bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and Characterization of Chemical Compounds that Inhibit Leucyl-tRNA Synthetase from Pseudomonas aeruginosa
Authors: Zamacona Regina , Chavero Pamela N. , Medellin Eduardo , Hu Yanmei , Hughes Casey A. , Quach Nathalie , Keniry Megan , Bullard James M. 
Published: August 2018

Background:
Pseudomonas aeruginosa is an opportunistic multi-drug resistance pathogen
implicated as the causative agent in a high-percentage of nosocomial and community acquired
bacterial infections. The gene encoding leucyl-tRNA synthetase (LeuRS) from P. aeruginosa was
overexpressed in Escherichia coli and the resulting protein was characterized.

Methods:
LeuRS was kinetically evaluated and the KM values for interactions with leucine, ATP and
tRNA were 6.5, 330, and 3.0 μM, respectively. LeuRS was developed into a screening platform using
scintillation proximity assay (SPA) technology and used to screen over 2000 synthetic and natural
chemical compounds.

Results:
The initial screen resulted in the identification of two inhibitory compounds, BT03C09 and
BT03E07. IC50s against LeuRS observed for BT03C09 and BT03E07 were 23 and 15 μM,
respectively. The minimum inhibitory concentrations (MIC) were determined against nine clinically
relevant bacterial strains. In time-kill kinetic analysis, BT03C09 was observed to inhibit bacterial
growth in a bacteriostatic manner, while BT03E07 acted as a bactericidal agent. Neither compound
competed with leucine or ATP for binding LeuRS. Limited inhibition was observed in
aminoacylation assays with the human mitochondrial form of LeuRS, however when tested in
cultures of human cell line, BT03C09 was toxic at all concentration whereas BT03E07 only showed
toxic effects at elevated concentrations.

Conclusion:
Two compounds were identified as inhibitors of LeuRS in a screen of over 2000 natural
and synthetic compounds. After characterization one compound (BT03E07) exhibited broad spectrum
antibacterial activity while maintaining low toxicity against human mitochondrial LeuRS as well as
against human cell cultures.
N-(Sulfamoylbenzoyl)-L-proline Derivatives as Potential Non-β-lactam ESBL Inhibitors: Structure-Based Lead Identification, Medicinal Chemistry and Synergistic Antibacterial Activities
Authors: Liu Xinyu , Dong Shengjie , Ma Yuru , Xu Hu , Zhao Hongxia , Gao Qingzhi 
Published: August 2018

Background:There is an urgent need to develop novel inhibitors against clinically widespread extended-spectrum β-lactamases (ESBLs) to meet the challenges of the ever-evolving threat of antibiotic resistances. Most existing ESBL inhibitors sharing a common chemical feature of β-lactam ring in their molecule, this structural characteristic makes them intrinsically susceptible to enzymatic breakdown by the resistance mechanisms employed by the bacteria.Objective:The aim of this study was to screen and discover novel lead compounds by using Lproline as initial scaffold to create a “non-sulfur, non-β-lactam” new chemotypes for potential ESBL inhibitors.Methods:Structure-based molecular docking and virtual screening were employed in the novel inhibitor generation process for lead compound screening and SAR analysis. Evaluation of the ESBL inhibitory activity of the lead compounds was performed in combination with three of the most susceptible antibiotics: ceftazidime, meropenem and ampicillin, against thirteen ESBL enzymes including four new CTX-M harboring strains and four KPC-2 producing species.Results:L-proline derived (S)-1-(2-sulfamoylbenzoyl)pyrrolidine-2-carboxylic acid (compound 6) as a “non-sulfur, non-β-lactam” and the most potential ESBL inhibitor was identified. Compound 6 possesses ideal anti-resistance activities by reducing MICs of ceftazidime, meropenem and ampicillin by 16-133, 32-133 and 67-267 fold respectiveily. The inhibitory mechanism of 6 with CTX-M, KPC-2 and penicillinase were proposed and probed with molecular docking analysis.Conclusion:Given that the simple proline derivative but promising synergistic antibacterial properties of compound 6 augers well for further investigations into its in vivo efficacy.
Norfloxacin Induced Recurrent Fixed Drug Eruption in a self Treated Adult Female Patient - A Case Report
Authors: Vikramjeet Singh , Angelika Batta , Nishtha Malik 
Published: August 2018

Background:
Fixed drug eruption is a clinical entity occurring at the same site each time the
drug is administered. They are usually found on lips, genitalia, abdomen, and legs but can occur at any
location. The eruptions usually occur within hours of administration of the drug and resolves
spontaneously. Most common drugs causing them include antimicrobials. Fluroquinolones especially
norfloxacin is commonly used in the treatment of gastrointestinal infections. Cutaneous adverse drug
reactions are very rare with norfloxacin.

Case Report:
In this case report, a young female, soon after taking Nofloxacin tablet, developed a
blister with erythema and itching after self treatment for urinary tract infection. It got cured after
stopping the drug and taking treatment from a dermatologist. It resolved as a hyper-pigmented scar. She
experienced a similar episode of drug eruption on the same site when she again self medicated herself
with Norfloxacin for diarrhoea. This time the reaction occurred within few hours and resolved with
hyperpigmentation after medication. She was advised not to indulge in self-treatment in future.
Suspecting association between the drug and the rash was confirmed and a diagnosis of Norfloxacin
induced fixed drug eruption was made.

Conclusion:
Causality assessment by Naranjo’s algorithm revealed a definite relationship between the
cutaneous adverse drug reaction and the offending drug.
Reversing Multidrug Resistance in Chemo-resistant Human Lung Adenocarcinoma (A549/DOX) Cells by Algerian Propolis Through Direct Inhibiting the P-gp Efflux-pump, G0/G1 Cell Cycle Arrest and Apoptosis Induction
Authors: Kebsa Wided , Lahouel Mesbah , Rouibah Hassiba , Zihlif Malek , Ahram Mamoun , Abu-Irmaileh Bashaer , Mustafa Ebtihal , Al-Ameer Hamzeh J. , Al Shhab Mohammad 
Published: August 2018

Background:
Lung cancer is one of the most common malignancies with the highest incidence and
mortality rate worldwide. Multidrug Resistance (MDR) continues to pose a major challenge for the clinicians and
pharmacologists to effectively treat this disease. A new approach using natural substances with moderate or low
cytotoxic properties become a promising hope for reversing multidrug resistance due to pgp- overexpression.

Objective:
This study aims to explore the efficacy of Algerian propolis in reversing multidrug resistance and
sensitizing chemo-resistant lung cancer cells (A549/DOX) to chemotherapy with DOX.

Methods:
Resistant lung adenocarcinoma A549/DOX cell line was developed and used as in vitro model for
MDR. Cell viability, Annexin V-PI apoptosis assay and cell cycle progression were tested to evaluate the reversal
effect of propolis alone or in combination with DOX. Caspases 3, 8 and 9 assays were conducted to determine
the type of apoptotic pathway. To investigate the mechanisms of MDR reversal agents, intracellular accumulation
of DOX and P-gp-pump activity were investigated.

Results:
Our results showed that the obtained chemo-resistant cells were 13-fold more resistant to DOX than the
parental A549 cells. Propolis showed dramatically cell growth inhibition on A549/DOX cells (The IC50 was
50.44± 0.07µg/ml). The killing effect of propolis was due to G0/G1 cell cycle arrest and apoptosis induction.
After 24hours treatment, propolis at 100 µg/ml caused cells accumulation in G0/G1 phase and increased
with 50, 65-fold the percentage of apoptotic population sub-G. Annexin V-PI assay showed that propolis
induces apoptosis with 53.57-fold at 100 µg/ml. It induced intrinsic apoptotic pathway by increasing caspase-3
(22.15-fold) and caspase-9 (16.73-fold) activities. The direct approach to investigate the mechanisms of reversal
agents is to detect the accumulation of P-gp substrates in resistant cells. Our results indicated that resistant cells
poorly accumulated Doxorubicin and rhodamine 123 (7-fold lower) when compared to parental A549 cells,
suggesting that chemo-resistant cells overexpress P-gp which pump DOX out of cells. Propolis inhibited in a
concentration-dependent manner, the pgp efflux-pump, enhancing thereby the intracellular level of DOX with
5.48- fold against 3.33 fold obtained with verapamil, the conventional P-gp inhibitor.

Conclusion:
Taken together, Algerian propolis reverses multidrug resistance in resistant human lung
adenocarcinoma cells through direct inhibiting the transport function of pgp-pump resulting in enhancing intracellular
DOX-accumulation, G0/G1 cell cycle arrest and apoptosis induction. Thus, propolis could be developed
as a chemotherapeutic agent for reversing multidrug resistance.
Critical microRNAs in Lung Cancer: Recent Advances and Potential Applications
Authors: Zarredar Habib , Ansarin Khalil , Baradaran Behzad , Shekari Najibeh , Eyvazi Shirin , Safari Fateme , Farajnia Safar 
Published: August 2018

Background:
MicroRNAs (miRNAs) play an important role in the regulation of various genes
involved in cell growth, development and the maintenance of body homeostasis. They are closely linked to
different human diseases, particularly in cancers. Amplification and overexpression of some miRNAs that are
called ‘oncomiRs’ or down-regulation of tumor suppressor miRNAs are associated with genetic alterations that
are sufficient to drive tumorigenesis in humans. Lung cancer is the leading cause of cancer-related deaths worldwide.
The high mortality rate of lung cancer is not changed even with recent advances in cancer treatment.
Several studies demonstrated that miRNAs are involved in the pathogenesis of lung cancer that they negatively
or positively regulate gene and protein expression by acting as oncogenes or tumor suppressors.

Objective:
This article reviewed the current knowledge on the role of miRNAs and their target genes in lung
cancer and discussed the potential use of some miRNAs as novel therapeutic agents in lung cancer.

Method:
Firstly, we collected and summarized all research and review and research articles in databases including
Scopus and PubMed. Then, we used related keywords that are important to lung cancer target therapy and
their diagnostic and prognostic values.

Results:
Based on collected articles and research, recognizing critical microRNA and controlling the expression
of this microRNA by antagonist oligonucleotides like antagomiRs or anti-miRs and microRNA mimicking will
have a remarkable role in treating lung cancer.

Conclusion:
Many research studies have shown that a combination of chemotherapy plus knockdown or
mimicking microRNA is effective and useful in the cancers treatment like lung cancer.
Preparation and Characterization of Large Unilamellar Vesicles Mixed With Trimethylchitosan (TMC): The Effect of Polyelectrolyte Concentration
Authors: Van Der Merwe S.M. , Bouropoulos N. , Katsamenis D.A. , Lampou O.L. , Fatouros D.G. 
Published: August 2018

Background:
The effect of different concentrations of the absorption enhancer Trimethyl Chitosan (TMC) to the physicochemical properties of Large Unilamellar Vesicles (LUV) comprised of L-a-Phospahtidyl Choline (PC) were investigated in the current study.

Methods:
The Degree of Quartenization (DQ) of trimethylchitosan was assessed with nuclear magnetic resonance (1H NMR). The vesicles were characterized by means of Dynamic Light Scattering (DLS), ζ-potential, Differential Scanning Calorimetry (DSC) and Contact Angle Goniometry (CAG) measurements.

Results:
The data showed that the surface charge of the PC liposomes was significantly altered as a function of the TMC concentration, giving evidence of presence of the polyelectrolyte to the liposome’s membrane. Varying the concentration of TMC affected the phase Transition Temperature (Tm) of the lipid, verifying the miscibility of the polyelectrolyte with the lipid bilayer. The association of the polymer with the liposomes was related to the amount of the polyelectrolyte present, reflecting changes to the wettability of the dispersion as measured by CAG.

Conclusion:
The results demonstrated that presence of TMC significantly modified the physical properties of liposomes. Such systems might have a potential use for mucosal delivery (e.g. nasal route of administration).
Behavior of Extended End-Plate Steel Beam to Column Connections
Authors: Al Fakih Kamal , Chin Siew Choo , Doh Shu Ing 
Published: August 2018

Background:
The main objective of this study is to simulate the behaviour of steel beam-to-column connections using the computer package of Finite Element Analysis (FEA) known as “ABAQUS”.

Objective:
This paper presents the investigations of extended End-Plate connections (EP). A one-model segment is examined under the impact of concentrated load and the exclusive boundary conditions were tested. The analysis of the nonlinear behaviour of the connection is a complicated science and needs to use programs to solve this problem. Experimental works are normally conducted for this type of studies which used more of money, time and effort. Therefore, with the availability of simulation applications, these problems can be addressed.

Results and Conclusion:
The results of the evaluation were compared with the experimental data from the available literature. In this case, nonlinearity materials were used. A sample study on EP connections was carried out using both material and geometric nonlinearities. The comparison of FEA results with corresponding experimental results confirms the correlation and convergence between them.
The Effect of Flat Dual-Cure Stabilizer Occlusal Splint in Pain Relief of Individuals Suffering from Migraine Headaches
Authors: Sahebi Majid , Zeighami Somayeh , Hajimahmoudi Mohammadreza 
Published: August 2018

Background:No study on the effect of dual-cure stabilizer splint without canine ramp in migraine patients is present.Objective:This study was conducted to determine the effects of maxillary flat dual-cure stabilizer occlusal splint on severity, frequency and episodes of headaches in individuals suffering from a migraine.Methods:In this interventional clinical trial, 30 eligible patients were divided into 2 groups (case and control); each group consisted of 8 men and 7 women. Dual-cure stabilizer splint was made for patients in the case group and they used the adjusted splint 20 hours a day for 6 weeks. The severity, frequency and episodes of migraine attacks before and after using the splint were determined. For grading pain, severity visual analogue scale was used. The data were analyzed usingSPSS20 and Kolmogorov-Smirnov test and paired t-test.Results:The severity, frequency, and episodes of migraine attacks before and after using the splint were reduced by 56%, 68%, and 72%, respectively. The reduction was statistically significant (p< 0.05).Discussion:Despite the effect of occlusal devices on the migraine disorder is controversial, the most researchers agree that using these appliances can be effective in reducing headache in migraine patients.Conclusion:Given the favorable effects of dual-cure stabilizer splint on reducing the severity, frequency and episodes of migraine headaches, the device can be used as an effective alternative therapy besides common pain-relieving methods.
Blood Cell Proteomics in Chronic Kidney Disease
Authors: Bonomini Mario , Pieroni Luisa , Ronci Maurizio , Sirolli Vittorio , Urbani Andrea 
Published: August 2018

Background:
The uremic syndrome mimes a systemic poisoning with the retention of numerous compounds which are normally removed by the kidney. The study of proteins and peptides, or proteomics, represents an important field of research for the investigation of blood and blood diseases.

Methods and Materials:
We focused our review on the results of proteomic investigations on blood cells of uremic patients with particular regard to the study of red blood cells, platelets, and monocytes.

Results:
In literature there are few, preliminary studies on platelets and monocytes while the knowledge on uremic erythrocytes is much wider. Proteomic investigations showed that erythrocyte membrane proteome of uremic patients, differs significantly from the proteome of healthy subjects, being characterized by an extensive remodeling which may influence visco-elastic properties of RBC such as deformability and involve diverse molecular pathways driving red blood cell signaling and removal.

Conclusion:
Proteomic technologies emerged as a useful tool in defining and characterizing both physiological and disease processes being able, among others, to give important insights into uremic anemia.
MicroRNA155 Expression in Relation to BDCAF Scored Behçet's Disease in an Egyptian Patients' Sample
Authors: Hassouna Sally S. , Tayel Manal Y. , ElKaffash Dalal M. , Abdelhady Ahmed M. , Elsayed Eman H. 
Published: August 2018

Objective:To discover the possibility of using microRNA155 (miRNA155) expression level as a biomarker of Behçet's Disease (BD) activity or remission.Methods:Thirty BD patients’ white blood cells (WBCs) miRNA155 expression was measured and compared to WBCs miRNA155 expression in 15 healthy subjects. Assessment of disease activity was done using Behçet's Disease Current Activity Form (BDCAF).Results:miRNA155 expression significantly decreases with the increase of BD activity scored by BDCAF.Conclusion:Increased miRNA155 may be used as a biomarker of BD remission and thus in the disease follow up. There could be a prospect of treating the diseaseviamicroRNA 155 effect enhancement.
Treatment of Type Two Slap Lesion With Anatomic Suture Anchor Repair Without Biceps Tenotomy Or Tenodesis
Authors: Prodromos Chadwick C. , Finkle Susan , Dawes Alexander , Baik Ji Young 
Published: August 2018

Background:
Poor results after repair of type 2 SLAP tears are relatively common and some have reported better results after biceps tenodesis or tenotomy than repair. In addition, some believe that the long head of the biceps is expendable. Therefore, many now favor biceps tenotomy or tenodesis over biceps anchor repair either in all patients or in older patients, reserving SLAP lesion repair only for young athletes.

Hypothesis:
We hypothesized that repair of the biceps anchor of the labrum would be effective in all patients regardless of age provided that care was taken not to overtighten the labrum and that rotator cuff pain as the primary pain generator had been ruled out.

Methods:
All patients with type 2 SLAP lesion repair by the senior author since he began repairing them with suture anchors were prospectively evaluated. Patients with more than one other concomitant procedure, simultaneous rotator cuff repair or worker’s compensation status were excluded.

Results:
77% of patients were available for minimum two year followup. No patient had subsequent surgery or manipulation under anesthesis as a result of their SLAP repair. Standardized shoulder test score increased by 4 points. Mean SANE score decreased from 53 pre-op to 14 post-op. Results were the same in those over versus under 40 years of age.

Conclusion:
Anatomic repair of Type 2 SLAP lesions at the biceps anchor without biceps tenodesis or tenotomy can produce good results in patients of all ages.
Mechanisms for Radioprotection by Melatonin; Can it be Used as a Radiation Countermeasure?
Authors: Amini Peyman , Mirtavoos-Mahyari Hanifeh , Motevaseli Elahe , Shabeeb Dheyauldeen , Musa Ahmed Eleojo , Cheki Mohsen , Farhood Bagher , Yahyapour Rasoul , Shirazi Alireza , Goushbolagh Nouraddin Abdi , Najafi Masoud 
Published: August 2018

Background:Melatonin is a natural body product that has shown potent antioxidant property against various toxic agents. For more than two decades, the abilities of melatonin as a potent radioprotector against toxic effects of ionizing radiation (IR) have been proved. However, in the recent years, several studies have been conducted to illustrate how melatonin protects normal cells against IR. Studies proposed that melatonin is able to directly neutralize free radicals produced by IR, leading to the production of some low toxic products.Discussion:Moreover, melatonin affects several signaling pathways, such as inflammatory responses, antioxidant defense, DNA repair response enzymes, pro-oxidant enzymes etc. Animal studies have confirmed that melatonin is able to alleviate radiation-induced cell death via inhibiting pro-apoptosis and upregulation of anti-apoptosis genes. These properties are very interesting for clinical radiotherapy applications, as well as mitigation of radiation injury in a possible radiation disaster. An interesting property of melatonin is mitochondrial ROS targeting that has been proposed as a strategy for mitigating effects in radiosensitive organs, such as bone marrow, gastrointestinal system and lungs. However, there is a need to prove the mitigatory effects of melatonin in experimental studies.Conclusion:In this review, we aim to clarify the molecular mechanisms of radioprotective effects of melatonin, as well as possible applications as a radiation countermeasure in accidental exposure or nuclear/radiological disasters.
Type 2 Diabetes Study, Introduction and Perspective
Authors: Lu Da-Yong , Che Jin-Yu , Yarla Nagendra Sastry , Zhu Hong , Lu Ting-Ren , Xu Bin , Putta Swathi 
Published: August 2018

Background:
The prevalence of Type 2 Diabetes Mellitus (T2DM) continues to rise globally. The T2DM prevalence is not only in developing countries, but also in developed countries now. Correspondingly, the therapeutics of T2DM calls for a change (higher efficiency) due to growing number of patients and increasing economic burdens globally. Entering into this millennium, both piecemeal pathways (idea driven) and exponential growth of human genomic study are developing quickly. Genetypic-phenotypic translation, modern diagnostics, pharmacology, drug developments, traditional Chinese medicine, personalized medicine and so on are promising disciplines for this change. The clinical anti-diabetic therapeutics, pathogenesis, drug development pipelines are especially highlighted.

Conclusion:
In summary, a general landscape and principle of T2DM is provided.
Inventaire archéologique – Fiche Nr 236
Authors: Collumbien Hugo 
Published: August 2018

Op 28 december 1901 stelde E. Coppieters Stochove in de rubriek “Goudsmederij - St-Michielskerk, schatten - XVIIe eeuw (1617)” in het Frans een fiche op over Zilveren Kruisbeelden van de Broederschap van het Heilig Kruis
Inventaire Archéologique - Fiche nr 237: Het Vaandel van de Onvrije Schippers.
Authors: Collumbien Hugo 
Published: August 2018

Op 1 februari 1902 stelde Victor De Muynck in de rubriek "Schilderijen - Oudheidkundig Museum, n° 787 - XVIIIe eeuw (1701)" in het Frans een fiche op over“Het Vaandel van de Onvrije Schippers”
De afkomst van Jacob Van Caneghem
Authors: Ervynck Gontran 
Published: August 2018

De figuur van Jacob van Caneghem, weldoener van het Blindenhuis aan de Coupure, werd aan de vergetelheid ontrukt dank zij een recent artikel in het tijdschrift (41e jrg. nr.6 (2012) blz.458-473). Er blijkt nochtans enige verwarring te bestaan betreffende zijn afkomst, hij was geen geboren Gentenaar. Dit stelt geen groot probleem, onze archieven, i.h.b. het Stadsarchief in de Zwarte Doos, zijn rijk genoeg om alle desbetreffende onzekerheden uit de wereld te helpen.
Anne de Laval (Delavaux-De La Vaux). Lomme 1625 - Gent 1671
Authors: Vande Casteele Lieve 
Published: August 2018

Het wonderbare leven van Anne de Laval deed een aantal geschiedschrijvers naar de pen grijpen. In 1625 in Lomme bij Rijsel als boerenmeisje geboren, zou zij na een heroïsche militaire carrière in het cisterciënzerinnenklooster bij Marquette-lez-Lille ingetreden zijn. Van daaruit zou ze naar het Gentse Bijlokeklooster zijn overgeplaatst, waar ze in 1671 overleed.