bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preparation, Characterization, and In Vitro pH-sensitivity Evaluation of Superparamagnetic Iron Oxide Nanoparticle- Misonidazole pH-sensitive Liposomes
Authors: Li Bibo , Li Biqiang , He Daiying , Feng Changyan , Luo Zhibin , He Mei 
Published: November 2018

Background:
The use of Misonidazole (MISO), the first and a potential hypoxic tumor cell
radiosensitizer, has been limited by peripheral neurotoxicity, thus discouraging phase III clinical trials.

Objective:
To develop a targeted drug delivery and tracing System with pH-sensitive liposomes
(SpHLs) and Superparamagnetic Iron Oxide Nanoparticles (SPIONs) to counter MISO-related adverse
effects and to enable tracing under magnetic resonance.

Methods:
SPION-MISO-SpHLs were prepared by a reverse evaporation and freeze-thawing method.
HPLC and phenanthroline spectrophotometry were established for MISO and Fe determination. The
characterization and in vitro pH-sensitivity of SPION-MISO-SpHLs were evaluated.

Results:
The maximal entrapment efficiencies of MISO and SPIONs in SPION-MISO-SpHLs were
30.2% and 23.7%, respectively. The cumulative release rates of MISO and SPIONs were respectively
2.49 and 2.47 times higher in pH 5.5 than in pH 7.4 buffer. The mean particle size of SPION-MISOSpHLs
was 950 nm. The zeta potential was -58.9 mV in pH 7.4 buffer and 36.3 mV in pH 5.5 buffer.
SEM imaging showed that SPION-MISO-SpHLs had similar spherical morphologies. SPIONs were
packed in the center of liposomes and were well dispersed in a TEM graph. Magnetization curve
showed that SPION-MISO-SpHLs retained superparamagnetic properties. SPION-MISO-SpHLs were
compared with MISO+SPION+blank liposome in hypoxia and control groups of A549 cells. MISO and
SPION concentrations in culture medium showed significant differences between the same concentration
groups (P < 0.0001) and at different times (P < 0.0001).

Conclusion:
SPION-MISO-SpHLs possess pH-dependent release ability and superparamagnetism, and
thus provides a system for targeted delivery and tracing under magnetic resonance.
Synthesis of Dihydropyrimidinones (DHPMs) and Hexahydro Xanthene Catalyzed by 1,4-Diazabicyclo [2.2.2] Octane Triflate Under Solvent-Free Condition
Authors: Deepa  , Yadav Geeta D. , Aalam Mohd J. , Chaudhary Pooja , Singh Surendra 
Published: November 2018

Objective:DABCO salts were evaluated as catalysts for the Biginelli reaction between 4- methoxybenzaldehyde, urea and ethyl acetoacetate under solvent-free conditions. 1,4-Diazabicyclo [2.2.2] octane triflate was found to be a simple, inexpensive, highly efficient catalyst for Biginelli reaction for a variety aromatic aldehyde with urea and ethyl acetoacetate at 80°C afforded corresponding 3,4-dihydropyrimidinones in 50-99% yields after 30-120 minutes. 1,3-Cyclohexadione was used in place of ethyl acetoacetate in the absence of urea this methodology is giving hexahydro xanthene derivatives in good to excellent yields after 3-4 hours.Methods:DABCO salt 4 (5 mol%), 4-methoxybenzaldehyde (0.73 mmol) and urea (0.73 mmol) were stirred for 10 minutes at 80°C, then ethyl acetoacetate (1.5 equiv.) was added and reaction mixture was stirred at 80°C for specified time. The resulting solution was stirred continuously and progress of the reaction was followed by TLC. The crude reaction mixture was purified by flash column chromatography on silica gel (hexane/ethyl acetate (1:2)) to give pure desired product.Results:Reaction conditions of the Biginelli reaction were optimized using 4-methoxybenzaldehyde (0.73 mmol), urea (0.73 mmol), and ethyl acetoacetate (5 equiv.) as model substrates catalyzed by 1,4-Diazabicyclo [2.2.2] octane triflate (5 mol%) in a different solvents, screening of different catalysts and different temperatures. Neat condition was found to be the best for the Biginelli condensation and corresponding 3,4- dihydropyrimidinones was obtained in good to excellent yields. When the reaction was carried out with benzaldehyde derivatives and cyclohexane-1,3-dione in place of ethyl acetoacetate in the absence of urea, solely corresponding hexahydro xanthene derivatives were obtained in 61-91% yields.Conclusion:In conclusion, we have applied salts of 1,4-Diaza-bicyclo [2.2.2] octane as catalysts in the Biginelli condensation and corresponding 3,4-dihydropyrimidinones were obtained in 50- 99% yields under solvent free conditions. This methodology is having advantages like simple work-up; low loading of catalyst and reaction was performed at moderate temperature under solvent-free conditions.
Synthesis of Limonin Derivatives with Improved Anti-inflammatory and Analgesic Properties
Authors: Jia Chengshu , Hu Bin , Ji Yingying , Su Yourui , Gong Guoqing , Zhu Qihua , Xu Yungen 
Published: November 2018

Background:
Limonoids represent an important class of natural products which possess a
broad range of biological activities. Albeit their enormous potentials as therapeutic candidates, they
usually suffer from low bioavailability, poor aqueous solubility and relatively weak biological
activities which result in significant challenges in the clinic applications. Therefore, the exploration
and development of novel limonin derivatives with improved drug-like properties through the
structural modifications recently have attracted great attention in the biological and medicinal
chemistry field.

Methods:
Based on the structural modifications of C17-furan ring in limonin, a series of limonin
derivatives was designed, synthesized and screened for their anti-inflammatory and analgesic
activities in vivo.

Results and Conclusion:
Preliminary pharmacological studies revealed that most tested compounds
exhibited more potent anti-inflammatory and analgesic efficacies than lead molecule limonin.
Especially, for compound 3f, it exhibited a stronger anti-inflammatory effect than that of naproxen
and comparable analgesic potency with aspirin. In the formalin test, 3f showed an obviously
attenuated phase-II pain response which indicated that it may produce an anti-inflammatory effect in
the periphery. Furthermore, the significantly low hERG inhibition (IC50 >100 μM) and high LD50
value of target molecule 3f further demonstrated it as a promising analgesic/anti-inflammatory
candidate with excellent drug-like profiles.
Synthesis, Antiproliferative, and Antioxidant Activities of Substituted N-[(1,3,4-Oxadiazol-2-yl) Methyl] Benzamines
Authors: Ahsan Mohamed Jawed , Bhandari Lakshya , Makkar Shally , Singh Rajan , Hassan Mohd. Zaheen , Geesi Mohammed H. , Bakht Mohamed Afroz , Jadav Surender Singh , Balaraju Tuniki , Riadi Yassine , Rani Sandhya , Khalilullah Habibullah , Gorantla Vasubabu , Hussain Afzal 
Published: November 2018

Background:Oxadiazole emerged as an important class of heterocyclic compound with diverse biological activities like anticancer, antitubercular, anticonvulsant, anti-tubulin, antimicrobial, anti-inflammatory, antioxidant etc.Objective:The objective of this study is to synthesis series of twelve substituted N-[(1,3,4-oxadiazol-2- yl)methyl]benzamines (6a-l) and their evaluation as antiproliferative and antioxidant agents.Methods:The substituted N-[(1,3,4-oxadiazol-2-yl)methyl]benzamines (6a-l) analogues were synthesized as per the reported procedure. The antiproliferative activity was tested against nine different panels cancer cell lines (leukemia, colon, renal, non-small cell lung, breast, CNS, melanoma, prostate, and ovarian cancer) at 10 µM drug concentrations as per the NCI US Protocol.Results:2-(5-((3-Chloro-4-fluorophenylamino)methyl)-1,3,4-oxadiazol-2-yl)phenol (6e) revealed the significant antiproliferative activity among the series of title compounds (6a-l). The compound, 6e showed maximum sensitivity towards CCRF-CEM, MCF-7, MOLT-4, T-47D, and SR cell lines with percent growth inhibitions (%GIs) of 79.92, 56.67, 39.62, 34.71 and 33.35, respectively. Furthermore, the compounds, 6e and 6c showed promising antioxidant activity with an IC50 value of 15.09 and 19.02 µM, respectively in DPPH free radicals (FR) scavenging activity.RConclusion:The present study may support a significant value in cancer drug discovery programme.
Synthesis of Novel 2,3-Dihydro-5,6-dimethoxy-2-((piperidin-4-yl)methyl) inden-1-one Derivatives as Acetyl Cholinesterase Inhibitors
Authors: Prasad Salekoppal B.B. , Mysore Sachin , Raj C.S. Ashok , Rangappa Kanchugarakoppalu S. , Mahadevaiah K. , Kumar Channapillekoppal S.A. 
Published: November 2018

Background:
Novel carboxamides and thioureas of 2,3-dihydro-5,6-dimethoxy-2-((piperidin-
4-yl)methyl) inden-1-one were synthesized and their potential anticholinesterase activities were evaluated.
The inhibition potency of the compounds 17a-j and 19a-j against AChE was measured and evaluated
using Ellman’s spectrophotometric method. Among carboxamides series, compound 17f, 17i, 17j
and among thiourea series, compound 19a, 19b were found to be the most active.

Methods:
The scaffold 2,3-dihydro-5,6-dimethoxy-2-((piperidin-4-yl)methyl) inden-1-one 16, key intermediate
of drug donepezil has been synthesised in three steps and derivatised as carboxamides and
thioureas for SAR studies. Compounds 17a-j and 19a-j were characterised by 1H NMR and LCMS. The
inhibitory activity and antiamnesic effect were studied using different sources such as electric eel
AChE, human serum AChE and rat brain homogenate AChE.

Results:
The results of bioassays indicated that among all the synthesized compounds tested, five compounds
17f, 17i, 17j, 19a and 19b shows IC50 at a dose of 67, 42, 64, 52 and 63 nM respectively against
electric eel, human serum and rat brain homogenate, which lead to the suggestion that compound 17i
might be considered to be a potent AChE inhibitor.

Conclusion:
Derivatives of 2,3-dihydro-5,6-dimethoxy-2-((piperidin-4-yl)methyl)inden-1-one with
different substitutions were synthesised and tested for their AChE activity. The order of potency is
17i>17j>17f and 19a>19b. The other compounds screened failed to elicit any inhibition of acetyl cholinesterase
from rat brain homogenate. It may be concluded from this study that, for effective binding
and blocking the AChE activity, molecule needs to bind with peripheral site and active site of the enzyme.
Therefore, it can be summarized that by changing the functional group and substitution in the
scaffold 2,3-dihydro-5,6-dimethoxy-2-((piperidin-4-yl)methyl)inden-1-one needs to be studied for better
AChE inhibitory activity in future research.
Effect of Chemical Oxidation Routes on the Properties of Chitosan- MWCNT Nanocomposites
Authors: Sánchez Alejandro Gomez , Prokhorov Evgen , Luna-Barcenas Gabriel , Kovalenko Yuriy , Rivera-Muñoz Eric M. , Raucci Maria G. , Buonocore Giovanna 
Published: November 2018

Background:
Chitosan-multiwall carbon nanotubes (CS-MWCNTs) nanocomposites are
an attractive material due to their biocompatibility and possibility to produce nanocomposites with
high conductivities and high mechanical properties. Both electrical and mechanical properties depend
upon the method of MWCNT chemical oxidation; this oxidation affects the interaction of CS
side groups with MWCNT’s surface groups. However, in the literature, there are no reports on how
different methods of MWCNT oxidation will affect the electrical and mechanical properties of related
nanocomposites.

Objective:
The objective of this work is to probe CS-MWCNT nanocomposite’s electrical and mechanical
properties by taking advantage of the presence of interfacial layer and its dependence on the
methods of MWCNTs chemical oxidation routes.

Methods:
Nanocomposites are prepared with non-functionalized MWCNT and functionalized
MWCNTs obtained by chemical oxidation treatments in HNO3 in H2SO4/NHO3 mixtures and commercially
carboxyl-terminated MWCNTs, respectively. Properties of MWCNTs and nanocomposites
were evaluated using SEM, FTIR, Raman, TGA, XRD, impedance and mechanical measurements.

Results:
It was shown that different chemical oxidation routes produce MWCNTs with a different
number of carboxylic groups and defects which influence the interaction between MWCNTs with CS
matrix and thickness of the interfacial layer between MWCNTs and CS matrix. Additionally, it was
shown that the formation of the interfacial layer dominates on the dispersion of MWCNTs and
affects on the electrical and mechanical percolation effects.

Conclusion:
It was shown that contrary to many studies previously reported, good dispersion of
MWCNT does not guarantee obtained nanocomposites with the best electrical and mechanical properties.
Sonic Hedgehog Signaling Activation Promotes Cardioprotective Strategies
Authors: Khera Himanshi , Awasthi Anupam , Mehan Sidharth 
Published: November 2018

Background:Hedgehog pathway plays a crucial role in the neovascularisation and angiogenesis during the embryonic stage in humans. Three genes of hedgehog protein isolated from humans are Sonic hedgehog, Desert hedgehog and Indian hedgehog gene. Two G-protein coupled receptors identified in the sonic hedgehog pathway served as patched receptor and smoothened receptor.Materials and Methods:Particularly, sonic hedgehog gene plays a versatile role in cellular homeostasis and can be a novel therapeutic target in the prevention of cardiovascular disorders. Further various sonic hedgehog modulators have been reported working as futuristic drug molecules in the modulation of cardiovascular dysfunctions.Results:However, there was limited literature availability that has summarized the possible mechanism of targeting Sonic hedgehog signaling pathway.Conclusion:Thus, the present review is aimed at exploring the role of targeting sonic hedgehog protein signaling and modulators as well as to enlighten that how targeting sonic hedgehog protein involves in the amelioration of atherosclerosis, ischemic heart diseases, vascular endothelial dysfunction, heart failure and congenital heart diseases.
Design, Synthesis and Evaluation of Novel 3/4-((Substituted benzamidophenoxy) methyl)-N-hydroxybenzamides/propenamides as Histone Deacetylase Inhibitors and Antitumor Agents
Authors: Anh Duong T. , Thuan Nguyen T. , Hai Pham-The , Huong Le-Thi-Thu , Yen Nguyen T.K. , Han Byung W. , Park Eun J. , Choi Yeo J. , Kang Jong S. , Hue Van T.M. , Han Sang-Bae , Nam Nguyen-Hai 
Published: November 2018

Background:Histone Deacetylase (HDAC) inhibitors represent an extensive class of targeted anticancer agents. Among the most explored structure moieties, hydroxybenzamides and hydroxypropenamides have been demonstrated to have potential HDAC inhibitory effects. Several compounds of these structural classes have been approved for clinical uses to treat different types of cancer, such as givinostat (ITF2357) and belinostat (PXD-101).Aims:This study aims at developing novel HDAC inhibitors bearing N-hydroxybenzamides and Nhydroxypropenamides scaffolds with potential cytotoxicity against different cancer cell lines.Methods:Two new series of N-hydroxybenzamides and N-hydroxypropenamides analogues (4a-j, 6a-j) designed based on the structural features of nexturastat A, AR-42, and PXD-101, were synthesized and evaluated for HDAC inhibitory potency as well as cytotoxicity against three human cancer cell lines (SW620 (colorectal adenocarcinoma), PC3 (prostate adenocarcinoma), and NCI-H23 (adenocarcinoma, non-small cell lung cancer). Molecular simulations were finally carried out to gain more insight into the structure-activity relationships.Results:It was found that the N-hydroxypropenamides (6a-e) displayed very good HDAC inhibitory potency and cytotoxicity. Various compounds, e.g. 6a-e, especially compound 6e, were up to 5-fold more potent than suberanilohydroxamic acid (SAHA) in terms of cytotoxicity. These compounds also comparably inhibited HDACs with IC50 values in the sub-micromolar range. Docking experiments showed that these compounds bound to HDAC2 at the enzyme active binding site with the same binding mode of SAHA, but with higher binding affinities.Conclusions:The two series of N-hydroxybenzamides and N-hydroxypropenamides designed and synthesized were potential HDAC inhibitors and antitumor agents. Further development of these compounds should be warranted.
Generation and Characterization of a Functional Nanobody Against Inflammatory Chemokine CXCL10, as a Novel Strategy for the Treatment of Multiple Sclerosis
Authors: Sadeghian-Rizi Tahereh , Behdani Mahdi , Khanahmad Hossein , Sadeghi Hamid Mirmohammad , Jahanian-Najafabadi Ali 
Published: November 2018

Background & Objective: Chemokines and their receptors play a pivotal role in the pathogenesis
of various autoimmune diseases such as multiple sclerosis, infectious diseases, and also in
cancer metastasis via attraction of the pathogenic immune cells into the inflammation sites.

Methods:
Inflammatory chemokine CXCL10 as a T helper (Th)1-chemokine directs chemotaxis of
many cell subsets especially Th1 into the central nervous system (CNS) via its receptor CXCR3 and it
has been put forward as a potential therapeutic target in the treatment of multiple sclerosis. Nanobodies
are the smallest intact antigen binding fragments derived from heavy chain-only antibodies occurring
in camelids with unique biochemical and biophysical features which render them superior to conventional
antibodies or antibody fragments. Here, we describe the generation, selection, and characterization
of CXCL10-specific Nanobodies from camel immunized with CXCL10. The obtained
Nanobodies displayed high affinity towards CXCL10 about 10-11-10-8 M.

Results:
Then a Nanobody with the highest affinity named 3Nb12 was selected and investigated as a
migration inhibitor of CXCR3+ cells. Chemotaxis assay results showed that 3Nb12 blocked CXCL10-
CXCR3 binding and potently inhibited chemotaxis of CXCR3-transfected HEK293T cells.

Conclusion:
The nanobody 3Nb12 might be a promising specific and powerful blocking agent of
CXCL10 function, which can be used for diagnostic, therapeutic and research purposes in MS.
Xuesaitong May Protect Against Ischemic Stroke by Modulating Microglial Phenotypes and Inhibiting Neuronal Cell Apoptosis via the STAT3 Signaling Pathway
Authors: Li Fangfang , Zhao Haiping , Han Ziping , Wang Rongliang , Tao Zhen , Fan Zhibin , Zhang Sijia , Li Guangwen , Chen Zhigang , Luo Yumin 
Published: November 2018

Background:
Xuesaitong mainly comprises Panax notoginseng saponins and has shown a
promising feature in an acute ischemic stroke model; however, its effect on long-term recovery following
stroke, and the related mechanisms, are unknown.

Methods:
The objective of this study was to investigate the long-term protective effects of xuesaitong
against ischemic stroke and its effect on microglial polarization. Experimental cerebral ischemia was induced
by middle cerebral artery occlusion (MCAO) for 45 min, and C57BL/6 mice were immediately injected
with xuesaitong or vehicle through the caudal vein at the onset of cerebral reperfusion consecutively
for 14 days. The animals were randomly divided into three groups: a sham-operated group, vehicle-treated
group and xuesaitong-treated group at a dose of 15μg/g. Subsequently, 2,3,5-triphenyltetrazolium chloride
staining was used to assess infarct volume, and adhesive removal tests and balance beam tests were used
to evaluate neurological deficits at days 1, 3, 7 and 14 following ischemia. Reverse-transcriptase polymerase
chain reaction and immunofluorescence staining for M1 markers (CD16, iNOS) and M2 markers
(CD206, arginase-1) were performed to characterize phenotypic changes in microglia. Elisa was used to
determine the release of pro-inflammatory and anti-inflammatory cytokines. TUNEL staining was conducted
to detect neuronal cell apoptosis, and western blots were used to determine the activation of signal
transducer and activator of transcription 3 (STAT3).

Results:
Our results revealed that xuesaitong treatment, compared with vehicle treatment, significantly
reduced cerebral infarct volume 1 and 3 days after MCAO and resulted in significant improvements in
long-term neurological outcomes. Furthermore, xuesaitong treatment, compared with vehicle treatment,
significantly reduced M1 markers and elevated M2 markers 7 and 14 days after MCAO at both
the mRNA and protein level in ipsilateral brain tissue. This finding was also accompanied by a reduction
in neuronal cell apoptosis and p-STAT3 transcription factor levels in the xuesaitong-treated group
compared with the vehicle-treated group.

Conclusion:
We demonstrated that xuesaitong has long-term neuroprotective effects against ischemic
stroke, possibly by promoting the polarization of microglia to an M2 phenotype and by inhibiting neuronal
cell death via down-regulation of the STAT3 signaling pathway, providing new evidence that
xuesaitong might be a promising therapeutic strategy for ischemic stroke.
Muito além de fractais, caleidoscópios ou conjuntos de Mandelbrot as teorias da informação e da comunicação
Authors: Pereira Rosane Da Conceição 
Published: November 2018

Este artigo constitui uma abordagem crítica sobre algumas contribuições epistemológicas de saberes diversos, em relação às teorias da informação e comunicação contemporâneas. Pretende abrir discussões e ressaltar o problema da constituição do complexo objeto informação e comunicação, além de oferecer inteligibilidade mais ampla quanto ao seu alcance e limites. É a tentativa de desviar os estudos nessa área para a afirmação de um conjunto de saberes em processo, a partir dos conceitos transdisciplinaridade e historicidade. Contudo, sem incorrer em um aglomerado de doxoi nem na utopia de uma ciência plenamente acabada, que apreenda o mundo como uma totalidade intricada, apenas de modo otimista ou pessimista. O trabalho é de continuar o processo com prudência, antes que apoiar visões caleidoscópicas ou mandelbrotianas sobre as ciências da informação e comunicação, afastadas da realidade latino-americana, sobretudo brasileira.
Divergências convergentes: a nova cultura radiofônica
Authors: Zaremba Lilian 
Published: November 2018

Há mais ou menos vinte anos o rádio começou a se transformar na digitalização e sob o impacto da chamada convergência dos massmedia, o computador e a telecomunicação, oferecendo terreno para o aparecimento de formas híbridas: as concepções tradicionais enfrentam o embate no mutante espaço cibernético. Mutatis Mutandis, mudar o que precisa ser mudado, o rádio se desloca no dial encruzilhada das opções. O médium das gigantescas organizações internacionais, o rádio público, comunitário ou pirata, atraídos por este ímã até então estranho da nova media eletrônica, temem ser dissolvidos por ela. A resistência dos padrões sucumbe na pressão comercial tornando urgente a preservação de algum espaço para reflexão. Este trabalho pretendeu operar nesta urgência contribuindo para o debate, vasculhando nas origens deste médium de comunicação a compreensão mesma do que seja e possa talvez continuar a ser, Rádio.
Discurso e Cinema: uma análise de LIMITE
Authors: Souza Tania C. Clemente de 
Published: November 2018

A primeira vez que vi LIMITE, de Mário Peixoto, ainda não tinha lido nada a respeito do filme. Três aspectos básicos me surpreenderam: a beleza da fotografia; a noção de tempo, trabalhada em duas dimensões: o cronológico e o psicológico e a narrativa, conduzida por essas duas dimensões do tempo.
A crítica à imprensa e seus problemas normativos
Authors: Lopes Luís Carlos 
Published: November 2018

Este artigo discute as posturas normativas existentes ou adotadas pela produção intelectual na forma de livros, artigos e sites específicos que avaliam e criticam a imprensa. Busca-se a compreensão, no sentido hermenêutico do termo, das suas regras de justificação implícitas e explícitas, sobretudo no que se refere às ‘verdades’ e ‘mentiras’ divulgadas e ‘retrabalhadas’ pelos receptores das mensagens jornalísticas. Discutem-se, baseado em Habermas, Bourdieu e outros, as intrincadas relações estabelecidas entre os jornalistas, donos dos meios de comunicação, poder político e vida social, sob o ponto de vista das crenças e do discurso moral. Pretende-se analisar os modelos de compreensão disponíveis e avançar em outros que sejam mais eficientes para o entendimento dos significados (sentidos) possíveis da imprensa brasileira e dos seus críticos internos e externos.