bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacophore & QSAR Guided Design, Synthesis, Pharmacokinetics
and In vitro Evaluation of Curcumin Analogs for Anticancer Activity
Authors: Alam Sarfaraz , Verma Surjeet , Fatima Kaneez , Luqman Suaib , Srivastava Santosh Kumar , Khan Feroz 
Published: May 2023

Background:
As a part of our discovery of plant-based lead molecules, we provide a
helpful tool, which helps in identification, designing, optimising, structural modifications, and prediction
of curcumin, to discover novel analogs with enhanced bioavailability, pharmacologically
safe, and anticancer potential.

Methods:
QSAR (Quantitative structure-activity relationship) and pharmacophore mapping models
were developed and further used to design, synthesize, pharmacokinetics, and in vitro evaluation of
curcumin analogs for anticancer activity.

Results:
The QSAR model yielded a high activity-descriptors relationship accuracy (r2) of 84%, a
high activity prediction accuracy (rcv2) of 81%, and external set prediction accuracy of 89%. The
QSAR study indicates that the five chemical descriptors were significantly correlated with anticancer
activity. The important pharmacophore features identified were a hydrogen bond acceptor, a
hydrophobic centre, and a negative ionizable centre. The model's predictive ability was evaluated
against a set of chemically synthesized curcumin analogs. Among the tested compounds, nine curcumin
analogs were found with IC50 values of 0.10 to 1.86 μg/mL. The active analogs were assessed
for pharmacokinetics compliance. EGFR was identified as a potential target of synthesized
active curcumin analogs through docking studies.

Conclusion:
Integrating in silico design, QSAR-driven virtual screening, chemical synthesis, and
experimental in vitro evaluation may lead to the early discovery of novel and promising anticancer
compounds from natural sources. The developed QSAR model and common pharmacophore generation
were used as a designing and predictive tool to develop novel curcumin analogs. This study
may help optimize the therapeutic relationships of studied compounds for further drug development
and their potential safety concerns. This study may guide compound selection and designing
novel active chemical scaffolds or new combinatorial libraries of the curcumin series.
Antibacterial Effects of Nanocomposites on Efflux Pump Expression and
Biofilm Production in Pseudomonas aeruginosa: A Systematic Review
Authors: Shakib Pegah , Saki Reza , Marzban Abdolrazagh , Goudarzi Gholamreza , Ghotekar Suresh , Cheraghipour Kourosh , Zolfaghari Mohammad Reza 
Published: May 2023

Background:
Pseudomonas aeruginosa is an opportunistic gram-negative pathogen
with multiple mechanisms of resistance to antibiotics.

Aim:
This systematic review aimed to study the antibacterial effects of nanocomposites on efflux
pump expression and biofilm production in P. aeruginosa.

Methods:
The search was conducted from January 1, 2000, to May 30, 2022, using terms such as
(P. aeruginosa) AND (biofilm) AND (antibiofilm activity) AND (anti-Efflux Pump Expression
activity) AND (nanoparticles) AND (Efflux Pump Expression) AND (Solid Lipid NPS) AND
(Nano Lipid Carriers). Many databases are included in the collection, including ScienceDirect,
PubMed, Scopus, Ovid, and Cochrane.

Results:
A list of selected articles was retrieved by using the relevant keywords. A total of 323
published papers were selected and imported into the Endnote library (version X9). Following the
removal of duplicates, 240 were selected for further processing. Based on the titles and abstracts of
the articles, 54 irrelevant studies were excluded. Among the remaining 186 articles, 54 were included
in the analysis because their full texts were accessible. Ultimately, 74 studies were selected
based on inclusion/exclusion criteria.

Conclusion:
Recent studies regarding the impact of NPs on drug resistance in P. aeruginosa found
that various nanostructures were developed with different antimicrobial properties. The results of
our study suggest that NPs may be a feasible alternative for combating microbial resistance in P.
aeruginosa by blocking flux pumps and inhibiting biofilm formation.
Aspartate β-hydroxylase (ASPH) Accelerates Intrahepatic Cholangiocarcinoma
Metastasis via Upregulating SHH Signaling Pathway
Authors: Zou Yiran , Lin Jianbo , Liu Jian , Zhang Fabiao , Yang Tingsong , Gong Jian , Jiang Tao , Zuo Jieliang , Song Ruimei , Shen Hao , Shen Feng , Li Jun 
Published: May 2023

Background:
Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy
with a poor prognosis. Aspartate β-hydroxylase (ASPH) is an α-ketoglutarate-dependent dioxygenase
involved in the post-translational hydroxylation of target proteins. ASPH has been demonstrated to be
upregulated in ICC, yet its role remains to be elucidated. This study aimed to investigate the potential
function of ASPH in ICC metastasis.

Methods:
Survival curves for the overall survival of pan-cancer data from The Cancer Genome Atlas
(TCGA) database was depicted using the Kaplan-Meier method and compared using the log-rank test.
The expression of ASPH, glycogen synthase kinase (GSK)-3β, phosphorylation GSK-3β (p-GSK-3β),
epithelial-mesenchymal transition (EMT) biomarkers, and sonic hedgehog (SHH) signaling elements
in ICC cell lines was analyzed by western blot. Wound healing and transwell assays were conducted to
examine the effects of ASPH knockdown and overexpression on cell migration and invasion. An immunofluorescence
assay was conducted to evaluate the expression of glioma-associated oncogene 2
(GLI2), GSK-3β and ASPH. The effect of ASPH on tumor in vivo was analyzed using a nude mouse
xenograft model.

Results:
Pan-cancer data showed that expressed ASPH was significantly correlated with a poor prognosis
in patients. ASPH knockdown inhibited the migration and invasion of human ICC cells lines
QBC939 and RBE. ASPH overexpression contributed to an increase in the N-cadherin and Vimentin,
resulting in the promotion of the EMT process. The p-GSK-3β levels decreased in the presence of
ASPH overexpression. The overexpression of ASPH led to an upregulation of the expression of SHH
signaling elements GLI2 and SUFU. The results of in vivo experiments with a lung metastasis model
in nude mice with ICC cell line RBE are consistent with these results.

Conclusion:
ASPH accelerated metastasis of ICC cells by facilitating EMT via a GSK-3β/SHH/GLI2
axis-dependent manner, in which phosphorylation of GSK-3β was downregulated and the SHH signaling
pathway was activated.
Preparation and Evaluation of Liposomes Containing Ethanol and Propylene
Glycol as Carriers for Nicotine
Authors: Wang Hui , Shao Qing , Zhang Yan , Ding Jing , Yang Miaomiao , Yang Liu , Wang Wenjie , Cui Pengfei , Dai Zunxiao , Ma Li 
Published: May 2023

Background:
Nicotine is a fat-soluble substance that is easily absorbed through the skin and
mucosal tissues of the human body. However, its properties, such as light exposure, heat decomposition,
and volatilization, restrict its development and application in external preparations.

Objective:
This study focused on the preparation of stable nicotine-encapsulated ethosomes.

Methods:
During their preparation, two water-phase miscible osmotic promoters, ethanol and propylene
glycol (PG), were added to obtain a stable transdermal delivery system. Skin nicotine delivery was enhanced
through the synergistic action of osmotic promoters and phosphatidylcholine in binary
ethosomes. Various characteristics of the binary ethosomes were measured, including the vesicle size,
particle size distribution, and zeta potential. In order to optimize the ratio of ethanol and PG, the skin
permeability test was performed on mice in vitro in a Franz diffusion cell to compare cumulative skin
permeabilities. The penetration depth and fluorescence intensity of rhodamine-B-entrapped vesicles in
isolated mouse skin samples were observed using laser confocal scanning microscopy.

Results:
When ethanol:PG was used in a ratio of 5:5 (w/w), binary ethosomes were found to be the
most stable, had the highest encapsulation rate (86.13 ± 1.40), smallest particle size (106.0 ± 11.0) nm,
maximum transdermal depth (180 μm), and maximum fluorescence intensity (160 AU). Nicotineencapsulated
ethosomes (ethanol: PG = 5:5, w/w) were an efficient and stable transdermal delivery
system.

Conclusion:
The nicotine-encapsulated ethosomes containing ethanol and PG are considered to be safe
and reliable as a transdermal administration agent, which does not irritate the skin.
Formulation, Preparation, and Evaluation of Bifunctional Micelle
with Glycyrrhizic Acid Containing Emodin for Toxicity Attenuation
Application
Authors: Wang Qixiao , Gu Chenlu , Adu-Frimpong Michael , Xu Qiumin , Chi Hao , Li Xiu , Chingozho Clayton Takura , Meng Deerdi , Fu Haizhen , Tong Shanshan , Xu Ximing 
Published: May 2023

Objective:
To prepare GA-Emo micelles and investigate the feasibility of using GA as both a
bifunctional drug and carrier.

Methods:
The preparation of GA-Emo micelles was accomplished via the thin-film dispersion method
with GA as the carrier. Size distribution, entrapment efficiency, and drug loading were used to evaluate
the characteristics of micelles. The absorption and transport properties of the micelles in Caco-2 cells
were investigated, while their pharmacodynamics in mice were preliminarily studied.

Results:
The optimal formulation featured a GA/Emo in weight ratio of 2:1 and an encapsulation efficiency
of 23.68%. The optimized GA/Emo was characterized as small uniform spheres with an average
micellar size of 168.64 ± 5.69 nm, a polydispersity index of 0.17 ± 0.01, and an electrically negative
surface (−35.33 ± 0.94 mV). Absorption and transport experiments with Caco-2 cells showed that the
absorption of GA-Emo micelles in small intestines was mainly passive transport, amid their transport
volume being significantly higher than that of Emo monomer. The intestinal wall thickness of the GAEmo
micelles group was significantly lower than that of the Emo group, which meant that the colonic
toxicity of the micelles was lower than unincorporated Emo.

Conclusion:
The advantages of GA as a bifunctional micelle carrier in formulation characters, drug
release, and toxicity attenuation provide a new idea for the application of the GA of natural medicine in
drug delivery for toxicity reduction.
Clinical Efficacy of Vaccaria segetalis Seeds and Gleditsia sinensis Lam Thorns on Prostate Cancer: A Preliminary Mechanism Analysis based on Network Pharmacology
Authors: Huang Hsiu-Hsien , Li Qiao-Feng , Zhang Lei , Wu Cheng-Yu 
Published: May 2023

Objective:
The mechanism of Vaccaria segetalis (VS) seeds and Gleditsia sinensis Lam (GS)
thorns in the treatment of prostate cancer (PC) was analyzed via network pharmacological analysis
methods and molecular docking.

Methods:
The Traditional Chinese Medicine Systems Pharmacology Database Platform (TCMSP) was
used to screen the PC’s effective components and targets; GeneCards and OMIM databases to search for
targets related to PC. The intersection target was uploaded to the STRING database to obtain a proteinprotein
interaction (PPI) network; and the key targets were screened from the PPI network via R language,
CytoNCA, and CytoHubba tools. Gene Ontology (GO) and Kyoto encyclopedia of genes and genome
(KEGG) pathway enrichment tools were used to analyze biological processes and molecular docking
of key targets via AutoDock Vina software.

Results:
A total of 13 compounds, 229 nodes, 879 edges, and 20 key targets were obtained through the
PPI network. Go and KEGG analysis showed that the intersection targets of VS and GS with PC were
mainly involved in regulating cell promotion, cell apoptosis, cell cycle, and reversing epithelialmesenchymal
transition (EMT) processing. Molecular docking revealed that the relevant targets of potential
PC were characterized with stabilized affinity. Specifically, the targets with better affinity included
estrogen receptor 1 (ESR1) with kaempferol, transcription factor p65 (RELA) with fisetin, kaempferol,
quercetin, and mitogen-activated protein kinase 1 (MAPK1) with fisetin, and G1/S-specific cyclin-D1
(CCND1) with fisetin, kaempferol, and quercetin.

Conclusion:
In summary, this study reveals potential molecular therapeutic mechanisms of VS and GS in
PC and provides a reference for the wide application of VS and GS in the clinical management of PC.
Methods of Synthesis, Characterization and Anticancer Potential of Herbal
Silver Nanoparticles: A Review
Authors: Chaudhary Devendar , Deep Aakash , Bansal Nitin , Rani Neeraj 
Published: May 2023

Abstract:
Cancer is a major cause of death for a huge amount of the population. A large population
is suffering from this chronic disease, and various treatments and therapies are developed for the diagnosis
of cancer. This review paper focuses on one of the treatments for cancer diagnosis, i.e., herbal
silver nanoparticles. Herbal silver nanoparticles are plant-based materials with very less and minimum
adverse effects of metals. Metal ions are reduced and stabilized by plant-based reducing and
stabilizing agents. Nanoparticles are synthesized by physical, chemical and biological methods. Biological
methods have very less toxic and have minimum side effects on the environment. Characterization
of synthesized nanoparticles is performed by various techniques like SEM, TEM, UV visible
spectroscopy and FTIR. However, full profile characterization of nanoparticles is still a challenge for
researchers. Herbal silver nanoparticles have many therapeutic activities like antioxidant, antibacterial
and various others, but this review paper has a focus on anticancer evaluation. Herbal silver nanoparticles
are reported for their anticancer activities on a large scale. In this review article, we will
discuss the methods of synthesis, characterization and anticancer potential of herbal silver nanoparticles.
Low Lactose Yogurt with Blueberry Jam: Development and Sensory Acceptance
Authors: de Oliveira Kelly Silva Degani , Teixeira Liliane Martins , Borba Carina Molins , Contessa Camila Ramão , Burkert Carlos André Veiga , de Medeiros Burkert Janaína Fernandes 
Published: May 2023

Introduction:
The lactose-intolerant public represents an important portion of the population;
however, the diversification of products that serve this population is still very limited.

Objective:
In this bias, this study aimed to develop a low-lactose yogurt added with blueberry jelly,
combining sensory and functional characteristics of the fruit.

Methods:
Different concentrations of β-galactosidase were evaluated in the fermentations, in addition
to four formulations of blueberry jelly that were sensorially tested for preference, a formulation
was selected and its global acceptance and purchase intent were verified.

Results:
The use of 1.5 g L- 1 of β-galactosidase allowed for a more significant reduction of lactose
during the fermentation process. Of the four jelly formulations tested, the whole fruit was
sensory preferred, and the low-lactose two-layer yogurt showed 86% acceptance and 74% purchase
intention.

Conclusion:
It was possible to develop a product with low lactose content and sensorially pleasant
to the consumer.
Risk of Systemic Autoimmune Diseases with Antiarrhythmic Drugs in
Arrhythmia Patients: A Retrospective Cohort Study
Authors: Lin Jiun-Jie , Chen Hung-Yi , Lin Mei-Chen , Hsu Chung-Y. 
Published: May 2023

Aim:
The risk factors for systemic autoimmune disease (SAD)s with antiarrhythmic drug(AAD)s in arrhythmia patients are still unclear. This study was discussed this risk factors for SADs with AADs in arrhythmia patients.

Methods:
This study was a retrospective cohort design and analyzed this relationship in an Asian population. Patients without a prior diagnosis of SADs were identified from Taiwan's National Health Insurance Research Database from January 1, 2000 to December 31, 2013. Cox regression models were estimated the hazard ratio (HR) with 95% confidence interval [CI] of SAD.

Results:
We estimated the data of participants aged ≧ 20 or ≦ 100 years old and free of SADs at baseline. AAD users (n = 138376) had a significantly increased risk of SADs over non-AAD users. There was a significant higher risk of developing SADs in all age and sex categories. The patients who received AADs, the autoimmune disease with the significantly higher risk was systemic lupus erythematous (SLE) (adjusted HR [aHR] 1.53, 95%CI, 1.04-2.26), Sjögren syndrome (SjS) (adjusted HR [aHR] 2.06, 95%CI, 1.59-2.66) and rheumatoid arthritis (RA) (aHR, 1.57, 95%CI, 1.26-1.94).

Conclusion:
We concluded that there were statistical associations between AADs and SADs, and the higher incidence was SLE, SjS and RA in arrhythmia patients.
Cyclization of 2-Aminopyridines as Binucleophile and Mucobromic Acid
as C3 Synthon: A New Access to Imidazo[1,2-a]Pyridines
Authors: Chen Qi , Li Huan-Qing , Chen Zhao-Hua , Chen Zu-Jia , Yang Kai , Zhang You-Cai , Wang Zhao-Yang 
Published: May 2023

Abstract:
For the first time, we have developed a strategy that provides an access to imidazo[
1,2-a] pyridines via the cyclization of 2-aminopyridine with mucobromic acid as C3
synthon. In the combination with theoretical calculation, the reaction mechanism is proposed.

Background:
2-Aminopyridines are the typical pyridine α-site derivatives, which have received
growing interest in using as a kind of synthons in organic synthesis and drug synthesis because
of their special binucleophilic framework.

Methods:
All these obtained compounds were characterized by NMR. Among them, 3a was
characterized by single-crystal X-ray analysis. All the theoretical calculation works were performed
by Gaussian software.

Results:
A series of the desired compounds can be synthesized at room temperature via a mild
procedure under the promotion of simple inorganic base K2CO3.

Conclusion:
This mild strategy fits the concept of green chemistry, providing a novel idea for
the construction of nitrogen-containing polyheterocyclic compounds.
EEG Brain Signal Processing for Epilepsy Detection
Authors: Jain Shruti , Paul Sudip , Sharma Kshitij 
Published: May 2023

Background:
Millions of neurons make up the human brain, and they play an important role in controlling the body's response to internal and external motor and sensory stimuli. These neurons can function as contact conduits between the human body and the brain. Analyzing brain signals or photographs will help one better understand cognitive function. These states are linked to a particular signal frequency that aids in the comprehension of how a complex brain system works.

Objective:
Electroencephalography (EEG) is a useful method for locating brain waves associated with different countries on the scalp. Epilepsy is a condition where the brain or some part of it is overactive and sends too many signals. This results in seizures causing muscles to twitch or whole-body convulsions.

Methods:
In this paper, the author has designed a model to predict epilepsy using machine learning algorithms and deep learning models. For the machine learning algorithm, different features were extracted and a particle swarm optimization algorithm was used to select the best feature which was classified using wavelet transform.Vgg16, Vgg19, and Inception V3 models are used for the detection of epilepsy.

Results:
The inception V3 model results in 97.87% accuracy which is better than all other techniques. 5.1% accuracy improvement has been observed using a machine learning algorithm. The model is compared using existing work and it has been observed that the proposed model results better.

Conclusion:
The technique for modeling EEG signals and insight brain signals recorded during surgical procedures has been identified in detail. 0.7% and 0.13% accuracy improvement were achieved when the model is validated on Kaggle and CHB-MIT datasets respectively.
Tegoprazan as a New Remedy for Gastrointestinal Diseases in Comparison
with its Therapeutic Predecessors: A Mini-Review
Authors: Anik Asif Hossain , Proma Farhana Alam , Saha Pranoy , Sarker Sabarni 
Published: May 2023

Abstract:
Potassium-competitive acid blockers (P-CABs), such as tegoprazan, are a new and diverse
class of drugs that can completely block the potassium-binding site of gastric H+/K+
ATPase, potentially overcoming the limitations of proton-pump inhibitors (PPIs). A number of
studies have compared the effectiveness as well as the safety profile of tegoprazan to PPIs and
other P-CABs for the treatment of gastrointestinal diseases. The current review study evaluates the
published works of literature related to clinical pharmacology and clinical trials of tegoprazan for
the treatment of diseases related to the gastrointestinal tract. According to the publications included
in the study, tegoprazan was found to be safe and well-tolerated and can be used to treat a
group of gastrointestinal diseases, including gastroesophageal reflux disease (GERD), non-erosive
reflux disease (NERD), and H. pylori combination therapy.
Hydrogenation Influences the Created Giant Dielectric Behaviors of
(Bi+W) Codoped Anatase TiO2
Authors: Dakhel A.A. 
Published: May 2023

Introductions:
TiO2 nanoparticles ceramic (NPs) codoped with Bi and W ions have
been synthesized by a hydrothermal technique. A portion of the prepared ceramic was posthydrogenated.
Ceramic NPs were characterized by traditional methods. Crystalline structures and
optical properties were investigated using X-Ray diffraction (XRD) and diffuse reflection spectroscopy,
respectively.

Methods:
The present work has focused on the creation of a colossal (giant) dielectric permittivity
(GP) behavior with the TiO2 host NCs through the Bi/W codoping to construct electronic core/shell
structures. In addition, the influence of post-hydrogenation on the created GP was also examined.

Results:
It was found a high permittivity of 3.69×104 at 1 kHz, which was reduced to 3.29×104
by the hydrogenation of the sample. This is attributed to the densification of the itinerant electrons
by the effect of the catalytic power of the doping W5+ ions to dissociate the adsorbed H2.

Conclusion:
The present values of GP are much higher than the permittivity of the pure TiO2 and
the Bi-doped TiO2 ceramic, which was attributed to the construction of core/shell electronics structures.
As a result, the doping process has been studied in detail in relation to scientific expectations.
The ability of Junior High School mathematics teachers writing Higher Order Thinking Skills (HOTS) questions
Authors: Hamdi Syukrul , Kartowagiran Badrun , Istiyono Edi , Rahman Hadi Nur 
Published: May 2023

This study is a survey research with a cross sectional survey design, which aims to describe the ability of junior high school mathematics teachers in writing HOTS items. The population of this study was junior high school mathematics teachers in Sleman Regency, while the sample was 21 teachers determined by non-stratified random sampling. The sample teachers came from 11 schools totaling 21 teachers. Each teacher created three HOTS items along with their grids. The question items made by the sample teachers were descriptive questions. The question items that had been prepared were then reviewed by two mathematics teachers from leading junior high schools in Yogyakarta. The next stage after validation is the trial. The number of respondents used was 263 students for testing teacher-made questions, namely 127 students in class VIII and 136 students in class VII. The results showed that the quality of the questions produced by the teacher based on the reliability estimation results obtained an estimate of 0.635 for class VII and 0.416 for class VIII. Likewise, the resulting differentiating power is less than 50% of the questions made by teachers who have differentiating power in the good, good, and very good categories. Factors that cause this include the lack of experience of teachers in writing HOTS questions. This is a special note to familiarize teachers with using HOTS questions in daily tests, UTS, and UAS proportionally so that the experience and ability of teachers to write HOTS questions increases.