bluuebunny/crossref_metadata_2025 huggingface dataset:
Splinting of Longitudinal Fracture: An Innovative Approach
Authors: Bansal Rashmi , Chowdhary Priyanka , Gurtu Anuraag , Mehrotra Nakul , Kishore Abhinav
Published: May 2016

Trauma may result in craze lines on the enamel surface, one or more fractured cusps of posterior teeth, cracked tooth syndrome, splitting of posterior teeth, and vertical fracture of root. Out of these, management of some fractures is of great challenge and such teeth are generally recommended for extraction. Literature search reveals attempts to manage such fractures by full cast crown, orthodontic wires, and so forth, in which consideration was given to extracoronal splinting only. However, due to advancement in materials and technologies, intracoronal splinting can be achieved as well. In this case report, longitudinal fractures in tooth #27, tooth #37, and tooth #46 had occurred. In #27, fracture line was running mesiodistally involving the pulpal floor resulting in a split tooth. In teeth 37 and 46, fractures of the mesiobuccal cusp and mesiolingual cusp were observed, respectively. They were restored with cast gold inlay and full cast crown, respectively. Longitudinal fracture of 27 was treated with an innovative approach using intracanal reinforced composite with Ribbond, external reinforcement with an orthodontic band, and full cast metal crown to splint the split tooth.
Effect of the Modification of the Start-Up Sequence on the Thermal Stresses for a Microgas Turbine
Authors: Tenango-Pirin Oscar , García J. C. , Castro-Gómez Laura , Rodríguez J. A. , Sierra F. , De Santiago Oscar , Rodríguez-Lelis J. M.
Published: May 2016

Microgas turbines (MGT) are an alternative for small-scale energy production; however, their small size becomes a drawback since it enhances the heat transfer among their components. Moreover, heat transfer drives to temperature gradients which become higher during transient cycles like start-up. The influence of different start-up curves on temperature and thermal stresses of a microgas turbine was investigated. Stationary and rotational blades of the turbine were numerically simulated using CFD and FEM commercial codes. Conjugated heat transfer cases were solved for obtaining heat transfer from fluid toward the blades. Changes of temperature gradients within the blades during the start-ups were calculated under transient state with boundary conditions according to each curve to assess accurate thermal stresses calculations. Results showed that the modification of the start-up curves had an impact on the thermal stresses levels and on the time when highest stresses appeared on each component. Furthermore, zones highly stressed were located near the constraints of blades where thermal strains are restricted. It was also found that the curve that had a warming period at the beginning of the start-up allowed reducing the peaks of stresses making it more feasible and safer for the turbine start-up operation.
ADrosophilaModel for Screening Antiobesity Agents
Authors: Men Tran Thanh , Thanh Duong Ngoc Van , Yamaguchi Masamitsu , Suzuki Takayoshi , Hattori Gen , Arii Masayuki , Huy Nguyen Tien , Kamei Kaeko
Published: May 2016

Although triacylglycerol, the major component for lipid storage, is essential for normal physiology, its excessive accumulation causes obesity in adipose tissue and is associated with organ dysfunction in nonadipose tissue. Here, we focused on theDrosophilamodel to develop therapeutics for preventing obesity. The brummer (bmm) gene inDrosophila melanogasteris known to be homologous with human adipocyte triglyceride lipase, which is related to the regulation of lipid storage. We established aDrosophilamodel for monitoringbmmexpression by introducing the green fluorescent protein (GFP) gene as a downstream reporter of thebmmpromoter. The third-instar larvae ofDrosophilashowed the GFP signal in all tissues observed and specifically in the salivary gland nucleus. To confirm the relationship betweenbmmexpression and obesity, the effect of oral administration of glucose diets onbmmpromoter activity was analyzed. TheDrosophilaflies given high-glucose diets showed higher lipid contents, indicating the obesity phenotype; this was suggested by a weaker intensity of the GFP signal as well as reducedbmmmRNA expression. These results demonstrated that the transgenicDrosophilamodel established in this study is useful for screening antiobesity agents. We also report the effects of oral administration of histone deacetylase inhibitors and some vegetables on thebmmpromoter activity.
Histone Lysine Methylation in TGF-β1 Mediated p21 Gene Expression in Rat Mesangial Cells
Authors: Guo Qiaoyan , Li Xiaoxia , Han Hongbo , Li Chaoyuan , Liu Shujun , Gao Wenhui , Sun Guangdong
Published: May 2016

Transforming growth factor beta1- (TGF-β1-) induced p21-dependent mesangial cell (MC) hypertrophy plays a key role in the pathogenesis of chronic renal diseases including diabetic nephropathy (DN). Increasing evidence demonstrated the role of posttranscriptional modifications (PTMs) in the event; however, the precise regulatory mechanism of histone lysine methylation remains largely unknown. Here, we examined the roles of both histone H3 lysine 4 and lysine 9 methylations (H3K4me/H3K9me) in TGF-β1 induced p21 gene expression in rat mesangial cells (RMCs). Our results indicated that TGF-β1 upregulated the expression of p21 gene in RMCs, which was positively correlated with the increased chromatin marks associated with active genes (H3K4me1/H3K4me2/H3K4me3) and negatively correlated with the decreased levels of repressive marks (H3K9me2/H3K9me3) at p21 gene promoter. TGF-β1 also elevated the recruitment of the H3K4 methyltransferase (HMT) SET7/9 to the p21 gene promoter. SET7/9 gene silencing with small interfering RNAs (siRNAs) significantly abolished the TGF-β1 induced p21 gene expression. Taken together, these results reveal the key role of histone H3Kme in TGF-β1 mediated p21 gene expression in RMC, partly through HMT SET7/9 occupancy, suggesting H3Kme and SET7/9 may be potential renoprotective agents in managing chronic renal diseases.
The Interactive Relationship between Pain, Psychosis, and Agitation in People with Dementia: Results from a Cluster-Randomised Clinical Trial
Authors: Habiger Torstein F. , Flo Elisabeth , Achterberg Wilco P. , Husebo Bettina S.
Published: May 2016

Background. Neuropsychiatric symptoms are common in people with dementia, and pain is thought to be an important underlying factor. Pain has previously been associated with agitation, and pain treatment has been shown to ameliorate agitated behaviour. So far, the association between pain and psychosis and the effect of pain treatment on psychotic symptoms is unclear. Furthermore, the impact of opioid treatment on psychosis is not established.Aim. To investigate the efficacy of a stepwise protocol for treating pain (SPTP) on psychosis and agitation measured with the Neuropsychiatric Inventory, Nursing Home version, and to explore the impact of opioid analgesics on psychosis.Method. Secondary analyses are from a cluster-randomised controlled trial including 352 patients with advanced dementia and agitation from 18 nursing homes in Western Norway. The intervention group received pain treatment according to SPTP.Results. Pain was associated with disinhibition (adjusted OR: 1.21, 95% CI: 1.10–1.34) and irritability (adjusted OR: 1.10, 95% CI: 1.01–1.21) at baseline. Pain treatment reduced agitation (p< 0.001, df = 1; 300) and aberrant motor behaviour (p= 0.017, df = 1; 300). Psychosis was reduced in people with at least one symptom at baseline (p= 0.034, df = 1; 135). The use of opioid analgesics did not increase psychotic symptoms.Study Registration. This trial is registered with ClinicalTrials.gov (NCT01021696), Norwegian Medicines Agency, EudraCT (EudraCTnr: 2008-007490-20).
Development and Evaluation of Stability of a Gel Formulation Containing the Monoterpene Borneol
Authors: Dantas Milla Gabriela Belarmino , Reis Silvio Alan Gonçalves Bomfim , Damasceno Camila Mahara Dias , Rolim Larissa Araújo , Rolim-Neto Pedro José , Carvalho Ferdinando Oliveira , Quintans-Junior Lucindo José , Almeida Jackson Roberto Guedes da Silva
Published: May 2016

Borneol is a bicyclic monoterpenoid alcohol commonly used in traditional Chinese and Indian medicine. It is extracted from the essential oil of various medicinal plants. It has antibacterial, analgesic, and anti-inflammatory action proven in studies that used oral and intraperitoneal applications of this monoterpene in mice. The current study was designed to develop a topical gel formulation containing the monoterpene borneol using carbopol as gel base and to evaluate its stability. The prepared formulation was subjected to physical characterization and physical-chemistry assessment. The gel was prepared from carbopol and 5% of borneol. The prepared gel was subjected to pharmacotechnical tests such as its pH, viscosity, conductivity, spreadability, centrifugation, and accelerated stability with freezing-thaw cycle. The borneol was successfully incorporated into the carbopol formulation. Borneol gel (BG5) showed good stability after eight months of its development and after 12 days in the freeze-thaw cycle, not showing statistical difference in pH value, conductivity, and viscosity before and after test. Furthermore, the formulation showed a good spreadability. Therefore, it was concluded that the formulation could be very promising alternative for the topical or transdermal treatment of skin diseases.
A Novel 1D Hybrid Chaotic Map-Based Image Compression and Encryption Using Compressed Sensing and Fibonacci-Lucas Transform
Authors: Zhang Tongfeng , Li Shouliang , Ge Rongjun , Yuan Min , Ma Yide
Published: May 2016

A one-dimensional (1D) hybrid chaotic system is constructed by three different 1D chaotic maps in parallel-then-cascade fashion. The proposed chaotic map has larger key space and exhibits better uniform distribution property in some parametric range compared with existing 1D chaotic map. Meanwhile, with the combination of compressive sensing (CS) and Fibonacci-Lucas transform (FLT), a novel image compression and encryption scheme is proposed with the advantages of the 1D hybrid chaotic map. The whole encryption procedure includes compression by compressed sensing (CS), scrambling with FLT, and diffusion after linear scaling. Bernoulli measurement matrix in CS is generated by the proposed 1D hybrid chaotic map due to its excellent uniform distribution. To enhance the security and complexity, transform kernel of FLT varies in each permutation round according to the generated chaotic sequences. Further, the key streams used in the diffusion process depend on the chaotic map as well as plain image, which could resist chosen plaintext attack (CPA). Experimental results and security analyses demonstrate the validity of our scheme in terms of high security and robustness against noise attack and cropping attack.
Hydropneumothorax in Children: A Rare Complication of a Bacterial Pneumonia
Authors: Ortega Carolina , Gonzales Carla , Soto-Martinez Manuel E. , Yock-Corrales Adriana
Published: May 2016

Hydropneumothorax is an uncommon presentation of a complicated pneumonia, and very few cases in the pediatric population have been reported. This is a case of a 5-month-old patient who presented to the emergency department (ED) with a three-day history of fever, diarrhea, and respiratory distress. His initial assessment suggested a lower respiratory tract infection and because of his respiratory distress and hypoxia a chest X-ray was performed. Other clinical information and radiologic studies will be discussed further, but his chest X-ray suggested a right-sided hydropneumothorax secondary to a complicated pneumonia. He completed 12 days of IV antibiotic treatment and required a chest tube for drainage. Patient was discharged home with a full recovery.
Presentation of Two Cases with Early Extracranial Metastases from Glioblastoma and Review of the Literature
Authors: Johansen Maria Dinche , Rochat Per , Law Ian , Scheie David , Poulsen Hans Skovgaard , Muhic Aida
Published: May 2016

Extracranial metastases from glioblastoma are rare. We report two patients with extracranial metastases from glioblastoma. Case 1 concerns a 59-year-old woman with multiple metastases that spread early in the course of disease. What makes this case unusual is that the tumor had grown into the falx close to the straight sinus and this might be an explanation to the early and extensive metastases. Case 2 presents a 60-year-old man with liver metastasis found at autopsy, and, in this case, it is more difficult to find an explanation. This patient had two spontaneous intracerebral bleeding incidents and extensive bleeding during acute surgery with tumor removal, which might have induced extracranial seeding. The cases presented might have hematogenous spreading in common as an explanation to extracranial metastases from GBM.
Effect of Harvest Year and Altitude on Nutritional and Biometric Characteristics of Blueberry Cultivars
Authors: Correia Sofia , Gonçalves Berta , Aires Alfredo , Silva Ademar , Ferreira Luís , Carvalho Rosa , Fernandes Hortense , Freitas Cândida , Carnide Valdemar , Paula Silva Ana
Published: May 2016

In recent years the consumption of small fruits has increased continuously and knowledge about the more suitable production requirements is essential. This study aims to evaluate the influence of harvest year and altitude on chemical composition of four blueberry cultivars, in order to create rentable opportunities for producers and minimize eventual losses in quality fruits. Dry mass, protein, fat, energy, free sugars, organic acids, and vitamin C contents were determined using HPLC-UV-DAD and spectrophotometric methods. Differences (p<0.05) in the concentrations of free sugars, organic acids, and vitamin C were found among years, while the altitude had no (p>0.05) influence. Citric acid was the main organic acid and fructose the most abundant sugar in blueberries. Fruits of “Ozarkblue” had the highest mass and volume whilst the “Bluecrop” was the cultivar with highest crude protein and fat contents. “Goldtraube” showed the highest content of sucrose and organic acids and “Duke” had the highest content of fructose.
Modeling of the Stepped Leader Initiation Process in an Altitude Triggered Lightning
Authors: Zhang Bo , Chen Bin , Shi Lihua , Chen Qiang
Published: May 2016

In an altitude triggered lightning, the potential and charge distribution of the triggering wire, a floating conductor, is unknown and changeable during the triggering process, which makes it difficult to simulate an altitude triggered lightning in a numerical work. To solve this problem, a 3D altitude triggered lightning model is developed in this paper, which contains two parts, a Thundercloud Model which is time-dependent and nonhydrostatic and takes 27 kinds of microphysical processes into consideration and a Triggering Model in which a charge conservation equation is introduced to describe the floating conductor and to ensure the overall neutrality of the leader channel. Numerical results of the stepped leader initiation process are given, which are in good agreement with experiment observations.
Practical Application of Columbia Classification for Focal Segmental Glomerulosclerosis
Authors: Han Man-Hoon , Kim Yong-Jin
Published: May 2016

Focal segmental glomerulosclerosis (FSGS) is a heterogeneous clinicopathological entity. Two frameworks for the classification of FSGS have been described: etiologic and morphologic. The etiologic classification is distinguished among genetic, adaptive, virus-associated, drug-induced, and idiopathic types. Morphologic classification is commonly referred to as the Columbia classification published in 2004, which distinguishes five variants: collapsing, tip, cellular, perihilar, and not otherwise specified (NOS). This classification is based on light microscopic patterns with rigorously defined specific criteria, which can be applied to primary and secondary forms of FSGS, and has been widely used over the past 10 years both as a diagnostic and as a prognostic clinical tool. This paper defines common histopathological features of FSGS, distinguished characters among five variants, and points out the confusion about terminology of variants, because most were proposed in the past with different definitions. Despite good interobserver reproducibility of this classification system, difficulty in its application may arise in the interpretation of lesions with mixed features of more than one variant in the same tissue specimen and with late lesions, because other variants may evolve into the NOS variant over time.
Chinese Herbal Medicine as an Adjunctive Therapy for Breast Cancer: A Systematic Review and Meta‐Analysis
Authors: Zhu Libing , Li Lingru , Li Yingshuai , Wang Ji , Wang Qi
Published: May 2016

Chinese herbal medicine (CHM) has been widely used as an adjunctive therapy for breast cancer, while its efficacy remains unexplored. The purpose of this study is to evaluate the efficacy of CHM combined with chemotherapy for breast cancer. The study results showed that CHM combined with chemotherapy significantly increased tumor response and KPS as compared to using chemotherapy alone (RR = 1.36; 95% CI = 1.24–1.48; P < 0.00001; RR = 1.38; 95% CI = 1.26–1.52; P < 0.00001, resp.). Besides, CHM as an adjunctive therapy significantly reduced the nausea and vomiting at toxicity grade of III–IV (RR = 0.37; 95% CI = 0.27–0.52; P < 0.00001). Moreover, the combined therapy significantly prevented the decline of WBC in patients under chemotherapy at toxicity grade of III–IV (RR = 0.49; 95% CI = 0.34–0.69; P < 0.00001) and prevented the decline of platelet at toxicity grade of III–IV or I–IV (RR = 0.29; 95% CI = 0.12–0.73; P = 0.008; RR = 0.77; 95% CI = 0.63–0.94; P = 0.009, resp.). This study suggests that CHM combined with chemotherapy in comparison with chemotherapy alone can significantly enhance tumor response, improve KPS, and alleviate toxicity induced by chemotherapy in breast cancer patients. However, a firm conclusion could not be reached due to the lack of high quality trials and large‐scale RCTs, so further trials with higher quality and larger scale are needed.
Performance Analysis of Cooperative Spectrum Sensing under Guaranteed Throughput Constraints for Cognitive Radio Networks
Authors: Al-Doseri H. F. , Mangoud M. A.
Published: May 2016

One of the main challenges in cognitive radio networks is the ability of secondary users to detect the primary user presence with high probability of detection. In previous research, optimizing cooperative sensing in cognitive radio networks is performed for either a targeted probability of detection or a false alarm. After setting one of the probabilities as an optimization constraint, the other is optimized. In this paper, a guaranteed constant throughput at the secondary users is introduced as a target while optimizing probability of detection for cooperative sensing. Both sensing time values and number of cooperated cognitive radio secondary users are investigated to maximize the probability of detection of primary user. AND and OR hard decision schemes are considered and compared with soft decision scheme which is weighted modified deflection coefficient scheme (W-MDC). It is illustrated that cooperation of all users and utilizing full frames for sensing time will not provide maximum probability of detection. A tradeoff between performances of cognitive radio networks with and without optimization is presented. The effects of varying network sizes, normalized target throughput, maximum frame duration times, and received signal-to-noise ratio at the fusion center are investigated for different fusion rules.
Personalized Clinical Trials in Hepatocellular Carcinoma Based on Biomarker Selection
Authors: Zhang Bingnan , Finn Richard S.
Published: May 2016

Background: Since the approval of sorafenib there have been numerous failures of new agents in Phase III studies for treatment of advanced hepatocellular carcinoma (HCC). These studies have generally ignored the molecular heterogeneity of HCC and they have not enrolled patients based on predictive markers of response. The development of molecular targeted therapeutics in HCC needs to model the approach that has been taken with great success in other solid tumors, to decrease the likelihood of failure in future studies. Summary: Here we review the paradigm taken with novel targeted agents in other solid tumors and highlight ongoing studies in HCC that are incorporating biomarkers in clinical development. Key Messages: With the appreciation of the molecular diversity of HCC, clinical development of new agents in HCC will need to be targeted towards those patients who are most likely to benefit. This strategy, based on biomarkers for patient selection, is more likely to yield positive results and mitigate the risk of continued negative Phase III studies.
How to Improve Therapeutic Ratio in Radiotherapy of HCC
Authors: Tsai Chiao-Ling , Hsu Feng-Ming , Cheng Jason Chia-Hsien
Published: May 2016

Background: During the past two decades, external-beam radiation technology has substantially changed from traditional two-dimensional to conformal three-dimensional to intensity-modulated planning and stereotactic body radiotherapy (SBRT). Summary: Modern techniques of radiotherapy (RT) are highly focused and capable of delivering an ablative dose to targeted hepatocellular carcinoma (HCC) tumors. SBRT is an option for selected patients with limited tumor volume and non-eligibility for other invasive treatments. Moreover, RT combined with a radiation sensitizer (RS) to increase the therapeutic ratio has shown promising results in select studies, prompting further investigation of this combination. With the undetermined role of RT in treatment guidelines and variation in patterns of treatment failure after RT in patient with HCC, useful biomarkers to guide RT decision-making and selection of patients are needed and emerging. Key Message: The objective of this review is to summarize the current RS with SBRT schemes and biomarkers for patient selection used to maximize the effect of RT on HCC.
Qiliqiangxin Attenuates Phenylephrine-Induced Cardiac Hypertrophy through Downregulation of MiR-199a-5p
Authors: Zhang Haifeng , Li Shanshan , Zhou Qiulian , Sun Qi , Shen Shutong , Zhou Yanli , Bei Yihua , Li Xinli
Published: May 2016

Background/Aims: Qiliqiangxin (QL), a traditional Chinese medicine, has long been used to treat chronic heart failure. Previous studies demonstrated that QL could prevent cardiac remodeling and hypertrophy in response to hypertensive or ischemic stress. However, little is known about whether QL could modulate cardiac hypertrophy in vitro, and (if so) whether it is through modulation of specific hypertrophy-related microRNA. Methods: The primary neonatal rat ventricular cardiomyocytes were isolated, cultured, and treated with phenylephrine (PE, 50 µmol/L, 48 h) to induce hypertrophy in vitro, in the presence or absence of pretreatment with QL (0.5 µg/ml, 48 h). The cell surface area was determined by immunofluorescent staining for α-actinin. The mRNA levels of hypertrophic markers including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (MYH7) were assayed by qRT-PCRs. The protein synthesis of cardiomyocytes was determined by the protein/DNA ratio. The miR-199a-5p expression level was quantified in PE-treated cardiomyocytes and heart samples from acute myocardial infarction (AMI) mouse model. MiR-199a-5p overexpression was used to determine its role in the anti-hypertrophic effect of QL on cardiomyocytes. Results: PE induced obvious enlargement of cell surface in cardiomyocytes, paralleling with increased ANP, BNP, and MYH7 mRNA levels and elevated protein/DNA ratio. All these changes were reversed by the treatment with QL. Meanwhile, miR-199a-5p was increased in AMI mouse heart tissues. Of note, the increase of miR-199a-5p in PE-treated cardiomyocytes was reversed by the treatment with QL. Moreover, overexpression of miR-199a-5p abolished the anti-hypertrophic effect of QL on cardiomyocytes. Conclusion: QL prevents PE-induced cardiac hypertrophy. MiR-199a-5p is increased in cardiac hypertrophy, while reduced by treatment with QL. miR-199a-5p suppression is essential for the anti-hypertrophic effect of QL on cardiomyocytes.
The Role of Interstitial Cells of Cajal in Acute Cholecystitis in Guinea Pig Gallbladder
Authors: Huang Zhen-peng , Qiu Hu , Yang Yan , Zhang Li , Yang Bin , Lin Meng-juan , Yu Bao-ping
Published: May 2016

Background/Aims: Acute cholecystitis is common in gallbladder motility disorder. Interstitial cells of Cajal (ICCs) in the gallbladder are involved in the regulation of gallbladder motility. The aim of this study was to explore the change of gallbladder ICCs in acute cholecystitis. Methods: Thirty adult guinea pigs were randomly divided into 3 groups: a sham-operated group (healthy controls) and 2 study groups. The animals in the study group were subjected to bile duct ligation and then to laparotomy and cholecystectomy at 24 and 48 hours after surgery. Immunohistochemistry, immunohistofluorescence, and laser confocal microscopy were performed to observe the shape, size, morphology, and density of gallbladder ICCs. Western blot and real-time PCR were performed to detect stem cell factor and c-kit protein and mRNA expression, respectively. Results: There were no differences in the shape, size, and morphology of the gallbladder ICCs in the control and the two acute cholecystitis groups. Density of gallbladder ICCs, SCF level, and c-kit protein and mRNA expression all decreased in the acute cholecystitis groups. Further, SCF level and c-kit protein and mRNA expression decreased with progress of acute cholecystitis (all P < 0.05). Conclusion: Acute cholecystitis can decrease ICCs through repression of SCF and c-kit expression and that ICCs loss play a role in acute cholecystitis.
MicroRNA-124 (MiR-124) Inhibits Cell Proliferation, Metastasis and Invasion in Colorectal Cancer by Downregulating Rho-Associated Protein Kinase 1(ROCK1)
Authors: Zhou Liqing , Xu Ziran , Ren Xiaoqiang , Chen Kaixuan , Xin Shiyong
Published: May 2016

Background/Aims: MiR-124 inhibits neoplastic transformation, cell proliferation, and metastasis and downregulates Rho-associated protein kinase (ROCK1) in Colorectal Cancer (CRC). The aim of this study was to further investigate the roles and interactions of ROCK1 and miR-124 and the effects of knockdown of ROCK1and MiR-124 in human Colorectal Cancer (CRC). Methods: Three Colorectal cancer cell lines (HCT116, HT29 and SW620) and one Human Colonic Mucosa Epithelial cell line (NCM460) were studied. The protein expression of ROCK1 was examined by Western-blot and qRT-PCR were performed to examine the expression levels of ROCK1 mRNA and miR-124. Furthermore, We performed transfection of cancer cell line (SW620) with pre-miR-124(mimics), anti-miR-124(inhibitor), ROCK1 siRNA and the control, then observed the affects of ROCK1 protein expression by westen-blot, cell proliferation by EDU (5-ethynyl-2'deoxyuridine assay) and expression levels of ROCK1mRNA by qRT-PCR . A soft agar formation assay, Migration and invasion assays were used to determine the effect of regulation of miR-124 and ROCK1, and survivin on the transformation and invasion capability of colorectal cancer cell. Results: MiR-124 expression was significantly downregulated in CRC cell lines compare to normal (P < 0.05). In contrast, ROCK1 protein expression was significantly increased in CRC cell lines compared to the normal (P < 0.05), whereas the gene (ROCK1mRNA) expression remained unaltered (P > 0.05). ROCK1 mRNA was unaltered in cells transfected with miR-124 mimic and miR-124 inhibitor, compared to normal controls. There was a significant reduction in ROCK1 protein in cells transfected with miR-124 mimic and a significant increase in cells transfected with miR-124 inhibitor (P < 0.05). Cell proliferation, transformation and invasion of cells transfected with miR-124 inhibitor were significantly increased compared to those in normal controls (P<0.05). However, cell proliferation, transformation and invasion of cells transfected with ROCK1 siRNA were significantly decreased compared to control (P < 0.05). Conclusions: In conclusion, our results demonstrated that miR-124 not only promoted cancer cell hyperplasia and significantly associated with CRC metastasis and progression, but also downregulated ROCK1 protein expression. More importantly, increased ROCK1 expression or inhibited miR-124 expression may constitute effective new therapeutic strategies for the treatment of renal cancer in the future.
Huang Qi Huai Granules Induce Apoptosis in Acute Lymphoblastic Leukemia Cells through the Akt/FoxO1 Pathway
Authors: Han Juan , Lin Ming , Zhou Dongfeng , Zhang Zhiquan , Jin Runming , Zhou Fen
Published: May 2016

Background/Aims: In recent years, a traditional Chinese medicine named Huang Qi Huai (HQH) has been frequently used in China for solid tumor therapy. However, the role of HQH on leukemia cells and its underlying mechanisms have not been elucidated. In this study, we investigated the effect of HQH on the proliferation and apoptosis of acute lymphoblastic leukemia (ALL) cell lines. Methods: Sup-B15 and Nalm-6 cells were treated with gradient doses of HQH for 24, 48 or 72 h. Cell viability was measured using a CCK8 assay and cell cycle distribution and apoptosis levels were analyzed using flow cytometry. Western blotting was used to assess the levels of proteins associated with the apoptotic pathway. Results: The results revealed that cell survival decreased significantly with increasing concentrations of HQH. HQH induced G2 cell-cycle arrest and cell apoptosis in a dose-dependent manner. HQH inhibited phosphorylated-Akt, phosphorylated- FoxO1 and Bcl2 expression and upregulated Bim, cleaved-caspase-3 and Bax expression in a dose-dependent manner, which suggests that HQH induces the apoptosis of ALL cells via the Akt/FoxO1 pathway. Conclusion: HQH is a potential complementary agent for the treatment of acute lymphoblastic leukemia.
Pioglitazone, a Peroxisome Proliferator-Activated Receptor γ Agonist, Ameliorates Chronic Kidney Disease by Enhancing Antioxidative Capacity and Attenuating Angiogenesis in the Kidney of a 5/6 Nephrectomized Rat Model
Authors: Sun Li , Yuan Quan , Xu Tianhua , Yao Li , Feng Jiangmin , Ma Jianfei , Wang Lining , Lu Changlong , Wang Danan
Published: May 2016

Background/Aims: Pioglitazone is a type of peroxisome proliferator-activated receptor γ agonist and is capable of alleviating renal ischemia-reperfusion injury. Methods: A5/6 nephrectomized rat model was established to induce renal impairments mimicking chronic kidney diseases (CKDs). The effect of pioglitazone on renal structure, function, antioxidative capacity, and angiogenesis in the nephrectomized rats was assessed. Moreover, the expression of HIF-1α, eNOS, VEGF, Flt-1 and Flk-1 was determined to reveal the possible pathways through which pioglitazone exerted its beneficial effect on CKDs. Results: Subtotal nephrectomy caused severe damages to rat renal tissues, and administration of pioglitazone dramatically restored the structure and function of the kidney, which was evidenced by Periodic acid- Schiff staining and the reduced levels of urinary proteins, blood urea nitrogen, and creatinine. Furthermore, pioglitazone decreased the level of malondialdehyde and increased the level of superoxide dismutase in the injured renal tissues, suggesting that the antioxidative capacity in the injured kidney was augmented by pioglitazone. Additionally, pioglitazone inhibited HIF-1α-dependent angiogenesis by down-regulating the expression of a panel of angiogenic factors. Conclusion: The current study demonstrates that pioglitazone benefits renal failure through activation of the antioxidative system and inhibition of angiogenesis in the injured kidney. Our study provides preliminary evidences for the potential application of this agent in the treatment of CKDs.
Concurrent Elevations of VEGF, Osteopontin and MCP-1 Serum Levels Are Independent Predictors of Survival in Patients with Diffuse Large B-Cell Lymphoma
Authors: Duletić-Načinović Antica , Gačić Vedrana , Valković Toni , Lučin Ksenija , Fišić Elizabeta , Žuvić-Butorac Marta , Seili-Bekafigo Irena , Jonjić Nives
Published: May 2016

Background: Diffuse large B-cell lymphomas (DLBCL) are heterogeneous diseases, and the identification of additional DLBCL risk factors is especially important. Methods: In this pilot study, we determined pretreatment serum levels of vascular endothelial growth factor (VEGF), osteopontin (OPN) and macrophage chemotactic protein-1 (MCP-1) in 67 newly diagnosed DLBCL patients before treatment with standard chemoimmunotherapy and in 30 healthy persons. Results: Serum levels of all three cytokines were significantly elevated in untreated patients compared to controls. VEGF and OPN concentrations were higher in patients with advanced Ann Arbor stage, B symptoms, Eastern Cooperative Oncology Group score ≥2, International Prognostic Index (IPI) ≥3 and partial/no remission. A high MCP-1 level was associated with advanced stage, increased IPI and bone marrow infiltration. In univariate analysis, elevated OPN and VEGF, and concurrent elevation of all three biomarkers, were identified as significant predictors of poor survival. Multivariate Cox analysis revealed that elevated OPN combined with elevated VEGF levels was one of the best parameter subsets predicting poorest survival. Conclusion: According to our preliminary results, serum levels of VEGF and OPN before treatment predict response to therapy and survival after chemoimmunotherapy, and may help to further stratify DLBCL patients into risk groups.
Functional Significance and Predictive Value of MicroRNAs in Pediatric Obesity: Tiny Molecules with Huge Impact?
Authors: Fischer-Posovszky Pamela , Roos Julian , Kotnik Primoz , Battelino Tadej , Inzaghi Elena , Nobili Valerio , Cianfarani Stefano , Wabitsch Martin
Published: May 2016

Obesity is a major health concern. While some children develop comorbidities such as insulin resistance and low-grade systemic inflammation upon weight gain, others stay metabolically healthy. There is an urgent need for clinically relevant markers with prognostic value related to disease development and intervention success. MicroRNAs (miRNAs) are established biomarkers for several disease states. Herein, we give a brief overview of miRNA biogenesis and function and the potential role of circulating miRNA in the context of pediatric obesity.
A Review of Pain Prevalence in Alzheimer's, Vascular, Frontotemporal and Lewy Body Dementias
Authors: van Kooten Janine , Binnekade Tarik T. , van der Wouden Johannes C. , Stek Max L. , Scherder Erik J.A. , Husebø Bettina S. , Smalbrugge Martin , Hertogh Cees M.P.M.
Published: May 2016

Background: Numerous studies have reported on pain in dementia. It has been hypothesized that pain perception differs between dementia subtypes, and therefore, the prevalence of pain differs between dementia subtypes. However, there remains a paucity of evidence on the differences in the prevalence of pain in different dementia subtypes. This review aimed to determine the prevalence of pain for the major dementia subtypes: Alzheimer's disease (AD), vascular dementia (VaD), frontotemporal dementia (FTD) and dementia with Lewy bodies (DLB). Summary: We found 10 studies that met our inclusion criteria. Most of these studies reported on AD; studies reporting the prevalence of pain in people with DLB were scarce, and for FTD, we found no studies. The sample-weighted prevalence of pain could only be calculated for AD, VaD and mixed dementia: AD 45.8% (95% confidence interval, CI: 33.4-58.5%), VaD 56.2% (95% CI: 47.7-64.4%) and mixed dementia 53.9% (95% CI: 37.4-70.1%). Key Messages: Studies investigating the prevalence of pain in dementia subtypes were scarce; however, we found a high prevalence of pain in dementia without significant differences between the dementia subtypes. More studies are required to draw firm conclusions on the differences in the prevalence of pain between dementia subtypes.
Gene Therapy for Pyoderma Gangrenosum: Optimal Transfection Conditions and Effect of Drugs on Gene Delivery in the HaCaT Cell Line Using Cationic Liposomes
Authors: Teagle Alexandra R. , Birchall James C. , Hargest Rachel
Published: May 2016

Background/Aims: Pyoderma gangrenosum (PG) is a rare ulcerative skin disease, currently treated empirically with immunosuppression. PG is a good target for gene therapy since the skin is easily accessible. This study used the FDA-approved vector Lipofectamine® 2000 to investigate in vitro transfection of skin keratinocytes. The aim was to determine an optimum transfection protocol, including the effect of drugs currently used to treat PG on the efficiency of gene transfer, since gene therapy is unlikely to be used as monotherapy. Methods: Cells of the HaCaT line were transfected with the lacZ reporter gene, and transgene expression was measured after a given time period. Conditions tested were: relative concentrations of DNA and Lipofectamine®, time from transfection to measurement of expression, pH, and exposure to clinically relevant drugs (hydrocortisone, methotrexate, infliximab). Results: The greatest levels of β-galactosidase expression were observed using a DNA:Lipofectamine® ratio of 1:5 (μg/μl) on day 3 after transfection, using culture medium at pH 7, and in the presence of hydrocortisone. Transfection efficiency was reduced by the presence of methotrexate and not significantly affected by infliximab. Conclusion: Gene therapy is a potential future strategy for the management of PG; this study is a step towards the development of a topical gene-based agent.
Chronic Hepatitis B Infection is Associated with Decreased Risk of Preeclampsia: A Meta-Analysis of Observational Studies
Authors: Huang Qi-tao , Chen Jian-hong , Zhong Mei , Hang Li-lin , Wei Shan-shan , Yu Yan-hong
Published: May 2016

Background/Aims: Preeclampsia is a complex multi-system obstetric syndrome and remains one of the leading causes contributing to maternal and perinatal mortality and morbidity. Previous epidemiological studies regarding the association between chronic hepatitis B virus (CHB) infection and the risk of preeclampsia have reported inconsistent results. Therefore, we conducted a meta-analysis to investigate the association between CHB infection and preeclampsia. Methods: The electronic database was searched until January 1st, 2016. Relevant studies reporting the association between CHB infection and the risk of preeclampsia were included and for further evaluation. Statistical analysis was performed using Stata 10.0 (Stata Corp). Results: Three observational cohort studies and eight case-control studies, including 11566 preeclampsia patients, were identified. A significant negative association between CHB infection and preeclampsia was observed (odds ratio = 0.77, 95% confidence interval, 0.65- 0.90, P=0.002, fixed-effect model). Conclusions: Findings from our meta-analysis indicate that CHB infection may decrease the risk of preeclampsia in Asian population. Future prospective cohorts in different countries with larger sample sizes are warranted to ascertain the causality and pathophysiological studies are required to explore the possible biological mechanisms involved.
Periplocin Extracted from Cortex Periplocae Induced Apoptosis of Gastric Cancer Cells via the ERK1/2-EGR1 Pathway
Authors: Li Lei , Zhao Lian-Mei , Dai Su-li , Cui Wen-Xuan , Lv Hui-Lai , Chen Liang , Shan Bao-En
Published: May 2016

Background/Aims: Periplocin is extracted from the traditional herbal medicine cortex periplocae, which has been reported to suppress the growth of cancer cells. However, little is known about its effect on gastric cancer cells. Methods: Gastric cancer cells were treated with periplocin, and cell viability was assessed using MTS assay. Flow cytometry and TUNEL staining were performed to evaluate apoptosis, and protein expression was examined by western blotting. Microarray analysis was used to screen for changes in related genes. Results: We found that periplocin had an inhibitory effect on gastric cancer cell viability in a dose-dependent manner. Periplocin inhibited cell viability via the ERK1/2-EGR1 pathway to induce apoptosis. Periplocin also inhibited the growth of tumor xenografts and induced apoptosis in vivo. Conclusion: Our results show that periplocin inhibits the proliferation of gastric cancer cells and induces apoptosis in vitro and in vivo, indicating its potential to be used as an antitumor drug.
GlyT1 Inhibitor NFPS Exerts Neuroprotection via GlyR Alpha1 Subunit in the Rat Model of Transient Focal Cerebral Ischaemia and Reperfusion
Authors: Huang Baosheng , Xie Qingsong , Lu Xiaocheng , Qian Tengda , Li Shuai , Zhu Ronglan , Yu Wan , Chen Gong , Chen Zheng , Xu Xinlong , Wang Tianlu , Li Lixin
Published: May 2016

Background/Aims: Glycine is a strychnine-sensitive inhibitory neurotransmitter in the central nervous system (CNS), especially in the spinal cord, brainstem, and retina. The objective of the present study was to investigate the potential neuroprotective effects of GlyT1 inhibitor N [3-(4'-fluorophenyl)-3-(4'-phenylphenoxy) propyl] sarcosine (NFPS) in the rat model of experimental stroke. Methods: In vivo ischaemia was induced by transient middle cerebral artery occlusion (tMCAO). The methods of Western Blotting, Nissl Staining and Morris water maze methods were applied to analyze the anti-ischaemia mechanism. Results: The results showed that high dose of NFPS (H-NFPS) significantly reduced infarct volume, neuronal injury and the expression of cleaved caspase-3, enhanced Bcl-2/Bax, and improved spatial learning deficits which were administered three hours after transient middle cerebral artery occlusion (tMCAO) induction in rats, while, low dose of NFPS (L-NFPS) exacerbated the injury of ischaemia. These findings suggested that low and high dose of NFPS produced opposite effects. Importantly, it was demonstrated that H-NFPS-dependent neuronal protection was inverted by salicylate (Sal), a specific GlyR ɑ1 antagonist. Such effects could probably be attributed to the enhanced glycine level in both synaptic and extrasynaptic clefts and the subsequently altered extrasynaptic GlyRs and their subtypes. Conclusions: These data imply that GlyT1 inhibitor NFPS may be a novel target for clinical treatment of transient focal cerebral ischaemia and reperfusion which are associated with altered GlyR alpha 1 subunits.
SATB1 is Correlated with Progression and Metastasis of Breast Cancers: A Meta-Analysis
Authors: Pan Zhongya , Jing Wei , He Keli , Zhang Li , Long Xinghua
Published: May 2016

Background/Aims: Several researches have evaluated the significance of SATB1 (Special AT-rich sequence binding protein 1) expression in breast cancers (BCs), but the results have been disputed, especially in the aspects of clinicopathological features and prognosis. Therefore, our study aimed to use a meta-analysis to summarize the clinical and prognostic relevance of SATB1 gene expression in BCs. Methods: A literature search of PubMed, EMBASE, Cochrane library, Chinese Wanfang and CNKI was performed to identify eligible studies. Ten studies total, comprising 5,185 patients (1,699 SATB1-positive and 3,486 SATB1-negative), were enrolled in our study, which was performed using Revman5.3 Software and Stata11.0 Software. Results: This meta-analysis showed that the expression of SATB1 was significantly higher in breast cancer than in normal tissues (OR = 12.28; 95%CI = 6.01-25.09), and was statistically related to several clinicopathological parameters, including lymph node metastasis (OR = 1.55, 95%CI = 1.01-2.39) and Tumor Node Metastasis(TNM) stage (OR = 0.35, 95%CI = 0.22-0.56). However, the level of SATB1 was not statistically associated with the age (OR = 1.13, 95%CI = 0.87-1.46), tumour size (OR = 0.72, 95%CI = 0.44-1.19), estrogen receptor (OR = 0.78, 95%CI = 0.55-1.09), progesterone receptor (OR = 0.64, 95%CI = 0.32-1.29), HER2 status (OR=1.98, 95%CI = 0.74-5.30), and histological type (OR = 0.49, 95%CI = 0.22-1.11). Conclusion: High expression of SATB1 was significantly correlated with tumourigenesis and metastasis of BCs, indicating poor prognosis for patients. SATB1 could serve as a potential marker for detection and prognosis evaluation of breast cancers.
Effect of Known Inhibitors of Ion Transport on Pendrin (SLC26A4) Activity in a Human Kidney Cell Line
Authors: Bernardinelli Emanuele , Costa Roberta , Nofziger Charity , Paulmichl Markus , Dossena Silvia
Published: May 2016

Background/Aims: Pendrin is a Cl-/I-/HCO3- exchanger playing a fundamental role in controlling blood pressure and airway function, therefore representing an attractive target for the treatment of hypertensive states and respiratory distresses. A review of the literature regarding the ability of some compounds (namely several known inhibitors of ion transport) to block pendrin activity revealed discordant findings. These incongruous findings may be due, in part, to the concentration of compound and/or the nature of the model system used in the study. Methods: Pendrin activity was evaluated by measuring pendrin-dependent iodide influx following overexpression of the transporter in a human kidney cell line, in the presence of selected test compounds or the respective vehicles. Results: Pendrin activity was significantly hampered by 0.1 mM 5-nitro-2-[(3-phenylpropyl)amino]benzoic acid (NPPB), niflumic acid and tenidap, but was resistant to 0.1 mM 4, 4′-diisothiocyano-2, 2′-stilbene-disulfonic acid (DIDS), furosemide and probenecid. Conclusions: The results of the present study indicate that clinically effective non-steroidal anti-inflammatory drugs (niflumic acid and tenidap) directly inhibit pendrin activity.
Chloroquine Increases Glucose Uptake via Enhancing GLUT4 Translocation and Fusion with the Plasma Membrane in L6 Cells
Authors: Zhou Qi , Yang Xinzhou , Xiong Mingrui , Xu Xiaolan , Zhen Li , Chen Weiwei , Wang Yan , Shen Jinhua , Zhao Ping , Liu Qing-Hua
Published: May 2016

Background/Aims: Chloroquine can induce an increase in the cellular uptake of glucose; however, the underlying mechanism is unclear. Methods: In this study, translocation of GLUT4 and intracellular Ca2+ changes were simultaneously observed by confocal microscope in L6 cells stably over-expressing IRAP-mOrange. The GLUT4 fusion with the plasma membrane (PM) was traced using HA-GLUT4-GFP. Glucose uptake was measured using a cell-based glucose uptake assay. GLUT4 protein was detected by Western blotting and mRNA level was detected by RT-PCR. Results: We found that chloroquine induced significant increases in glucose uptake, glucose transporter GLUT4 translocation to the plasma membrane (GTPM), GLUT4 fusion with the PM, and intracellular Ca2+ in L6 muscle cells. Chloroquine-induced increases of GTPM and intracellular Ca2+ were inhibited by Gallein (Gβγ inhibitor) and U73122 (PLC inhibitor). However, 2-APB (IP3R blocker) only blocked the increase in intracellular Ca2+ but did not inhibit GTPM increase. These results indicate that chloroquine, via the Gβγ-PLC-IP3-IP3R pathway, induces elevation of Ca2+, and this Ca2+ increase does not play a role in chloroqui-ne-evoked GTPM increase. However, GLUT4 fusion with the PM and glucose uptake were significantly inhibited with BAPTA-AM. This suggests that Ca2+ enhances GLUT4 fusion with the PM resulting in glucose uptake increase. Conclusion: Our data indicate that chloroquine via Gβγ-PLC-IP3-IP3R induces Ca2+ elevation, which in turn promotes GLUT4 fusion with the PM. Moreover, chloroquine can enhance GLUT4 trafficking to the PM. These mechanisms eventually result in glucose uptake increase in control and insulin-resistant L6 cells. These findings suggest that chloroquine might be a potential drug for improving insulin tolerance in diabetic patients.