bluuebunny/crossref_metadata_2025_split huggingface dataset:
Importance of correcting for fluorescence quenching in fluorescence-based prediction of trihalomethane formation potential
Authors: Saipetch K. , Yoshimura C. 
Published: March 2019

AbstractFluorescence excitation–emission matrix (EEM) spectroscopy is often used to determine the levels of trihalomethane (THM) precursors in natural organic matter. However, humic substances are known to quench the fluorescence of amino acids and proteins. To date, none of the EEM-based models for predicting THM formation potential (THMFP) have explicitly accounted for these quenching effects. Thus, we investigated the importance of correcting for fluorescence quenching during THMFP prediction. Fluorescence titration experiments revealed that the correction improved the accuracy of THM prediction. EEM-based models using the corrected fluorescence intensity displayed the highest accuracy (R2 &gt; 0.99; mean absolute error 8.1 μg/L and 13.9 μg/L for chloroform and bromoform, respectively) among models using individual parameters of EEM intensity, dissolved organic carbon (DOC), ultraviolet absorbance at 254 nm (UV254), specific UV254 (SUVA254) and differential ultraviolet absorbance at 272 nm (ΔUV272). Thus, EEM-based models require both the fluorescence intensity of a humic-like component and the corrected fluorescence intensity of a protein-like component for accurate THMFP prediction, for both chlorination and bromination processes. We also found it to be unnecessary to combine DOC with EEM intensity in terms of prediction accuracy, as long as the fluorescence quenching correction is applied.
Pressure distribution of bottom rollers below the aerator device
Authors: Wang Yu , Wu Jianhua , Ma Fei , Qian Shangtuo 
Published: March 2019

Abstract
With regard to high water head and large flow velocity in the spillway tunnels of hydraulic projects in China, the aerator device has been introduced and is widely used to prevent cavitation damage. The bottom rollers in the nappe cavity below the aerator device are a serious concern in designing suitable cavity regimes; however, observation of roller size may be inaccurate due to high flow turbulence and de-aeration in the jet impact region. In this study, a novel approach is proposed to predict roller sizes using pressure distribution of the bottom rollers. Pressure distribution characteristics are experimentally investigated under different geometrical parameters of aerator device and hydraulic conditions. The results specify the influence of the relative step height and working gate opening on pressure distribution. The simplified estimating formula of pressure distribution is derived within relative errors of 15%. The evaluation of the applicability of the proposed equation shows test data are in good agreement with the calculated value. Research results provide a reference for estimating bottom rollers of similar engineering.
Inhibitory Effects of Usnic and Carnosic Acid on Some Metabolic Enzymes: An In vitro Study
Authors: Ceylan Hamid , Demir Yeliz , Beydemir Şükrü 
Published: March 2019

Background:
Natural products are produced via primary and secondary metabolism in
different organisms. The compounds obtained via secondary metabolism are not essential for the
survival of the organism, but they can have a different value for humans.

Objective:
The objective of this study was to examine inhibitory effects of Usnic Acid (UA), a
well-known lichen secondary metabolite, and Carnosic Acid (CA), the primary antioxidant
compound of Rosmarinus officinalis L., on purified Human Paraoxonase, (PON1), Glutathione
Reductase (GR) and Glutathione S-Transferase (GST). These enzymes have antioxidant properties
and a protective effect on the oxidation of free radicals. Hence, deficiencies of such enzymes inside
cells can result in a buildup of toxic substances and cause some metabolic disorders.

Methods:
UA and CA were tested in various concentrations against human GST, PON1, and GR
activity in vitro and they reduced human GST, PON1, and GR activity.

Results:
UA Ki constants were calculated as 0.012±0.0019, 0.107±0.06 and 0.21±0.1 mM for GST,
PON1, and GR enzymes. CA Ki constants were determined as 0.028±0.009, 0.094±0.03 and
0.79±0.33 mM, for GST, PON1, and GR enzymes. UA and CA showed competitive inhibition for
GR and GST enzymes, while they exhibited non-competitive inhibition for PON1.

Conclusion:
These findings indicate that UA and CA could be useful in drug development studies.
LncRNAs: Potential Novel Prognostic and Diagnostic Biomarkers in Colorectal Cancer
Authors: Dastmalchi Narges , Safaralizadeh Reza , Nargesi Mirsaed Miri 
Published: March 2019

Background:
Long non-coding RNAs (lncRNAs), a type of regulatory RNAs, play a key
role in numerous cellular pathways. Ectopic expression of this group of non-coding RNAs has been
specified to be involved in numerous diseases. Moreover, the role of lncRNAs in the initiation and
development of cancers including colorectal cancer (CRC) has been acknowledged.

Objective:
In the present review, the role of lncRNAs as prognostic and diagnostic biomarkers in
CRC as well as the molecular mechanisms of their contribution to development of CRC has been
addressed.

Results:
The presented studies have indicated the ectopic expression of various lncRNAs in CRC.
Some lncRNAs which were considered as tumor suppressors were downregulated in the colorectal
cancerous tissues compared with healthy controls; however, some with oncogenic effects were
upregulated. LncRNAs contribute to tumor development via various molecular mechanisms such as
epigenetically controlling the expression of target genes, interacting with miRNAs as their sponge,
etc.

Conclusion:
LncRNAs that have been recognized as prognostic biomarkers may pave the way for
clinical management to offer adjuvant treatments for patients with CRC.
Scaffold Based Search on the Desferithiocin Archetype
Authors: Shyam Mousumi , Dev Abhimanyu , Sinha Barij Nayan , Jayaprakash Venkatesan 
Published: March 2019

:Iron overload disorder and diseases where iron mismanagement plays a crucial role require orally available iron chelators with favourable pharmacokinetic and toxicity profile. Desferrithiocin (DFT), a tridentate and orally available iron chelator has a favourable pharmacokinetic profile but its use has been clinically restricted due to its nephrotoxic potential. The chemical architecture of the DFT has been naturally well optimized for better iron chelation and iron clearance from human biological system. Equally they are also responsible for its toxicity. Hence, subsequent research has been devoted to develop a non-nephrotoxic analogue of DFT without losing its iron clearance ability.:The review has been designed to classify the compounds reported till date and to discuss the structure activity relationship with reference to modifications attempted at different positions over pyridine and thiazoline ring of DFT. Compounds are clustered under two major classes: (i) Pyridine analogues and (ii) phenyl analogue and further each class has been further subdivided based on the presence or absence and the number of hydroxy functional groups present over pyridine or phenyl ring of the DFT analogues. Finally a summary and few insights into the development of newer analogues are provided.
Tph2 Genetic Ablation Contributes to Senile Plaque Load and Astrogliosis in APP/PS1 Mice
Authors: Xu Chao-Jin , Wang Jun-Ling , Jing-Pan  , Min-Liao  
Published: March 2019

Background:
Amyloid-β (Aβ) accumulation plays a critical role in the pathogenesis of Alzheimer’s
disease (AD) lesions. Deficiency of Serotonin signaling recently has been linked to the increased
Aβ level in transgenic mice and humans. In addition, tryptophan hydroxylase-2 (Tph2), a second
tryptophan hydroxylase isoform, controls brain serotonin synthesis. However, it remains to be determined
that whether Tph2 deficient APP/PS1mice affect the formation of Aβ plaques in vivo.

Methods:
Both quantitative and qualitative immunochemistry methods, as well as Congo red staining
were used to evaluate the Aβ load and astrogliosis in these animals.

Results:
we studied alterations of cortex and hippocampus in astrocytes and senile plaques by Tph2
conditional knockout (Tph2 CKO) AD mice from 6-10 months of age. Using Congo red staining and
immunostained with Aβ antibody, we showed that plaques load or plaques numbers significantly increased
in Tph2 CKO experimental groups at 8 to 10 months old, compared to wild type (WT) group,
respectively. Using GFAP+ astrocytes immunofluorescence method, we found that the density of GFAP+
astrocytes markedly enhanced in Tph2 CKO at 10 months. We showed Aβ plaques co-localized
autophagic markers LC3 and p62. Nevertheless, we did not observe any co-localization between GFAP+
astrocytes and autophagic markers, but detected the co-localization between βIII-tubulin+ neurons and
autophagic markers.

Conclusion:
Overall, our work provides the preliminary evidence in vivo that Tph2 plays a role in amyloid
plaques generation.
Imidazole and 1,2,4-Triazole-based Derivatives Gifted with Antitubercular Activity: Cytotoxicity and Computational Assessment
Authors: Zampieri Daniele , Cateni Francesca , Moneghini Mariarosa , Zacchigna Marina , Laurini Erik , Marson Domenico , De Logu Alessandro , Sanna Adriana , Mamolo Maria G. 
Published: March 2019

Background:Mycobacterium Tuberculosis (Mtb) is the causative pathogen of Tuberculosis (TB) and outbreaks are more common among immunosuppressed persons infected with HIV. The current treatment regimens are lengthy and toxic, yet the therapy has remained unchanged for many decades, so there is a need to find new structures with selective mechanism of action. Moreover, the increased incidence of severe disseminated infections produced by undiagnosed Multidrug-resistant (MDR), worsen clinical treatment and contribute the spread of the disease.Objective:The aim of our study was to evaluate the potential of imidazole and triazole moieties for antimycobacterial activity, by synthesizing some 1-(1-(aryl)-2-(2,6-dichlorophenyl)hydrazono)ethyl- 1H-imidazole and 1H-1,2,4-triazole derivatives 2a-l.Methods:The title compounds were obtained via classical organic synthesis. The antimicrobial activity was evaluated using the method of microdilution and the cytotoxicity assay was performed by MTT method.Results:The results indicated that the presence of both the imidazole ring and that of the 2,6- dichlorosubstituted phenyl moiety, is more relevant for inhibitory activity against Mtb than the triazole nucleus and the unsubstituted phenyl ring. Among the series, (E)-1-(2-(5-chlorothiophen-2-yl)-2-(2- (2,6-dichlorophenyl)hydrazono)ethyl)-1H-imidazole derivative 2f and (Z)-1-(2-([1,1’-biphenyl]-4-yl)- 2-(2-(2,6-dichlorophenyl)hydrazono)ethyl]-1H-imidazole derivatives 2e exhibited a promising antimycobacterial property and the latter also displayed a safe cytotoxic profile.Conclusion:The synthesized compounds were studied for their antitubercular activity. Among the series, the compounds 2e and 2f appeared to be the most promising agents and, according to the docking assessment, the compounds could be CYP51 inhibitors. These evidences could be useful for the future development of new antimycobacterial derivatives targeting CYP51 with more specificity for the mycobacterial cell enzyme.
Synthesis and In Vitro Enzymatic Studies of New 3-Aryldiazenyl Indoles as Promising Helicobacter pylori IMPDH Inhibitors
Authors: Jangra Sachin , Purushothaman Gayathri , Juvale Kapil , Ravi Srimadhavi , Menon Aishwarya , Thiruvenkatam Vijay , Kirubakaran Sivapriya 
Published: March 2019

Background & Objective:Helicobacter pylori infection is one of the primary causes of peptic ulcer followed by gastric cancer in the world population. Due to increased occurrences of multi-drug resistance to the currently available antibiotics, there is an urgent need for a new class of drugs against H. pylori. Inosine 5′-monophosphate dehydrogenase (IMPDH), a metabolic enzyme plays a significant role in cell proliferation and cell growth. It catalyses guanine nucleotide synthesis. IMPDH enzyme has been exploited as a target for antiviral, anticancer and immunosuppressive drugs. Recently, bacterial IMPDH has been studied as a potential target for treating bacterial infections. Differences in the structural and kinetic parameters of the eukaryotic and prokaryotic IMPDH make it possible to target bacterial enzyme selectively.Methods:In the current work, we have synthesised and studied the effect of substituted 3-aryldiazenyl indoles on Helicobacter pylori IMPDH (HpIMPDH) activity. The synthesised molecules were examined for their inhibitory potential against recombinant HpIMPDH.Results:In this study, compounds 1 and 2 were found to be the most potent inhibitors amongst the database with IC50 of 0.8 ± 0.02µM and 1 ± 0.03 µM, respectively.Conclusion:When compared to the most potent known HpIMPDH inhibitor molecule C91, 1 was only four-fold less potent and can be a good lead for further development of selective and potent inhibitors of HpIMPDH.
Bicycloheptylamine-Doxorubicin Conjugate: Synthesis and Anticancer Activities in σ2 Receptor-Expressing Cell Lines
Authors: Alamri Mohammed A. , Ates-Alagoz Zeynep , Adejare Adeboye 
Published: March 2019

Background:
Novel bicycloheptylamines were designed and synthesized. These compounds
were found to be selective for sigma-2 receptors. These receptors have been found to be up
to 10 fold over-expressed in certain cancer cell lines, leading to investigation of possible uses as a
biomarker in diagnosis and/or treatment especially in cancers with poor prognosis.

Objective:
The aim was to conjugate a novel sigma-2 receptor ligand to doxorubicin to examine
anticancer activities, with and without conjugation, and therefore possibilities in drug delivery.

Methods:
Conjugation was conducted using N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide
HCl as a coupling agent. Affinity towards the sigma-2 receptor was tested using ligand-receptor
binding studies. Anticancer activities against cancer cell lines were carried out using cell viability
assays. Caspase dependency was tested using Z-VAD-FMK, a pan-caspase inhibitor, to begin to
investigate mechanisms of action.

Results:
The target compound retained affinity towards the sigma-2 receptor and exhibited potent
anticancer activities on cancer cell lines expressing the sigma-2 receptor. The potencies exceeded
those of doxorubicin, the lead sigma-2 receptor ligand, as well as non-covalent combination of
both drugs. The activity was also found to be caspase-dependent.

Conclusion:
The conjugation of target bicycloheptylamines with cytotoxic moieties may yield potent
and selective molecules for detection and/or treatment of certain cancers.
QSPR Models to Predict Thermodynamic Properties of Cycloalkanes Using Molecular Descriptors and GA-MLR Method
Authors: Joudaki Daryoush , Shafiei Fatemeh 
Published: March 2019

Aims and Objectives:
QSPR models establish relationships between different types of structural
information to their observed properties. In the present study the relationship between the molecular descriptors
and quantum properties of cycloalkanes is represented.

Materials and Methods:
Genetic Algorithm (GA) and Multiple Linear Regressions (MLR) were successfully
developed to predict quantum properties of cycloalkanes. A large number of molecular descriptors were
calculated with Dragon software and a subset of calculated descriptors was selected with a genetic algorithm
as a feature selection technique. The quantum properties consist of the heat capacity (Cv)/ Jmol-1K-1
entropy(S)/ Jmol-1K-1 and thermal energy(Eth)/ kJmol-1 were obtained from quantum-chemistry technique at
the Hartree-Fock (HF) level using the ab initio 6-31G* basis sets.

Results:
The Genetic Algorithm (GA) method was used to select important molecular descriptors and then
they were used as inputs for SPSS software package. The predictive powers of the MLR models were discussed
using Leave-One-Out (LOO) cross-validation, leave-group (5-fold)-out (LGO) and external prediction
series. The statistical parameters of the training and test sets for GA–MLR models were calculated.

Conclusion:
The resulting quantitative GA-MLR models of Cv, S, and Eth were obtained:[r2=0.950, Q2=0.989,
r2
ext=0.969, MAE(overall,5-flod)=0.6825 Jmol-1K-1], [r2=0.980, Q2=0.947, r2
ext=0.943, MAE(overall,5-flod)=0.5891Jmol-1K-1],
and [r2=0.980, Q2=0.809, r2
ext=0.985, MAE(overall,5-flod)=2.0284 kJmol-1]. The results showed that the predictive
ability of the models was satisfactory, and the constitutional, topological indices and ring descriptor
could be used to predict the mentioned properties of 103 cycloalkanes.
Azithromycin-induced Aphthous Stomatitis: A Case Series
Authors: Moghadam Ehsan T. , Tafazoli Ali 
Published: March 2019

Background:
Azithromycin is one of the most popular antibiotics in current clinical
practice. This medication generally considered to be safe and well-tolerated in different demographic
populations. Like any other drug, azithromycin use is not without risk and adverse effects.
In recent years, cardiovascular accidents have been announced as its major and most important side
effect. But azithromycin use can be accompanied with less recognized complications which are
significantly discomforting. In this article, we presented a neglected adverse effect of azithromycin
in medical literature which is aphthous stomatitis.

Methods:
We detected three cases with this complication in our center during a one-year period. All
the accessible clinical data were recorded and PubMed database was explored to assess the relevant
literature.

Results:
The patients had aphthous stomatitis within 24 hours of the first dose which was healed in
about 2 to 3 weeks. Naranjo scoring system showed a probable stage for this adverse drug reaction.
There was no such a report in our database search process.

Conclusion::
It could be stated that aphthous stomatitis is an important adverse effect of azithromycin
that can affect the patient’s quality of life during therapy and in the majority of cases, it can be
neglected by healthcare practitioners.
Harnessing Stem Cells and Neurotrophic Factors with Novel Technologies in the Treatment of Parkinson’s Disease
Authors: Conese Massimo , Cassano Roberta , Gavini Elisabetta , Trapani Giuseppe , Rassu Giovanna , Sanna Enrico , Di Gioia Sante , Trapani Adriana 
Published: March 2019

:
Parkinson’s disease (PD) is characterized by loss of dopaminergic neurons, oxidative stress
and neuroinflammation. The classical therapeutic approach with L-DOPA is not able to control motor
symptoms in the long term, thus new disease-modifying or neuroprotective treatments are urgently
required in order to match such yet unmet clinical needs. Success in cell-based therapy has been accomplished
at a clinical level with human fetal mesencephalic tissue, but ethical issues and a shortage
of organs clearly underline the need for novel sources of dopaminergic neurons. Mesenchymal stem
cells (MSCs) can be obtained from different adult and fetal tissues that are normally discarded as
waste, including adipose tissue, placenta, umbilical cord, and dental tissues. Their neuroregenerative,
anti-inflammatory and immunomodulatory properties are mainly mediated by the secretion of an array
of bioactive molecules and are heightened when MSCs form tri-dimensional structures called spheroids.
Not only can MSCs spontaneously produce neurotrophic factors (NFs) but they can be engineered
to synthetize and secrete them in vivo. The aim of this review is to provide a picture of results
gained with MSC secretome and spheroids in PD, as well as the possibility of harnessing MSC-based
therapy with the use of nano- and micro-structured materials for NF delivery.
Synergistic Effect of Novel EGFR Inhibitor AZD8931 and p38α siRNA in Lung Adenocarcinoma Cancer Cells
Authors: Zarredar Habib , Farajnia Safar , Ansarin Khalil , Baradaran Behzad , Aria Maryam , Asadi Milad 
Published: March 2019

Background:Lung cancer is the leading cause of cancer-related death with less than 5-year survival rate for both men and women worldwide. EGFR and MAPK signaling pathways have a critical role in proliferation and progression of various cancers, including lung cancer. P38 map kinase plays different role in various tissue hence showing a tissue-dependent behavior. It acts as an oncogene in some tissues while plays as tumor suppressor in some other tissues. The aim of this study was to investigate the combined effect of P38 αspecific siRNA and EGFR inhibitor on apoptosis and proliferation of A549 lung cancer cell line.Objective:This article is dedicated to the synergistic effect of novel EGFR inhibitor AZD8931 and P38 α siRNA in lung adenocarcinoma cancer cells proliferation and apoptosis.Methods and Materials:The A549 lung cancer cells were treated with P38 α- siRNA and EGFR inhibitor alone or in combination. The cytotoxic effects of P38 α- siRNA and EGFR inhibitor were determined using MTT assay. Relative P38 α and EGFR mRNA levels were measured by QRT-PCR. Induction of apoptosis were measured by FACS analysis.Results:The expression of mRNA related to P38 α, EGFR, and Her2 genes was reduced to 23.4%, 52.4%, and 75, respectively, after treatment of their inhibitors. Also, MTT assay showed that the cell viability after treatment with p38 α SiRNA, EGFR inhibitor and their combination was reduced to 51.02%, 48.9%, and 25.11%, respectively. FACS results indicated that p38 α siRNA, EGFR inhibitor and their combination, reduced the population of live cells to 49.5%, 32.2% and 14.3% in comparison to the population of untreated control cells (99.5%).Conclusion:The results of this study indicated that p38 α and EGFR might play an important role in the development and growth of lung cancer and might be a potential therapeutic target for the treatment of lung cancer.
An HHV-8 Positive HIV Negative Multicentric Castleman’s Disease, who Responded well to Rituximab Alone
Authors: Kounatidis Dimitris , Rontogianni Dimitra , Sampaziotis Dimitrios , Vardaka Maria , Giatra Chara , Dolapsakis Christodoulos , Margellou Evangelia , Vallianou Natalia G. 
Published: March 2019

Background:
Multicentric Castleman Disease (MCD) presents with enlarged lymph
nodes in multiple regions and systemic inflammatory symptoms, due to the dysregulation of cytokines,
most commonly interleukin-6 (IL-6). Human herpes virus-8 (HHV-8) is strongly related to
MCD (HHV-8-associated MCD) and is being implicated in cytokine dysregulation in patients, the
majority of whom are HIV positive or immunosuppressed. Preferred treatment of HHV-8-
associated MCD depends on the presence or not of concurrent Kaposi sarcoma and on whether the
patient has life-threatening organ failure or poor performance status thought to be related to HHV-
8-associated MCD.

Case Presentation:
Herein, we describe a female patient with HHV-8 positive, HIV negative MCD,
who responded well to the administration of rituximab once weekly for four weeks alone for three
cycles.

Conclusion:
HHV-8 positive, HIV negative MCD treatment modalities are only anecdotal due to
the rarity of this form of MCD. Administration of rituximab alone seems to be beneficial among
patients with good performance status and the absence of life-threatening organ failure in cases of
HHV-8 positive, HIV negative MCD.