bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disulfidptosis and its Role in Peripheral Blood Immune Cells after a Stroke: A New Frontier in Stroke Pathogenesis
Authors: Liu Shan-peng , Liu Cuiying , Xu Baohui , Zhou Hongmei , Zhao Heng 
Published: February 2024

Background:
Stroke-Induced Immunodepression (SIID) is characterized by apoptosis
in blood immune populations, such as T cells, B cells, NK cells, and monocytes, leading to the
clinical presentation of lymphopenia. Disulfidptosis is a novel form of programmed cell death
characterized by accumulating disulfide bonds in the cytoplasm, resulting in cellular dysfunction
and eventual cell death.

Objective:
In this study, we investigated the association between disulfidptosis and stroke by
analyzing gene sequencing data from peripheral blood samples of stroke patients.

Methods:
Differential gene expression analysis identified a set of disulfidptosis-related genes
(DRGs) significantly associated with stroke. Initial exploration identified 32 DRGs and their
interactions. Our study encompassed several analyses to understand the molecular mechanisms
of DRGs in stroke. Weighted Gene Co-Expression Network Analysis (WGCNA) uncovered
modules of co-expressed genes in stroke samples, and differentially expressed gene (DEG) analysis
highlighted 1643 key genes.

Results:
These analyses converged on four hub genes of DRGs (SLC2A3, SLC2A14, SLC7A11,
NCKAP1) associated with stroke. Immune cell composition analysis indicated positive correlations
between hub genes and macrophages M1, M2, and neutrophils and negative associations
with CD4+ and CD8+ T cells, B cells, and NK cells. Sub-cluster analysis revealed two distinct
clusters with different immune cell expression profiles. Gene Set Enrichment Analysis (GSEA)
demonstrated enrichment of apoptosis-related pathways, neurotrophin signaling, and actin cytoskeleton
regulation. Associations between hub genes and apoptosis, necroptosis, ferroptosis, and
cuproptosis, were also identified.

Conclusion:
These results suggest that the DRG hub genes are interconnected with various cell
death pathways and immune processes, potentially contributing to stroke pathological development.
Follow-up Comparisons of Two Plasma Biomarkers of Alzheimer’s
Disease, Neurofilament Light Chain, and Oligomeric Aβ: A Pilot Study
Authors: Shim YongSoo 
Published: February 2024

Background and Objective:
Recent evidence suggests that blood-based biomarkers
might be useful for Alzheimer’s disease (AD). Among them, we intend to investigate whether neurofilament
light (NfL) and multimer detection system-oligomeric Aβ (MDS-OAβ) values can be
useful in screening, predicting, and monitoring disease progression and how the relationship between
NfL and MDS-OAβ values changes.

Methods:
Eighty participants with probable AD dementia, 50 with mild cognitive impairment
(MCI), and 19 with subjective cognitive decline (SCD) underwent baseline and follow-up evaluations
of the Mini-Mental Status Examination (MMSE) and both plasma biomarkers.

Results:
Baseline MDS-OAß (p=0.016) and NfL (p=0.002) plasma concentrations differed significantly
among groups, but only NfL correlated with baseline MMSE scores (r=-0.278, p=0.001). In
follow-up, neither correlated with MMSE changes overall. However, in SCD and MCI participants
(n=32), baseline MDS-OAß correlated with follow-up MMSE scores (r=0.532, p=0.041). Linear
regression revealed a relationship between baseline MDS-OAβ and follow-up MMSE scores. In
SCD and MCI participants, plasma NfL changes correlated with MMSE changes (r=0.564,
p=0.028).

Conclusion:
This study shows that only in participants with SCD and MCI, not including AD dementia,
can MDS-OAß predict the longitudinal cognitive decline measured by follow-up MMSE.
Changes of NfL, not MDS-OAß, parallel the changes of MMSE. Further studies with larger samples
and longer durations could strengthen these results.
Neuronatin Promotes the Progression of Non-small Cell Lung Cancer by
Activating the NF-κB Signaling
Authors: Xiong Huanwen , Chen Guohua , Fang Ke , Gu Weiguo , Qiu Feng 
Published: February 2024

Background and Objective:
Understanding the regulatory mechanisms involving neuronatin
(NNAT) in non-small cell lung cancer (NSCLC) is an ongoing challenge. This study aimed
to elucidate the impact of NNAT knockdown on NSCLC by employing both in vitro and in vivo approaches.

Methods:
To investigate the role of NNAT, its expression was silenced in NSCLC cell lines A549
and H226. Subsequently, various parameters, including cell proliferation, invasion, migration, and
apoptosis, were assessed. Additionally, cell-derived xenograft models were established to evaluate
the effect of NNAT knockdown on tumor growth. The expression of key molecules, including cyclin
D1, B-cell leukemia/lymphoma 2 (Bcl-2), p65, matrix metalloproteinase (MMP) 2, and nerve
growth factor (NGF) were examined both in vitro and in vivo. Nerve fiber density within tumor tissues
was analyzed using silver staining.

Results:
Upon NNAT knockdown, a remarkable reduction in NSCLC cell proliferation, invasion,
and migration was observed, accompanied by elevated levels of apoptosis. Furthermore, the expression
of cyclin D1, Bcl-2, MMP2, and phosphorylated p65 (p-p65) showed significant downregulation.
In vivo, NNAT knockdown led to substantial inhibition of tumor growth and a concurrent
decrease in cyclinD1, Bcl-2, MMP2, and p-p65 expression within tumor tissues. Importantly,
NNAT knockdown also led to a decrease in nerve fiber density and downregulation of NGF expression
within the xenograft tumor tissues.

Conclusion:
Collectively, these findings suggest that neuronatin plays a pivotal role in driving NSCLC
progression, potentially through the activation of the nuclear factor-kappa B signaling cascade.
Additionally, neuronatin may contribute to the modulation of tumor microenvironment innervation
in NSCLC. Targeting neuronatin inhibition emerges as a promising strategy for potential
anti-NSCLC therapeutic intervention.
Curcumin Inhibits Vasculogenic Mimicry via Regulating ETS-1 in Renal
Cell Carcinoma
Authors: Chong Yue , Xu Shan , Liu Tianjie , Guo Peng , Wang Xinyang , He Dalin , Zhu Guodong 
Published: February 2024

Background:
Metastatic renal cell carcinoma (RCC) poses a huge challenge once it has
become resistant to targeted therapy. Vasculogenic mimicry (VM) is a novel blood supply system
formed by tumor cells that can circumvent molecular targeted therapies. As one of the herbal remedies,
curcumin has been demonstrated to play antineoplastic effects in many different types of human
cancers; however, its function and mechanism of targeting VM in RCC remains unknown.

Objective:
Here, in the work, we explored the role of curcumin and its molecular mechanism in
the regulation of VM formation in RCC.

Methods:
RNA-sequencing analysis, immunoblotting, and immunohistochemistry were used to detect
E Twenty Six-1(ETS-1), vascular endothelial Cadherin (VE-Cadherin), and matrix metallopeptidase
9 (MMP9) expressions in RCC cells and tissues. RNA sequencing was used to screen
the differential expressed genes. Plasmid transfections were used to transiently knock down or
overexpress ETS-1. VM formation was determined by tube formation assay and animal experiments.
CD31-PAS double staining was used to label the VM channels in patients and xenograft
samples.

Results:
Our results demonstrated that VM was positively correlated with RCC grades and stages
using clinical patient samples. Curcumin inhibited VM formation in dose and time-dependent manner
in vitro. Using RNA-sequencing analysis, we discovered ETS-1 as a potential transcriptional
factor regulating VM formation. Knocking down or overexpression of ETS-1 decreased or increased
the VM formation, respectively and regulated the expression of VE-Cadherin and MMP9.
Curcumin could inhibit VM formation by suppressing ETS-1, VE-Cadherin, and MMP9 expression
both in vitro and in vivo.

Conclusion:
Our finding might indicate that curcumin could inhibit VM by regulating ETS-1,
VE-Cadherin, and MMP9 expression in RCC cell lines. Curcumin could be considered as a potential
anti-cancer compound by inhibiting VM in RCC progression.
Treatment of Reactive Orange 16 Dye-Bearing Wastewater by
Electro-Fenton Process with Stainless-Steel Electrodes: Statistical
Optimization and Operational Analysis
Authors: Ahmad Imran , Basu Debolina 
Published: February 2024

Abstract:
In the current work, the Electro-Fenton (EF) based Reactive Orange 16 (RO16) dye treatment
was studied and compared with central composite (CC) and Taguchi design (TD) statistical
optimization tools. Color removal (RC) and COD decay (RCOD) were chosen responses for the effect
of pH (A), electrolysis time (B), initial dye concentration (C), and current density (D). The facecentred
CC design and L16 orthogonal array were used in the experimental procedures. At optimal
conditions, the coefficient of determination (R2) values of 0.99 for CC and 0.97 for TD suggest statistical
significance and good model agreement. The results of the ANOVA and Prob. > F values supported
the model’s successful experimental data fitting. Taguchi method was found as an appropriate
methodology for parameter percentage contributions with fewer experimental runs. Moreover, the S/N
ratio charts proved to be a successful CC design replacement. The current density and pH were found
to be the most important factors for the EF process. A higher biodegradability (BOD5/COD) and minimum
iron concentration (0.45 mg/L) in the effluent sludge demonstrated good environmental disposal
suitability. In the last, the effect of various inhibitors/scavengers (SO4
−2, PO4
−3, EDTA, etc.) on the
EF process performance was also carried out.
QSAR Analysis and Molecular Docking Studies of Aryl Sulfonamide Derivatives as Mcl-1 Inhibitors and the Influence of Structure and Chirality on the Inhibitory Activity
Authors: Chen Jia , Ma Yang , Zou Jian-Wei , Hu Sheng , Huang Meilan , Hu Guixiang 
Published: February 2024

Background:
Mcl-1 is a kind of antiapoptotic protein and its overexpression is closely
related to the occurrence of cancer. Aryl sulfonamide derivatives are expected to become new anticancer
agents due to their high inhibitory activity on the Mcl-1 protein.

Objective:
The study aimed to establish the QSAR model with good prediction ability and elaborate
the influence of structure and chirality on the inhibitory activity.

Methods:
Multiple QSAR models were built with different types of descriptors and modeling methods.
The molecular docking was performed on compounds 45, 25, 26, 24R, and 24S. The MCCV
method was used to perform rigorous validations with up to 216
= 65,536 samplings for MLR, SVM,
LSSVM, RF, and GP methods based on the model of 2D and 3D combined descriptors.

Results:
The models based on 2D and 3D combined descriptors demonstrated non-linear LSSVM, RF, and GP methods based on the model of 2D and 3D combined descriptors. Results: The models based on 2D and 3D combined descriptors demonstrated non-linear LSSVM and GP methods to provide better results (R2>0.94, R2CV > 0.86). The predictive performances of MCCV tests have been basically coincident with the single test set’s results. The hydrogen bond acceptor at the appropriate position of the substituent on the chiral center could form the hydrogen bond interaction with residue ASN260, resulting in stronger interaction and higher inhibitory activity. The interaction differences between R and S configurations could be mainly attributed to two residues, HIS224 and ASN260. Furthermore, the steric effect of the substituent on chiral carbon atoms was crucial. A high steric effect could prevent the binding of the substituent and protein, resulting in low inhibitory activity.

Conclusion:
The study may provide theoretical guidance on the design and synthesis of novel aryl
sulfonamide derivatives with high inhibitory activity
Ultrasound-assisted Aqueous Two-Phase Extraction of Flavonoids from
Scutellariae Radix and Evaluation of their Bioactivities In Vitro
Authors: Ge Zhenkai , Zhao Yongheng , Ling Xu , Zhu Chenpan , Hao Xincai 
Published: February 2024

Background:
Scutellariae Radix, one of the most widely used herbs in Traditional Chinese
Medicine, exhibits various biological activities due to its chemical components, which stand out
for a number of flavonoids. In this study, Ultrasound-assisted aqueous two-phase extraction (UAATPE)
was employed for the first time to obtain a high extraction rate and high purity of flavonoids
from Scutellariae Radix.

Methods:
The Box-Behnken response surface method (RSM) was utilized to optimize the extraction
conditions with the application of the new aqueous two-phase system (ATPS) composed of ethanol
and ammonium sulfate. The major influence factors, including ethanol concentration, ammonium
sulfate concentration, liquid-to-solid ratio, sonication time, and extraction temperature, were investigated
by the single-factor experiment. The compositional characterization of flavonoids was characterized
with HPLC-UV. Scanning electron microscopy (SEM) was applied to research the surface
morphology of raw material. Furthermore, the bioactivities of the extract obtained by UA-ATPE
were studied in vitro.

Results:
The optimal extraction conditions were as follows: the ethanol content was 26.12% (w/w),
the ammonium sulfate content was 20.02% (w/w), the liquid-to-solid ratio was 40 mL/g, the sonication
time was 5 min with the ultrasonic power of 250 W, and the operating process was performed
at room temperature. Compared with the traditional extraction methods, UA-ATPE exhibited higher
extraction efficiency and better extraction selectivity. The DPPH and ABTS radical scavenging tests
showed that enriched products possessed strong antioxidant activity.

Conclusion:
The study confirmed that the developed method of UA-ATPE could be used as an efficient,
eco-friendly, and low-consumption method for the extraction and purification of flavonoids
from Scutellariae Radix.
Preparation & Characterization of Sustained-release Floating Microsphere of Digestive Enzymes
Authors: Prajapati Bhupendra G. , Bhagat Anand , Basu Biswajit 
Published: February 2024

Introduction:
Pepsin is a proteolytic enzyme which is widely used as a digestive aid. Its
dose is 300 mg - 1 gm per day in divided doses. Its biological half-life is around 3.5 hrs. Pepsin is
active only in the acidic pH of the stomach; its activity decreases tremendously in the basic pH. So,
it is required to retain in the stomach for maximum proteolytic activity. The goal of the current effort
is to develop and assess an oral controlled floating drug delivery system for pepsin that will shorten
its stay in the stomach and result in a longer effect.

Methods:
The 12-hour sustained effect of pepsin floating microspheres was planned. This also improves
the stability of the Pepsin by immobilizing them on the microsphere. Pepsin is widely used in
chronic gastritis, so developing a floating drug delivery system is therefore necessary. In light of the
aforementioned principles, a critical need for the creation of a dosage form to administer Pepsin in
the stomach and boost the enzyme's effectiveness, enabling sustained action, was identified. The current
study used a methodical strategy to create floating microspheres of Pepsin dosage forms.

Results:
Optimization was done for floating ability, yield, entrapment efficiency, and release study
using different concentrations of ethylcellulose & HPMC E4M. For parameter optimization and to
demonstrate the significant impact of variables, 32 full factorial designs were used. The manufactured
microspheres had good encapsulation rates, excellent floating, & excellent micromeritic properties as
single-unit dosage forms.

Conclusion:
It has been demonstrated that pepsin prepared as floating microspheres can be used to
improve proteolytic activity and extend pepsin's gastric residence.
From Pathophysiology to Personalized Treatment Strategies for Psoriasis
Authors: Barak Aashima , Sharma Anjali , Arora Deepshi , Mittal Vishnu , Gupta Akash , Grover Rohit 
Published: February 2024

Background:
Psoriasis is a chronic inflammatory and proliferative skin disorder characterized
by redness and elevated patches covered in scaly, silvery-white skin. The National Psoriasis
Foundation categorizes psoriasis into mild, moderate, and severe, impacting 2% to 5% of the global
population. This article explores the types, development, and severity categories of psoriasis, delving
into its pathophysiology. It also reviews both conventional and herbal topical therapies and their marketed
formulations.

Aim:
The study aimed to contribute to the development of personalized treatment approaches for
individuals with psoriasis.

Objectives:
This article explores the types, development, and severity categories of psoriasis, delving
into its pathophysiology. It also reviews both conventional and herbal topical therapies and their marketed
formulations.

Methods:
The article relies on a comprehensive review of existing literature and research studies on
psoriasis. Information on types, severity categories, pathophysiology, and available treatments, both
conventional and herbal, is gathered and analyzed.

Results:
The results highlight the potential advantages of incorporating herbal therapies into treatment
plans for individuals with psoriasis, especially for those with severe cases.

Conclusion:
In conclusion, the article emphasizes the importance of individualized treatment plans
for managing psoriasis. Both conventional and herbal topical formulations can be viable options,
particularly for severe cases. By considering the safety profiles, side effects, and biological activities
associated with these treatments, healthcare experts can collaborate with patients to create personalized
and effective strategies for addressing the complexities of psoriasis management.
Interaction of Fe2O3 and Fe3O4 Nanoparticle with Pathogenic Bacteria:
A In-silico Molecular Mechanism Study
Authors: Luktuke Sahil , Raj Aditya , Santra Sourav , Das Sudip , Chakravorty Arghya , Ramesh Karthikeyan , Nila Balaji , K Harjeet , Sankar Sana Siva , Raghavan Vimala 
Published: February 2024

Background::
Magnetic materials like iron, nickel, and cobalt have been a subject of
interest among the scientific and research community for centuries. Owing to their unique properties,
they are prevalent in the mechanical and electronic industries. In recent times, magnetic materials
have undeniable applications in biotechnology and nanomedicine. Bacteria like Salmonella enterica,
Clostridium botulinum, Bacillus subtilis, etc, pose a hazard to human health and livestock. This
ultimately leads to huge yields and economic losses on a global scale. Antimicrobial resistance has
become a significant public health concern in recent years, with the increasing prevalence of drugresistant
infections posing a significant threat to global health. Many coherent studies have
successfully reported magnetic metal oxide nanoparticles to be highly selective, specific, and
effective in neutralizing pathogens through various mechanisms like cell membrane disruption, direct
contact-mediated killing, or by generating Reactive Oxygen Species (ROS) and numerous costimulatory
and inflammatory cytokines. Therefore, we explored the inhibitory effects of iron oxide
nanoparticles (NPs) on various pathogenic bacteria via an in-silico approach. This method helped us
to understand the active sites where the iron oxide NPs bind with the bacterial proteins.

Methods::
The 3D crystal structures of all the pathogenic proteins of Streptococcus pneumoniae,
Pseudomonas aeruginosa, Vibrio cholerae, Salmonella enterica, Shigella flexneri, Clostridium
botulinum and nanoparticles (Fe2O3 and Fe3O4) under study were downloaded from RCSB PDB and
ChemSpider official websites respectively. It was followed by the in-silico molecular Docking using
PyRx and AutoDock Vina and analyzed on LigPlot.

Results::
This study interprets the efficacy of the Fe2O3 and Fe3O4 nanoparticles against all the test
bacteria. At the same time, Fe2O3 and Fe3O4 formed the most stable complexes with cholera
enterotoxin subunit B and lectin II (PA-IIL) mutant S23A of Pseudomonas aeruginosa, respectively.

Conclusion::
As in this era of AMR, researchers have been exploring alternative strategies to combat
bacterial infections, including using magnetic nanoparticles as a potential treatment. They possess
unique physical and chemical properties that make them attractive candidates for antimicrobial
therapy, including their ability to penetrate bacterial biofilms and selectively target pathogenic
bacteria while leaving healthy cells unharmed. This study examined the inhibitory effects of iron
oxide (magnetic) nanoparticles, namely Fe2O3 and Fe3O4, on various bacterial proteins involved in
cell-to-cell interactions and pathogenesis.
Berberine: A Multi-Target Natural PCSK9 Inhibitor with the Potential to
Treat Diabetes, Alzheimer’s, Cancer and Cardiovascular Disease
Authors: Coppinger Caroline , Pomales Briana , Movahed Mohammad Reza , Marefat Meredith , Hashemzadeh Mehrnoosh 
Published: February 2024

Abstract:
Berberine is a natural product with a wide range of pharmacological effects. It has
antimicrobial, anti-cancer, anti-inflammatory, anti-hyperlipidemic, neuroprotective, and cholesterollowering
properties, among others. It has been used in traditional Chinese and Ayurvedic medicine
for 3000 years and is generally well-tolerated with few side effects. Its main drawback is low oral
bioavailability, which has hindered widespread clinical use. However, recent interest has surged
with the emergence of evidence that berberine is effective in treating cancer, diabetes, Alzheimer’s
disease, and cardiovascular disease via multiple mechanisms. It enhances insulin sensitivity and secretion
by pancreatic β-cells in Type 2 Diabetes Mellitus in addition to reducing pro-inflammatory
cytokines such as IL-6, IL-1β, TLR4 and TNF-α. These cytokines are elevated in Alzheimer’s disease,
cardiovascular disease, and diabetes. Reductions in pro-inflammatory cytokine levels are associated
with positive outcomes such as improved cognition, reduced cardiovascular events, and
improved glucose metabolism and insulin sensitivity. Berberine is a natural PCSK9 inhibitor, which
contributes to its hypolipidemic effects. It also increases low-density lipoprotein receptor
expression, reduces intestinal cholesterol absorption, and promotes cholesterol excretion from the
liver to the bile. This translates into a notable decrease in LDL cholesterol levels. High LDL
cholesterol levels are associated with increased cardiovascular disease risk. Novel synthetic berberine
derivatives are currently being developed that optimize LDL reduction, bioavailability, and other
pharmacokinetic properties.