bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Docking of Natural Phenolic Compounds for the Screening of Urease Inhibitors
Authors: Kataria Ritu , Khatkar Anurag 
Published: April 2019

Background:Bacterial ureases have been the cause of various human and animal pathogenicity including hepatic encephalopathy, hepatic coma urolithiasis, gastric and peptic ulcers, pyelonephritis, and urinary catheter encrustation by the production of ammonia. Hence, in view of the side effects of existing drugs, there is a strong need to discover, more safe, effective and potent compounds for the treatment of infections caused by urease.Methods:For this purpose, several natural phenolic compounds have been screened by molecular modelling techniques, wherein the phenolic compounds were docked to the active site of Jack bean urease (PDB ID 3LA4) using the Schrodinger docking software.Results:The lead compounds were identified via in-silico screening technique where docking score, binding energy, ADME and toxicity data were considered to screen the lead compounds as compared with the available standard drugs. From the docking study of screened natural phenolic compounds, five compounds diosmin, morin, chlorogenic acid, capsaicin and resveratrol were selected based upon their better affinity towards the receptor and were considered for further wet lab studies.Conclusion:The in-silico results were confirmed by in vitro experiments by use of the Jack bean urease using Weatherburn method.
Intricate Regulation of Phosphoenolpyruvate Carboxykinase (PEPCK) Isoforms in Normal Physiology and Disease
Authors: Seenappa Venu , Joshi Manjunath B. , Satyamoorthy Kapaettu 
Published: April 2019

Background:The phosphoenolpyruvate carboxykinase (PEPCK) isoforms are considered as rate-limiting enzymes for gluconeogenesis and glyceroneogenesis pathways. PEPCK exhibits several interesting features such as a) organelle-specific isoforms (cytosolic and a mitochondrial) in vertebrate clade, b) tissue-specific expression of isoforms and c) organism-specific requirement of ATP or GTP as a cofactor. In higher organisms, PEPCK isoforms are intricately regulated and activated through several physiological and pathological stimuli such as corticoids, hormones, nutrient starvation and hypoxia. Isoform-specific transcriptional/translational regulation and their interplay in maintaining glucose homeostasis remain to be fully understood. Mounting evidence indicates the significant involvement of PEPCK isoforms in physiological processes (development and longevity) and in the progression of a variety of diseases (metabolic disorders, cancer, Smith–Magenis syndrome).Objective:The present systematic review aimed to assimilate existing knowledge of transcriptional and translational regulation of PEPCK isoforms derived from cell, animal and clinical models.Conclusion:Based on current knowledge and extensive bioinformatics analysis, in this review we have provided a comparative (epi)genetic understanding of PCK1 and PCK2 genes encompassing regulatory elements, disease-associated polymorphisms, copy number variations, regulatory miRNAs and CpG densities. We have also discussed various exogenous and endogenous modulators of PEPCK isoforms and their signaling mechanisms. A comprehensive review of existing knowledge of PEPCK regulation and function may enable identification of the underlying gaps to design new pharmacological strategies and interventions for the diseases associated with gluconeogenesis.
Axonopathy Likely Initiates Neuropathological Processes Via a Mechanism of Axonal Leakage in Alzheimer's Mouse Models
Authors: Gao Ge , He Jing , Luo Yi , Sun Yan , Zhou Yanping , Zhang Junxia , Xing Ying , Dai Jiapei 
Published: April 2019

Background:The formation of hyperphosphorylated tau and the production of β-amyloid are thought to be critical steps contributing to the pathological mechanisms in Alzheimer’s disease (AD). However, there has been a long-lasting debate over their importance in the onset of AD. Recent studies have demonstrated that axonopathy is considered as an early neuropathological change of AD. However, the exact relationship between the development of axonopathy and the classic neuropathological changes such as senile plaques (SPs) and neurofibrillary tangles (NFTs) is unclear.Objective:The aim of this study was to investigate whether the formation of SPs and NFTs is associated with the development of axonal leakage.Method and Results:Here we show that the formation and development of axonal leakage - a novel axonopathy is an age-dependent process, accompanied by swellings of axons and varicosities and associated with chronic oxidative stress induced by thiamine deficient (TD) diet in Kunming mice. In an APP/PS1 transgenic mouse model of AD, axonal leakage appears at 3 months, becomes more obvious at 6 months and severe, beyond 1 year. We also show that slight axonal leakage is related to the formation of hyperphosphorylated tau, but not plaques, and that only severe axonal leakage accompanied by the extensive swollen axons and varicosities, and overproduction of β-amyloid leads to the formation of SPs and hyperphosphorylated tau.Conclusion:These data provide an explanation of the common origin and development of SPs and NFTs, and suggest that axonal leakage might be a key event in the development of the neuropathological processes in AD.
Brain Stimulation in Obsessive-Compulsive Disorder (OCD): A Systematic Review
Authors: Rapinesi Chiara , Kotzalidis Georgios D. , Ferracuti Stefano , Sani Gabriele , Girardi Paolo , Del Casale Antonio 
Published: April 2019

Background:Obsessive-compulsive disorder (OCD) is a highly prevalent, severe, and chronic disease. There is a need for alternative strategies for treatment-resistant OCD.Objective:This review aims to assess the effect of brain stimulation techniques in OCD.Methods:We included papers published in peer-reviewed journals dealing with brain stimulation techniques in OCD. We conducted treatment-specific searches for OCD (Technique AND ((randomized OR randomised) AND control* AND trial) AND (magnetic AND stimulation OR (rTMS OR dTMS)) AND (obsess* OR compuls* OR OCD)) on six databases, i.e., PubMed, Cochrane, Scopus, CINAHL, PsycINFO, and Web of Science to identify randomised controlled trials and ClinicalTrials.gov for possible additional results.Results:Different add-on stimulation techniques could be effective for severely ill OCD patients unresponsive to drugs and/or behavioural therapy. Most evidence regarded deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS), while there is less evidence regarding transcranial direct current stimulation (tDCS), electroconvulsive therapy, and vagus nerve stimulation (for these last two there are no sham-controlled studies). Low-frequency TMS may be more effective over the supplementary motor area or the orbitofrontal cortex. DBS showed best results when targeting the crossroad between the nucleus accumbens and the ventral capsule or the subthalamic nucleus. Cathodal tDCS may be better than anodal in treating OCD. Limitations. We had to include methodologically inconsistent underpowered studies.Conclusion:Different brain stimulation techniques are promising as an add-on treatment of refractory OCD, although studies frequently reported inconsistent results. TMS, DBS, and tDCS could possibly find some use with adequate testing, but their standard methodology still needs to be established.
Non-Alcoholic Fatty Liver Disease Treatment in Patients with Type 2 Diabetes Mellitus; New Kids on the Block
Authors: Athyros Vasilios G. , Polyzos Stergios A. , Kountouras Jiannis , Katsiki Niki , Anagnostis Panagiotis , Doumas Michael , Mantzoros Christos S. 
Published: April 2019

Background:
Non-alcoholic fatty liver disease (NAFLD), affecting over 25% of the general
population worldwide, is characterized by a spectrum of clinical and histological manifestations ranging
from simple steatosis (>5% hepatic fat accumulation without inflammation) to non-alcoholic steatohepatitis
(NASH) which is characterized by inflammation, and finally fibrosis, often leading to liver cirrhosis,
and hepatocellular carcinoma. Up to 70% of patients with type 2 diabetes mellitus (T2DM) have
NAFLD, and diabetics have much higher rates of NASH compared with the general non-diabetic population.

Objective:
The aim of this study is to report recent approaches to NAFLD/NASH treatment in T2DM
patients. To-date, there are no approved treatments for NAFLD (apart from lifestyle measures).

Results:
Current guidelines (2016) from 3 major scientific organizations suggest that pioglitazone and
vitamin E may be useful in a subset of patients for adult NAFLD/NASH patients with T2DM. Newer
selective PPAR-γ modulators (SPPARMs, CHRS 131) have shown to provide even better results with
fewer side effects in both animal and human studies in T2DM. Newer antidiabetic drugs might also be
useful, but detailed studies with histological outcomes are largely lacking. Nevertheless, prior animal
and human studies on incretin mimetics, glucagon-like peptide-1 receptor agonists (GLP-1 RA) approved
for T2DM treatment, have provided indirect evidence that they may also ameliorate
NAFLD/NASH, whereas dipeptidyl dipeptidase-4 inhibitors (DDP-4i) were not better than placebo in
reducing liver fat in T2DM patients with NAFLD. Sodium-glucoseco-transporter-2 inhibitors (SGLT2i)
have been reported to improve NAFLD/NASH. Statins, being necessary for most patients with T2DM,
may also ameliorate NAFLD/NASH, and could potentially reinforce the beneficial effects of the newer
antidiabetic drugs, if used in combination, but this remains to be identified.

Conclusion:
Newer antidiabetic drugs (SPPARMs, GLP-1 RA and SGLT2i) alone or in combination
and acting alone or with potent statin therapy which is recommended in T2DM, might contribute substantially
to NAFLD/NASH amelioration, possibly reducing not only liver-specific but also cardiovascular
morbidity. These observations warrant long term placebo-controlled randomized trials with appropriate
power and outcomes, focusing on the general population and more specifically on T2DM with
NAFLD/NASH. Certain statins may be useful for treating NAFLD/NASH, while they substantially
reduce cardiovascular disease risk.
Study of Possible Relation between Fasting Plasma Glucagon, Gestational Diabetes and Development of Type 2 DM
Authors: Okba Ashraf , Hosny Salwa Seddik , Elsherbeny Alyaa , Kamal Manal Mohsin 
Published: April 2019

Background and Aims:
Women who develop GDM (gestational diabetes mellitus) have a
relative insulin secretion deficiency, the severity of which may be predictive for later development of
diabetes. This study aimed to investigate the role of fasting plasma glucagon in the prediction of later
development of diabetes in pregnant women with GDM.

Materials and Methods:
The study was conducted on 150 pregnant women with GDM after giving
informed oral and written consents and being approved by the research ethical committee according to
the declaration of Helsinki. The study was conducted in two phases, first phase during pregnancy and
the second one was 6 months post-partum, as we measured fasting plasma glucagon before and after
delivery together with fasting and 2 hour post-prandial plasma sugar.

Results:
Our findings suggested that glucagon levels significantly increased after delivery in the majority
14/25 (56%) of GDM women who developed type 2 DM within 6 months after delivery compared
to 6/20 (30%) patients with impaired fasting plasma glucose (IFG) and only 22/105 (20%) non
DM women, as the median glucagon levels were 80,76, 55, respectively. Also, there was a high statistical
difference between fasting plasma glucagon post-delivery among diabetic and non-diabetic
women (p ≤ 0.001). These results indicated the useful role of assessing fasting plasma glucagon before
and after delivery in patients with GDM to predict the possibility of type 2 DM.

Conclusion:
There is a relatively high glucagon level in GDM patients, which is a significant pathogenic
factor in the incidence of subsequent diabetes in women with a history of GDM. This could be
important in the design of follow-up programs for women with previous GDM.
Synthesis and Biological Evaluation of 5-benzyl-3-pyridyl-1H-1,2,4-triazole Derivatives as Xanthine Oxidase Inhibitors
Authors: Li Song-Ye , Zhang Ting-Jian , Wu Qing-Xia , Olounfeh Kamara M. , Zhang Yi , Meng Fan-Hao 
Published: April 2019

Background:
Topiroxostat is an excellent xanthine oxidase (XO) inhibitor, possessing a
specific 3,5-diaryl-1,2,4-triazole framework.

Objective:
The present work was aimed to investigate the preliminary structure-activity relationship
(SAR) of 2-cyanopyridine-4-yl-like fragments of topiroxostat analogues.

Methods:
A series of 5-benzyl-3-pyridyl-1H-1,2,4-triazole derivatives (1a-j and 2a-j) were designed
and synthesized by replacement of the 2-cyanopyridine-4-yl moiety with substituted benzyl
groups. XO inhibitory activity in vitro was evaluated. Furthermore, molecular modeling simulations
were performed to predict the possible interactions between the synthesized compounds and
XO binding pocket.

Results:
The SARs analysis demonstrated that 3,5-diaryl-1,2,4-triazole framework is not essential;
in spite of its lower potency, 5-benzyl-3-pyridyl-1H-1,2,4-triazole is an acceptable scaffold for XO
inhibitory activity to some extent. A 3′-nitro and a 4′-sec-butoxy group link to the benzyl moiety
will be welcome. Furthermore, the most promising compound, 1h, was identified with an IC50
value of 0.16 μM, and the basis of XO inhibition by 1h was rationalized through the aid of molecular
modelling studies.

Conclusion:
Compound 1h could be a lead compound for further investigation and the present
work may provide some insight into the search for more structurally diverse XO inhibitors with
topiroxostat as a prototype.
New Insights in Design and Development of Antitubercular Drugs
Authors: Yadav Snehlata , Narasimhan Balasubramanian 
Published: April 2019

Background:
Tuberculosis, an infectious disease caused mainly by the Mycobacterium
tuberculosis accounts for the highest number of deaths worldwide. Despite curing millions, the currently
used drug regimens are bounded by various limitations such as long course of therapy, emergence of
resistance and permanent tissue damage. The treatment of multidrug-resistant and extremely drugresistant
tuberculosis is a challenging task due to its reliance on second-line drugs which are less potent
and more toxic than those used in the clinical management of drug-susceptible tuberculosis. Therefore,
the major challenges in the upcoming years are to overcome the emergence of increased number of
multidrug-resistant as well as extensively drug-resistant strains and the ineptness of the current treatment
regimens against latent tuberculosis. Bedaquiline and Delamanid are the only new anti-TB drugs
that have been currently approved since more than 40 years after discovery of isoniazid. Bedaquiline is
the first diarylquinoline derivative that has showed resilient culture conversion at 24 weeks in phase IIb
trials.

Methods:
Extensive literature search on the topic was undergone using a focused question.

Results:
Fifty-eight research articles from journals of repute are included in the review. The vaccine and
peptide-based conjugates are recent developments against Mycobacterium for selective and specific
targeting to the desired tissues.

Conclusion:
In this review, we have focused on the different classes of chemical as well as plant based
compounds as potent antitubercular agents against multidrug-resistant tuberculosis strains. This review
falls light on the importance of research been undergoing in different parts of the world to combat the
ever increasing problem of mycobacterial resistance and the various treatment options available for the
treatment of tuberculosis.
Comparison of Different Extraction Methods for the Phenolic Compounds Recovery with the Antioxidant Activity of Bougainvillea x buttiana
Authors: Abarca-Vargas Rodolfo , Petricevich Vera L. 
Published: April 2019

Background:
Bougainvillea x buttiana has long been used as a Mexican conventional medicinal
drug to cure different sicknesses.

Objective:
In this work, the consequences of ethanol combination and temperature extraction for
phenolic compound recovery with the biological activity in Bougainvillea x buttiana extracts were
investigated.

Materials and Methods:
The phenolic recovery from Bougainvillea x buttiana was determined by
comparing the effects of ethanol 0%, 50-100% (v/v) and extraction temperature (26, 45 and 64°C).
The total phenolic content was investigated using spectrophotometric methods. Antioxidant activity
from different Bougainvillea x buttiana extracts was evaluated by determining their potential to scavenge
the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical. The chemical compositions and cytotoxic
effect of extracts were determined using GC-MS techniques and the crystal violet technique,
respectively.

Results:
Our results confirmed that all extractions with different concentrations and temperatures had
significant effects over the total phenolic contents and antioxidant activity (DPPH) of the extracts.
The best recuperation of the total phenol content was observed in extracts with 60% ethanol at 26°C
(201.08 mgEGA/g dry extract). Extracts with 100% ethanol at 26°C showed the highest antioxidant
activity (IC50 was 286.75 μg/mL). GC-MS revealed the presence of various phytochemical contents
with polar and non-polar properties. The phenolic compounds were investigated as to the structure,
quantity and position of the hydroxyl groups on the benzene ring.

Conclusion:
The ethanolic extract of Bougainvillea x buttiana was confirmed to have high phenolic
content and contain pharmacologically active compounds, with potent antioxidant effects and low cytotoxic
effects.
Triphenylethylene-Coumarin Hybrid TCH-5c Suppresses Tumorigenic Progression in Breast Cancer Mainly Through the Inhibition of Angiogenesis
Authors: Cui Naipeng , Lin Dan-Dan , Shen Yang , Shi Jian-Guo , Wang Bing , Zhao Ming-Zhi , Zheng Lishuang , Chen Hua , Shi Jian-Hong 
Published: April 2019

Background:
Coumarins are a wide group of naturally occurring compounds which exhibit a wide range
of biological properties such as anti-cancer activities. Here, we characterized the biological functions of three
Triphenylethylene-Coumarin Hybrids (TCHs) both in cell culture and nude mouse model.

Methods:
Cell proliferation assay was performed in the cell cultures of both EA.hy926 endothelial cell and breast
cancer cell lines treated with different concentrations of compound TCH-10b, TCH-5a and TCH-5c. Flowcytometry
assay and Western blotting were used to further investigate the effect and mechanism of TCH-5c on EA.hy926
cell proliferation and cell cycle. The effects of TCH-5c on endothelial cell migration and angiogenesis were determined
using cytoskeleton staining, migration assay and tube formation assay. Inhibition of breast cancer cell line
derived VEGF by TCH-5c was shown through ELISA and the use of conditioned media. SK-BR-3 xenograft mouse
model was established to further study the anti-tumorigenic role of compound TCH-5c in vivo.

Results:
We found that compound TCH-5c has inhibitory effects on both vascular endothelial cells and breast cancer
cell lines. Compound TCH-5c inhibited proliferation, resulted in cell death, increased p21 protein expression to
induce G0/G1 arrest and changed endothelial cell cytoskeleton organization and migration in EA.hy926 endothelial
cells. Compound TCH-5c also inhibited breast cancer cell line derived VEGF secretion, decreased breast cancer
cell-induced endothelial cell tube formation in vitro and suppressed SK-BR-3 breast cancer cell-initiated tumor
formation in vivo.

Conclusion:
Our study demonstrates that the coumarin derivative TCH-5c exerts its anti-cancer effects by 1. inhibiting
endothelial cell proliferation, migration. 2. suppressing tube formation and angiogenesis induced by breast
cancer cells in vitro and in vivo. Our results have potential implications in developing new approaches against breast
cancer.
Novel Thiazine Substituted 9-Anilinoacridines: Synthesis, Antitumour Activity and Structure Activity Relationships
Authors: Kalirajan R. , Gaurav K. , Pandiselvi A. , Gowramma B. , Sankar S. 
Published: April 2019

Background:
9-anilinoacridines are acting as DNA-intercalating agents which plays an important
role as antitumor drugs, due to their anti-proliferative properties. Some anticancer agents contain 9-
anilinoacridines such as amsacrine (m-AMSA), and nitracrine (Ledakrine) have been already developed.

Methods:
In this study, novel 9-anilinoacridines substituted with thiazines 4a-r were designed, synthesized,
characterized by physical and spectral data and their cytotoxic activities against DLA cell lines were evaluated.

Results:
Among those compounds, 4b, c, e, g, i, j, k, m, o, p, q, r exhibited significant short term in vitro cytotoxic
activity against Daltons lymphoma ascites (DLA) cells with CTC50 value of 0.18 to 0.31μM. The compounds
4b, c, e, g, i, j, k, m, o, p, q, r are also exhibited significant long term in vitro anti-tumour activity
against human tumor cell lines, HEp-2 (laryngeal epithelial carcinoma) by Sulforhodamine B assay with CTC50
value of 0.20 to 0.39μM. The compounds 4b, i, j exhibited significant in vivo antitumor activity with % Increase
in Life Span (ILS) 48-82%.

Conclusion:
Results obtained in this study clearly demonstrated that many of the thiazine substituted 9-
anilinoacridines exert interesting anti-tumour activity. The compounds 4b, i, j have significant anti-tumour
activity and useful drugs after further refinement. The above derivatives will encourage to design future antitumor
agents with high therapeutic potentials.
Fluoroquinolones and the Risk of Aortic Aneurysm or Aortic Dissection: A Systematic Review and Meta-Analysis
Authors: Rawla Prashanth , El Helou Marie Line , Vellipuram Anantha R. 
Published: April 2019

Objective:
We performed a systematic review and meta-analysis to explore the risk of an
aortic aneurysm or aortic dissection following fluoroquinolone administration.

Methods:
PubMed, Cochrane library, ClinicalTrials.gov, Embase and Google Scholar were systematically
reviewed for controlled studies including adult patients exposed to fluoroquinolones with a
primary outcome of aortic aneurysm or aortic dissection.

Results:
The meta-analysis was conducted by pooling the effect estimates of four controlled observational
studies (one case-control, one case-crossover and two cohort studies). Fluoroquinolone administration
more than doubled the risk to develop aortic aneurysm or aortic dissection within 60 days
following fluoroquinolone exposure (adjusted Relative Risk [RR] (95% confidence interval [CI]) =
2.14 (1.93 - 2.36); I2 = 15.8%). The quality of the finding was rated as moderate.

:
The risk increase for aortic aneurysm alone was found to be significant (adjusted RR (95% CI) =
2.23 (2.01 - 2.45); I2 = 0%) while the risk increase for aortic dissection alone was not found to be
significant (adjusted RR = 1.88 (0.11 - 3.65); I2 = 74%).

:
In subgroup analysis, the risk increase for aortic aneurysm or aortic dissection appeared to be higher
in females compared to males (RR = 1.87 (1.24 - 2.51); I2 = 0% versus RR = 1.58 (1.25 - 1.92); I2 =
0%, respectively) and higher in older patients compared to younger patients (RR = 1.72 (1.37 - 2.07);
I2 = 0% versus RR = 1.47 (0.91 - 2.04); I2 = 0%, respectively).

:
Subgroup analysis of two studies which measured the duration-response analysis found that as the
duration of fluoroquinolone therapy increased from 3 to 14 days to greater than 14 days, there was an
increased risk of aortic aneurysm or dissection.

Conclusion:
The findings of this meta-analysis confirm the positive association between fluoroquinolones
and the development of aortic aneurysm or dissection. The data tend to show that this association
may be majorly driven by aortic aneurysm. Additionally, some risk factors appear to prevail including
prolonged fluoroquinolone treatment and older age.