bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current Computational Methods for Protein-peptide Complex
Structure Prediction
Authors: Yang Chao , Xu Xianjin , Xiang Changcheng 
Published: October 2023

Abstract:
Peptide-mediated protein-protein interactions (PPIs) play an important role in
various biological processes. The development of peptide-based drugs to modulate PPIs
has attracted increasing attention due to the advantages of high specificity and low toxicity.
In the development of peptide-based drugs, one of the most important steps is to determine
the interaction details between the peptide and the target protein. In addition to
experimental methods, recently developed computational methods provide a cost-effective
way for studying protein-peptide interactions. In this article, we carefully reviewed
recently developed protein-peptide docking methods, which were classified into three
groups: template-based docking, template-free docking, and hybrid method. Then, we
presented available benchmarking sets and evaluation metrics for assessing protein-peptide
docking performance. Furthermore, we discussed the use of molecular dynamics simulations,
as well as deep learning approaches in protein-peptide complex prediction.
Synthesis of Spiro-oxindoles (Spiroindolones) via Oxidative Ring Contraction
Approach
Authors: Sharma Yogesh Brijwashi , Sravani Sattu , Hazra Abhijit 
Published: October 2023

Abstract:
Ring contraction reaction is among the several vital strategies in organic synthesis that
can provide very diversified and useful molecular architecture. Among these strategies, the oxidative
ring contraction is of special interest as it can give a more straightforward way of designing and
synthesizing several complex natural products, specifically the oxindole alkaloids and some newer
oxindole analogs. Even this methodology can be expanded to prepare dispiro-bisoxindoles-type
compounds besides the dipolar cycloaddition methodology. In this review, we have tried to collect
the reports on oxidative ring contraction reactions using several oxidants, like tert-Butyl hypochlorite,
oxaziridine, dimethyldioxirane, N-bromosuccinimide, etc., in different reaction conditions
for the synthesis of spiro-oxindole natural products as well as newer synthetic analogs.
Sustainable Synthesis of Phenazines: A Review of Green Approaches
Authors: Shah Drashti , Bambharoliya Tushar , Patel Dharti , Patel Krina , Patel Niyati , Nagani Afzal , Bhavsar Vashisth , Mahavar Anjali , Patel Ashish 
Published: October 2023

Abstract:
Owing to its momentous significance in the development of new medications, phenazine,
and its analogues are successful heterocyclic scaffolds as well as essential building blocks for
developing physiologically active chemicals. Traditionally, phenazine and its derivatives have been
synthesized using chemical methods that involve toxic organic solvents, dangerous reagents, and
the risk of hazardous metal contamination in the final products. These drawbacks have significantly
limited the widespread application of phenazine derivatives in therapeutic treatments and the
pharmaceutical industry. Consequently, there is a growing demand for environmentally friendly
methods that can address these challenges with less environmental damage. As a result, it is now
possible to employ green and highly efficient methods for the synthesis of phenazine and its derivatives.
These methods include mechanosynthesis, solvent-free and catalyst-free synthesis, green solventbased
synthesis, ultrasound-assisted synthesis, microwave-assisted synthesis, and other similar approaches. In
light of the fact that the phenazine backbone is a widely present biologically active component and the growing
need to decrease the use of hazardous solvents, catalysts, and energy, this review has provided a summary of
various sustainable and facile synthetic strategies of phenazine derivatives.
5-Aminotetrazoles – An Overview of Synthetic Methodologies through the
Desulfurization of Thioureas
Authors: Moraes Adriana Marques , da Silva Tiago Lima , de Mattos Marcio C.S. 
Published: October 2023

Abstract:
Tetrazoles are important heterocycles in diverse branches of chemistry. Among the 5-substituted tetrazoles,
the 5-amino derivatives are the most important by far as they show high chemical versatility and relevant
applications in material chemistry, catalysis, agrochemistry, etc. Particularly in medicinal chemistry, they
present a wide range of pharmacological properties. In the present review, we focus on the synthesis of 5-
aminotetrazol from the desulfurization processes of thioureas using metal salts, hypervalent iodine compounds
and halogenated reagents.
Liver Metabolomics Analysis Revealing Key Metabolites Associated with
Different Stages of Nonalcoholic Fatty Liver Disease in Hamsters
Authors: Gao Shan-Shan , Shen Yue-Liang , Chen Yun-Wen , Wei Xiu-Zhi , Hu Jing-Jing , Wang Jue , Wu Wen-Jing 
Published: October 2023

Background and Aim:
Nonalcoholic fatty liver disease (NAFLD) is not only the top
cause of liver diseases but also a hepatic-correlated metabolic syndrome. This study performed
untargeted metabolomics analysis of NAFLD hamsters to identify the key metabolites to discriminate
different stages of NAFLD.

Methods:
Hamsters were fed a high-fat diet (HFD) to establish the NAFLD model with different
stages (six weeks named as the NAFLD1 group and twelve weeks as the NAFLD2 group, respectively).
Those liver samples were analyzed by untargeted metabolomics (UM) analysis to
investigate metabolic changes and metabolites to discriminate different stages of NAFLD.

Results:
The significant liver weight gain in NAFLD hamsters was observed, accompanied by
significantly increased levels of serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein
cholesterol (LDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase
(AST). Moreover, the levels of TG, LDL-C, ALT, and AST were significantly higher in the
NAFLD2 group than in the NAFLD1 group. The UM analysis also revealed the metabolic
changes; 27 differently expressed metabolites were detected between the NAFLD2 and
NAFLD1 groups. More importantly, the levels of N-methylalanine, allantoin, glucose, and glutamylvaline
were found to be significantly different between any two groups (control, NAFLD2
and NAFLD1). Receiver operating characteristic curve (ROC) curve results also showed that
these four metabolites are able to distinguish control, NAFLD1 and NAFLD2 groups.

Conclusion:
This study indicated that the process of NAFLD in hamsters is accompanied by different
metabolite changes, and these key differently expressed metabolites may be valuable diagnostic
biomarkers and responses to therapeutic interventions.
Comprehensive Review on Phytoconstituents-based Nanomedicine for the
Treatment of Atopic Dermatitis
Authors: Varshney Mayuri , Bahadur Shiv 
Published: October 2023

Abstract:
Atopic dermatitis (AD) is known as a chronic disease characterized by eczematous
and pruritus skin lesions. The pathology behind atopic dermatitis etiology is loss of epidermal
barrier, which prevents the production of protein filaggrin that can induce T-cell infiltration and
inflammation. Treatment of AD is majorly based on limiting skin repair as well as reducing inflammation
and itching. There are several remedies available for the treatment of AD, such as
Janus kinase and calcineurin inhibitors, topical corticosteroids, and phosphodiesterase-4 inhibitors.
The conventional formulations in the market have limited safety and efficacy. Hence, effective
treatment of atopic dermatitis requires the development of novel, efficacious, reliable, and
specific therapies. Recent research data have revealed that some naturally occurring medicinal
plants have potential applications in the management of AD through different mechanisms. The
nanotechnology-based therapeutics have gained a lot of attention in the last decade for the improvement
in the activity of drugs having low absorption due to poor solubility, thus leading to
lesser bioavailability. Therapies based on nanotechnology can be an effective way to overcome
these obstacles. Due to their effective propensity to provide better drug diffusion and bioavailability
as well as drug targeting potential at the desired site of action, these approaches may have
decreased adverse drug effects, better penetration, and enhanced therapeutic efficacy. Hence, this
review highlights the potential of phytoconstituents-based novel formulations for the treatment
of atopic dermatitis. Furthermore, recent patents on therapeutic approaches to atopic dermatitis
have also been briefly described.
Effect of Glycemic Disorders and Habits on the Concentration of Selected Neurotrophic Factors in Patients with Lumbosacral Intervertebral Disc Degeneration
Authors: Staszkiewicz Rafał , Sobański Dawid , Bryś Kamil , Och Waldemar , Garczarek Michał , Ulasavets Uladzislau , Stasiowski Michał , Dammermann Werner , Strojny Damian , Grabarek Beniamin Oskar 
Published: October 2023

Background:Unhealthy habits, such as overeating processed and high-calorie foods, alcohol abuse, and smoking, negatively impact human health. It has been suggested that the inflammatory process and the resulting growth of nerve fibers within the intervertebral disc (IVD) fissures is the main reason for the pain accompanying IVD degeneration (IVDD).Objectives:The aim of this study was to determine whether smoking, alcohol consumption, overweight/obesity, or diabetes comorbidity contribute to the development of IVDD and how the aforementioned factors affect the levels of brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), and growth associated protein 43 (GAP-43) in the study and control groups (intervertebral discs, IVDs from cadavers, and serum samples from voluntary blood donors).Methods:The study group comprised 113 patients diagnosed with IVDD who qualified for microdiscectomy. Two control groups (I and II) were used in this study. The first included 81 IVDs obtained from Caucasian human cadavers. Control group II, on the other hand, included serum samples obtained from 113 voluntary blood donors. The expression profiles of BDNF, GDNF, and GAP-43 were determined by enzyme-linked immunosorbent assay (ELISA).Results:Our statistical analysis confirmed that patients who were overweight/obese, smoked tobacco, consumed alcohol, or had diabetes had a higher risk of IVDD (OR > 1). Statistical analysis showed that BDNF, GAP-43, and GDNF concentrations were significantly higher in the IVDs and serum samples obtained from the study group compared to the control group (p < 0.05). In addition, higher levels of BDNF, GDNF, and GAP-43 were noted in IVDD patients who consumed alcohol, smoked tobacco, were overweight/obese, or had comorbid diabetes compared to patients without these risk factors (p < 0.05).Conclusion:We showed that changes in energy metabolism, habits, and lifestyle, as well as the degenerative process of IVD in the lumbosacral spine contribute to changing the concentration profile of the analyzed neurotrophic factors.
Folate-chitosan Coated Quercetin Liposomes for Targeted Cancer
Therapy
Authors: Chang Chun-hui , Han De-en , Ji Yu-ying , Wang Meng-yan , Li Dong-hong , Xu Zhi-ling , Li Jia-hao , Huang Sheng-nan , Zhu Xia-li , Jia Yong-yan 
Published: October 2023

Background:
Although quercetin exhibits promising anti-tumor properties, its clinical
application is limited due to inherent defects and a lack of tumor targeting.

Objective:
This study aimed to prepare and characterize active targeting folate-chitosan modified
quercetin liposomes (FA-CS-QUE-Lip), and its antitumor activity in vitro and in vivo was
also studied.

Materials and Methods:
Box-Behnken Design (BBD) response surface method was used to select the optimal
formulation of quercetin liposomes (QUE-LP). On this basis, FA-CS-QUE-LP was obtained by
connecting folic acid chitosan complex (FA-CS) and QUE-LP. The release characteristics in vitro
of QUE-LP and FA-CS-QUE-LP were studied. Its inhibitory effects on HepG2 cells were studied
by the MTT method. The pharmacokinetics and pharmacodynamics in vivo were studied in
healthy Wistar mice and S180 tumor-bearing mice, respectively.

Results:
The average particle size, zeta potential and encapsulation efficiency of FA-CS-QUELP
were 261.6 ± 8.5 nm, 22.3 ± 1.7 mV, and 98.63 ± 1.28 %, respectively. FA-CS-QUE-LP had a
sustained release effect and conformed to the Maloid-Banakar release model (R2=0.9967). The
results showed that FA-CS-QUE-LP had higher inhibition rates on HepG2 cells than QUE-Sol (P
< 0.01). There was a significant difference in AUC, t1/2, CL and other pharmacokinetic parameters
among QUE-LP, FA-CS-QUE-LP, and QUE-Sol (P < 0.05). In in vivo antitumor activity
study, the weight inhibition rate and volume inhibition rate of FA-CS-QUE-LP were 30.26% and
37.35%, respectively.

Conclusion:
FA-CS-QUE-LP exhibited a significant inhibitory effect on HepG2 cells, influenced
the pharmacokinetics of quercetin in mice, and demonstrated a certain inhibitory effect on S180
tumor-bearing mice, thus offering novel avenues for cancer treatment.
Clinical Research Progress of BTK Inhibitors in the Treatment of
Autoimmune Diseases
Authors: Lin Pei , Zhang Dandan , Lin Jun 
Published: October 2023

Abstract:
Bruton tyrosine kinase (BTK) is an important protein of the tyrosine kinase family and
plays a key role in signal transduction, proliferation, migration, and survival in B lymphocytes.
The inhibition of BTK is a promising therapy for various autoimmune diseases (AD) involving abnormal
B cell function, such as rheumatoid arthritis (RA), multiple sclerosis (MS), and systemic
lupus erythematosus (SLE). This article briefly summarizes the role of BTK in the BCR signaling
pathway, the development process of BTK inhibitors, and especially the latest progress of their
clinical trials for the treatment of AD.
Design, Docking, Characterisation, and Synthesis of Pyrimidine Derivatives
for Antidepressant Activity
Authors: Jadhav Ashwini , Shingade Sunil G. , Dessai Prachita G. , Biradar Bheemanagouda S. , MamleDesai Shivalingrao 
Published: October 2023

Background:
According to the report, in 2022, the prevalence rate of depression in India
was 4.50%, and the cases stood at 56,675,969. The development of antidepressant agents has reduced
the number of depressant and suicidal cases. Many researchers have found that pyrimidine
possesses antidepressant activity. With this background, we thought of synthesizing pyrimidine derivatives.

Objective:
The objective of this study is to carry out molecular docking, synthesis, characterization,
and evaluation of 2-((4,6-diphenylpyrimidin-2-yl)oxy)-N-phenylacetamide derivatives (17-26) as in
vivo antidepressant agent.

Method:
The designed compounds were checked for their activity using Molegro virtual docker
(MVD) and were further synthesized. Benzaldehyde reacted with acetophenone to give compound
(3), which gave compound (4) upon reaction with urea. In another reaction, substituted anilines (5)
were reacted with chloroacetyl chloride (6) to yield compounds (7-16), which upon further reaction
with compound (4) yielded the final derivatives (17-26). The synthesized compounds were characterized
by spectral analysis and checked for their antidepressant activity.

Result:
The MolDock scores of the derivatives ranged from -147.097 to −182.095, whereas of active
ligand IXX_801 was −115.566. All the synthesized pyrimidine derivatives showed better affinity
towards the Cryo-EM structure of the wild-type human serotonin transporter complexed with
vilazodone, imipramine, and 15B8 Fab protein (PDB ID: 7LWD) as compared to standard drug
clomipramine (−101.064). All the synthesized derivatives were screened for antidepressant activity
at a 100mg/kg dose level compared to the standard clomipramine HCl at a dose level of 20mg/kg.
Among all the synthesized derivatives, compound 24 showed the most potent antidepressant activity,
and Compound 20 showed moderate antidepressant activity, which reduced the duration of immobility
times to 35.42% and 31.97% at 100mg/kg dose level when compared to the control, respectively.

Conclusion:
Compound 24 showed the highest MolDock score as well as found to be the most potent
antidepressant agent.
Mechanisms Underlying the Therapeutic Effects of Banzhilian-Baihuasheshecao for Treating Pancreatic Ductal Adenocarcinoma Based on Bioinformatics Strategy
Authors: Zhou Xianqiang , Zhang Tiansong 
Published: October 2023

Introduction:
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of
cancer-related deaths. Banzhilian (BZL) and Baihuasheshecao (BHSSC) are classical Chinese herbs
used in tumor therapy. However, the underlying mechanisms of BZL-BHSSC in treating PDAC have
not been identified. Combining network pharmacology with single-cell RNA sequencing (scRNAseq),
this study systematically explored the potential mechanisms of BZL-BHSSC in the treatment of
PDAC.

Methods:
The bioactive ingredients of BZL-BHSSC were screened from the Traditional Chinese
Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, while the
PDAC-related datasets were obtained from the Gene Expression Omnibus (GEO) database. Based on
the dataset GSE62452, we adopted differential expression analysis and weighted gene co-expression
network analysis (WGCNA) to screen the signature genes of PDAC. To reveal the cell types of the
pharmacological targets of BZL-BHSSC against PDAC, we performed scRNA-seq analysis and
principal component analysis (PCA) on the dataset GSE111672. Molecular docking and immunohistochemical
staining were used to validate our initial results.

Results:
We obtained 29 bioactive ingredients from BZL-BHSSC and screened 210 signature genes
of PDAC. Using network pharmacology, we identified 7 key therapeutic targets CDK1, MYC,
CCNB1, TOP2A, CLDN4, NUF2, and MET, revealing that baicalein, quercetin, and luteolin are core
components for the efficacy of BZL-BHSSC. The main signaling pathways involved in therapy were
the PI3K-AKT signaling pathway and the p53 signaling pathway. The molecular docking results
verified the strong binding activity (binding energy > -7 kJ/mol) between active ingredients and targets.
The scRNA-seq results informed that cells from 3 PDAC samples could aggregate into 19 clusters
and 3 cell types. The target genes were almost concentrated on the immune cells. Immunoinfiltration
analysis suggested that the expression of Macrophages M0 and Dendritic cells activated
was significantly upregulated in the PDAC group (p<0.001), while the opposite was true for B cells
naïve and T cells CD8 expression (p<0.05).

Conclusion:
We concluded that BZL-BHSSC can improve the overall survival prognosis of PDAC
patients by interfering with the signature genes of PDAC through direct and indirect pathways and
improving immunity. Our study provides a basis for subsequent studies.
Refractory Adult-onset Still’s Disease Treated with a Combination of
Methotrexate and Etanercept
Authors: El Hasbani Georges , Ahmad Yaser , Cassetta Michael 
Published: October 2023

Background:
Adult-onset Still’s disease (AOSD) is a challenging diagnosis because of
the variability in clinical presentation and lack of gold-standard diagnostic investigations. Even after
diagnosis, the treatment is challenging, especially when the disease is refractory to first-line
therapy. Multiple pharmacotherapeutic options exist for refractory AOSD, but treatment failures
still occur. Etanercept, a Tumor necrosis factor (TNF)-alpha inhibitor, is one of the options that
has been rarely used for refractory AOSD, with various outcomes ranging from no response to
complete remission.

Case Presentation:
In this case, we highlight how a previously healthy lady had refractory AOSD
to glucocorticoids, methotrexate, and hydroxychloroquine combination therapy. There was no response
to interleukin (IL)-1 therapy, which necessitated a switch to a combination of etanercept,
low-dose methotrexate, and low-dose glucocorticoids with complete remission for a total of three-
-year follow-up.

Conclusion:
The combination of methotrexate and Etanercept can maintain remission in patients
with refractory AOSD.
Case Report of MPO+ ANCA Vasculitis with Pauci-immune GN
Associated with Invasive Ductal Carcinoma of the Breast
Authors: Mohammed Biniyam Teka , Uzodi Nnenna , Gotimukul Ashwini , Kokebie Rediet 
Published: October 2023

Background:
Malignancy-associated vasculitis usually presents in the form of polyarteritis
nodosa or leukocytoclastic vasculitis. However, ANCA vasculitis associated with malignancy
is rare. Here, we present a case of MPO+ ANCA vasculitis with pauci-immune GN associated
with invasive ductal carcinoma of the breast.

Case Presentation:
A 66-year-old female with a history of rheumatoid arthritis, Hashimoto's thyroiditis,
and psoriasis presented with multiple joint pain, body aches, petechial rash, paresthesia
and numbness, and deranged renal function a month after diagnosis of localized left breast invasive
ductal carcinoma. Renal biopsy showed crescentic pauci-immune glomerulonephritis, and
serology was positive for Perinuclear Antineutrophil Cytoplasmic Antibody (P-ANCA) and
myeloperoxidase (MPO). The disease course was complicated by diverticulitis with peritonitis
and intraperitoneal abscess collection, which required laparoscopic peritoneal lavage and additional
interventional radiology-guided drainage of the abscess. We treated the patient successfully
with steroids, rituximab, and mastectomy for left breast malignant lesions, resulting in the resolution
of symptoms, normalization of inflammatory markers, and ANCA seroconversion.

Conclusion:
Treating ANCA-associated Vasculitis (AAV) in surgical emergencies like bowel perforation
can be challenging. Individualized treatment strategy tailored to patients' acute needs is
crucial. In this case, we considered malignancy-associated vasculitis and pursued treatment that fit
the patient's clinical situation in a multidisciplinary approach.
Current Vaccination Practice in Diabetic (Diabetes I) Patients
Authors: Kumar Yati , Sundaram Sonali , Yadav Deepika 
Published: October 2023

Abstract:
The worldwide prevalence of diabetes, an endocrine condition, is rising quickly. The
alarming rise of diabetes in recent years has emerged as a major contributor to premature death
and illness among persons of working age. The potential use of immunomodulatory drugs to
prevent diabetes has been a source of worry in light of recent advances in our understanding of
the role of autoimmune responses in the development of diabetes. Vaccines can work in a variety
of ways, including by eliminating autoreactive T-cells or by blocking the connections between
immune cells. Most diabetes vaccines that have been created so far have only been evaluated
in animal models, with just a small number having undergone successful human trials. In
this article, the authors also look at the clinical trial research that are currently being conducted
to create a prototype diabetes vaccine.