bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of Sphingosine Kinases Inhibitors: Challenges and Recent Developments
Authors: Magli Elisa , Corvino Angela , Fiorino Ferdinando , Frecentese Francesco , Perissutti Elisa , Saccone Irene , Santagada Vincenzo , Caliendo Giuseppe , Severino Beatrice
Published: April 2019

Background:

Sphingosine kinases (SphKs) catalyze the phosphorylation of sphingosine to form the bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P). S1P is an important lipid mediator with a wide range of biological functions; it is also involved in a variety of diseases such as inflammatory diseases, Alzheimer’s disease and cancer.

Methods:

This review reports the recent advancement in the research of SphKs inhibitors. Our purpose is also to provide a complete overview useful for underlining the features needed to select a specific pharmacological profile.

Discussion:

Two distinct mammalian SphK isoforms have been identified, SphK1 and SphK2. These isoforms are encoded by different genes and exhibit distinct subcellular localizations, biochemical properties and functions. SphK1 and SphK2 inhibition can be useful in different pathological conditions.

Conclusion:

SphK1 and SphK2 have many common features but different and even opposite biological functions. For this reason, several research groups are interested in understanding the therapeutic usefulness of a selective or non-selective inhibitor of SphKs. Moreover, a compensatory mechanism for the two isoforms has been demonstrated, thus leading to the development of dual inhibitors.
Catheter-related Bloodstream Infections: A Root Cause Analysis in a Series of Simultaneous Ochrobactrum anthropi Infections
Authors: Caroleo Benedetto , Malandrino Pasquale , Liberto Aldo , Condorelli Dario , Patanè Federico , Maiese Aniello , Casella Filomena , Geraci Diego , Ricci Pietrantonio , Di Mizio Giulio
Published: April 2019

Objective:

Catheter-related bloodstream infections (CRBSIs) pathogenesis is complex and multifactorial mostly due to cutaneous microorganisms migration through the catheter insertion site and catheter tip colonization. Ochrobactrum anthropi is a gram-negative bacterium belonging to the Brucellaceae and related infections are especially observed in immunocompromised patients.

Methods:

Therefore, O. anthropi infection prevention and surveillance are relevant issues for healthcare system and risk management, in order to improve healthcare quality and patient safety. Four cases of anthropi-related CRBSIs occurring in immunodepressed patients under chemotherapy treatment are reported and the possible prevention and surveillance strategies are analyzed.

Results:

In the reported cases, all infections occurred almost simultaneously in the Oncology Unit, leading to hypothesize an identical infection source. Subsequently, a clinical audit was performed in order to investigate infection origin and implement prevention and control strategies. Clinical audit allowed to identify the hand hygiene defects as the primary source of the infections, responsible for catheter flushing solution contamination.

Conclusion:

The aim of this study is to reveal how through correct root cause analysis and clinical audit, several measures could be undertaken in order to promote the prevention of the CRBSIs risk
Feasibility of Using Adjunctive Optogenetic Technologies in Cardiomyocyte Phenotyping – from the Single Cell to the Whole Heart
Authors: Bub Gil , Daniels Matthew J.
Published: April 2019

In 1791, Galvani established that electricity activated excitable cells. In the two centuries that followed, electrode stimulation of neuronal, skeletal and cardiac muscle became the adjunctive method of choice in experimental, electrophysiological, and clinical arenas. This approach underpins breakthrough technologies like implantable cardiac pacemakers that we currently take for granted. However, the contact dependence, and field stimulation that electrical depolarization delivers brings inherent limitations to the scope and experimental scale that can be achieved. Many of these were not exposed until reliable in vitro stem-cell derived experimental materials, with genotypes of interest, were produced in the numbers needed for multi-well screening platforms (for toxicity or efficacy studies) or the 2D or 3D tissue surrogates required to study propagation of depolarization within multicellular constructs that mimic clinically relevant arrhythmia in the heart or brain. Here the limitations of classical electrode stimulation are discussed. We describe how these are overcome by optogenetic tools which put electrically excitable cells under the control of light. We discuss how this enables studies in cardiac material from the single cell to the whole heart scale. We review the current commercial platforms that incorporate optogenetic stimulation strategies, and summarize the global literature to date on cardiac applications of optogenetics. We show that the advantages of optogenetic stimulation relevant to iPS-CM based screening include independence from contact, elimination of electrical stimulation artefacts in field potential measuring approaches such as the multi-electrode array, and the ability to print re-entrant patterns of depolarization at will on 2D cardiomyocyte monolayers.
Healthcare-Associated Infections Due to Multidrug-Resistant Organisms: a Surveillance Study on Extra Hospital Stay and Direct Costs
Authors: Giraldi Guglielmo , Montesano Marzietta , Napoli Christian , Frati Paola , La Russa Raffaele , Santurro Alessandro , Scopetti Matteo , Orsi Giovanni B.
Published: April 2019

Background:

The increasing antimicrobial resistance poses a challenge to surveillance systems
and raises concerns about the impact of multidrug-resistant organisms on patient safety.

Objective:

The study aimed to estimate extra hospital stay and economic burden of infections due to alert
organisms - mostly multidrug-resistant - in a teaching hospital.

Methods:

The present retrospective matched cohort study was conducted based on the analysis of hospital
admissions at Sant’Andrea Teaching Hospital in Rome from April to December 2015. Extra hospital
stay was the difference in the length of stay between each case and control. All the patients developing
an infection due to an alert organism were considered cases, all others were eligible as controls. The
costs of LOS were evaluated by multiplying the extra stay with the hospital daily cost.

Results:

Overall, 122 patients developed an infection due to alert organisms and were all matched with
controls. The attributable extra stay was of 2,291 days (mean 18.8; median 19.0) with a significantly increased
hospitalization in intensive care units (21.2 days), bloodstream infections (52.5 days), and infections
due to Gram-negative bacteria (mean 29.2 days; median 32.6 days). Applying the single day hospital
cost, the overall additional expenditure was 11,549 euro per patient. The average additional cost of
antibiotic drugs for the treatment of infections was about 1,200 euro per patient.

Conclusion:

The present study presents an accurate mapping of the clinical and economic impact of infections
attributable to alert organisms demonstrating that infections due to multidrug-resistant organisms
are associated with higher mortality, longer hospital stays, and increased costs.

Article Highlights Box:

The increasing antimicrobial resistance poses a challenge for surveillance
systems and raises concerns about the impact of multidrug-resistant organisms on patient safety.
• Healthcare-associated infections (HAIs) have historically been recognized as a significant public health
problem requiring close surveillance.
• Despite several and reliable findings have been achieved on clinical issues, our knowledge on the economic
impact of healthcare-associated infections due to multidrug-resistant organisms needs to be widened.
• Estimating the cost of infections due to multidrug-resistant organisms in terms of extra hospital stay
and economic burden is complex, and the financial impact varies across different health systems.
• Evaluations of social and economic implications of hospital infections play an increasingly important
role in the implementation of surveillance systems.
• The costs of infection prevention and control programs and dedicated personnel are relatively low and
self-sustainable when efficient.
Anti-tumor Drug Targets Analysis: Current Insight and Future Prospect
Authors: Wang Sheng , Zhou Dexi , Xu Zhenyu , Song Jing , Qian Xueyi , Lv Xiongwen , Luan Jiajie
Published: April 2019

The incidence and mortality of malignant tumors are on the rise, which has become the second leading cause of death in the world. At present, anti-tumor drugs are one of the most common methods for treating cancer. In recent years, with the in-depth study of tumor biology and related disciplines, it has been gradually discovered that the essence of cell carcinogenesis is the infinite proliferation of cells caused by the disorder of cell signal transduction pathways, followed by a major shift in the concept of anti-tumor drugs research and development. The focus of research and development is shifting from traditional cytotoxic drugs to a new generation of anti-tumor drugs targeted at abnormal signaling system targets in tumor cells. In this review, we summarize the targets of anti-tumor drugs and analyse the molecular mechanisms of their effects, which lay a foundation for subsequent treatment, research and development.
Monoamines and their Derivatives on GPCRs: Potential Therapy for Alzheimer’s Disease
Authors: Farfán-García Eunice D. , Márquez-Gómez Ricardo , Barrón-González Mónica , Pérez-Capistran Teresa , Rosales-Hernández Martha C. , Pinto-Almazán Rodolfo , Soriano-Ursúa Marvin A.
Published: April 2019

Albeit cholinergic depletion remains the key event in Alzheimer’s Disease (AD), recent information
describes stronger links between monoamines (trace amines, catecholamines, histamine, serotonin,
and melatonin) and AD than those known in the past century. Therefore, new drug design strategies focus
efforts to translate the scope on these topics and to offer new drugs which can be applied as therapeutic
tools in AD. In the present work, we reviewed the state-of-art regarding genetic, neuropathology and neurochemistry
of AD involving monoamine systems. Then, we compiled the effects of monoamines found in
the brain of mammals as well as the reported effects of their derivatives and some structure-activity relationships.
Recent derivatives have triggered exciting effects and pharmacokinetic properties in both murine
models and humans. In some cases, the mechanism of action is clear, essentially through the interaction
on G-protein-coupled receptors as revised in this manuscript. Additional mechanisms are inhibition of
enzymes for their biotransformation, regulation of free-radicals in the central nervous system and others
for the effects on Tau phosphorylation or amyloid-beta accumulation. All these data make the monoamines
and their derivatives attractive potential elements for AD therapy.
Pharmacological Management of Diabetic Nephropathy
Authors: Papademetriou Vasilios , Alataki Sofia , Stavropoulos Konstantinos , Papadopoulos Christodoulos , Bakogiannis Kostas , Tsioufis Kostas
Published: April 2019

Introduction:

Diabetes mellitus (DM) is one of the most common diseases worldwide. Its adverse effects on several body organs, have made treatment of DM a priority. One of the most serious complications of DM is diabetic nephropathy (DN).

Objective:

The aim of this review is to critically discuss available data on the pharmacological management of DN.

Objective:

A comprehensive review of the literature was performed to identify studies assessing the impact of several drug classes on DN.

Results:

Several studies have been conducted in order to find a novel and effective treatment of DN. So far, the cornerstone therapy of DN consists of renin-angiotensin system (RAS) inhibitors, agents that decrease the synthesis of intrarenal angiotensin II or block its receptors. Their antiproteinuric and antihypertensive effects can not only decelerate the progress of DN but prevent its onset as well. Novel antidiabetic drugs, such as sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide- 1 receptor agonists (GLP-1 RA), are promising agents in the therapy of DN, due to their positive effect on renal and cardiovascular adverse events. From lipid-lowering agents, atorvastatin improves DN up to stage 3 and substantially reduces CVD.

Conclusion:

RAS inhibitors, SGLT-2i and GLP-1 agonists were found to be beneficial for the treatment of DN. Larger renal trials are needed in order to incorporate these drugs into the first line treatment of DN.
The Incidence of Adverse Drug Reactions in Patients Treated with Statins in the Emirates: A Retrospective Cohort Study
Authors: Shehab Abdulla , Bhagavathula Akshaya S. , Elnour Asim A. , Al-Rasadi Khalid , Al-Shamsi Saif
Published: April 2019

Aim:

We investigated the incidence of adverse drug reactions (ADRs) in patients treated with
statins for cardiovascular (CV) risk among the United Arab Emirates (UAE) population.

Methods:

This is a retrospective cohort study conducted among statin users attending 2 tertiary care
centres: Al Ain and Tawam hospitals in Al Ain city, UAE. We retrieved the clinical profile of all the
patients taking statins from January 2011 to January 2015 using our electronic database (Cerner®).

Results:

Among 556 patients (418 men; 138 women) taking statins, 237 ADRs were reported (186 men;
51 women). The incidence of ADRs was 40.7%, and was more frequent among patients at “high CV
disease (CVD) risk” and “moderate CVD risk” than other risk categories. High CVD risk (odds ratio,
1.67; 95% confidence interval [CI], 1.19-2.34), vitamin D deficiency 1.45 (95% CI, 0.89-2.38), type 2
diabetes 1.22 (95% CI, 0.84-1.77) and hypertension 1.13 (95% CI, 0.70-1.83) are some of the factors
that were associated with statin ADRs.

Conclusion:

The incidence of ADRs among statin users was 42.6%, and frequent ADRs (49%) were
noted in patients with high CVD risk. Early identification of these ADRs should improve patient adherence
to life-saving statin treatment.
Novel Coupled Molecules from Active Structural Motifs of Synthetic and Natural Origin as Immunosuppressants
Authors: Minhas Richa , Bansal Gulshan , Bansal Yogita
Published: April 2019

Introduction:

Nitric oxide (NO) is an important mediator in the pathogenesis and control
of immune system-related disorders and its levels are modulated by inducible NO synthase
(iNOS). Oxidative stress is another pathological indication in majority of autoimmune disorders.
The present study aims at the development of coupled molecules via selection of pharmacophores
for both immunomodulatory and antioxidant activities through iNOS inhibition.

Methods:

Variedly substituted coumarin moieties are coupled with naturally occurring phenols
through an amide linkage and were predicted for activities using computer-based program PASS.
The compounds predicted to have dual activities were synthesized. Docking studies were carried
out against iNOS (PDB 1R35) and compounds having good docking score were evaluated for immunomodulatory
and antioxidant activities.

Results:

The synthesized compounds were found to be pure and were obtained in good yields.
Compounds with maximum docking score (YR1a, YR2e, YR2c and YR4e) were selected for
evaluation by in vitro models. Compounds YR2e and YR2c markedly inhibited the reduction of
NBT dye and showed maximum % iNOS inhibition. In DPPH assay, compound YR4e was observed
as the most potent antioxidant (EC50 0.33 µM/mL). Based on these studies, compounds
YR2e and YR2c were selected for haemagglutination test. Compound YR2e was observed as the
most active immunosuppressant with maximal inhibitory ability of iNOS and NBT reduction and
lower HAT value of 3.5.

Conclusion:

Compound YR2e can be utilized as a pharmacological agent in the prevention or
treatment of immunomodulatory diseases such as tumors, rheumatoid arthritis, ulcerative colitis,
organ transplant and other autoimmune disorders.
Bioinorganic Chemistry of Platinum(IV) Complexes as Platforms for Anticancer Agents
Authors: Nagyal Little , Kumar Amit , Sharma Rishipal , Yadav Rohit , Chaudhary Pratibha , Singh Rajeev
Published: April 2019

The current review focuses on the comprehensive studies of platinum-based complexes that
are known to exhibit anticancer properties. The research on metal-particle work has helped in treating
sicknesses which plays an imperative part in therapeutic bioinorganic science. Understanding the biochemistry
of the detoxification mechanism of metals can help in advancing as well as enhancing the
anticancer property of metal complexes for several types of a tumour. The classifications of complexes
discussed have been done on the basis of Platinum oxidation states and binding sites of the ligands.
Further background and current status of Pt(IV) complexes are briefly explained along with a special
reference to Structural Activity Relationships and Mode of Action. The coordination chemistry of
Pt(IV) has been summarised and Pt(IV) complexes are reviewed on the basis of binding of Pt(IV) with
Human Serum Albumin and DNA. Finally, the results were summarized and concluded emphasizing on
the most important features.
PCR: An Effective, Faster and Relevant Method for the Detection of Clinical Isolates of Candida albicans
Authors: Zaidi Kamal Uddin , Mani Abin , Parmar Richa , Thawani Vijay
Published: April 2019

Background:

Candida albicans is associated with infectious diseases with colonization,
in both immunocompromised and immunocompetent patients. Antibiotic treatment can develop
candidiasis.

Objective:

Evaluation of ITS 4 and ITS5 primer expression on clinical isolates of C. albicans.

Methods:

Fifty clinical isolates of C. albicans were collected from different sites viz. Catheter Tip
(CT), High Vaginal Swab (HVS) and Urine (U).

Results:

Using the universal fungal primers ITS4 and ITS5, PCR produced a single monomorphic
amplification at 520 bp indicating that the strains are of same genetic identity.

Conclusion:

This is an effective, faster and relevant method for the detection and characterization
of clinically isolated strains of C. albicans.
HS-MMGKG: A Fast Multi-objective Harmony Search Algorithm for Two-locus Model Detection in GWAS
Authors: Sun Liyan , Liu Guixia , Su Lingtao , Wang Rongquan
Published: April 2019

Background::

Genome-Wide Association Study (GWAS) plays a very important role in
identifying the causes of a disease. Because most of the existing methods for genetic-interaction
detection in GWAS are designed for a single-correlation model, their performances vary
considerably for different disease models. These methods usually have high computation cost and
low accuracy.

Method::

We present a new multi-objective heuristic optimization methodology named HSMMGKG
for detecting genetic interactions. In HS-MMGKG, we use harmony search with five
objective functions to improve the efficiency and accuracy. A new strategy based on p-value and
MDR is adopted to generate more reasonable results. The Boolean representation in BOOST is
modified to calculate the five functions rapidly. These strategies take less time complexity and
have higher accuracy while detecting the potential models.

Results::

We compared HS-MMGKG with CSE, MACOED and FHSA-SED using 26 simulated
datasets. The experimental results demonstrate that our method outperforms others in accuracy and
computation time. Our method has identified many two-locus SNP combinations that are
associated with seven diseases in WTCCC dataset. Some of the SNPs have direct evidence in CTD
database. The results may be helpful to further explain the pathogenesis.

Conclusion::

It is anticipated that our proposed algorithm could be used in GWAS which is helpful
in understanding disease mechanism, diagnosis and prognosis.
Synthesis of New Dihydroquinopimaric Acid Analogs with Nitrile Groups as Apoptosis-Inducing Anticancer Agents
Authors: Tretyakova Elena V. , Salimova Elena V. , Parfenova Lyudmila V. , Yunusbaeva Milyausha M. , Dzhemileva Lilya U. , D’yakonov Vladimir A. , Dzhemilev Usein M.
Published: April 2019

Background:

Cyan-containing compounds are of great interest as potential anticancer agents. Terpenoids
can severe as a natural matrix for the development of promising derivatives with antitumor activity.

Methods:

The 2-cyanoethoxy methyl dihydroquinopimarate derivatives (5-9) were synthesized by the reaction of
the intermediates (1-4) with acrylonitrile in the presence of alkali (30% KOH solution) using triethylbenzylammonium
chloride. The cytotoxicity evaluation was carried out according to the National Cancer Institute (NCI) Protocol,
while apoptosis was studied by flow cytometric analysis of Annexin V and 7-aminoactinomycin D staining and
cell cycle was analyzed using the method of propidium iodide staining.

Results:

Synthesis of new dihydroquinopimaric acid derivatives with nitrile groups was carried out. The obtained
cyanoethyl derivatives were converted into tetrazole, amine, oxadiazole and amidoxime analogs. The primary
screening for antitumor activity showed the highest cytotoxic potency of the cyanoethyl-substituted compounds.
The introduction of cyanoethyl groups at C-1, C-4 and C-1, C-4, C-20 positions of dihydroquinopimaric acid
methyl ester provided antiproliferative effect towards the Jurkat, K562, U937, and HeLa tumor cell cultures
(CC50=0.045-0.154µM). These nitrile derivatives are effective inducers of tumor cell apoptosis affecting the S and
G2 phases of the cell cycle in a dose-dependent manner.

Conclusion:

The cyanoethyl analogs of dihydroquinopimaric acid reported herein are apoptosis inducers and cytotoxic
agents. These findings will be useful for the further design of more potent cytotoxic agents based on natural
terpenes.
The Possibility of Preventive and Therapeutic Use of Green Tea Catechins in Prostate Cancer
Authors: Rogovskii Vladimir S. , Popov Sergey V. , Sturov Nikolai V. , Shimanovskii Nikolai L.
Published: April 2019

Background:

Prostate cancer is one of the most frequent types of cancer. Despite the existence of various treatment strategies, treatment of prostate cancer still presents serious difficulties (especially in advanced stages). Polyphenols have been extensively assessed in terms of their potential use for prostate cancer treatment and prevention. Catechins are among the most well-known polyphenols in this respect.

Objective:

In this review, we summarize clinical study results concerning catechin applications with regard to prostate cancer treatment and prevention. We discuss some of the main mechanisms of the anticarcinogenic action of catechins.

Conclusion:

The main mechanisms of the anticarcinogenic action of catechins are subdivided into two major types: (i) direct action on cancer cells and (ii) indirect effect based on catechins’s impact on the microenvironment of cancer cells, particularly in relation to the immune system. At this level catechins might reduce tumor-associated inflammation and immune tolerance.
Evaluation of Antitumor Activity and Hepatoprotective Effect of Mitomycin C Solubilized in Chamomile Oil Nanoemulsion
Authors: Al-Otaibi Waad A. , Alkhatib Mayson H. , Wali Abdulwahab N.
Published: April 2019

:

The present study aimed to investigate the antitumor activity and hepatoprotective effect of the MTC, when combined with CHAM oil nanoemulsion (NE), (CHAM-MTC) on the tumor growth.

Materials/Methods:

The in vitro study assessed the antineoplastic effect of CHAM-MTC on the MCF-7 breast cancer cells while the in vivo therapeutic effectiveness and toxicities of CHAM-MTC were evaluated in Ehrlich Ascites Carcinoma (EAC) bearing mice. One hundred female Swiss albino mice, divided equally into non-EAC group (negative control), untreated EAC group (positive control) and three EAC groups received once intraperitoneal injection of 0.2ml CHAM-NE, 0.2ml Normal Saline (NS) contained MTC (1mg/kg) and 0.2ml CHAM-NE mixed with MTC (1mg/kg), respectively.

Results:

The in vitro results indicated that CHAM-NE could potentiate the effect of MTC in sub-effective concentrations since the half-maximal inhibitory concentration (IC50) was reduced by a factor of 21.94 when compared to the MTC-NS. The in vivo study revealed that mice treated with CHAM-MTC showed a significant increase in the median survival time (MST= 37 days) when compared to the MTC-NS treated group (MST= 29.50 days). In addition, CHAM-MTC showed protective ability against the oxidative stress and hepatic damage induced by EAC and MTC treatment.

Conclusion:

The combination of MTC with CHAM-NE could be valuable in enhancing the therapeutic efficacy of MTC against EAC and in eliminating MTC-induced hepatotoxicity.
Novel Curcumin Inspired Antineoplastic 1-Sulfonyl-4-Piperidones: Design, Synthesis and Molecular Modeling Studies
Authors: Fawzy Nehmedo G. , Panda Siva S. , Fayad Walid , El-Manawaty May A. , Srour Aladdin M. , Girgis Adel S.
Published: April 2019

Background:

Curcumin is a well-known example of plant origin exhibiting promising diverse biological
properties such as, anti-inflammatory and antitumor as well as poor pharmacokinetic/pharmacodynamic
properties. This is why effective agents based on its chemical scaffold were explored.

Methods:

A set of 3,5-bis(ylidene)-1-(alkylsulfonyl)piperidin-4-ones were synthesized in excellent yield (80-
96%) through dehydrohalogenation reaction of 3,5-bis(ylidene)-4-piperidinones with the corresponding alkane
sulfonyl chloride in the presence of triethylamine. Antiproliferative properties of the synthesized compounds
(dienone/curcumin inspired analogues) were studied by the standard MTT technique.

Results:

Most of the synthesized compounds revealed antiproliferative properties against HCT116 (colon) and
A431 (skin/squamous) cancer cell lines with IC50 values at sub-micromolar level. Compound 36 also exhibited
potency against MCF7 (breast) and A549 (lung) cancer cell lines (IC50 = 2.23, 4.27µM, respectively) higher than
that of the reference standards (IC50 = 3.15, 5.93µM for 5-fluorouracil and doxorubicin against MCF7 and A549
cell lines, respectively). Cytotoxic properties of the synthesized compounds against non-cancer RPE1 cell line
supported the safety profile of the effective agents against normal cells. Molecular modeling (3Dpharmacophore
and 2D-QSAR) studies validated the observed bio-properties and explained the parameters
governing activity. Inhibitory properties of compounds 27 and 29 (representative examples of the promising
antiproliferative agents synthesized) supported their mode of action against topoisomerase IIα

Conclusion:

The synthesized scaffold is a promising antitumor agent (with special selectivity against colon and
skin/squamous cancer cell lines) so, it can be considered for further investigation and development of highly
effective hits/leads based on the computational models obtained.
Dual Anti-cancer and Anti-Itch Activity of PD176252 Analogues: Design, Synthesis and Biological Evaluation
Authors: Yu Ming-Jun , Yao Sen , Li Ting-Ting , Yang Rui , Yao Ri-Sheng
Published: April 2019

Background:

Cancer patients treated with targeted anti-cancer drug suffer from itch or pruritus. Itch or pruritus is an unpleasant sensation that brings about a negative impact on quality of life, and serious itch may lead to dose reduction and even discontinuation. Gastrin releasing peptide receptor (GRPR) plays a critical role in itch, inflammation and cancer, and GRPR antagonist has obvious effect on cancer, inflammation and itch. The aim of this paper is to develop a new agent with anti-cancer and anti-itch activity.

Methods:

A series of GRPR antagonist PD176252 analogues (3a-3l) were designed and synthesized. Both anticancer and anti-itch activities were evaluated. Anti-cancer activity was evaluated in three human cancer cell lines in vitro, the anti-itch activity in evaluated with Kunming mice by intrathecal injection of chloroquine phosphate as a modeling medium. And the cytotoxicity on normal cells was evaluated.

Results:

Of the tested compounds, compound 3i showed potently anti-cancer activity to all cancer cell lines tested with IC50 values of 10.5µM (lung), 11.6µM (breast) and 12.8µM (liver) respectively and it also showed significant inhibition of the scratching behavior. Comparing with PD17625, compound 3i and 3g gave better inhibition activities against all cancer cell lines, compound 3b, 3c and 3i showed better anti-itch activity. The compound 3i is safe for normal breast and liver normal cells, but it has high cytotoxicity on normal lung cell.

Conclusion:

The synthesized compounds have dual anti-cancer and anti-itch activity, so the development of drug with dual anti-tumor and anti-itch property is possible.
Insights into the Structure of Amyloid Fibrils
Authors: E. Marshall Karen , C. Serpell Louise
Published: April 2019

Various proteins and peptides are able to self assemble into amyloid fibrils that are associated with disease.
Structural characterisation of these fibres is limited by their insoluble and heterogeneous nature. However, advances in
various techniques including X-ray diffraction, cryo-electron microscopy and solid state NMR have provided detailed
information on various amyloid fibrils, from the long range order and macromolecular structure to the atomic interactions
that promote assembly and stabilise the amyloid core. The cross-β model has been widely accepted as a generic structure
for most amyloid fibrils and is discussed in detail. It is clear, however, that polymorphisms are present, even in fibrils
formed from the same precursor protein, and that these may represent differences in packing at a molecular level. To fully
understand the roles of particular residues in amyloid formation and structure, short peptides can be used in conjunction
with mutagenesis studies to assess their effects. The structural insights gained using a combination of techniques to study
both full-length, disease related peptides and short fragments are essential if progress is to be made towards understanding
why these fibres form and how to prevent their formation.
HIF-1α Promotes A Hypoxia-Independent Cell Migration
Authors: Li Liyuan , Madu Chikezie O. , Lu Andrew , Lu Yi
Published: April 2019

Hypoxia-inducible factor-1α (HIF-1α) is known as a transactivator for VEGF gene promoter. It can be induced by hypoxia. However, no study has been done so far to dissect HIF-1α-mediated effects from hypoxia or VEGF-mediated effects. By using a HIF-1α knockout (HIF-1α KO) cell system in mouse embryonic fibroblast (MEF) cells, this study analyzes cell migration and HIF-1α, hypoxia and VEGF activation. A hypoxia-mediated HIF-1α induction and VEGF transactivation were observed: both HIF-1α WT lines had significantly increased VEGF transactivation, as an indicator for HIF-1α induction, in hypoxia compared to normoxia; in contrast, HIF-1α KO line had no increased VEGF transactivation under hypoxia. HIF-1α promotes cell migration: HIF-1α-KO cells had a significantly reduced migration compared to that of the HIF-1α WT cells under both normoxia and hypoxia. The significantly reduced cell migration in HIF-1α KO cells can be partially rescued by the restoration of WT HIF-1α expression mediated by adenoviral-mediated gene transfer. Interestingly, hypoxia has no effect on cell migration: the cells had a similar cell migration rate under hypoxic and normoxic conditions for both HIF-1α WT and HIF-1α KO lines, respectively. Collectively, these data suggest that HIF-1α plays a role in MEF cell migration that is independent from hypoxia-mediated effects.
Lorenzo Milani y sus fines educativos, cincuenta años después
Authors: Serna Alcántara Gonzalo Aquiles , Machorro Cabello Miguel Ángel
Published: April 2019

A manera de sencillo homenaje por su obra a favor de los niños empobrecidos, citamos brevemente los fines educativos de Lorenzo Milani, que consideramos siguen vigentes.
Chinese college students' optimism and social creativity mediated by creative self-efficacy and hope
Authors: Zhang Yunshu , Liu Wenling , Liu Ying , Huang Zhaoming , Liu Qiaoyun
Published: April 2019

We explored the impact of optimism on social creativity and the mediating roles of hope and creative self-efficacy(CSE) in this relationship. Participants were 766 college students at 8 universities in China, who completed the Social Creativity Questionnaire for College Students, the
Life Orientation Test-Revised, the Adult Dispositional HopeScale, and the Short Scale of Creative Self. The results showed that optimism was not a significant predictor of the social creativity of college students, but its effect could be indirectly predicted through the individual mediators
of CSE and hope,as well as the chain mediating effect of CSE and hope. Thus, we can conclude that optimism, CSE, and hope influence the social creativity of Chinese college students.
EXPLORANDO A CONSTRUÇÃO DA CARREIRA GERENCIAL: AS RELAÇÕES E INTERAÇÕES ENTRE GERENTES SENIORES E JUNIORES
Authors: Campos Rafaella Cristina , Cappelle Mônica Carvalho Alves , Baeta Odemir Vieira
Published: April 2019

O objetivo deste artigo é explorar aspectos da carreira gerencial no contexto atual de empresas privadas, no ponto de vista de recrutadores seniores de alto escalão hierárquico e juniores recém-contratados. A construção da carreira do indivíduo ganha destaque e passa a ser o foco permanente ao monitorar o status quo e as projeções futuras frente ao posicionamento das organizações que buscam sempre a melhor maneira de reter seus talentos. A pesquisa desenvolvida é qualitativa e a geração de dados se deu por meio de entrevistas e a técnica de análise de conteúdo serviu de base para auxiliar na interpretação dos dados. Foi possível constatar que a construção de carreira gerencial é distinta num contexto sócio-histórico-cultural, similar nas características globais do desenvolvimento profissional de um gerente, tais como habilidades técnicas e interpessoais e que há colisão de gerações de gerentes nas organizações, sendo estas interessadas em desenvolver e manter concomitantemente as duas gerações em convívio e produção, visando treinamentos de aproximação de técnicas e vivências.
ARRANJOS ORGANIZACIONAIS DE BIOTÉRIOS EM UNIVERSIDADES PÚBLICAS BRASILEIRAS
Authors: Moroni Fábio Tonissi , Loebel Eduardo
Published: April 2019

Os biotérios são instalações que oferecem serviços de apoio para a reprodução, manutenção e experimentos com animais de laboratórios na pesquisa biomédica em diferentes organizações, incluindo as universidades públicas brasileiras. A recente demanda por alinhamento das práticas administrativas com os procedimentos definidos pela legislação brasileira requer formas organizacionais e modelos de gestão éticos e eficazes. O objetivo geral deste artigo é colocar em debate a questão dos arranjos organizacionais de biotérios em universidades públicas brasileiras. Os objetivos específicos são: 1) desenvolver uma equivalência categórica da tipologia proposta por CGEE (2003) com os arranjos organizacionais propostos por Mintzberg (2012); 2) constatar, por meio de um levantamento empírico, uma representação dos arranjos organizacionais típicos na realidade brasileira; 3) discutir as bases de um modelo de desenvolvimento organizacional, as possibilidades e limitações dos arranjos organizacionais típicos estudados. O presente trabalho empregou o método tipológico, conforme Marconi e Lakatos (2005). Como resultado, discute-se as bases de um modelo de desenvolvimento organizacional e apresenta-se um mapeamento das possibilidades e limitações de arranjos organizacionais típicos em relação aos processo de pesquisa translacional. A conclusão é que três formas organizacionais ideais estruturam os biotérios em universidades públicas brasileiras. Propomos uma trajetória de desenvolvimento organizacional por meio da interconexão de tipos de ideias ao longo do tempo. Cada tipo ideal, na prática, carrega um conjunto de possibilidades e limitações. O processo de gestão deveria considera-las. As contribuições são o avanço das questões sobre os arranjos organizacionais de biotérios aos públicos acadêmico e prático no campo de pesquisa translacional.
AS COMPETÊNCIAS DE GESTORES HOTELEIROS: REFLEXÕES ENTRE FORMAÇÃO E ATUAÇÃO PROFISSIONAL EM HOTELARIA NO BREJO PARAIBANO
Authors: Lima Thales batista de , Sinésio Ielsem de Sousa
Published: April 2019

A gestão por competências potencializa resultados nas organizações e desenvolve a qualidade das pessoas em que nelas trabalham. Na linguagem organizacional, competência é um “mix” de conhecimento, habilidades e atitudes que o indivíduo possui para estar adequado no desempenho de um cargo em uma organização. Nessa perspectiva, o artigo objetiva analisar as competências de gestores hoteleiros localizados no brejo paraibano. O estudo utilizou uma abordagem qualitativa, método dedutivo e descritivo sobre a percepção dos gestores. Assim, foi realizada uma entrevista semiestruturada com quatro gestores, cuja interpretação dos dados ocorreu por meio da análise compreensiva e interpretativa dos dados. Os resultados obtidos demonstram que a hotelaria do brejo paraibano apesar de ter gestores com competências suficientes para conduzirem os meios de hospedagem que gerenciam, necessitam de uma melhor condução sobre uma gestão por competência. É necessário qualificar o hoteleiro da região, sobretudo, com competências congruentes a de uma formação em Hotelaria, de maneira que atenda melhor ao contexto hoteleiro da região. Conclui-se que, o fundamental para um profissional hoteleiro é possuir conhecimentos teóricos e práticos para que em conjunto com os demais colaboradores possam agregar valor social e econômico à organização.
A Influência Positiva Da Responsabilidade Social Corporativa No Comportamento De Consumidores: Uma Meta-Análise
Authors: Serrano André Luiz Marques , Pansani Daniel , Santana Grazielle , Franco Vithor Rosa
Published: April 2019

As atividades de Responsabilidade Social Corporativa (RSC), principalmente a partir dos anos 90, têm sido assunto tratado na produção acadêmica mundial. Diversos artigos mostram que a preocupação e execução de RSC têm impactos diretos no comportamento de consumidores, representando, inclusive, um ponto estratégico nos planejamentos empresariais relacionados a marketing e vendas, por exemplo. Este artigo objetiva verificar o impacto da RSC praticada pelas empresas no comportamento dos consumidores, respondendo a seis hipóteses (H) que consideram que a RSC tem impacto positivo nas variáveis de Percepção do Consumidor (PC). Os comportamentos avaliados, especificamente, são: Lealdade (H2), Confiança (H3), Satisfação (H4), Intenção de Compra (H5) e Identificação dos Consumidores (H6), além do conjunto de todas essas variáveis (H1). Para tanto, efetuou-se uma meta-análise da produção acadêmica que correlaciona as variáveis de comportamento às de RSC, gerando uma amostra de 33 artigos, corrigida para 36, considerando que 3 dos artigos aplicaram a mesma correlação para duas situações diferentes. O estudo da meta-análise considerou a correção do erro amostral e o erro de medição de RSC e de todas as variáveis de PC. Na aplicação dos testes estatísticos, todas as hipóteses foram confirmadas. Por ordem de força de correlação, as variáveis de comportamento podem ser assim classificadas em relação à RSC: Confiança, Satisfação, Identificação do Consumidor, Intenção de Compra e Lealdade. Na literatura pesquisada, destaca-se que não foi encontrado artigo que efetuasse meta-análise para estudos de relacionamento destas variáveis.
POLÍTICAS E PRÁTICAS DO PROCESSO DE EXPATRIAÇÃO: UM ESTUDO DE CASO EM UMA MULTINACIONAL BRASILEIRA
Authors: Gallon Shalimar - , Cerutti Priscila Sardi , Maciel Alessandra Costenaro , Oliva Eduardo de Camargo
Published: April 2019

A expatriação é um processo corrente na condução dos negócios internacionais. No entanto, quando os resultados de um projeto internacional não são alcançados, a falha é atrelada à pessoa enviada ao exterior, em vez de ser percebida como um processo que, por vezes, é mal preparado. Para tanto, essa pesquisa se constitui em estudo de caso qualitativo em uma empresa brasileira que busca analisar as políticas e práticas de Gestão de Pessoas do processo de expatriação. A coleta de dados ocorreu por meio de entrevistas com base em um roteiro semiestruturado, totalizando 23 participantes. Na análise de dados, foi utilizado o software Max-Qda (2007) para auxiliar a organização das categorias de análise, baseada na técnica de análise de conteúdo. Os resultados mostram que a empresa tem desenvolvido e implantado novas políticas e práticas de expatriação, conforme o processo foi sendo desenvolvido. É tratada como uma viagem do empregado e, para tanto, apresenta políticas e práticas de caráter burocrático. Isso acarreta na perda do conhecimento internacional que envolve a expatriação, por não ter políticas e práticas que busquem maximizar o aprendizado dos expatriados na organização.
MENSURAÇÃO DAS VANTAGENS COMPETITIVAS DO CAPITAL INTELECTUAL: UM ESTUDO EM UMA COOPERATIVA DE CRÉDITO NO SUL DO BRASIL
Authors: Berger Werlang Nathalia , Vieira de Souza Junior Ataide
Published: April 2019

O propósito deste artigo é mensurar o impacto do capital intelectual sobre a vantagem competitiva, a partir da visão dos colaboradores de uma cooperativa de crédito e de investimento do sul do país. Embora este tema tenha sido amplamente estudado, a maior parte dos trabalhos têm se concentrado nos aspectos específicos do capital intelectual. Para a execução deste estudo, foi realizada uma pesquisa com os colaboradores de uma cooperativa de crédito e de investimento do sul do país com uma amostra de 100 colaboradores. A fim de atingir os objetivos da pesquisa, foi desenvolvido um estudo de natureza descritiva e de abordagem quantitativa, operacionalizado por meio de uma survey. Por meio de análises estatísticas univariadas e de correlação, foi possível identificar que o capital intelectual possui influência sobre a vantagem competitiva da cooperativa em estudo. Além disso, destaca-se práticas relevantes da cooperativa, a qual busca o conhecimento mútuo para a resolução de questões do cotidiano de trabalho, e dispõe de mecanismos e setores especializados a fim de difundir o conhecimento como forma de melhoria na organização.
COMPORTAMENTO DE COMPRA POR IMPULSO EM SITES DE COMPRAS COLETIVAS / IMPULSIVE PURCHASE BEHAVIOR IN COLLECTIVE SHOPPING SITES
Authors: Reck Danúbia , Basso Kenny
Published: April 2019

Este trabalho aborda o comportamento de compra por impulso em sites de compras coletivas. Os objetivos deste trabalho são verificar qual a relação dos antecedentes (fatores situacionais, variáveis demográficas, fatores técnicos, processos afetivos e percepção de desconto) com a compra por impulso em sites de compras coletivas, e verificar qual o impacto da compra por impulso nas emoções positivas e negativas dos clientes de sites de compras coletivas. Para isso fez-se necessário rever os conceitos de impulsividade, compra por impulso, antecedentes da compra por impulso e as suas consequências. Para o objetivo ser atingido foi desenvolvida uma pesquisa descritiva, quantitativa com questionários fechados que foi aplicada em 142 estudantes de uma Faculdade do norte do Estado do Rio Grande do Sul, que compraram em sites de compras coletivas nos últimos doze meses. Para as análises foram utilizadas técnicas de estatísticas descritivas, correlação e regressão. Os resultados encontrados demonstram que fatores situacionais, processos afetivos e percepção de desconto são influenciadores da compra por impulso em sites de compras coletivas, através das análises também foi possível verificar que os consumidores de sites de compras coletivas percebem emoções positivas e negativas após realizarem uma compra por impulso nesses ambientes.
RELAÇÃO ENTRE O PODER DO CLIENTE E PRÁTICAS DE CONTABILIDADE GERENCIAL
Authors: Almeida Karla Katiuscia Nóbrega , Callado Antônio André Cunha
Published: April 2019

A teoria da contingência apresenta potencial explicativo sobre os fatores determinantes para adoção de práticas de contabilidade gerencial. Dentre esses fatores, o poder do cliente apresenta resultados empíricos contraditórios sobre sua relação com o nível de sofisticação das práticas de contabilidade gerencial, sinalizando a necessidade de realizar mais pesquisas sobre o tema. Assim, este estudo objetivou identificar a relação entre a percepção do poder do cliente e a adoção de práticas de contabilidade gerencial em uma indústria gráfica. Para tanto, realizou-se pesquisa exploratório-descritiva, de natureza qualitativa, por meio de estudo de caso único. Os resultados encontrados permitiram concluir que o alto poder do cliente percebido na empresa estudada incentiva a adoção de práticas de contabilidade gerencial relacionada ao custo e controle financeiro tradicionais e baixa ênfase orçamentária, e estimula, simultaneamente, a adoção de práticas de contabilidade gerencial relativas à avaliação de desempenho avançadas. No entanto, para confirmação dessa relação se acrescenta o poder explicativo de outros fatores contingencias que dizem respeito a estratégia, porte e concorrência.
O PROFISSIONAL DE SECRETARIADO E A COMUNICAÇÃO INTERNA HOSPITALAR: ATUAÇÃO POR MEIO DA ASSESSORIA
Authors: Do Nascimento Geisi Gaiewski , Nunes Duarte Jansem Quelli , Kruchelski Marcielly , Angnes Juliane Sachser , Monteiro Caroline
Published: April 2019

Entende-se que a comunicação interna para as organizações hospitalares deve ser vista como a ferramenta principal para que se atinja as suas necessidades e, vinculado a isso, aponta-se a necessidade um profissional que atue na comunicação interna hospitalar por meio da assessoria para que se alcance a qualidade na prestação dos serviços. Diante do exposto, a pesquisa teve como objetivo geral mapear a atuação do Profissional de Secretariado Executivo na comunicação interna por meio da assessoria hospitalar. Trata-se de uma pesquisa descritiva, de abordagem quantitativa. Como instrumento de coleta de dados questionários foram aplicados aos funcionários dos hospitais localizados em um município da região do Centro-Oeste do Paraná. O universo da pesquisa corresponde a aproximadamente 80 funcionários, obteve-se retorno de 41 questionários, o que caracteriza 51,25% da amostra. Os resultados da pesquisa apontam que o Profissional de Secretariado Executivo está apto para atuar no ambiente hospitalar, e seu desempenho colabora para o aperfeiçoamento da comunicação interna desse ambiente por meio da assessoria.
OUTSOURCING NA INDÚSTRIA PARANAENSE: UM ESTUDO EMPÍRICO
Authors: Anjos Edenise Aparecida dos , Moura Ivanildo Viana , Brito Adriely Camparoto , Aquino Bianca , Almeida Lauro Brito de , Pacheco Vicente
Published: April 2019

Uma técnica muito utilizada nas indústrias é o outsourcing, que consiste na prática de comprar produtos e serviços externos, fornecendo ideia de algo originário de fora da organização. A questão de pesquisa é: quais os critérios recorrentes para a tomada de decisão na adesão do outsourcing? buscando-se investigar na percepção dos gestores, os critérios e as variáveis considerados relevantes para tomada de decisão de adesão ao outsourcing. A pesquisa empírica realizada é descritiva com enfoque quantitativo, a população é formada por 2.775 industrias paranaenses cadastradas junto a Federação das Indústrias do Paraná (FIEP). O instrumento de pesquisa foi adaptado de Moschuris (2015), a coleta de dados ocorreu nos meses de junho e julho de 2016 e, ao término foram consideradas respostas fornecidas por 48 industrias. Os achados da pesquisa evidenciam que dos 11 critérios estratégicos apresentados, as variáveis consideradas mais relevantes na percepção dos gestores respondentes foram custo e qualidade.