bluuebunny/crossref_metadata_2025 huggingface dataset:
A Large Left Ventricle Myxoma: Presenting with Epigastric Pain and Weight Loss
Authors: Fakhari Solmaz , Bilehjani Eissa
Published: December 2016

Cardiac myxomas are the most common benign tumors found in the heart. They usually appear in the left atrium. Those originating from the left ventricle (LV) are rare. Although clinical presentation may vary, dyspnea and embolism are the most commonly reported symptoms. In the present case study, a 27-year-old woman with a large myxoma originating from the left ventricular free wall is studied. She had atypical complaints, mainly epigastric discomfort, nausea, vomiting, and anorexia. She was hospitalized for acute abdomen, but subsequent investigations revealed a large myxoma that fully filled the LV and severely compromised the flow of the aortic and mitral valves. After successful emergency tumor resection, all symptoms disappeared. The uncommon presentation caused by these tumors is discussed in this study.
Hyaluromycin, a Novel Hyaluronidase Inhibitor, Attenuates Pancreatic Cancer Cell Migration and Proliferation
Authors: Kohi Shiro , Sato Norihiro , Koga Atsuhiro , Hirata Keiji , Harunari Enjuro , Igarashi Yasuhiro
Published: December 2016

Pancreatic ductal adenocarcinoma (PDAC) is characterized by accelerated production and degradation of hyaluronan (HA), a major component of extracellular matrix involved in the malignant phenotype of cancer. In particular, increased hyaluronidase (HYAL) activity plays a critical role in cancer progression, at least in part, by producing low-molecular-weight- (LMW-) HA or small fragments of HA, suggesting HYAL as a target for cancer treatment. Hyaluromycin, a new member of the rubromycin family of antibiotics, was isolated from the culture extract of a marine-derivedStreptomyces hyaluromycinias a HYAL inhibitor. We investigated the antitumor effects of hyaluromycin in PDAC cells. We examined the effects of hyaluromycin on the proliferation and migration of PDAC cells. To elucidate the mechanisms underlying the effect of hyaluromycin on PDAC cells, we examined the concentration of LMW-HA in the conditioned media after treating PDAC cells with hyaluromycin. We demonstrate that hyaluromycin inhibits proliferation and migration of PDAC cells. We also found that these antitumor effects of hyaluromycin were associated with a decreased concentration of LMW-HA and a decreased phosphorylation of ribosomal protein S6. Our results suggest that hyaluromycin is a promising new drug against this highly aggressive neoplasm.
Effectiveness of High Intensity Laser Therapy for Reduction of Pain in Knee Osteoarthritis
Authors: Angelova Anna , Ilieva Elena M.
Published: December 2016

Introduction. Osteoarthritis is the most common type of arthritis. It is the main cause of chronic musculoskeletal pain and disability among the elderly population. Aim. This is a pilot, randomized clinical study about the effect of high intensity laser therapy in patients with osteoarthritis of the knee (OA of the knee). Material and Method. 72 patients (aged between 39 and 83 years) with (clinically and radiographically proved) OA of the knee were included in the study. They were randomized in two groups: therapeutic (test) one (n=37, 65,11 ± 1,40 (mean ± SD) years old; patients were treated with HILT) and control group (n=35, 64,71 ± 1,98; patients receive sham laser). Both groups had seven sessions of treatment. VAS and dolorimetry were used for assessment of pain before and after the therapy. Pedobarometric analysis (static and dynamic) was used to assess comparatively the contact surface area and maximum pressure under the heel. Results. Pain levels measured by VAS and dolorimetry decreased significantly in the therapeutic group after seven days of treatment (p< 0,001). Conclusion. The results after seven days of treatment show more intensive and cumulative effect after the application of high intensity laser therapy in comparison to sham laser. This is the reason why HILT can be a method of choice in the treatment of gonarthrosis.
Nonmedical Use of Antihistaminergic Anxiolytics and Other Prescription Drugs among Persons with Opioid Dependence
Authors: Dahlman Disa , Abrahamsson Tove , Kral Alex H. , Hakansson Anders
Published: December 2016

Background. Nonmedical prescription drug use (NMPDU) is an increasing problem, insufficiently studied among people in opioid maintenance treatment (OMT). This study investigates the prevalence of and factors associated with NMPDU for drug classes insufficiently described in opioid-dependent populations, including antihistaminergic anxiolytics and central stimulants.Methods. Study participants were recruited at two OMT clinics in Malmo, Sweden, between October 2014 and December 2015 (N=73) and interviewed about their use, motivations for use, and acquisition and administration of prescription drugs.Results. The majority of the sample reported lifetime NMPDU: 60% for benzodiazepine-like hypnotics (z-drugs), 21% for pregabalin, 19% for stimulants, and 12%–15% for antihistaminergic anxiolytics. Lower age was associated with nonmedical benzodiazepine use (Adjusted Odds Ratio = 0.89; 95% Confidence Interval = 0.82–0.97). Illicit acquisition was reported by 61% of people using z-drugs, 46% of people using pregabalin, and 38% of people using prescription stimulants, but only by 6–10% of people using antihistaminergic anxiolytics.Conclusions. The substantial nonmedical use of pregabalin, z-drugs, and prescription stimulants found in this study suggests that clinicians should prescribe these drugs with great caution. Nonmedical use of antihistaminergic anxiolytics does not seem to be a clinical issue among people in OMT in a Swedish setting, but we propose future studies to monitor their use.
Mechanisms of Acquired Drug Resistance to the HDAC6 Selective Inhibitor Ricolinostat Reveals Rational Drug-Drug Combination with Ibrutinib
Authors: Amengual Jennifer E. , Prabhu Sathyen A. , Lombardo Maximilian , Zullo Kelly , Johannet Paul M. , Gonzalez Yulissa , Scotto Luigi , Serrano Xavier Jirau , Wei Ying , Duong Jimmy , Nandakumar Renu , Cremers Serge , Verma Akanksha , Elemento Olivier , O'Connor Owen A.
Published: December 2016

Purpose: Pan-class I/II histone deacetylase (HDAC) inhibitors are effective treatments for select lymphomas. Isoform-selective HDAC inhibitors are emerging as potentially more targeted agents. ACY-1215 (ricolinostat) is a first-in-class selective HDAC6 inhibitor. To better understand the discrete function of HDAC6 and its role in lymphoma, we developed a lymphoma cell line resistant to ACY-1215.

Experimental Design: The diffuse large B-cell lymphoma cell line OCI-Ly10 was exposed to increasing concentrations of ACY-1215 over an extended period of time, leading to the development of a resistant cell line. Gene expression profiling (GEP) was performed to investigate differentially expressed genes. Combination studies of ACY-1215 and ibrutinib were performed in cell lines, primary human lymphoma tissue, and a xenograft mouse model.

Results: Systematic incremental increases in drug exposure led to the development of distinct resistant cell lines with IC50 values 10- to 20-fold greater than that for parental lines. GEP revealed upregulation of MAPK10, HELIOS, HDAC9, and FYN, as well as downregulation of SH3BP5 and LCK. Gene-set enrichment analysis (GSEA) revealed modulation of the BTK pathway. Ibrutinib was found to be synergistic with ACY-1215 in cell lines as well as in 3 primary patient samples of lymphoma. In vivo confirmation of antitumor synergy was demonstrated with a xenograft of DLBCL.

Conclusions: The development of this ACY-1215–resistant cell line has provided valuable insights into the mechanistic role of HDAC6 in lymphoma and offered a novel method to identify rational synergistic drug combinations. Translation of these findings to the clinic is underway. Clin Cancer Res; 23(12); 3084–96. ©2016 AACR.
Targeting the ATR/CHK1 Axis with PARP Inhibition Results in Tumor Regression in BRCA-Mutant Ovarian Cancer Models
Authors: Kim Hyoung , George Erin , Ragland Ryan L. , Rafail Stavros , Zhang Rugang , Krepler Clemens , Morgan Mark A. , Herlyn Meenhard , Brown Eric J. , Simpkins Fiona
Published: December 2016

Purpose: PARP inhibition (PARPi) has modest clinical activity in recurrent BRCA-mutant (BRCAMUT) high-grade serous ovarian cancers (HGSOC). We hypothesized that PARPi increases dependence on ATR/CHK1 such that combination PARPi with ATR/CHK1 blockade results in increased cell death and tumor regression.

Experimental Design: Effects of PARPi (olaparib), CHK1 inhibition (CHK1i;MK8776), or ATR inhibition (ATRi;AZD6738) alone or in combination on survival, colony formation, cell cycle, genome instability, and apoptosis were evaluated in BRCA1/2MUT HGSOC cells. Tumor growth in vivo was evaluated using a BRCA2MUT patient-derived xenograft (PDX) model.

Results: PARPi monotherapy resulted in a decrease in BRCAMUT cell survival, colony formation and suppressed but did not eliminate tumor growth at the maximum tolerated dose (MTD) in a BRCA2MUT PDX. PARPi treatment increased pATR and pCHK1, indicating activation of the ATR–CHK1 fork protection pathway is relied upon for genome stability under PARPi. Indeed, combination of ATRi or CHK1i with PARPi synergistically decreased survival and colony formation compared with single-agent treatments in BRCAMUT cells. Notably, PARPi led to G2 phase accumulation, and the addition of ATRi or CHK1i released cells from G2 causing premature mitotic entry with increased chromosomal aberrations and apoptosis. Moreover, the combinations of PARPi with ATRi or CHK1i were synergistic in causing tumor suppression in a BRCA2MUT PDX with the PARPi–ATRi combination inducing tumor regression and in most cases, complete remission.

Conclusions: PARPi causes increased reliance on ATR/CHK1 for genome stability, and combination PARPi with ATR/CHK1i is more effective than PARPi alone in reducing tumor burden in BRCAMUT models. Clin Cancer Res; 23(12); 3097–108. ©2016 AACR.
Single-Nucleotide Polymorphisms and Cancer Risk, Tumor Recurrence, or Survival of Head and Neck Cancer Patients
Authors: Laytragoon-Lewin Nongnit , Cederblad Lena , Andersson Bengt-Åke , Olin Mattias , Nilsson Mats , Rutqvist Lars Erik , Lundgren Jan , Engström Mats , Tytor Wieslaw , Löfgren Sture , Lewin Freddi
Published: December 2016

Objective: This paper aims at studying the influence of single-nucleotide polymorphisms (SNPs) on cancer risk, tumor recurrence, and survival in head and neck (H&N) cancer patients. Methods: A total of 45 SNPs in 41 genes were investigated. A total of 174 Caucasian H&N cancer patients and 245 healthy blood donors were enrolled in the study. Results: Ten SNPs were associated with H&N cancer risk, but the identified SNPs differed among males and females. Some of the SNPs were related to immune response genes. The immune response gene SNPs were also related to survival. In particular, we noted that the tumor necrosis factor alpha (TNFα) rs1800629 could have an influence on cancer risk, tumor recurrence as well as survival. Conclusion: Genetic variation of the TNFα rs1800629 might be useful as a biomarker in clinical decision-making since it was found to be related to cancer risk, tumor recurrence, and survival of H&N cancer patients.
The Role of HMGB1 in Pial Arteriole Dilating Reactivity following Subarachnoid Hemorrhage in Rats
Authors: Xu Haoliang , Changyaleket Benjarat , Valyi-Nagy Tibor , Dull Randal O. , Pelligrino Dale A. , Schwartz David E. , Chong Zhao Zhong
Published: December 2016

High-mobility group box 1 protein (HMGB1) has been implicated in inflammatory responses, and is also associated with cerebral vasospasm after subarachnoid hemorrhage (SAH). However, there are no direct evident links between HMGB1 and cerebral vasospasm. We therefore investigated the effects of HMGB1 on pial arteriole reactivity following SAH in rats. We initially found that SAH induced a significant decrease in pial arteriole dilating responses to sciatic nerve stimulation (SNS), hypercapnia (CO2), and the topical suffusion of acetylcholine (ACh), adenosine (ADO), and s-nitroso-N-acetylpenicillamine (SNAP) over a 7-day period after SAH. The percent change of arteriolar diameter was decreased to the lowest point at 48 h after SAH, in response to dilating stimuli (i.e., it decreased from 41.0 ± 19.0% in the sham group to 11.00 ± 0.70% after SNS) (n = 5, p < 0.01). HMGB1 infusion in the lateral ventricle in normal rats for 48 h did not change the pial arteriole dilating response. In addition, inhibitors of HMGB1-receptor for advanced glycation end-product or HMGB1-toll-like receptor 2/4 interaction, or the HMBG1 antagonist did not improve pial arteriole reactivity 48 h after SAH. These findings suggest that HMGB1 may not be a major player in cerebral vascular dilating dysfunction after SAH.
Human Immunodeficiency Virus Lymphadenitis Patterns on Fine-Needle Aspiration Cytology
Authors: Agnihotri Mona , Naik Leena , Chaudhari Sachin , Kothari Kanchan
Published: December 2016

Objective: The aim of this work was to study the microscopic patterns of human immunodeficiency virus (HIV) lymphadenitis on fine-needle aspiration cytology (FNAC) and correlate them with cluster of differentiation 4 (CD4) counts. Study Design: A retrospective study of known HIV-positive patients who underwent lymph node FNAC over a period of 5 years (2009-2013) was undertaken. The cytology slides were retrieved and reviewed. Out of 317 cases, 38 (11.7%) were diagnosed as HIV lymphadenitis. We analysed the cytomorphological patterns of HIV lymphadenitis and correlated them with the CD4 cell counts. Results: Smears of HIV lymphadenitis were classified akin to histology patterns (A, B, and C) depending on cellularity, number of tingible body macrophages, mitosis, apoptotic bodies, plasma cells, Warthin-Finkeldey giant cells, and proliferating blood vessels. Thirty-one cases showed pattern A, 3 showed pattern B, and 4 were of pattern C. Pattern A had the highest CD4 cell count. Conclusion: Histologic patterns of HIV lymphadenitis are recognisable on FNAC smears. These can offer a clue to the diagnosis and guide further workup, even in the absence of history. The changes can mimic those of the infective lymphadenitis, Castleman disease, and lymphoma. Hence, the clinical history, serological correlation, and awareness of cytomorphology can aid the correct diagnosis.
Mechanisms of IhERG/IKr Modulation by α1-Adrenoceptors in HEK293 Cells and Cardiac Myocytes
Authors: Urrutia Janire , Alday Aintzane , Gallego Mónica , Malagueta-Vieira L. Layse , Aréchiga-Figueroa Ivan Arael , Casis Oscar , Sánchez-Chapula José Antonio
Published: December 2016

Background: The rapid delayed rectifier K+ current (IKr), carried by the hERG protein, is one of the main repolarising currents in the human heart and a reduction of this current increases the risk of ventricular fibrillation. α1-adrenoceptors (α1-AR) activation reduces IKr but, despite the clear relationship between an increase in the sympathetic tone and arrhythmias, the mechanisms underlying the α1-AR regulation of the hERG channel are controversial. Thus, we aimed to investigate the mechanisms by which α1-AR stimulation regulates IKr. Methods: α1-adrenoceptors, hERG channels, auxiliary subunits minK and MIRP1, the non PIP2-interacting mutant D-hERG (with a deletion of the 883-894 amino acids) in the C-terminal and the non PKC-phosphorylable mutant N-terminal truncated-hERG (NTK-hERG) were transfected in HEK293 cells. Cell membranes were extracted by centrifugation and the different proteins were visualized by Western blot. Potassium currents were recorded by the patch-clamp technique. IKr was recorded in isolated feline cardiac myocytes. Results: Activation of the α1-AR reduces the amplitude of IhERG and IKr through a positive shift in the activation half voltage, which reduces the channel availability at physiological membrane potentials. The intracellular pathway connecting the α1-AR to the hERG channel in HEK293 cells includes activation of the Gαq protein, PLC activation and PIP2 hydrolysis, activation of PKC and direct phosphorylation of the hERG channel N-terminal. The PKC-mediated IKr channel phosphorylation and subsequent IKr reduction after α1-AR stimulation was corroborated in feline cardiac myocytes. Conclusions: These findings clarify the link between sympathetic nervous system hyperactivity and IKr reduction, one of the best characterized causes of torsades de pointes and ventricular fibrillation.
MiR-520b/e Regulates Proliferation and Migration by Simultaneously Targeting EGFR in Gastric Cancer
Authors: Li Shuang , Zhang Haiyang , Ning Tao , Wang Xinyi , Liu Rui , Yang Haiou , Han Yueting , Deng Ting , Zhou Likun , Zhang Le , Bai Ming , Wang Xia , Ge Shaohua , Ying Guoguang , Ba Yi
Published: December 2016

Background: MicroRNAs (miRNAs) have been demonstrated to play a crucial role in tumorigenesis. Previous studies have shown that miR-520b/e acts as a tumor suppressor in several tumors. Other studies indicated that epidermal growth factor receptor (EGFR) is highly expressed in many tumors, and involved in the development of tumors, such as cell proliferation, migration, angiogenesis and apoptosis. However, the correlation of miRNAs and EGFR in gastric cancer (GC) has not been adequately investigated. Our aim was to explore the relationship. Methods: The expression levels of EGFR and miR-520b/e were examined by RT-PCR and Western blot. We also investigated the relationship between EGFR and miR-520b/e in GC cell lines by relevant experiments. Results: In this study, we found that miR-520b/e inhibits the protein expression of EGFR by directly binding with the 3'-untranslated region (3'-UTR). And it was shown that the down-regulation of miR-520b/e promotes cell proliferation and migration by negative regulation of the EGFR pathway, while over-expression of miR-520b/e inhibits these properties. In addition, the biological function of EGFR in GC cell lines was validated by silencing and over-expression assays respectively. Conclusions: Taken together, our results demonstrate that miR-520b/e acts as a tumor suppressor by regulating EGFR in GC, and provide a novel marker and insight for the potential therapeutic target of GC.
Elevated THBS2, COL1A2, and SPP1 Expression Levels as Predictors of Gastric Cancer Prognosis
Authors: Zhuo Chuanjun , Li Xubin , Zhuang Hongqing , Tian Shunli , Cui Hailong , Jiang Ronghuan , Liu Chuanxin , Tao Ran , Lin Xiaodong
Published: December 2016

Background/Aims: Gastric cancer (GC) is an important health problem. Classification based on molecular subtypes may help to determine the prognosis of patients with GC. Tumor invasion and metastasis are important factors affecting the prognosis of cancer. We aimed to identify genes related to tumor invasion and metastasis, which may serve as indicators of good GC prognosis. Methods: Tumor tissues and adjacent normal tissues were collected from 105 patients with primary GC who were treated by undergoing radical surgery. Samples were used for tissue microarray analysis. Identified genes with altered expression were further analyzed using the Gene Ontology (Go) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The expression levels of THBS2, COL1A2 and SPP1 were analyzed by RT-PCR, western blot and immunohistochemistry. The overall survival curves of patients with high and low expression of each gene of interest were plotted and compared. Results: Forty-three genes were identified. THBS2, COL1A2 and SPP1 were selected for further analysis. Altered expression levels of THBS2, COL1A2 and SPP1 in tumor tissues were confirmed. Patients with low THBS2 expression had a better prognosis; the expression of COL1A2 and SPP1 might not affect the prognosis of patients with GC. Conclusion: THBS2, but not COL1A2 and SPP1, may serve as an indicator of GC prognosis.
MiR-22 may Suppress Fibrogenesis by Targeting TGFβR I in Cardiac Fibroblasts
Authors: Hong Yuan , Cao Huaming , Wang Qiang , Ye Jianlin , Sui Lijun , Feng Jinhua , Cai Xiaojun , Song Huizhu , Zhang Xiuhong , Chen Xichuang
Published: December 2016

Background/Aims: Cardiac fibrosis after myocardial infarction (MI) has been identified as a key factor in the development of heart failure, but the mechanisms undelying cardiac fibrosis remained unknown. microRNAs (miRNAs) are novel mechanisms leading to fibrotic diseases, including cardiac fibrosis. Previous studies revealed that miR-22 might be a potential target. However, the roles and mechanisms of miR-22 in cardiac fibrosis remained ill defined. The present study thus addressed the impact of miR-22 in cardiac fibrosis. Methods: After seven days following coronary artery occlusion in mice, tissues used for histology were collected and processed for Masson's Trichrome staining. In addition, cardiac fibroblasts were transfected with mimics and inhibitors of miR-22 using Lipofectamin 2000, and luciferase activity was measured in cell lysates using a luciferase assay kit. Western blotting was used to detect the expression of collagen1, α-SMA and TGFβRI proteins levels, and real time-PCR was employed to measure the Col1α1, Col3α1, miR-22 and TGFβRI mRNA levels. Results: In this study, we found that miR-22 was dynamically downregulated following MI induced by permanent ligation of the left anterior descending coronary artery for 7 days, an effect paralleled by significant collagen deposition. Inhibition of miR-22 with AMO-22 resulted in increased expression of Col1α1, Col3α1 and fibrogenesis in cultured cardiac fibroblasts. Conversely, overexpression of miR-22 in cultured cardiac fibroblasts significantly abrogated angiotensin II-induced collagen formation and fibrogenesis. Furthermore, we found that TGFβRI is a direct target for miR-22, and downregulation of TGFβR may have mediated the antifibrotic effect of miR-22. Conclusion: Our data clearly demonstrate that miR-22 acts as a novel negative regulator of angiotensin II-induced cardiac fibrosis by suppressing the expression of TGFβRI in the heart and may represent a new potential therapeutic target for treating cardiac fibrosis.
Improvement of Huangqi Decoction on Endothelial Dysfunction in 5/6 Nephrectomized Rats
Authors: Chu Shuang , Wang Li , Mao Xiao-dong , Peng Wen
Published: December 2016

Background/Aims: Endothelial dysfunction is a major factor in the progression of chronic kidney disease, which correlates with oxidative stress and NO deficiency. Huangqi decoction (HQD) is a potential anti-oxidant ingredient in renoprotection. However, the underlying mechanisms remained identified. Therefore, we investigated whether HQD exhibit improvement in endothelial dysfunction in the 5/6 nephrectomy (Nx) rat model. Methods: Male Wistar rats (180 - 250 g) were divided into sham, Nx and Nx + HQD (0.05, 0.15 and 0.45 g/kg) group, respectively. Renal function and histology were examined with ELISA and Immunohistochemical analysis. Endothelium-dependent relaxation of rat aortas was investigated by isometric tension recordings. Oxidative stress and NO bioavailability were detected by ELISA, DHE-staining, DAF-2 staining and western blotting. Results: Compared with Nx rats, HQD treatment reversed the functional and structural changes of kidney significantly. Besides, endothelium-dependent relaxation of rat aortas was also improved by HQD treatment. NADPH oxidase and ROS generation were inhibited while NO bioavailability was enhanced. Conclusion: HQD can act as a potent prescription for the treatment of endothelium related vascular complications.
Effects of CDKN2A (p16INK4A/p14ARF) Over-Expression on Proliferation and Migration of Human Melanoma A375 Cells
Authors: Bai Ming , Yu Nan-Ze , Long Fei , Feng Cheng , Wang Xiao-Jun
Published: December 2016

Objective: This study aims to investigate the effects of CDKN2A (p16INK4A/p14ARF) over-expression on the proliferation and migration of human melanoma A375 cells. Methods: Melanoma tissues and pigmented nevi tissues were collected. Human melanoma A375 cells were transfected by CDKN2A (p16INK4A) and CDKN2A (p14ARF) over-expressing vectors and then assigned into blank, negative control (NC), p16INK4A and p14ARF groups. The expression of CDKN2A (p16INK4A) and CDKN2A (p14ARF) mRNA and protein was detected by qRT-PCR and Western blotting. CCK-8, flow cytometry and Transwell assays were applied to observe cell proliferation, the cell cycle and apoptosis, and migration and invasion, respectively. The model of subcutaneous xenografts in nude mice was established to measure cell growth in vivo. Results: Compared with pigmented nevi tissues, CDKN2A (p16INK4A) and CDKN2A (p14ARF) mRNA and protein expression were significantly decreased in melanoma tissues. CDKN2A (p16INK4A) and CDKN2A (p14ARF) over-expression inhibited proliferation, migration, invasion and progression from G0/G1 to S phase of A375 cells and xenograft tumor growth, but promoted apoptosis. Conclusion: Our study demonstrated that over-expression of CDKN2A (p16INK4A) and CDKN2A (p14ARF) suppressed proliferation and migration of human melanoma A375 cells.
Zedoarondiol Inhibits Platelet-Derived Growth Factor-Induced Vascular Smooth Muscle Cells Proliferation via Regulating AMP-Activated Protein Kinase Signaling Pathway
Authors: Mao Huimin , Tao Tianqi , Song Dandan , Liu Mi , Wang Xiaoren , Liu Xiuhua , Shi Dazhuo
Published: December 2016

Background/Aims: Vascular smooth muscle cells (VSMCs) proliferation contributes significantly to atherosclerosis and in-stent restenosis. Platelet-derived growth factor-BB (PDGF-BB) plays a vital role in VSMCs proliferation. Zedoarondiol, a sesquiterpene lactone compound, has an anti-inflammatory activity. However, the role of zedoarondiol in PDGF-BB-mediated VSMCs proliferation remains unclear. In this study, we investigated the effects of zedoarondiol on PDGF-BB-induced VSMCs proliferation and explored the possible mechanisms. Methods: The inhibitory effects of zedoarondiol on PDGF-BB-induced VSMCs proliferation were evaluated by direct cell counting and the Cell Counting Kit-8 (CCK-8) assay. DNA synthesis was examined by bromodeoxyuridine (BrdU) incorporation assay. Cell cycle was assessed by propidium iodide staining. Western blotting was performed to determine the expression of cyclin-dependent kinase 2 (CDK2), cyclin E, p53, p21, total and phosphorylated adenosine monophosphate-activated protein kinase (AMPK), acetyl CoA carboxylase (ACC), mammalian target of rapamycin (mTOR), and p70 ribosomal protein S6 kinase (p70S6K). Results: Zedoarondiol suppressed PDGF-BB-induced VSMCs proliferation and DNA synthesis, and induced cell cycle arrest in G0/G1 phase. In addition, zedoarondiol activated AMPK and ACC, inhibited the phosphorylation of mTOR and p70S6K, increased the expression of p53 and p21, and decreased the expression of CDK2 and cyclin E. Compound C (an AMPK inhibitor) abrogated, whereas 5-aminoimidazole-4-carboxamide 1-β-ribofuranoside (AICAR, an AMPK activator) enhanced zedoarondiol-mediated inhibition of VSMCs proliferation and DNA synthesis. Conclusion: Zedoarondiol inhibits PDGF-BB-induced VSMCs proliferation via AMPK-mediated down-regulation of the mTOR/p70S6K pathway and up-regulation of the p53/p21 pathway. These findings suggest that zedoarondiol might be a promising compound against atherosclerosis and in-stent restenosis.
Effects of Leptin on Na+/Ca2+ Exchanger in PC12 Cells
Authors: Zhang Zijuan , Sun Shuguang , Du Caixia , Li Wei , Zhang Juan , Zhu Yanqin , Liu Peilin , Xing Ying
Published: December 2016

Background/Aims: Alzheimer's disease (AD) is known to be related to alterations in neuronal intracellular calcium activity ([Ca2+]i). The present study revealed the distinct role of leptin in Na+/Ca2+-exchanger activity. Methods: [Ca2+]i was determined utilizing Fura-2 fluorescence. The activity of NCX was measured by removal of extracellular Na+ in the presence of external Ca2+. Na+/Ca2+-exchanger activity was further quantified from whole cell currents following removal of extracellular Na+. Na+/Ca2+-exchanger isoform NCX1 transcript levels and protein abundance were quantified by RT-PCR and Western blotting, respectively. Results: Exposure of PC12 cells to 30 µM amyloid (Aβ42) increased [Ca2+]i, an effect significantly blunted by 6 hours incubation with leptin before Aβ42 treatment. Moreover, leptin treatment significantly increased Na+/Ca2+-exchanger mediated Ca+ transport and current, NCX1 transcript level as well as NCX1 membrane protein abundance. Conclusion: We show that leptin blunts Aβ42-evoked [Ca2+]i increase by increasing expression and activity of Na+/Ca2+-exchanger NCX1.
Bufalin Inhibits hTERT Expression and Colorectal Cancer Cell Growth by Targeting CPSF4
Authors: Zhang Ningning , Xie Yunpeng , Tai Yidi , Gao Yingying , Guo Wei , Yu Wendan , Li Jia , Feng Xu , Hao Jiaojiao , Gao Yue , Zhao Xinrui , Liao Yina , Jiang Wei , Liu Ge , Deng Wuguo , Cui Xiaonan
Published: December 2016

Background/Aims: Bufalin can induce apoptosis in certain human cancer cell lines, but bufalin has not yet been thoroughly evaluated in colorectal cancer cells. Cleavage and polyadenylation specific factor 4 (CPSF4) and human telomerase reverse transcriptase (hTERT) play important roles in colorectal cancer growth. The aim of this study was to investigate the roles and interactions of bufalin, CPSF4 and hTERT and the effects of bufalin in human colorectal cancer. Methods: We treated LoVo and SW620 cells with bufalin to investigate the effect of bufalin on proliferation, apoptosis and migration. We verified the relationship between CPSF4 and hTERT using pulldown assays, luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays. Results: Bufalin inhibited the proliferation and migration of and induced apoptosis in LoVo and SW620 cells. We identified CPSF4 as an hTERT promoter-binding protein in colorectal cancer cells. Conclusion: Our study identified bufalin as a potential small molecule inhibitor for cancer therapy.
Blocking Mammalian Target of Rapamycin (mTOR) Attenuates HIF-1α Pathways Engaged-Vascular Endothelial Growth Factor (VEGF) in Diabetic Retinopathy
Authors: Wei Jie , Jiang Hua , Gao Hongrui , Wang Guangjie
Published: December 2016

Background/Aims: Prior studies demonstrate that hypoxia inducible factor subtype 1α (HIF-1α) in retinal tissues is involved in development of diabetic retinopathy (DR). In this report, we particularly examined the role played by mammalian target of rapamycin (mTOR) in regulating expression of HIF-1α and its downstream pathway, namely vascular endothelial growth factor (VEGF). Methods: Streptozotocin (STZ) was systemically injected to induce hyperglycemia in rats. ELISA and Western Blot analysis were employed to determine the levels of HIF-1α and VEGF as well as expression of mTOR pathways in retinal tissues of control rats and STZ rats. Results: Our results show that HIF-1α and VEGF as well as VEGF receptor subtype 2 (VEGFR-2) were increased in STZ rats. Also, the protein expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1), p70 ribosomal S6 protein kinase 1 (S6K1) pathways were amplified in diabetic retina compared with controls. Blocking mTOR by using rapamycin significantly attenuated activities of HIF-1α and VEGF signaling pathways. Conclusion: Our data for the first time revealed specific signaling pathways engaged in the development of DR, including the activation of mTOR and HIF-1α -VEGF mechanism. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of DR often observed in clinics.
Exogenous Hydrogen Sulfide Attenuates High Glucose-Induced Cardiotoxicity by Inhibiting NLRP3 Inflammasome Activation by Suppressing TLR4/NF-κB Pathway in H9c2 Cells
Authors: Huang Zena , Zhuang Xiaodong , Xie Chuli , Hu Xun , Dong Xiaobian , Guo Yue , Li Shaofen , Liao Xinxue
Published: December 2016

Background/Aims: This study aimed to investigate whether exogenous hydrogen sulfide (H2S) confered cardiac protection against high glucose (HG)-induced injury by inhibiting NLRP3 inflammasome activation via a specific TLR4/NF-κB pathway. Methods: H9c2 cardiac cells were exposed to 33 mM glucose for 24 h to induce HG-induced cytotoxicity. The cells were pretreated with NaHS (a donor of H2S) before exposure to HG. Cell viability, cell apoptosis, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and TLR4, NF-κB, NLRP3 inflammasome, IL-1β, IL-18 and caspase-3 expression were measured by standard methods. Results: H2S attenuated HG-induced cell apoptosis, ROS expression and loss of MMP and reduced the expression of NLRP3, ASC, pro-caspase-1, caspase-1, IL-1β, IL-18 and caspase-3. In addition, H2S inhibited the HG-induced activation of TLR4 and NF-κB. Furthermore, NLRP3 inflammasome activation was regulated by the TLR4 and NF-κB pathway. Conclusion: The present study demonstrated for the first time that H2S appears to suppress HG-induced cardiomyocyte inflammation and apoptosis by inhibiting the TLR4/NF-κB pathway and its downstream NLRP3 inflammasome activation. Thus H2S might possess potential in the treatment of diabetic cardiomyopathy.
One-Year Outcomes of the Treat-and-Extend Approach with Aflibercept in Age-Related Macular Degeneration: Effects on Typical Choroidal Neovascularization and Retinal Angiomatous Proliferation
Authors: Castro-Navarro Verónica , Cervera-Taulet Enrique , Montero-Hernández Javier , Navarro-Palop Catalina
Published: December 2016

Objective: To investigate functional/morphological outcomes of the treat-and-extend regimen (TER) with aflibercept in typical choroidal neovascularization (CNV) and retinal angiomatous proliferation (RAP) secondary to exudative age-related macular degeneration (AMD). Methods: This was a retrospective study of 37 eyes treated with 2 mg aflibercept according to a TER protocol. Examinations included best corrected visual acuity (BCVA), numbers of injections, and visits needed. Additionally, quantitative/qualitative analyses with fluorescein angiography and spectral- domain optical coherence tomography were conducted at baseline as well as at 3, 6, and 12 months. Results: BCVA significantly improved from 0.6 ± 0.27 to 0.4 ± 0.34 logMAR. The final mean numbers of injections were 8.03 ± 1.27 and 7.28 ± 0.75 and the numbers of visits 6.5 ± 1.09 and 7.14 ± 1.57 in typical CNV and in RAP or atypical CNV, respectively, and they did not differ between the different subtypes of CNV (p > 0.05). Conclusions: Aflibercept in TER is effective for all exudative AMD subtypes. The patient's visual gain, the mean number of injections, and the number of visits needed did not depend on the subtype of CNV.
Mutations in Genes Coding for Synaptonemal Complex Proteins and Their Impact on Human Fertility
Authors: Geisinger Adriana , Benavente Ricardo
Published: December 2016

Human infertility is often classified as idiopathic in both males and females. Meiotic errors may account for at least part of these cases. As the synaptonemal complex (SC, a meiosis-specific protein scaffold) is essential for successful meiosis progression, in this paper, we analyzed the mutations in genes coding for SC components described in infertile patients to assess to what extent alterations in the SC can be related to human infertility. So far, mutations in SYCP3 and SYCE1 genes have been reported. While most SYCP3 mutations are heterozygous mutations with dominant-negative effect on the region encoding the C-terminal coiled coil of the protein, SYCE1 mutations are homozygous, which is consistent with a recessive inheritance. Similarities and differences between males and females as well as between mice and humans have been found and are discussed herein. The results suggest that a low percentage of human infertility cases may be explained by mutations in genes coding for SC components. The characterization of these mutations, together with available information from the study of knockout mice, will enable a deeper understanding of the underlying molecular bases for some of the cases of idiopathic infertility.
A Novel Heterozygous Intragenic Sequence Variant in DLX6 Probably Underlies First Case of Autosomal Dominant Split-Hand/Foot Malformation Type 1
Authors: Ullah Asmat , Hammid Anam , Umair Muhammad , Ahmad Wasim
Published: December 2016

Split-hand and foot malformation (SHFM; MIM 183600) is a rare human genetic limb malformation. It is characterized by missing digital rays in the hands and feet. SHFMs vary in severity from mild abnormalities affecting a single limb to acute malformations involving all 4 limbs. It is inherited, as part of both a syndromic and nonsyndromic disorder, in an autosomal recessive, autosomal dominant, and X-linked patterns. So far, 9 loci of hand and foot malformation have been mapped on human chromosomes. The present study describes a family with 2 affected individuals segregating SHFM in an autosomal dominant fashion. Sanger sequencing of the genes involved in SHFM was performed to identify the disease-causing variant. Sequence analysis revealed the first heterozygous missense variant (c.632T>A, p.Val211Glu) in the distal-less homeobox 6 (DLX6) gene, located in chromosome 7q21, causing SHFM in the present family. This study supports the evidence of DLX6 as an SHFM-causing gene.
When Diarrhea Can Become Deadly: Legionnaires’ Disease Complicated by Bowel Obstruction
Authors: Prichard Wesley , Fick Laurel
Published: December 2016

Legionnaires’ disease may present with a broad spectrum of illnesses and nonspecific extrapulmonary symptoms including diarrhea. To our knowledge, bowel obstruction has not been reported as a manifestation of Legionella. We present a unique case of Legionnaires’ disease contributing to a small bowel obstruction.
Pregnant Woman with Atypical Hemolytic Uremic Syndrome Delivered a Healthy Newborn under Eculizumab Treatment
Authors: Demir Erol , Yazici Halil , Ozluk Yasemin , Kilicaslan Isin , Turkmen Aydin
Published: December 2016

Pregnancy-associated thrombotic microangiopathy is a very rare condition; however, it significantly increases fetal or maternal morbidity and mortality. Pregnancy may trigger atypical hemolytic uremic syndrome (aHUS) or thrombotic thrombocytopenic purpura. The risk for pregnancy-associated aHUS is highest during the second pregnancy. The outcome is usually poor with 50–60% mortality; renal dysfunction and hypertension are the rule in those who survive the acute episode. After the development of complement regulation mechanisms and aHUS pathogenesis, eculizumab has been widely used as a first-line treatment in aHUS. Eculizumab has been produced to minimize immunogenicity and Fc-mediated functions, including recruitment of inflammatory cells and complement activation, and using eculizumab in first-line treatment improves kidney function. Recent studies showed that early diagnosis and rapid use of eculizumab in first-line treatment improve outcomes. We demonstrate a case with pregnancy-triggered aHUS occurring in the second trimester, who was successfully treated and delivered a healthy baby under eculizumab treatment.
Sociologias da literatura: do reflexo à reflexividade
Authors: Hoelz Maurício , Botelho André Pereira
Published: December 2016

A “sociologia da literatura” vem conhecendo maior pluralização de perspectivas que tem tornado a compreensão da literatura mais matizada em relação à ideia de “reflexo” que marcou sua tradição de pesquisa, como indicam os balanços bibliográficos publicados nas últimas três décadas em periódicos de língua inglesa que analisamos neste artigo. Contudo, literatura e sociedade seguem sendo concebidos, em geral, como externos um ao outro, e não como reflexivamente relacionados. Mobilizando as perspectivas teóricas de Anthony Giddens e Niklas Luhmann para qualificar a ideia de reflexividade, argumentamos que elas podem constituir pontos de partida diferentes, mas igualmente consistentes para uma agenda renovada da sociologia da literatura.
Intelectuales de la Educación en la reconstrucción de la democracia en la Argentina
Authors: Isola Nicolás José
Published: December 2016

No final da ditadura na Argentina, em 1983, a reconstituição dos espaços de produção de conhecimento em educação mereceu uma série de debates sobre a modernização interrompida e o futuro da educação nacional. Estava em disputa a intenção de consolidar consensos que fortalecessem o discurso e as capacidades educacionais do Estado. Ao analisar os documentos e intervenções intelectuais, discuto tanto as tensões quanto as possibilidades que se apresentam nos depoimentos dos acadêmicos da Educação na Argentina na luta para o fortalecimento de uma burocracia estatal especializada.As conclusões permitem considerar três tensões: (i) a debilidade técnico-burocrática e estatística do sistema educativo; (ii) a falta de coesão deste espaço profissional; e (iii) a dificuldade para estabelecer um programa científico moderno, com acesso a posições de poder no Estado
Violência e justiça criminal na área metropolitana de Brasília: dinâmicas organizacionais e representações sociais
Authors: Machado Bruno Amaral , Grossi Porto Maria Stela
Published: December 2016

O artigo tem como base empírica pesquisa sobre os homicídios na AMB (Área Metropolitana de Brasília). O ponto de partida foi a análise georeferencial das mortes registradas no ano de2010. A partir desse marco, computadas as 565 mortes registradas, foi realizado o estudo do fluxo do sistema de justiça criminal em três cidades selecionadas: Luziânia, Cidade Ocidental e Águas Lindas de Goiás. Neste artigo, o foco são as dinâmicas entre as diferentes organizações do sistema de justiça criminal, bem como as representações sociais de seus distintos atores.
Los aportes de Lucío Mendieta y Núñez a la institucionalización de la Sociología en México (1939-1951)
Authors: Olvera Serrano Margarita
Published: December 2016

Lucio Mendieta y Núñez é considerado o líder do processo de institucionalização da sociologia no México como disciplina autônoma universitária. Este artigo analisa os momentos cruciais de sua trajetória.
An economic evaluation of the Brazilian job training policy (PLANSEQ
Authors: Petterini Francis Carlo
Published: December 2016

O PLANSEQ é um dos principais instrumentos da política pública de qualificação profissional no Brasil. Através dele as organizações empresariais podem usar recursos públicos para ofertar cursos nas áreas onde identificam problemas de oferta de trabalho. Neste artigo se avalia o impacto de um projeto realizado em Fortaleza, em 2009, que qualificou mais de 1,5 mil trabalhadores desempregados. Estimou-que que este projeto do PLANSEQ pode ter aumentado em até 20 pontos percentuais a probabilidade de um indivíduo qualificado encontrar emprego
A dureza do fazer. A práxis na urbanística de Saturnino de Brito a partir do seu plano de saneamento para a cidade de Santos (1905-1910)
Authors: Bernardini Sidney Piochi
Published: December 2016

O artigo pretende discutir a atuação do engenheiro sanitarista Saturnino de Brito durante o período que chefiou a Comissão de Saneamento de Santos do governo estadual de São Paulo, entre 1905 e 1910. Brito foi incumbido de realizar as obras de saneamento daquela cidade que, por longos anos, havia sido assolada por epidemias de febre amarela, dizimando parte de sua população. Ao enfrentar uma série de obstáculos e dificuldades que foram interpostos durante o processo de execução destas obras, a conduta do engenheiro demonstrou a sua habilidade em combinar conhecimentos variados para lidar com as problemáticas intrínsecas ao plano desenvolvido.
Pier Paolo Pasolini, poeta
Authors: Rebechi Junior Arlindo
Published: December 2016

Apresentação do poeta italiano Pier Paolo Pasolini, em suas diversas fases de produção.
O que dizem as licenças? Flexibilização da legislação e recrutamento privado de trabalhadores indígenas no Estado do Maranhão (1680-1755)
Authors: Dias Camila Loureiro , Bombardi Fernanda Aires
Published: December 2016

Nesse artigo, sistematizamos as informações contidas nas licenças concedidas a moradores para realizarem descimentos e resgates particulares no Estado do Maranhão e Grão-Pará durante o período colonial. Comparando com os eventos econômicos e sociais e com a legislação do período, procuramos apreender a evolução do sistema de recrutamento de trabalhadores indígenas na região amazônica, especialmente durante primeira metade do século XVIII
Cambios y permanencias en la cultura material cotidiana no privilegiada: un mundo complejo. Castilla (y Portugal) a finales del antiguo régimen
Authors: García Fernández Máximo
Published: December 2016

Lentamente, entre los siglos XVI al XIX, los grupos intermedios se afirmaron en el universo urbano castellano y portugués, adquiriendo protagonismo efectivo en los procesos de transformación social. Trataremos de comprender mejor su ascenso a partir de la visualización pública de su cultura material cotidiana y relacionando la posesión y el valor cultural de ciertos enseres con prácticas rupturistas y modernizadoras (o de imitación aristocrática).
Notas sobre a concepção hobbesiana das relações do desejo e da razão com o tempo
Authors: Torres João Carlos Brum
Published: December 2016

O propósito deste artigo é discutir o modo como Hobbes concebe a relação do desejo com o tempo, entendido o ponto como o esforço para determinar se e como o filósofo atribui privilégios práticos ou ao presente, ou ao passado, ou ao futuro, ou se, alternativamente, sua posição é de neutralidade com relação a essa questão. O desenvolvimento da análise mostra que aqui o progresso depende criticamente do modo como Hobbes concebe a racionalidade dos comportamentos humanos. Essa ligação da racionalidade com o tempo não constitui, contudo, todo o necessário para o trabalho elucidativo a que se propõe o artigo, o qual depende ainda da consideração de vários elementos doutrinários complementares, notadamente a explicação do modo como Hobbes entende a natureza metafísica do tempo, da vida e das paixões que a animam; de sua concepção dos sinais, dos nomes e, em geral da linguagem e da relação desta com o cálculo, assim como de sua tese sobre o estatuto da felicidade humana. A partir da retomada articulada desses diferentes aspectos, o artigo concluirá mostrando que Hobbes, ao introduzir a distinção entre bem aparente e bem real, sustentará que, malgrado a shortsightness a que nos compelem as paixões, a capacidade que nos dá a razão de calcular causas e consequências nos permite visualizar prudencialmente o futuro, de modo que, podendo recurvar a linha do tempo e, assim, anular o privilégio que espontaneamente damos ao presente, não só também podemos, mas devemos, fazer do futuro o guia para construção de nossas vidas.
Introdução aos excertos de Marx sobre James Mill (1844): ou sobre o reconhecimento
Authors: Caux Luiz Philipe de
Published: December 2016

O artigo apresenta e justifica de forma sucinta a tradução dos “Excertos do livro de James Mill ‘Éléments d’économie politique’”, escritos por Karl Marx à época dos Manuscritos Econômico-Filosóficos (1844). Nestas anotações, além de se debruçar sobre os temas tratados nos Manuscritos (dinheiro, alienação, ser genérico, trabalho, propriedade privada etc.), Marx trata de forma única no corpo de sua obra o tema do reconhecimento como tomado de Hegel, conceituando as relações no interior da sociedade civil como relações conflituosas de reconhecimento. O texto possui, assim, implicações tanto para a interpretação de Marx quanto como contribuição para a teoria do reconhecimento contemporânea.