bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current Perspectives of Diabetic Dyslipidemia and Treatment Modalities
Authors: AKKUS Gamze 
Published: January 2025

Introduction:
Diabetes mellitus is associated with an increased risk of
atherosclerosis related to dyslipidemia. Although the terms hyperlipidemia and Diabetes
Mellitus [DM] or diabetic dyslipidemia are interrelated to each other, these two conditions
have some differences.

Aim:
This study aimed to highlight possible mechanisms of hyperlipidemia and/or dyslipidemia
in diabetic patients, which can be treated with available and newer hypolipidemic
drugs. We also re-checked current specific guidelines and their recommendations
on the management of patients with diabetic dyslipidemia.

Method:
Comprehensive search of peer-reviewed journals was performed based on a
wide range of keywords, including diabetes mellitus, dyslipidemia, hyperlipidemia, insulin
resistance, free-fatty acids, cardiovascular disease, SCORE-2 calculation, statins,
PCSK-9 inhibitors, and fibrates.

Discussion:
Diabetic patients with dyslipidemia, including decreased HDL cholesterol,
a predominance of small dense LDL particles, and increased triglyceride levels, are
more prone to suffering from micro and macrovascular complications regardless of plasma
fasting glucose levels. Recent guidelines suggested using the validated scoring system
called SCORE2-Diabetes. Moderate to high dosages of statins, aiming for LDL
cholesterol reduction, is still the cornerstone in the management of diabetic patients with
dyslipidemia. Nowadays, other recommended non-statin drugs, including proprotein convertase
subtilisin/kexin type 9 [PCSK9] inhibitors or other novel therapeutic agents
[bempedoic acid, inclisiran], are particularly important and given place in recently published
guidelines.

Conclusion:
The risk of developing atherosclerotic cardiovascular diseases in people
with DM is relatively higher than in patients’ without DM. Optimal management of
lipid parameters and achieving desired target values in lipid parameters are still a challenging
issue for clinicians.
Mechanism Study on the Regulation of Th1/Th2 in the Treatment of Idiopathic Membranous Nephropathy by Shengyang Yiwei Decoction
Authors: Wu Yuan , Zhang Xue-Qin , An Heng-Tong , Wang Shuai-Jie , Zhao Ya-Yun , Chen Zhi-Qiang 
Published: January 2025

Background:
Shengyang Yiwei Decoction showed efficacy in idiopathic membranous
nephropathy treatment, and this study aimed to assess the underlying molecular mechanisms.

Methods:
Rats with passive Heymann nephritis were divided into the model group, the Shengyang
Yiwei Decoction group, the JAK2 inhibitor group, and the STAT3 inhibitor group. Healthy
rats served as the normal control. 24-hour urinary protein excretion, IgG deposition, renal histopathology,
the expression levels of synaptopodin, nephrin, podocalyxin, interferon-γ, interleukin-
4, T-box expressed in T cells, GATA binding protein-3, and relevant pathway proteins were
measured.

Results:
Within the model group, a notable elevation in the 24-h urinary protein level was observed,
accompanied by evident IgG deposition, increased glomerular volume, eosinophilic deposits,
diminished expression of podocyte marker proteins, and a discernible imbalance in
Th1/Th2 cellular immunity. Conversely, in Shengyang Yiwei Decoction and both inhibitor
groups, enhancements were observed across the aforementioned indexes.

Conclusion:
Shengyang Yiwei Decoction may reduce glomerular podocyte injury through the
suppression of the JAK2/STAT3 signaling pathway and modulation of the Th1/Th2 immune balance.
The Anaphylactic and Anti-allergenic Properties of Shuanghuanglian: A Review
Authors: Jiang Xin , Li Ji , Yao Xiaohui , Ding Hao 
Published: January 2025

Abstract:
Shuanghuanglian (SHL) and its primary constituents have demonstrated protective effects
against allergenic diseases. This review examines the anaphylactic and anti-allergenic activities
of SHL and its constituents. We also discuss potential avenues for future research, particularly
regarding the expansion of the clinical applications of SHL formulations (oral or nebulized)
for the treatment of allergenic disorders.
For this review, we searched the PubMed, Web of Science, and China National Knowledge Infrastructure
databases for relevant publications. Additionally, details of the essential active components
and target genes of SHL were obtained from the Traditional Chinese Medicine Systems
Pharmacology database (TCMSP), and information on allergy-related genes was collected from
the GeneCards and Online Mendelian Inheritance in Man(OMIM) databases. Lists of both the
SHL target and disease-related genes were imported into the ‘Draw Venn Diagram’ tool on the
website (http://bioinformatics.psb.ugen /web tools/Venn/). A protein–protein interaction network
for SHL and disease targets was constructed with reference to the Search Tool for the Retrieval
of Interacting Genes/Proteins (STRING) database, and the potential pathways were identified
based on Kyoto Encyclopaedia of Genes and Genome enrichment analyses.
The allergenic reactions induced by SHL injection (intravenous) and its main constituents (intraperitoneal
or intravenous injection) have been verified in animal experiments. Furthermore, the
protective effects of SHL injection (intraperitoneal) and its individual Chinese herb components
(intragastric administration), namely, Flos Lonicerae, Radix Scutellariae, and Fructus Forsythiae,
as well as their main constituents (intraperitoneal or intragastric administration), have been
verified in asthma, rhinitis, atopic dermatitis, and both IgE- and non-IgE-mediated systemic allergic
responses. The network pharmacology analysis revealed that the therapeutic effects of
SHL might be primarily mediated through the regulation of the IL-17 and TNF-α signalling
pathways and Th17 cell differentiation.
Accumulated research data provide a theoretical basis for the clinical application of SHL (via extravascular
routes) in the treatment of allergenic diseases.
TSPOAP1-AS1: A Novel Biomarker for the Prognosis and Therapeutic Target in Cervical Cancer
Authors: Li Jinyuan , Ye Zhen , Gan Yuhong , Li Dongbing , Chen Yibiao 
Published: January 2025

Background:
TSPOAP1 antisense RNA 1 (TSPOAP1-AS1) is a long non-coding RNA
(lncRNA) that has received widespread attention in oncology research in recent years. Its role and
mechanism in some cancers have gradually been revealed. However, it is not clear what role
TSPOAP1-AS1 plays in cervical cancer (CESC).

Objective:
In this study, bioinformatic analysis and experimental validation were carried out to investigate
the relationship between TSPOAP1-AS1 and CESC.

Methods:
The relationships between clinical characteristics in patients with CESC, TSPOAP1-AS1
expression, prognostic factors, regulation network, and immune infiltration of TSPOAP1-AS1 were
evaluated using statistics and The Cancer Genome Atlas database. Real-Time Quantitative Reverse
Transcription PCR was used to test TSPOAP1-AS1, miR-17-5p, and AGFG2 expression in CESC cell
lines.

Results:
CESC patients exhibited markedly reduced expression of TSPOAP1-AS1. There was a significant
correlation between low expression of TSPOAP1-AS1 in CESC patients and the clinical stage (p
< 0.05), weight (p < 0.05), and BMI (p < 0.05). Lower expression of TSPOAP1-AS1 in patients with
CESC was associated with poorer overall survival (OS) (p = 0.014) and disease-specific survival
(DSS) (p = 0.030). There was also an independent correlation between high expression of TSPOAP1-
AS1 (p = 0.036) and DSS in patients with CESC. TSPOAP1-AS1 was involved in the ribosome, oxidative
phosphorylation, antigen processing and presentation, cell adhesion molecules (CAMs), the
chemokine signaling pathway, neuroactive ligand-receptor interaction, and primary immunodeficiencies.
The infiltration of immune cells and the expression of TSPOAP1-AS1 were found to be correlated.
A ceRNA network of TSPOAP1-AS1/miR-17-5p/AGFG2 was constructed in CESC. In CESC, a
ceRNA network involving TSPOAP1-AS1/miR-17-5p/AGFG2 was successfully established. When
comparing CESC cell lines with HcerEpic, the expression of TSPOAP1-AS1 and AGFG2 decreased
significantly, and the expression of miR-17-5p increased significantly.

Conclusion:
In CESC patients, low expression of TSPOAP1-AS1 was associated with poor survival
and immune infiltration. It may be effective to use TSPOAP1-AS1 as a biomarker of prognosis and
therapeutic target in CESC.
COL1A1, COL1A2, CHN1, and FN1 Promote Tumorogenesis and Act as Markers of Diagnosis and Survival in Gastric Cancer Patients
Authors: Yichao Yan , Yongbai Li , Hailiang Liang , Dongbo Chen , Bo Li , Murshed Abduh 
Published: January 2025

Objectives:
This study aimed to comprehensively investigate the molecular landscape
of gastric cancer (GC) by integrating various bioinformatics tools and experimental validations.

Methodology:
GSE79973 dataset, limma package, STRING, UALCAN, GEPIA, OncoDB,
cBioPortal, DAVID, TISIDB, Gene Set Cancer Analysis (GSCA), tissue samples, RT-qPCR,
and cell proliferation assay were employed in this study.

Results:
Analysis of the GSE79973 dataset identified 300 differentially expressed genes
(DEGs), from which COL1A1, COL1A2, CHN1, and FN1 emerged as pivotal hub genes using
protein-protein interaction network analysis. Subsequent validation across The Cancer Genome
Atlas (TCGA) datasets confirmed their up-regulation in GC tissues compared to normal controls.
Promoter methylation analysis revealed decreased methylation levels of these hubs in GC
tissues, suggesting their potential role in tumorigenesis. Mutational analysis using cBioPortal
showcased frequent mutations in these genes, particularly FN1, further highlighting their significance
in GC pathogenesis. Survival analysis indicated their correlation with reduced overall
survival rates among GC patients, supported by the development of a robust prognostic model.
Prediction of hub-associated miRNAs and gene enrichment analysis provided insights into their
regulatory mechanisms and downstream pathways, implicating their involvement in extracellular
matrix remodeling and cell migration. Drug sensitivity analysis revealed correlations between
hub gene expression and drug response, while RT-qPCR validation confirmed their upregulation
in clinical GC samples. Finally, functional assays demonstrated the impact of FN1
knockdown on cellular proliferation, colony formation, and wound healing capacities.

Conclusion:
Overall, this study elucidates the crucial role of COL1A1, COL1A2, CHN1, and
FN1 in GC pathogenesis and underscores their potential as diagnostic markers and therapeutic
targets.
Development of Lentiviral Packaging Cells and Scale Up of Production to Meet the Growing Demand in Cell and Gene Therapy
Authors: van Heuvel Yasemin , Stitz Jörn 
Published: January 2025

Abstract:
Gamma-Retroviral (RVVs) and lentiviral vectors (LVVs) represent indispensable tools
in somatic gene therapy, mediating the efficient, stable transfer of therapeutic genes into a variety
of human target cells. LVVs, in contrast to RVVs, are capable of stably genetically modifying
non-proliferating target cells, making them the superior instrument in cell and gene therapy. To
date, the LVV manufacturing process employs human embryonic kidney cells (HEK293) and derivatives
thereof transiently transfected with multiple plasmids encoding the required viral vector
components. Alternatively, stable packaging cell lines were developed and engineered to express
all vector components in trans. Currently, these cells are mostly cultured in cell stacks, where they
grow adherently in 2D layers, limiting the scale-up of vector production. The production of viral
vectors using stable suspension cell lines enables larger-scale production and higher yields under
controlled conditions. Here, we review the improvements made to enhance vector safety and production
yield. Current advancements in the establishment of stable packaging cell lines enabling
inducible and constitutive LVV production are summarized and discussed. Manufacturing processes
for lentiviral vectors using bioreactors with perfusion systems are required to meet the growing
demand in cell and gene therapy and to reduce production and therapy costs.
Recent Developments in Oral Drug Delivery of Prokinetic Agents: Nanoparticles and Beyond
Authors: Dass Rameshwar , Bhatia Meenakshi , Rath Goutam , Dhingra Ashwani K. 
Published: January 2025

Abstract:
Prokinetic agents are drugs used to enhance gastrointestinal motility and treat disorders
such as Gastroesophageal Reflux Disease (GERD) and gastroparesis. pH-dependent release systems
offer targeted drug delivery, allowing prokinetic agents to be released specifically in desired
regions of the gastrointestinal tract. This optimizes drug efficacy and minimizes systemic side effects.
Gastroretentive formulations enable sustained drug release, which is particularly beneficial
in conditions requiring prolonged gastric residence time, such as gastroparesis. Nanoparticles have
emerged as promising carriers for improving prokinetic agent delivery and enhancing drug stability,
solubility, and absorption. These nano-systems protect drugs from degradation, leading to improved
bioavailability and controlled drug release. Furthermore, incorporating mucoadhesive technologies
promotes prolonged drug-mucosa interactions, facilitating enhanced drug absorption and
reducing dosing frequency. These recent advancements have the potential to revolutionize the oral
drug delivery of prokinetic agents, offering improved therapeutic outcomes, enhanced patient compliance,
and reduced side effects. However, scalability, biocompatibility, and safety challenges
warrant further investigation and validation through preclinical and clinical studies. This review
highlights recent advances in oral drug delivery systems for prokinetic agents, focusing on innovative
approaches such as pH-dependent release, gastroretentive formulations, nanoparticles, and mucoadhesive
technologies. In conclusion, integrating advanced oral drug delivery systems for prokinetic
agents presents a promising avenue for managing gastrointestinal disorders. Continued research
and collaboration among academia, industry, and healthcare professionals are crucial to unlocking
the full potential of these innovations and ultimately translating them into clinically effective
treatments for patients.
Improvement in Compatibility and Drug Release Performance of Hot-Melt Pressure-Sensitive Adhesives by Physical Blending Technique
Authors: Yang Jiayi , Yin Shuo , Wu Tan , Zhang Yangyang , Zhu Chunyun , Feng Nianping , Guo Teng 
Published: January 2025

Background:
Hot-melt Pressure-sensitive Adhesives (HMPSA) are eco-friendly pressuresensitive
adhesives, with the potential of being used as substrates for transdermal patches. However,
due to the low hydrophilicity of HMPSA, the application is limited in the field of Traditional Chinese
Medicine (TCM) plasters.

Methods:
Three modified HMPSA were prepared with acrylic resin EPO, acrylic resin RL100, and
Polyvinylpyrrolidone (PVP) as the modifying materials. The physical compatibility between HMPSA
and the modifying materials was investigated through in vitro release performance, viscosity, softening
point, cohesion, and fluidity, so as to determine the most effective modifying material. The impact
of the modified HMPSA on the release properties of different TCM ingredients was elucidated
by the performance of water absorption and contact angle behavior.

Results:
With the addition of the modifying materials, both the viscosity and the softening point of
HMPSA were improved, with the flowability reduced and the cohesion maintained. The morphological
and structural changes reflected the physical compatibility between HMPSA and the three modifying
materials. According to the results of in vitro release experiments, PVP effectively improved
the release performance of paeoniflorin, ephedrine hydrochloride, and cinnamaldehyde in HMPSA,
with no significant impact on the release performance of eugenol. The changes in the drug release
performance of HMPSA may be attributed to the improved hydrophilicity of HMPSA after physical
modification.

Conclusion:
The compatibility and the drug release performance of HMPSA were effectively enhanced
after the addition of the modifying materials by the physical blending technique. Among the
three modifying materials, PVP has been found to be an ideal modifying material for HMPSA in the
field of TCM plasters due to its effects on drug release performance.
Aryl Hydrocarbon Receptor Establishes a Delicate Balance between the Level of the Trace Amine Tryptamine and Monoamine Oxidase Activity in the Brain and Periphery in Health and Conditions such as Neurodegenerative, Neurodevelopmental, and Psychiatric Disorders
Authors: Kot Marta 
Published: January 2025

Abstract:
The purpose of this review was to analyse the literature regarding the correlation between
the level of tryptamine, aryl hydrocarbon receptor (AHR) signalling pathway activation, and monoamine
oxidase (MAO)-A and MAO-B activity in health and conditions such as neurodegenerative,
neurodevelopmental, and psychiatric disorders. Tryptamine is generated through the decarboxylation
of tryptophan by aromatic amino acid decarboxylase (AADC) in the central nervous system (CNS),
peripheral nervous system (PNS), endocrine system, and gut bacteria. Organ-specific metabolism of
tryptamine, which is mediated by different MAO isoforms, causes this trace amine to have different
pharmacokinetics between the brain and periphery. Reactive oxygen species (ROS) generated by
MAO can influence miRNA-CYP enzyme regulatory network and affect mitochondrial function.
Tryptamine regulates AHR function by acting as an endogenous ligand for AHR, initiating AHR activation
and inhibiting the expression of the CYP1A1 and CYP1A2 genes. The dysregulation of
AHR signalling, triggered by endogenous tryptamine binding, can disrupt the regulation of prolactin
levels. Depending on the tryptamine concentration and context, tryptamine can be beneficial or
harmful. By acting as an agonist of inhibitory serotonin receptors and trace-amine associated receptor
1 (TAAR1) and an antagonist of excitatory serotonin receptors, it can engage in diverse physiological
interactions with serotonin. Increased tryptamine production is observed under hypoxic conditions
and is associated with hypoxia-inducible factor 1α (HIF-1α) activation, leading to AHR activation.
Dysregulation of the association between tryptamine levels, AHR signalling pathway activation,
and MAO activity are observed in Alzheimer’s disease (AD), Parkinson’s Disease (PD), Autism
Spectrum Disorder (ASD) and schizophrenia.
Physically Crosslinked Polymeric Network for Controlled and Mucoadhesive Release of Miconazole for Topical Ocular Delivery
Authors: Farooq Umar , Rasul Akhtar , Mehmood Yasir , Shahid Hira , Bin Jardan Yousef A. , Ibenmoussa Samir , Bourhia Mohammed 
Published: January 2025

Background:
Eudragit L100, filled with miconazole and gelatinous polymeric eye drops,
is designed to sustain the drug release and increase ocular effect.

Methods:
The solvent diffusion technique was used to obtain the polymeric solution. The formulations
developed were fully characterized and examined.

Results:
The optimized drug had a particle size of 71.15 2.3 nm, a zeta potential of approx. 2.57 to
0.76 mV, a polydispersity index of approx. 0.184 and a capture efficiency of 0.10% of 58.049. The
prepared efforts showed a fungicidal effect on Candidiasis albicans cultures.

Conclusion:
The polymeric solution containing the drug-filled with miconazole (MZ) showed an
abrupt release in the first hours, followed by the pattern of sustained drug release. A higher cumulative
corneal permeability was observed from MZ-containing polymeric solution, which prolonged
MZ release in goat eyes. Mucoadhesive liners containing miconazole-loaded Eudragit L100 polymeric
solution provide a promising approach to the ocular administration of miconazole (a fungicide)
for the treatment of ocular infections requiring long-term drug administration.
Machine-Learning Based Computed Tomography Radiomics Nomgram For Predicting Perineural Invasion In Gastric Cancer
Authors: Huang Pei , Li Sheng , Deng Zhikang , Hu Fangfang , Jin Di , Xiong Situ , Fan Bing 
Published: January 2025

Objective:
The aim of this study was to develop and validate predictive models for perineural invasion (PNI) in gastric cancer (GC) using clinical factors and
radiomics features derived from contrast-enhanced computed tomography (CE-CT) scans and to compare the performance of these models.

Methods:
This study included 205 GC patients, who were randomly divided into a training set (n=143) and a validation set (n=62) in a 7:3 ratio. Optimal
radiomics features were selected using the least absolute shrinkage and selection operator (LASSO) algorithm. A radiomics model was constructed
utilizing the optimal among five machine learning filters, and a radiomics score (rad-score) was computed for each participant. A clinical model
was built based on clinical factors identified through multivariate logistic regression. Independent clinical factors were combined with the radscore
to create a combined radiomics nomogram. The discrimination ability of the models was evaluated by receiver operating characteristic
(ROC) curves and the DeLong test.

Results:
Independent predictive factors of the clinical model included tumor T stage, N stage, and tumor differentiation, with AUC values of 0.777 and
0.809 in the training and validation sets. The radiomics model was constructed using the support vector machine (SVM) classifier with the best
AUC (0.875 in the training set and 0.826 in the validation set). The combined radiomics nomogram, which combines independent clinical
predictors and the rad-score, demonstrated better predictive performance (AUC=0.889 in the training set; AUC=0.885 in the validation set).

Conclusion:
The nomogram integrating independent clinical predictors and CE-CT radiomics was constructed to predict PNI in GC. This model demonstrated
favorable performance and could potentially assist in prognosis evaluation and clinical decision-making for GC patients.