The inhibitory effect was comparable to that of the PARP-1 inhibitor 3-Aminobenzamide (3-AB). In addition, SalB reversed the depletion of cellular NAD(+) induced by AngII. Moreover, overexpression of PARP-1 attenuated the anti-hypertrophic effect of SalB. These observations suggested that SalB prevented the cardiomyocytes from AngII-induced hypertrophy, at least partially through inhibition of PARP-1. Moreover, SalB attenuated the generation of oxidative stress via suppression of NADPH oxidase 2 and 4, which might probably contribute to the inhibition of PARP-1. These present findings may shed new light on the understanding of the cardioprotective effect of SalB.
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Primary small cell neuroendocrine carcinoma of the tonsil: a case report and review of the literature.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Small cell neuroendocrine carcinoma (NEC) that originates in the tonsil is extremely rare and carries a poor prognosis. Only a few cases of this tumor have been reported so far and the standard treatment protocol remains uncertain. Here we describe a 74-year-old woman presented with throat pain for about 2 months. Computed tomography (CT) scan revealed a 3.4×1.8 cm tumor with moderate enhancement in the left tonsil and a 1.3×1.0 cm neck mass in left level II. A biopsy of the tonsillar mass was performed and histologic examination revealed small round to oval tumor cells were arranged in cords or nests, containing hyperchromatic nuclei and scant cytoplasm. Mitotic figures were readily identified. Immunohistochemical staining showed that tumor cells were strongly positive for CD56, focally positive for PCK and negative for LCA. A diagnosis of primary small cell NEC of the left tonsil was obtained. The patient was treated by six cycles of cisplatin combined with etoposide and the masses showed initial complete response. But recurrence in the left neck was found 9 months after initial diagnosis and the patient refused any further treatment. With a review of the literature, the nomenclature, clinicopathological characteristics and treatment modalities of this rare tumor are discussed.
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Increased risk for developing major adverse cardiovascular events in stented Chinese patients treated with dual antiplatelet therapy after concomitant use of the proton pump inhibitor.
PLoS ONE
PUBLISHED: 01-01-2014
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Some clinical studies have demonstrated that the proton pump inhibitor (PPI) could decrease clopidogrel platelet response and increase major adverse cardiovascular events (MACE) in white or black subjects. However, that remains to be determined in Chinese patients. In this study, we sought to determine whether there could be an increased risk for developing MACE after concomitant use of dual antiplatelet therapy (DAT) and a PPI in Chinese patients treated with percutaneous coronary intervention (PCI) and stenting.
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[Effect of nasal cavity expansion surgery on chronic nasal obstructive diseases on the blood supply of the cerebral arterial system].
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 12-17-2013
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To investigate the effect of nasal cavity expansion surgery on the abnormal blood supply of the cerebral arterial system.
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[Curative effects on standardized management of community patients with coronary heart disease complicated with chronic heart failure].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 12-05-2013
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To explore the effects on the standardized management of patients with coronary atherosclerotic heart disease complicated with chronic heart failure.
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Polyclonal antibody targeting SOX11 cannot differentiate mantle cell lymphoma from B-cell non-Hodgkin lymphomas.
Am. J. Clin. Pathol.
PUBLISHED: 11-15-2013
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To determine whether SOX11 is a diagnostic marker of mantle cell lymphoma (MCL).
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[Catheter ablation of epicardial accessory pathway associated with coronary sinus musculature].
Zhonghua Xin Xue Guan Bing Za Zhi
PUBLISHED: 09-12-2013
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To report the single-center clinical experience of catheter ablation of epicardial accessory pathway associated with coronary sinus musculature.
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[Determination pharmacokinetics parameters of raw and different processed epimediums by pharmacology effect method].
Zhong Yao Cai
PUBLISHED: 09-10-2013
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To determine the pharmacokinetics parameters of raw and different processed epimediums with pharmacology effect method.
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Spatial-temporal expressions of Crumbs and Nagie oko and their interdependence in zebrafish central nervous system during early development.
Int. J. Dev. Neurosci.
PUBLISHED: 08-18-2013
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A vast number of apicobasal polarity proteins play essential roles in the polarization and morphogenesis of the neuroepithelia. Crumbs (Crb) type I transmembrane cell-cell adhesion proteins are among these proteins. Five crb genes have been identified in zebrafish. However, their expressional and functional differences during early neural development remain to be fully elucidated. Here, we study the spatial-temporal expression patterns and functions of Crb1, Crb2a, and Crb2b in the central nervous system (CNS) during the neurulation period. We show that: 1, the optic vesicle and undifferentiated retinal neuroepithelium only express Crb2a; 2, Crb1 and Crb2a expressions overlap extensively in the undifferentiated neural tube epithelium; 3, Crb2b expression is the weakest of the three and is restricted to the ventral-most regions of the anterior CNS; and 4, Nok and Crb proteins require each other for their apical localization in neuroepithelium. The commencements of Crb1, Crb2a, and Crb2b expressions follow a spatial-temporal spread from anterior to posterior and from ventral to dorsal and lag behind that of adherens junction components, such as ZO-1 and actin bundles. Genetic and morpholino suppression analyses suggest that in regions where these Crb expressions overlap, they are functionally redundant in maintaining apicobasal polarity of the undifferentiated neuroepithelium.
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[Comparative study on effect of crude and different processed products of epimedium on pharmacokinetics characteristics in mice].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 08-17-2013
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To study different impacts of crude epimedium and extracts from different processed epimedium on pharmacokinetic characteristic parameters in mice. To explore the rationality of its processed products, mice were orally administered with crude epimedium and extracting solutions from heated epimedium and processed epimedium. With increased SOD value as an indicator, the relationship between time and equivalent body dose was obtained by using the pharmacological effect method. DAS 2.0 software was adopted to compare their pharmacokinetic parameters. The results showed significant differences in such pharmacokinetic parameters as Cmax and AUC of processed epimedium, heated epimedium and crude epimedium, namely processed epimedium > heated epimedium > crude epimedium. We could come to the conclusion that heated epimedium showed increased bioavailability, while epimedium processed with sheep oil could further promote in vivo absorption.
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Real polymer-free sirolimus- and probucol-eluting versus biodegradable polymer sirolimus-eluting stents for obstructive coronary artery disease: DKPLUS-Wave 1, a multicenter, randomized, prospective trial.
Cardiovasc Ther
PUBLISHED: 06-26-2013
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Polymer-free sirolimus- and probucol-eluting stents (Real Dual drug-eluting stents [DES]) is as effective as first-generation DES in treating coronary artery stenosis. It is unknown whether sirolimus-eluting stents containing biodegradable polymer (Excel) would be superior to real Dual DES. This study aimed to investigate the difference in target vessel revascularization (TVR) at 12 months in patients with coronary artery disease treated by the implantation of Dual DES or Excel stents.
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Glutamine synthetase functions as a negative growth regulator in glioma.
J. Neurooncol.
PUBLISHED: 05-25-2013
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Our recent study demonstrated that glutamine synthetase (GS) may not only serve as a glutamate-converting enzyme in glial cells, but may also function as a regulator of astrocyte migration after injury. In this report, we showed that GS expression increased in cultured rat C6 glioma cells that underwent long-term serially propagation. The stable overexpression of GS in C6 glioma cells resulted in growth arrest and motility suppression; however the stable knockdown of GS resulted in motility enhancement. In correlation with cell aggregation, N-cadherin levels increased at sites of cell-cell contact in C6 cells overexpressing GS, and decreased in C6 cells with stable GS knockdown; total N-cadherin expression levels remained unchanged in these cells. In addition, levels of p21, a potent cyclin-dependent kinase inhibitor, increased, while cyclin D1 levels decreased in C6 cells overexpressing GS. Our additional studies showed that N-cadherin-mediated cell-cell contacts were implicated in GS-induced cell growth arrest and impairment of cell migration, as evidenced by the inhibition of GS on cell growth and motility by the neutralizing anti-N-cadherin monoclonal antibody (GC-4 mAb). Collectively, these observations suggest a novel mechanism of growth regulation by GS that involves N-cadherin mediated cell-cell contact.
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Axonal and glial responses to a mid-thoracic spinal cord hemisection in the Macaca fascicularis monkey.
J. Neurotrauma
PUBLISHED: 05-13-2013
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A comprehensive understanding of the pathology of spinal cord injury (SCI) in non-human primates may facilitate greatly the development of new strategies to promote recovery in humans with SCI. Relatively few studies, however, have been conducted to systemically examine pathological changes in the monkey, a non-human primate, after SCI. We report axonal, glial, and fibrotic responses in the spinal cord of monkey Macaca fascicularis after a thoracic (T) 8-9 lateral hemisection. We examined these changes at three regions--i.e., the lesion epicenter, the peri-lesion area, and the lateral white matter of the intact, contralateral hemicord at 7 (subacute) and 30 (early chronic) days post-injury. The lateral hemisection resulted in a marked axon and myelin loss, along with tissue loss, at the lesion epicenter at both time points. Unexpectedly, axonal loss and myelin degeneration, along with reactive gliosis and microglia/macrophages activation, were also observed in the contralateral spared hemicord, indicating a spread of the initial damage to the contralateral side. In addition, activated microglia/macrophages were found both within the injury epicenter and the peri-lesion area, indicating that they participate in injury-induced immune responses that may exacerbate the secondary damage. In contrast to rodents, substantial reactive astrocytic responses at the lesion border were not observed in the monkey. Conversely, a deposit of robust fibrotic scar was observed at the injury epicenter, which filled the space originally created by the hemisection. Thus, understanding the pathology of monkey SCI may provide clinically relevant information in designing repair strategies targeting specific problems associated with human SCIs.
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Two new diterpenoids from cell cultures of Salvia miltiorrhiza.
Chem. Pharm. Bull.
PUBLISHED: 05-08-2013
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A new spiroketallactone, epi-danshenspiroketallactone A (1) and a new C18-norditerpenoid, normiltioane (2) along with 21 known compounds, were isolated from cell cultures of Salvia miltiorrhiza. Their structures were elucidated on the basis of extensive spectroscopic analyses. In the in vitro assays, the compounds 9-11, 21-23 exhibited the significant antitumor activity with the IC(50) ranges of 1.0-8.3 µM.
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The BH3-only protein Puma plays an essential role in p53-mediated apoptosis of chronic lymphocytic leukemia cells.
Leuk. Lymphoma
PUBLISHED: 04-30-2013
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The purpose of this study was to explore the characteristics and functions of BH3-only proteins Puma, Noxa and Bim in the prognosis, therapy and drug resistance of chronic lymphocytic leukemia (CLL). Puma, Noxa and Bim mRNAs were evaluated by real-time quantitative reverse transcriptase-polymerase chain reaction, and correlations between their expression levels and CLL prognostic markers were analyzed. Primary CLL samples were treated in vitro with fludarabine to investigate the role of Puma, Noxa and Bim in the response to chemotherapeutic drugs which act through activation of the p53 pathway. We found that a low expression level of Puma was associated with some markers of poor prognosis. However, the level of Noxa or Bim was not different in patients with CLL with variant clinical features and prognostic factors. Puma expression was up-regulated after fludarabine treatment in primary CLL cells, but there was no significant difference for Noxa and Bim. Up-regulation of Puma occurred only in CLL cells with functional p53. CLL cells with p53 abnormalities were deficient in the activation of Puma by chemotherapeutics. These results suggest that a lack of Puma induction may contribute to the development of resistance to anticancer agents in CLL.
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Poly IC triggers a cathepsin D- and IPS-1-dependent pathway to enhance cytokine production and mediate dendritic cell necroptosis.
Immunity
PUBLISHED: 04-23-2013
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RIG-I-like receptors (RLRs) sense virus-derived RNA or polyinosinic-polycytidylic acid (poly IC) to exert antiviral immune responses. Here, we examine the mechanisms underlying the adjuvant effects of poly IC. Poly IC was taken up by dendritic cells (DCs), and it induced lysosomal destabilization, which, in turn, activated an RLR-dependent signaling pathway. Upon poly IC stimulation, cathepsin D was released into the cytoplasm from the lysosome to interact with IPS-1, an adaptor molecule for RLRs. This interaction facilitated cathepsin D cleavage of caspase 8 and the activation of the transcription factor NF-?B, resulting in enhanced cytokine production. Further recruitment of the kinase RIP-1 to this complex initiated the necroptosis of a small number of DCs. HMGB1 released by dying cells enhanced IFN-? production in concert with poly IC. Collectively, these findings suggest that cathepsin D-triggered, IPS-1-dependent necroptosis is a mechanism that propagates the adjuvant efficacy of poly IC.
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Estimating the hyperfine coupling parameters of the avian compass by comprehensively considering the available experimental results.
Phys Rev E Stat Nonlin Soft Matter Phys
PUBLISHED: 04-22-2013
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Migratory birds can utilize the geomagnetic field for orientation and navigation through a widely accepted radical-pair mechanism. Although many theoretical works have been done, the available experimental results have not been fully considered, especially the temporary disorientation induced by the field which is increased by 30% of the geomagnetic field and the disorientation of the very weak resonant field of 15 nT. In this paper, we consider the monotonicity of the singlet yield angular profile as the prerequisite of direction sensitivity, and find that for some optimal values of the hyperfine coupling parameters (that is, the order of 10^{-7}?10^{-6} meV) the experimental results available so far can be satisfied. We also investigate the effects of two decoherence environments and demonstrate that, in order to satisfy the available experimental results, the decoherence rate should be lower than the recombination rate. Finally, we investigate the effects of the fluctuating magnetic noises and find that the vertical noise destroys the monotonicity of the profile completely, but the parallel noise preserves the monotonicity perfectly and even can enhance the direction sensitivity.
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Analysis of hsa-miR-30a-5p expression in human gliomas.
Pathol. Oncol. Res.
PUBLISHED: 04-20-2013
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Our previous study demonstrated that miR-30a-5p was upregulated in six malignant glioma cell lines by microRNA(miRNA) array. For further verification of this finding, the expression of miR-30a-5p in 7 more malignant glioma cell lines, 43 freshly resected glioma samples and 75 archival paraffin embedded glioma specimens with different grade of malignancy were examined by qRT-PCR and in situ hybridization(ISH). Here, we present the first evidence that miR-30a-5p is overexpressed in glioma cell lines and glioma samples as compared to the normal brain tissues (NBTs), and its expression level is positively correlated with tumor grade of malignancy. It is concluded that miR-30a-5p may have the potential as a diagnostic or prognostic marker of gliomas and as the target of miRNA-based glioma therapy in further studies.
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Upregulation of Nox4 promotes angiotensin II-induced epidermal growth factor receptor activation and subsequent cardiac hypertrophy by increasing ADAM17 expression.
Can J Cardiol
PUBLISHED: 04-09-2013
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Activation of epidermal growth factor receptor (EGFR) plays an important role in angiotensin II (Ang II)-induced cardiac hypertrophy, but little is known about the underlying mechanism that results in EGFR activation. In this study, we aimed to confirm the important role of nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) in Ang II-induced EGFR activation and subsequent cardiac hypertrophy by upregulating expression of a disintegrin and metalloproteinase (MMP)-17 (ADAM17).
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Increased expression of S100A8 and S100A9 in patients with diffuse cutaneous systemic sclerosis. A correlation with organ involvement and immunological abnormalities.
Clin. Rheumatol.
PUBLISHED: 04-09-2013
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S100A8 and S100A9 play important roles in immune and inflammatory disorders. The role of the two proteins in systemic sclerosis (SSc) remains unknown. Fifty-seven diffuse cutaneous SSc (dcSSc) patients, 31 limited cutaneous SSc (lcSSc) patients were recruited in the present study. The expression of S100A8 and S100A9 in plasma was measured using an enzyme-linked immunosorbent assay and the mRNA levels in peripheral blood were assessed using reverse transcriptase quantitative PCR. The expression and distribution of S100A8, S100A9, and receptor for advanced glycation end products (RAGE), in skin tissues was analyzed by immunohistochemistry. The plasma concentrations of S100A8 and S100A9 were significantly higher in dcSSc patients than in normal controls and lcSSc patients. Both S100A8 and S100A9 levels were significantly increased in dcSSc patients with lung or kidney involvement. Increased plasma levels of S100A8 and S100A9 in dcSSc patients were associated with several autoantibodies. Transcription levels of S100A8 and S100A9 in peripheral blood were found elevated in both dcSSc and lcSSc patients than normal controls. Immunohistochemistry demonstrated higher S100A8 and S100A9 expression in sclerotic skin than in normal skin. The number of S100A8, S100A9, or RAGE positive fibroblasts was also significantly increased. Highly elevated expression of both S100A8 and S100A9 was found in dcSSc patients. There was close correlation with disease severity and serological abnormalities, suggesting that the two proteins may play important roles in the development of systemic sclerosis.
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CYP2C19 polymorphism and antiplatelet effects of clopidogrel in Chinese stroke patients.
Pharmazie
PUBLISHED: 04-06-2013
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Recently published data indicate that CYP2C19*2 allele is the major determinant of metabolic bioactivation of clopidogrel and thereby variability of antiplatelet effect of clopidogrel in white or black patients undergoing elective coronary stent placement. The conclusion may not be fully generalized or extrapolated to the Chinese people due to significantly higher frequencies of the CYP2C19*2 or *3 variant alleles. We sought to investigate whether the CYP2C19*2 or *3 alleles affects platelet reactivity of clopidogrel in Chinese stroke patients. The study included 183 consecutive Chinese stroke patients after loading with clopidogrel 300 mg. Platelet function was assessed by adenosine diphosphate-induced (ADP 20 micromol/L) platelet aggregation and by light transmittance aggregometry (LTA) after seven 75-mg maintenance doses of clopidogrel before discharge. CYP2C19*2 or *3 genotypes were determined by time-of-flight mass spectrometer (MALDI/TOF-MS). In those patients who were carriers of 1 mutant allele (mutant heterozygotes, CYP2C19*1/*2 or *1/*3), ADP-induced maximum platelet aggregation (MPA) were significantly different compared with wild-type homozygous patients [37.2% (IQR, 19.6 to 50.5%) versus 23.6% (IQR, 14.0 to 35.4%), respectively; P=0.002]. In addition, in the patients who were carriers of 2 mutant allele (mutant homozygotes, CYP2C19*2/*2, *2/*3 or *3/*3,), MPA were also significantly different compared with wildtype homozygous patients [35.7% (IQR, 21.0 to 78.1%) versus 23.6% (IQR, 14.0 to 35.4%, respectively; P = 0.039]. By multivariable linear regression, CYP2C19*2 or *3 loss-of-function alleles were independently associated with ADP-induced MPA measurements (partial R2 = 0.138, P = 0.001). CYP2C19*2 or *3 allele does link to increased MPA and clopidogrel response.
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Efffect of the ABCC3 -211C/T polymorphism on clopidogrel responsiveness in patients with percutaneous coronary intervention.
Clin. Exp. Pharmacol. Physiol.
PUBLISHED: 03-26-2013
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Multidrug resistance protein 3 (MPR3), encoded by the ATP-binding cassette, subfamily C (CFTR/MRP), member 3 (ABCC3) gene, functions as an important drug efflux transporter. The ABCC3 -211C/T polymorphism is associated with decreased MRP3 mRNA expression, and low MRP3 mRNA expression is associated with increased clopidogrel response in patients. The aim of the present study was to determine whether the -211C/T polymorphism is associated with altered antiplatelet effects and clinical outcomes in clopidogrel-treated patients. A subcohort of 249 patients not carrying the CYP2C19*2, *3 or *17 variant was identified from a total of 617 consecutive clopidogrel-treated patients undergoing percutaneous coronary intervention and then categorized into three groups on the basis of their ABCC3 -211C/T genotype. Baseline data, clinical characteristics and DNA samples were collected for all patients. Light transmittance aggregometry was used to determine ADP-induced maximum platelet aggregation (MPA) in blood samples obtained from patients on Day 3 after starting daily clopidogrel maintenance doses. Genotyping of CYP2C19*2, *3 and *17 variants and the ABCC3 -211C/T polymorphism was performed using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. The primary clinical end-point was a definite stent thrombosis (ST) episode, whereas secondary end-points were other major adverse cardiovascular events within 12 months after stenting. There were no differences in MPA values according to ABCC3 -211C/T genotype. A multiple linear regression model revealed that the ABCC3 -211C/T polymorphism was not independently associated with ADP-induced MPA measurements; a multiple logistic regression model revealed that carrying the ABCC3 -211C allele was not associated with the risk of developing an ST event in clopidogrel-treated patients not harbouring CYP2C19*2, *3 and *17 variants. In conclusion, the ABCC3 -211C/T polymorphism seems not to be associated with altered antiplatelet effects and clinical outcomes in clopidogrel-treated patients.
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Posteromedial approach in treatment of talar posterior process fractures.
J Invest Surg
PUBLISHED: 03-20-2013
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To evaluate the surgical outcomes of talar, posterior process displaced fractures with posteromedial approach. From January 2008 to December 2010, 18 patients with displaced fracture of talar posterior process were treated in our department. Open reduction and screw fixation through posteromedial approach was performed after soft tissue swelling were subsided. The results were evaluated with Visual Analog Scale Pain Score (VAS) and American Orthopedic Foot and Ankle Society (AOFAS) scores. The average follow-up period was 16.8 months. There was no wound infection or nerve injury. There was no screw loosening, implant breakage, nonunion, or malunion. The average AOFAS score was 83.1, and the VAS score was 1.4. Two patients developed posttraumatic subtalar joint arthritis 1 year after operation, and one of them had subtalar arthrodesis performed due to pain and walking disability. Posteromedial approach can provide a good surgical exposure to the posterior portion of the talus without compromising the surrounding neurovascular structures. Small fragment screws can provide stable fixation and early mobilization of the ankle and subtalar joint. Open reduction and internal fixation via posteromedial approach is an effective and reliable method for the treatment to displaced fractures of the posterior process of the talus.
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Periconiasins A-C, new cytotoxic cytochalasans with an unprecedented 9/6/5 tricyclic ring system from endophytic fungus Periconia sp.
Org. Lett.
PUBLISHED: 03-18-2013
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Periconiasins A-C (1-3), new cytochalasans with an unprecedented 9/6/5 tricyclic ring system, were isolated from the endophytic fungus Periconia sp. F-31. Their structures and absolute configurations were elucidated by extensive spectroscopic and X-ray crystallographic analyses. Their biosynthesis is proposed to occur from an unusual seven acetate/malonate polyketide backbone attached to one leucine moiety by a PKS-NRPS followed by Diels-Alder and other reactions. 1 and 2 showed significant cytotoxicity against human HCT-8 cancer cells.
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Temporospatial expression and cellular localization of glutamine synthetase following traumatic spinal cord injury in adult rats.
Mol Med Rep
PUBLISHED: 03-13-2013
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Glutamine synthetase (GS) is an enzyme involved in an endogenous mechanism of protection against glutamate neurotoxicity and is important in the regulation of astrocyte migration. To date, limited information is available concerning the expression of GS in normal spinal cords and following injury. In the present study, GS expression was identified in astrocytes, oligodendrocytes and microglia in normal rat spinal cords. Following traumatic spinal cord injury (SCI), the glutamate concentration increased rapidly at 1 h and returned to baseline rapidly. However, the GS activity and protein levels were found to decrease at 4 h and then increase gradually from day 3 following SCI. The quantification of astrocytes, oligodendrocytes and activated microglia/macrophages, as well as immunohistochemistry staining of day 7 post?injured spinal cords, indicated that the astrocytes and microglia/macrophages contributed to the increase in GS. Collectively, the results provided evidence for the temporospatial expression and location of GS following SCI and suggested that the changes in GS levels may contribute to glutamate neurotoxicity and glial cell response following SCI.
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Chinese nomogram to predict probability of positive initial prostate biopsy: a study in Taiwan region.
Asian J. Androl.
PUBLISHED: 03-08-2013
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Several nomograms for prostate cancer detection have recently been developed. Because the incidence of prostate cancer is lower in Chinese men, nomograms based on other populations cannot be directly applied to Chinese men. We, therefore, developed a model for predicting the probability of a positive initial prostate biopsy using clinical and laboratory data from a Chinese male population. Data were collected from 893 Chinese male referrals, 697 in the derivation set and 196 in the external validation set, who underwent initial prostate biopsies as individual screening. We analyzed age, prostate volume, total prostate-specific antigen (PSA), PSA density (PSAD), digital rectal examinations (DRE) and transrectal ultrasound (TRUS) echogenicity. Logistic regression analysis estimated odds ratio, 95% confidence intervals and P values. Independent predictors of a positive biopsy result included advanced age, small prostate volume, elevated total PSA, abnormal digital rectal examination, and hyperechoic or hypoechoic TRUS echogenicity. We developed a predictive nomogram for an initial positive biopsy using these variables. The area under the receiver-operating characteristic curve for the model was 88.8%, which was greater than that of the prediction based on total PSA alone (area under the receiver-operating characteristic curve 74.7%). If externally validated, the predictive probability was 0.827 and the accuracy rate was 78.1%, respectively. Incorporating clinical and laboratory data into a prebiopsy nomogram improved the prediction of prostate cancer compared with predictions based solely on the individual factors.
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Band filling and correlation controlling electronic properties and magnetism in K(x)Fe(2-y)Se2: a slave boson study.
J Phys Condens Matter
PUBLISHED: 02-19-2013
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We investigate the electronic and magnetic properties of K(x)Fe(2-y)Se2 materials at different band fillings utilizing the multi-orbital Kotliar-Ruckenstein slave boson mean-field approach. We find that the ground state of KFe2Se2 is a paramagnetic (PM) bad metal with intermediate correlation, in contrast with the previous antiferromagnetic (AFM) results obtained by the local density approximation. Our PM metallic ground state suggests that KFe2Se2 is the parent phase of superconducting K(x)Fe(2-y)Se2, supporting a recent scanning tunneling spectroscopy experiment. For pure Fe2+-based systems, the ground state is a striped AFM (SAFM) metal with a spin density wave gap partially opened near the Fermi level. In comparison, for Fe3+-based compounds, besides SAFM, a Néel AFM metal without orbital ordering is observed, and an orbital selective Mott phase (OSMP) accompanied by an intermediate-spin to high-spin transition is also found, giving a possible scenario of an OSMP in K(x)Fe(2-y)Se2. These results demonstrate that the band filling and correlation control the Fermi surface topology, electronic state and magnetism in K(x)Fe(2-y)Se2.
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Interaction of 14-3-3? with KCMF1 suppresses the proliferation and colony formation of human colon cancer stem cells.
World J. Gastroenterol.
PUBLISHED: 02-14-2013
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To investigate the biological function of 14-3-3? protein and to look for proteins that interact with 14-3-3? protein in colon cancer stem cells.
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miR-92b controls glioma proliferation and invasion through regulating Wnt/beta-catenin signaling via Nemo-like kinase.
Neuro-oncology
PUBLISHED: 02-14-2013
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Nemo-like kinase (NLK) is an evolutionarily conserved protein kinase involved in Wnt/beta-catenin signaling, which has been reported to be associated with gliomagenesis. In the present study, we aimed to identify a concrete mechanism of Wnt/beta-catenin pathway regulation by microRNAs (miRNAs) in glioma.
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Glucocorticoid receptor ? regulates injury-mediated astrocyte activation and contributes to glioma pathogenesis via modulation of ?-catenin/TCF transcriptional activity.
Neurobiol. Dis.
PUBLISHED: 02-09-2013
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Astrocytes react to central nervous system (CNS) injury and participate in gliotic responses, imparting negative, as well as positive effects on axonal regeneration. Despite the considerable biochemical and morphological changes astrocytes undergo following insult, and the known influence of steroids on glial activation, details surrounding glucocorticoid receptor expression and activity are lacking. Such mechanistic information is essential for advancing and enhancing therapies in the treatment of CNS injuries. Using an in vitro wound-healing assay, we found glucocorticoid receptor ? (GR?), not GR?, is upregulated and acts as a regulator of gliosis after injury. In addition, our results suggest that GR? interacts with ?-catenin and is a necessary component for proliferation and migration in both injured astrocytes and glioma cells. Further analysis indicated GR?/?-catenin interaction as a key modulator of astrocyte reactivity through sustained Wnt/?-catenin/TCF signaling in its dominant-negative effect on GR? mediated trans-repression by a GSK-3?-independent manner. These findings expand our knowledge of the mechanism of GR? action in promoting astrocyte proliferation and migration following injury and in glioma. This information furthers our understanding the function of glucocorticoid receptor in CNS injury and disease, as well as in the basic biochemical responses astrocytes undergo in response to injury and glioma pathogenesis.
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Fenofibrate ameliorates cardiac hypertrophy by activation of peroxisome proliferator-activated receptor-? partly via preventing p65-NF?B binding to NFATc4.
Mol. Cell. Endocrinol.
PUBLISHED: 02-06-2013
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Fenofibrate, a specific peroxisome proliferator-activated receptor alpha (PPAR-?) agonist, was reported to inhibit cardiac hypertrophy. However, the detailed molecular mechanisms and particularly the transcriptional components that are decisive in this process remain to be elucidated. Here we found that fenofibrate ameliorated cardiac hypertrophy in vitro and in vivo. Fenofibrate prevented nuclear translocation of nuclear factor of activated T-cells c4 (NFATc4) and p65 subunit of nuclear factor-kappa B (p65-NF?B) induced by pressure overload or angiotensinII (AngII). Moreover, fenofibrate increased the association of PPAR-? with NFATc4 in nucleus, which inhibited the interaction of NFATc4 with p65-NF?B. Our results suggested that the anti-hypertrophic effect of fenofibrate may be partially attributed to activation of PPAR-?, which decreases the binding of p65-NF?B to NFATc4 and thereby inhibits transactivation of NFATc4.
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Effects of combining methylprednisolone with rolipram on functional recovery in adult rats following spinal cord injury.
Neurochem. Int.
PUBLISHED: 02-05-2013
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Methylprednisolone (MP) has been widely used as a standard therapeutic agent for the treatment of spinal cord injury (SCI). Because of its controversial beneficial effects, the combination of MP and other pharmacological agents aimed at enhancing functional recovery is desirable. The phosphodiesterase 4 (PDE4) inhibitor rolipram has been implicated in promotion of regeneration due to elevating cAMP. In the present study, we sought to determine the effects of MP and rolipram, administered in combination, after spinal cord injury (SCI) in adult rats. Here we show that in vitro administration of rolipram and MP significantly increased neuron survival and promoted neurite outgrowth of neurons on the inhibitory substrate CSPGs by upregulation of MMP-2 expression; in vivo administration of rolipram and MP inhibited CSPG expression and increase CSPG digestion after rat SCI. Rolipram and MP combining treatment promoted significant neuroprotection through reduced motoneuron death, minimized lesion cavity, and increased regeneration of lesioned corticospinal tract (CST) axons beyond the lesion site after SCI. Enhanced functional recovery was also observed. Overall, our study strongly suggested that the combination treatment of MP and rolipram may represent a promising strategy for clinically applicable pharmacological therapy for rapid initiation of neuroprotection after SCI.
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Dysfunctional co-expression network analysis of familial hypercholesterolemia.
J Cardiol
PUBLISHED: 02-04-2013
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Familial hypercholesterolemia (FH) is an inherited disorder of blood lipid metabolism characterized by high serum low-density lipoprotein cholesterol levels and premature coronary artery disease. In this study, we used a system biology approach to identify co-expressed gene pairs that were potentially involved in the progression of FH and constructed a conserved co-expression network using these genes. A total of 4232 co-expressed relationships were identified and we verified the significance by random permutation. FH patients showed differences in lipoprotein and cholesterol metabolism in circulating monocytes and lymphocytes compared to healthy controls. We hope our study could aid in understanding of FH and could provide the basis for FH biomarker identification.
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Comparison of minimally invasive percutaneous plate osteosynthesis with open reduction and internal fixation for treatment of extra-articular distal tibia fractures.
Injury
PUBLISHED: 02-02-2013
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Minimally invasive percutaneous plate osteosynthesis (MIPPO) has become a widely accepted technique to treat distal tibia fractures. However, it remains unclear whether this strategy of biological osteosynthesis with a bridge plate is superior to that of absolute stability with traditional open reduction and internal fixation (ORIF).
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High expression of cyclic nucleotide phosphodiesterase 7B mRNA predicts poor prognosis in mantle cell lymphoma.
Leuk. Res.
PUBLISHED: 01-30-2013
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In order to determine the relationship between expression of cyclic nucleotide phosphodiesterase isoform 7B (PDE7B) and mantle cell lymphoma (MCL) progression, PDE7B mRNA expression was measured by qRT-PCR in 21 untreated MCL patients with bone marrow involvement and 20 healthy donors. The expression level of PDE7B was markedly higher in MCL patients compared with normal controls (P=0.001), and the higher level of PDE7B expression was associated with unfavorable cytogenetic characteristics in MCL. It was showed that higher expression of PDE7B might be a novel unfavorable prognostic indicator in MCL, which possess important clinical significance.
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Characterization of transgenic zebrafish lines that express GFP in the retina, pineal gland, olfactory bulb, hatching gland, and optic tectum.
Gene Expr. Patterns
PUBLISHED: 01-25-2013
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Transgenic animals are powerful tools to study gene function invivo. Here we characterize several transgenic zebrafish lines that express green fluorescent protein (GFP) under the control of the LCR(RH2)-RH2-1 or LCR(RH2)-RH2-2 green opsin regulatory elements. Using confocal immunomicroscopy, stereo-fluorescence microscopy, and Western blotting, we show that the Tg(LCR(RH2)-RH2-1:GFP)(pt112) and Tg(LCR(RH2)-RH2-2:GFP)(pt115) transgenic zebrafish lines express GFP in the pineal gland and certain types of photoreceptors. In addition, some of these lines also express GFP in the hatching gland, optic tectum, or olfactory bulb. Some of the expression patterns differ significantly from previously published similar transgenic fish lines, making them useful tools for studying the development of the corresponding tissues and organs. In addition, the variations of GFP expression among different lines corroborate the notion that transgenic expression is often subjected to position effect, thus emphasizing the need for careful verification of expression patterns when transgenic animal models are utilized for research.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.