bluuebunny/crossref_metadata_2025 huggingface dataset:
Water safety assessment and spatio-temporal changes in Dongting Lake, China on the basis of water regime during 1980–2014
Authors: Wan Rongrong , Wang Peng , Dai Xue , He Zheng
Published: June 2019

The drastic changes in water regime are of great importance for maintaining water security in lakes with violent seasonal fluctuations. Based on hydrological data of Dongting Lake, the second largest freshwater lake in China, during 1980–2014, a set of water safety assessment methods suitable for seasonal lakes was constructed. Results demonstrated the following. (1) The year 2003 was a major time point for changes in water regime in Dongting Lake between 1980 and 2014. (2) The water regime changes in different parts of Dongting Lake exhibited certain similarities in periodicity and overall change trends. Among them, South Dongting Lake presented the best water security status, followed by East Dongting Lake and West Dongting Lake. (3) Compared with 1980–2002, the complexity of the water safety level change in East Dongting Lake increased in 2003–2014, as manifested in the tendency of the distribution of water safety levels to change sharply. (4) The influence of dry years on the water safety of Dongting Lake was greater than that of rainy years. The multi-time, multi-scale and multi-target lake water safety assessment method based on water regimes provides new ideas and methods for global research on seasonal lake water safety.
Discovery of the Magdalena ore body. The leading role of geophysical methods for the exploration of a deep volcanogenic massive sulphide deposits (VMS) in the Iberian Pyrite Belt
Authors: Granda Sanz Ángel , Granda París Teresa , Pons Juan Manuel , Videira Juan Carlos
Published: June 2019

The Magdalena volcanogenic massive sulphide (VMS) deposit, located in the province of Huelva (Spain) and discovered by Minas de Aguas Teñidas S.A.U. (MATSA) in 2013 constitutes the largest discovery to be made in the Iberian Pyrite Belt (IPB) in recent decades. During a first phase of exploration, the deposit was discovered by drill testing a conductivity anomaly that was first detected during an airborne (helicopter) transient electromagnetic survey (VTEM) in 2011. Drill-hole MA-01 intersected the massive sulphide body at a depth of between 225 m and 248 m. Throughout the drilling campaign of the sulphide body later named “Masa 1”, the drill holes were surveyed using Downhole TEM and Mise-à-la-Masse geophysical methods and during this work the Downhole TEM results from drill hole MA-21, which was originally drilled to 320 m, detected the presence of a deeper and larger sulphide body. The appearance of an off-hole, down-hole TEM anomaly in hole MA-21 was fundamental in the discovery of “Masa 2” which was made once the drill rig was recollared on the original MA-21 pad and drilled to a depth of 530 m. This second sulphide lens (“Masa 2”) was not detected by the initial VTEM survey because it was beyond the range for the system and was subsequently drill tested at depths between 350 and 1,000 m. The discovery of the Magdalena deposit has demonstrated the crucial role of certain geophysical methods for the detection of deep VMS deposits and confirms the prospectivity of the IPB as a metallogenic area of undoubted potential as far as the existence of similar deposits are concerned.
Lucas Mallada mineral collection. The legacy of an Aragonese to the “Escuela Normal de Maestros” of Huesca
Authors: Calvo Rebollar M. , Lucha López P.
Published: June 2019

The Faculty of Human Sciences and Education of Huesca preserves a remarkable collection of geological materials, mainly minerals, that belonged to Lucas Mallada and that was donated in 1925 to its predecessor institution, the Normal School of Teachers, by the heirs of this geologist. This collection has been recently inventoried and studied. An important part of the specimens are related to the work of Mallada as a member of the Geological Map Commission and come from localities where it is currently impossible to obtain samples of this type and some of them can even be considered unique. The valorization of these specimens represents a significant contribution to the history of Spanish geology and to the topographic mineralogy of our country.
The Spanish Petroleum Systems and the Overlooked Areas and Targets
Authors: Martínez del Olmo W.
Published: June 2019

The structural complexity of the Spanish territory hampered the development of large sedimentary basins with a time-space evolution that could have allowed the accumulation and preservation of large hydrocarbon deposits. In spite of this, including the few exploratory wells drilled (3.13 wells / 1,000 square miles), Spain (including on and offshore) has up to eight geological systems with present or past commercial hydrocarbon fields: the Gulf of Cadiz-Guadalquivir Miocene foreland basin, the Cretaceous of the Betic ranges, the Jurassic and Lower Miocene of the Western Mediterranean Sea, the Albian sands of the Rioja Paleogene foreland basin, the Platform-Basin of the onshore Cantabrian basin, the Ypresian of the Pyrenees thrust belts, and the westward continuity of the Aquitania foreland basin in the Gulf of Biscay. There are other remaining areas that supposedly contain an exploratory potential that could be much higher than the systems mentioned above: the deep waters of the Mediterranean and Cantabrian seas and the Atlantic Ocean of the Canary Islands, the Mesozoic covered by the olistostromes of the Betic ranges, the onshore Triassic sandy reservoirs and the onshore Carboniferous sub-basins found throughout the mainland. These areas have an even lower level of exploration (0.26 wells / 1,000 square miles).
Efeito do consumo de frutas in natura e vegetais na pressão arterial de adultos
Authors: Silva Pereira Taísa Sabrina , Batista Milena Santos , Bisi Molina Maria del Carmen
Published: June 2019

Effect of in natura and vegetable fruit intake on adult blood pressure
The Role of NIR Fluorescence in MDR Cancer Treatment: From Targeted Imaging to Phototherapy
Authors: Wang Zengtao , Meng Qingqing , Li Shaoshun
Published: June 2019

Background:

Multidrug Resistance (MDR) is defined as a cross-resistance of cancer cells
to various chemotherapeutics and has been demonstrated to correlate with drug efflux pumps. Visualization
of drug efflux pumps is useful to pre-select patients who may be insensitive to chemotherapy,
thus preventing patients from unnecessary treatment. Near-Infrared (NIR) imaging is an attractive
approach to monitoring MDR due to its low tissue autofluorescence and deep tissue penetration.
Molecular NIR imaging of MDR cancers requires stable probes targeting biomarkers with high
specificity and affinity.

Objective:

This article aims to provide a concise review of novel NIR probes and their applications
in MDR cancer treatment.

Results:

Recently, extensive research has been performed to develop novel NIR probes and several
strategies display great promise. These strategies include chemical conjugation between NIR dyes
and ligands targeting MDR-associated biomarkers, native NIR dyes with inherent targeting ability,
activatable NIR probes as well as NIR dyes loaded nanoparticles. Moreover, NIR probes have been
widely employed for photothermal and photodynamic therapy in cancer treatment, which combine
with other modalities to overcome MDR. With the rapid advancing of nanotechnology, various
nanoparticles are incorporated with NIR dyes to provide multifunctional platforms for controlled
drug delivery and combined therapy to combat MDR. The construction of these probes for MDR
cancers targeted NIR imaging and phototherapy will be discussed. Multimodal nanoscale platform
which integrates MDR monitoring and combined therapy will also be encompassed.

Conclusion:

We believe these NIR probes project a promising approach for diagnosis and therapy
of MDR cancers, thus holding great potential to reach clinical settings in cancer treatment.
Synthesis and Antitumor Activity Assay of Epoxy Bicyclo[4.2.2]deca-2,4,7,(9)- tri(tetra)enes and Tricyclo[9.4.2.02,10]heptadeca-2,12,14,16-tetraene
Authors: D'yakonov Vladimir A. , Kadikova Gulnara N. , Gazizullina Guzel F. , Dzhemileva Lilya U. , Tulyabaev Artur R. , Dzhemilev Usein M.
Published: June 2019

Triepoxides were synthesized for the first time in high yields (80-85%) by oxidation
of substituted bicyclo[4.2.2]deca-2,4,7,9-tetraenes, bicyclo[4.2.2]deca-2,4,7-trienes,
and tricyclo[9.4.2.02,10]heptadeca-2,12,14,16-tetraene with an excess of m-chloroperbenzoic
acid. The structures of the epoxy derivatives were reliably proved using modern
spectral methods and X-ray diffraction analysis. A high antitumor activity in vitro was
found for triepoxides against the Jurkat, K562, U937 tumor cell lines and normal fibroblasts.
Expanding the Biotherapeutics Realm via miR-34a: “Potent Clever Little” Agent in Breast Cancer Therapy
Authors: Mohammady Mohsen , Ghetmiri Seyed I. , Baharizade Mahtab , Morowvat Mohammad H. , Torabi Susan
Published: June 2019

Background:

One of the most prevalent cancers befell to women is considered to be breast cancer (BC). It is also the deadliest among the female population after lung cancer. Additionally, several studies have demonstrated that there is an association between microRNA34-a and breast cancer.

Method:

We searched PubMed, Web of Science, and Google Scholar up to December 2018. Those studies which have been studied miR-34a and its tumor-suppressing capabilities were considered as the most important topics. Moreover, we extracted articles which were solely focused on microRNA-34a in breast cancer therapy. Finally, 80 articles were included.

Results:

In comparison with the normal tissues, down-regulation of miR-34a expression is shown considerably in tumor cells. Overexpression of miR-34a acts as a tumor suppressor by transcriptional regulating one of the signaling pathways (TP53), NOTCH, and transforming growth factor beta (TGF-β), Bcl- 2 and SIRT1genes, HDAC1 and HDAC7, Fra-1, TPD52, TLR Via CXCL10. Moreover, drug resistance declines which lead to the apoptosis, cell cycle arrest and senescence. As a result, the proliferation, invasion and metastasis of the tumor are suppressed. The Mrx34 drug contains miR-34a mimic and a lipid vector. MiR-34a as the active ingredient portrays the role of a tumor suppressor. This drug has recently entered the clinical trials studies.

Conclusion:

These findings suggest a robust cause for developing miR-34a as a therapeutic agent to target BC. In that scenario, miR-34a is strongly useful to introduce new therapeutic goals for BC. Moreover, this review aims to confirm the signal pathways, therapeutic and diagnostic values of miR- 34a in BC and beyond.
Physico-chemical Changes Induced in the Serum Proteins Immunoglobulin G and Fibrinogen Mediated by Methylglyoxal
Authors: Rehman Shahnawaz , Faisal Mohammad , Alatar Abdulrahman A. , Ahmad Saheem
Published: June 2019

Background:

Non-enzymatic glycation of proteins plays a significant role in the pathogenesis
of secondary diabetic complications via the formation of advanced glycation end products (AGEs) and
increased oxidative stress. Methylglyoxal (MG), a highly reactive dicarbonyl of class α-oxoaldehyde
that generates during glucose oxidation and lipid peroxidation, contributes to glycation.

Objective:

This comparative study focuses on methylglyoxal induced glycoxidative damage suffered by
immunoglobulin G (IgG) and fibrinogen, and to unveil implication of structural modification of serum
proteins in diabetes-associated secondary complications.

Methods:

The methylglyoxal induced structural alterations in IgG and fibrinogen were analyzed by UVvis,
fluorescence, circular dichroism and Fourier transform infrared (FT-IR) spectroscopy. Ketoamine
moieties, carbonyl contents, 5-Hydroxymethylfurfural (HMF) and malondyaldehyde were also quantified.
Free lysine and arginine estimation, detection of non-fluorogenic carboxymethyllysine (CML) and
fibril formation were confirmed by thioflavin T (ThT) assay.

Results:

Structural alterations, increased carbonyl contents and ketoamines were reported in MG glycated
IgG and fibrinogen against their native analogues.

Conclusion:

The experiment results validate structural modifications, increased oxidative stress and
AGEs formation. Thus, we can conclude that IgG-AGEs and Fib-AGEs formed during MG induced glycation
of IgG and fibrinogen could impede normal physiology and might initiates secondary complications
in diabetic patients.
Immunomodulators: Friends or Enemies in Surgery for Crohn’s Disease?
Authors: Landerholm Kalle , Kalman Disa , Wallon Conny , Myrelid Pär
Published: June 2019

Crohn’s disease may severely impact the quality of life and being a chronic disease it requires
both medical and surgical treatment aimed at induction and maintenance of remission to prevent
relapsing symptoms and the need for further surgery. Surgery in Crohn’s disease often has to be
performed in patients with well-known risk factors of post-operative complications, particularly intraabdominal
septic complications. This review will look at the current knowledge of immunomodulating
therapies in the peri-operative phase of Crohn’s disease. The influence of immunomodulators on postoperative
complications is evaluated by reviewing available clinical reports and data from animal
studies. Furthermore, the effect of immunomodulators on preventing or deferring primary as well as
repeat surgery in Crohn’s disease is reviewed with particular consideration given to high-risk cohorts
and timing of prophylaxis.
Recent Advances in the HPLC Analysis of Tricyclic Antidepressants in Bio-Samples
Authors: Manousi Natalia , Samanidou Victoria F.
Published: June 2019

:

Tricyclic Antidepressants (TCAs) are a group of the main category of antidepressant drugs,
which are commonly prescribed to treat major depressive disorder. Determination of TCA drugs is
very important for clinical and forensic toxicology, especially for therapeutic drug monitoring in various
biofluids. High Performance Liquid Chromatography (HPLC) is a well-established technique for
this purpose. A lot of progress has been made in this field since the past 10 years. Novel extraction
techniques, and novel materials for sample preparation, novel columns and novel applications of analysis
of various biofluids for the determination of TCAs in combination with other drugs are some typical
examples. Moreover, advances have been performed in terms of Green Analytical Chemistry principles.
Herein, we aim to discuss the developed HPLC methods that were reported in the literature for
the time span of 2008-2018.
Current Status in the Discovery of Covalent Janus Kinase 3 (JAK3) Inhibitors
Authors: Dai Jun , Yang LiXi , Addison Glynn
Published: June 2019

The search for inhibitors of the Janus kinase family (JAK1, JAK2, JAK3 and TYK2) has
been ongoing for several decades and has resulted in a number of JAK inhibitors being approved for
use in patients, such as tofacitinib for the treatment of autoimmune diseases such as Rheumatoid Arthritis
(RA). Although initially thought to be a JAK3 selective inhibitor, tofacitinib was subsequently
found to possess significant activity to inhibit JAK1 and JAK2 which has contributed to some adverse
side effects. A selective JAK3 inhibitor should only have an effect within the immune system since
JAK3 is solely expressed in lymphoid tissue; this makes JAK3 a target of interest in the search for
treatments of autoimmune diseases. A method to obtain selectivity for JAK3 over the other JAK family
members, which has attracted more scientific attention recently, is the targeting of the active site cysteine
residue, unique in JAK3 within the JAK family, with compounds containing electrophilic warheads
which can form a covalent bond with the nucleophilic thiol of the cysteine residue. This review encompasses
the historical search for a covalent JAK3 inhibitor and the most recently published research
which hasn’t been reviewed to date. The most important compounds from the publications reviewed
the activity and selectivity of these compounds together with some of the more important biological
results are condensed in to an easily digested form that should prove useful for those interested in the
field.
A Review on Anticancer Potentials of Benzothiazole Derivatives
Authors: Pathak Nandini , Rathi Ekta , Kumar Nitesh , Kini Suvarna G. , Rao C. Mallikarjuna
Published: June 2019

:

Benzothiazole is an organic compound bearing a heterocyclic nucleus (thiazole) which imparts
a broad spectrum of biological activities to it. The significant and potent activity of benzothiazole
moiety influenced distinctively by nature and position of substitutions. This review summarizes the
effect of various substituents in recent trends and approaches to design and develop novel
benzothiazole derivatives for anticancer potential in different cell lines by interpreting the Structure-
Activity Relationship (SAR) and mechanism of action of a wide range of derivatives. The list of
derivatives is categorized into different groups and reviewed for their anticancer activity. The
structure-activity relationship for the various derivatives revealed an excellent understanding of benzothiazole
moiety in the field of cancer therapy against different cancer cell line. Data obtained from the
various articles showed the potential effect of benzothiazole moiety and its derivatives to produce the
peculiar and significant lead compound. The important anticancer mechanisms found are tyrosine
kinase inhibition, topoisomerase inhibition and induction of apoptosis by Reactive Oxygen Species
(ROS) activation. Therefore, the design and development of novel benzothiazole have broad scope in
cancer chemotherapy.
Strategies to Control Human Lymphatic Filarial Infection: Tweaking Host’s Immune System
Authors: Murthy Puvvada Kalpana
Published: June 2019

Human lymphatic filariasis (LF), a parasitic infection caused by the nematodes Wuchereria bancrofti, Brugia malayi and B. timori, and transmitted by mosquito, results in a debilitating disease commonly identified as ‘elephantiasis’. LF affects millions of people in India and several other tropical and sub-tropical countries imposing a huge economic burden on governments due to disability associated loss of man-hours and for disease management. Efforts to control the infection by WHO’s mass drug administration (MDA) strategy using three antifilarials diethylcarbamazine, albendazole and ivermectin are only partly successful and therefore, there is an immediate need for alternative strategies. Some of the alternative strategies being explored in laboratories are: enhancing the immune competence of host by immunomodulation, combining immunomodulation with antifilarials, identifying immunoprophylactic parasite molecules (vaccine candidates) and identifying parasite molecules that can be potential drug targets. This review focuses on the advances made in this direction.
Computational Analysis of Therapeutic Enzyme Uricase from Different Source Organisms
Authors: Nelapati Anand Kumar , PonnanEttiyappan JagadeeshBabu
Published: June 2019

Background:

Hyperuricemia and gout are the conditions, which is a response of accumulation of uric acid in the blood and urine. Uric acid is the product of purine metabolic pathway in humans. Uricase is a therapeutic enzyme that can enzymatically reduces the concentration of uric acid in serum and urine into more a soluble allantoin. Uricases are widely available in several sources like bacteria, fungi, yeast, plants and animals.

Objective:

The present study is aimed at elucidating the structure and physiochemical properties of uricase by insilico analysis.

Methods:

A total number of sixty amino acid sequences of uricase belongs to different sources were obtained from NCBI and different analysis like Multiple Sequence Alignment (MSA), homology search, phylogenetic relation, motif search, domain architecture and physiochemical properties including pI, EC, Ai, Ii, and were performed.

Results:

Multiple sequence alignment of all the selected protein sequences has exhibited distinct difference between bacterial, fungal, plant and animal sources based on the position-specific existence of conserved amino acid residues. The maximum homology of all the selected protein sequences is between 51-388. In singular category, homology is between 16-337 for bacterial uricase, 14-339 for fungal uricase, 12-317 for plants uricase, and 37-361 for animals uricase. The phylogenetic tree constructed based on the amino acid sequences disclosed clusters indicating that uricase is from different source. The physiochemical features revealed that the uricase amino acid residues are in between 300- 338 with a molecular weight as 33-39kDa and theoretical pI ranging from 4.95-8.88. The amino acid composition results showed that valine amino acid has a high average frequency of 8.79 percentage compared to different amino acids in all analyzed species.

Conclusion:

In the area of bioinformatics field, this work might be informative and a stepping-stone to other researchers to get an idea about the physicochemical features, evolutionary history and structural motifs of uricase that can be widely used in biotechnological and pharmaceutical industries. Therefore, the proposed in silico analysis can be considered for protein engineering work, as well as for gout therapy.
Definition of Opportunistic Infections in Immunocompromised Children on the Basis of Etiologies and Clinical Features: A Summary for Practical Purposes
Authors: Riccardi Niccolò , Rotulo Gioacchino Andrea , Castagnola Elio
Published: June 2019

:

Opportunistic Infections (OIs) still remain a major cause of morbidity and death in children
with either malignant or nonmalignant disease.

:

OIs are defined as those infections occurring due to bacteria, fungi, viruses or commensal organisms
that normally inhabit the human body and do not cause a disease in healthy people, but become
pathogenic when the body's defense system is impaired. OIs can also be represented by unusually
severe infections caused by common pathogens. An OI could present itself at the onset of a
primary immunodeficiency syndrome as a life-threatening event. More often, OI is a therapyassociated
complication in patients needing immunosuppressive treatment, among long-term hospitalised
patients or in children who undergo bone marrow or solid organ transplantation.

:

The aim of the present review is to provide a comprehensive and ‘easy to read’ text that briefly
summarises the currently available knowledge about OIs in order to define when an infection
should be considered as opportunistic in pediatrics as a result of an underlying congenital or acquired
immune-deficit.
An Insight of Alpha-amylase Inhibitors as a Valuable Tool in the Management of Type 2 Diabetes Mellitus
Authors: Bashary Roqia , Vyas Manish , Nayak Surendra Kumar , Suttee Ashish , Verma Surajpal , Narang Rakesh , Khatik Gopal L.
Published: June 2019

Background:

Among the millions of people around the world, the most prevalent metabolic
disorder is diabetes mellitus. Due to the drawbacks which are associated with commercially available
antidiabetic agents, new therapeutic approaches are needed to be considered. Alpha-amylase is a membrane-
bound enzyme which is responsible for the breakdown of polysaccharides such as starch to
monosaccharides which can be absorbed.

Methods:

We searched the scientific database using alpha-amylase, diabetes, antidiabetic agents as the
keywords. Here in, only peer-reviewed research articles were collected which were useful to our current
work.

Results:

To overcome the research gap, the alpha-amylase enzyme is regarded as a good target for antidiabetic
agents to design the drug and provide an alternate approach for the treatment of type 2 diabetes
mellitus. Basically, alpha-amylase inhibitors are classified into two groups: proteinaceous inhibitors,
and non-proteinaceous inhibitors. Recently, non-proteinaceous inhibitors are being explored
which includes chalcones, flavones, benzothiazoles, etc. as the potential antidiabetic agents.

Conclusion:

Herein, we discuss various potential antidiabetic agents which are strategically targeted
alpha-amylase enzyme. These are having lesser side effects as compared to other antidiabetic agents,
and are proposed to prevent the digestion and absorption of glucose leading to a decrease in the blood
glucose level.
Digoxin in Atrial Fibrillation: An Old Topic Revisited
Authors: Ferrari Filipe , Santander Igor R.M.F. , Stein Ricardo
Published: June 2019

Digoxin has been used for more than 50 years in patients with Atrial Fibrillation (AF),
with the goal of Controlling Heart Rate (HR) and restoring sinus rhythm. In the last two decades,
several studies have correlated therapeutic use of digoxin with increased mortality. However, such
studies have potential biases that cannot be disregarded, mainly because they are cross-sectional
experiments or post-hoc analyses of Randomized Controlled Trials (RCTs). Despite uncertainties
regarding the safety of digoxin in this setting, it remains one of the most prescribed drugs for AF
worldwide. On the other hand, the absence of any RCTs designed to evaluate mortality makes a definitive
conclusion more difficult to reach; therefore, this medication must be used with care. In this
review, we explored the therapeutic use of digoxin in the context of AF, discussed mortality data by
means of critical analysis in the light of the best available evidence, and position ourselves in relation
to more rigorous control of serum levels of this drug in daily practice.
Quantitative Analysis of 5-Hydroxymethylfurfural in Linezolid Injection by High Performance Liquid Chromatography
Authors: Batista Jéssica Maurício , Fernandes Christian
Published: June 2019

Background:

Linezolid is a synthetic broad-spectrum antibacterial belonging to the class of
oxazolidinones. Linezolid for intravenous infusion is isotonized with dextrose. In acidic environment,
the dehydration of dextrose produces furan derivatives, 5-hydroxymethylfurfural (5-HMF) being the
main one. The determination of this degradation product is of fundamental importance, since there is
evidence it is cytotoxic, genotoxic, mutagenic and carcinogenic. However, there is no official method
for the determination of 5-HMF in drug products.

Objective:

The aim of this study was to develop and validate a high performance liquid chromatographic
method to quantify 5-HMF in injection of linezolid.

Methods:

The chromatographic separation, after optimization, was performed on C18 (150 x 4.6 mm,
5 μm) column. Mobile phase was composed of 14 mM potassium phosphate buffer pH 3.0 ([H+] = 1.0 x
10-3) and methanol in gradient elution at 1.0 mL min-1. The injection volume was 10 μL and detection
was performed at 285 nm.

Results:

The method was optimized and validated, showing selectivity, linearity in the range from 0.075
to 9.0 μg mL-1, precision (RSD ≤ 2.0%), accuracy (mean recovery of 100.07%) and robustness for temperature
and pH variation.

Conclusion:

The method was shown to be adequate to determine 5-HMF in injection containing linezolid
in routine analysis.
A Reliable HPLC-ELSD Method for Determination of Cholesterol, Phosphatidylcholine, Lysophosphatidylcholine Content and the Stability of a Liposomal Formulation
Authors: de Magalhães Benedetti Naiara Ieza Gallo , Costa Veloso Danillo Fabrini Maciel , Nascimento Thais Leite , Almeida Diniz Danielle Guimarães , Maione-Silva Lorena , Lima Eliana Martins
Published: June 2019

Background:

Liposomes continue to play an important role in drug delivery research due to their ability to improve transport and targeting of a wide range of active molecules. Analysis of liposomal components is a key point in the characterization and evaluation of formulation stability. The aim of this work was to develop and validate an HPLC-ELSD method for the characterization and quality control of liposomes.

Methods:

HPLC-ELSD method was validated by assessing selectivity, linearity, precision, accuracy, limit of detection and quantitation. The mobile phase consisted of a 0.1% (v/v) of trifluoroacetic acid (TFA) and methanol in gradient elution. Initial rate was 20:80 (0.1% TFA: methanol), with a ramp reaching 100% methanol. HPLC-MS/MS was used to confirm the presence of the fatty acid mixture in the analyzed lipids, as well as sub-products generated under pre-determined conditions in the stability study.

Results:

A HPLC-ELSD method has been developed to detect and measure cholesterol, phosphatidylcholine and lysophosphatidylcholine. High specificity, sensitivity and linearity within the predetermined range for all the compounds analyzed (R2>0.99) were obtained. Accuracy and precision results for all the compounds were within the acceptance limit of ≤5% and 90-110%, respectively. Mass spectrometry results showed complementary information about the phospholipid composition to evaluate the degree of degradation of liposomes over different storage conditions.

Conclusion:

The method was successfully applied as a quality control tool for the analysis of a wide range of lipids, present in liposomal formulations. HPLC-MS/MS was used to ensure complete elucidation of the lipid components and the detected lyso-forms.
A Bayesian Regularized Artificial Neural Network for Simultaneous Determination of Loratadine, Naproxen and Diclofenac in Wastewaters
Authors: Mohammadpoor Mojtaba , Kakhki Roya Mohammadzadeh , Assadi Hakimeh
Published: June 2019

Background::

Simultaneous determination of medication components in pharmaceutical
samples using ordinary methods have some difficulties and therefore these determinations usually
were made by expensive methods and instruments. Chemometric methods are an effective way to
analyze several components simultaneously.

Objective::

In this paper, a novel approach based on Bayesian regularized artificial neural network
is developed for the determination of Loratadine, Naproxen, and Diclofenac in water using UV-Vis
spectroscopy.

Methods:

A dataset is collected by performing several chemical experiments and recording the UV-Vis
spectra and actual constituent values. The effect of a different number of neurons in the hidden
layer was analyzed based on final mean square error, and the optimum number was selected. Principle
Component Analysis (PCA) was also applied to the data. Other back-propagation methods,
such as Levenberg-Marquardt, scaled conjugate gradient, and resilient backpropagation, were tested.

Results::

In order to see the proposed network performance, it was performed on two crossvalidation
methods, namely partitioning data into train and test parts, and leave-one-out technique.
Mean square errors between expected results and predicted ones implied that the proposed method
has a strong ability in predicting the expected values.

Conclusion::

he results showed that the Bayesian regularization algorithm has the best performance
among other methods for simultaneous determination of Loratadine, Naproxen, and Diclofenac
in water samples.
Epigenetic Regulator Signatures in Regenerative Capacity
Authors: Albogami Sarah
Published: June 2019

Background::

Regeneration is the process by which body parts lost as a result of injury are
replaced, as observed in certain animal species. The root of regenerative differences between organisms
is still not very well understood; if regeneration merely recycles developmental pathways in the adult
form, why can some animals regrow organs whereas others cannot? In the regulation of the regeneration
process as well as other biological phenomena, epigenetics plays an essential role.

Objective::

This review aims to demonstrate the role of epigenetic regulators in determining regenerative
capacity.

Results::

In this review, we discuss the basis of regenerative differences between organisms. In addition,
we present the current knowledge on the role of epigenetic regulation in regeneration, including
DNA methylation, histone modification, lysine methylation, lysine methyltransferases, and the SET1
family.

Conclusion::

An improved understanding of the regeneration process and the epigenetic regulation
thereof through the study of regeneration in highly regenerative species will help in the field of regenerative
medicine in future.
RO3280: A Novel PLK1 Inhibitor, Suppressed the Proliferation of MCF-7 Breast Cancer Cells Through the Induction of Cell Cycle Arrest at G2/M Point
Authors: Ergul Mustafa , Bakar-Ates Filiz
Published: June 2019

Background:

As a member of serine/threonine-protein kinase, Polo‐like kinase 1 (PLK1)
plays crucial roles during mitosis and also contributes to DNA damage response and repair.
PLK1 is aberrantly expressed in many types of tumor cells and increased levels of PLK1 is
closely related to tumorigenesis and poor clinical outcomes. Therefore, PLK1 is accepted as
one of the potential targets for the discovery of novel anticancer agents. The objective of this
study was to assess the cytotoxic effects of a novel PLK1 inhibitor, RO3280, against MCF-7,
human breast cancer cells; HepG2, human hepatocellular carcinoma cells; and PC3, human
prostate cancer cells, as well as non-cancerous L929 fibroblast cells.

Methods:

Antiproliferative activity of RO3280 was examined using the XTT assay. Flow
cytometry assay was performed to evaluate cell cycle distribution, apoptosis, multicaspase
activity, mitochondrial membrane potential, and DNA damage response. We also examined
apoptosis with fluorescence imaging studies.

Results:

According to the results of XTT assay, although RO3280 displayed potent cytotoxicity in all treated
cancer cells, the most sensitive cell line was identified as MCF-7 cells that were selected for further studies. The
compound induced a cell cycle arrest in MCF-7 cells at G2/M phase and significantly induced apoptosis, multicaspase
activity, DNA damage response, and decreased mitochondrial membrane potential of MCF-7 cells.

Conclusion:

Overall, RO3280 induces anticancer effects promoted mainly by DNA damage, cell cycle arrest,
and apoptosis in breast cancer cells. Further studies are needed to assess its usability as an anticancer agent with
specific cancer types.
Serum Vitamin D Levels in Children with Immune Thrombocytopenia
Authors: Lassandro Giuseppe , Carriero Francesco , Palmieri Viviana , Palladino Valentina , Amoruso Anna , Gallone Maria Filomena , Del Vecchio Giovanni C. , Tafuri Silvio , Russo Giovanna , Valente Federica , Giordano Paola
Published: June 2019

Objective:

Immune thrombocytopenia (ITP) is an acquired immuno-mediated disorder characterized
by thrombocytopenia with an increased risk of bleeding. In recent years 1,25[OH]2D3 has
been rediscovered as an immune modulator. We decided to evaluate serum Vitamin D levels in a cohort
of children with immune thrombocytopenia in order to discover if Vitamin D concentrations may
predict ITP duration.

Methods:

Thirty children were enrolled in this study (sixteen with chronic ITP and fourteen with
newly diagnosed ITP) to assess serum Vitamin D levels.

Results::

The results showed that 80% of the enrolled children presented a D hypovitaminosis status.
Children with newly diagnosis ITP showed no statistically significantly higher median values of Vitamin
D compared to chronic ITP.

Conclusions::

This study may suggest that Vitamin D deficiency does not represent a chronicity factor
for ITP. However, further studies are needed to understand the role of Vitamin D in ITP pathogenesis.
Atorvastatin Inhibited ROS Generation and Increased IL-1β And IL-6 Release by Mononuclear Cells from Diabetic Patients
Authors: dos Anjos Paula M.F. , Volpe Caroline M.O. , Miranda Thaís C. , Nogueira-Machado José A.
Published: June 2019

Background:

Atorvastatin (ATV) inhibits the conversion of 3-Hydroxy-3-Methylglutaryl
Coenzyme A (HMG-CoA) to mevalonate formation and promotes lowering of the LDL cholesterol
fraction. However, ATV exhibits pleiotropic metabolic actions beyond cholesterol-lowering properties.

Objective:

We aimed to evaluate the effect of ATV on oxidizing species generation and cytokine secretion
in Peripheral Blood Mononuclear Cells (PBMNC) of Type 2 Diabetes Mellitus (T2DM) patients
in comparison to healthy control.

Methods:

Both NADPH-oxidase-dependent and mitochondrial ROS generation were assessed by
chemoluminescence luminol-dependent assay and fluorometric experiment, using Dichlorofluorescein
Assay (DCFH-DA), respectively. IL-1β and IL-6 were quantified by classical ELISA.

Results:

ATV inhibited NADPH-oxidase dependent ROS generation, but showed no effect on mitochondrial
ROS generation and activated IL-1β and IL-6 secretions in PBMNC from control and T2DM
patients. ROS generation and cytokine secretion in the presence of an inhibitor of Protein Kinase Cβ
(iPKCβ) and ATV led to similar results. The secretion of IL-1β, PDB-induced in the presence of
iPKCβ, but not ATV, was increased. ATV and iPKCβ exacerbated PDB-induced IL-6 secretion. LPS
activated the secretion of IL-1β and IL-6 which was potentiated by ATV.

Conclusion:

ATV inhibited ROS generation and activated IL-1 β/IL-6 secretion in PBMNC of diabetes
patients. Its effect was not affected by the hyperglymemia.
Thyroid and Eye: Where They Meet in Clinical Practice
Authors: El-Eshmawy Mervat M. , Shahin Maha
Published: June 2019

Objective:

Thyroid Hormones (TH) are essential for normal growth, development and continued
optimal function of most of the body organs including the eye. TH signaling plays a central role
in the regulation of retinal development and maturation. Deficiency in TH during fetal and early postnatal
development impairs growth of the eye and proliferation of all retinal cell types. The present
article reviews the most important topics of the different derangements in thyroid function and structure
and its relation with eye diseases.

Methods:

A literature search strategy was conducted for all English-language literature.

Results:

From a clinical practice viewpoint, it should be mentioned that both hypothyroidism and hyperthyroidism
are accompanied by ocular diseases i.e. thyroid-associated ophthalmopathy, diabetic
retinopathy and age-related macular degeneration. Although the orbit and globe are not common sites
for metastatic thyroid cancers, orbital metastasis may be the primary clinical manifestation of thyroid
carcinoma. Finally, some medications as amiodarone may be accompanied by both thyroid dysfunction
and adverse ocular events.

Conclusion:

Thyroid disorders and eye diseases are interrelated through several mechanisms thus,
awareness of this relation has a great impact on early diagnosis and treatment.
Cannabis and Cannabinoids on Treatment of Inflammation: A Patent Review
Authors: Nascimento Menezes Pedro Modesto , Valença Pereira Emanuella Chiara , Gomes da Cruz Silva Maria Eduarda , da Silva Bismarques Augusto Oliveira , de Souza Duarte Filho Luiz Antonio Miranda , de Lima Araújo Tarcísio Cícero , Bezerra Lima Kátia Simoni , Silva Fabrício Souza , Rolim Larissa Araújo
Published: June 2019

Background:

The inflammatory process is a physiological response to a vast number of harmful stimulus that takes place in order to restore homeostasis. Many drugs used in pharmacotherapy are effective to control inflammatory responses, however, there is a range of adverse effects attributed to steroidal and non-steroidal anti-inflammatory drugs (NSAIDs). In this sense, herbal medicine and derivatives have gained more attention because of their effectiveness and safety, showing the importance of medicinal plants, especially the Cannabis genus and the cannabinoid derivatives.

Objective:

The aim of this prospection was to identify data related to patents involving Cannabis and cannabinoids for the treatment of inflammation.

Method:

To do so, a search for patents was conducted to evaluate the anti-inflammatory activity of Cannabis and cannabinoids. Four specialized databases for patent research were consulted using the terms "cannabis", "cannabidiol", "cannabinoids" and "THC" associated with "inflammation".

Results:

A total of 370 patents were found, of which 17 patents met the inclusion criteria. Although reports show synergistic effects of the plant components, patents involving Cannabis and cannabinoids focus on isolated substances (CBD e THC).

Conclusion:

However, patents related to Cannabis and cannabinoids are promising for future use of the plant or its derivatives on the treatment of inflammation.
Tumor-DNA Based Vaccines Fail to Induce Autoimmune Disease in Mice
Authors: O-Sullivan InSug , Lichtor Terry , Glick Roberta , Cohen Edward P.
Published: June 2019

Allogeneic cellular cancer vaccines that express tumor antigens specified by tumor-DNA have been found to be effective in the treatment of mice with intracerebral breast cancer, a metastasis model system. The vaccines were prepared by the transfer of genomic DNA from a spontaneously arising adenocarcinoma of the mammary gland into a mouse fibroblast cell line (LM). The immunity in tumor-bearing mice treated by immunization with the DNA-based vaccines was specific for the type of tumor from which the DNA was obtained. It was driven mainly by CD8+ T-cells. Here, we present data indicating that animals receiving the therapeutic vaccines failed to exhibit signs of autoimmunity, as indicated by an examination of various H/E stained organs and tissues including brain for infiltrating inflammatory cells and by the absence of serum anti-nuclear antibody (ANA) in the immunized mice. In addition, tumors derived from the vaccine itself
failed to develop in immune-competent tumor-free mice injected with the non-irradiated allogeneic vaccines alone.
Synthesis, Biological Evaluation and Molecular Docking Study of Pyrazole, Pyrazoline Clubbed Pyridine as Potential Antimicrobial Agents
Authors: Desai Nisheeth C. , Vaja Darshita V. , Jadeja Krunalsinh A. , Joshi Surbhi B. , Khedkar Vijay M.
Published: June 2019

Introduction:

In continuation of our efforts to find new antimicrobials, herein we report
the synthesis of various pyrazole, pyrazoline, and pyridine based novel bioactive heterocycles (3a-t).

Methods:

Newly synthesized compounds were analysed for their antimicrobial activity. Compounds
3c, 3h, 3i, 3k, 3n, and 3q showed significant antimicrobial activity.

Results:

Molecular docking study for the most active analogues against DNA gyrase subunit b
(PDB ID: 1KZN) corroborated well with the observed antimicrobial potency exhibiting significant
binding affinity.

Conclusion:

Interpretation of the chemical structures reported in this paper was based on IR, 1H
NMR, 13C NMR, and mass spectral data.
Association Between Fat-soluble Vitamins and Lipid Profile in the Overweight Population
Authors: Piran Sadegh , Sarmasti Sahar , Shabani Mohammad , Kakavandi Naser , Hosseni Bita , Khosravi Mohsen , Resaee Shima , Soltanmohammadi Elham , Naseri Faezeh , Mohammadi Asghar , Najafi Mohammad
Published: June 2019

Background &Aims:

It is well-known that the coronary artery stenosis is related to lipid profile. This is a descriptive cross-sectional study to investigate the relationship between the serum fat-soluble vitamins (A, E and D), circulating proprotein convertase subtilisin/kexin type 9 (PCSK9), and lipid profile in the study population.

Methods:

A total of 120 overweight subjects were participated in this study. The circulating PCSK9 and vitamin D were measured by ELISA technique. The serum vitamin A and vitamin E amounts were simultaneously measured by the HPLC method. The Serum Small Dense LDLCholesterol (sdLDL-C) values were evaluated using heparin-Mg2+ precipitation technique. The lipid profile was measured by routine laboratory techniques.

Results:

The serum vitamin E values correlated significantly to vitamin A (r= 0.47, P= 0.0001), VLDL-C (r= 0.30, P= 0.002), total cholesterol (r= 0.309, P= 0.001), PCSK9 (r= 0.233, P= 0.01) and total triglyceride (r= 0.61, P= 0.0001) values. The circulating PCSK9 values correlated significantly to LDL-C (r= 0.17, P= 0.05) and total cholesterol (r= 0.23, P= 0.009) values. However, there were not correlations between the levels of serum D and A vitamins, the serum LDL-C, sdLDL-C and total cholesterol values.

Conclusion:

The data showed the correlations between serum vitamin E and PCSK9-related LDLC values lower than the normal range. Furthermore, the results suggested a nutritional need on the patents considering supplementation or fortification of vitamin E for the overweight subjects with higher LDL-C levels.
THE COGNITIVE MODELING TECHNOLOGY FOR THE FINANCIAL ANALYSIS OF THE FINANCIAL-ECONOMY ACTIVITY OF THE ORGANIZATION
Authors: Vetrov A. N.
Published: June 2019

Objective. The increase in the efficiency of functioning of the (credit) organization due to the realization of procedure of the horizontal, vertical and trend (microscopic) financial analysis based on the formed innovative analytical coefficients system in the parametrical cognitive models block. Method. The financial analysis of the highly-integrated enterprises and (credit) organizations. Result. The innovative parametrical cognitive models block is the information basis of the (microscopic) financial analysis, contains the cognitive models for the horizontal, vertical and trend financial analysis of the enterprise or (credit) organization based on the formed analytical coefficients system, each from which acts as the difficult repertoire of parameters (indicators), echeloned to a number of portraits and stratificated to the several independent sets located on two different levels of the specified hierarchy (structure). Conclusion. The financial analysis of the highly-integrated (credit) organizations initiates the need of the accounting of a wide range of the different scientific fundamental and applied directions of modern science, and also causes the need of use of the innovative device of research.
Developing a problem-based local history module to improve the critical thinking ability of senior high school students
Authors: Mujiyati Novita , Warto Warto , Sutimin Leo Agung
Published: June 2019

This research aims at developing a problem-based local history module as learning media to improve the critical thinking ability of Senior High School students. This research employed a research and development (RD) method referring to ADDIE development design. The procedure of designing ADDIE development included (1) analyzing to identify the learning media needed, (2) designing to organize the material of module corresponding to basic competency and indicator, (3) developing to obtain the finished product of module through validation and limited and large-scale trials, (4) implementing the module during learning process, and (5) evaluating to find out the effectiveness of module. The results of the research show that the problem-based local history module effectively improves the students’ critical thinking ability. Through this module, the students are directed to understand a variety of aspects affecting a problem and relating it to the knowledge owned. The problems organized in the module are contemporary and related to the student environment. The process of connecting new knowledge to preexisting knowledge enables the students to develop their own knowledge and to improve their critical thinking ability in solving the problems.