bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zhenwu Decoction Modulates PDE3A to Alleviate Inflammation in Diabetic Nephropathy
Authors: Yao Fang , Chen Xueqing 
Published: January 2025

Background:
Diabetic nephropathy, a complex microvascular complication of diabetes,
poses substantial health and economic challenges globally. ZWD, known for its multi-component
composition, has demonstrated potential therapeutic effects in DN, yet its molecular mechanisms
require further elucidation to support its clinical application.

Aim:
This study aimed to comprehensively investigate the active components, target molecules, and
molecular mechanisms of Zhenwu Decoction (ZWD), a Traditional Chinese Medicine (TCM) formula,
in the treatment of diabetic nephropathy (DN), with a focus on its anti-inflammatory effects
through the modulation of the PDE3A-mediated cAMP-PKA-NFκB axis.

Objective:
The primary objective was to identify the active components of ZWD, their targets, and
the underlying molecular pathways through which ZWD exerts its therapeutic effects on DN, specifically
focusing on the modulation of inflammation in renal cells under high glucose conditions.

Method:
A combined approach of network pharmacology, single-cell transcriptomics, and molecular
docking analyses was employed to investigate the active components, target molecules, and underlying
mechanisms of ZWD in treating DN. A high-glucose-induced HK-2 cell model was established
to simulate in vitro DN conditions. Cell viability was assessed using the CCK-8 assay, while quantitative
real-time PCR (qPCR) and Western blotting were employed to quantify gene expression and
protein levels, respectively.

Results:
Our analysis uncovered 141 active components in ZWD, which targeted 171 proteins involved
in pathways related to hypoxia response, neuroactive ligand-receptor interaction, urotensin II
signaling, and other pathways implicated in diabetes and vascular diseases. Among these, 75 overlapping
genes were pinpointed as potential therapeutic targets of ZWD for DN. Protein-protein interaction
networks revealed three functional clusters of targets potentially associated with oxidative
stress responses, lipid metabolism, and hormonal regulation. Cell-type specific analyses showed
differential expression of these targets in DN, particularly in proximal tubular epithelial cells. Notably,
through molecular docking, we discovered a strong binding affinity between PDE3A and betasitosterol.
In vitro experiments confirmed that ZWD extract modulated PDE3A expression, leading
to the suppression of the PKA/AMPK/NF-κB axis and attenuation of high glucose-induced inflammation
in HK-2 cells.

Conclusion:
This study identified that Zhenwu Decoction (ZWD) suppressed high glucose-induced
inflammation in renal cells by inhibiting the PDE3A-mediated cAMP-PKA-NFκB axis, highlighting
the potential of ZWD as an effective adjunct therapy for diabetic nephropathy and paving the way for
innovative anti-inflammatory treatments.
Using Multi-Omics Methods to Understand Gouty Arthritis
Authors: Gao Siming , Song Hui 
Published: January 2025

Abstract:
Gouty arthritis is a common arthritic disease caused by the deposition of monosodium
urate crystals in the joints and the tissues around it. The main pathogenesis of gout is the inflammation
caused by the deposition of monosodium urate crystals. Omics studies help us evaluate
global changes in gout during recent years, but most studies used only a single omics approach to
illustrate the mechanisms of gout. In this review, we review the genomics, transcriptomics, epigenetics,
proteomics, and metabolomics of gout, observing that different genes, DNA methylation,
miRNAs, LncRNAs, circRNAs, proteins, and metabolites are found between hyperuricemia, acute
gout arthritis, and chronic gout arthritis, and some of them are associated with disease activity,
prognosis or treatment, which help us broaden our understanding of the pathogenesis and provide
important clues for valuable biomarkers. To our knowledge, this is the first study that combines
all omics studies from genomics to metabolomics and may serve as a reference for future studies
to identify the key underlying pathways in gout.
An Integrative Computational Approach for the Identification of C-Abl Kinase Inhibitors from Anti-Parkinson Plant-Derived Bioactive
Authors: Umar Haruna Isiyaku , Ashimiyu-Abdusalam Zainab , Kumar Neeraj , Kuthi Najwa Ahmad , Victor Omoboyede , Abdulsalam Zainab Naeem , Aribo Elizabeth Oluwabunmi , Bello Ridwan Opeyemi , Bin Jardan Yousef A. , Nafidi Hiba-Allah , Bourhia Mohammed 
Published: January 2025

Background:
Oxidative stress is strongly linked to neurodegeneration through the activation
of c-Abl kinase, which arrests α-synuclein proteolysis by interacting with parkin interacting substrate
(PARIS) and aminoacyl tRNA synthetase complex-interacting multifunctional protein 2
(AIMP2). This activation, triggered by ataxia-telangiectasia mutated (ATM) kinase, leads to dopaminergic
neuron loss and α-synuclein aggregation, a critical pathophysiological aspect of Parkinson’s
disease (PD). To halt PD progression, pharmacological inhibition of c-Abl kinase is essential. Despite
three generations of tyrosine kinase inhibitors (TKIs) being explored for PD treatment, they present
significant concerns including poor blood-brain barrier penetration, off-target effects, and severe side
effects. Notably, there are currently no FDA-approved c-Abl kinase inhibitors in clinical usage for PD
treatment, highlighting the urgent need for potent, safe, and cost-effective alternatives.

Objective:
This study aims to identify potential c-Abl kinase inhibitors from plant-derived compounds
with reported anti-Parkinson's potential and their derivatives using molecular docking, molecular
dynamics simulations (MDS), and in silico pharmacokinetics and toxicity profiling.

Methods:
Seventy-eight compounds sourced from literature were docked against c-Abl kinase using
Maestro 12.5. The top three hit compounds, along with nilotinib (control drug), were subjected
to drug-likeness, ADMET profiling using the AI Drug Lab server and 100 ns MDS using Desmond.

Results:
Amburoside A, diarylheptanoid MS13, and dimethylaminomethyl-substituted-curcumin
showed binding affinities close to nilotinib, with values of -12.615, -12.556, and -11.895 kcal/mol
respectively, compared to nilotinib's -16.826 kcal/mol. The three plant-derived compounds exhibited
excellent structural stability and favorable ADMET profiles, including optimal blood-brain barrier
permeation

Conclusion:
The three hit compounds identified in this study show potential as c-Abl kinase inhibitors.
Given the absence of FDA-approved c-Abl kinase inhibitors for PD, these findings are significant
as they could contribute new therapeutic options for the treatment and management of PD.
However, further in vitro and in vivo experiments are necessary to validate these findings.
Poly-(2-aminothiophenol) Functionalized Petroleum Coke for Fast Simultaneous Sequestration of Cd(II) and Pb(II) Ions from Industrial Effluents
Authors: Yakout Amr A. , Almalki Sultan G. , Alshitari Wael H. 
Published: January 2025

Background:
Nowadays, the challenge between clean water production and promoting an
eco-friendly sorbent for the simultaneous fast and efficient removal of heavy metal ions is a hot topic
and has attracted much attention.

Objective:
The objective of this study was to fabricate a novel material (PATP@PET) by incorporating
poly-(2-amino thiophenol; PATP) into the matrix of Saudi Arabian petroleum coke (PET) for
simultaneous fast and efficient removal of heavy metal ions.

objective:
The fabrication of a novel material (PATP@PET) by incorporating poly-(2-amino thiophenol; PATP) into the matrix of Saudi Arabian petroleum coke (PET) for simultaneous fast and efficient removal of heavy metal ions

Method:
The FTIR, EDX, SEM, and XRD techniques assessed the chemical structure and surface
morphology of the thio-functionalized petcoke. The effects of medium pH, mass dosage of sorbent,
metal ion concentration, and coexisting ions were investigated and optimized using batch sorption.

Result:
The excellent sorption capacity of PATP@PET sorbent towards the divalent lead and cadmium
ions (98.44% and 312.5 mg.g-1 for Pb(II) and 90.15% and 217.4 mg.g-1 for Cd(II)) was realized
by strong complex formation with the sulfur atoms of green petcoke and the thiol groups of poly-2-
aminothiophenol moieties. The adsorption equilibrium data was best fitted to the pseudo-secondorder
kinetic model and Langmuir adsorption isotherm. The reusability performance was tested for
10 cycles, and the simultaneous removal of Pb(II) and Cd(II) ions from industrial effluents was accomplished
in 30 minutes with 100% removal efficiency at pH 6-7.

Conclusion:
PTAP-PET also demonstrated amazing performance for Cd(II) and Pb(II) removal in
industrial wastewater samples. Subsequently, PTAP-PET contributes to developing fast, efficient,
low-cost water remediation solutions for heavy metal ions that can potentially be translated into industrial-
scale applications.
Bioactive Products Targeting C-Met As Potential Antitumour Drugs
Authors: Zhao Liying , Qian Chunmei , Ma Xiaoqi , Wang Xiaoyu 
Published: January 2025

Abstract:
Mesenchymal‒epithelial transition factor (c-Met), a receptortyrosine kinase (RTK), plays a vital role in
cell proliferation, migration and invasion, and tumour metastasis

Objective:
With increasing duration of treatment, many tumours gradually develop drug resistance. Therefore,
novel antitumour drugs need to be developed to treat patients with tumours. Targeting c-met inhibitors may be an
effective treatment strategy.

Methods:
Scientific databases such as ScienceDirect, PubMed, the Wiley Online Library, and Social Sciences
Citation Index were used to collect information. All the relevant literature was reviewed, and the available literature
was screened. The upstream and downstream pathways of c-Met and their relevance to antitumour effects
were searched based on the articles' title, abstract, and full text. The c-Met-targeting drugs with antitumour effects
are summarized below. A "citation within a citation" or snowballing approach was used in this screening process
to identify additional papers that may have been missed in the initial literature screening process. High-quality
studies published in peer-reviewed journals were summarized and prioritized for citation in the review.

Results:
In recent years, research on small-molecule targeted drugs has developed rapidly. Many results have also
been achieved in the synthesis and isolation of c-Met inhibitors from natural compounds and traditional Chinese
medicines.

Conclusion:
This article summarizes the developments in anti-c-Met drugs, which are synthesized and isolated
from natural compounds and traditional Chinese medicine (TCM). This study provides primary resources for the
development of c-Met inhibitors.
Schisanhenol Inhibits the Proliferation of Hepatocellular Carcinoma Cells by
Targeting Programmed Cell Death-ligand 1 via the STAT3 Pathways
Authors: zhang Zhihong , Zhong Yiwen , Han Xu , Hu Xueyang , Wang Yuhan , Huang Lei , Li Siying , Li Ziqing , Wang Chunmei , Li He , Sun Jinghui , Zhuang Wenyue , Wang Mengyang , Chen Jianguang , Liu Wei , Liu Chang , Guo Xin , Yuan Siyu , Wu Jiping 
Published: January 2025

Background::
Programmed cell death-ligand 1 (PD-L1) is overexpressed in tumor cells, which promotes
tumor cell survival and cell proliferation and causes tumor cells to escape T-cell killing. Schisanhenol, a
biphenyl cyclooctene lignin-like compound, was extracted and isolated from the plant named Schisandra rubriflora
(Franch.).

Purpose:
In this work, we studied the anticancer potential of schisanhenol and explored whether schisanhenol
mediated its effect by inhibiting the expression of PD-L1 in vitro and in vivo.

Materials and Methods:
In vitro, we performed western blot, immunofluorescence, immunoprecipitation, and
colony formation assays to study the proteins, genes, and pathways related to the anti-tumour activity of schisanhenol.
In vivo, we explored the antitumor activity of schisanhenol through orthotopic liver transplantation and
subcutaneous transplantation tumor models of hepatocellular carcinoma (HCC) cells.

Results:
We found that schisanhenol decreased the viability of HCC cells. It inhibited the expression of programmed
cell death ligand-1 (PD-L1), which plays a pivotal role in tumorigenesis. Subsequently, schisanhenol
suppressed the expression of PD-L1 by decreasing the activation of STAT3. Furthermore, we found that schisanhenol
inhibited the activation of STAT3 via JAK/STAT3 (T705), Src/STAT3 (T705), and
PI3K/AKT/mTOR/STAT3 (S727) pathways. Colony formation tests showed that schisanhenol suppressed cell
proliferation by inhibiting PD-L1. Schisanhenol also enhanced cytotoxic T lymphocytes (CTL) activity and regained
their ability to kill tumour cells in co-culture. Finally, in vivo observation confirmed the antitumor activity
of schisanhenol.

Conclusion:
Schisanhenol inhibits the proliferation of HCC cells by targeting PD-L1 via the STAT3 pathways.
These findings prove that schisanhenol is a valuable candidate for HCC therapeutics and reveal previously unknown
characteristics of schisanhenol.
Rhizopogon luteolus and Ganoderma adspersum Extracts Inhibit Invasion through the
Crosstalk between Anti-oxidant Activity and Apoptosis Induced by pAKT/Rb
Authors: Demiray Aydın , Karagür Ege Rıza , Tel-Cayan Gülsen , Tokgün Onur , Akça Hakan , Duru Mehmet Emin 
Published: January 2025

Objective:
Lung cancer is the primary cause of cancer-related deaths globally. Protein kinase B (AKT)
protein is associated with many pathways in non-small cell lung cancer (NSCLC), such as proliferation, migration,
invasion, and apoptosis. Mushrooms have a long history of being used in traditional medicine to treat various
diseases. Scientists have been exploring the potential of mushrooms for their antioxidant and anticancer properties.
In our study, the anti-oxidant, invasion, and apoptosis effects of mushroom extracts were investigated in
NSCLC.

Materials and Methods:
Non-Small Cell Lung Cancer cell lines H1299, PC-3, and PC-14 were used in our study.
After obtaining the extracts of Rhizopogon luteolus and Ganoderma adspersum, IC50 value was calculated as
25.04-11.73-16.54 ng/ul for R. luteolus and 2.97-1.53-1.01 μg/ul for G. adspersum, respectively, in H1299, PC3
and PC14 cell lines. Afterward, proliferative and invasion effects, as well as apoptosis and anti-oxidant effects,
were investigated using the IC50 dose. Western blotting was performed to investigate the pathways of these effects.

Results:
According to the results of our study, Rhizopogon luteolus and Ganoderma adspersum extracts have
anti-proliferative and anti-invasive effects on non-small lung cancer cell lines and induced apoptosis, which has
been found to increase the anti-oxidant effect. It was found that this effect was due to cross-talk between antioxidant
activity and the AKT-Rb pathway.

Conclusion:
We anticipate that Rhizopogon luteolus and Ganoderma adspersum extracts will be effective in
cancer treatment by suppressing lung cancer cells via p-Akt and Rb.
Oral Microbiota Associated with Clinical Efficacy of Ustekinumab in Crohn’s Disease
Authors: Xu Feiyang , Xie Rui , He Le , Wang Honggang , Zhu Yifan , Yang Xiaozhong , Yu Huiming 
Published: January 2025

Background:
Crohn’s Disease (CD) is a chronic inflammatory gastrointestinal disease.
Ustekinumab (UST) has been utilized as a therapeutic option for CD patients. However, approximately
40-60% of patients exhibit an inadequate response to UST. Accumulating evidence has
confirmed the involvement of oral bacteria in the development of CD. Nevertheless, the relationship
between oral microbiota and the efficacy of UST therapy in CD patients has remained unexplored.

Materials and Methods:
We recruited 28 healthy individuals and 53 CD patients, 47 of whom
completed the entire UST therapy. Oral samples and clinical data were collected. The clinical response
and clinical remission were defined based on the CDAI score. Oral samples were analyzed
by 16S rRNA gene sequencing. The analysis of sequence data was performed by QIIME and R.

Results:
We revealed the oral microbial difference between the Healthy Control (HC) group and
the CD group. The enrichment of Fusobacteria, Leptotrichia, Capnocytophaga, and Campylobacter,
and the diminution of Haemophilus and Rothia were observed in the CD group. Differences
in oral microbiota were also identified among patients with different efficacy of UST. Compared
to the response and remission groups, both the non-response and non-remission groups
showed significantly higher levels of Fusobacteria and Leptotrichia. Predictive models for clinical
response and clinical remission in UST were developed based on oral microbiota, with the
Area Under the Curve (AUC) value of 0.944 and 0.930, respectively.

Conclusion:
Oral microbiota was relevant to the UST efficacy in patients with CD based on the
predictive model. These findings suggest that oral microbiota could serve as a non-invasive prognostic
biomarker for UST treatment in CD patients.
New Horizons in the Study of WNT and JAK/STAT Signaling Pathways in Cardiometabolic Diseases
Authors: Anatolyevna Snimshchikova Irina , Olegovna Plotnikova Mariia , Sergeevna Kulakova Anastasiia 
Published: January 2025

Aim
Despite advances in diagnosis and treatment, cardiometabolic diseases remain a major worldwide health problem. A new direction in identifying biomarkers that increase diagnostics predictive potential is the study of the WNT and JAK/STAT signaling pathways. Experimental and clinical studies have provided mixed evidence that determined the purpose of the study. This study aimed to examine the characteristics of the production of certain JAK/STAT and WNT signaling proteins in cardiometabolic pathology patients.

Materials and Methods
The research involved patients with myocardial infarction and cardiometabolic syndrome, as well as healthy individuals. Measurement of proteins STAT-1, STAT-3, STAT-6, β-catenin, sclerostin, WIF-1, GSK-3 α, and β, DVL-1 serum concentrations was carried out by ELISA.

Results
We established a wide range of JAK/STAT and WNT signaling protein values in the patient’s blood serum. In cardiometabolic syndrome, there was an increase in the concentrations of β-catenin, DVL-1, GSK-3α, and GSK-3β and a decrease in STAT-1, 3, compared with healthy individuals. During myocardial infarction, an increase in β-catenin, WIF-1, and DVL-1 and a decrease in sclerostin, GSK-3α, STAT-1, STAT-3, and STAT-6 were recorded compared with healthy individuals. The most significant intergroup differences were found for β-catenin, WIF -1, DVL-1, GSK-3α and STAT-6. Statistically significant correlations between the levels of a number of JAK/STAT and WNT signaling proteins and lipid profile parameters were revealed.

Conclusion
The data received about changes in the production of proteins of the WNT and JAK/STAT signaling pathways expand the molecular mechanisms of cardiometabolic diseases' immunopathogenesis understanding.
Teaching in the Digital Age—Developing a Support Program for Nursing Education Providers: Design-Based Research
Authors: Walzer Stefan , Barthel Carolin , Pazouki Ronja , Marx Helga , Ziegler Sven , Koenig Peter , Kugler Christiane , Jobst Stefan 
Published: January 2025

Background
Health care systems and the nursing profession worldwide are being transformed by technology and digitalization. Nurses acquire digital competence through their own experience in daily practice, but also from education and training; nursing education providers thus play an important role. While nursing education providers have some level of digital competence, there is a need for ongoing training and support for them to develop more advanced skills and effectively integrate technology into their teaching.

Objective
This study aims to develop a needs-based support program for nursing education providers to foster digital competencies and to test this intervention.

Methods
We used a design-based research approach, incorporating iterative development with expert consultation to create and evaluate a support program for nursing education providers. Focus groups were conducted online to assess needs, and thematic content analysis was used to derive key insights. The support program was then refined through expert feedback and subjected to a feasibility and satisfaction test, with participant evaluations analyzed descriptively.

Results
Six main categories emerged from the focus groups, highlighting key areas, including the use of digital technology, ongoing support needs, and the current state of digitalization in nursing education. The support program was developed based on these findings, with expert validation leading to adjustments in timing, content prioritization, and platform integration. Preliminary testing showed good overall satisfaction with the support program, although participants suggested improvements in content relevance and digital platform usability.

Conclusions
Although the feasibility test showed high satisfaction with the support program, low participation rates and limited perceived knowledge gain were major concerns. The results suggest that while the program was well received, further refinements, including a focus on competency-based approaches and addressing workplace barriers, are needed to increase participation and effectiveness of such interventions. The findings of this research can be used as a basis for the development of similar programs in other educational and health care contexts.
EVALUATION OF ANTIOXIDANT ACTIVITY OF EXTRACT COMBINATION OF GINGER AND LEMONGRASS
Authors: Faradiba  , Syarif Rezki Amriati , Anggrayni Anggi , Praditha Elyana , Amalia Alifiya Reski 
Published: January 2025

Aim and objective: This study to determine the antioxidant activity of the combination of ginger (Zingiber officinale) and lemongrass (Cymbopogon citratus) on reducing DPPH (2,2-diphenyl-1-picrylhydrazyl).
Methods: Quantitative measurement of the antioxidant activity of ginger and lemongrass extracts, as well as a combination of both with a concentration ratio of 1:1, 2:1, 1:2 using a UV-Vis spectrophotometer at a wavelength of 516 nm to determine the IC50 value.
Results: IC50 value of ginger extract 10.76 µg/mL, lemongrass extract 26.69 µg/mL, IC50 value 6.69 µg/mL for combination with concentration ratio 1:1, IC50 value 3.32 µg/mL for combination with concentration ratio 2:1. IC50 value 9.34 µg/mL for combination with concentration ratio 1:2
Conclusions: The combination of ginger and lemongrass extracts has synergistic antioxidant activity that can increase the antioxidant effect from the strong category to very strong category.

Peer Review History:
Received 17 October 2024; Reviewed 9 November; Accepted 18 December; Available online 15 January 2025
Academic Editor: Dr. Ahmad Najib, Universitas Muslim Indonesia, Indonesia, ahmad.najib@umi.ac.id
Average Peer review marks at initial stage: 5.5/10
Average Peer review marks at publication stage: 7.0/10