bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Value and Therapeutic Significance of CCL Chemokines in Gastric Cancer
Authors: Tian Yonggang , Xie Yunqian , Yi Guirong , Wu Fanqi , Dang Xiaoyu , Bai Feihu , Wang Jun , Zhang Dekui 
Published: August 2024

Background:
Gastric cancer is one of the most common malignant tumours of the
gastrointestinal tract, which has a significant negative impact on human health.

Aims:
CCL chemokines play important roles in a variety of tumor microenvironments; nevertheless,
gastric cancer has surprisingly limited associations with CCL chemokines.

Methods:
In our study, we comprehensively utilized bioinformatics analysis tools and databases
such as cBioPortal, UALCAN, GEPIA, GeneMANIA, STRING, and TRRUST to clarify the
clinical significance and biology function of CCL chemokines in gastric cancer.

Results:
The mRNA expression levels of CCL1/3/4/5/7/8/14/15/18/20/21/22/26 were up-regulated,
while the mRNA expression levels of CCL2/11/13/16/17/19/23/24/25/28 were down-regulated.
The chemokine significantly associated with the pathological stage of gastric cancer is
CCL2/11/19/21. In gastric cancer, the expression level of CCL chemokines was not associated
with disease-free survival, but low expression of CCL14 was significantly associated with
longer overall survival. Therein, associated with the regulation of CCL chemokines are only 10
transcription factors (RELA, NFKB1, STAT6, IRF3, REL, SPI1, STAT1, STAT3, JUN and
SP1). The major biological process and functional enrichment of CCL chemokines are to induce
cell-directed migration.

Conclusion:
These results may indicate that CCL chemokines may be immunotherapeutic targets
and promising prognostic biomarkers for gastric cancer.
Identification of Potential Inhibitors from Medicinal Plant-based Phytochemicals for the Influential C4 Target of Diabetic Retinopathy by Molecular Docking Studies
Authors: Alagarsamy Veerachamy , Sulthana Mohaideen Thasthagir , Solomon Viswas Raja , Satishchandra Aithamraju , Kulkarni Vishaka Sumant , Narendhar Bandi , Murugesan Sankaranarayanan , Muzaffar-Ur-Rehman Mohammed , Chandu Ala 
Published: August 2024

Introduction:
Diabetic retinopathy is the major cause of vision failure in diabetic patients, and the
current treatment involves the practice of glucocorticoids or VEGF antagonists that are “off-label”. A few
small organic molecules against DR were discovered many years ago. Nutraceuticals are naturally available
functional foods that endorse different health benefits, including vitamins, antioxidants, minerals, fatty acids,
and amino acids that can defer the development of some diseases.

Methods:
Numerous studies reported that nutraceuticals encourage multiple therapeutic benefits and provide
protection against various diseases. In diabetes, nutraceuticals contribute to improving insulin sensitivity,
metabolism regulation, and lower hyperglycemia. The major aim of this study is to discover the most active
drug from natural or plant sources. In this work, 42 phytochemical constituents from 4 kinds of plants were
docked with the C4 target of diabetic retinopathy by an in silico molecular docking study.

Results:
According to the binding energy, all the phytoconstituents possessed good to high attraction towards
the target, and 6 phytochemicals, such as terchebulin, punicalagin, chebulagic acid, casuarinin, punicalin, and
pedunculagin, disclosed superior binding energy towards the target than standard ruboxistaurin via the interactions
of conventional hydrogen bonding, pi-alkyl interactions, etc. Molecular dynamic simulation studies further
established the stability of the phytoconstituents, and ADMET studies proved the safety profile of these
phytoconstituents.

Conclusion:
Hence, the current study suggested that the phytochemicals from various herbs inhibit the C4 target
of diabetic retinopathy and can be utilized as lead compounds to develop analogs or repurposed for the
treatment of DR.
Nobiletin Regulates Polyinosinic-polycytidylic Acid-induced Inflammation in Macrophages Partially via the PPAR-γ Signaling Pathway
Authors: Yue Ying-Xing , Huang Shan-Shan , Weng Ying-Zheng , Lu Yan , Jia Bing-Bing , Yang Zhou-Xin 
Published: August 2024

Introduction:
Macrophage dysregulation is a common pathogenic feature of viruses that provides
extensive targets for antiviral therapy. Nobiletin, a polymethoxylated flavonoid found in citrus fruits, has a
multitude of effects.

Methods:
We investigated the effect of nobiletin on polyinosinic-polycytidylic acid (poly(I:C))-induced inflammation
in RAW264.7 cells.

Results:
Nobiletin inhibited the production of poly(I:C)-induced inflammatory factors, including tumor necrosis
factor (TNF)-α, interleukin (IL)-6, and CXCL10. High-throughput sequencing revealed that nobiletin inhibited
the expression of TNF-α, IL-6, and CXCL10 and promoted the expression of CD206, Chil3, and
Vcam1. In the Kyoto Encyclopedia of Genes and Genomes enrichment analyses, the upregulated differential
genes were significantly enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway.
The PPAR-γ inhibitor T0070907 significantly reversed the inhibitory effects of nobiletin on IL-6 and CXCL10
but had no significant effect on TNF-α secretion.

Conclusion:
Thus, nobiletin regulated poly(I:C)-induced inflammatory responses in RAW264.7 cells partially
via the PPAR-γ signaling pathway.
Biological and Photocatalytic Activities of Silver Nanoparticles Synthesized from the Leaf Extract of Euphorbia royleana Boiss
Authors: Begum Hussan Ara , Yaseen Sana , Zada Amir , Musa Muhammad , Khan Asif , Sheheryar  , Alrefaei Abdulwahed Fahad , Almutairi Mikhlid H. , Ali Sajid , Azmat Rafia , Hamayun Muhammad 
Published: August 2024

Introduction:
Silver nanoparticles (AgNPs) have gained significance due to their practical use in
the medicinal field, especially in the treatment of tumors and cancer. The current article explores a green synthetic
method for the preparation of AgNPs using leaf extract of Euphorbia royleanas.

Methods:
The synthesis was conducted at different parameters like concentration of AgNO3, pH, salt concentration,
temperature and time to optimize best results for their biochemical applications. It was validated
through UV-V spectroscopy (400-450 nm) with 1:3 (concentration ratio of leaf ethanolic extract and 1 mM
AgNO3 solution) at a pH value of 8 at 35oC, which were the best optimization conditions. The FTIR spectral
bands showed the presence of C-N and –OH functional groups, indicating that –OH stretching and the aliphatic
-C-H stretching were involved in the reduction of Ag ions. The XRD pattern showed the face-centered cubic
structure of silver nanoparticles. The results of SEM revealed that AgNPs were predominantly spherical in
shape, mono-dispersed, and arranged in scattered form. EDX analysis testified the presence of metallic silver
along with other elements like Cl, C, and O.

Results:
The investigation of biochemical parameters showed that AgNPs were influential in the discoloration
of dye wastewater (methylene blue ), where 80% of dye color was removed in 20 min, followed by the significant
(p < 0.05) analgesic activity with an inhibition percentage of 86.45% at a dose of 500 mg/kg.

Conclusion:
Similarly, the antioxidant activity with the highest percent inhibition was 55.4% (p < 0.0001),
shown by the AgNPs at 500 μg/mL. AgNPs showed a 30 mm zone of inhibition at 100 μl/mL against Aspergillus
niger. It was concluded that AgNPs provide a baseline in medical technology for the treatment of simple
to chronic diseases.
Hydrogen Peroxide Induces Ethanol-inducible CYP2E1 via the NF-kB-classical Pathway: CYP2E1 mRNA Levels are not High in Alcoholic Hepatitis
Authors: Tamura Akiyoshi , Milas Siswanto Ferbian , Yoshimura Takumi , Oguro Ami , Imaoka Susumu 
Published: August 2024

Aims:
The aim of the present study is to elucidate the mechanism of CYP2E1 induction
as a causative factor of alcoholic hepatitis (AH) and its relationship with inflammation.

Background:
Chronic alcohol consumption induces CYP2E1, which is involved in the development
of alcoholic hepatitis (AH). However, the mechanisms underlying the induction of CYP2E1
by alcohol remain unclear. Therefore, we herein investigated the induction of drug-metabolizing
enzymes, particularly CYP2E1, by hydrogen peroxide (H2O2), the concentration of which is elevated
under inflammatory conditions.

Objective:
The mechanisms underlying the induction of CYP2E1 by H2O2 were examined with a
focus on Keap1, a target factor of H2O2.

Methods:
We assessed changes in the expression of drug-metabolizing enzymes in the human
hepatoma cell line, Hep3B, following treatment with H2O2, and evaluated changes in the expression
of the NFkB-related factor RelA(p65) after the knockdown of Keap1, a regulator of Nrf2
expression by reactive oxygen species. We also performed a promoter analysis using the upstream
region of the CYP2E1 gene. We herein used the GSE89632 series for non-alcoholic hepatitis
(NASH) and the GSE28619 series for AH.

Results:
The induction of CYP2E1 by H2O2 was significantly stronger than that of other drugmetabolizing
enzymes. On the other hand, the knockdown of Keap1, a target of H2O2, markedly
increased RelA(p65), an NFkB factor. Furthermore, the overexpression of RelA(p65) strongly
induced the expression of CYP2E1. Four candidate p65-binding sequences were identified upstream
of the CYP2E1 gene, and promoter activity assays showed that the third sequence was
responsive to the overexpression of RelA(p65). We used the GSE89632 series for NASH and the
GSE28619 series for AH in the present study. The expression of CYP2E1 mRNA in the liver was
significantly lower in AH patients than in HC patients, but was similar in HC patients and NASH
patients.

Conclusion:
We herein demonstrated that the expression of CYP2E1 was induced by H2O2. The
overexpression of RelA(p65) also induced CYP2E1 mRNA expression, whereas H2O2 did not
after the knockdown of RelA. These results suggest that H2O2 acts on Keap1 to upregulate RelA
(p65) in the NFkB system. One of the mechanisms underlying the induction of CYP2E1 was dependent
on the H2O2-Keap1-RelA axis. The results of the database analysis revealed that the expression
of CYP2E1 in the liver was significantly lower in AHH patients than in NASH patients,
suggesting that CYP2E1 is not the main cause of AH; however, CYP2E1 may exacerbate the
pathogenesis of AH.
Recent Advances in the Development of Alpha-Glucosidase and Alpha-Amylase Inhibitors in Type 2 Diabetes Management: Insights from In silico to In vitro Studies
Authors: Khan Fariya , Khan Mohsin Vahid , Kumar Ajay , Akhtar Salman 
Published: August 2024

:
Diabetes is a metabolic disorder caused by high glucose levels, leading to serious
threats such as diabetic neuropathy and cardiovascular diseases. One of the most reliable
measures for controlling postprandial hyperglycemia is to reduce the glucose level by inhibiting
enzymes in the digestive system, such as Alpha-Glucosidase and Alpha-Amylase. Here, we have
investigated the use of inhibitors to inhibit carbohydrate metabolism in order to restrict glucose
levels in diabetic patients. Acarbose, Voglibose, and Miglitol are three inhibitors approved by the
FDA that efficiently inhibit these two enzymes and thereby minimising hyperglycemia but are also
significantly helpful in reducing the risk of cardiovascular effects. We also provide insight into
the other known inhibitors currently available in the market. The adverse effects associated with
other inhibitors emphasise the demand for the latest in silico screening and in vitro validation in
the development of potent inhibitors with greater efficacy and safety for the treatment of Type 2
diabetes. The recent findings suggest that Alpha-Glucosidase and Alpha-Amylase play a major
role in carbohydrate metabolism and triggering the increase in glucose levels. This review provides
the latest scientific literature findings related to these two enzymes as well as the role of
primary and secondary inhibitors as potential candidates. Moreover, this review elaborates the
framework on the mechanism of action, different plant sources of extraction of these enzymes, as
well as kinetic assay of inhibitors and their interaction that can be used in future prospects to develop
potential leads to combat Type 2 diabetes.
Determination of Diphenidol in Mouse Plasma and Application to a Pharmacokinetic Study Using Uplc-Ms/Ms
Authors: Lin Rong , Dong Xicheng , Huang Wenwen , Wang Xianqin , Ma Jianshe 
Published: August 2024

Objective:
Difenidol is widely used in clinical practice due to its good anti-dizziness
effect and low side effect rate. This aim was to develop an ultra-high performance liquid chromatography-
tandem mass spectrometry (UPLC-MS/MS) method for the selective and straightforward
measurement of diphenidol in mouse plasma.

Methods:
A total of eighteen mice were divided into three groups: six for intravenous administration
at a dose of 0.2 mg/kg, six for oral administration at a dose of 0.4 mg/kg, and another six for
oral administration at a dose of 1.6 mg/kg. The analytes were extracted using acetonitrile-mediated
protein precipitation following the addition of the internal standard (IS), midazolam. On an Acquity
HSS T3 column (50 mm × 2.1 mm, 1.8 μm). The quantification process involved the use of
multiple reactions monitoring (MRM) mode, with target fragment ions m/z 310.2→128.9 for
diphenidol and m/z 326.2→291.4 for IS.

Results:
For diphenidol, calibration curves showed a linear distribution between 0.2 and 50
ng/mL. The accuracy of the method was between 94.6% and 110.4%, and the mean recovery of
diphenidol in mouse plasma was over 76.5%. The intra-day and inter-day precision RSDs were
both limited to 14%. The bioavailability of diphenidol in mice was determined to be 19.9% and
23.56% for the oral dose of 0.4 mg/kg and 1.6 mg/kg, respectively.

Conclusion:
The UPLC-MS/MS was successfully applied to study the pharmacokinetics of
diphenidol in mice, to which it was administered orally and intravenously.
Successful Identification of Key Phytoconstituents of Emblica officinalis as Potential Multitargeting Anti-Inflammatory and Antifungal Agents
Authors: Choudhary Diksha , Rani Nidhi , Kaur Rajwinder 
Published: August 2024

Introduction:
Fungal infections are growing more rapidly and becoming a public
health concern worldwide. The use of herbal medicines is now increasing due to their many
functional properties with fewer side effects. Emblica officinalis, an important medicinal plant,
exhibits many therapeutic properties.

Methods:
In this article, the active phytoconstituents of Emblica officinalis were explored for
their multitargeting activity as anti-inflammatory and antifungal by computational analysis.

Results:
A total of nine phytoconstituents including 3,6-di-O-galloyl-D-glucose, Mucic acid-
1,4-lactone-2-O-gallate, Mucic acid-1,4-lactone-5-O-gallate, Mucic acid-1,4-lactone-3-O-gallate,
Mucic acid-1,4-lactone-3,5-di-O-gallate, 2,6-dimethoxy-4-(2-hydroxyethyl)phenol-1-Obeta-
D-glucopyranoside, Apigenin-7-O-(6'-butyryl-beta-glucopyranoside), S-eriodictoyl-7-O-
(6'-O-trans-p-coumaryl)-beta-D-glucopyranoside, and 1,2,3,4,6-penta-O-galloyl glucose
showed better results as compared to standard drugs taken in the study.

Conclusion:
Further, these constituents indicated good ADME properties during the SwissADME
online analysis.
Management of Rheumatoid Arthritis By Development of Nanocarriers
and their Significance Over Conventional Dosage Forms
Authors: khan Hafsa , Yadav Nita , Sharma Shipra , Rawat Reetika 
Published: August 2024

Background:
Rheumatoid Arthritis is one of the most common auto-immune diseases
that cause inflammation. It is characterized by pain, stiffness, tenderness, and swelling in joints,
which may even lead to heart, lungs, or brain-related problems where age is the major factor involved,
as around 55% older adults have been affected by it. Treatments including non-steroidal anti-
inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs) etc., that are
modified and formulated as nanocarriers for enhanced bioavailability, majorly aim at enhancing the
rate and extent of drug reaching the bloodstream such as solid-lipid nanoparticles, liposomes, polymeric-
micelles, polymeric nanoparticles etc. are used in the management of rheumatoid arthritis.

Methods:
The following tools (Pubmed, Scopus, Google search engine, Google Scholar, Medline
Search Engine, Elsevier) were used in the literature search.

Results:
Through the literature review, the development of nanocarrier shows a promising approach
in the management of rheumatoid arthritis as compared to the conventional drug treatment such as
biologic agents and non-steroidal anti-inflammatory drugs etc.

Conclusion:
Rheumatoid Arthritis is a condition that occurs when the immune system, which normally
helps to protect the body from infection and disease, attacks its own tissues. The disease
causes pain, swelling as well as loss of function in joints. Therefore, life-long management is required
by reducing the dose frequency and dosage regimen, which can be effectively approached by
the development of a nano-carrier for significant drug uptake and low toxicity.
MiRNA Dysregulation in Brain Injury: An In Silico Study to Clarify the
Role of a MiRNA Set
Authors: Sessa Francesco , Pomara Cristoforo , Schembari Flavia , Esposito Massimiliano , Capasso Emanuele , Pesaresi Mauro , Osuna Eduardo , Ulas Efehan , Zammit Christian , Salerno Monica 
Published: August 2024

Background:
The identification of specific circulating miRNAs has been proposed as a
valuable tool for elucidating the pathophysiology of brain damage or injury and predicting patient outcomes.

Objective:
This study aims to apply several bioinformatic tools in order to clarify miRNA interactions
with potential genes involved in brain injury, emphasizing the need of using a computational approach
to determine the most likely correlations between miRNAs and target genes. Specifically, this study
centers on elucidating the roles of miR-34b, miR-34c, miR-135a, miR-200c, and miR-451a.

Methods:
After a careful evaluation of different software available (analyzing the strengths and limitations),
we applied three tools, one to perform an analysis of the validated targets (miRTarBase), and
two to evaluate functional annotations (miRBase and TAM 2.0).

Results:
Research findings indicate elevated levels of miR-135a and miR-34b in patients with traumatic
brain injury (TBI) within the first day post-injury, while miR-200c and miR-34c were found to
be upregulated after 7 days. Moreover, miR-451a and miR-135a were found overexpressed in the serum,
while miRNAs 34b, 34c, and 200c, had lower serum levels at baseline post brain injury.

Conclusion:
This study emphasizes the use of computational methods in determining the most likely
relationships between miRNAs and target genes by investigating several bioinformatic techniques to
elucidate miRNA interactions with potential genes. Specifically, this study focuses on the functions of
miR-34b, miR-34c, miR-135a, miR-200c, and miR-451a, providing an up-to-date overview and suggesting
future research directions for identifying theranomiRNAs related to brain injury, both at the
tissue and serum levels.
Influence of Breast Cancer Awareness Month on Public Interest of Breast Cancer in High-Income Countries Between 2012 and 2022: Google Trends Analysis
Authors: Ramadan Majed , Aboalola Doaa , Aouabdi Sihem , Alghamdi Tariq , Alsolami Mona , Samkari Alaa , Alsiary Rawiah 
Published: August 2024

Background
Breast cancer is the most common cancer among women worldwide. High-income countries have a greater incidence and mortality rate of breast cancer than low-income countries. As a result, raising awareness about breast cancer is crucial in increasing the chances of early detection and treatment. Social media has evolved into an essential tool for Breast Cancer Awareness Month campaigns, allowing people to share their breast cancer stories and experiences while also providing a venue for education and support.

Objective
The aim of this study was to assess the level of public interest in searches linked to breast cancer among a sample of high-income nations with a sizable internet user base from 2012 to 2022. We also sought to compare the proportional search volume for breast cancer during Breast Cancer Awareness Month with that during other months of the year.

Methods
Google Trends was used to retrieve data on internet user search behaviors in the context of breast cancer from 2012 to 2022. Seven countries were evaluated in this study: Australia, Canada, Ireland, New Zealand, the United Kingdom, Saudi Arabia, and the United States, in addition to global data. Breast cancer relative search volume trends were analyzed annually, monthly, and weekly from 2012 to 2022. The annual percent change (APC) was calculated for each country and worldwide. Monthly and weekly data were used to identify potential trends.

Results
A fluctuating pattern in APC rates was observed, with a notable increase in 2018 and a significant decrease in 2020, particularly in Saudi Arabia. Monthly analysis revealed a consistent peak in search volume during October (Breast Cancer Awareness Month) each year. Weekly trends over a 20-year period indicated significant decreases in Australia, Canada, New Zealand, and the United States, while increases were noted in Ireland. Heatmap analysis further highlighted a consistent elevation in median search volume during October across all countries.

Conclusions
These findings underscore the impact of Breast Cancer Awareness Month and suggest potential influences of governmental COVID-19 pandemic control measures in 2020 on internet search behavior.
Barriers and Facilitators to the Use of Wearable Robots as Assistive Devices: Qualitative Study With Older Adults and Physiotherapists
Authors: Reicherzer Leah , Scheermesser Mandy , Kläy Adrian , Duarte Jaime E , Graf Eveline S 
Published: August 2024

Abstract

Background
Light wearable robots have the potential to assist older adults with mobility impairments in daily life by compensating for age-related decline in lower extremity strength. Physiotherapists may be the first point of contact for older adults with these devices.

Objective
The aims of this study were to explore views of older adults and physiotherapists on wearable robots as assistive devices for daily living and to identify the barriers and facilitators to their use.

Methods
Six older adults (aged 72‐88 years) tested a wearable robot (Myosuit) and participated in semistructured interviews. A focus group with 6 physiotherapists who had a minimum of 5 years of professional experience and specialized in geriatrics was conducted. Data were analyzed using thematic qualitative text analysis.

Results
Older adults perceived benefits and had positive use experiences, yet many saw no need to use the technology for themselves. Main barriers and facilitators to its use were the perception of usefulness, attitudes toward technology, ease of use, and environmental factors such as the support received. Physiotherapists named costs, reimbursement schemes, and complexity of the technology as limiting factors.

Conclusions
A light wearable robot—the Myosuit—was found to be acceptable to study participants as an assistive device. Although characteristics of the technology are important, the use and acceptance by older adults heavily depend on perceived usefulness and need.