bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Immunogenic Potential of PCSK9 Peptide Vaccine in Mice
Authors: Ataei Sarina , Momtazi-Borojeni Amir Abbas , Ganjali Shiva , Banach Maciej , Sahebkar Amirhossein 
Published: September 2022

Aim:
To evaluate the immunogenic potential of the carrier-free peptide-based
anti-PCSK9 (proprotein convertase subtilisin/kexin 9) vaccine in albino mice.

Methods:
The immunogenic pcsk9 peptide and 0.4% alum adjuvant were mixed thoroughly
at a 1:1 ratio and used as a vaccine formulation. To assess the humoral immune response,
animals' blood was sampled two weeks after the last immunization. The ELISA
method was employed to measure serum anti-PCSK9 antibody titers, PCSK9 concentrations,
and PCSK9/LDLR interaction.

Results:
ELISA analysis showed significant induction of IgG antibody titers by PCSK9
peptide vaccine in vaccinated mice sera compared to the control mice (in male and female
mice were 12000±586 and 11566±642, respectively, p<0.001). Mechanistic analyses
showed a significant reduction in serum PCSK9 concentrations by vaccine-induced
antibodies in vaccine groups compared to the control groups (in male mice by 29±5
ng/mL (22.4%), p<0.001 and female mice by 26±5 ng / mL (21.0%), p<0.001). Serum
concentrations of PCSK9 in control and vaccine groups were 131±8.6 ng / mL and
102±8.1 ng/ml in male mice and 124±6 ng/ml and 98±10 ng/ml in female mice, respectively.
Moreover, vaccine-induced antibodies inhibited the PCSK9-LDLR interaction in
male and female groups by 34% and 26%, respectively. No significant difference was detected
between the male and female groups in all tests (p>0.05).

Conclusions:
According to our results, the PCSK9 peptide vaccine provoked the humoral
immune system in albino mice to produce functional antibodies that inhibit plasma PCSK9.
These effects were seen in both genders without any significant difference.
Hydrophobic Tag Tethering Degradation, The Emerging Targeted
Protein Degradation Strategy
Authors: Gao Jieke , Zhang Jiantao , Han Xiaoli , Zhou Jinming 
Published: September 2022

Abstract:
Targeted protein degradation (TPD) strategies have become a new trend in
drug discovery due to the capability of triggering the degradation of protein of interest
(POI) selectively and effectively in recent decades. Particularly, the hydrophobic tag
tethering degrader (HyTTD) has drawn a lot of attention and may offer a promising strategy
for new drug research and development in the future. Herein, we will give an
overview of the development of HyTTD, the structure-activity relationship (SAR) between
HyTTD and linkers, HyTs, and ligand motifs, as well as the various HyTTDs targeting
different targets, thus offering a rational strategy for the design of HyTTDs in further
TPD drug discovery.
Development of Peptide-based Metallo-β-lactamase Inhibitors as a New Strategy to
Combat Antimicrobial Resistance: A Mini-review
Authors: Chen Sheng , Cheng Qipeng , Zeng Ping , Chi Chan Edward Wai 
Published: September 2022

Abstract:
Global dissemination of antimicrobial resistance (AMR) not only poses a significant threat to human
health, food security, and social development but also results in millions of deaths each year. In Gram-negative
bacteria, the primary mechanism of resistance to β-lactam antibiotics is the production of β-lactamases, one of
which is carbapenem-hydrolyzing β-lactamases known as carbapenemases. As a general scheme, these enzymes
are divided into Ambler class A, B, C, and D based on their protein sequence homology. Class B β-lactamases
are also known as metallo-β-lactamases (MBLs). The incidence of recovery of bacteria expressing metallo-β-
lactamases (MBLs) has increased dramatically in recent years, almost reaching a pandemic proportion. MBLs
can be further divided into three subclasses (B1, B2, and B3) based on the homology of protein sequences as
well as the differences in zinc coordination. The development of inhibitors is one effective strategy to suppress
the activities of MBLs and restore the activity of β-lactam antibiotics. Although thousands of MBL inhibitors
have been reported, none have been approved for clinical use. This review describes the clinical application potential
of peptide-based drugs that exhibit inhibitory activity against MBLs identified in past decades. In this
report, peptide-based inhibitors of MBLs are divided into several groups based on the mode of action, highlighting
compounds of promising properties that are suitable for further advancement. We discuss how traditional
computational tools, such as in silico screening and molecular docking, along with new methods, such as
deep learning and machine learning, enable a more accurate and efficient design of peptide-based inhibitors of
MBLs.
Potential Nevadensin from Ocimum basilicum as Antibacterial Agent
against Streptococcus mutans: In Vitro and In Silico Studies
Authors: Putri Salsabila Aqila , Nur Shadrina Aldina Amalia , Julaeha Euis , Kurnia Dikdik 
Published: September 2022

Background:
Streptococcus mutans is one of the bacteria that contributes to biofilm
formation and causes dental caries. The inhibition of SrtA, gbpC, and Ag I/II is a promising target
to be developed as an antibacterial. Ocimum bacilicum is known to have antibacterial activity.

Aim and Objective:
The aim of this study is to evaluate the potential nevadensin as antibacterial
against S. mutans.

Methods:
Antibacterial analysis was carried out by disc diffusion and micro-dilution methods and
the in-silico study was performed with ligand-protein docking.

Results:
The result showed that the MIC and MBC values of nevadensin are 900 and 7200 μg/mL,
respectively. The binding energy of nevadensin to SrtA, gbpC, and Ag I/II were -4.53, 8.37, -6.12
kcal/mol, respectively.

Conclusion:
Nevadensin shows moderate activity as an antibacterial against S. mutans. Meanwhile,
in silico studies showed it has the same binding strength as chlorhexidine in inhibiting SrtA,
whereas to gbpC and Ag I/II, it has a weaker binding affinity. Therefore, nevadensin has the potential
as a natural antibacterial against S. mutans by inhibiting SrtA.
Re-Analysis of Published Datasets in Search of Novel Urogenital Diseases
Biomarkers
Authors: Vitorino Rui , Perpétuo Luís , Thongboonkerd Visith , Ferreira Rita , Guedes Sofia , Amado Francisco 
Published: September 2022

Background:
Exosome research is a current trend in functional proteomics as it provides im-portant data on the pathophysiology and pathogenesis of diseases. The scientific outputs re-garding these topics often only approach disease-protein/peptide/exosome or mecha-nism-protein/peptide/exosome association. Approaching all three aspects could be the key to a better understanding of the pathophysiology and uncovering novel biomarkers for urogenital diseases. The focus of this work is to study exosome datasets to understand the possible role of underlying proteins in disease manifestation. We also attempt to link 4 different diseases that affect renal functions and are genetically inherited.

Methods:
For this purpose, the existing literature is consulted to understand the importance of exosomes in disease prediction, diagnosis and therapy. Available biotechnological methods of exosome analysis and the tools of proteomic analysis, data mining and visualization are dis-cussed. The database PRIDE is selected to query the information of several datasets related to urinary exosome analysis.

Results:
We have obtained a list of 19 proteins/genes involved in the mentioned diseases. On this list, we found a proteomic fingerprint consisting of Rab-7a, PDCD6, and CDC42, among others, and we are exploring their biological significance and underlying processes.

Conclusion:
APOA1, CD59, CD9, IGHG1, RAB7A, RAP1A, SEMG1 and SEMG2 are common in four urogenital diseases, and are involved in interactions with podosomes and endosomes, re-modeling of chylomicrons, regulation of interleukin production, regulation of endopeptidase activity, and establishment of apical/basal polarity of epithelial cells.
Small-Molecule Drugs in Immunotherapy
Authors: Su Qing , Hao Xuanrun , Chen Zhongliang , Li Haining , Wei Minqin , Zuo Zhili 
Published: September 2022

Abstract:
Immunotherapy has been increasingly used in the treatment of cancer. Compared with
chemotherapy, immunotherapy relies on the autoimmune system with fewer side effects. Small
molecule immune-oncological medicines usually have good bioavailability, higher tissue and tumor
permeability, and a reasonable half-life. In this work, we summarize the current advances in the
field of small molecule approaches in tumor immunology, including small molecules in clinical trials
and preclinical studies, containing PD1/PD-L1 small molecule inhibitors, IDO inhibitor, STING
activators, RORγt agonists, TGF-β inhibitors, etc. PD-1/DP-L1 is the most attractive target at present.
Some small molecule drugs are being in clinical trial studies. Among them, CA-170 has attracted
much attention as an oral small molecule drug. IDO is another popular target after PD-1/PDL1.
The dual IDO and PD-1 inhibitor can improve the low response of PD-1 and has a good synergistic
effect. STING is a protein that occurs naturally in the human body and can enhance the body's
immunity. RORγt is mainly expressed in cells of the immune system. It promotes the differentiation
of Th17 cells and produces the key factor IL-17, which plays a key role in the development of autoimmune
diseases. TGFβ signaling exhibits potent immunosuppressive activity on the coordinate
innate and adaptive immunity, impairing the antitumor potential of innate immune cells in the tumor
microenvironment. It is worth mentioning that immunotherapy drugs can often achieve better effects
when used in combination, which will help defeat cancer.
Docking and Pharmacokinetic Studies for Screening Terpenoids from
Erythroxylum Species as Anticancer Agents
Authors: Unavane Supriya A. , Syed Sabeena , Jain Hemant Kumar , Bansode Amol 
Published: September 2022

Background:
Cancer still remains a disease of concern with various side effects of synthetic
chemotherapeutic agents. Hence, there is a continued need to develop safer therapies with fewer side effects.
Erythroxylum species is a widely available source of various phytoconstituents, especially terpenoids.

Objective:
To carry out the docking studies of a few terpenoids on validated targets like EGFR, VEGFR,
CDK, and tubulin protein which are overexpressed in many types of cancers, and to estimate the pharmacokinetic
and drug-likeness properties of these molecules using in silico techniques.

Materials:
Protein structures were retrieved from Protein Data Bank, and the terpenoids were docked on
each of the protein targets using Autodock 4.2. SwissADME was used to predict the pharmacokinetic and
drug-likeness properties.

Results:
Compounds show good binding affinity and inhibition constant for all targets except for tubulin,
where few ligands could bind. They exhibit an excellent pharmacokinetic profile, and no significant violations
in drug-likeness parameters were observed.

Conclusion:
Compound 2 was found to be the most active agent against VEGFR, CDK, and tubulin,
whereas compound 7 was most effective at EGFR. These compounds can be continued for further studies.
The Effect of Metformin on Bad, Bak, and Bim Pro-apoptotic Factors: A Molecular Dynamic Simulation Study
Authors: Mostafavi-Pour Zohreh , Jamali Navid , Saffari-Chaleshtori Javad , Samare-Najaf Mohammad 
Published: September 2022

Background:Recent investigations have demonstrated that metformin treatment can decrease tumor incidence and growth using cell cycle arrest and induction of apoptosis pathway. However, it is not clear how metformin affects the factors involved in the apoptotic process.Objective:The present study aimed to determine the effect of metformin on Bak, Bad, and Bim pro-apoptotic proteins using docking and dynamics simulation studies.Method:The 3D structure of molecules was retrieved from PubChem and RCSB servers. Simulation and docking studies were conducted by Gromacs and AutoDock software. Next, molecular dynamics analysis was performed using Gromacs software. Moreover, LigPlot+V.4.5.3 software was applied for the determination of the hydrogen and hydrophobic interactions at the binding sites.Result:Our findings demonstrated that metformin has the highest affinity for binding the Bak protein. This binding occurred using four amino acid residues within the binding site of Bak with the minimum binding energy (-5.70 kcal/mol). The molecular docking of metformin to these pro-apoptotic factors significantly decreased the total energy and increased the coil secondary structure of Bak protein.Conclusion:According to our findings, metformin can alter the molecular dynamics property of these proteins which results in increased activity of these pro-apoptotic proteins and induction of apoptosis.
Lifestyle Among Fertile and Infertile Women: A Case-Control Study in the West of Iran
Authors: Jenabi Ensiyeh , Ayubi Erfan , Khazaei Salman , Abdoli Sara 
Published: September 2022

Background:In the studies conducted in Iran, the determining role of lifestyle as a multifactorial concept of infertility in infertile Iranian women has rarely been investigated.Objective:to compare the lifestyles of fertile and infertile women in Iran.Method:This case-control study was conducted on 400 women in 2022. The control group includes women aged 18-45 years, with no history of infertility and who had at least one child. The case group includes women whose primary infertility has been diagnosed and confirmed by a gynecologist and who were referred to the infertility ward in the west of Iran for treatment. The Miller-smith lifestyle assessment inventory was used in this study. We applied a significance level of 0.05 using the Stata ver. 14.Results:In multivariable analysis after adjusting for age, BMI, women's education, husband's education, women's Job, age at menarche, and menstrual cycle, the infertile women had higher scores on the Miller-Smith lifestyle questionnaire than fertile women [linear regression coefficient=21.21; 95% confidence interval: 20.56 to 21.86; p<0.001].Conclusion:The situations of lifestyle components such as time of rest, attending club and social activities, physical activity, recreation, having close friends, and religious beliefs were better in fertile women, as compared to infertile women.
Novel Anti-diabesity Peptide Alkaloids from Allophylus africanus P. Beauv
Authors: Balogun Olaoye Solomon , Liu Shu , Zhong Zheng , Liu Zhiqiang 
Published: September 2022

Aim:
The aim of the study was to characterize and investigate the mechanism of action
of anti-hyperglycemic and anti-hyperlipidemic constitutents of Allophylus africanus.

Background:
Allophylus africanus P. Beauv is a medicinal plant commonly used in sub-Sahara
Africa for the treatment of metabolic disorders and infectious diseases.

Objectives:
The objective of the study was to isolate and characterize anti-hyperglycemic and antihyperlipidemic
chemical constituents from Allophylus africanus, and to investigate the mechanism
of their enzymatic inhibitions.

Methods:
The chemical constituents were isolated using various column chromatographic techniques.
The anti-hyperlipidemic and anti-hyperglycemic properties of the chemical constituents
were investigated by measuring their inhibitory effects on porcine pancreatic lipase and α-
glucosidase enzymes. Fluorescence quenching constants obtained from Stern−Volmer plots were
used to determine the mechanisms of inhibitory action.

Results:
Twelve compounds, of which three were new peptide alkaloids, ethylamino asperphenamate
(10), allophylane (11) and allophyline (12), were isolated. The new peptide alkaloids and
asperphenamate (9) inhibited porcine pancreatic lipase in a dose-dependent manner with IC50 < 90
μM. Also, 9, 12, stigmasta-5, 22-dien-3-O-β-D-glucoside (3) and eudesmenol (5) inhibited α-
glucosidase enzymes with IC50 < 165 μM, which was lower than that of standard drug, acarbose
(432.16 ± 6.52 μM). From the Stern-Volmer plots, 9 and 10 indicated a static quenching, while 11
and 12 suggested the occurrence of both static and dynamic quenching mechanisms on porcine
pancreatic lipase. On α-glucosidase, only 12 exhibited a concurrent static and dynamic quenching
mechanism.

Conclusion:
The anti-diabesity compounds obtained from A. africanus established its potential for
the treatment of metabolic disorders. Among the isolated compounds, three have been reported for
the first time in nature while others have been reported for the first time in the plant.
Exploring the Mechanism of the Baishao Luoshi Formula against Poststroke
Spasticity by Network Pharmacology and Experimental Validation
Authors: Zeng Shanshan , Xie Le , Mao Guo , Xie Yao , Cao Sijia , Liu Dong , Wu Dahua 
Published: September 2022

Background:
Post-stroke spasticity (PSS) is a major cause of disability, leading to severely
impaired upper-limb flexibility and ability to walk and move, significantly affecting the
quality of life of cerebral infarction patients. There is currently no recognized effective therapy.
Alternatively, Chinese traditional medicine has shown promise for PSS treatment. In this regard,
the BSLSF has been reported to be effective; however, its underlying mechanism remains unclear.

Objective:
The objective of this study is to clarify the main targets and pathways of Baishao Luoshi
Formula (BSLSF) during PSS treatment, laying the foundation for further research on its
pharmacological effects.

Method:
In this study, network pharmacology and experimental verification were conducted to
explore the potential mechanism of BSLSF systematically. After obtaining active ingredients of
BSLSF from the TCMSP database, SwissTarget-Prediction and PharMapper were used to uncover
BSLSF targets. PSS-related targets were gathered with GeneCards and Online Mendelian Inheritance
in Man. The differentially expressed genes between BSLSF and PSS were identified by a
Venn plot. The drug-active ingredient-target interaction network and Protein-protein interaction
(PPI) were constructed using Cytoscape and further analyzed using the MCC algorithm of Cyto-
Hubba plugin. Then, Pathway enrichment and GO biological process enrichment analyses were
performed. Subsequently, a mice model of middle cerebral artery occlusion (MCAO) was established
for the in vivo experiments.

Result:
We found that AKT1, TNF, CASP3, VEGFA, and CREB1 were potential targets during
PSS treatment. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG)
pathway enrichment analyses showed that the mechanism of PSS was closely related to synaptic
plasticity. And the immunohistochemical staining showed that BSLSF protected against ischemic
stroke via the CCR5/CREB signaling pathway and probably affected synaptic plasticity.

Conclusion:
our study validated that treatment with BSLSF protected against ischemic stroke via
the CCR5/CREB signaling pathway and could affect synaptic plasticity. In a sense, this study provides
the basis for further extensive and in-depth analysis of BSLSF, enabling the quest for new
drug targets at the same time.
Stem Cells as a Therapeutic Choice in Dermatological Disorders
Authors: Legiawati Lili , Suseno Lis Surachmiati , Sitohang Irma Bernadette S. , Yusharyahya Shannaz Nadia , Ardelia Athaya , Paramastri Kanya 
Published: September 2022

Abstract:
Stem cells are known for their extraordinary properties, mainly their potency, self-renewal, and
clonality. In recent years, we have witnessed notable advancements in the field of cell therapy. Due to its
remarkable properties and versatility, this cutting-edge therapy has now become a potentially promising
cure for many diseases. Stem cell-based therapies have been utilized to treat various dermatological conditions,
for instance, autoimmune skin disorders, atopic dermatitis, skin aging, wound healing, scar treatment,
and many others. This article aims to serve as an overview of cell-based therapy's current application
in dermatology field.
PCSK9 A/G (rs505151) Gene Polymorphism and its Expression at the
Molecular Level in Patients with Coronary Artery Disease
Authors: Srivastava Kamna , Aggarwal Shelly , Narang Rajiv , Saluja Daman 
Published: September 2022

BACKGROUND:
PCSK9 (Proprotein convertase subtilisin/kexin type 9) plays a key role in cholesterol homeostasis and Coronary artery disease (CAD). Many studies have extrapolated the association of PCSK9 gene with low density lipoprotein cholesterol (LDL-C) levels and CAD but with contradicting results. There is no such study available stating the intergenotypic variations in the levels of expression of PCSK9 and LDL-C and their correlations with CAD risk factors in patients with CAD.

OBJECTIVE:
We aim to explore the association of PCSK9 A/G (rs505151) polymorphism and its expression at mRNA and protein level in patients with CAD. Additionally, it is investigated how the levels of LDL-C, PCSK9, BMI, and systolic blood pressure (SBP) in patients with CAD and in healthy participants relate to the PCSK9 intergenotypic variation.

METHODS:
Angiographically confirmed CAD patients [n=250] and controls [n=250] were genotyped by PCR followed by RFLP techniques. Real time PCR and Western Blot methods were used to investigate PCSK9's differential expression.

RESULTS:
Odds ratio being the index of association revealed a statistically significant association of PCSK9 A/G (rs505151), A Vs G= 4.94 [1.37-7.79] polymorphism with CAD. In patients with the GG genotype, there is a correlation between higher PCSK9 gene expression and circulating LDL-C levels.

CONCLUSION:
Our study shows a significant association of PCSK9 gene polymorphism with CAD. We also observed an increased expression of PCSK9 gene in patients with G allele. In our study, PCSK9 A/G (rs505151) gene and LDL-C emerged as independent risk factors. To determine whether upregulated PCSK9 gene expression can act as a prognostic marker for CAD, more follow-up research is required.
A Comprehensive Review of Various Machine Learning Techniques used
in Load Forecasting
Authors: Mohan Divya Priyadharshini , Subathra MSP 
Published: September 2022

Background:
Load forecasting is a crucial element in power utility business load forecasting and has influenced key decision-makers in the industry to predict future energy demand with a low error percentage to supply consumers with load-shedding-free and uninterruptible power. By applying the right technique, utility companies may save millions of dollars by using load prediction with a lower proportion of inaccuracy.

Aims:
This study paper aims to analyse the recently published papers (using the New York Independent System Operator's database) on load forecasting and find the most optimised forecasting method for electric load forecasting.

Methods:
An overview of existing electric load forecasting technology with a complete examination of multiple load forecasting models and an in-depth analysis of their MAPE benefits, challenges, and influencing factors is presented. The paper reviews hybrid models which are created by combining two or more predictive models, each offering better performance due to their algorithm's merits. Hybrid models outperform other machine learning (ML) approaches in accurately forecasting power demand.

Result:
Through the study it is understood that hybrid methods show promising features. Deep learning algorithms were also studied for long-term forecasting.

Conclusion:
In the future, we can extend the study by extensively studying the deep learning methods.