bluuebunny/crossref_metadata_2025 huggingface dataset:
Epilutein for Early-Stage Age-Related Macular Degeneration: A Randomized and Prospective Study
Authors: Forte Raimondo , Panzella Lucia , Cesarano Ida , Cennamo Gilda , Eidenberger Thomas , Napolitano Alessandra
Published: October 2017

Purpose: The hypothesis that oral supplementation of the epilutein/lutein combination could augment the macular pigment optical density (MPOD) in patients with age-related macular degeneration (AMD) was tested. Methods: In a prospective randomized interventional study, 40 consecutive patients with early-stage AMD were recruited. After a 2-week run-in period, patients were randomly treated with a daily oral administration of 8 mg epilutein and 2 mg lutein (group 1) or 10 mg lutein (group 2) for 2 months. At baseline (BL) and 1-month (M1) and 2-month visits (M2), all patients underwent a complete ophthalmological examination, including measurement of MPOD in a 7° area (Visucam 200; Carl Zeiss Meditec, Milan, Italy). Xanthophylls were quantified in plasma, as well as the HDL, non-HDL, and erythrocyte fractions at each study visit. Results: Twenty-one patients (mean age 69.4 ± 6.7 years, 35 eyes) were included in group 1. Mean MPOD was 0.203 ± 0.02 optical density units (ODU) at BL, and increased to 0.214 ± 0.04 ODU at M1 (p = 0.008) and 0.206 ± 0.03 ODU at M2 (p = 0.04). Sixteen patients (mean age 72.0 ± 6.3 years, 29 eyes) were included in group 2. Mean MPOD was 0.215 ± 0.03 at BL, which reduced to 0.202 ± 0.03 ODU at M1 (p = 0.003) and 0.207 ± 0.02 ODU at M2 (p < 0.001). A rise in the systemic level of total xanthophylls was observed at M1 for both groups. At M2, total xanthophylls were significantly increased only in group 1 and decreased in group 2. Conclusion: In patients with early-stage AMD, the administration of lutein in combination with epilutein was associated with an increased MPOD compared to the administration of lutein alone.
Acid-Base and Electrolyte Disorders in Patients with and without Chronic Kidney Disease: An Update
Authors: Dhondup Tsering , Qian Qi
Published: October 2017

Kidneys play a pivotal role in the maintenance and regulation of acid-base and electrolyte homeostasis, which is the prerequisite for numerous metabolic processes and organ functions in the human body. Chronic kidney diseases compromise the regulatory functions, resulting in alterations in electrolyte and acid-base balance that can be life-threatening. In this review, we discuss the renal regulations of electrolyte and acid-base balance and several common disorders including metabolic acidosis, alkalosis, dysnatremia, dyskalemia, and dysmagnesemia. Common disorders in chronic kidney disease are also discussed. The most recent and relevant advances on pathophysiology, clinical characteristics, diagnosis, and management of these conditions have been incorporated.
Looking Beyond the Cyclosporine “Swish and Spit” Technique in a Recalcitrant Case of Erosive Lichen Planus Involving the Tongue
Authors: Gupta Aastha , Sardana Kabir , Gautam Ram Kishan
Published: October 2017

Oral lichen planus is a relatively common autoimmune disease affecting the middle-aged population. Although no treatment is necessary for a benign asymptomatic case, in case of erosive lichen planus, topical corticosteroids form the mainstay of treatment. In case of failure, apart from tacrolimus, cyclosporine, using the “swish and spit” technique, is a valid therapeutic intervention. In our case, though, this therapeutic option had to be replaced by the systemic use of cyclosporine with gratifying results.
Immunolocation of Aquaporin 8 in Human Cataractous Lenticular Epithelial Cells
Authors: Hayashi Rijo , Hayashi Shimmin , Fukuda Kazunori , Sakai Miki , Machida Shigeki
Published: October 2017

Purpose/Aim: Aquaporin 8 (AQP8) is a diffusion facilitator of hydrogen peroxide (H2O2) through cell membranes. The purpose of this study was to confirm and localize AQP8 in human lenticular epithelial cells (LECs). Materials and Methods: Lenticular anterior capsule samples, including LECs, were collected during cataract surgery of cataract patients after informed consent. The localization of AQP8 was detected by immunohistochemical staining using an antibody to AQP8. Real-time polymerase chain reaction (RT-PCR) was also used to determine the AQP8 mRNA expression levels. The PCR products were analyzed by gel electrophoresis following analyses of band density. Results: Immunohistochemical staining showed AQP8 was distributed throughout the whole area of the anterior capsulotomy. AQP8 labeling was observed surrounding and within the cytoplasm of LECs. RT-PCR and gel electrophoresis also revealed the presence of AQP8 mRNA in the lenticular anterior capsule. The results of immunohistochemical staining were comparable to those of RT-PCR and gel electrophoresis. Conclusions: The results of this study indicate the distribution of AQP8 in human LECs. This is the first investigation confirming the presence of AQP8 in human LECs.
Montreal Cognitive Assessment in a 63- to 65-year-old Norwegian Cohort from the General Population: Data from the Akershus Cardiac Examination 1950 Study
Authors: Ihle-Hansen Håkon , Vigen Thea , Berge Trygve , Einvik Gunnar , Aarsland Dag , Rønning Ole Morten , Thommessen Bente , Røsjø Helge , Tveit Arnljot , Ihle-Hansen Hege
Published: October 2017

Aims: To investigate Montreal Cognitive Assessment (MoCA) test scores in a cohort aged 63–65 years from a general population in relation to the proposed cut-off score of 26 for mild cognitive impairment (MCI) and to explore the impact of education. Methods: MoCA scores were assessed in the Akershus Cardiac Examination 1950 Study, a cross-sectional cohort study of all men and women born in 1950 living in Akershus County, Norway. The participants were aged 63–65 at the time of data collection. Results: MoCA scores were available in 3,413 participants, of which 47% had higher education (>12 years). The mean MoCA score was 25.3 (95% confidence interval [CI] 25.2–25.4), and 49% had a score below the suggested cut-off of 26 points. Those with higher education had significantly higher scores (mean 26.2, 95% CI 26.1–26.3 vs. 24.4, 95% CI 24.3–24.6, p < 0.001). Conclusions: Approximately 50% scored below the cut-off score of 26 points, suggesting that the cut-off score may have been set too high to distinguish normal cognitive function from MCI. Educational level had a significant impact on MoCA scores.
Parental Origin of the Retained X Chromosome in Monosomy X Miscarriages and Ongoing Pregnancies
Authors: Grande Maribel , Stergiotou Iosifina , Pauta Montse , Marquès Borja , Badenas Cèlia , Soler Anna , Yaron Yuval , Borrell Antoni
Published: October 2017

Objective: To assess the distribution of the parental origin of the retained X chromosome in monosomy X, either in miscarriages or in ongoing pregnancies. Method: The parental origin of the X chromosome was determined in monosomy X pregnancies, either miscarriages or ongoing pregnancies. Microsatellite marker patterns were compared between maternal and fetal samples by quantitative fluorescence polymerase chain reaction. Distributions of maternally and paternally derived X chromosome were assessed in miscarriages and in ongoing pregnancies using two-tailed Fisher exact test. Results: Forty monosomy X pregnancies were included in the study: 26 miscarried at 5-16 weeks, and 14 ongoing pregnancies were diagnosed at 11-20 weeks. The retained X chromosome was maternally derived in 67% of the cases. In miscarriages, maternal and paternal X chromosome were retained in a similar proportion (54% [95% CI: 35-73%] vs. 46% [95% CI: 27-65%]), while in ongoing pregnancies, the maternal rate was 13 times higher (93% [95% CI: 79-100%)] vs. 7% [95% CI: 0-20%]). Conclusions: The retained X chromosome in individuals with monosomy X should theoretically be maternally derived in 2/3 of the cases. Our study suggests a preferential early miscarriage in pregnancies with a retained paternally derived X chromosome. This may explain the observation that 75-90% of individuals with monosomy X retain the maternal X chromosome.
Phylogenetic Analysis of Torque Teno Virus in Thalassemic Children in Egypt
Authors: Hassuna Noha A. , Naguib Eman , Abdel-Fatah Medhat , Mousa Suzan M. Omar
Published: October 2017

Objective: Torque teno virus (TTV) is a ubiquitous virus that is commonly associated with blood transfusion. The main aims of this study were to evaluate the incidence of TTV in polytransfused children with thalassemia and to determine for the first time the prevalent TTV genotypes in Egypt. Methods: TTV was detected in 2 groups by nested PCR: the first group comprised 200 children with thalassemia, and the second included age- and sex-matched healthy children with no history of blood transfusion. Results: TTV was detected in 60 and 57%, respectively, of the children with thalassemia and the healthy children. Among the TTV-positive children with thalassemia, 71.6% were HCV positive. No hepatitis B surface antigen was detected in the thalassemic children. Significant elevations of alanine transaminase and aspartate transaminase were found in TTV-positive patients with thalassemia compared to TTV-negative patients. Phylogenetic analysis of sequenced TTV isolates showed close relationships to genotypes 1 and 2. Conclusion: TTV is highly prevalent among children with thalassemia in Egypt, with a relatively high infection rate also detected among healthy children.
Quercetin Inhibits Cell Migration and Invasion in Human Osteosarcoma Cells
Authors: Lan Haifeng , Hong Wei , Fan Pan , Qian Dongyang , Zhu Jianwei , Bai Bo
Published: October 2017

Background/Aims: Osteosarcoma is a malignant tumor associated with high mortality; however, no effective therapies for the disease have been developed. Several studies have focused on elucidating the pathogenesis of osteosarcoma and have aimed to develop novel therapies for the disease. Quercetin is a vital dietary flavonoid that has been shown to have a variety of anticancer effects, as it induces cell cycle arrest, apoptosis, and differentiation and is involved in cell adhesion, metastasis and angiogenesis. Herein, we aimed to investigate the effects of quercetin on osteosarcoma migration and invasion in vitro and in vivo and to explore the molecular mechanisms underlying its effects on osteosarcoma migration and invasion. Methods: Cell viability, cell cycle activity and cell apoptosis were measured using CCK-8 assay and flow cytometry, and cell migration and invasion were evaluated by wound healing and transwell assays, respectively. The mRNA and protein expression levels of several proteins of interest were assessed by real-time quantitative PCR and western blotting, respectively. Moreover, a nude mouse model of human osteosarcoma lung metastasis was established to assess the anti-metastatic effects of quercetin in vivo. Results: We noted no significant differences in cell cycle activity and apoptosis between HOS and MG63 cells and control cells. Treatment with quercetin significantly attenuated cell migration and invasion in HOS and MG63 cells compared with treatment with control medium. Moreover HIF-1α, VEGF, MMP2, and MMP9 mRNA and protein expression levels were significantly downregulated in HOS cells treated with quercetin compared with HOS cells treated with controls. Additionally, treatment with quercetin attenuated metastatic lung tumor formation and growth in the nude mouse model of osteosarcoma compared with treatment with controls. Conclusion: Our findings regarding the inhibitory effects of quercetin on cell migration and invasion suggest that quercetin may have potential as a therapy for human osteosarcoma.
Geniposide Attenuates Post-Ischaemic Neurovascular Damage via GluN2A/AKT/ ERK-Dependent Mechanism
Authors: Huang Baosheng , Chen Panhong , Huang Lei , Li Shuai , Zhu Ronglan , Sheng Tao , Yu Wan , Chen Zheng , Wang Tianlu
Published: October 2017

Background/Aims: Calcium-permeable ionotropic NMDAR-mediated hyperactivity is regarded as the critical factor in modulating the development of ischaemic stroke. Recently, there has been increasing interest in preventing post-stroke neuronal death by focusing on intervening in the function of subpopulations of NMDARs and their downstream signalling. Geniposide, an iridoid glycoside, has been found to have cytoprotective functions in various conditions. However, it is still unclear whether and how geniposide affects neuronal insult under experimental stroke. Methods: We demonstrate that dose-dependent geniposide significantly decreased the infarct volume in tMCAO models. Results: A medium level of geniposide improved anti-apoptotic functions and inhibited BBB leakage/haemorrhage via elevating GluN2A-containing NMDAR expression in tMCAO rats. Importantly, these effects could be eliminated by co-treatment of geniposide with the GluN2A antagonist NVP but not the GluN2B inhibitor ifenprodil. Moreover, geniposide’s protection was due to the enhancement of GluN2A-dependent survival signals, including pAKT, pERK and PSD-95. Conclusion: The results suggest that geniposide protects neurons against post-ischaemic neurovascular injury through the activation of GluN2A/AKT/ERK pathways. As a very promising natural agent, geniposide may be a future therapeutic for stroke patients.
Bullous Exudative Retinal Detachment after Retinal Pattern Scan Laser Photocoagulation in Diabetic Retinopathy
Authors: Nishikawa Shohei , Kunikata Hiroshi , Aizawa Naoko , Nakazawa Toru
Published: October 2017

Laser retinal photocoagulation is the gold standard treatment for diabetic retinopathy. We describe 3 cases in which bullous exudative retinal detachment (ERD) developed after pattern scan laser photocoagulation (PASCAL) in diabetic retinopathy. ERD spontaneously resolved in all 3 cases with various visual courses. This case series highlights 2 key points: first, ERD can occur regardless of gender, age, glycemic control, or vitreous status and despite a moderate number of laser shots, even with PASCAL; second, ERD in nonvitrectomized eyes may cause irreversible visual loss, even if the ERD resolves within 1 month.
Corneal Collagen Cross-Linking Combined with an Artiflex Iris-Fixated Anterior Chamber Phakic Intraocular Lens Implantation in a Patient with Progressive Keratoconus
Authors: Hashmani Sharif , Hashmani Nauman , Memon Roha Saeed
Published: October 2017

We present here the case of a 24-year-old male who experienced progressive keratoconus and vision loss which adversely affected his ability to carry out everyday tasks. This landed him in the Hashmanis Hospital for consultation. He had a preoperative best corrected visual acuity of 6/12. He underwent multiple Oculus Pentacam examinations, which showed progressive keratoconus. Corneal collagen cross-linking (CXL) was performed to stabilize his cornea and, subsequently, an Artiflex anterior chamber iris-fixated phakic intraocular lens (ACIF-PIOL) was implanted to alleviate his refractive errors. The patient achieved a postoperative uncorrected visual acuity of 6/12. This report shows that CXL combined with ACIF-PIOL can be safe and effective in those with progressive keratoconus.
Contributions and Future Directions for Structural Biology in the Study of Allergens
Authors: Mueller Geoffrey A.
Published: October 2017

Allergy is defined as an inappropriate immune response to something normally considered harmless. The symptomatic immune response is driven by IgE antibodies directed against allergens. The study of allergens has contributed significantly to our understanding of allergic disease in 3 main areas. First, identifying allergens as the cause of symptoms and developing allergen standards has led to many advances in exposure assessment and patient diagnostics. Second, a biochemical understanding of allergens has suggested a number of hypotheses related to the mechanisms of allergic sensitization. And finally, studies of allergen-antibody interactions have contributed to understanding the cross-reactivity of allergens, mapping patient epitopes, and the development of hypoallergens. In this review, a few select cases are highlighted where structural biology, in particular, has contributed significantly to allergen research and provided new avenues for investigation.
Health-Related Quality of Life of Patients with Hidradenitis Suppurativa Measured with the 15D Instrument and Comparison with the General Population and Patients with Psoriasis
Authors: Kluger Nicolas , Sintonen Harri , Ranta Martta , Serlachius Martina
Published: October 2017

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease significantly impacting health-related quality of life (HRQoL). We measured the HRQoL of Finnish HS patients and compared it with that of the general population and psoriasis patients. Methods: Twenty-six diagnosed HS patients completed the 15D HRQoL questionnaire (15D), the Dermatology Life Quality Index (DLQI), and the Beck Depression Inventory-21 (BDI-21). The correlation between the results of these instruments was analyzed and the 15D results were compared with an age-standardized general population and psoriasis patients. Results: Compared with an age-standardized general population, HS patients scored statistically significantly worse on several 15D dimensions. A statistically significant difference compared to psoriasis patients was detected on the sexual activity dimension. Even though not statistically significant, the observed mean values of the remaining dimensions suggest that clinically important differences may exist. The 15D score negatively correlated with the DLQI score (r = -0.492; p = 0.011) and the BDI-21 score (r = -0.592; p = 0.001). Conclusions: HS is a serious condition, with an impact at least comparable to that of psoriasis. This study shows that the 15D is a feasible tool for examining HRQoL in HS patients.
A Tale of Two Lymphomas
Authors: Parihar Vikrant , Crotty Paul , McNamara Deidre
Published: October 2017

We present a patient with coeliac disease who developed refractory coeliac disease II, which was complicated by the development of metachronous lymphomas.
Pneumoperitoneum after Endoscopic Retrograde Cholangiopancreatography due to Rupture of Intrahepatic Bile Ducts and Glisson’s Capsule in Hepatic Metastasis: A Case Report and Review of Literature
Authors: Khan Zubair , Darr Umar , Nawras Mohamad , Bawany Muhammad , Bieszczad Jacob , Alaradi Osama , Nawras Ali
Published: October 2017

Introduction: Endoscopic retrograde cholangiopancreatography (ERCP) has been proven to be a safe and effective method for diagnosis and treatment of biliary and pancreatic disorders. Major complications of ERCP include pancreatitis, hemorrhage, cholangitis, and duodenal perforation. We report a third case in literature of pneumoperitoneum after ERCP due to rupture of intrahepatic bile ducts and Glisson’s capsule in a peripheral hepatic lesion. Case Report: A 50-year-old male with a history of metastatic pancreatic neuroendocrine tumor and who had a partially covered metallic stent placed in the biliary tree 1 year ago presented to the oncology clinic with fatigue, abdominal pain, and hypotension. He was planned for ERCP for possible cholangitis secondary to obstructed previously placed biliary stent. However, the duodenoscope could not be advanced to the level of the major papilla because of narrowed pylorus and severely strictured duodenal sweep. Forward-view gastroscope was then passed with careful manipulation to the severely narrowed second part of the duodenum where the previously placed metallic stent was visualized. Balloon sweeping of stenting was done. Cholangiography did not show any leak. Following the procedure, the patient underwent CT scan of the abdomen that showed pneumoperitoneum which was communicating with pneumobilia through a loculated air collection in necrotic hepatic metastasis perforating Glisson’s capsule. The patient was managed conservatively. Conclusion: In our case, pneumoperitoneum resulted from rupture of intrahepatic bile ducts and Glisson’s capsule in hepatic metastasis. This case emphasizes the need for close clinical and radiological observation of patients with hepatic masses (primary or metastatic) subjected to ERCP.
Survey of KI, WU, MW, and STL Polyomavirus in Cancerous and Non-Cancerous Lung Tissues
Authors: Csoma Eszter , Bidiga László , Méhes Gábor , Katona Melinda , Gergely Lajos
Published: October 2017

Background/Aims: The pathogenesis of the human polyomavirus (PyV) KI, WU, MW, and STL has not been elucidated yet. Respiratory transmission is suggested, but the site of the replication, tissue, and cell tropism is not clarified. KIPyV and WUPyV DNA and/or antigen were detected in normal lung tissues previously by others. In fact, a KIPyV DNA sequence was found in lung cancer samples. Up to date, there is no publication about the DNA prevalence of MWPyV and STLPyV neither in normal nor in cancerous lung tissues. The aim of the present study was to examine the DNA prevalence of these polyomaviruses in cancerous and non-cancerous lung tissue samples, in order to study the possible site for viral replication and/or persistence, and the potential association of these viruses with lung carcinogenesis as well. Methods: 100 cancerous and 47 non-cancerous, formalin-fixed paraffin-embedded lung tissue samples were studied for KIPyV, WUPyV, MWPyV, and STLPyV by real-time PCR. Results and Conclusion: Neither of the viruses was found in samples from small-cell, non-small-cell (adenocarcinoma, squamous-cell carcinoma and large-cell neuroendocrine lung cancer), mixed-type and non-differentiated lung carcinoma, and non-cancerous lung tissues (from patients with pneumonia, emphysema and fibrosis).
Bevacizumab for Refractory Gastrointestinal Bleeding in Rendu-Osler-Weber Disease
Authors: Bernardes Carlos , Santos Sara , Loureiro Rafaela , Borges Verónica , Ramos Gonçalo
Published: October 2017

Rendu-Osler-Weber disease, also known as hereditary hemorrhagic telangiectasia, is a rare autosomal dominant disorder which is often characterized by recurrent epistaxis, mucocutaneous and gastrointestinal telangiectasias, and visceral arteriovenous malformations. Patients with gastrointestinal involvement can present with a wide spectrum of severity, which may vary from uncomplicated iron deficiency anemia to continuous and refractory bleeding. We present the case of a 62-year-old female, who was admitted with anemia following several episodes of melena, and whose endoscopic examination revealed multiple angiodysplasias in the stomach and small bowel. Despite endoscopic and medical treatment attempts with hormonal agents and octreotide, she developed persistent hemorrhage and severe anemia, requiring frequent red blood cell transfusions. Immediately after initiating bevacizumab (7.5 mg/kg, every 3 weeks), complete cessation of bleeding episodes was observed. Currently, after 1 year of follow-up, she maintained sustained remission without the occurrence of adverse events.
Estimation of Urinary Creatinine Excretion and Prediction of Renal Function in Morbidly Obese Patients: New Tools from Body Composition Analysis
Authors: Donadio Carlo , Moriconi Diego , Berta Rossana , Anselmino Marco
Published: October 2017

Background/Aims: In obese subjects the accuracy of prediction of renal function is quite low. The aim of this study was to obtain a more accurate estimate of urinary creatinine excretion (UCr), creatinine clearance (CCr), and GFR from body cell mass (BCM). Methods: Seventy-three adult morbidly obese patients (BMI 35.2-64.5 kg/m2) were examined. BCM was calculated from body impedance analysis. CCr was measured (mCCr) and was predicted from BCM and antropometric data (MR-BCMCCr), with Cockcroft and Gault (C&GCCr) and Salazar and Corcoran (S&CCCr) formulas. GFR was predicted from BCM (BCM GFR) and with MDRD and CKD-EPI formulas. Results: Multiple regression (MR) indicated a strict linear correlation between UCr, BCM and anthropometric data. UCr predicted from MR equation (MR-BCMUCr) was very similar to measured UCr. MR-BCMCCr (168±46 mL/min) and mCCr (167±51 mL/min) were also similar, while significant differences were found between mCCr, C&GCCr and S&CCCr. The correlation and the agreement between MR-BCMCCr and mCCr were closer and prediction error was lower than the other formulas. BCM GFR (125±32 mL/min) had close correlations and agreements with MDRD GFR and CKD EPI formulas. Conclusions: In morbidly obese patients the measurement of BCM meliorates the prediction of UCr and CCr, and allows the prediction of GFR.
Overexpression of M3 Muscarinic Receptor Suppressed Adverse Electrical Remodeling in Hypertrophic Myocardium Via Increasing Repolarizing K+ Currents
Authors: Chen Xue , Bai Yan , Sun Hanqi , Su Zhenli , Guo Jing , Sun Chuan , Du Zhimin
Published: October 2017

Background/Aims: Cardiac hypertrophy (CH) is an adaptive response to diverse cardiovascular conditions, which is accompanied by adverse electrical remodeling manifested as abnormal K+ channel activities. M3 subtype of muscarinic acetylcholine receptor (M3-mAChR) is a novel regulator of cardiac electrical activity. In this study we aim to explore if the overexpression of M3-mAChR could attenuate the adverse electrical remodeling in CH and then uncover its underlying electrophysiological mechanisms. Methods: Transgenic mice with M3-mAChR overexpression (M3-TG) and wild type (WT) mice were subjected to transverse aortic constriction (TAC) to induce CH. Myocardial hypertrophy and cardiac function were quantified by the measurement of echocardiography, electrocardiogram, heart weight and tibia length. Whole-cell and signal-cell patch-clamp were employed to record electrophysiological properties by acute isolation of acutely isolated ventricular cardiomyocytes and Western blot was carried out to evaluate the Kir2.1and Kv4.2/4.3 protein levels in left ventricular tissue. Results: Compared with WT group, the elevation of cardiac index, including heart weight/body weight index and heart weight/tibia length index confirmed the myocardial hypertrophic growth induced by TAC. Echocardiography detection revealed that the TAC-treated mice showed an obvious increase in the thickness of left ventricular posterior wall (LVPW) and ejection fraction (EF) due to compensatory hypertrophy, which attenuated by the overexpression of M3-mAChR. Pressure overload induced a prolongation of QTc interval in WT mice, an effect blunted in M3-TG mice. Furthermore, compared with WT mice, M3-mAChR overexpression in hypertrophic myocardium accelerated cardiac repolarization and shortened action potential duration, and thus correcting the prolongation of QTc interval. Moreover, M3-TG mice have the greater current density of IK1 and Ito in ventricular myocytes after TAC compared with WT mice. Finally, compared with WT mice, M3-TG mice expressed higher levels of Kir2.1 in ventricular myocytes. Conclusion: M3-mAChR overexpression protected against adverse electrical remodeling in CH by enhancing potassium currents and promoting repolarization.
Microarray Expression Profile and Functional Analysis of Circular RNAs in Osteosarcoma
Authors: Liu Weihai , Zhang Jiajun , Zou Changye , Xie Xianbiao , Wang Yongqian , Wang Bo , Zhao Zhiqiang , Tu Jian , Wang Xiaoshuai , Li Hongyi , Shen Jingnan , Yin Junqiang
Published: October 2017

Background/Aims: Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. However, the molecular mechanisms regulating osteosarcoma tumorigenesis and progression are still poorly understood. Circular RNAs (circRNAs) have been identified as microRNA sponges and are involved in many important biological processes. This study aims to investigate the global changes in the expression pattern of circRNAs in osteosarcoma and provide a comprehensive understanding of differentially expressed circRNAs. Methods: Microarray based circRNA expression was determined in osteosarcoma cell lines and compared with hFOB1.19, which was used as the normal control. We confirmed the microarray data by real time-qPCR in both osteosarcoma cell lines and tissues. The circRNA/microRNA/mRNA interaction network was predicted using bioinformatics. Gene Ontology analysis and 4 annotation tools for pathway analysis (KEGG, Biocarta, PANTHER and Reactome) were used to predict the functions of differentially expressed circRNAs. Results: We revealed a number of differentially expressed circRNAs and 12 of them were confirmed, which suggests a potential role of circRNAs in OS. Among these differentially expressed circRNAs, hsa_circRNA_103801 was up-regulated in both osteosarcoma cell lines and tissues, while hsa_circRNA_104980 was down-regulated. The most likely potential target miRNAs for hsa_circRNA_103801 include hsa-miR-370-3p, hsa-miR-338-3p and hsa-miR-877-3p, while the most potential target miRNAs of hsa_circRNA_104980 consist of hsa-miR-1298-3p and hsa-miR-660-3p. Functional analysis found that hsa_circRNA_103801 was involved in pathways in cancer, such as the HIF-1, VEGF and angiogenesis pathway, the Rap1 signaling pathway and the PI3K-Akt signaling pathway, while hsa_circRNA_104980 was related to some pathways such as the tight junction pathway. Conclusions: This study has identified the comprehensive expression profile of circRNAs in osteosarcoma for the first time. And the ceRNA network prediction and bioinformatics functional analysis could provide a comprehensive understanding of hsa_circRNA_103801 and hsa_circRNA_104980, which may be involved in the initiation and progression of osteosarcoma. The present study indicates that circRNAs may play important roles in osteosarcoma and thus serve as biomarkers of osteosarcoma diagnosis and treatment.
Nicotine-Induced Airway Smooth Muscle Cell Proliferation Involves TRPC6-Dependent Calcium Influx Via α7 nAChR
Authors: Hong Wei , Peng Gongyong , Hao Binwei , Liao Baoling , Zhao Zhuxiang , Zhou Yumin , Peng Fang , Ye Xiuqin , Huang Lingmei , Zheng Mengning , Pu Jinding , Liang Chunxiao , Yi Erkang , Peng Huanhuan , Li Bing , Ran Pixin
Published: October 2017

Background/Aims: The proliferation of human bronchial smooth muscle cells (HBSMCs) is a key pathophysiological component of airway remodeling in chronic obstructive pulmonary disease (COPD) for which pharmacotherapy is limited, and only slight improvements in survival have been achieved in recent decades. Cigarette smoke is a well-recognized risk factor for COPD; however, the pathogenesis of cigarette smoke-induced COPD remains incompletely understood. This study aimed to investigate the mechanisms by which nicotine affects HBSMC proliferation. Methods: Cell viability was assessed with a CCK-8 assay. Proliferation was measured by cell counting and EdU immunostaining. Fluorescence calcium imaging was performed to measure intracellular Ca2+ concentration ([Ca2+]i). Results: The results showed that nicotine promotes HBSMC proliferation, which is accompanied by elevated store-operated calcium entry (SOCE), receptor-operated calcium entry (ROCE) and basal [Ca2+]i in HBSMCs. Moreover, we also confirmed that canonical transient receptor potential protein 6 (TRPC6) and α7 nicotinic acetylcholine receptor (α7 nAChR) are involved in nicotine-induced upregulation of cell proliferation. Furthermore, we verified that activation of the PI3K/Akt signaling pathway plays a pivotal role in nicotine-enhanced proliferation and calcium influx in HBSMCs. Inhibition of α7 nAChR significantly decreased Akt phosphorylation levels, and LY294002 inhibited the protein expression levels of TRPC6. Conclusion: Herein, these data provide compelling evidence that calcium entry via the α7 nAChR-PI3K/Akt-TRPC6 signaling pathway plays an important role in the physiological regulation of airway smooth muscle cell proliferation, representing an important target for augmenting airway remodeling.
Fangchinoline Induces Apoptosis, Autophagy and Energetic Impairment in Bladder Cancer
Authors: Fan Bo , Zhang Xiaoyu , Ma Yongliang , Zhang Aili
Published: October 2017

Background/Aims: Tetrandrine and Fangchinoline (Fcn) are two natural products that are found in Stephania tetrandra. Tetrandrine is a known anti-bladder cancer compound, but the effects of Fcn on bladder cancer have been previously unclear. In the present study, we focused on the anti-tumor effects of Fcn on bladder cancer. Methods and Results: We treated T24 and 5637 bladder cancer cell lines with Fcn in vitro. We observed that Fcn inhibited the viability of bladder cancer cells in a concentration-dependent manner. The expression of PCNA, a biomarker of proliferation, was down-regulated. Fcn treatment induced both apoptosis and autophagy in bladder cancer cells, as shown by the increased cleavage of caspase-3, an up-regulated LC3-II/LC3-I ratio and the down-regulated p62 level. Blocking autophagy with 3-MA (3-Methyladenine) enhanced Fcn-induced apoptosis, indicating that Fcn-induced autophagy was adaptive. Additionally, we observed that Fcn treatment inhibited mTOR and reduced the intracellular ATP levels. The exogenous addition of methyl pyruvate (MP) to compensate metabolic substrates alleviated Fcn-induced apoptosis and autophagy. Conclusions: Our data indicated that Fcn caused an impairment in energy generation, which led to apoptosis and adaptive autophagy in bladder cancer. These results demonstrated that Fcn may be a potential candidate for use in the prevention and treatment of bladder cancer.
Inhibition of Prenylation Promotes Caspase 3 Activation, Lamin B Degradation and Loss in Metabolic Cell Viability in Pancreatic β-Cells
Authors: Syeda Khadija G. , Kowluru Anjan
Published: October 2017

Background/Aims: Lamins are intermediate filament proteins that constitute the main components of the lamina underlying the inner-nuclear membrane and serve to organize chromatin. Lamins (e.g., lamin B) undergo posttranslational modifications (e.g., isoprenylation) at their C-terminal cysteine residues. Such modifications are thought to render optimal association of lamins with the nuclear envelop. Using human islets, rodent islets, and INS-1 832/13 cells, we recently reported significant metabolic defects under glucotoxic and endoplasmic reticulum (ER) stress conditions, including caspase 3 activation and lamin B degradation. The current study is aimed at further understanding the regulatory roles of protein prenylation in the induction of the aforestated metabolic defects. Methods: Subcellular phase partitioning assay was done using Triton X-114. Cell morphology and metabolic cell viability assays were carried out using standard methodologies. Results: We report that exposure of pancreatic β-cells to Simvastatin, an inhibitor of mevalonic acid (MVA) biosynthesis, and its downstream isoprenoid derivatives, or FTI-277, an inhibitor of farnesyltransferase that mediates farnesylation of lamins, leads to activation of caspase 3 and lamin B degradation. Furthermore, Simvastatin-treatment increased activation of p38MAPK (a stress kinase) and inhibited ERK1/2 (regulator of cell proliferation). Inhibition of farnesylation also resulted in the release of degraded lamin B into the cytosolic fraction and promoted loss in metabolic cell viability. Conclusion: Based on these findings we conclude that protein prenylation plays key roles in islet β-cell function. These findings affirm further support to the hypothesis that defects in prenylation pathway induce caspase-3 activation and nuclear lamin degradation in pancreatic β-cells under the duress of metabolic stress (e.g., glucotoxicity).
The Rs4938723 Polymorphism Reduces Expression of MicroRNA-34b and Increases the Risk of Recurrence after Endoscopic Dissection in Early Gastric Cancer
Authors: Yu Kuaiyun
Published: October 2017

Background: In respect to the effect of MET1 upon the recurrence of Early gastric cancer (EGC) after endoscopic dissection (ESD) treatment, we aimed to investigate the molecular mechanism, including the potential regulator and signaling pathways of MET1 in this study. Methods: We searched the miRNA database online (www.mirdb.org) with the “seed sequence” located within the 3’-UTR of the target gene, and then validated MET1 to be the direct gene via luciferase reporter assay system. Real-time PCR and western-blot were used to determine the expression of miR-34b mRNA and MET1 mRNA and protein in different treating group. Results: MET1 was the direct gene of miR-34b by searching the miRNA database online and constructing luciferase reporter. We also investigated the negative regulatory relationship between miR-34b and MET1 via studying the relative luciferase activity at different concentrations of miR-34b mimics. Further, since rs4938723 polymorphism was previously reported to be interfering with the expression of miR-34b, we investigated the expression level of different genotypes including TT (N=20), TC (N=9) and CC (N=3), which supported the hypothesis that the presence of minor allele (C) of rs4938723 polymorphism compromised the expression of miR-34b. Meanwhile, we also conducted real time PCR and Western blot analysis to study the mRNA and protein expression level of MET1 among different genotypes or cells treated with different concentration of miR-34b mimics/inhibitors, indicating the negative regulatory relationship between miR-34b and MET1.We also investigated the relative viability of EGC cells when transfected with miR-34b mimics (50nM and 100nM) and miR-34b inhibitors (100nM) to validate miR-34b to be negatively interfering with the viability of EGC cells. Conclusion: These data confirmed miR-34b rs4938723 polymorphism was also recognized as a biomarker to predict recurrence after ESD in EGC patients via analysis upon the recurrence-free rate among different genotypes of EGC patients.
Coronary Artery Diameter is Inversely Associated with the Severity of Coronary Lesions in Patients Undergoing Coronary Angiography
Authors: Zhou Fang-Fang , Liu Yun-hai , Ge Peng-Cheng , Chen Zhao-Hong , Ding Xiao-Qing , Liu Jie-Yin , Jia Qiao-Wei , An Feng-Hui , Li Li-Hua , Wang Lian-Sheng , Ma Wen-Zhu , Yang Zhi-Jian , Jia En-Zhi
Published: October 2017

Background: The diameters of the coronary arteries have been suggested to be a potential predictor of coronary artery disease (CAD). However, whether the diameters of the coronary arteries are associated with the coronary lesion severity on angiography has not been determined. Methods: One hundred sixty-seven consecutive adult patients (109 men and 58 women) aged 31–84 years who underwent coronary angiography for suspected or known CAD were enrolled. The known catheter tip diameter was used as the calibration to measure the diameters of coronary arteries, and the severity of coronary lesions was evaluated with the vessel score and Gensini score. Results: In patients with a higher vessel score and Gensini score, the diameters of the left main (LM), left anterior descending (LAD), left circumflex (LCX), and right coronary arteries (RCA) were smaller (all p<0.05) than those in patients with lower scores. Multiple linear regression analysis indicated that the average coronary artery diameter was significantly associated with the Gensini score (β=-0.444, p<0.00001). Moreover, the diameters of the coronary arteries were potential predictors of CAD, with areas under the receiver operating characteristic curves of 0.268 for average diameter (95% confidence interval [CI]: 0.183–0.353, p<0.00001), 0.356 for the LM diameter (95% CI: 0.266–0.445, p=0.005), 0.214 for the LAD diameter (95% CI: 0.136–0.291, p<0.00001), 0.366 for the LCX diameter (95% CI: 0.271–0.461, p=0.009), and 0.346 for the RCA diameter (95% CI: 0.245–0.447, p=0.003). Conclusion: The diameters of coronary arteries are inversely associated with the severity of CAD.
H3 Relaxin Protects Against Myocardial Injury in Experimental Diabetic Cardiomyopathy by Inhibiting Myocardial Apoptosis, Fibrosis and Inflammation
Authors: Zhang Xiaohui , Pan Liya , Yang Kelaier , Fu Yu , Liu Yue , Chi Jinyu , Zhang Xin , Hong Siting , Ma  Xiao , Yin Xinhua
Published: October 2017

Background/Aims: Apoptosis, fibrosis and NLRP3 inflammasome activation are involved in the development of diabetic cardiomyopathy (DCM). Human recombinant relaxin-3 (H3 relaxin) is a novel bioactive peptide that inhibits cardiac injury; however, whether H3 relaxin prevents cardiac injury in rats with DCM and the underlying mechanisms are unknown. Methods: To investigate the effect of H3 relaxin on DCM, we performed a study using H3 relaxin treatment in male Sprague-Dawley (SD) rats with streptozotocin (STZ)-induced diabetes (DM). We measured apoptosis, fibrosis and NLRP3 inflammasome markers in the rat hearts four and eight weeks after the rats were injected with STZ (65 mg/kg) by western blot analysis. Subsequently, 2 or 6 weeks after the STZ treatment, the rats were treated with H3 relaxin [2 µg/kg/d (A group) or 0.2 µg/kg/d (B group)] for 2 weeks. Cardiac function was evaluated by echocardiography to determine the extent of myocardial injury in the DM rats. The protein levels of apoptosis, fibrosis and NLRP3 inflammasome markers were used to assess myocardial injury. In addition, we determined the plasma levels of IL-1β and IL-18 using a Milliplex MAP Rat Cytokine/Chemokine Magnetic Bead Panel kit. Results: The protein expression of cleaved caspase-8, caspase-9 and caspase-3 as well as fibrosis markers increased at 4 and 8 weeks in the STZ-induced diabetic hearts compared with the levels in the control group. Furthermore, the NLRP3 inflammasome was substantially activated in STZ-induced diabetic hearts, leading to increased IL-1β and IL-18 levels. Compared with the DM group, the A group exhibited substantially better cardiac function. The protein levels of apoptosis markers were attenuated by H3 relaxin, indicating that H3 relaxin inhibited myocardial apoptosis in the hearts of diabetic rats. The protein expression of fibrosis markers was inhibited by H3 relaxin. Additionally, the protein expression and activation of the NLRP3 inflammasome were also effectively attenuated by H3 relaxin. Conclusions: This study is the first to demonstrate that H3 relaxin plays an anti-apoptotic, anti-fibrotic and anti-inflammatory role in DCM.
Iodine Promotes Tumorigenesis of Thyroid Cancer by Suppressing Mir-422a and Up-Regulating MAPK1
Authors: Wang Junyi  , Yang Haiou , Si Yiran , Hu Dongzhi , Yu Yang , Zhang Yan  , Gao Ming , Zhang Haiyang
Published: October 2017

Background/Aims: Iodine may trigger tumorigenesis and development of thyroid carcinoma, but the mechanisms involved remained elusive. MicroRNA (MiRNAs) are known to be involved in each stage of cancer development; however, the role of miRNAs in iodine-induced tumorigenesis of thyroid carcinoma remained unknown. In this study, we aimed at investigating miRNA related signaling pathway in thyroid cancer cells. Methods: Levels of miRNAs and mRNAs were determined using RT-qPCR and proteins were quantified by western blotting. Cell migration and proliferation were checked using Transwell assay and CCK8 assay respectively. Tumor xenografts in nude mice were established by subcutaneous injection of cancer cells. Results: Mitogen activated protein kinase 1 (MAPK1) was significantly up-regulated, while miR-422a was down-regulated in thyroid cancer cells cultured with high iodine; miR-422a directly bound to the 3’UTR of MAPK1 mRNA. Moreover, miR-422a negatively regulated MAPK1 expression, and down-regulated miR-422a promoted proliferation and migration of TPC-1 cells. In vivo studies also confirmed that iodine promoted tumor growth by suppressing miR-422a and up-regulating MAPK1. Conclusions: Our study illustrates a new pathway comprising iodine, miRNA and MAPK1, and defines a novel mechanism in thyroid cancer.
The Impact of Chronic Repetitive Leg Ischemia on Left Ventricular Function and Severity of Coronary Atherosclerosis in Patients with Acute Coronary Syndrome
Authors: Gungor Mutlu , Yildirim Erkan
Published: October 2017

Objective: The purpose of this study was to assess the impact of the presence of peripheral arterial disease (PAD) on left ventricular (LV) function in patients with coronary artery disease (CAD) presenting with acute coronary syndrome (ACS). Subjects and Methods: The medical records of the patients who were referred to Ankara Bayindir Hospital, Ankara, Turkey, due to a first episode of ACS were reviewed. Patients with concomitant PAD and CAD (group 1) were compared with those who had CAD only (group 2). The Mann-Whitney U and χ2 tests were used to compare continuous and categorical variables, respectively. Results: Baseline demographic data of 53 patients with PAD + CAD (42 men and 11 women; mean age 62.5 ± 9.5 years) and a group of 60 patients with CAD only (41 men and 19 women; mean age 59.9 ± 9.8 years) were similar, except for the serum creatinine level which was higher in group 1 than in group 2 (1.32 ± 0.34 vs. 1.03 ± 0.22 mg/dL, p < 0.001). Patients with CAD + PAD had significantly higher Gensini scores (62.6 ± 19.7 vs. 41.4 ± 26.8, p = 0.004) and more 3-vessel disease than patients with CAD alone (62.2 vs. 31.6%, p < 0.045). There was a significant difference between the 2 groups regarding the LV ejection fraction at the time of the diagnosis (52.0 ± 8.2% in the CAD + PAD group and 43.7 ± 13.3% in the CAD-alone group; p = 0.017). Conclusion: CAD concomitant with PAD was associated with preserved LV function at early stages of diagnosis in patients with ACS.
Antibiotic Resistance Trends in Methicillin-Resistant Staphylococcus aureus Isolated in Kuwait Hospitals: 2011-2015
Authors: Udo Edet E. , Boswihi Samar S.
Published: October 2017

Objective: The aim of this study was to determine antibiotic resistance trends and carriage of staphylococcal cassette chromosome mec (SCCmec) genetic elements in methicillin-resistant Staphylococcus aureus (MRSA) isolated in Kuwait hospitals to ascertain whether they were healthcare associated (HA-MRSA) or community associated (CA-MRSA). Materials and Methods: In total, 6,922 MRSA isolates obtained from different clinical samples were tested for resistance to antibiotics, urease production, and carriage of SCCmec elements. Results: All MRSA isolates were susceptible to linezolid, vancomycin, and teicoplanin. However, some isolates were resistant to kanamycin (2,979; 43%), ciprofloxacin (2,955; 42.7%), erythromycin and clindamycin (2,935; 42.4%), fusidic acid (2,858; 41.2%), gentamicin (2,665; 38.5%), tetracycline (2,652; 38.3%), and trimethoprim (2,324; 33.5%). Whereas the prevalence of resistance to most antibiotics showed annual variations, those resistant to chloramphenicol and rifampicin increased from 2.6 and 0.1% to 9.6 and 1.6%, respectively, and high-level mupirocin resistance declined from 9.3% in 2011 to 3.6% in 2015. In total, 3,244 (53.9%) of the isolates carried SCCmec IV followed by SCCmec III (1,737; 28.8%) and SCCmec V (890; 14.8%). SCCmec I (21; 0.3%) and II (79; 0.8%) occurred sporadically. A total of 3,651 (60.7%) of the isolates belonged to the CA-MRSA genotype and 2,290 isolates (38.1%) were identified as HA-MRSA. Conclusion: This study demonstrates changes in antibiotic resistance patterns of MRSA over time and reinforces the value of surveillance in detecting such changes for the benefit of infection control and patient management.