bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Pragmatic Approach in Eastern Europe
Authors: Borisova Elena 
Published: April 2024

The paper is an attempt to briefly outline the history and the present state of the pragmatic approach to language in Eastern Europe, namely Slavic regions of theformer Soviet Union (Russia, Ukraine, and Belorussia) as well as Bulgaria and Serbia. Pragmatic studies in Poland and former Czechoslovakia are not reviewed as better known by scholars who are interested in linguistic pragmatics. It is our point that some results from Eastern Europe are relevant not only for the study of Slavic languagesbut also for the general linguistic pragmatics and therefore may be of interest for those who do not have reading knowledge of Slavic languages. The authors present a general view of the studies belonging to the pragmatic domain: the behavior and interaction of the participants of communicative events, its reflection in linguistic units, the analysis of specific aspects of communication, such as emotions, humor, implicite information etc. In Section 1 and 2 the predecessors of pragmatic approach are mentioned: Stylistics, Rhetoric, studies of funtional sentence perspective and verbal etiquette. In Section 3 the development and the state of the art of Pragmatics proper in USSR is outlined followed by Section 4 devoted to the studies based on the Conceptual Metaphor theory and Section 5 devoted to the studies bordering Pragmatics: studies of the speech influence, language of Internet, affectiveness in language, humor and irony and some other topics. In Section 6 the specifics of the EastEuropean pragmatic studies is discussed. The paper was conceived as an introduction to the collection of articles presented in this volume and those that shall appear in the next volumes of the journal “Fundamental Linguistics”.
Adjuvant Anti-tumor Therapy with Polyphenolic Compounds: A Review
Authors: Gareev Ilgiz , Jiang Jianhao , Beylerli Ozal , Beilerli Aferin , Ilyasova Tatiana , Shumadalova Alina , Bai Yunlong , Du Weijie , Yang Baofeng 
Published: April 2024

Abstract:
The search for effective methods of treatment and prevention of oncological
diseases, despite the successes achieved in recent decades, remains one of the most urgent
issues in modern medicine. It is known that chemotherapy and radiation therapy are
based on the induction of cell death by increasing the intracellular concentration of reactive
oxygen species (ROS). To increase the effectiveness of chemo- and radiotherapy, inducing
and increasing oxidative stress in tumor cells has been proposed. A new class of
promising adjuvants in combination with anticancer therapy, which has already been
shown to be effective in preclinical and clinical studies, includes natural and synthetic
polyphenols. Polyphenolic compounds not only exhibit antitumor activity but also significantly
reduce the resistance of tumor cells to chemo- and radiotherapy. However, almost
all chemotherapeutic drugs and regimens of radiation treatment have a damaging
toxic effect on normal tissues, which significantly affects the quality of life of patients,
and treatment options for managing these side effects are limited. In this regard, some of
the most promising agents for the management of toxic side effects are natural polyphenols.
This study discusses the possible molecular mechanisms and prospects for
the clinical use of natural and synthetic polyphenolic compounds in chemo- and radiotherapy.
In addition, the protective role/effect of polyphenols on the effects of chemoand
radiotherapy in tumor patients is discussed.
Improved Stability of Aspergillus oryzae α-Amylase Immobilized on Polyaniline Tin
Oxide Nanocomposites
Authors: Khan Mohd Jahir , Ahmad Abrar 
Published: April 2024

Abstract:
In the present study, an immobilization support, Polyaniline tin oxide nanocomposite (PANI-SnO2-
NC) was synthesized by in situ polymerization of aniline and ammonium peroxydisulphate. The prepared nanocomposite
was characterized by various state-of-the-art techniques. The average size of native SnO2-NPs and
PANI-SnO2-NC was 65±19 nm and 93±15 nm, respectively. An important industrial enzyme, α-amylase from
Aspergillus oryzae was immobilized on PANI-SnO2-NC, which retained 87% enzyme activity. The improved
stability of the immobilized enzyme was noticed against pH and temperature, as it retained 65% activity at 60 °C
while the free enzyme exhibited 41% activity under similar experimental conditions. Moreover, PANI-SnO2-
NC-immobilized α-amylase produced starch (26.42 mg mL–1) more efficiently than free enzyme (20.90 mg mL–
1) after 8 h in batch hydrolysis. PANI-SnO2-NC-bound α-amylase exhibited 54% activity after eight repeated
uses. Molecular docking analysis of α-amylase with PANI suggested the ligand binding site to be located quite
far away from the active site of the enzyme.
Network Pharmacology and Experimental Validation of Jinwei Decoction for Enhancement of Glucocorticoid Anti-Inflammatory Effect in COPD through miR-155-5p
Authors: Wu Jian-Jun , Zhang Ping-An , Chen Ming-Zhe , Du Wei-Sha , Zhang Yi , Jiao Yang , Li Xin 
Published: April 2024

Background:
Jinwei decoction can enhance the anti-inflammatory effect of glucocorticoid
(GC) on chronic obstructive pulmonary disease (COPD) by restoring the activity of human
histone deacetylase-2 (HDAC2). However the upstream mechanism of Jinwei decoction on
HDAC2 expression is not clear.

Objective:
To explore the target of Jinwei decoction to enhance the anti-inflammatory effect of
GC on COPD through microRNA155-5p (miR-155-5p) by network pharmacology and experimental
verification.

Methods:
The TCMSP database was used to screen active ingredients and target genes of Jinwei
decoction, and miRWalk2.0 was used to predict downstream target genes of miR-155-5p.
COPD-related genes were identified by searching GeneCards, Grugbank and OMIM databases;
Venny 2.1 was used to screen intersection genes; Gene Ontology (GO) and Kyoto Encyclopedia
of Genes and Genomes (KEGG) pathways of intersection genes were analyzed by R software.
Protein-protein interactions (PPIs) were analyzed by Cytoscape 3.7.2 software to identify core
genes. Finally, interactions between main compounds and potential targets were verified by molecular
docking. A COPD cell model was established by 5% cigarette smoke extract (CSE)-
induced bronchial epithelial cell (BEAS-2B), and the results of network pharmacology were
verified by in vitro experiments.

Results:
Two hundred thirty-one active ingredients, 352 Jinwei decoction drug targets, 5949
miR-155-5p target genes, 8286 COPD target genes, and 127 intersection genes were identified.
Twelve core proteins of PPI networks may be involved. GO enrichment analysis showed that
regulation of membrane potential， response to steroid hormone, and histone modification were
involved; KEGG pathway enrichment analysis concentrated in the PI3K-Akt, mitogen-activated
protein kinase (MAPK), HIF-1, and other signaling pathways. The molecular docking results
showed that quercetin, luteolin and stigmasterol have higher affinity with PTGS2, HIF1A and
AKT1. The results of cell experiments revealed that Jinwei decoction not only enhances the anti-
inflammatory effect of GC in the COPD cell model but also reverses the high expression of
miR-155-5p、PI3k、Akt, and low expression of HDAC2, thereby inhibiting the inflammatory
response of COPD.

Conclusion:
Jinwei decoction can regulate HDAC2 activity and enhance the anti-inflammatory
effect of GC on COPD by modulating miR-155-5p. Its mechanism of action may be related to
its effect on the PI3K-Akt through miR-155-5p.
The Protective Effects of Modified Dachaihu Decoction against
LPS-induced Acute Lung Injury via Modulating PI3K/Akt Signalling Pathway
Authors: Li Jincan , Huang Jiechun , Ai Gaoxiang , Zheng Xiaohong , Chen Baoyi , Gong Shiting , Lu Xiaowei , Su Ziren , Chen Jiannan , Xie Qingfeng , Li Yucui , Yan Fang 
Published: April 2024

Background:
Modified Dachaihu decoction (MDD) is a herbal prescription that has
shown promising therapeutic benefits in ameliorating pulmonary diseases in clinical practice.
However, the detailed mechanisms remain unclear.

Objective:
This study aimed to elucidate the lung-protective effects of MDD against acute lung
injury (ALI) and the involvement of underlying mechanisms.

Methods:
High-performance liquid chromatography (HPLC) was performed to identify the main
active ingredients of MDD. Network pharmacological method was adapted to explore the potential
mechanisms. Mice were orally administered MDD (11.25, 22.5, and 45 g/kg) once daily for
7 days. H&E staining was performed to evaluate histological changes in the lungs. Levels of inflammatory
cytokines and oxidative stress markers were measured to determine the extent of
lung injury. Total protein content in bronchoalveolar lavage fluid (BALF) and lung wet/dry
weight ratio were measured to assess the severity of pulmonary edema. TUNEL staining and
immunohistochemistry analysis were performed to detect apoptosis. RT-qPCR and western blotting
were performed to validate the mechanisms involved.

Results:
About 10 main active ingredients of MDD were identified. Notably, treatment with
MDD resulted in a remarkable reduction in total protein content in BALF and lung W/D weight
ratio, as well as substantial mitigation of the inflammatory response and oxidative stress. Mechanistically,
the PI3K/Akt signalling pathway was activated. Moreover, MDD pretreatment
downregulated p53 and caspase-9 mRNA expression and decreased the Bax/Bcl-2 ratio to ameliorate
lung apoptosis.

Conclusions:
MDD exhibited pronounced therapeutic effects via attenuating inflammatory response,
oxidative stress, and apoptosis. These therapeutic effects could be attributed to the synergistic
effect of the main active ingredients and are believed to be associated with the activation
of the PI3K/Akt pathway.
Nutriose, a Dextrin-based Natural Polysaccharide Polymer with Beneficial
Activities as a Candidate for Future Drug Delivery: A Review
Authors: Ghosh Debaprasad , Jain Anushka , Tyagi Mansi , Katiyar Deepti , Mittal Ashu 
Published: April 2024

Abstract:
Nutriose is a dextrin-based soluble fiber prepared from starch. Cereals such as maize,
wheat, and barley are the primary sources of nutrients for commercial production. Nutriose is
resistant to digestion by human enzymes in the stomach and small intestine. It is mostly undamaged
when it enters the colon after traveling through the digestive tract, where it generates shortchain
fatty acids (SCFAs) as byproducts. These SCFAs, which include butyrate, propionate, and
acetate, have a number of health advantages. They foster an environment in the colon that is advantageous
for gut health-promoting bacteria like lactobacilli and bifidobacteria. Nutriose fermentation
leads to a more balanced composition of the gut microbiota, which may have advantages
for the immune system, better digestion, and increased nutrient absorption. As a result,
nutriose is currently being utilized as a prebiotic. Several publications have previously demonstrated
the impact of nutriose on stimulating gut mucosal immunity and boosting colonic fermentation
and excretion in rats. Nanoformulations and nutrisomes have already been prepared
and evaluated in recent years. A novel nutriose-based polymeric coating mix has already been
tested as a potential colon-targeting material. As a natural polysaccharide, nutriose’s possible
uses in pharmaceuticals may increase in the near future. The purpose of this study is to critically
analyze existing data to determine the potential of nutriose as a natural polymer for various drug
delivery systems.
Gegen Qinlian Decoction Modulates Atherosclerosis and Lipid Metabolism Through Cellular Interplay and Signaling Pathways
Authors: Zhang Zhiwei , Zhou Yu , Lv Qin , Gao Kun , Li Zhiguo , Miao Qing , Shen Li 
Published: April 2024

Objective:
The objective of this study is to investigate Gegen Qinlian decoction
(GQD) effects on lipid metabolism and explore its mechanism for preventing and treating atherosclerosis.

Methods:
An atherosclerotic rat model was established;, and after an 8-week high-fat diet, atherosclerosis
and non-alcoholic fatty liver disease were assessed. Subsequently, GQD was administered
at low and high doses. Histopathological aortic wall changes, hepatic lipid deposition,
and blood lipid changes were evaluated. ELISA indicated the influence of TNF-α and IL-13, and
Western blotting revealed MerTK, ABCA1, and LXR-α expression. A foam macrophage model
was established, and Cell activity was detected by the MTT method. ELISA indicated the influence
of PPAR-γ. The expression of ABCA1, ABCA7, ABCG1, GAS6, MerTK, SCARB1, LXR-
α and LXR-β mRNA were detected by qPCR， and Western blotting revealed MerTK and
LXR-α expression. The impact of drug-containing serum of GQD on efferocytosis-related factors
was studied.

Results:
GQD improved atherosclerosis and non-alcoholic fatty liver disease and reduced serum
low-density lipoprotein levels in the high-dose group. The high- and low-dose groups showed
upregulated ABCA1, MerTK, and LXR-α expression in blood vessels and the liver, respectively.
GQD decreased serum TNF-α and increased IL-13 levels. PPAR-γ expression was elevated in
the high-, and low-dose groups. In the high-and low-dose groups, ABCA7, GAS6, SCARB1,
and LXR-α, ABCA1 and MerTK, and ABCG1 gene expression were upregulated, respectively.
Both low- and high-dose serum-containing drugs promoted LXR-β gene expression, and LXR-α
protein expression was improved in the high-dose group.

Conclusion:
GQD improves rat atherosclerosis and hepatic lipid metabolism by regulating
PPAR-γ, LXR-α, LXR-β, ABCA1, ABCA7, and ABCG1 expression and augmenting cellular
intercalation through the GAS6/TAM pathway
Advances in Aerosol Formulation for Targeted Delivery of Therapeutic Agents from Nose to Brain
Authors: Verma Shristy , Sharma Pramod Kumar , Malviya Rishabha 
Published: April 2024

Abstract:
The intricate anatomical and physiological barriers that prohibit pharmaceuticals from
entering the brain continue to provide a noteworthy hurdle to the efficient distribution of medications
to brain tissues. These barriers prevent the movement of active therapeutic agents into the
brain. The present manuscript aims to describe the various aspects of brain-targeted drug delivery
through the nasal route. The primary transport mechanism for drug absorption from the nose to
the brain is the paracellular/extracellular mechanism, which allows for rapid drug transfer. The
transcellular/intracellular pathway involves the transfer across a lipoidal channel, which regulates
the entry or exit of anions, organic cations, and peptides. Spectroscopy and PET (positron emission
tomography) are two common methods used for assessing drug distribution. MRI (Magnetic
resonance imaging) is another imaging method used to assess the efficacy of aerosol drug delivery
from nose to brain. It can identify emphysema, drug-induced harm, mucus discharge, oedema, and
vascular remodeling. The olfactory epithelium's position in the nasal cavity makes it difficult for
drugs to reach the desired target. Bi-directional aerosol systems and tools like the “OptiNose” can
help decrease extranasal particle deposition and increase particle deposition efficiency in the primary
nasal pathway. Direct medicine administration from N-T-B, however, can reduce the dose
administered and make it easier to attain an effective concentration at the site of activity, and it
has the potential to be commercialized.
Food-derived Peptides as Promising Neuroprotective Agents: Mechanism
and Therapeutic Potential
Authors: Patel Kavita , Mani Ashutosh 
Published: April 2024

Abstract:
Many food-derived peptides have the potential to improve brain health and slow down
neurodegeneration. Peptides are produced by the enzymatic hydrolysis of proteins from different
food sources. These peptides have been shown to be involved in antioxidant and anti-inflammatory
activity, neuro-transmission modulation, and gene expression regulation. Although few peptides
directly affect chromatin remodeling and histone alterations, others indirectly affect the neuroprotection
process by interfering with epigenetic changes. Fish-derived peptides have shown
neuroprotective properties that reduce oxidative stress and improve motor dysfunction in Parkinson's
disease models. Peptides from milk and eggs have been found to have anti-inflammatory
properties that reduce inflammation and improve cognitive function in Alzheimer's disease models.
These peptides are potential therapeutics for neurodegenerative diseases, but more study is required
to assess their efficacy and the underlying neuroprotective benefits. Consequently, this review
concentrated on each mechanism of action used by food-derived peptides that have neuroprotective
advantages and applications in treating neurodegenerative diseases. This article highlights
various pathways, such as inflammatory pathways, major oxidant pathways, apoptotic pathways,
neurotransmitter modulation, and gene regulation through which food-derived peptides interact at
the cellular level.
Synthesis, Antiproliferative Evaluation, and Molecular Docking of Thieno[3,2-e]indazole Derivatives
Authors: Mohareb Rafat M. , Mikhail Ibram Refat , Gamaan Marwa Soliman , Alwan Ensaf S. 
Published: April 2024

Background:
Although indazole derivatives are rare and may not be available easily in
nature, there are many reports demonstrating their pharmaceutical and other applications.

Objective:
This study aimed to synthesize new indazole derivatives and evaluate their antiproliferative
activity to produce new anti-cancer agents.

Methods:
Compounds 3a-c were synthesized through the reaction. The 2-aryllidenecyclohexane-1,3-
dione derivatives 3a-c were obtained through the reaction of cyclohexane-1,3-dione with aromatic
aldehydes used for the synthesis of thieno-[3,2-e]indazole derivatives. These derivatives were characterized
by extensive analytical and spectral studies and were further used as starting materials for
some heterocyclic transformations to produce biologically active compounds. The antiproliferative
activities of the newly synthesized compounds were evaluated against the six cancer cell lines, A549,
HT-29, MKN-45, U87MG, SMMC-7721, and H460. Most of the tested compounds exhibited high
cytotoxicity except a few compounds.

Results:
In this study, new compounds were synthesized, characterized, and evaluated toward the
selected six cancer cell lines. All tested compounds displayed potent c-Met enzymatic activity with
IC50 values ranging from 0.25 to 10.30 nM and potent prostate PC-3 cell line inhibition with IC50
values ranging from 0.17 to 9.31 μM.

Conclusion:
The results obtained in this work demonstrated that the variations in substituents within
the aryl moiety, together with the attached heterocyclic ring, have a notable influence on the antiproliferative
activity. The results obtained in this work encourage further work in the future.
A Linear and Nonlinear QSAR Analysis of Benzimidazole Derivative XY123 in Prostate Cancer Treatment
Authors: Li Bing , Liu Xiaoqiang 
Published: April 2024

Background:
Metastatic Castration-Resistant Prostate Cancer (mCRPC) represents a
critical challenge in current prostate cancer treatment. Benzimidazole Derivative XY123 has
emerged as a novel inhibitor for its treatment.

Objective:
This study aims to establish a robust Quantitative Structure-Activity Relationship (QSAR)
model for predicting the activity of Benzimidazole Derivative XY123 derivatives, aiding the development
of novel anti-prostate cancer drugs.

Methods:
Utilizing CODESSA software, descriptors were computed based on various moieties of
Benzimidazole Derivative XY123 derivatives. Multiple linear regression models were constructed,
and both linear and nonlinear QSAR models were developed using heuristics and gene expression
programming.

Results:
The linear model with two descriptors demonstrated the best predictive capacity for inhibitor
activity, while the nonlinear model generated through Gene Expression Programming (GEP)
exhibited correlation coefficients of 0.83 and 0.82 for the training and test sets, respectively. The
average errors were 0.03 and 0.05, indicating the stability and the improved predictive ability of the
nonlinear model.

Conclusion:
The QSAR linear model has an advantage over the nonlinear model in optimizing Benzimidazole
Derivative XY123, providing a direction for the development of effective drugs for
mCRPC treatment.
Bronchial Asthma and Mucociliary Clearance - A Bidirectional Relationship
Authors: Oppova Daša , Bánovčin Peter , Ďurdík Peter , Babničová Michaela , Jeseňák Miloš 
Published: April 2024

:
The integrity of the airway epithelium plays an important role in the defence against
pathogens and various immunogenic stimuli from the external environment. Properly functioning
mucociliary clearance is an indispensable part of the respiratory system defence and it relies on adequate
viscoelastic properties of mucus, as well as the intact function of a significant number of
healthy ciliated cells. The movement of the cilia can be affected by many endogenous and exogenous
factors. Complex mucociliary clearance dysfunction can be seen as a part of the respiratory
system inflammation. Bronchial asthma is one of the most common inflammatory diseases of the
respiratory system. It is characterised by structural and functional changes in the airways. The last
decades of bronchial asthma research point to asthmatic inflammation as the cause of airway remodelling
with subsequent impairment of mucociliary transport function.
Changes in the respiratory epithelium in patients with bronchial asthma include hypertrophy of secretory
cells, overproduction of mucus, increase in mucus viscosity, decline of ciliated cells, decrease
of ciliary beat frequency, and more. Cytokines of T2-high type of asthmatic inflammation,
such as interleukin IL-13 and IL-4, have been shown to contribute to these changes in the airway
epithelium significantly. There is strong evidence of cytokine-induced overexpression of important
transcription factors, which results in hyper- and metaplasia of secretory cells and also transdifferentiation
of ciliary cells. Impaired mucociliary clearance increases the risk of airway infection
and contributes to the worsening of bronchial asthma control.