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Find video protocols related to scientific articles indexed in Pubmed.
[Clinical and laboratory characteristics of chronic active Epstein-Barr virus infection in children.]
Zhongguo Dang Dai Er Ke Za Zhi
PUBLISHED: 11-20-2014
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To study the clinical and laboratory characteristics of chronic active Epstein-Barr virus (EBV) infection (CAEBV) in children and to provide a basis for the diagnosis and treatment of CAEBV.
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A highly efficient and eco-friendly method for the synthesis of 1,3-indandione ring-fused 3-oxindoles bearing two contiguous quaternary stereocenters via an aldol reaction in aqueous media.
Org. Biomol. Chem.
PUBLISHED: 11-11-2014
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A highly efficient and environmentally benign method for the synthesis of oxindoles featuring two contiguous quaternary carbon centers via an aldol reaction starting from various 3-substituted oxindoles has been established. A wide variety of such featured multi-substituted 1,3-indandione ring-fused 3-oxindole scaffolds were obtained smoothly in good yields (up to 98%) employing the most green of solvents, namely water, as reaction medium. Furthermore, their biological activity has been preliminarily demonstrated by in vitro evaluation against human prostate cancer cells PC-3, human lung cancer cells A549 and human leukemia cells K562 by MTT-based assays, using the commercially available standard drug, cisplatin, as a positive control. Gratifyingly, compounds , , and exhibited the best levels of in vitro inhibitory activity against human leukemia cells K562, which were almost 2.0, 2.8, 2.5 and 2.2 times, respectively, the activity of the positive control, cisplatin. Compound had 2.7 times the activity of the positive control, cisplatin, against PC-3 cancer cells, and , and showed levels of in vitro inhibitory activity against PC-3 cancer cells that were comparable to that of cisplatin. Compounds , and had good inhibitory ability against human lung cancer cells A549. The results indicated that 1,3-indandione ring-fused 3-oxindole analogs may be useful leads for further biological screenings.
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[Source and contamination of polycyclic aromatic hydrocarbons in surface soil in karst underground river basin].
Huan Jing Ke Xue
PUBLISHED: 10-24-2014
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Surface soil (0-20 cm) from various agricultural sites in Laolongdong underground river basin was collected to determine the concentrations, compositional profiles, and sources of 16 priority polycyclic aromatic hydrocarbons (PAHs). PAHs were measured by GC/MC. The total concentrations of PAH16 ranged from 277-3 301 ng x g(-1), with a mean of 752.6 ng x g(-1) +/- 635.5 ng x g(-1), and 57%, 29% and 14% of soil samples were slightly, moderately and heavily polluted by PAHs, respectively. The PAH compositional profiles were dominated by 2,3 ring compounds, which accounted for 28.72% -72.68% (a mean of 48.20%) of the total PAHs, while 4 ring and 5,6 ring PAHs accounted for an average of 7.77% and 34.03%, respectively. Soil organic matter (SOM) was found to be significantly correlated with the 16 PAHs and total PAHs. However, pH value was slightly correlated with the 16 PAHs and total PAHs. Isomer pair ratios and Principal component analysis (PCA) suggested vehicles, coal, petroleum and biomass combustion as the main sources of PAHs, and another major source was petroleum.
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The impact of IKZF1 deletion on the prognosis of acute lymphoblastic leukemia: An updated meta-analysis.
Cancer Biomark
PUBLISHED: 10-23-2014
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Various studies have reported that IKZF1 deletion (IKZF1-d) is a poor prognostic factor for acute lymphoblastic leukemia (ALL) patients, however they do not agree on the level of significance for this deletion.
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Bats as the Main Prey of Wintering Long-eared Owl in Beijing: Integrating Biodiversity Protection and Urban Management.
Integr Zool
PUBLISHED: 10-16-2014
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The loss of biodiversity from urbanized areas is one of the major environmental problems challenging policy makers throughout the world. Solutions to this problem are urgently required in China. We carried out a case study of wintering long-eared owls (Asio otus Linnaeus, 1758) and their main prey to illustrate the negative effects of urbanization combined with ineffective conservation of biodiversity in Beijing. Field monitoring of owl numbers at two roosting sites from 2004 to 2012 showed that the owl population had fallen rapidly in metropolitan Beijing. Analysis of pellet contents identified only seven individuals of two species of shrew. The majority of mammalian prey comprised four bat and seven rodent species making up 29.3% and 29.5% of the prey items, respectively. Prey composition varied significantly among years at the two sample sites. At the urban site the consumption of bats and rodents declined gradually over time, while predation on birds increased. In contrast, at the suburban site the prey composition showed an overall decrease in the number of bats, a sharp increase and a subsequent decrease in bird prey, and the number of rodent prey fell to a low point. Rapid development of real estate and inadequate green-field management in city parks resulted in negative effects on the birds and small mammal habitat of urban areas in Beijing. We suggest that measures to conserve biodiversity should be integrated into future urban planning to maintain China's rich biodiversity while also achieving sustainable economic development. This article is protected by copyright. All rights reserved.
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Versatile palladium-catalyzed C-H olefination of (hetero)arenes at room temperature.
Chem. Commun. (Camb.)
PUBLISHED: 09-27-2014
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The room-temperature oxidative C-H/C-H cross-couplings between (hetero)arenes and alkenes, coumarins or quinones have been reported by using a highly electrophilic palladium species [Pd(TFA)2], generated in situ from Pd(OAc)2 and TFA, as the catalyst and cheap (NH4)2S2O8 as the oxidant under air.
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Comparative study of radial head resection and prosthetic replacement in surgical release of stiff elbows.
Int Orthop
PUBLISHED: 09-21-2014
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Elbow trauma can compromise the arc of elbow flexion and forearm rotation. This study aimed at comparing the outcomes of radial head resection and prosthetic replacement in the surgical release of post traumatic elbow stiffness and associated restriction in forearm rotation.
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Network-Based Robust H?/H? Control for Linear Systems With Two-Channel Random Packet Dropouts and Time Delays.
IEEE Trans Cybern
PUBLISHED: 09-16-2014
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This paper focuses on the robust output feedback H?/H? control issue for a class of discrete-time networked control systems with uncertain parameters and external disturbance. Sensor-to-controller and controller-to-actuator packet dropouts and time delays are considered simultaneously. According to the stochastic characteristic of the packet dropouts and time delays, a model based on a Markov jump system framework is proposed to randomly compensate for the adverse effect of the two-channel packet dropouts and time delays. To analyze the robust stability of the resulting closed-loop system, a Lyapunov function is proposed, based on which sufficient conditions for the existence of the H?/H? controller are derived in terms of linear matrix inequalities, ensuring robust stochastic stability as well as the prescribed H? and H? performance. Finally, an angular positioning system is exploited to demonstrate the effectiveness and applicability of the proposed design strategy.
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Visualized detection of melamine in milk by supramolecular hydrogelations.
Chem. Commun. (Camb.)
PUBLISHED: 09-13-2014
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We reported a visualized detection system for melamine based on supramolecular dydrogelations.
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Diverse Epigenetic Mechanisms of Human Disease.
Annu. Rev. Genet.
PUBLISHED: 09-05-2014
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Epigenetic control of gene expression programs is essential for normal organismal development and cellular function. Abrogation of epigenetic regulation is seen in many human diseases, including cancer and neuropsychiatric disorders, where it can affect disease etiology and progression. Abnormal epigenetic profiles can serve as biomarkers of disease states and predictors of disease outcomes. Therefore, epigenetics is a key area of clinical investigation in diagnosis, prognosis, and treatment. In this review, we give an overarching view of epigenetic mechanisms of human disease. Genetic mutations in genes that encode chromatin regulators can cause monogenic disease or are incriminated in polygenic, multifactorial diseases. Environmental stresses can also impact directly on chromatin regulation, and these changes can increase the risk of, or directly cause, disease. Finally, emerging evidence suggests that exposure to environmental stresses in older generations may predispose subsequent generations to disease in a manner that involves the transgenerational inheritance of epigenetic information. Expected final online publication date for the Annual Review of Genetics Volume 48 is November 23, 2014. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
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Effect of Cryotherapy after Elbow Arthrolysis: A Prospective, Single-blinded, Randomized Controlled Study.
Arch Phys Med Rehabil
PUBLISHED: 09-03-2014
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To investigate the effect of cryotherapy after elbow arthrolysis on elbow pain, blood loss, analgesic consumption, range of motion and long-term elbow function.
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Corticosteroid administration is associated with improved outcome of patients presenting high inflammatory cytokine levels during septic shock.
Pediatr Blood Cancer
PUBLISHED: 08-30-2014
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This study aimed to investigate the corticosteroid effects on pediatric hematology/oncology patients with septic shock.
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Complete mitochondrial genome of Eagle Owl (Bubo bubo, Strigiformes; Strigidae) from China.
Mitochondrial DNA
PUBLISHED: 08-27-2014
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Abstract In the present study, the complete mitochondrial genome sequence of Bubo bubo using PCR amplification, sequencing and assembling has been obtained for the first time. The total length of the mitochondrial genome was 16,250??bp, with the base composition of 29.88% A, 34.16% C, 14.35% G, and 21.58% T. It contained 37 genes (2 ribosomal RNA genes, 13 protein-coding genes and 22 transfer RNA genes) and a major non-coding control region (D-loop region). The complete mitochondrial genome sequence of Bubo bubo provides an important data set for further investigation on the phylogenetic relationships within Strigiformes.
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[Bioinformatics analysis of the expansin gene family in rice].
Yi Chuan
PUBLISHED: 08-22-2014
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Expansin refers to a family of nonenzymatic proteins found in the plant cell wall with important roles in plant cell growth, developmental processes, and resistance to stress. Whole rice genome sequencing revealed that it contains 58 expansin genes, which belong to 4 subfamilies (A (34), B (19), LA (4) and LB (1)). All the genes were located on 10 of 12 rice chromosomes where several subfamily members clustered. Each of expansin genes ranged from 687 bp to 1128 bp in size. Sequence alignment showed that all expansins had three structural domains with two conserved amino acids of cystine in N-terminus and tryptophan in C-terminus. The amino acid identity of members among different subfamilies was less than 35%, while that among the same subfamily was more than 35%. Most genes of A subfamily had 1 or 2 introns, while genes of B, LA and LB subfamily had 3, 4 and 4 introns, respectively. Statistics analysis of codon usage showed that expansins in rice have 26 high-frequency codons which are more biased than those in other species. These bioinformatics findings will be helpful for the further study of the function and evolution of expansin genes.
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A pro-inflammatory role for Th22 cells in Helicobacter pylori-associated gastritis.
Gut
PUBLISHED: 08-18-2014
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Helper T (Th) cell responses are critical for the pathogenesis of Helicobacter pylori-induced gastritis. Th22 cells represent a newly discovered Th cell subset, but their relevance to H. pylori-induced gastritis is unknown.
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How substrate specificity is imposed on a histone demethylase--lessons from KDM2A.
Genes Dev.
PUBLISHED: 08-17-2014
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Histone lysine methylation and demethylation regulate histone methylation dynamics, which impacts chromatin structure and function. To read and erase the methylated histone residues, lysine demethylases must specifically recognize the histone sequences and methylated sites and discriminate the degree of these methylations. In this issue of Genes & Development, Cheng and colleagues (pp. 1758-1771) determine a crystal structure of histone lysine demethylase KDM2A that specifically targets lower degrees of H3K36 methylation. The results reveal the structural basis for H3K36 substrate specificity and suggest mechanisms of Lys36 demethylation. This KDM2A-H3K36 complex structure, coupled with functional studies, provides needed insight into the process and regulation of histone demethylation.
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Preparation and antitumor effect of a toxin-linked conjugate targeting vascular endothelial growth factor receptor and urokinase plasminogen activator.
Exp. Biol. Med. (Maywood)
PUBLISHED: 08-14-2014
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The aberrant signaling activation of vascular endothelial growth factor receptor (VEGFR) and urokinase plasminogen activator (uPA) is a common characteristic of many tumors, including lung cancer. Accordingly, VEGFR and uPA have emerged as attractive targets for tumor. KDR (Flk-1/VEGFR-2), a member of the VEGFR family, has been recognized as an important target for antiangiogenesis in tumor. In this study, a recombinant immunotoxin was produced to specifically target KDR-expressing tumor vascular endothelial cells and uPA-expressing tumor cells and mediate antitumor angiogenesis and antitumor effect. Based on its potent inhibitory effect on protein synthesis, Luffin-beta (L?) ribosome-inactivating protein was selected as part of a recombinant fusion protein, a single-chain variable fragment against KDR (KDRscFv)-uPA cleavage site (uPAcs)-L?-KDEL (named as KPLK). The KDRscFv-uPAcs-L?-KDEL (KPLK) contained a single-chain variable fragment (scFv) against KDR, uPAcs, L?, and the retention signal for endoplasmic reticulum proteins KDEL (Lys-Asp-Glu-Leu). The KPLK-expressing vector was expressed in Escherichia coli, and the KPLK protein was isolated with nickel affinity chromatography and gel filtration chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis test demonstrated KPLK was effectively expressed. Result of in vitro cell viability assay on non-small cell lung cancer (NSCLC) H460 cell line (uPA-positive cell) revealed that KPLK significantly inhibited cell proliferation, induced apoptosis, and accumulated cells in S and G2/M phases, but the normal cell line (human submandibular gland cell) was unaffected. These effects were enhanced when uPA was added to digest KPLK to release L?. For in vivo assay of KPLK, subcutaneous xenograft tumor model of nude mice were established with H460 cells. Growth of solid tumors was significantly inhibited in animals treated with KPLK up to 21 days, tumor weights were decreased, and the expression of angiogenesis marker CD31 was downregulated; meanwhile, the apoptosis-related protein casspase-3 was upregulated. These results suggested that the recombinant KPLK may have therapeutic applications on tumors, especially uPA-overexpressing ones.
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Small Bowel Endoscopy Diagnostic Yield and Reasons of Obscure GI Bleeding in Chinese Patients.
Gastroenterol Res Pract
PUBLISHED: 08-11-2014
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Aim. To investigate the diagnostic yield and etiologies of patients with obscure gastrointestinal bleeding (OGIB) using capsule endoscopy (CE) or double-balloon enteroscopy (DBE). Method. We studied the data of 532 consecutive patients with OGIB that were referred to Xinqiao Hospital in Chongqing from December 2005 to January 2012. A lesion that was believed to be the source of the bleeding (ulceration, mass lesion, vascular lesion, visible blood, inflammation, or others) was considered to be a positive finding. We analyzed the diagnostic yield of CE and SBE and the etiologies of OGIB. Result. CE and SBE have similar diagnostic yields, at 71.9% (196/231) and 71.8% (251/304), respectively. The most common etiology was erosions/ulceration (27.1%) followed by mass lesion (19.4%) and angiodysplastic/vascular lesions (13.9%). By stratified analysis, we found that erosions/ulceration (27.1%) was the most common etiology for the 21-40-year age group. Mass lesion was the most common etiology in the 41-60-year age group. However, in the >60 years age group, angiodysplastic/vascular lesions were significantly increased compared with the other groups, even though erosions/ulceration was most common. Conclusion. In this study, we found that CE and SBE have similar diagnostic yields and erosions/ulceration was the most common reason for OGIB, followed by mass lesion and angiodysplasias.
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Polyploid giant cancer cells with budding and the expression of cyclin E, S-phase kinase-associated protein 2, stathmin associated with the grading and metastasis in serous ovarian tumor.
BMC Cancer
PUBLISHED: 08-08-2014
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We previously reported that polyploid giant cancer cells (PGCCs) exhibit cancer stem cell properties and express cell cycle-related proteins. HEY PGCCs induced by cobalt chloride generated daughter cells and the daughter cells had a strong migratory and invasive ability. This study is to compare the expression of cyclin E, S-phase kinase-associated protein 2 (SKP2), and stathmin between PGCCs with budding and control HEY cells, and determine the clinicopathological significance of cell cycle-related protein expression in ovarian tumors.
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Endoscopic submucosal dissection for superficial esophageal cancer with near-circumferential lesions: our experience with 40 patients.
Surg Endosc
PUBLISHED: 08-02-2014
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Nowadays, there are few reports indicating whether early esophageal cancers (EsC) with near-circumferential lesions are still appropriate for the endoscopic submucosal dissection (ESD) procedure.
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?-? Stacking Induced Enhanced Molecular Solubilization, Singlet Oxygen Production, and Retention of a Photosensitizer Loaded in Thermosensitive Polymeric Micelles.
Adv Healthc Mater
PUBLISHED: 07-29-2014
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Cancer photodynamic therapy (PDT) by photosensitizers (PS)-loaded polymeric micelles (PM) is hampered by the tendency of PS to aggregate in PM and/or by premature release of PS in the blood circulation. In the present study, aromatic thermosensitive PM, characterized by ?-? stacking interaction, are used to encapsulate an axially solketal-substituted silicon phthalocyanine (Si(sol)2 Pc) with enhanced loading capacity, smaller size, and significantly improved retention of Si(sol)2 Pc compared with systems based on thermosensitive PM lacking aromatic groups. Interestingly, Si(sol)2 Pc is much less prone to aggregation in the aromatic PM, i.e., the amount of Si(sol)2 Pc that could be encapsulated without aggregation is 330 times higher in the aromatic PM than in the nonaromatic PM. Furthermore, Si(sol)2 Pc in the aromatic PM in a molecularly dissolved (non-aggregated) form displays three times more efficient singlet oxygen production than Si(sol)2 Pc aggregated in the non-aromatic PM. As a result, the photocytotoxicity of Si(sol)2 Pc-loaded aromatic PM to B16F10 cells is increased, compared with that of the non-aromatic PM, while no significant cytotoxicity is observed in the dark. Fluorescence-activated cell sorting (FACS) and confocal laser scanning microscopy (CLSM) analysis shows cell uptake of Si(sol)2 Pc loaded in the aromatic PM, and the Si(sol)2 Pc is taken up by the cells together with the micelles. The efficient singlet oxygen production of Si(sol)2 Pc dissolved in the aromatic PM makes it an interesting formulation for cancer PDT.
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The lncRNA PCAT29 inhibits oncogenic phenotypes in prostate cancer.
Mol. Cancer Res.
PUBLISHED: 07-16-2014
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Long noncoding RNAs (lncRNA) have recently been associated with the development and progression of a variety of human cancers. However, to date, the interplay between known oncogenic or tumor-suppressive events and lncRNAs has not been well described. Here, the novel lncRNA, prostate cancer-associated transcript 29 (PCAT29), is characterized along with its relationship to the androgen receptor. PCAT29 is suppressed by DHT and upregulated upon castration therapy in a prostate cancer xenograft model. PCAT29 knockdown significantly increased proliferation and migration of prostate cancer cells, whereas PCAT29 overexpression conferred the opposite effect and suppressed growth and metastases of prostate tumors in chick chorioallantoic membrane assays. Finally, in prostate cancer patient specimens, low PCAT29 expression correlated with poor prognostic outcomes. Taken together, these data expose PCAT29 as an androgen-regulated tumor suppressor in prostate cancer.
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Association of p53/p21 expression and cigarette smoking with tumor progression and poor prognosis in non-small cell lung cancer patients.
Oncol. Rep.
PUBLISHED: 07-14-2014
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Non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancer cases. Cigarette smoking is the number one risk factor which is attributed to more than four out of five cases of lung cancers. The prognostic impact of cell cycle regulation-associated tumor suppressors including p53 and p21 for NSCLC is still controversial. In the present study, we examined p53 and p21 expression using immunoblotting in tumor and adjacent non-cancerous tissues from NSCLC patients. Moreover, tissue microarrays (TMAs) including 150 specimens was used to examine p53 and p21 expression by immunohistochemical staining (IHC). The association between p53/p21 and various clinicopathological characteristics was evaluated. Kaplan-Meier overall survival was used to analyze the association between p53/p21 expression and prognosis of NSCLC patients, as well as the association of cigarette smoking with p53/p21 expression and prognosis. The results of the immunoblotting showed that expression of p53 and p21 in tumor tissues was significantly higher than that in the matched adjacent non-cancerous tissues (P<0.001 and P<0.05, respectively). The IHC results showed that 50.67% of the cases had high expression of p21; however, the percentage of patients having high expression of p53 was 31.3%. Univariate and Cox regression models were used to evaluate the factors related to prognosis with p53 and p21 expression. Multivariate analysis indicated that p53 expression was an independent prognostic factor for NSCLC (P=0.005), while p21 could not serve as an independent prognostic factor (P=0.123). In addition, smoking history was closely related to lung cancer risk (P=0.041), but could not be an independent assessment factor (P=0.740). In this study, we further demonstrated the association of p53/p21 expression and cigarette smoking. Our results suggest that cigarette smoking and overexpression of p53 or p21 are associated with poor prognosis. The combination of p53/p21 expression and smoking history may be a useful biomarker for tumor progression and prognosis of NSCLC patients.
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NRT test in auditory neuropathy patients with cochlear implants.
Acta Otolaryngol.
PUBLISHED: 06-18-2014
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In patients with auditory neuropathy (AN), waveforms of neural response telemetry (NRT) could be present, showing characteristics of low incidence, low differentiation, and large variation.
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The Morphology and Electrophysiology of the Cochlea of the Miniature Pig.
Anat Rec (Hoboken)
PUBLISHED: 06-04-2014
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Objective: To report the cochlear morphology and electrophysiology of Chinese experimental miniature pigs. Methods: Twenty Chinese experimental miniature pigs were used in this study. Auditory brainstem responses (ABR), cochlear endolymphatic potentials (EP), and the potassium concentrations of cochlear endolymph were recorded. Hair cell morphology was examined using electron microscopy. Results: The capsule of cochlea of the miniature pig has three and one-half turns which contains a 39 mm long membranous labyrinth. The organ of Corti in the labyrinth encompasses three rows of outer hair cells and one row of inner hair cells. The stereocilia of the hair cells in the apical turn of the cochlea were significantly longer than those in the basal turn. The vestibular apparatus consists of three semicircular canals and the otolith organs. The average threshold of the ABR was 35 - 45 dB SPL (n = 20) from 4 to 32 kHz. There was no significant difference in the threshold or latency of the ABR between 1-day-old and 30-day-old miniature pigs. The average EP value was 77.3 ± 14 mV (n = 9) and the average potassium concentration was 147.1 ± 13 mM (n = 5) recorded from the second turn of the cochlea. Conclusion: These studies on the cochlear morphology and electrophysiology of the miniature pigs help to establish the Chinese experimental miniature pig as an animal model for future studies in otology and audiology. This article is protected by copyright. All rights reserved.
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Self-assembling choline mimicks with enhanced binding affinities to C-LytA protein.
Sci Rep
PUBLISHED: 06-03-2014
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Streptococcus pneumoniae (pneumococcus) causes multiple illnesses in humans. Exploration of effective inhibitors with multivalent attachment sites for choline-binding modules is of great importance to reduce the pneumococcal virulence. In this work, we successfully developed two self-assembling choline mimicks, Ada-GFFYKKK' and Nap-GFFYKKK', which have the abilities to self-assemble into nanoparticles and nanofibers, respectively, yielding multivalent architectures. Additionally, the best characterized choline-binding module, C-terminal moiety of the pneumococcal cell-wall amidase LytA (C-LytA) was also produced with high purity. The self-assembling Ada-GFFYKKK' and Nap-GFFYKKK' show strong interactions with C-LytA, which possess much higher association constant values to the choline-binding modules as compared to the individual peptide Fmoc-K'. This study thus provides a self-assembly approach to yield inhibitors that are very promising for reducing the pneumococcal virulence.
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Phase II study of Afatinib as third-line treatment for patients in Korea with stage IIIB/IV non-small cell lung cancer harboring wild-type EGFR.
Oncologist
PUBLISHED: 05-27-2014
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This phase II single-arm trial evaluated afatinib, an irreversible inhibitor of the ErbB receptor family as third-line treatment of Korean patients with advanced non-small cell lung cancer (NSCLC) and tumors with wild-type EGFR. Currently, no standard therapy exists for these patients.
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Vitamin D, parathyroid hormone and risk factors for coronary artery disease in a Chinese elderly population.
J Cardiovasc Med (Hagerstown)
PUBLISHED: 05-16-2014
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Low vitamin D status has been shown to be associated with coronary artery disease; most studies have involved in adults, but few have involved elderly people. We planned to research the association between vitamin D, parathyroid hormone (PTH) and coronary artery disease in elderly people.
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BS69/ZMYND11 Reads and Connects Histone H3.3 Lysine 36 Trimethylation-Decorated Chromatin to Regulated Pre-mRNA Processing.
Mol. Cell
PUBLISHED: 05-05-2014
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BS69 (also called ZMYND11) contains tandemly arranged PHD, BROMO, and PWWP domains, which are chromatin recognition modalities. Here, we show that BS69 selectively recognizes histone variant H3.3 lysine 36 trimethylation (H3.3K36me3) via its chromatin-binding domains. We further identify BS69 association with RNA splicing regulators, including the U5 snRNP components of the spliceosome, such as EFTUD2. Remarkably, RNA sequencing shows that BS69 mainly regulates intron retention (IR), which is the least understood RNA alternative splicing event in mammalian cells. Biochemical and genetic experiments demonstrate that BS69 promotes IR by antagonizing EFTUD2 through physical interactions. We further show that regulation of IR by BS69 also depends on its binding to H3K36me3-decorated chromatin. Taken together, our study identifies an H3.3K36me3-specific reader and a regulator of IR and reveals that BS69 connects histone H3.3K36me3 to regulated RNA splicing, providing significant, important insights into chromatin regulation of pre-mRNA processing.
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Endoscopic treatment of delayed colon perforation: the enteroscopy overtube approach.
Endoscopy
PUBLISHED: 04-28-2014
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Delayed perforation is a rare complication of therapeutic colonoscopy, and it is severe and sometimes lethal. This paper reports on a new minimally invasive method for the treatment of delayed colonic perforation.
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[Variation characteristics and environmental significant of trace elements under rainfall condition in karst groundwater].
Huan Jing Ke Xue
PUBLISHED: 04-12-2014
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Chemical dynamics of Qingmuguan karst groundwater system were continuously monitored during the rainfall events. A series of high-resolution concentrations data on trace elements, such as barium, strontium, iron, manganese, aluminum, and other major elements were acquired. Correlation analysis and analysis of concentration curve were employed to identify the sources and migration path of the trace elements. And the formation process of trace elements in groundwater was discussed with the geological background of underground river basin. Research shows that barium and strontium derived from carbonate dissolution appeared to be stored in features such as fissures and pores. These two ions were recharged into the underground river by diffusion during precipitation, which resulted in small changes in the their concentration. However total iron, total manganese and aluminum derived from soil erosion varied relatively widely with strong response to rainfall, attributing to the migration of total iron and aluminum with overland flow to recharge the subterranean river directly via sinkholes while total manganese via soil-rock porous media. The results showed that concentrations of all the five trace elements were below 1 mg x L(-1), and the highest concentrations of total iron, total manganese and aluminum exceeded the limit of drinking water. To some extent, the concentrations of total iron and aluminum may be an indicator for soil erosion and water quality.
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Frequent discordance between ERG gene rearrangement and ERG protein expression in a rapid autopsy cohort of patients with lethal, metastatic, castration-resistant prostate cancer.
Prostate
PUBLISHED: 04-08-2014
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ERG rearrangements in localized prostate cancer can be detected with high sensitivity and specificity by immunohistochemistry (IHC). However, recent data suggest that ERG IHC may be less sensitive for ERG rearrangements in castration-resistant prostate cancer (CRPC). Thus, we sought to examine ERG protein expression in a cohort of rapid autopsy patients with lethal metastatic CRPC (mCRPC).
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Vitamin D and nifedipine in the treatment of Chinese patients with grades I-II essential hypertension: a randomized placebo-controlled trial.
Atherosclerosis
PUBLISHED: 03-28-2014
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Low vitamin D status has been shown to be associated with hypertension. We planned to research the effect of vitamin D and nifedipine in the treatment of patients with essential hypertension.
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Resistin might not be a risk factor for carotid artery atherosclerosis in elderly Chinese males.
J Geriatr Cardiol
PUBLISHED: 03-04-2014
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To investigate the correlation between the serum resistin level and carotid artery atherosclerosis in elderly Chinese males.
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CD64 expression is increased in patients with severe acute pancreatitis: clinical significance.
Gut Liver
PUBLISHED: 02-24-2014
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Upregulated CD64 expression on neutrophils is the most useful marker for acute bacterial infections and systemic inflammation. However, it is unknown whether CD64 is involved in the pathogenesis of acute pancreatitis (AP). This study was designed to determine whether CD64 is implicated in severe acute pancreatitis (SAP), and thus, is a suitable marker for SAP.
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Parity and pancreatic cancer risk: evidence from a meta-analysis of twenty epidemiologic studies.
Sci Rep
PUBLISHED: 02-17-2014
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Multiple studies have hypothesized parity is associated with pancreatic cancer risk but obtained conflicting results. We conducted a meta-analysis (including a dose-response approach) of current available epidemiologic studies to investigate the association between parity and risk of pancreatic cancer. Ten cohort studies and ten case-control studies including 8205 cases were eligible for inclusion. The combined RR (relative risk) of pancreatic cancer for the parous vs. nulliparous was 0.91 (95% CI, confidence interval = 0.85-0.97, I(2) = 39.0%, P(h) = 0.01). We observed an inverse association between giving birth to two children pancreatic cancer risk with RR of 0.86 (95% CI = 0.80-0.93, I(2) = 8.7%, P(h) = 0.36). And no evidence supported there was non-linear (P = 0.33) or linear relationship (P = 0.14) between number of parity and risk of pancreatic cancer. Findings from this meta-analysis indicate that giving birth to two children has the lowest pancreatic cancer risk, mechanism of this protective effect needs further investigation.
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Roles of the calcium sensing receptor in digestive physiology and pathophysiology (review).
Int. J. Oncol.
PUBLISHED: 02-14-2014
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Calcium participates in most of the biological processes in the human body. The calcium sensing receptor (CaSR), as an important regulator of calcium homeostasis, is expressed in all of the organs of the digestive system. CaSR plays a key role in gastrointestinal physiological function and in the occurrence of digestive disease. For example, the inactivation or mutation of the CaSR gene usually leads to one of several disorders of calcium metabolism. High dietary Ca2+ may stimulate CaSR activation and could both inhibit tumor development and increase the chemotherapeutic sensitivity of cancer cells in colon cancer tissues. Further, CaSR has also been reported to have a potential role in the treatment for diarrheal diseases and the form of pancreatitis that is associated with carbonate stones. Therefore, CaSR is an important target for treating digestive diseases, and the calcimimetics (CaSR agonist) have been confirmed as practical, feasible and effective clinical therapies for hyperparathyroidism. This review intends to explore the role of CaSR in digestive physiology and pathophysiology as well as current treatments utilizing CaSR?based therapeutics.
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The non-reverse transcriptase activity of the human telomerase reverse transcriptase promotes tumor progression (review).
Int. J. Oncol.
PUBLISHED: 02-14-2014
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In human cancer, high expression of telomerase is correlated with tumor aggressiveness and metastatic potential. Human telomerase reverse transcriptase (hTERT), which regulates telomere length, can promote tumor development. Most research on hTERT has been focused on its crucial function of telomere maintenance. However, there are many phenomena that cannot be explained by its reverse transcriptase activity. Accumulating evidence suggests that hTERT has functions independent of its protective function at the telomere ends, such as increasing the anti-apoptotic capacity of cells, enhancing DNA repair, maintaining stem cells and regulating gene expression. This review will provide an update on the non-reverse transcriptase activity of hTERT and its contribution to tumor formation, metastasis and cancer stem cell maintenance. Repression of the non-reverse transcriptase activity of hTERT may be a new strategy for tumor therapy.
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Synthesis, characterization and in vitro and in vivo investigation of C3F8-filled poly(lactic-co-glycolic acid) nanoparticles as an ultrasound contrast agent.
Mol Med Rep
PUBLISHED: 02-06-2014
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The present study aimed to prepare perfluoropropane (C3F8)-filled poly(lactic-co-glycolic acid) (PLGA) nanoparticles and investigate the feasibility of using PLGA nanoparticles as an ultrasound contrast agent. The PLGA nanoscale ultrasound contrast agent was prepared using a modified double-emulsion solvent evaporation method. Camphor in the form of a sublimable porogen was added to render the nanoparticles hollow and enable C3F8 gas introduction. Various physicochemical properties of PLGA nanoparticles, including morphology, size and dispersion, were analyzed by electron microscopy and dynamic laser scattering. In vitro ultrasound imaging of C3F8-filled PLGA nanoparticles was also investigated under various imaging conditions. Further in vivo ultrasound imaging was conducted on male rats following intratesticular injection of PLGA nanoparticles. C3F8-filled PLGA nanoparticles with a mean diameter of 152.0±58.08 nm were obtained. Electron microscopy revealed spherical-shaped nanoparticles with smooth surfaces, a capsular morphology and a large hollow within. In vitro ultrasound imaging of hollow PLGA nanoparticles indicated marked signal enhancement. Local intensity of the acoustical signal continued to increase during PLGA-nanoparticle injection into the testicle and the ability of hollow PLGA nanoparticles to enhance ultrasound imaging in vivo was demonstrated. The enhancement image of testicular tissue following injection with C3F8-filled PLGA nanoparticles was sustained for a minimum of five minutes. In conclusion, the hollow C3F8-filled PLGA nanoparticles were demonstrated to have potential for applications as a novel ultrasound contrast agent.
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A chromatin-dependent role of the fragile X mental retardation protein FMRP in the DNA damage response.
Cell
PUBLISHED: 02-04-2014
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Fragile X syndrome, a common form of inherited intellectual disability, is caused by loss of the fragile X mental retardation protein FMRP. FMRP is present predominantly in the cytoplasm, where it regulates translation of proteins that are important for synaptic function. We identify FMRP as a chromatin-binding protein that functions in the DNA damage response (DDR). Specifically, we show that FMRP binds chromatin through its tandem Tudor (Agenet) domain in vitro and associates with chromatin in vivo. We also demonstrate that FMRP participates in the DDR in a chromatin-binding-dependent manner. The DDR machinery is known to play important roles in developmental processes such as gametogenesis. We show that FMRP occupies meiotic chromosomes and regulates the dynamics of the DDR machinery during mouse spermatogenesis. These findings suggest that nuclear FMRP regulates genomic stability at the chromatin interface and may impact gametogenesis and some developmental aspects of fragile X syndrome.
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Vasoactive intestinal peptide receptor-based imaging and treatment of tumors (Review).
Int. J. Oncol.
PUBLISHED: 01-24-2014
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Vasoactive intestinal peptide receptors (VIPRs) are members of the G-protein-coupled receptor superfamily. These receptors are overexpressed in many common malignant tumors and play a major role in the progression and angiogenesis of a number of malignancies. Therefore, VIPRs may be a valuable target for the molecular imaging of tumors and therapeutic interventions. The specific natural ligand or its analogs can be labeled with a radionuclide and used for tumor receptor imaging, which could be used to visualize VIPR-related surface protein expression in vivo and to monitor the in vivo effects of molecular drugs on tumors. Moreover, the involvement of VIPRs in malignant transformation and angiogenesis renders them potential therapeutic targets for cancer treatment. A variety of VIP antagonists and cytotoxic VIP conjugates have been synthesized and evaluated for VIPR-targeted molecular therapy. The importance of VIPRs in tumor biology and the ability to predict responses to targeted therapy and monitor drug interventions suggest that VIP receptor-based imaging and treatment will be critical for the early diagnosis and management of cancer. Here, we review the current literature regarding VIPRs and their natural ligands and the involvement of VIPRs in tumor growth and angiogenesis, with an emphasis on the present use of VIPRs for the molecular imaging of tumors and therapies targeting VIPRs.
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Preliminary performance of cochlear implants in post-lingual patients with auditory neuropathy.
Acta Otolaryngol.
PUBLISHED: 01-20-2014
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Auditory restoration can be obtained by using cochlear implants (CIs) in post-lingual patients with auditory neuropathy (AN). However, improvements in postoperative speech recognition for these patients varied.
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Severe haze episodes and seriously polluted fog water in Ji'nan, China.
Sci. Total Environ.
PUBLISHED: 01-17-2014
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Haze episodes often hit urban cities in China recently. Here, we present several continuous haze episodes with extremely high PM2.5 levels that occurred over several weeks in early 2013 and extended across most parts of the northern and eastern China-far exceeding the Beijing-Tianjin-Hebei region. Particularly, the haze episode covered ~1 million km(2) on January 14, 2013 and the daily averaged PM2.5 concentration exceeded 360 ?g m(-3) in Ji'nan. The observed maximum hourly PM2.5 concentration in urban Ji'nan reached 701 ?g m(-3) at 7:00 am (local time) in January 30. During these haze episodes, several fog events happened and the concurrent fog water was found to be seriously polluted. For the fog water collected in Ji'nan from 10:00 pm in January 14 to 11:00 am in January 15, sulfate, nitrate, and ammonium were the major ions with concentrations of 1.54 × 10(6), 8.98 × 10(5), and 1.75 × 10(6) ?eq L(-1), respectively, leading to a low in-situ pH of 3.30. The sulfate content in the fog sample was more than 544 times as high as those observed in other areas. With examination of the simultaneously observed data on PM2.5 and its chemical composition, the fog played a role in scavenging and removing fine particles from the atmosphere during haze episodes and thus was seriously contaminated. However, the effect was not sufficient to obviously cleanse air pollution and block haze episodes.
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Advances in nanomedicine for head and neck cancer.
Front Biosci (Landmark Ed)
PUBLISHED: 01-07-2014
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The quality of life of patients with head and neck squamous cell carcinoma (HNSCC) has been improved because of advances in surgical and radiotherapeutic techniques as well as organ-preservation methods. Despite such progresses, survival rates are dismal because of frequent recurrences, distant metastases and the development of secondary primary tumors. Nanoparticles have distinct characteristics such as a high surface/volume ratio and surface charge and size that can be easily modified. Because of such inherent features, nanoparticles are used in imaging, adjuvant radiotherapy, and drug- or gene-delivery. Thus, nanomedicine holds great promise in the diagnosis and treatment of cancer. In the present review, we summarize recent advances in nanomedicine in the diagnosis and treatment of head and neck cancer. We first review the application of inorganic nanoparticles to photo-thermal and magneto-thermal radiotherapy. We also discuss the use of organic nanoparticles in drug- or gene-delivery during chemotherapy. We then review the application of inorganic nanoparticles as radiotherapy enhancers. Finally, we address the factors that influence the biodistribution of nanoparticles in vivo.
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Glutathione-triggered formation of a Fmoc-protected short peptide-based supramolecular hydrogel.
PLoS ONE
PUBLISHED: 01-01-2014
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A biocompatible method of glutathione (GSH) catalyzed disulfide bond reduction was used to form Fmoc-short peptide-based supramolecular hydrogels. The hydrogels could form in both buffer solution and cell culture medium containing 10% of Fetal Bovine Serum (FBS) within minutes. The hydrogel was characterized by rheology, transmission electron microscopy, and fluorescence emission spectra. Their potential in three dimensional (3D) cell culture was evaluated and the results indicated that the gel with a low concentration of the peptide (0.1 wt%) was suitable for 3D cell culture of 3T3 cells. This study provides an alternative candidate of supramolecular hydrogel for 3D cell culture and cell delivery.
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Transgenic tobacco plants overexpressing a grass PpEXP1 gene exhibit enhanced tolerance to heat stress.
PLoS ONE
PUBLISHED: 01-01-2014
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Heat stress is a detrimental abiotic stress limiting the growth of many plant species and is associated with various cellular and physiological damages. Expansins are a family of proteins which are known to play roles in regulating cell wall elongation and expansion, as well as other growth and developmental processes. The in vitro roles of expansins regulating plant heat tolerance are not well understood. The objectives of this study were to isolate and clone an expansin gene in a perennial grass species (Poa pratensis) and to determine whether over-expression of expansin may improve plant heat tolerance. Tobacco (Nicotiana tabacum) was used as the model plant for gene transformation and an expansin gene PpEXP1 from Poa pratensis was cloned. Sequence analysis showed PpEXP1 belonged to ?-expansins and was closely related to two expansin genes in other perennial grass species (Festuca pratensis and Agrostis stolonifera) as well as Triticum aestivum, Oryza sativa, and Brachypodium distachyon. Transgenic tobacco plants over-expressing PpEXP1 were generated through Agrobacterium-mediated transformation. Under heat stress (42°C) in growth chambers, transgenic tobacco plants over-expressing the PpEXP1 gene exhibited a less structural damage to cells, lower electrolyte leakage, lower levels of membrane lipid peroxidation, and lower content of hydrogen peroxide, as well as higher chlorophyll content, net photosynthetic rate, relative water content, activity of antioxidant enzyme, and seed germination rates, compared to the wild-type plants. These results demonstrated the positive roles of PpEXP1 in enhancing plant tolerance to heat stress and the possibility of using expansins for genetic modification of cool-season perennial grasses in the development of heat-tolerant germplasm and cultivars.
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Elevated interleukin-32 expression is associated with Helicobacter pylori-related gastritis.
PLoS ONE
PUBLISHED: 01-01-2014
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Interleukin-32 (IL-32) is a recently discovered proinflammatory cytokine involved in inflammatory diseases. We investigated the expression of IL-32 and its regulation mechanism in the inflammatory response of patients with Helicobacter pylori (H. pylori) infection.
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Macrophage migration inhibitory factor polymorphism and the risk of ulcerative colitis and Crohns disease in Asian and European populations: a meta-analysis.
BMJ Open
PUBLISHED: 12-25-2013
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To determine whether macrophage migration inhibitory factor (MIF) gene polymorphism is associated with the risk of inflammatory bowel disease (IBD).
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[Math1 gene therapy for kanamycin and furosemide-induced deaf guinea pigs].
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 12-10-2013
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To observe the morphology and function changes of cochlear hair cells before and after math1 gene injection into the cochlea of deaf guinea pigs which were induced by kanamycin and furosemide. To explore the feasibility of Math1 gene for medicine-induced deafness therapy.
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The histone demethylase LSD1/KDM1A promotes the DNA damage response.
J. Cell Biol.
PUBLISHED: 11-13-2013
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Histone demethylation is known to regulate transcription, but its role in other processes is largely unknown. We report a role for the histone demethylase LSD1/KDM1A in the DNA damage response (DDR). We show that LSD1 is recruited directly to sites of DNA damage. H3K4 dimethylation, a major substrate for LSD1, is reduced at sites of DNA damage in an LSD1-dependent manner. The E3 ubiquitin ligase RNF168 physically interacts with LSD1 and we find this interaction to be important for LSD1 recruitment to DNA damage sites. Although loss of LSD1 did not affect the initial formation of pH2A.X foci, 53BP1 and BRCA1 complex recruitment were reduced upon LSD1 knockdown. Mechanistically, this was likely a result of compromised histone ubiquitylation preferentially in late S/G2. Consistent with a role in the DDR, knockdown of LSD1 resulted in moderate hypersensitivity to ?-irradiation and increased homologous recombination. Our findings uncover a direct role for LSD1 in the DDR and place LSD1 downstream of RNF168 in the DDR pathway.
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Correlation between maximum phonetically balanced word recognition score and pure-tone auditory threshold in elder presbycusis patients over 80 years old.
Acta Otolaryngol.
PUBLISHED: 11-11-2013
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Abstract Conclusions: The maximum phonetically balanced word recognition score (PBmax) showed poor correlation with pure-tone thresholds in presbycusis patients older than 80 years. Objectives: To study the characteristics of monosyllable recognition in presbycusis patients older than 80 years of age. Methods: Thirty presbycusis patients older than 80 years were included as the test group (group 80+). Another 30 patients aged 60-80 years were selected as the control group (group 80-) . PBmax was tested by Mandarin monosyllable recognition test materials with the signal level at 30 dB above the averaged thresholds of 0.5, 1, 2, and 4 kHz (4FA) or the maximum comfortable level. The PBmax values of the test group and control group were compared with each other and the correlation between PBmax and predicted maximum speech recognition scores based on 4FA (PBmax-predict) were statistically analyzed. Results: Under the optimal test conditions, the averaged PBmax was (77.3 ± 16.7) % for group 80- and (52.0 ± 25.4) % for group 80+ (p < 0.001). The PBmax of group 80- was significantly correlated with PBmax-predict (Spearman correlation = 0.715, p < 0.001). The score for group 80+ was less statistically correlated with PBmax-predict (Spearman correlation = 0.572, p = 0.001).
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Relation of Low Vitamin D to Nonvalvular Persistent Atrial Fibrillation in Chinese Patients.
Ann Noninvasive Electrocardiol
PUBLISHED: 11-08-2013
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Low vitamin D status has been associated with increased risk of cardiovascular disease. Atrial fibrillation (AF) is the most common cardiac arrhythmia. We evaluated the association between low vitamin D and AF.
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Enoyl coenzyme a hydratase domain-containing 2, a potential novel regulator of myocardial ischemia injury.
J Am Heart Assoc
PUBLISHED: 10-11-2013
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We reported previously that Brown Norway (BN) rats are more resistant to myocardial ischemia/reperfusion (I/R) injury than are Dahl S (SS) rats. To identify the unique genes differentially expressed in the hearts of these rats, we used DNA microarray analysis and observed that enoyl coenzyme A hydratase-containing domain 2 (ECHDC2) is highly expressed (?18-fold) in the SS hearts compared with the BN hearts.
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Vibrant Soundbridge implantation via the third window in two Chinese patients with severe bilateral congenital aural atresia.
Acta Otolaryngol.
PUBLISHED: 10-09-2013
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Abstract Conclusion: In patients with undeveloped vestibular/oval windows and inaccessible round windows, Vibrant Soundbridge (VSB) implantation performed by placing the transducer into a reconstructed window on the inner tympanum wall demonstrated significant improvement in hearing and verbal communication ability. Objective: To report our surgical experience with new placement of the VSB in pediatric patients with undeveloped vestibular windows, inaccessible round windows, and severe bilateral congenital aural atresia (CAA). Methods: In two patients with bilateral CAA selected for middle ear implantation, CT scans revealed severe middle ear malformation including inaccessible round windows, absence of vestibular/oval windows, and abnormal facial nerve anatomy. The transducer of the VSB was implanted into a window drilled at the inner tympanum wall in both patients. Results: The surgery was successful. Pure-tone air conduction thresholds across the frequencies of 0.25-8 Hz were improved by 35 dB (preoperation, 69.2 dB; postactivation, 34 dB) in patient 1 and 46.6 dB (preoperation, 75.8 dB; postactivation, 24.2 dB) in patient 2. Normal hearing thresholds were achieved in the range of 1-8 kHz in both patients. A sentence recognition rate of up to 100% (65 dB SPL in a quiet room) was attained by both patients after surgery and VSB activation at 3 months postoperatively.
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Whats the Mtrr with your grandparents?
Cell Metab.
PUBLISHED: 10-08-2013
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Reduced folate levels can cause developmental defects and megaloblastic anemia. Padmanabhan et al. (2013) show that mutation in mice of a folate metabolism gene, Mtrr, which encodes for methionine synthase reductase, causes developmental defects not only in the mutant progeny, but also in genetically wild-type descendants for up to four generations.
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Airborne submicron particulate (PM1) pollution in Shanghai, China: Chemical variability, formation/dissociation of associated semi-volatile components and the impacts on visibility.
Sci. Total Environ.
PUBLISHED: 10-05-2013
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Hourly mass concentrations of water-soluble ions in PM1 and gasses (NH3, HNO3, HCl) were on-line measured with a Monitor for AeRosols and Gases Analyzer (MARGA) in Shanghai from Oct. 1 to Nov. 16, 2012. During the field campaign, 7 haze episodes (total 157h) were identified. 845h were identified as non-haze periods, excluding fog events and wet precipitation. The average mass concentration of PM1 and total water-soluble ions (TWSI) in PM1 in haze episodes were 78.9±29.9?g/m(3) and 47.2±17.2?g/m(3), 3.11 times (from 1.49 to 4.06 times) and 3.28 times (1.96 to 4.34 times) as those in non-haze periods, respectively. TWSI accounted for 60.4±18.8% of PM1 mass loading in the whole campaign. With the ascending PM1 mass concentration from 2.5 to 125.0?g/m(3) from non-haze periods to haze episodes, average contribution of TWSI to PM1 mass loading decreased from 86.1% to 54.2%, while different species altered. Contribution of NO3(-) increased from 14.0% to 26.8%, while SO4(2-) decreased from 39.5% to 15.0% and NH4(+) remained around 13.7%. Relationship of visibility with PM1 and TWSI was addressed in specific RH ranges. It was found that hourly TWSI mass concentration showed better correlation with visibility. Formation/dissociation of semi-volatiles (NH4NO3 and NH4Cl) was also investigated and demonstrated. NH4NO3 and NH4Cl tended to partition into gas phase in non-haze periods. Particularly, strong dissociation from 11:00 LT to 17:00 LT was observed. In haze episodes, HNO3 and HCl tended to react with NH3 to form particulate matters. Interestingly, we found that formation/dissociation of NH4NO3 and NH4Cl exerted great impacts on visibility. Excluding the strong dissociation hours (11:00 LT to 17:00 LT) in correlation analysis of PM1 and visibility, correlation coefficients (R(2)) increased from 0.5762 to 0.7738 at RH<50%. No significant difference was observed in other RH ranges. In addition, Strong NH3 and HNO3 reaction resulted in the enhancement of NH4NO3 mass fraction, therefore increased associated water content in PM1 under high RH condition and contributed to visibility degradation.
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In vivo delivery of Atoh1 gene to rat cochlea using a dendrimer-based nanocarrier.
J Biomed Nanotechnol
PUBLISHED: 09-11-2013
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Gene therapy is a promising clinical solution to hearing loss. However suitable gene carriers for the auditory system are currently unavailable. Given the unique structure of the inner ear, the route of delivery and gene transfer efficiency are still not optimal at present. This study presented a non-viral delivery system of in vivo delivery of Atoh1 gene (a potentially therapeutic gene for hearing loss) to rat cochlea. We treated polyamidoamine (PAMAM) dendrimers by activating and modifying with Na-carboxymethyl-beta-cyclodextrins (CM-beta-CD) in sequence. A novel gene carrier (CM-beta-CD modified activated PAMAM dendrimers, CMAP) was then constructed. CMAP nanoparticles could bind pRK5-Atoh1-EGFP plasmids to form vector-DNA complexes (dendriplexes) with a mean particle size of 132 +/- 20 nm and zeta potential of 31 +/- 3 mV. These dendriplexes were locally applied on the round window membrane and delivered to the inner ear by passive gradient permeation. Results showed that the Atoh1 gene was successfully transferred into the cells as indicated by the green fluorescence detected in the inner ear. A relatively selective gene transfer with high efficiency was achieved in the auditory hair cells but not much in other cell types in the cochlea. Auditory brainstem response was determined seven days after inoculation, indicating good tolerance. This approach may provide a novel tool for inner ear gene therapy and initiate the applications of biomaterials to treat auditory disorders.
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The G2/M regulator histone demethylase PHF8 is targeted for degradation by the anaphase-promoting complex containing CDC20.
Mol. Cell. Biol.
PUBLISHED: 08-26-2013
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Monomethylated histone H4 lysine 20 (H4K20me1) is tightly regulated during the cell cycle. The H4K20me1 demethylase PHF8 transcriptionally regulates many cell cycle genes and is therefore predicted to play key roles in the cell cycle. Here, we show that PHF8 protein levels are the highest during G2 phase and mitosis, and we found PHF8 protein stability to be regulated by the ubiquitin-proteasome system. Purification of the PHF8 complex led to the identification of many subunits of the anaphase-promoting complex (APC) associated with PHF8. We showed that PHF8 interacts with the CDC20-containing APC (APC(cdc20)) primarily during mitosis. In addition, we defined a novel, KEN- and D-box-independent, LXPKXLF motif on PHF8 that is required for binding to CDC20. Through various in vivo and in vitro assays, we demonstrate that mutations of the LXPKXLF motif abrogate polyubiquitylation of PHF8 by the APC. APC substrates are typically cell cycle regulators, and consistent with this, the loss of PHF8 leads to prolonged G2 phase and defective mitosis. Furthermore, we provide evidence that PHF8 plays an important role in transcriptional activation of key G2/M genes during G2 phase. Taken together, these findings suggest that PHF8 is regulated by APC(cdc20) and plays an important role in the G2/M transition.
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Inhibition of myeloperoxidase decreases vascular oxidative stress and increases vasodilatation in sickle cell disease mice.
J. Lipid Res.
PUBLISHED: 08-16-2013
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Activated leukocytes and polymorphonuclear neutrophils (PMN) release myeloperoxidase (MPO), which binds to endothelial cells (EC), is translocated, and generates oxidants that scavenge nitric oxide (NO) and impair EC function. To determine whether MPO impairs EC function in sickle cell disease (SCD), control (AA) and SCD mice were treated with N-acetyl-lysyltyrosylcysteine-amide (KYC). SCD humans and mice have high plasma MPO and soluble L-selectin (sL-selectin). KYC had no effect on MPO but decreased plasma sL-selectin and malondialdehyde in SCD mice. MPO and 3-chlorotyrosine (3-ClTyr) were increased in SCD aortas. KYC decreased MPO and 3-ClTyr in SCD aortas to the levels in AA aortas. Vasodilatation in SCD mice was impaired. KYC increased vasodilatation in SCD mice more than 2-fold, to ?60% of levels in AA mice. KYC inhibited MPO-dependent 3-ClTyr formation in EC proteins. SCD mice had high plasma alanine transaminase (ALT), which tended to decrease in KYC-treated SCD mice (P = 0.07). KYC increased MPO and XO/XDH and decreased 3-ClTyr and 3-nitrotyrosine (3-NO?Tyr) in SCD livers. These data support the hypothesis that SCD increases release of MPO, which generates oxidants that impair EC function and injure livers. Inhibiting MPO is an effective strategy for decreasing oxidative stress and liver injury and restoring EC function in SCD.
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In vitro and ex vivo evaluation of a multi-epitope heparinase vaccine for various malignancies.
Cancer Sci.
PUBLISHED: 07-31-2013
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Previous studies have indicated that heparanase (Hpa) might represent a candidate universal tumor-associated antigen. However, vaccine therapy targeting only one cytotoxic T lymphocyte (CTL) epitope is suboptimal in preventing cancer. In the present study, we designed heparanase multi-epitope vaccines to increase the immune response to standard single heparanase epitopes. The results showed that multi-epitope vaccines Hpa525 + 277 + 405 + 16 and Hpa8 + 310 + 315 + 363 induced higher Hpa-specific lysis of various cancer cells from different tissues in a HLA-A2-restricted and heparanase-specific manner compared with the single epitope vaccines Hpa525, Hpa277, Hpa405, Hpa16, Hpa8, Hpa310, Hpa315 and Hpa363, both in vitro and ex vivo. Heparanase multi-epitope vaccines not only induced the heparanase-specific CTL to lyse tumor cells but also increased CTL secretion of interferon-?. However, these heparanase-specific CTL did not lyse heparanase-expressing autologous lymphocytes and dendritic cells, which confirms the safety of these multi-epitope vaccines. Therefore, the present study provides theoretical evidence for the use of heparanase multi-epitope vaccines for clinical application.
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N-acetyl lysyltyrosylcysteine amide inhibits myeloperoxidase, a novel tripeptide inhibitor.
J. Lipid Res.
PUBLISHED: 07-24-2013
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Myeloperoxidase (MPO) plays important roles in disease by increasing oxidative and nitrosative stress and oxidizing lipoproteins. Here we report N-acetyl lysyltyrosylcysteine amide (KYC) is an effective inhibitor of MPO activity. We show KYC inhibits MPO-mediated hypochlorous acid (HOCl) formation and nitration/oxidation of LDL. Disulfide is the major product of MPO-mediated KYC oxidation. KYC (?4,000 ?M) does not induce cytotoxicity in bovine aortic endothelial cells (BAECs). KYC inhibits HOCl generation by phorbol myristate acetate (PMA)-stimulated neutrophils and human promyelocytic leukemia (HL-60) cells but not superoxide generation by PMA-stimulated HL-60 cells. KYC inhibits MPO-mediated HOCl formation in BAEC culture and protects BAECs from MPO-induced injury. KYC inhibits MPO-mediated lipid peroxidation of LDL whereas tyrosine (Tyr) and tryptophan (Trp) enhance oxidation. KYC is unique as its isomers do not inhibit MPO activity, or are much less effective. Ultraviolet-visible spectral studies indicate KYC binds to the active site of MPO and reacts with compounds I and II. Docking studies show the Tyr of KYC rests just above the heme of MPO. Interestingly, KYC increases MPO-dependent H?O? consumption. These data indicate KYC is a novel and specific inhibitor of MPO activity that is nontoxic to endothelial cell cultures. Accordingly, KYC may be useful for treating MPO-mediated vascular disease.
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Emerging roles for chromatin as a signal integration and storage platform.
Nat. Rev. Mol. Cell Biol.
PUBLISHED: 07-13-2013
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Cells of a multicellular organism, all containing nearly identical genetic information, respond to differentiation cues in variable ways. In addition, cells are plastic, able to execute their specialized function while maintaining the ability to adapt to environmental changes. This is achieved through multiple mechanisms, including the direct regulation of chromatin-based processes in response to stimuli. How signal transduction pathways directly communicate with chromatin to change the epigenetic landscape is poorly understood. The preponderance of covalent modifications on histone tails coupled with a relatively small number of functional outputs raises the possibility that chromatin acts as a site of signal integration and storage.
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Parallel SCF adaptor capture proteomics reveals a role for SCFFBXL17 in NRF2 activation via BACH1 repressor turnover.
Mol. Cell
PUBLISHED: 06-10-2013
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Modular cullin-RING E3 ubiquitin ligases (CRLs) use substrate binding adaptor proteins to specify target ubiquitylation. Many of the ~200 human CRL adaptor proteins remain poorly studied due to a shortage of efficient methods to identify biologically relevant substrates. Here, we report the development of parallel adaptor capture (PAC) proteomics and its use to systematically identify candidate targets for the leucine-rich repeat family of F-box proteins (FBXLs) that function with SKP1-CUL1-F-box protein (SCF) E3s. In validation experiments, we identify the unstudied F-box protein FBXL17 as a regulator of the NFR2 oxidative stress pathway. We demonstrate that FBXL17 controls the transcription of the NRF2 target HMOX1 via turnover of the transcriptional repressor BACH1 in the absence or presence of extrinsic oxidative stress. This work identifies a role for SCF(FBXL17) in controlling the threshold for NRF2-dependent gene activation and provides a framework for elucidating the functions of CRL adaptor proteins.
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A multiplex cytokine score for the prediction of disease severity in pediatric hematology/oncology patients with septic shock.
Cytokine
PUBLISHED: 05-28-2013
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Although many inflammatory cytokines are prognostic in sepsis, the utility of cytokines in evaluating disease severity in pediatric hematology/oncology patients with septic shock was rarely studied. On the other hand, a single particular cytokine is far from ideal in guiding therapeutic intervention, but combination of multiple biomarkers improves the accuracy. In this prospective observational study, 111 episodes of septic shock in pediatric hematology/oncology patients were enrolled from 2006 through 2012. Blood samples were taken for inflammatory cytokine measurement by cytometric bead array (CBA) technology at the initial onset of septic shock. Interleukin (IL)-6 and IL-10 were significantly elevated in majority of patients, while tumor necrosis factor (TNF)-? and interferon (IFN)-? were markedly increased in patients with high pediatric index of mortality 2 (PIM2) score and non-survivors. All the four cytokines paralleled the PIM2 score and differentially correlated with hemodynamic disorder and fatal outcomes. The pediatric multiplex cytokine score (PMCS), which integrated the four cytokines into one score system, was related to hemodynamic disorder and mortality as well, but showed more powerful prediction ability than each of the four cytokines. PMCS was an independent predictive factor for fatal outcome, presenting similar discriminative power with PIM2, with accuracy of 0.83 (95% CI, 0.71-0.94). In conclusion, this study develops a cytokine scoring system based on CBA technique, which performs well in disease severity and fatality prediction in pediatric hematology/oncology patients with septic shock.
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Flexible long-range loops in the VH gene region of the Igh locus facilitate the generation of a diverse antibody repertoire.
Immunity
PUBLISHED: 05-13-2013
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The immunoglobulin heavy-chain (Igh) locus undergoes large-scale contraction in pro-B cells, which facilitates VH-DJH recombination by juxtaposing distal VH genes next to the DJH-rearranged gene segment in the 3 proximal Igh domain. By using high-resolution mapping of long-range interactions, we demonstrate that local interaction domains established the three-dimensional structure of the extended Igh locus in lymphoid progenitors. In pro-B cells, these local domains engaged in long-range interactions across the Igh locus, which depend on the regulators Pax5, YY1, and CTCF. The large VH gene cluster underwent flexible long-range interactions with the more rigidly structured proximal domain, which probably ensures similar participation of all VH genes in VH-DJH recombination to generate a diverse antibody repertoire. These long-range interactions appear to be an intrinsic feature of the VH gene cluster, because they are still generated upon mutation of the E? enhancer, IGCR1 insulator, or 3 regulatory region in the proximal Igh domain.
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Characterization of Cd-, Pb-, Zn-resistant endophytic Lasiodiplodia sp. MXSF31 from metal accumulating Portulaca oleracea and its potential in promoting the growth of rape in metal-contaminated soils.
Environ Sci Pollut Res Int
PUBLISHED: 04-26-2013
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The aim of this study was to characterize the features of a Cd-, Pb-, and Zn-resistant endophytic fungus Lasiodiplodia sp. MXSF31 and to investigate the potential of MXSF31 to remove metals from contaminated water and soils. The endophytic fungus was isolated from the stem of Portulaca oleracea growing in metal-contaminated soils. The maximum biosorption capacities of MXSF31 were 3.0?×?10(3), 1.1?×?10(4), and 1.3?×?10(4) mg kg(-1) for Cd, Pb, and Zn, respectively. The biosorption processes of Cd, Pb, and Zn by MXSF31 were well characterized with the pseudo-second-order kinetic model. The biosorption isotherm processes of Pb and Zn by the fungus were fitted better with the Langmuir model, while the biosorption processes of Cd was better fitted with the Freundlich model. The biosorption process of MXSF31 was attributed to the functional groups of hydroxyl, amino, carbonyl, and benzene ring on the cell wall. The active biomass of the strain removed more Cd, Pb, and Zn (4.6?×?10(4), 5.6?×?10(5), and 7.0?×?10(4) mg kg(-1), respectively) than the dead biomass. The inoculation of MXSF31 increased the biomass of rape (Brassica napus L.), the translocation factor of Cd, and the extraction amount of Cd by rape in the Cd?+?Pb-contaminated soils. The results indicated that the endophytic fungus strain had the potential to remove heavy metals from water and soils contaminated by multiple heavy metals, and plants accumulating multiple metals might harbor diverse fungi suitable for bioremediation of contaminated media.
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Glucocorticoids can increase the survival rate of patients with severe viral hepatitis B: a meta-analysis.
Eur J Gastroenterol Hepatol
PUBLISHED: 04-02-2013
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Severe viral hepatitis B is a disease associated with significant morbidity and mortality. Clinical controlled trials show that the efficacy of treatment of severe viral hepatitis B with glucocorticoids remains debatable. Therefore, we carried out this meta-analysis to evaluate the safety, efficacy, and side effects of glucocorticoid therapy for severe viral hepatitis B.
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The Effects of Low Vitamin D on Coronary Artery Disease.
Heart Lung Circ
PUBLISHED: 02-28-2013
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Coronary Artery Disease (CAD) remains a major cause of morbidity and mortality in the world. Low vitamin D status has been shown to be associated with increased risk of developing cardiovascular disease, hypertension and obesity. We planned to research the association between low vitamin D status and the severity of CAD.
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microRNA detection in feces, sputum, pleural effusion and urine: novel tools for cancer screening (Review).
Oncol. Rep.
PUBLISHED: 02-02-2013
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microRNAs (miRNAs) are short non-coding RNA sequences that play important roles in the regulation of gene expression. They have significant regulatory functions in basic cellular processes, including differentiation, proliferation and apoptosis. miRNAs are differentially expressed in tumors, compared with normal tissues. Importantly, miRNAs are also stable and abundantly present in body fluids and feces. The high reproducibility, sensitivity and specificity of miRNAs in body fluids and feces enable miRNAs to be used as potential molecular markers for cancer screening. An increasingly large number of research studies have reported the role of miRNAs in this field. In the present review, we focused mainly on the application of detecting miRNAs in stool, sputum, pleural effusion and urine, to detect colon, lung and urological cancers, highlighting the role of miRNAs in early diagnosis and prognosis.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

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.