bluuebunny/crossref_metadata_2025_split huggingface dataset:
Common Pathological Mechanisms and Risk Factors for Alzheimer’s Disease and Type-2 Diabetes: Focus on Inflammation
Authors: Moyse Emmanuel , Haddad Mohamed , Benlabiod Camelia , Ramassamy Charles , Krantic Slavica 
Published: November 2019

Background :Diabetes is considered as a risk factor for Alzheimer’s Disease, but it is yet unclear whether this pathological link is reciprocal. Although Alzheimer’s disease and diabetes appear as entirely different pathological entities affecting the Central Nervous System and a peripheral organ (pancreas), respectively, they share a common pathological core. Recent evidence suggests that in the pancreas in the case of diabetes, as in the brain for Alzheimer’s Disease, the initial pathological event may be the accumulation of toxic proteins yielding amyloidosis. Moreover, in both pathologies, amyloidosis is likely responsible for local inflammation, which acts as a driving force for cell death and tissue degeneration. These pathological events are all inter-connected and establish a vicious cycle resulting in the progressive character of both pathologies.Objective:To address the literature supporting the hypothesis of a common pathological core for both diseases.Discussion:We will focus on the analogies and differences between the disease-related inflammatory changes in a peripheral organ, such as the pancreas, versus those observed in the brain. Recent evidence suggesting an impact of peripheral inflammation on neuroinflammation in Alzheimer’s disease will be presented.Conclusion:We propose that it is now necessary to consider whether neuroinflammation in Alzheimer’s disease affects inflammation in the pancreas related to diabetes.
Synthesis, Biological Evaluation and Molecular Docking Studies of Novel Di-hydropyridine Analogs as Potent Antioxidants
Authors: Sudhana Saddala Madhu , Adi Pradeepkiran Jangampalli 
Published: November 2019

Aims:
The aim of this study is to synthesize, characterize and biological evaluation of 3-ethyl 5-
methyl2-(2-aminoethoxy)-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate derivatives.

Background:
An efficient synthesis of two series of novel carbamate and sulfonamide derivatives of amlodipine,
3-ethyl 5-methyl 2-(2-aminoethoxy)-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (amlodipine)
1 were chemical synthesized process.

Materials & Methods:
In this process, various chloroformates 2(a-e) and sulfonyl chlorides 4(a-e) on reaction
with 1 in the presence of N,N–dimethylpiperazine as a base in THF at 50-550 oC, the corresponding title compounds
3(a-e) and 5(a-e) in high yields. Furthermore, the compounds 3(a-e) and 5(a-e) were evaluated for antioxidant
activity (DPPH method), metal chelating activity, hemolytic activity, antioxidant assay (ABTS
method), cytotoxicity, molecular docking and in silico ADMET properties.

Result:
Results revealed that 5a, 5e, 3d, 3a and 5c exhibited high antioxidant, metal chelating activities, but
5a, 5e and 3d exhibited low activity. The molecular docking studies and ADMET of suggested ligands showed
the best binding energies and non-toxic properties.

Conclusion:
The present in silico and in vitro evaluations suggested that these dihydropyridine derivatives act
as potent antioxidants and chelating agents which may be useful in treating metals induced oxidative stress
associated diseases.
In-silico Subtractive Proteomic Analysis Approach for Therapeutic Targets in MDR Salmonella enterica subsp. enterica serovar Typhi str. CT18
Authors: Rahman Noor , Muhammad Ijaz , Nayab Gul E. , Khan Haroon , Filosa Rosanna , Xiao Jianbo , Hassan Sherif T.S. 
Published: November 2019

Objective:
In the present study, an attempt has been made for subtractive proteomic analysis
approach for novel drug targets in Salmonella enterica subsp. enterica serover Typhi str.CT18 using
computational tools.

Method:
Paralogous, redundant and less than 100 amino acid protein sequences were removed by using
CD-HIT. Further detection of bacterial proteins which are non-homologous to host and are essential for
the survival of pathogens by using BLASTp against host proteome and DEG`s, respectively. Comparative
Metabolic pathways analysis was performed to find unique and common metabolic pathways. The
non-redundant, non-homologous and essential proteins were BLAST against approved drug targets for
drug targets while Psortb and CELLO were used to predict subcellular localization.

Result:
There were 4473 protein sequences present in NCBI Database for Salmonella enterica subsp.
enterica serover Typhi str. CT18 out of these 327 were essential proteins which were non-homologous
to human. Among these essential proteins, 124 proteins were involved in 19 unique metabolic pathways.
These proteins were further BLAST against approved drug targets in which 7 cytoplasmic proteins
showed druggability and can be used as a therapeutic target.

Conclusion:
Drug targets identification is the prime step towards drug discovery. We identified 7 cytoplasmic
druggable proteins which are essential for the pathogen survival and non-homologous to human
proteome. Further in vitro and in vivo validation is needed for the evaluation of these targets to combat
against salmonellosis.
Cytotoxicity of Anchusa arvensis Against HepG-2 Cell Lines: Mechanistic and Computational Approaches
Authors: Hussain Sajid , Ullah Farhat , Sadiq Abdul , Ayaz Muhammad , Shah Azhar-ul-Haq Ali , Ali Shah Syed Adnan , Shah Syed Majid , Nadhman Akhtar , Ullah Farman , Wadood Abdul , El-Shazly Mohamed 
Published: November 2019

Background:
Liver cancer is a devastating cancer with increasing incidence and mortality
rates worldwide. Plants possess numerous therapeutic properties, therefore the search for novel, naturally
occurring cytotoxic compounds is urgently needed.

Methods:
The anticancer activity of plant extracts and isolated compounds from Anchusa arvensis (A.
arvensis) were studied against the cell culture of HepG-2 (human hepatocellular carcinoma cell lines)
using 3-(4,5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) assay. Apoptosis was investigated
by performing Acridine orange –ethidium bromide staining, styox green assay and DNA interaction
study. We also used tools for computational chemistry studies of isolated compounds with the tyrosine
kinase.

Results:
In MTT assay, the crude extract caused a significant cytotoxic effect with IC50 of 34.14 ± 0.9
μg/ml against HepG-2 cell lines. Upon fractionation, chloroform fraction (Aa.Chm) exhibited the highest
antiproliferative activity with IC50 6.55 ± 1.2 μg/ml followed by ethyl acetate (Aa.Et) fraction (IC50,
24.59 ± 0.85 μg/ml) and n-hexane (Aa.Hex) fraction (IC50 29.53 ± 1.5μg/ml). However, the aqueous
(Aa.Aq) fraction did not show any anti-proliferative activity. Bioactivity-guided isolation led to the isolation
of two compounds which were characterized as para–methoxycatechol (1) and decane (2) through
various spectroscopic techniques. Against HepG-2 cells, compound 1 showed marked potency with IC50
6.03 ± 0.75 μg/ml followed by 2 with IC50 18.52 ± 1.9 μg/ml. DMSO was used as a negative control and
doxorubicin as a reference standard (IC50 1.3 ± 0.21 μg/ml). It was observed that compounds 1-2 caused
apoptotic cell death evaluated by Acridine orange –ethidium bromide staining, styox green assay and
DNA interaction study, therefore both compounds were tested for molecular docking studies against tyrosine
kinase to support cytotoxic activity.

Conclusion:
This study revealed that the plant extracts and isolated compounds possess promising antiproliferative
activity against HepG-2 cell lines via apoptotic cell death.
Identification of Potential Dual Negative Allosteric Modulators of Group I mGluR Family: A Shape Based Screening, ADME Prediction, Induced Fit Docking and Molecular Dynamics Approach Against Neurodegenerative Diseases
Authors: Prabhu Sitrarasu Vijaya , Singh Sanjeev Kumar 
Published: November 2019

Background:
Glutamate is the principal neurotransmitter in the human brain that exerts its
effects through ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors
(mGluRs). The mGluRs are a class of C GPCRs that play a vital role in various neurobiological functions,
mGluR1 and mGluR5 are the two receptors distributed throughout the brain involved in cognition,
learning, memory, and other important neurological processes. Dysfunction of these receptors can cause
neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, X-fragile syndrome, anxiety,
depression, etc., hence these receptors are high profile targets for pharmaceutical industries.

Objective:
The objective of our study is to find the novel dual negative allosteric modulators to regulate
both mGluR1 and mGluR5.

Methods:
In this study, shape screening protocol was used to find the dual negative allosteric modulators
for both mGluR1 and mGluR5 followed by ADME prediction, induced-fit docking (IFD) and molecular
dynamics simulations. Further, DFT analysis and MESP studies were carried out for the selected
compounds.

Results:
Around 247 compounds were obtained from the eMolecules database and clustered through the
CANVAS module and filtered with ADME properties. Furthermore, IFD revealed that the top four
compounds (16059796, 25004252, 4667236 and 11670690) having good protein-ligand interactions and
binding free energies. The molecular electrostatic potential of the top compounds shows interactions in
the amine group and the oxygen atom in the negative potential regions. Finally, molecular dynamics
simulations were performed with all the selected as well as the reported compound 29 indicates that the
screened hits have better stability of protein ligand complex.

Conclusion:
Hence, from the results, it is evident that top hits 16059796, 25004252, 4667236 and
11670690 could be a novel and potent dual negative allosteric modulators for mGluR1 and mGluR5.
Unexpected Reactions of Terminal Alkynes in Targeted “Click Chemistry’’ Coppercatalyzed Azide-alkyne Cycloadditions
Authors: Ali Tammar H. , Heidelberg Thorsten , Hussen Rusnah S.D. , Tajuddin Hairul A. 
Published: November 2019

Background:
High efficiency in terms of reaction yield and purity has led to the extensive
utilization of copper-catalyzed azide-alkyne cycloaddition (CuAAC) in various fields of chemistry. Its
compatibility with low molecular weight alcohols promotes the application in surfactant synthesis to tackle the
miscibility constraints of the reactants.

Objective:
For the tuning of surfactant properties, double click coupling of the antipode precursors was
attempted. Failure of the CuAAC to provide the targeted product in combination with unexpected reaction
outputs led to an investigation of the side reaction.

Methods:
The CuAAC-based coupling of sugar azide with propargyl building block in the presence of copper-
(I) catalyst exclusively led to the mono-coupling product in a respectable yield of almost 80%. Besides the
unexpected incomplete conversion, the loss of the remaining propargyl group, as indicated by both NMR and
MS. On the other hand, application of substantial amounts of CuSO4 under reducing conditions in refluxing
toluene/water furnished the alkyne dimer in a moderate yield of 43%, while no change of azide compound was
noticed.

Results:
The Cu(I)-catalyst applied for azide-alkyne cycloadditions enables the homo-coupling of certain
terminal alkynes at a higher temperature. Moreover, aromatic propargyl ethers may be cleaved to furnish the
corresponding phenol. The copper-catalyzed coupling appeared highly sensitive towards the alkyne compound.
Only selected derivatives of propargyl alcohol were successfully dimerized.

Conclusions:
The observed failure of the Huisgen reaction for the synthesis of sugar-based surfactants may
indicate non-recognized constrains of the reaction, which could affect its wide application in bioconjugation.
The temperature requirement for the alternative dimerization of terminal alkynes renders this side reaction nonrelevant
for typical click couplings, while narrow substrate diversity and moderate yield limit its synthetic
application.
Development of Novel Glitazones as Antidiabetic Agents: Molecular Design, Synthesis, Evaluation of Glucose Uptake Activity and SAR Studies
Authors: Srinivas Mahendra Gowdru , Prabhakaran Prabitha , Mandal Subhankar Probhat , Sivamani Yuvaraj , Guddur Pranesh , Kumar Bommenahally Ravanappa Prashantha 
Published: November 2019

Background:
Thiazolidinediones and its bioisostere, namely, rhodanines have become
ubiquitous class of heterocyclic compounds in drug design and discovery. In the present study, as
part of molecular design, a series of novel glitazones that are feasible to synthesize in our laboratory
were subjected to docking studies against PPAR-γ receptor for their selection.

Methods and Results:
As part of the synthesis of selected twelve glitazones, the core moiety, pyridine
incorporated rhodanine was synthesized via dithiocarbamate. Later, a series of glitazones were
prepared via Knovenageal condensation. In silico docking studies were performed against PPARγ
protein (2PRG). The titled compounds were investigated for their cytotoxic activity against 3T3-L1
cells to identify the cytotoxicity window of the glitazones. Further, within the cytotoxicity window,
glitazones were screened for glucose uptake activity against L6 cells to assess their possible antidiabetic
activity.

Conclusion:
Based on the glucose uptake results, structure activity relationships are drawn for the
title compounds.
Bioactive Compounds and Distinctive Pharmacological Activity Guided Review of Aegle marmelos: A Miraculous Plant of Indigenous Medicine System
Authors: Ghosh Sourav , Kumar Arvind , Sachan Neetu , Chandra Phool 
Published: November 2019

Background:
It is always thought that traditional herbal drugs are safe, effective and economical
and are used worldwide for healing purposes. Aegle marmelos, belonging to family Rutaceae, is
an important medicinal plant of the indigenous medicine system in India. Despite the study on ethnobotanical
uses and the presence of bioactive compounds, there was only a handful of research on A. marmelos.
The therapeutic use of bioactive compounds is not explored properly.

Objective:
The objective of this study is to provide comprehensive data on the botanical description,
ethnobotany, isolated bioactive compounds and their therapeutic effects according to the pharmacology
of A. marmelos and its future prospects for further scientific investigation for the development of effective
bioactive compounds.

Methods:
Literature searches were performed in various databases, such as PubMed, SciFinder and
Google Scholar, for peer-reviewed research literature pertaining to the bioactive compounds present and
distinctive pharmacological activities of A. marmelos.

Results:
The literature review indicates that different parts of A. marmelos possess various ethnobotanical
uses. A large number of bioactive compounds isolated from different parts of the plant were reviewed
which mainly belong to alkaloids, terpenoids, steroids, coumarins, flavonoids and carbohydrate
in nature. The plant also possesses a wide range of pharmacological activities, such as antidiarrheal,
antimicrobial, anticancer, hepatoprotective, antifertility, anti-inflammatory, wound healing, radioprotective,
hypoglycemic and cardioprotective activity.

Conclusion:
It is clearly proven that different parts of A. marmelos possess numerous therapeutic effects
for treating various ailments of human beings. As the scientists anticipated to develop new drugs
from natural sources, investigation of modern drugs from A. marmelos should be emphasized. Still,
extensive research studies are required on A. marmelos as it is the most important plant of the indigenous
medicine system in India. Therefore, this review could be used as a good source of information for
researchers who wish to proceed their exploration of A. marmelos.
Effect of Pregnenolone Derivatives on the Selective Inhibition of 5α-Reductase 2 Activity
Authors: Cabeza Marisa , Bautista Lucero , Bratoeff Eugene , Soriano Juan , Heuze Yvonne 
Published: November 2019

Background:Benign prostatic hyperplasia and prostate cancer are androgen-dependent diseases, and dihydrotestosterone (DHT), a 5α-reduced metabolite of testosterone (T), has been implicated as a causative factor in the progression of these diseases. The 5α-reductase enzyme (5α-R) converts T to DHT, which is responsible for increasing cell proliferation, and hence inhibition of this enzyme could lead to potential treatments for these afflictions.Objective:This study focused on evaluating the biological activity of three series of pregnenolone derivatives as inhibitors of 5α-R and as antiandrogens on androgen-dependent glands.Method:To determine the biological activity of these compounds, we evaluated the effect of each one on suppressing the activity of both types of isozymes of 5α-R (1 and 2) by 50% (IC50). Using animal studies, we assessed the effect of these derivatives on the weight of the prostate, seminal vesicles, and diameter of the flank organs of castrated hamsters previously dosed with 1 mg/Kg T.Results:In vitro experiments showed that derivatives 1f, 2b, and 3d were very effective inhibitors of the activity of 5α-R2, showing IC50 values of 21.8, 20, and 15 nM, respectively. Derivatives 2b and 3b showed a lower inhibition effect on 5α-R1.:The data also indicated that derivatives 2b, 1f, 3b, and 3d were very active in reducing prostate weight in the hamster model of benign prostatic hyperplasia.Discussion:Pharmacological experiments showed that pregnenolone derivatives possess an antiandrogenic effect because of the inhibition of DHT production in androgen-dependent glands.Conclusion:The pregnenolone derivatives studied suppressed type 2 5α-reductase activity and because of this, the weight and dimension of androgen-dependent organs were decreased.
Somatostatin Type 2 Receptor Antibody Enhances Mechanical Hyperalgesia in the Dorsal Root Ganglion Neurons after Sciatic Nerve-pinch Injury: Evidence of Behavioral Studies and Bax Protein Expression
Authors: Xiang Qiong , Li Jing-Jing , Li Chun-Yan , Tian Rong-Bo , Li Xian-Hui 
Published: November 2019

Background:Our previous study has indicated that somatostatin potently inhibits neuropathic pain through the activation of its type 2 receptor (SSTR2) in mouse dorsal root ganglion and spinal cord. However, the underlying mechanism of this activation has not been elucidated clearlyObjective:The aim of this study is to perform the pharmacological studies on the basis of sciatic nerve-pinch mice model and explore the underlying mechanism involving SSTR2.Methods:On the basis of a sciatic nerve-pinch injury model, we aimed at comparing the painful behavior and dorsal root ganglion neurons neurochemical changes after the SSTR2 antibody (anti- SSTR2;5μl,1μg/ml) administration in the mouse.Results:After pinch nerve injury, we found that the mechanical hyperalgesia and severely painful behavior (autotomy) were detected after the application of SSTR2 antibody (anti-SSTR2; 5μl, 1μg/ml) on the pinch-injured nerve. The up-regulated phosphorylated ERK (p-ERK) expression and the apoptotic marker (i.e., Bax) were significantly decreased in DRGs after anti-SSTR2 treatment.Conclusion:The current data suggested that inhibitory changes in proteins from the apoptotic pathway in anti-SSTR2-treated groups might be taking place to overcome the protein deficits caused by SSTR2 antibody and supported the new therapeutic intervention with SSTR2 antagonist for neuronal degeneration following nerve injury.
Preventive Effects of Mallotus japonicus Cortex Extracts on Dextran Sulfate Sodium-Induced Ulcerative Colitis in C57 BL/6J Mice
Authors: Kimura Yoshiyuki 
Published: November 2019

Background:
The cortex of Mallotus japonicus (Euphorbiaceae) has traditionally been
used to treat gastric ulcers, duodenal ulcers, and gastric hyperacidity in Japan. A large number of
studies have recently focused on its effects on Inflammatory Bowel Disease (IBD).

Objective:
The aim of the present study was to examine the effects of M. japonicus (MJ) extracts on
large intestinal diarrhea and inflammation using Inflammatory Bowel Disease (IBD) mouse models.

Methods:
The present study used 3% Dextran Sulfate Sodium (DSS)-treated colitis models. Red
blood cell, platelet, and leukocyte counts in addition to hematocrit (Ht), hemoglobin (Hb), and colonic
cytokine and chemokine levels were measured in DSS-treated C57BL/6J mice during the experimental
period.

Results:
The Disease Activity Index (DAI) was lower in 3% DSS-treated mice orally administered
MJ (200 and 500 mg/kg) than in mice administered 3% DSS only. Furthermore, MJ inhibited decreases
in red blood cell and platelet counts as well as Hb and Ht levels in DSS-treated mice. Colon
histology using direct fast scarlet staining revealed that MJ prevented mucosal membrane ulceration
and eosinophil infiltration of the mucosal membrane induced by the DSS treatment. Increases in
colonic Monocyte Chemoattractant Protein 1 (MCP)-1, interleukin (IL)-1β, and Tumor Necrosis
Factor (TNF)-α levels in DSS-treated mice were reduced by orally administered MJ extracts.

Conclusion:
The present results suggest that M. japonicus cortex extracts are an effective treatment
for IBD through the inhibition of increases in colonic IL-1β, TNF-α, and MCP-1 levels and eosinophil
infiltration of the colon in DSS-treated mice.
Meningkatkan Kemampuan Menyanyikan Lagu Wajib Nasional dengan Metode Solfegio Di Sekolah Dasar
Authors: Destrinelli D , Wijayanti Mei Nur 
Published: November 2019

This research aimed at improving the capability of singing the National Anthems of the students of class IV of SDN 111/I Muara Bulian by employing the Solfegio method. The results of the research are expected to be useful for the development of musical science (singing) in particular, to be a reference for the next research and to be an additional information as well as consideration for either teachers or schools to employ the Solfegio method during learning musics (singing).This class action research employed Kemis and Mc. Taggart model using phases such as : planning, action, observing, and reflecting. The subject of the research was thirty four students of class IV SDN 111/I Muara Bulian. The data were collected through observation and dual analysis, i.e. the descriptive qualitative analysis and the simple statistics quantitative analysis. Based on the results of the research, it can be concluded that to improve the capability of singing the National Anthems of the Students of Class IV SDN 111/I Muara Bulian can be accomplished through carrying out the Solfegio method during class musics (singing) by practicing to sing: (1) the musical scale, (2) the interval tone, and (3) the melody.
Pengembangan Lembar Kerja Kelompok Berbasis Keterampilan Proses untuk Melatih Percaya Diri Siswa
Authors: Arsil A 
Published: November 2019

Tujuan pada penelitian ini adalah mengembangkan sebuah lembar kerja kelompok berbasis keterampilan proses untuk melatih percaya diri siswa yang valid, praktis dan efektif. Fokus pada muatan IPA kelas 5 sekolah dasar, subtema hubungan antar makhluk hidup dalam ekosistem, materi rantai makanan. Jenis penelitian yaitu R & D, menggunakan metode pengembangan Sugiyono 2015. Subjek penelitian adalah siswa kelas 5 SDN 17/I Rantau Puri Kabupaten Batanghari, Jambi. Hasil validasi lembar kerja kelompok melalui angket oleh ahli media, materi dan bahasa dalam kategori valid setelah dilakukan revisi. Hasil angket, juga menunjukkan respon positif (sangat baik) yang didapatkan dari guru terhadap penggunaan lembar kerja kelompok berbasis keterampilan proses sebesar 91,1% dan respon siswa sebesar 95,5%. Hasil observasi terhadap sikap percaya diri siswa telah mengalami peningkatan sebesar 71,43%. Kesimpulan bahwa pengembangan lembar kerja kelompok berbasis keterampilan proses telah memenuhi kriteria valid dan praktis dipergunakan pada proses pembelajaran muatan IPA kajian rantai makanan serta terbukti efektif dalam melatih dan meningkatkan kepercayaan diri siswa.

Kata Kunci : keterampilan proses, percaya diri