bluuebunny/crossref_metadata_2025_split huggingface dataset:
VITPOR AI, A Coagulation Factor XIIa Inhibitor from Porphyra yezoensis: In Vivo Mode of Action and Assessment of Platelet Function Analysis
Authors: L. Venkatraman Kalkooru , A. Syed Azeemullah , Indumathi Parimelazhagan , Mehta Alka 
Published: November 2019

Background:
Thrombosis represents as the prime contributor to the burden of diseases,
worldwide. Conventional anticoagulants for thrombosis therapy have a common bleeding side
effect. Bioactive peptides are studied to be an effective alternative for currently available
therapeutic drugs.

Objective:
In this study, VITPOR AI peptide, a previously reported coagulation FXIIa inhibitor
from Nori (Porphyra yezoensis), was assessed for its inhibitory activity against FXIIa and its in
vivo mode of action.

Methods:
In vivo efficacy as well as the antithrombotic property of the peptide was evaluated in
mice model by ex vivo activated Partial Thromboplastin Time assay, tail transection model and
whole blood clotting time. The enzyme kinetics was studied using chromogenic substrate assay.

Results:
The kinetic behaviour of VITPOR AI showed that the peptide is a competitive inhibitor of
FXIIa. Peptide showed significant inhibition of platelet adhesion and aggregation. VITPOR AI
exhibited significant antithrombotic activity. Furthermore, ex vivo activated Partial Thromboplastin
Time assay revealed that VITPOR AI exhibited potent anticoagulant activity in vivo. Tail bleeding
assay revealed that the peptide did not prolong bleeding time in mice even at a higher dose of
5 mg/kg. Cytotoxicity studies of the peptide against human blood leukocytes indicated the safety of
the peptide.

Conclusion:
VITPOR AI could be prospected as a potent anticoagulant with Factor XIIa inhibition,
antiplatelet aggregation and antithrombotic activity. It was also studied to have no bleeding side
effect.
Tweaking α-Galactoceramides: Probing the Dynamical Mechanisms of Improved Recognition for Invariant Natural Killer T-cell Receptor in Cancer Immunotherapeutics
Authors: Washah Houda , Agoni Clement , Olotu Fisayo A. , Munsamy Geraldene , Soliman Mahmoud E.S. 
Published: November 2019

Background:The last few decades have witnessed groundbreaking research geared towards immune surveillance mechanisms and have yielded significant improvements in the field of cancer immunotherapy. This approach narrows down on the development of therapeutic agents that either activate or enhance the recognitive function of the immune system to facilitate the destruction of malignant cells. The α -galactosylceramide derivative, KRN7000, is an immunotherapeutic agent that has gained attention due to its pharmacological ability to activate CD1d-restricted invariant natural killer T(iNKT) cells with notable potency against cancer cells in mouse models; a therapeutic success was not well replicated in human models. Dual structural modification of KRN7000 entailing the incorporation of hydrocinnamoyl ester on C6" and C4-OH truncation of the sphingoid base led to the development of AH10-7 which, interestingly, exhibited high potency in human cells.Objective/Methods:Therefore, to gain molecular insights into the structural dynamics and selective mechanisms of AH10-7 for human variants, we employed integrative molecular dynamics simulations and thermodynamic calculations to investigate the inhibitory activities of KRN7000 andAH10-7 on hTCR-CD1d towards activating iNKT.Results:Interestingly, our findings revealed that AH10-7 exhibited higher affinity binding and structural effects on hTCR-CD1d, as mediated by the incorporated hydrocinnamoyl ester moiety which accounted for stronger intermolecular interactions with ‘non-common’ binding site residues.Conclusions:Findings extracted from this study further reveal important molecular and structural perspectives that could aid in the design of novel α-GalCer derivatives for cancer immunotherapeutics.
C-reactive Protein, Infection, and Outcome After Acute Ischemic Stroke: A Registry and Systematic Review
Authors: Wang Lu , Li Yuxiao , Wang Changyi , Guo Wen , Liu Ming 
Published: November 2019

Background:
A number of studies have explored the prognostic role of CRP in patients
with acute ischemic stroke, however, the results have been inconclusive. The aim of our study was
to investigate the impact of infection on the association between CRP and 3-month functional outcome
by performing a registry study and systematic review.

Methods:
Patients admitted within 24 hours of acute ischemic stroke onset and had CRP measured
within 24 hours after admission were included. Patients admitted between June 2016 and December
2018 in Chengdu Stoke Registry were enrolled. The PubMed database was searched up to July
2019 to identify eligible studies. Poor outcome was defined as modified Rankin Scale scores at
3-month more than 3.

Results:
Totally, 368 patients in the registry and 18 studies involving 15238 patients in the systematic
review were included. A statistically significant association between CRP values on admission
and 3-month poor outcome in patients without infection was found, both in our registry
(CRP per 1-mg/L increment, OR 1.04, 95% CI 1.01 to 1.07, p=0.008) and meta-analysis (CRP per
1-mg/dL increment, OR 1.66 [95% CI 1.37 to 2.01, p<0.001]). In patients with infection, CRP was
not associated with a 3-month poor outcome according to registry data (OR 1.00, 95% CI 0.99 to
1.01, p=0.663) and meta-analysis (OR 1.01, 95% CI 0.99 to 1.01, p=0.128).

Conclusion:
High CRP value was independently associated with a 3-month poor outcome after
stroke in patients without infection. Further studies are required to examine the value of infection
on CRP measures and long-term functional outcomes.
Well-defined Graphene Oxide as a Potential Component in Lung Cancer Therapy
Authors: Zuchowska Agnieszka , Jastrzebska Elzbieta , Mazurkiewicz-Pawlicka Marta , Malolepszy Artur , Stobinski Leszek , Trzaskowski Maciej , Brzozka Zbigniew 
Published: November 2019

Background:
Graphene oxide (GO) has unique physical and chemical properties that can
be used in anticancer therapy - especially as a drug carrier. Graphene oxide, due to the presence of
several hybrid layers of carbon atoms (sp2), has a large surface for highly efficient drug loading. In
addition, GO with a large number of carboxyl, hydroxyl and epoxy groups on its surface, can charge
various drug molecules through covalent bonds, hydrophobic interactions, hydrogen bonds and electrostatic
interactions.

Objective:
The aim of our work was to evaluate the possibility of future use of graphene oxide as an
anticancer drug carrier.

Method:
In this paper, we present GO synthesis and characterization, as well as a study of its biological
properties. The cytotoxic effect of well-defined graphene oxide was tested on both carcinoma
and non-malignant cells isolated from the same organ, which is not often presented in the literature.

Results:
The performed research confirmed that GO in high concentrations (> 300 µgmL-1) selectively
decreased the viability of cancer cell line. Additionally, we showed that the GO flakes have a
high affinity to cancer cell nucleus which influences their metabolism (inhibition of cancer cell proliferation).
Moreover, we have proved that GO in high concentrations can cause cell membrane
damage and generate reactive oxygen species on a low level mainly in cancer cells.

Conclusion:
The proposed GO could be useful in anticancer therapy. A high concentration of GO
selectively causes the death of tumor cells, whereas GO with low concentration could be a potential
material for anticancer drug loading.
Rosmarinic Acid as a Potent Influenza Neuraminidase Inhibitor: In Vitro and In Silico Study
Authors: Mahalapbutr Panupong , Sangkhawasi Mattanun , Kammarabutr Jirayu , Chamni Supakarn , Rungrotmongkol Thanyada 
Published: November 2019

Background:
Neuraminidase (NA), a major glycoprotein found on the surface of the influenza
virus, is an important target for the prophylaxis and treatment of influenza virus infections. Recently,
several plant-derived polyphenols, especially caffeic acid analogs, have been reported to exert
the inhibitory activity against NA.

Objective:
Herein, we aimed to investigate the anti-influenza NA activity of caffeic acid and its hydroxycinnamate
analogues, rosmarinic acid and salvianolic acid A, in comparison to a known NA inhibitor,
oseltamivir.

Methods:
In vitro MUNANA-based NA inhibitory assay was used to evaluate the inhibitory activity of
the three interested hydroxycinnamic compounds towards the influenza NA enzyme. Subsequently, allatom
molecular dynamics (MD) simulations and binding free energy calculations were employed to elucidate
the structural insights into the protein-ligand complexations.

Results:
Rosmarinic acid showed the highest inhibitory activity against NA with the IC50 of 0.40 μM
compared to caffeic acid (IC50 of 0.81 μM) and salvianolic acid A (IC50 of >1 μM). From 100-ns MD
simulations, the binding affinity, hot-spot residues, and H-bond formations of rosmarinic acid/NA complex
were higher than those of caffeic acid/NA model, in which their molecular complexations was
driven mainly by electrostatic attractions and H-bond formations from several charged residues (R118,
E119, D151, R152, E227, E277, and R371). Notably, the two hydroxyl groups on both phenyl and
phenylacetic rings of rosmarinic acid play a crucial role in stabilizing NA through a strongly formed Hbond(
s).

Conclusion:
Our findings shed light on the potentiality of rosmarinic acid as a lead compound for further
development of a potential influenza NA inhibitor.
Effectiveness of Passion Fruit Peel Flour (Passiflora edulis L.) versus Turmeric Flour (Curcuma longa L.) on Glycemic Control: Systematic Review and Meta-Analysis
Authors: Sousa Danilo F. , Veras Vivian S. , Freire Vanessa E.C.S. , Paula Maria L. , Serra Maria A.A.O. , Costa Ana C.P.J. , da Conceição S.O. Cunha Maria , Queiroz Maria V.O. , Damasceno Marta M.C. , Paes Francisco E.R. , Freitas Roberto W.J.F. , Araújo Márcio F.M. 
Published: November 2019

Background::
It is undeniable that diabetes may cause several health complications for the
population. Many of these complications are associated with poor glycemic control. Due to this, strategies
to handle this problem are of great clinical importance and may contribute to reducing the various
complications from diabetes.

Objective: :
The aim of this study was to compare the effectiveness of the passion fruit peel flour versus
turmeric flour on glycemic control.

Methods:
This is a systematic review and meta-analysis following the PRISMA protocol. The following
inclusion criteria were applied: (1) Case-control studies, cohort studies, and clinical trials, due to the
improved statistical analysis and, in restrict cases, cross-sectional studies; (2) Articles published in any
language. The databases used for the search were PubMed, Scopus, Web of Science, Cochrane, and LILACS.
A bias analysis and a meta-analyses were undertaken using R Studio (version 3.3.1) using effect-
size models.

Results: :
A total of 565 studies were identified from which 11 met the inclusion and exclusion criteria.
Through isolated analysis, the effectiveness of turmeric flour on glycemic control was in the order of
0.73 CI (Confidence Interval) (from 0.68 to 0.79) and the effectiveness of passion fruit peel flour was
0.32 CI (0.23 to 0.45). The joint analysis resulted in 0.59 CI (0.52 to 0.68). The assessment of blood
glucose was by glycated hemoglobin levels. All values were significant at a p < 0.05 level.

Conclusion:
Both interventions showed significant effects on glycemic control.
Anticholinesterase and Antioxidant Activities of Spilanthes filicaulis Whole Plant Extracts for the Management of Alzheimer’s Disease
Authors: Elufioye Taiwo O. , Unachukwu Cynthia C. , Oyedeji Adebola O. 
Published: November 2019

Background:Spilanthes filicaulis is a tropical herb implicated as a memory enhancer in ethnomedicine.Objective:The study investigated acetyl/butyryl cholinesterase inhibitory and antioxidant activities of different extracts of S. filicaulis whole plant and correlated them to its phytochemical constituents.Methods:The powdered whole plant was successively extracted with n-hexane, ethyl acetate and methanol. Acetyl cholinesterase (AChE) and Butyryl cholinesterase (BuChE) inhibitory activity were evaluated by Ellman colorimetry assay. Antioxidant activity was tested using 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, ferric reducing power and nitric oxide scavenging assays. Total phenolic, flavonoid and tannin were estimated using standard methods. Correlation was determined using Quest Graph™ Regression Calculator.Results:Various extracts exhibited concentration-dependent AChE and BuChE inhibitory activity with ethyl acetate extract being the highest with IC50 of 0.77 μg/mL and 0.92 μg/mL for AChE and BuChE respectively. The ethyl acetate extract also showed the highest reducing power when compared with the other extracts. The methanol extract had slightly higher phenolic and flavonoid content and showed the highest DPPH radical scavenging effect. DPPH scavenging, AChE and BuChE inhibition had high correlation with the total flavonoid content with R2 values of 1.00, 0.800 and 0.992 respectively while nitric oxide scavenging had high correlation with phenolics and tannins with R2 = 0.942 and 0.806 respectively.Conclusion:These results show that the extracts of the whole plant of S. filicaulis possess significant AChE/BuChE inhibitory and antioxidant properties, mostly due to its flavonoid content, suggesting the possible use of the plant in neurodegenerative diseases such as AD.
Dose and Sequence Dependent Synergism from the Combination of Oxaliplatin with Emetine and Patulin Against Colorectal Cancer
Authors: Alam Md. Nur , Yu Jun Q. , Beale Philip , Huq Fazlul 
Published: November 2019

Background:
Colorectal cancer is the third most commonly diagnosed cancer in the world, causing
many deaths every year. Combined chemotherapy has opened a new horizon in treating colorectal cancer. The
objective of the present study is to investigate the activity of oxaliplatin in combination with emetine and patulin
against colorectal cancer models.

Methods:
IC50 values of oxaliplatin, emetine and patulin were determined against human colorectal cancer cell
lines (HT-29 and Caco-2) using MTT reduction assay. Synergistic, antagonistic and additive effects from the
selected binary combinations were determined as a factor of sequence of administration and added concentrations. Proteomics was carried out to identify the proteins which were accountable for combined drug action applying to the selected drug combination.

Results:
Oxaliplatin in combination with patulin produced synergism against human colorectal cancer models
depending on dose and sequence of drug administration. Bolus administration of oxaliplatin with patulin proved
to be the best in terms of synergistic outcome. Altered expressions of nine proteins (ACTG, PROF1, PPIA,
PDIA3, COF1, GSTP1, ALDOA, TBA1C and TBB5) were considered for combined drug actions of oxaliplatin
with patulin.

Conclusion:
Bolus administration of oxaliplatin with patulin has the potential to be used in the treatment of
colorectal cancer, and would warrant further evaluation using suitable animal model.
Hydrophobization of Kraft-type Cellulose and Microfiber Cellulose Obtained from Soybean Husk in Ultrasonic Field
Authors: Mejia Blanca I.M. , Kharissova Oxana V. , Kharisov Boris I. 
Published: November 2019

Background:
The addition of nanoparticles to cellulose paper can improve its mechanical
strength, chemical stability, biocompatibility and hydrophobic properties. Silica nanoparticles are known
to be inert, hydrophobic, biocompatible, biodegradable and have a good distribution in being deposited on
surfaces. The main characteristics of 20 nm SiO2 nanoparticles are good chemical and thermal stability
with a melting point of 1610-1728°3C, a boiling point of 2230°C with a purity of 99.5%.

Objective:
To carry out the hydrophobization of paper based on Kraft cellulose and on cellulose obtained
from soybean husk with 20-nm size SiO2 nanoparticles and to study hydrophobicity, morphology
and topography of the prepared composites.

Methods:
The ground and roasted soybean husk was treated with a NaOH, washed and dried. Hydrophobization
of paper was carried in aqueous medium by SiO2 addition in weight ratios “paper-SiO2” of
0.01-0.05 wt.%, stirring, filtration and drying. The obtained cellulose sheet composites were characterized
by Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), FTIRspectroscopy,
Mullen proofs of hydrophobicity, and contact angle measurements.

Results:
The mechanical properties of paper nanocomposites (tensile strength and compression) increased
considerably by varying the concentrations. The tensile strength increased by 41-46% and the
compressive strength increased by 55-56%. The existence of fiber nanofoils, good adhesion of 20-nm
SiO2 nanoparticles to the paper surface, and their homogeneous distribution were observed.

Conclusion:
Cellulose was successfully obtained from soybean husk, applying the alkaline-based extraction
method. A good reinforcement of cellulose fibers is observed due to the outstanding characteristics
of the silicon dioxide nanoparticles.
The Mechanical Alloying of Magnetite Concentrate with Biochar
Authors: Öztürk Elif Aranci , Boyrazli Mustafa , Turan Mehmet Deniz , Erdemoğlu Murat 
Published: November 2019

Aim:In this work, the effect of milling time on the mechanical alloying of the mixture containing the magnetite concentrate and biomass waste was investigated.Materials and Methods:The ore’s grade consisting of hematite and magnetite minerals was increased from 49.87% Fe to 67.29% Fe using the low intensity wet magnetic separator. Biomass waste which was supplied from ÇAYKUR black tea facilities, used as a carbon source was subjected to carbonization processes at 800°C for 1440 min. After the carbonization process, the carbon and sulphur contents of the biomass were measured as 94.68% and 0.03%, respectively. For the mechanical alloying process, a mixture consisting of magnetite concentrate with a grain size of -45 μm and biomass which was added two times the amount of carbon required for the reduction of magnetite to metallic iron was used.Result:After the mechanical alloying process which was carried out at different times, it was observed in the particle size analysis that the particle size of 90% of the mixture was reduced to about 4 μm. In SEM (Scanning Electron Microscopy) images, cube-like particles along with the spherical particles were observed depending on the mechanical alloying times. After 45 minutes of alloying, it was observed that the carbonized product milled together with magnetite concentrate was partially integrated into the crystal structure.Conclusion:The carbonized tea plant waste milled together with magnetite concentrate was partially integrated into the crystal structure. And the mechanical alloying provide to increase in the specific surface area in parallel with the grain size decrease in the study. Thus, in the later stage of the study, the milled powder acquired more ability to react.
Chitosan-induced Synergy for Extended Antimicrobial Potency and Enhanced In Vitro Drug Release of Free Base Ciprofloxacin Nanoplexes
Authors: Abioye Amos , Sanyaolu Adekunle , Dudzinska Paulina , Adepoju-Bello Aderonke Ayinke , Coker Herbert A.B. 
Published: November 2019

Background:
Ciprofloxacin free base is practically insoluble in aqueous medium
(0.0011 and 0.09 mg/mL at 25 and 37°C respectively). Its inorganic salt form (ciprofloxacin
hydrochloride) is more soluble in water (1.35 mg/mL) however when administered orally,
it exhibits decreased solubility in the stomach due to common ion effects. Ciprofloxacin
free base was used in this study because of its greater hydrophobicity than its hydrochloride
salt, which is required for effective permeability and potent antibacterial activity.

Objective:
The purpose of this study is to enhance oral solubility and bacterial cell permeability
of the free base ciprofloxacin (CPX) using a single step CPX-chitosan (CT) selfassembly
to form nanoplexes with organic counterions. It was envisioned that this would
allow the delivery of larger amounts of active drug into the microorganisms.

Methods:
Ciprofloxacin-chitosan nanocomplex (nanoplex) was prepared using low energy
electrostatic self-assembly technique previously described. Formation of eutectic nanoplex
was confirmed using FTIR, DSC, TGA and SEM. The saturated solubility, in vitro release
kinetics and mechanism of drug release were determined using mathematical models. Potency
and synergism were determined from the inhibition zones, minimum inhibitory concentration
(MIC) and Fractional Inhibitory Concentration (FIC) of the nanoplexes using
Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus.

Results:
Formation of CPX-CT eutectic adduct polymeric nanoplexes was confirmed with
FT-IR and DSC and SEM revealed the conversion of rod-like crystals of CPX (117 μm
long) into spherical nanostructures (23-503 nm) dictated by pH, ionic strength and concentration
of CT. The solubility of free base CPX increased to a maximum of 32.77 mg/mL
compared to 0.0011-0.09 mg/mL reported in literature and dissolution efficiency increased
to a maximum of 100% within 72 h. The synergistic effect of CT on antimicrobial activity
of CPX was quantified, for the first time, using Fractional Inhibitory Concentration (FIC)
of the nanoplexes. FIC was less than 0.5 in both Gram positive (0.031-0.250) and Gram
negative (0.036-0.281) microorganisms used in this study, confirming synergistic enhancement
of antimicrobial efficacy of CPX.

Conclusion:
It is evident that the design of drug-polymer nanocomplex formulation provides
a platform for the synergistic enhancement of therapeutic potency of antibiotics.
Clinical Impact of Gastric Acid Suppressants Use on the Efficacy of Gefitinib in Patients with Advanced Adenocarcinoma of the Lung Harboring Common EGFR Mutations
Authors: Kwok Wang Chun , Man Ho James Chung , Leung Lam David Chi , Sze Lui Macy Mei , Man Ip Mary Sau , Chun Tam Terence Chi 
Published: November 2019

Background:
Gefitinib was approved by the Food and Drug Administration (FDA) of the
United States (US) for the treatment of advanced non-small cell carcinoma harboring sensitizing epidermal
growth factor receptor (EGFR) mutations. The use of gastric acid-suppressing medication inhibits
gefitinib absorption and reduces its plasma concentration, but retrospective studies on whether
there is the corresponding repercussion on progression-free survival (PFS) have yielded variable results,
mainly due to heterogeneity in study cohorts and study designs.

Objectives:
To assess the clinical impact of the use of gastric acid-suppressing medication in patients
on first-line gefitinib for NSLC harboring common EGFR mutation.

Methods:
This is a retrospective cohort study conducted in a single, tertiary referral center in Hong
Kong S.A.R., which included 193 Chinese patients with advanced adenocarcinoma of lung harboring
common sensitizing EGFR mutations who received gefitinib as the first-line treatment. The progression-
free survival (PFS) and overall survival (OS) for patients who took gastric acid-suppressing
agents, namely histamine-2 receptor antagonists (H2RA) or proton pump inhibitors (PPI), were compared
with those who did not take such medication (control group).

Results:
Despite the universal practice to separate the medicating time of gastric acid suppressants
and EGFR-TKIs by 12 hours, patients who were on gastric acid suppressants had significantly shorter
PFS, especially for those on proton pump inhibitor (Median 368 vs. 189 vs. 166 days - For control,
H2RA group and PPI group respectively, p-value <0.001). The OS is also significantly shorter for
those taking gastric acid suppressants (Median 825 vs. 485 vs. 422 days - For control, H2RA group
and PPI group respectively, p-value <0.001).

Conclusions:
The co-administration of gastric acid suppressants with gefitinib is associated with
shorter progression-free survival and overall survival.