bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis and Validation of Tyrosine Metabolism-related Prognostic Features for Liver Hepatocellular Carcinoma Therapy
Authors: Cui Zhongfeng , Liu Chunli , Li Hongzhi , Wang Juan , Li Guangming 
Published: March 2024

Aims:
To explore tyrosine metabolism-related characteristics in liver hepatocellular carcinoma
(LIHC) and to establish a risk signature for the prognostic prediction of LIHC. Novel prognostic
signatures contribute to the mining of novel biomarkers, which are essential for the construction
of a precision medicine system for LIHC and the improvement of survival.

Background:
Tyrosine metabolism plays a critical role in the initiation and development of LIHC.
Based on the tyrosine metabolism-related characteristics in LIHC, this study developed a risk signature
to improve the prognostic prediction of patients with LIHC.

Objective:
To investigate the correlation between tyrosine metabolism and progression of LIHC
and to develop a tyrosine metabolism-related prognostic model.

Methods:
Gene expression and clinicopathological information of LIHC were obtained from The
Cancer Genome Atlas (TCGA) database. Distinct subtypes of LIHC were classified by performing
consensus cluster analysis on the tyrosine metabolism-related genes. Univariate and Lasso Cox regression
were used to develop a RiskScore prognosis model. Kaplan-Meier (KM) survival analysis
with log-rank test and area under the curve (AUC) of receiver operating characteristic (ROC)
were employed in the prognostic evaluation and prediction validation. Immune infiltration, tyrosine
metabolism score, and pathway enrichment were evaluated using single-sample gene set enrichment
analysis (ssGSEA). Finally, a nomogram model was developed with the RiskScore and
other clinicopathological features.

Results:
Based on the tyrosine metabolism genes in the TCGA cohort, we identified 3 tyrosine
metabolism-related subtypes showing significant prognostic differences. Four candidate genes selected
from the common differentially expressed genes (DEGs) between the 3 subtypes were used
to develop a RiskScore model, which could effectively divide LIHC patients into high- and lowrisk
groups. In both the training and validation sets, high-risk patients tended to have worse overall
survival, less active immunotherapy response, higher immune infiltration and clinical grade,
and higher oxidative, fatty, and xenobiotic metabolism pathways. Multivariate analysis confirmed
that the RiskScore was an independent indicator for the prognosis of LIHC. The results from pan--
cancer analysis also supported that the RiskScore had a strong prognostic performance in other
cancers. The nomogram demonstrated that the RiskScore contributed the most to the prediction of
LIHC prognosis.

Conclusion:
Our study developed a tyrosine metabolism-related risk model that performed well in
survival prediction, showing the potential to serve as an independent prognostic predictor for LIHC
treatment.
Ranunculin, Protoanemonin, and Anemonin: Pharmacological and Chemical Perspectives
Authors: Sirak Betelhem , Aragaw Misgana , Tadesse Solomon 
Published: March 2024

Abstract:
Ranunculin, a glucoside, serves as a chemotaxonomic marker in Ranunculaceae
plants. When these plants are damaged, an enzyme β−glucosidase triggers the
conversion of ranunculin into protoanemonin through hydrolysis. Subsequently, protoanemonin
undergoes cyclodimerization to form anemonin. The inherent instability of
ranunculin and the rapid dimerization of protoanemonin render them unsuitable for use
in biological assays. Conversely, anemonin stands out as the optimal molecule for bioassays
and demonstrates diverse biological properties, including anti-inflammatory, anti-infective,
and anti-oxidant effects. Among these, anemonin exhibits the greatest promise
in addressing conditions such as arthritis, cerebral ischemia, and ulcerative colitis. Its potential
medical uses are enhanced by its capacity to inhibit nitric oxide synthesis and successfully
counteract lipopolysaccharide-induced inflammation. This review describes
the chemistry and biological properties of anemonin and its precursors, including discussions
on extraction, isolation, synthesis, and investigations into bioactivity and pharmacokinetics.
Cholesteryl Ester Transfer Protein (CETP) Variations in Relation to Lipid
Profiles and Cardiovascular Diseases: An Update
Authors: Dabravolski Siarhei , Orekhov Nikolay A. , Melnichenko Alexandra , Sukhorukov Vasily N. , Popov Mikhail A. , Orekhov Alexander 
Published: March 2024

Abstract:
Lipid metabolism plays an essential role in the pathogenesis of cardiovascular and metabolic diseases.
Cholesteryl ester transfer protein (CETP) is a crucial glycoprotein involved in lipid metabolism by transferring
cholesteryl esters (CE) and triglycerides (TG) between plasma lipoproteins. CETP activity results in reduced
HDL-C and increased VLDL- and LDL-C concentrations, thus increasing the risk of cardiovascular and
metabolic diseases. In this review, we discuss the structure of CETP and its mechanism of action. Furthermore,
we focus on recent experiments on animal CETP-expressing models, deciphering the regulation and
functions of CETP in various genetic backgrounds and interaction with different external factors. Finally, we
discuss recent publications revealing the association of CETP single nucleotide polymorphisms (SNPs) with
the risk of cardiovascular and metabolic diseases, lifestyle factors, diet and therapeutic interventions. While
CETP SNPs can be used as effective diagnostic markers, diet, lifestyle, gender and ethnic specificity should also
be considered for effective treatment.
The Potential Mechanism of Liujunzi Decoction in the Treatment of Breast
Cancer based on Network Pharmacology and Molecular Docking Technology
Authors: Sun Mei , Lv Feng , Qin Chunmeng , Du Dan , Li Wenjun , Liu Songqing 
Published: March 2024

Background:
Liujunzi Decoction (LJZD) is a potential clinical treatment for Breast Cancer (BC),
but the active ingredients and mechanisms underlying its effectiveness remain unclear.

Objective:
The study aimed to investigate the target gene of LJZD compatibility and the possible mechanism
of action in the treatment of breast cancer by using network pharmacology and molecular docking.

Methods:
Based on TCMSP, ETCM, and BATMAN database searching and screening to obtain the ingredients
of LJZD, the related targets were obtained. Breast cancer-related targets were collected through GEO,
Geencards, OMIM, and other databases, and drug-disease Venn diagrams were drawn by R. The PPI network
map was constructed by using Cytoscape. The intersecting targets were imported into the STRING database,
and the core targets were analyzed and screened. The intersected targets were analyzed by the DAVID
database for GO and KEGG enrichment. AutoDock Vina and Gromacs were used for molecular docking and
simulation of the core targets and active ingredients.

Results:
126 active ingredients of LJZD were obtained; 241 targets related to breast cancer were sought after
screening, and 180 intersection targets were identified through Venn diagram analysis. The core targets were
FOS and ESR1. KEGG enrichment analysis mainly involved PI3K/Akt, MAPK, and other signaling pathways.

Conclusion:
This study has explored the possible targets and signaling pathways of LJZD in treating breast
cancer through network pharmacology and bioinformatics analysis. Molecular docking and simulation have
further validated the potential mechanism of action of LJZD in breast cancer treatment, providing essential experimental
data for future studies.
Targeted Bacterial Keratitis Treatment with Polyethylene Glycol-Dithiothreitol-Boric Acid Hydrogel and Gatifloxacin
Authors: Shen Xiao , Huang Chunlian , Bai Jianhai , Wen Jing 
Published: March 2024

Introduction/Objective:
To prolong the ocular residence time of gatifloxacin and enhance
its efficacy against bacterial keratitis, this study developed a velocity-controlled polyethylene
glycol-dithiothreitol-boric acid (PDB) hydrogel loaded with gatifloxacin.

Methods:
First, the basic properties of the synthesized PDB hydrogel and the gatifloxacin-loaded
PDB hydrogel were assessed. Secondly, the in vitro degradation rate of the drug-loaded PDB was
measured in a simulated body fluid environment with pH 7.4/5.5. The release behavior of the
drug-loaded PDB was studied using a dialysis method with PBS solution of pH 7.4/5.5 as the release
medium. Finally, a mouse model of bacterial keratitis was established, and tissue morphology
was observed using hematoxylin-eosin staining. Additionally, mouse tear fluid was extracted
to observe the antibacterial effect of the gatifloxacin-loaded PDB hydrogel.

Results:
The results showed that the PDB hydrogel had a particle size of 124.9 nm and a zeta potential
of -23.3 mV, with good porosity, thermosensitivity, viscosity distribution, rheological properties,
and high cell compatibility. The encapsulation of gatifloxacin did not alter the physical
properties of the PDB hydrogel and maintained appropriate swelling and stability, with a high
drug release rate in acidic conditions. Furthermore, animal experiments demonstrated that the gatifloxacin-
loaded PDB hydrogel exhibited superior therapeutic effects compared to gatifloxacin eye
drops and displayed strong antibacterial capabilities against bacterial keratitis.

Conclusion:
This study successfully synthesized PDB hydrogel and developed a gatifloxacin drug
release system. The hydrogel exhibited good thermosensitivity, pH responsiveness, stability, and
excellent biocompatibility, which can enhance drug retention, utilization, and therapeutic effects
on the ocular surface.
Review of Phytosomes and Ethosomes: Groundbreaking Approaches for
Delivering the Phytochemical Components of Plants
Authors: Raghav Asha , Attri Meenakshi , Chaudhary Hema 
Published: March 2024

Abstract:
Phytoconstituents have been widely used since ancient times to form a complex with
phospholipids due to their various therapeutic actions. Despite having strong pharmacodynamic efficiency,
numerous phytoconstituents have shown lower in vivo bioavailability and few adverse effects.
Phytochemicals soluble in water exhibit poor absorption, leading to a limited therapeutic impact.
Phytosome nanotechnology overcomes this limitation by creating a bound of phytochemicals
with phospholipids. This method exhibits improved absorption because phytosomes inhibit significant
herbal extract components from being degraded by gastric juices and gut flora. This improves
bioavailability, increases clinical benefit, and ensures delivery to tissues without compromising nutritional
stability. This review also aims to highlight those vesicular systems that could be used in
phytosome technology. Additionally, this review highlights the preparation, advantage, characterization,
applications, and recent development of phytosome and ethosome with a list of recent patents
and marketed formulations and their uses.
Proton Pump Inhibitors and Cognitive Health: Review on Unraveling the
Dementia Connection and Co-morbid Risks
Authors: Khan Zuber , Mehan Sidharth , Saifi Mohd. Anas , Gupta Ghanshyam Das , Narula Acharan S. , Kalfin Reni 
Published: March 2024

Abstract:
Dementia, an international health issue distinguished by the impairment of daily functioning
due to cognitive decline, currently affects more than 55 million people worldwide, with
the majority residing in low-income and middle-income countries. Globally, dementia entails significant
economic burdens in 2019, amounting to a cost of 1.3 trillion US dollars. Informal caregivers
devote considerable hours to providing care for those affected. Dementia imposes a greater
caregiving and disability-adjusted life-year burden on women. A recent study has established a
correlation between prolonged Proton Pump Inhibitor (PPI) usage and dementia, in addition to
other neurodegenerative conditions. PPIs are frequently prescribed to treat peptic ulcers and
GERD (gastroesophageal reflux disease) by decreasing stomach acid secretion. They alleviate
acid-related symptoms through the inhibition of acid-secreting H+-K+ ATPase. In a number of observational
studies, cognitive decline and dementia in the elderly have been linked to the use of
PPIs. The precise mechanism underlying this relationship is unknown. These drugs might also alter
the pH of brain cells, resulting in the accumulation of amyloid-beta (Aβ) peptides and the development
of Alzheimer's disease (AD). Despite the compelling evidence supporting the association
of PPIs with dementia, the results of studies remain inconsistent. The absence of a correlation
between PPI use and cognitive decline in some studies emphasizes the need for additional research.
Chronic PPI use can conceal underlying conditions, including cancer, celiac disease, vitamin
B12 deficiency, and renal injury, highlighting dementia risk and the need for further investigations
on cognitive health.
TBOPP, a DOCK1 Inhibitor, Potentiates Cisplatin Efficacy in Breast Cancer by Regulating Twist-mediated EMT
Authors: Chen Xin , Zhou Zhenbang , Tang Pengting , Du Feiya , Wang Shuqian , Yao Jia , Zhang Shufen , Huang Jiajing , Lu Xuemei , Chen Wei , Yu Xiaofang , Liu Yu , Liu Hao 
Published: March 2024

Background:
DOCK1 has been reported to be involved in tumor progression and re-sistance.1-(2-(30-(trifluoromethyl)-[1,10-biphenyl]-4-yl)-2-oxoethyl)-5-pyrrolidinylsulfonyl2(1H)- pyridone (TBOPP) is a selective DOCK1 inhibitor; however, the role and molecular mechanisms of DOCK1 and its inhibition in breast cancer (BC) resistance remain poorly understood. Objective: This study aims toinvestigate the underlying mechanisms of DOCK1 in BC resistance.

Methods:
DOCK1 or Twist siRNA and Twist plasmid were used to explore the function of DOCK1 in vitro experiments. A mouse xenograft model was used for in vivo experiments.

Results:
In the present study, we demonstrated that DOCK1 siRNA promoted cisplatin sensitivity in BC cells. Moreover, TBOPP also enhances the therapeutic effect of cisplatin both in vitro and in vivo. Mechanistically, DOCK1 siRNA inhibited EMT. Twist 1 is one of the EMT-inducing transcription factors and is known to induce EMT. To further reveal the effect of DOCK in BC cells, we co-transfected with DOCK1 and Twist1 siRNA to BC cells and found that co-transfection with DOCK1 and Twist siRNA could not further enhance the cisplatin sensitivity of BC cells. Moreo ver, DOCK1 siRNA failed to reverse the effect of Twist 1 up-regulation.

Conclusion:
Taken together, these results demonstrate that DOCK1 may function as a potential therapeutic target in BC and that combining cisplatin with TBOPP may provide a promising therapeutic strategy for cisplatin-resistant BC patients.
Incretin Therapy and Insulin Signaling: Therapeutic Targets for Diabetes And Associated Dementia
Authors: Joshi Deepika 
Published: March 2024

:
Dementia is the primary cause of disability and dependence among the elderly population
worldwide. The population living with dementia is anticipated to double in the next 17
years. Recent studies show the fact that compared to people without diabetes, people with Type 2
Diabetes (T2D) have about a 60% increased chance of developing dementia. In addition to cholinergic
function being downregulated, improper insulin signalling also has a negative impact on
synaptic plasticity and neuronal survival. Type 2 diabetes and dementia share various similar
pathophysiological components. The ageing of the population and the ensuing rise in dementia
prevalence are both results of ongoing medical advancements. It is possible that restoring insulin
signaling could be a helpful therapy against dementia, as it is linked to both diminished cognitive
function and the development of dementia, including AD. This review article comprehensively
focused on scientific literature to analyze the relationship of Dementia with diabetes, recent experimental
studies, and insight into incretin-based drug therapy for diabetes-related dementia.
Opportunities and Regulatory Challenges of Functional Foods and
Nutraceuticals During COVID-19 Pandemic
Authors: Jose Jobin , Ndang Keyidaule , Chethana Madhusoodhana Ballakkuraya , Chinmayi Chikmagalur Srinath , Afrana Khatheeja , Gopan Gopika , Parambi Della Grace Thomas , Munjal Kavita , Chopra Hitesh , Dhyani Archana , Kamal Mohammad Amjad 
Published: March 2024

:
The novel Coronavirus has brought global mortality, disruption, and a significant loss
of life. A compromised immune system is a known risk factor for all viral influenza infections.
Due to the perceived “immune-boosting” properties of nutraceutical products, sales of dietary supplements have grown globally. In recent years, consumers have increasingly demanded nutraceutical products rather than curative synthetic medicines for preventive therapies for the coronavirus
disease outbreak of 2019 (COVID-19). Healthy foods and nutraceuticals have become daily diet
plans for consumers. Although there has been an increase in demand, there is no such regulation
and harmonized process, which stands as a barrier to the approval of these products. Therefore,
many misbranded and spurious products are entering the market, which may harm consumers.
This article focuses on the role of functional foods and nutraceutical in the management of
COVID-19 also focuses on the different nutraceutical regulations in each country and compare the
similarities and differences of the following countries: India, the USA (United States of America),
the EU (European Union), and China. The comparative study of nutraceutical regulations in India,
the USA, Europe, and China shows that there is a difference regarding the nutraceutical regulations; however, despite the differences, it is observed that it has the same underlying objective,
i.e., ensuring the safety of the consumers by maintaining the product quality.
Biochemical and In Silico Studies on Triazole Derivatives as Tyrosinase
Inhibitors: Potential Treatment of Hyperpigmentation Related Skin
Disorders
Authors: Choudhary Yusra , Atia-tul-Wahab  , epub Humaira , Siddiqui Salman , Khan Majid , Khan Khalid M. , Asseri Amer H. , Choudhary M. Iqbal , Atta-ur-Rahman  
Published: March 2024

Introduction::
Tyrosinase is a versatile, glycosylated copper-containing oxidase enzyme
that mainly catalyzes the biosynthesis of melanin in mammals. Its overexpression leads to the
formation of excess melanin, resulting in hyperpigmentary skin disorders, such as dark spots,
melasma, freckles, etc. Therefore, inhibition of tyrosinase is a therapeutic approach for the treatment
of hyperpigmentation.

Method::
The current study focused on evaluating tyrosinase inhibitory activities of triazole derivatives
1-20, bearing different substituents on the phenyl ring. 17 derivatives have shown a potent
tyrosinase inhibition with IC50 values between 1.6 to 13 μM, as compared to the standard drug, i.e.,
kojic acid (IC50 = 24.1 ± 0.5 μM). Particularly, compounds 11 and 15 displayed 12 times more
potent inhibitory effects than the kojic acid.

Result::
The structure-activity relationship revealed that substituting halogens at the C-4 position
of the benzene ring renders remarkable anti-tyrosinase activities. Compounds 1-3 and 8 showed a
competitive type of inhibition, while compounds 5, 11, and 15 showed a non-competitive mode of
inhibition. Next, we performed molecular docking analyses to study the binding modes and interactions
between the ligands (inhibitors) and the active site of the tyrosinase enzyme (receptor). Besides
this, we have assessed the toxicity profile of inhibitors on the BJ human fibroblast cell line.

Conclusion::
The majority of the newly identified tyrosinase inhibitors were found to be noncytotoxic.
The results presented herein form the basis of further studies on triazole derivatives as
potential drug leads against tyrosinase-related diseases.
Effects of Salvianolate Injection on the Pharmacodynamics and
Pharmacokinetics of Warfarin in Rats In vivo
Authors: Zhao Yue , Sun Jiahui , Xu Shiwei , Liu Yan , Qin Mengnan , Yang Chunjuan , Liu Gaofeng 
Published: March 2024

Background::
Both Salvianolate Injection and warfarin are widely prescribed in patients
with cardiovascular diseases, but the interaction between them is unknown and needs to be investigated.

Objective::
This research aims to study the effects and mechanism of Salvianolate Injection on the
pharmacodynamics and pharmacokinetics of warfarin in rats.

Methods::
Male Wistar rats were intraperitoneally injected Salvianolate Injection (18 mg/kg) with or
without oral administration of warfarin (0.2 mg/kg). A coagulation analyzer evaluated prothrombin
time (PT) and activated partial thromboplastin time (APTT). International normalized ratio (INR)
was calculated based on PT. UPLC-MS/MS combined with a chiral column was used to separate and
measure the plasma concentration of R-warfarin and S-warfarin. Agilent SB-C18 column (1.8 μm,
2.1 mm × 50 mm) was used for separation, column temperature at 20°C. The isocratic mobile phase
was acetonitrile-aqueous ammonium acetate (5 mM, pH 4) at a flow rate of 0.2 mL/min and 11.5 min
for each injection. Pharmacokinetic parameters were calculated using DAS 2.0 software.

Results::
Salvianolate Injection increased PT and INR (p < 0.05), while APTT was unaffected (p >
0.05). Compared with the warfarin group, the co-administration of Salvianolate Injection and singledose
warfarin enlarged PT and INR (p < 0.05). Similar increases in pharmacokinetic parameters of
R-warfarin and S-warfarin, including Cmax, AUC0-t, AUC0-∞, t1/2, and CL/F (p < 0.05), were observed
in the co-administration group. A steady-state study of warfarin indicated that PT and INR in the coadministration
group are longer than those in the warfarin group (p < 0.05). On days 7th and 8th of
warfarin treatment (two and three days after Salvianolate Injection treatment), the plasma concentration
of R-warfarin increased by 47.22% and 50.16% (p < 0.05), and plasma concentration of Swarfarin
increased by 32.39% and 45.99% (p < 0.05), respectively.

Conclusion::
Salvianolate Injection exhibits an anticoagulation effect in rats. Salvianolate Injection
can enhance the anticoagulant effect of warfarin by slowing metabolism and increasing the concentration
of both enantiomers. These results suggest that the combination of Salvianolate Injection and
warfarin should be avoided or closely monitored in case of increasing bleeding risk.
Hyperoxic-hypoxic Paradox: Breast Cancer Microenvironment and an Innovative
Treatment Strategy
Authors: Ray Suman Kumar , Mukherjee Sukhes 
Published: March 2024

Abstract:
A small therapeutic range of oxygen is required for effective metabolism. As a result, hypoxia (low
oxygen concentration) is one of the most potent inducers of gene expression, metabolic alterations, and regenerative
processes, such as angiogenesis, stem cell proliferation, migration, and differentiation. The cellular response
is controlled by sensing the increased oxygen levels (hyperoxia) or hypoxia via specific chemoreceptor cells.
Surprisingly, changes in free oxygen concentration instead of absolute oxygen levels may be regarded as a deficiency
of oxygen at the cellular level. Recurrent intermittent hyperoxia may trigger many mediators of cellular
pathways typically generated during hypoxia. The dilemma of hyperoxic-hypoxic conditions is known as the
hyperoxic-hypoxic paradox. According to the latest data, the hypoxic microenvironment, crucial during cancer
formation, has been demonstrated to play a key role in regulating breast cancer growth and metastasis. Hypoxic
circumstances cause breast cancer cells to respond in a variety of ways. Transcription factors are identified as
hypoxia-inducible factors (HIFs) that have been suggested to be a factor in the pathobiology of breast cancer and
a possible therapeutic target, driving the cellular response to hypoxia. Breast cancer has a dismal prognosis due to
a high level of resistance to practically all well-known cancer management that has been related to hypoxia-based
interactions between tumor cells and the stromal milieu. We attempt to review the enigma by exploring the starring
roles of HIFs in breast cancer, the HIF paradox, and the hyperoxic-hypoxic enigma.