bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Anti-lung Cancer Mechanism of Qingzao Jiufei Decoction was Studied based on Network Pharmacology, Molecular Docking, and Experimental
Verification
Authors: Wen Xiaoli , Cai Fangyan , Tan Min , Zhang Ge , Zhang Xiang , Xie Lihua , Yao Ziheng , Liu Hongning 
Published: February 2025

Background:
Lung cancer (LC) is one of the most common cancers in the world, with both
its incidence and mortality rates ranking at the top position among all types of cancers, posing a serious
threat to human health. Qingzao Jiufei Decoction (QD) has been used clinically to treat lung cancer,
but its mechanism of action remains unclear.

Objective:
This study aims to elucidate the potential pharmacological mechanisms of QD in treating
LC through network pharmacology, molecular docking, molecular dynamics simulation (MDS), and
animal experiment validation.

Methods:
Active components of QD were screened utilizing the TCMSP and HREB databases, and
potential targets were predicted using network pharmacology methods. Relevant targets for LC were
identified from the Genecards, OMIM, and TTD databases. Intersecting targets between QD and LC
were imported into the STRING 12.0 database and Cytoscape 3.10.0 software to create proteinprotein
interaction (PPI) network diagrams, and Gene Ontology (GO) function analysis and Kyoto
Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted through
using the DAVID database to identify core active components and key targets. Molecular docking
was employed to assess the binding affinity of core active components with key targets in lung cancer,
and MDS was used to evaluate the stability of the target-active component complexes. An in vivo
lung cancer model was used to verify the therapeutic effects of QD, and Western blot analysis was
used to confirm the pharmacological mechanisms of QD in treating lung cancer.

Results:
Network pharmacology analysis has identified 9 core components and 9 key targets. GO and
KEGG analyses have revealed a total of 185 signaling pathways, with the PI3K-Akt signaling pathway
and MAPK signaling pathway being the two most significantly enriched pathways. Molecular
docking results showed that all 9 core components and 9 key targets exhibited significant binding activity
(binding energy < -5 kcal/mol). MDS study further simulated and confirmed strong and stable
interactions between targets and active components. In an in vivo lung cancer model, QD significantly
inhibited tumor growth, while Western blot analysis demonstrated that QD exerted its therapeutic effects
on lung cancer by inhibiting the phosphorylation of ERK, JNK, and p38 in the MAPK signaling
pathway.

Conclusion:
This experimental study found that QD can significantly inhibit the growth of lung cancer
through a multifaceted approach involving various components, targets, and pathways, providing
a foundation for the development and clinical application of new drugs targeting lung cancer for QD.
Furthermore, it offers valuable insights into anti-tumor research with Traditional Chinese Medicine
(TCM) and facilitates a more comprehensive interpretation of TCM principles through the lens of
modern science.
Pharmacokinetic Interactions of Paxlovid Involving CYP3A Enzymes and P-gp Transporter: An Overview of Clinical Data
Authors: Maideen Naina Mohamed Pakkir , Kandasamy Krishnaveni , balasubramanian Rajkapoor 
Published: February 2025

Background:
The US FDA has approved paxlovid, a combination of nirmatrelvir and ritonavir, as
the first oral treatment for the management of mild-to-moderate COVID-19 patients.

Objective:
The purpose of this review article is to explore the clinical data that is currently available regarding
the drug-drug interactions (DDIs) of paxlovid with various medications.

Methods:
Keywords, such as drug interactions, paxlovid, ritonavir, nirmatrelvir, pharmacokinetic interactions,
CYP3A, and P-glycoprotein, were used to search online databases, including LitCOVID, Scopus, Embase, EBSCO
host, Google Scholar, ScienceDirect, Cochrane Library, and reference lists.

Results:
Paxlovid interacted with a variety of medications due to strong inhibition of CYP3A4 and P-gp transporter
protein by ritonavir and the dual function of nirmatrelvir as a substrate and inhibitor of CYP3A enzymes
and P-gp transporter protein. Numerous case reports and other studies determined that the risk of toxicities
of several drugs, including anticoagulants (warfarin, rivaroxaban), calcium channel blockers (nifedipine,
manidipine, verapamil), statins (atorvastatin), immunosuppressants (tacrolimus), antiarrhythmics (amiodarone),
antipsychotics (clozapine, quetiapine), and ranolazine have been enhanced by the concomitant administration
of paxlovid.

Conclusion:
Adverse effects of paxlovid from DDIs can range from less-than-ideal therapeutic responses to
potentially fatal toxicities. Effective management requires close observation, adjustments to dosage, and assessment
of substitute treatments. Collaboration between pharmacists and other medical professionals is necessary
to guarantee effective and safe treatment outcomes of paxlovid therapy.
Detailed Review of Melatonin and its Role in Managing the Symptoms of Depression
Authors: Dedmari Tooba , Ramzan Sameena , Hussain Masoodi Mubashir , Hassan Mir Reyaz 
Published: February 2025

Abstract:
Depression, which is emerging as one of the most widely prevalent
neuropsychiatric disorders worldwide, has affected people across all age groups.
However, it is currently primarily affecting adults aged 18 to 25. The condition is
characterized by disrupted sleep cycles, diurnal variation, and disturbed core body
temperature rhythms. Currently, the anti-depressant medications that are prescribed
and authorized, such as tricyclic antidepressants (TCAs), selective serotonin reuptake
inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine
oxidase inhibitors (MAOIs), benzodiazepines, anxiolytics, and antihistamines have
demonstrated effective outcomes. However, the findings from the STAR*D
(Sequenced Treatment Alternatives to Relieve Depression) study are disappointing.
The results show that currently available antidepressants yield only minimal
improvements in effectiveness for patients who did not respond to their initial
medication. Melatonin has emerged as a promising option for tackling these issues.
Moreover, due to its diverse abilities to regulate circadian rhythms and promote
synchronization, melatonin offers an alternative therapeutic approach to alleviate the
side effects and target the underlying causes of depression linked to an impaired
circadian system. This review intends to provide a comprehensive overview of
melatonin, including aspects such as its structural analysis, biosynthesis, regulation,
catabolism, and involvement in various physiological processes, particularly
highlighting its antidepressant activity.
Music Therapy may Decrease Radial Artery Spasm Rates and Increase Satisfaction during Coronary Angiography
Authors: Aslan Muzaffer , Okşen Doğaç , Yavuz Yunus Emre , Kaynak Çağdaş 
Published: February 2025

Introduction:
With the widespread use of the radial artery in catheterization procedures,
radial artery spasm (RAS) is frequently considered an undesirable event. It is known that anxiety
increases RAS, and listening to music helps individuals control anxiety during the procedure. This
study aimed to investigate the effects of music concerts on RAS.

Methods:
In this prospective study, imaging and interventional coronary catheterization procedures
using the radial artery were included. One group listened to a musical recital during the procedure,
while the other group was treated in a quiet environment. The demographics, procedural parameters,
and complications of both groups were compared.

Results:
The study included a total of 147 patients, with an average age of 51.6 ± 11.1 years. Of these,
78 patients (53%) listened to music, while 69 patients (46.9%) underwent catheterization in a quiet
environment. The impact of music therapy on the RAS was found to be significant (11.5% vs.
20.3%; p=0.035). While music therapy showed a potential to reduce RAS rates, its effect was not
statistically significant in multivariate analysis (p=0.055).

Conclusion:
Music is a feasible, simple, and inexpensive method for reducing anxiety levels in patients.
Listening to music during catheterization can reduce procedural discomfort and the frequency
of undesirable events by helping people control their anxiety.
AraMultiOmics: A Platform for Generating Multi-Omics Features for Studying Symbiosis in Arabidopsis thaliana and Arbuscular Mycorrhizal Fungi
Authors: Kang Jee Eun 
Published: February 2025

Background:
Recent investigation revealed that arbuscular mycorrhizal fungi (AMF)
brought major changes in the transcriptome of non-host plant- Arabidopsis thaliana (A. thaliana)
within the AM network constructed by the hyphae of AMF connecting multiple plant roots. Although
there is enormous omics data available for A. thaliana, most AM-related information has
been restricted to transcriptome studies.

Objective:
We aimed to provide a comprehensive toolset for analyzing AM signaling-driven molecular
interactions in A. thaliana.

Methods:
We developed ten modules: 1) Epigenetic regulation in protein–nucleic acid interactions
(PNI), 2) DNA structure and metal binding profiles, 3) Transcription factor (TF) binding profiles, 4)
Protein domain–domain interactions (DDI), 5) Profiling of protein-metal and protein-ligand interactions
with complex structures (PLP) based on alignment of similar protein structures, 6) Carbohydrate-
lipid-protein interactions (CLP) – analysis of lipidome-proteome interactions, Nglycosylation/
glycan structure data, and carbohydrate-active enzyme/substrate predictions, 7) Metabolic
pathway analysis, 8) Multiple omics association studies, 9) Gene Ontology (GO) and Plant
Ontology (PO) analysis, and 10) Medicago transcriptome and epigenetic information.

Results:
For the program demonstration, we generated various comparative datasets based on differentially
expressed genes (DEGs) from Arabidopsis thaliana (A. thaliana) of non-arbuscular mycorrhizal
(non-AM) and arbuscular mycorrhizal (AM) phenotypes, as well as DEGs from Medicago
truncatula (M. truncatula). These datasets were analyzed using statistical methods and artificial
neural networks. The program demonstrated a range of advantages in studying molecular interactions
related to AM symbiosis.

Conclusion:
To aid in the inference of AM-driven changes and the identification of AM-derived
molecules during AM symbiosis, the program offers a user-friendly platform for generating datasets
with key features, which can then be integrated with various downstream statistical methods. The
program code is freely available for download at www.artfoundation.kr.

other:
It also provides various multi-omics approaches in A. thaliana study.
Visible Light-Induced Catalyst-Free Synthesis of Dibenzo[a,g]carbazoles
Authors: Qin Shuangqi , Li Mingrui , Zhang Fang-Lin , Xu Haixing 
Published: February 2025

aims:
to develop a mild and efficient synthetic method for the synthesis of dibenzo[a,g]carbazoles

background:
the conventional methods usually include the extending of the conjugate structure of carbazole-based molecules. Recently, photoredox catalysis has been applied into the synthesis of these dibenzocarbazole compounds, however, the existing methods still suffer the vulnerabilities, such as the addition of noble metal catalysts, highly functionalized starting materials, and metal salts, which could not give satisfaction from the practical perspective.

objective:
a photochemical catalyst-free and metal-free route to these important dibenzocarbazole compounds holds significant superiority and great potential to be developed.

method:
The visible light-induced synthesis of dibenzocarbazole is designed as a two-step one-pot reaction via 6π electrocyclization and consequent dehydrogenation, which would be realized by screening of reaction conditions.

result:
a series of dibenzo[a,g]carbazoles were successfully afforded via this method under purple LE at room temperature

conclusion:
the visible light-induced catalyst-free and metal-free synthetic method to dibenzo[a,g]carbazoles has been successfully developed.

other:
this method offers a promising alternative for the construction of benzocarbazole compounds
Network Pharmacology and Experimental Validation to Reveal the Pharmacological Mechanisms of Gynostemma pentaphylla against Acute Pharyngitis
Authors: Zhong Juan , Wu Xiaozhong , Huang Chunxi , Li Yongqiang , Huang Min , Xu Liuyan , Lu Jianfeng , Pang Lili , Huang Qiuju , Chen Jing 
Published: February 2025

Background:
Acute pharyngitis (AP) is a prevalent ailment. Gynostemma pentaphylla
(GP), a traditional Chinese medicine (TCM), may treat AP due to its anti-tumor and anti-inflammatory
properties, but this remains unexplored.

Methods:
This study utilized the TCMSP and Swiss Target Prediction databases to analyze GP's
chemical composition and target proteins. The Genecards database was used to identify targets relevant
to AP. A PPI network diagram of drug-disease intersection targets was created using the
STRING database, and Cytoscape was utilized to create a network visualization diagram of “GP
active components-targets-AP” in order to determine key active components of GP in treating AP.
Gene ontology (GO) and biological pathway (KEGG) enrichment analyses were conducted on targets
in the David database. Molecular docking verification of key targets and components was performed
using AutoDock Vina software. In animal experiments, a rat model of AP was induced by
a 15% concentrated ammonia solution, and HE staining was conducted to observe histopathological
changes in the rat pharynx after intragastric administration of Houyanqing. ELISA was used to
detect expression levels of serum interleukin-1-beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis
factor (TNF-α).

Results:
A total of 18 active ingredients were screened from GP, among which Ruvoside _ qt,
Rhamnazin, 3 ' -methyleriodictyol, and sitosterol were five key active ingredients. The key targets
involved EGFR, STAT3, MAPK3, SRC, AKT1, etc. KEGG enrichment analysis showed that GP
mainly acted on Pathways in cancer, P13K-AKT signaling Pathways, JAK-STAT signaling pathways,
and other signaling pathways. Molecular docking results showed that four core compounds
and five key targets met the energy matching. Animal experiments showed that compared with the
normal group, the expression levels of IL-1β, IL-6, and TNF-α in the AP model group were significantly
up-regulated (P < 0.05). In addition, compared with the model group, intragastric administration
of the dexamethasone group and gypenosides group could alleviate the up-regulation of inflammatory
factors in model rats, and the levels of IL-1β, IL-6, and TNF-α were decreased (P <
0.05).

Conclusion:
This study predicted the possible targets of GP in the treatment of AP through network
pharmacology. The results suggest that gypenosides may inhibit the expression of inflammatory
factors by regulating Pathways in cancer, P13K-AKT, and JAK-STAT signaling pathways to
treat AP.
GluN2B of NMDA Receptor and Calmodulin: Balanced Calcium Regulation to Combat Alzheimer's Disease
Authors: Tiwari Prashant , KADIRI SUNIL KUMAR , Khobragade Deepak Shamrao , Dubey Sonal 
Published: February 2025

Abstract:
N-methyl-D-Aspartate receptor (NMDAR) mediated excitatory glutamatergic neurotransmission
is essential for synaptic plasticity and neuronal survival. However, excessive NMDAR activation
results in excitotoxicity and encourages cell death, as well as providing a probable explanation
for the development of Alzheimer's disease (AD) like pathology. It’s possible because of Mg2+ ions,
which block NMDA receptors while at rest and are unable to do so under synaptic plasticity. Earlier
studies have reported that blocking NMDAR by Mg2+ can improve AD. Further, calcium homeostasis
can be another convincing explanation for AD. Thereby, calcium plays an etiological factor in synaptic
plasticity and can cause Alzheimer's disease. According to studies, calcium homeostasis is
maintained by calmodulin, however, calcium imbalance because of calmodulin can result in excitotoxicity.
Additionally, the endoplasmic reticulum can disturb the body's calcium homeostasis by
malfunctioning mitochondria. An attempt has been made to review the different subunits of NMDA
receptors, Calmodulin and Mitochondrial calcium release and their physiological roles to understand
the possible aetiology for the mitigation of AD.
The Effect of Foot Reflexology on the Sexual Function of Lactating Women: A Randomized Clinical Trial
Authors: Ghanbari Zahra , Valiani Mahboubeh , Kohan Shahnaz 
Published: February 2025

Background:
Sexual health is an essential part of women's lives at different ages. Pregnancy,
childbirth, and breastfeeding can affect women's sexual function by inducing biological,
psychological, and social changes. Due to the prevalence of sexual dysfunction in lactating women
and the effects of reflexology therapies on it, this study was conducted to investigate the effect
of foot reflexology on the sexual function of lactating women.

Materials and Methods:
This randomized clinical trial was conducted in selected health centers of
Isfahan in 2022 on 64 lactating women (32 women in each group of intervention and control). The
samples were selected using the convenience sampling method and were randomly divided into
two groups with a random number table. Each participant in the intervention group received 10
sessions of foot reflexology, and each session lasted for 50 minutes (25 minutes for each foot) and
was held every three days. The female sexual function index (FSFI) questionnaire was completed
before the intervention and four weeks after the end of it. The control group received routine care
and completed the questionnaire before the intervention and 9 weeks later. Data were analyzed using
SPSS version 20 and independent/paired t-tests.

Results:
Data analysis showed that the subjects of the two groups were homogeneous in demographic
and fertility characteristics at the beginning of the study. The total mean score of sexual
function in the intervention group was 20.36 ± 4.16 before the intervention and 28.05 ± 2.89 after
the intervention. In the control group, this score was 20.51 ± 3.75 before the intervention and
20.54 ± 3.71 nine weeks after it. A comparison of the total mean score of sexual function and dimensions
showed a significant difference between the two groups four weeks after the intervention
(p <0.001). In the intervention group, significant changes were observed in the total mean
score of sexual function and its dimensions four weeks after the intervention compared to before
the intervention. However, in the control group, there were no significant changes in this score
and its dimensions nine weeks later compared to before the intervention.

Conclusion:
Based on the results of this study, lactating women in the two groups did not have a
desirable sexual function before the intervention. However, foot reflexology in the present study
could effectively improve the sexual function of women in the reflexology group. Therefore, it is
recommended to employ foot reflexology therapy in health centers to help lactating women restore
their sexual function.
Urban-Rural Differences in the Association Between Internet Use Trajectories and Depressive Symptoms in Chinese Adolescents: Longitudinal Observational Study
Authors: Liu Yujie , Ge Xin , Wang Ying , Yang Xue , Liu Shangbin , Xu Chen , Xiang Mi , Hu Fan , Cai Yong 
Published: February 2025

Background
Internet use exhibits diverse trajectories during adolescence, which may contribute to depressive symptoms. Currently, it remains unclear whether the association between internet use trajectories and depressive symptoms varies between urban and rural areas.

Objective
This study aimed to investigate the association between internet use trajectories and adolescent depressive symptoms and to explore variation in this association between urban and rural areas.

Methods
This longitudinal study used 3-wave data from the 2014-2018 China Family Panel Study. Weekly hours of internet use and depressive symptoms were measured using self-reported questionnaires. Latent class growth modeling was performed to identify the trajectories of internet use. Multivariable logistic regressions were used to examine the association between internet use trajectories and depressive symptoms, stratified by rural and urban residence.

Results
Participants were 2237 adolescents aged 10 to 15 years at baseline (mean age 12.46, SD 1.73 years). Two latent trajectory classes of internet use were identified: the low-growth group (n=2008, 89.8%) and the high-growth group (n=229, 10.2%). The high-growth group was associated with higher odds of depressive symptoms (OR 1.486, 95% CI 1.065-2.076) compared to the low-growth group. In the stratified analysis, the association between internet use trajectories and depressive symptoms was significant solely among rural adolescents (OR 1.856, 95% CI 1.164-2.959).

Conclusions
This study elucidates urban-rural differences in the associations between trajectories of internet use and adolescent depressive symptoms. Our findings underscore the importance of prioritizing interventions for rural adolescents’ internet use behaviors to mitigate negative effects on their mental health.