bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ferroptosis-related Biotargets and Network Mechanisms of Maslinic Acid
Against Myocardial Ischemia-reperfusion Injury: An Integrated
Bioinformatic and Experimental Approach
Authors: Li Qi , He Guiyuan , Zheng Rujie , Liu Chunlei , Wang Che , Liu Zhihao , Li Zhuqing , Lu Chengzhi 
Published: January 2025

Background:
Maslinic acid (MA), a pentacyclic triterpenoid compound derived from
leaves and fruits of Olea europaea, bears multi-pharmacological properties. Our previous studies
found that MA exerted a cardioprotective effect by modulating oxidative stress, inflammation,
and apoptosis during myocardial ischemia-reperfusion injury (MIRI). Nevertheless, data regarding the anti-ferroptosis effects of MA on MI/RI remains unidentified

Aim of the Study:
This study aimed to explore the effects of MA on ferroptosis induced by
MI/RI, with a focus on elucidating the underlying mechanisms through an integrated approach of
network pharmacology and experimental validation.

Materials and Methods:
Several public databases and a protein-protein interaction (PPI) network were used to identify the core targets shared by MI/RI, ferroptosis, and MA. The molecular
function, cell component, biological process, and potential signaling pathways of core genes
were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes
(KEGG) enrichment. Subsequently, molecular docking and in vitro experiments were carried out
to further validate network pharmacology results.

Results:
A total of 21 unique intersection genes were obtained as potential targets of MA in
treating MI/RI-induced ferroptosis. The 10 hub genes with the highest interaction scores were
identified from PPI analysis. GO and KEGG enrichment showed the contribution of the core
genes to pharmacological actions and mechanisms in MA treatment of MI/RI, especially the ferroptosis-related signaling pathways. Additionally, MA docked well with ranked core targets, including MAPK, MTOR, STAT3, PTGS2, and MDM2. Subsequently, in vitro experiments revealed that MA notably alleviated oxidative damage, reduced ferrous iron overload and ferroptosis, and regulated the expression of ferroptosis-related genes (GPX4, PTGS2, and ACSL4) in
erastin-induced H9c2 cells. Meanwhile, MA could significantly reduce phosphorylation of
MAPK (ERK1/2) levels in H9c2 cells.

Conclusion:
By utilizing network pharmacology and experimental data, our study revealed the
correlation between MA and ferroptosis following MI/RI, and concluded that MA might protect
against MI/RI by reducing ferroptosis through the ERK1/2 signaling pathway. This finding offered fresh insights into the pharmacological mechanisms of MA against MI/RI.
Pharmacological and Therapeutic Potential of a Natural Flavonoid Icariside II in Human Complication
Authors: Singh Dhirendra , Singh Randhir 
Published: January 2025

Abstract:
Emerging challenges to human health necessitate a coordinated effort to find both preventative
and therapeutic techniques, with natural products at the forefront of attempts to gain novel
medicines and minimize disease transmission and related death. The medicinal potential of
chemicals contained in plants has been known for centuries, leading to its use in homes and clinics
for the treatment of numerous disorders. Despite global advancements, plant-based medicines continue
to be utilized to treat various pathological illnesses or as alternatives to contemporary pharmaceuticals.
The safety and low toxicity of natural products have led to their increasing acceptability
for the prevention or treatment of many ailments. Flavonoids are biologically active compounds
that are classified as polyphenols, which are a type of secondary metabolite found in all plants.
Icariside II (ICA-II) is one of the secondary metabolites that belong to the flavonoid category of
phytochemicals and is present in Epimedium brevicornum Maxim. In recent years, ICA-II has
been discovered to show anti-inflammatory, antioxidant, anticancer, renal protecting, and cardiac
protective effects, as well as several other biological characteristics. This review is focused on the
exploration of the pharmacological activities of ICA-II. ICA-II is considered a prospective candidate
for future clinical investigations due to a number of therapeutic properties.
Illuminating the Role of Wound Healing-Related Hub Genes in Colorectal
Adenocarcinoma: Molecular Mechanisms, Prognostic Implications, and
Therapeutic Potential
Authors: Yan Yichao , Liang Hailiang , Li Yongbai , Chen Dongbo , Li Bo , Murshed Abduh 
Published: January 2025

Background:
Colorectal adenocarcinoma [COAD] is a prevalent and lethal form of
cancer. Understanding the molecular mechanisms underlying COAD progression is crucial for
developing effective diagnostic and therapeutic strategies

Methods:
This study aims to explore wound healing-related genes in COAD and their potential roles in tumorigenesis and prognosis using in silico and in vitro methodology

Results:
A set of 70 genes associated with the "wound healing" term ere extracted from the
Gene Ontology [GO] database [GO:0042060] and a protein-protein interaction [PPI] network
was constructed using the STRING database. The PPI network was analyzed with the CytoHubba plugin in Cytoscape, identifying four major hub genes: MMP2, FN1, NF1, and PTK7.
We then analyzed the expression of these hub genes across 16 COAD cell lines and nine normal colon cell lines using RT-qPCR, finding significant overexpression in COAD cell lines.
ROC curve analysis confirmed the diagnostic potential of these genes, with MMP2, FN1, and
NF1 showing high AUC values. Expression validation using the TCGA COAD cohort, OncoDB, and HPA databases corroborated these findings, highlighting the overexpression and
high protein levels of these genes in COAD. Promoter methylation analysis indicated lower
methylation levels in COAD samples, suggesting dysregulation through epigenetic mechanisms. Genetic alteration analysis via cBioPortal revealed a spectrum of mutations, with FN1
being the most frequently mutated. Prognostic analysis using a KM plotter showed that high
expression of the hub genes is associated with poorer overall survival [OS] and disease-free
survival [DFS]. Functional state correlations via CancerSEA suggested that these genes promote cell cycle, proliferation, metastasis, and stemness in COAD. Expression analysis in immune cells and drug sensitivity analyses highlighted the roles of MMP2, FN1, and NF1 in
macrophages and drug resistance. A miRNA-mRNA network constructed using miRNet identified hsa-miR-200a-3p as a central regulator. Finally, functional assays in HCT116 cells
demonstrated that knockdown of MMP2 and FN1 reduced proliferation, colony formation,
and wound healing, suggesting these genes as potential therapeutic targets in COAD.

Conclusion:
In conclusion, our study identifies MMP2, FN1, NF1, and PTK7 as key wound
healing-related hub genes in COAD.
Design and Synthesis of 1-(4-Bromo-2-(Pyrrolidine-1-Yl) Benzyl) Piperidine-Based Derivatives as Anti-Tubulin Agents
Authors: Guguloth Rambabu , Gubbiyappa Shiva Kumar 
Published: January 2025

Background:
Piperidines are among the essential synthetic fragments for designing
drugs and play a significant role in the pharmaceutical industry. The synthesis of newer derivatives
by incorporating different amines paves the way for the introduction of novel drug combinations
for current cancer treatments.

Method:
The new combinations of 1-(4-bromo-2-(pyrrolidine-1-yl) benzyl) piperidine derivatives
were synthesized by adding various amino groups. All the synthesized derivatives were characterized
using NMR and LC-MS. The anti-cancer activity of all the synthesized derivatives was studied
on three different cell lines, A549 (lung cancer), HCT-116 (colon cancer), and MCF-7(breast
cancer), using an MTT assay. The most potent compounds, 7h and 7k were further evaluated for
cell cycle and tubulin polymerization inhibitory activity. Further, in-silico analysis for the same
properties was performed using molecular docking using MM/GBSA and validated by RMSD.

Results:
All the synthesized derivatives showed selective cytotoxic potential against different cancer
cell lines. Most of the derivatives displayed comparable anticancer potential in comparison to
5-FU. The most potent derivative, 7h, further arrests the cancer cells in the G2/M phase and prevents
tubulin polymerization. The same was further confirmed using molecular docking on the
colchicine binding site.

Conclusion:
The derivative that arrests the cancer cells in the G2/M phase of the cell cycle and
induces depolymerization can be developed as a good lead for further development.
Marine Xanthones as Promising Phosphodiesterase-5 Inhibitors in the
Management of Erectile Dysfunction: An In silico Approach
Authors: Tien Lam Do , Thi Thuy Phan , Xuan Ha Nguyen , Le Thi My Chau 
Published: January 2025

Objectives:
Phosphodiesterase-5 (PDE5) is an enzyme that promotes the degradation of
cGMP in the blood, leading to a restriction in regulating blood flow in the penis, thereby reducing
cGMP causing difficulties for men in achieving hardness (erectile dysfunction). Natural products
with fewer side effects are being developed in many different treatment strategies and are necessary
today. The current study aims to evaluate this enzyme's in silico inhibitory potential and marine xanthones
through computational models.

Methods:
The database of marine xanthones was collected from previously published literature. Protein
structures were downloaded from the RCSB protein data bank (PDB ID: 1UDT). Molecular
docking studies were performed using the AutoDock Vina v1.2.3 program to conduct screening.
Molecular dynamics simulations were carried out with the GROMACS program to assess structural
stability, and gmx_MMPBSA was used to make free-binding energy calculations for each PDE5
protein complex with potential compounds. Furthermore, Density Functional Theory (DFT) was
applied in this study to calculate the atomic properties of the molecules based on quantum mechanics
using the Gaussian 09 program.

Results:
Molecular docking revealed that 21 compounds (staprexanthone A (69), emerixanthone E
(89), emerixanthone A (90), emerixanthone C (91), varixanthone (92), aspergixanthone H (95), austocystin
L (98), austocystin M (99), emerixanthone D (109), 15-acetyl tajixanthone hydrate (117),
tajixanthone hydrate (118), 16-chlorotajixanthone (119), citreamicin ε A (131), citreamicin ε B
(132), engyodontochone A (146), citreamicin θ B (151), citreaglycon A (152), dehydrocitreaglycon
A (153), neocitreamicin I (159), citreamicin α (161), ukixanthomycin A (165)) had superior binding
affinities (ΔG < -11 kcal/mol) compared to the control inhibitor. Molecular dynamics confirmed the
stability of the protein-ligand complexes. MM/GBSA analysis showed nine compounds (91, 98, 109,
118, 119, 151, 159, 161, 131) had binding energies comparable to or better than sildenafil. Quantum
mechanical estimates indicated their potential as electron donors and acceptors, highlighting their
antagonistic potential.

Conclusion:
These promising marine xanthones warrant further research to assess their PDE5 inhibitory
activity in vitro and in vivo. This could provide valuable insights for developing new natural
resource-based drugs to prevent or treat erectile dysfunction.
Microbial and Chemical Safety Aspects of Postbiotics: As their Tools in Improving Food Safety
Authors: Khani Nader , Shakeri Amir Hessam , Bonyadi Mojtaba , Khorrami Ramin , Rad Aziz Homayouni 
Published: January 2025

Abstract:
Various factors, including physical, chemical, and biological hazards threaten food safety.
Among these, the significance of microbial (bacteria and fungi) and chemical (biogenic
amines, mycotoxins, and heavy metals) contamination cannot be overstated. In recent years, a novel
approach has emerged for effectively managing these risks, which relies on probiotics and postbiotics.
Recent research suggests that postbiotics show promise as potential alternatives to probiotic
cells and can be valuable in improving food safety. The term “postbiotics” refers to soluble substances,
including enzymes, teichoic acids, muropeptides from peptidoglycans, polysaccharides,
proteins, and peptides. These substances are either produced by live bacteria or released when bacterial
cells break down. Postbiotics have gained significant attention due to their unique chemical
composition, well-established dosing guidelines, extended shelf life, and the Existence of different
signaling molecules that may possess antioxidant, anti-inflammatory, anti-obesity, immunomodulatory,
anti-hypertensive, and immunomodulatory properties. This review emphasizes the definition
of postbiotics and their role in reducing microbial and chemical contaminants to ensure food
safety.
Magnetic Resonance Imaging Study on Older Patients with Cognitive Impairment and Depression
Authors: Zhang Shuang , Qin Yuping , Ding Meng , yang Jining , Zhang Tao 
Published: January 2025

Background:
Understanding brain changes in older patients with depression and their relationship with cognitive abilities may aid in the diagnosis of depression
in this population. This study aimed to explore the association between brain lesions and cognitive performance in older patients with depression.

Methods:
We utilized magnetic resonance imaging data from a previous study, which included older adults with and without depression. Smoothed Regional
Homogeneity (ReHo) and local brain Amplitude of Low-frequency Fluctuation (ALFF) values were assessed to examine brain activity

Results:
The analysis revealed decreased ReHo in the left middle temporal gyrus, left middle frontal gyrus, and left precuneus, as well as increased local
ALFF in the right middle occipital gyrus, left postcentral gyrus, and right precentral gyrus in older patients with depression. These alterations may
contribute to behavioral and cognitive changes. However, no significant relationship was found between ReHo values and Montreal Cognitive
Assessment (MoCA) scores. In contrast, increased local ALFF in the left postcentral gyrus and right precentral gyrus was negatively correlated
with MoCA scores.

Conclusion:
This study demonstrated a significant association between regional brain alterations in patients with depression and cognitive behavior. Thus, this
work identified functional brain regions and cognitive performance in older adults with depression, highlighting specific brain regions that play a
crucial role in cognitive abilities in this population.
Intracranial Structural Malformations in Children in Tibet: CT and MRI Findings in a Single Tertiary Center
Authors: Yin Xuan , Ciren Dawa , Guojie Ciren , Zhang Guofu , Wang Jimei , Zhang He 
Published: January 2025

Objectives:
The objective of this study was to summarize the findings of children’s intracranial congenital or developmental malformations found during
imaging procedures in the Tibetan plateau.

Methods:
We retrospectively reviewed the imaging data of the suspected patients who presented with the central nervous system (CNS) malformations and
were enrolled either through the clinic or after ultrasound examinations between June 2019 and June 2023 in our institution. All imaging data were
interpreted by two experienced radiologists through consensus reading.

Results:
In this study, we recruited 36 patients, including two neonates, 17 infants and 17 children. Seven cases underwent an MRI examination, while the
others had a CT scan. Polygyria and pachygyria malformation were the most common type of congenital neurological malformations (7 cases,
31.8%), followed by cystic changes of the cerebral parenchyma (3 cases, 13.6%). Cerebral atrophy was the most common type of secondary CNS
abnormality(8 cases, 57.1%), followed by communicative hydrocephalus (3 cases, 21.4%). Five patients in the congenital group and 4 patients in
the secondary group had complex malformations. In the current study group, there were 8 deaths, 12 cases with neurological sequelae, 1 case with
normal development, and 15 cases lost to follow-up. There were no significant differences between the primary and secondary CNS groups in
terms of the outcome for both the infants and children groups.

Conclusions:
CNS malformations in the Tibetan Plateau are associated with high mortality and morbidity rates. Better utilization of imaging modalities could
help design tailored treatments as early as possible.
Improving Diagnostic Accuracy in Acute Pulmonary Embolism: Insights from Spectral Dual-energy CT
Authors: Shen Mei-Ling , Zhang Han-Wen , Liu Li-Hong , Liu Wei-Ming , Zhong Hua , Huang Biao , Wang Yu-li , Lin Fan 
Published: January 2025

Purpose:
This study aims to evaluate the clinical efficacy of spectral dual-energy detector computed tomography (SDCT) and its associated parameters in
diagnosing acute pulmonary embolism (APE).

Methods:
Retrospective analysis of imaging data from 86 APE-diagnosed patients using SDCT was conducted. Virtual monoenergetic images (VMIs) at 40,
70, and 100 KeV, Iodine concentration (IC) maps, Electron Cloud Density Map (ECDM), Effective atomic number (Z-eff) maps, and Hounsfield
unit attenuation plots (VMI slope) were reconstructed from pulmonary artery phase CT images. The subtraction (SUB) and ratios of VMIs were
calculated, and two experienced radiologists evaluated the patients. The Mann-Whitney U test assessed the parameter ability to differentiate
between normal and obstructed lung fields and detect emboli in the pulmonary artery. Receiver Operating Characteristic Curves (ROC) were
generated for performance evaluation.

Results:
Significant differences (p<0.001) in 40KeV, Ratio, SUB, and Z-eff were found between normal and embolized lung fields. Logistic regression
demonstrated good detection performance for Z-eff (AUC=0.986), SUB (AUC=0.975), and IC (AUC=0.974). Parameters such as 40KeV
(AUC=0.990), 70KeV (AUC=0.980), 100KeV (AUC=0.962), SUB (AUC=0.990), Z-eff (AUC=0.999), and IC (AUC=1.000) exhibited good
detection capabilities for identifying emboli in the pulmonary artery.

Conclusion:
SDCT facilitates the identification of diseased lung fields and localization of emboli in the pulmonary artery, thereby improving diagnostic
efficiency in APE.
Assessment of Prostate MR Image and Predictive Value for Benign Prostate Disease among Different DWI Sequences
Authors: Dan Hanli , Yang Lu , Tan Yuchuan , Zhang Yipeng , Tan Yong , Zhang Jing , Li Min , Lin Meng , Zhang Jiuquan 
Published: January 2025

Background:
Early diagnosis of prostate cancer can improve the survival rate of patients on the premise of high-quality images. The prerequisite for early
diagnosis is high-quality images. ZOOMit is a method for high-resolution, zoomed FOV imaging, allowing diffusion-weighted images with high
contrast and resolution in short acquisition times. RESOLVE DWI is an advanced MRI technique developed to obtain high-resolution diffusionweighted
images with reduced susceptibility-related artifacts.

Objective:
This study aimed to compare the image quality of conventional single-shot Echo-planar Imaging (ss-EPI), Diffusion-weighted Imaging (DWI),
zoomed FOV imaging (ZOOMit) DWI, and readout segmentation of long variable echo-trains (RESOLVE) DWI sequences for prostate imaging,
and optimize the strategy to obtain high-quality Magnetic Resonance Imaging (MRI) in order to discriminate malignant and benign prostate
diseases.

Methods:
Fifty-one patients were enrolled, including 31 with prostate cancer, 11 with prostate benign disease, and 9 with bladder cancer. Patients underwent
MRI scans using T2-weighted (T2W), ss-EPI DWI, ZOOMit DWI, and RESOLVE DWI (b = 0, 50, 1400 s/mm2) sequences using a 3.0T MRI
scanner. Subjective scores of image quality were evaluated by two independent radiologists. Differences in the subjective scores and objective
parameters among the three sequences were compared. The agreement and consistency between the findings of the two raters were evaluated with
Kappa or Intra-class Correlation Coefficient (ICC). Receiver Operating Characteristic (ROC) curves were used to distinguish malignant and benign
prostate disease.

Results:
The agreement of subjective scores of 51 patients was high or moderate between the two radiologists (kappa: 0.529–0.880). ZOOMit displayed the
highest clarity and the lowest distortion and artifacts compared to ss-EPI and RESOLVE. The two radiologic technicians obtained moderate or
high consistency of objective measurement (ICC: 0.527–0.924). In the ROC analysis, ADCmean and Prostate Imaging Reporting and Data System
(PI-RADS) scores for three sequences were comparable in differentiating prostate cancer from benign prostate disease (all p>0.05), in which
ZOOMit indicated the highest Area Under the Curve (AUC) (0.930 and 0.790, respectively).

Conclusion:
Compared to the other two sequences, ZOOMit can be deemed preferable to improve prostate MRI diffusion imaging as it has exhibited the
highest AUC in identifying prostate cancer.
Sound Touch Viscosity (STVi) for Thyroid Gland Evaluation in Healthy Individuals: A Pilot Study
Authors: Mao Feng , Jiang Yuemingming , Wang Yunzhong , Xu Zhenbin , Wei Zhuo , Zhu Xueli , Chen Libin , Zhang Shengmin 
Published: January 2025

Objective:
This prospective study aimed to establish the typical viscosity range of the thyroid gland in healthy individuals using a new method called the
Sound Touch Viscosity (STVi) technique with a linear array transducer.

Methods:
Seventy-eight healthy volunteers were enrolled between March, 2023 and April, 2023. Thyroid viscosity was measured using the Resona R9
ultrasound system equipped with a linear array transducer (L15-3WU). Each patient had three valid viscosity measurements taken for each thyroid
lobe, and the average values were analyzed. Thyroid gland stiffness was measured and analyzed simultaneously

Results:
The study included 51 women and 27 men with an average age of 48 years. The mean viscosity measurement for a normal thyroid gland was 1.10
± 0.41 Pa.s (ranging from 0.38 to 2.25 Pa.s). There were no significant differences in viscosity between the left and right lobes of the thyroid gland.
We found no significant variations in viscosity based on gender, age, or body mass index (BMI). There was a notable positive correlation between
thyroid viscosity and stiffness measurements (r = 0.717, p < 0.001).

Conclusion:
Our findings suggest that STVi is a highly reliable method for assessing the thyroid. This technique holds promise as a new, non-invasive approach
to evaluating thyroid parenchyma viscosity.