bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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

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

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.
Synthesis, and In-silico Studies of Indole-chalcone Derivatives Targeting
Estrogen Receptor Alpha (ER-α) for Breast Cancer
Authors: Choudhari Rahul Charudatta , Kaur Kamalpreet , Das Agnidipta , Jaitak Vikas
Published: October 2023

Background:

Breast cancer is the prominent reason of death in women worldwide,
and the cases are increasing day by day. There are many FDA-approved drugs for treating breast
cancer. Due to drug resistance, and problems in selectivity, there is a need to develop more effective
agents with few side effects. Indole derivatives have demonstrated significant pharmacological
potential as anti-breast cancer agents. Further, chalcone derivatives incorporating heterocyclic
scaffolds play a significant role in medicine. Indole-chalcone-based compounds offer the
potential for improved biological activity and enhanced drug-like properties. It prompted us to
explore the synthesis of Indole-Chalcone derivatives targeting estrogen receptor alpha (ER-α) to
discover potent anti-breast cancer agents.

Objectives:

To synthesize indole-chalcone derivatives and study their binding interactions for
ER-α protein by molecular docking for breast cancer treatment.

Methods:

In this study, indole-chalcone derivatives have been synthesized using conventional
heating. With the help of Schrodinger software, molecular interaction as well as ADME (Adsorption,
Distribution, Metabolism, and Excretion) studies of the compounds were conducted.

Results:

Among all the synthesized compounds, four compounds (1, 2, 3, and 4) showed better
docking scores (-10.24 kcal/mol, -10.15 kcal/mol, -9.40 kcal/mol, -9.29 kcal/mol, respectively)
than the standard tamoxifen (-8.43 kcal/mol).

Conclusion:

From In-silico studies, we can conclude that four compounds from the synthesized
series fit into the active site of ER-α. ADME properties of synthesized derivatives were found in
the acceptable range. In the future, these compounds can be further explored for biological activity.
DMR_Kmeans: Identifying Differentially Methylated Regions Based on
k-means Clustering and Read Methylation Haplotype Filtering
Authors: Peng Xiaoqing , Cui Wanxin , Kong Xiangyan , Huang Yuannan , Li Ji
Published: October 2023

Introduction::

Differentially methylated regions (DMRs), including tissue-specific DMRs
and disease-specific DMRs, can be used in revealing the mechanisms of gene regulation and screening diseases. Up until now, many methods have been proposed to detect DMRs from bisulfite sequencing data. In these methods, differentially methylated CpG sites and DMRs are usually identified based on statistical tests or distribution models, which neglect the joint methylation statuses
provided in each read and result in inaccurate boundaries of DMRs.

Methods::

In this paper, a method, named DMR_Kmeans, is proposed to detect DMRs based on kmeans clustering and read methylation haplotype filtering. In DMR_Kmeans, for each CpG site, the
k-means algorithm is used to cluster the methylation levels from two groups, and the methylation
difference of the CpG is measured based on the different distributions in clusters. Methylation haplotypes of reads are employed to extract the methylation patterns in a candidate region. Finally, DMRs
are identified based on the methylation differences and the methylation patterns in candidate regions.

Result::

Comparing the performance of DMR_Kmeans and eight DMR detection methods on the
whole genome bisulfite sequencing data of six pairs of tissues, the results show that DMR_Kmeans
achieves higher Qn and Ql, and more overlapped promoters than other methods when given a certain
threshold of methylation difference greater than 0.4, which indicates that the DMRs predicted by
DMR_Kmeans with accurate boundaries contain less CpGs with small methylation differences than
those by other methods.

Conclusion::

Furthermore, it suggests that DMR_Kmeans can provide a DMR set with high quality
for downstream analysis since the total length of DMRs predicted by DMR_Kmeans is longer and
the total number of CpG sites in the DMRs is greater than those of other methods.
A Deep Neural Network Model with Attribute Network Representation for
lncRNA-Protein Interaction Prediction
Authors: Wei Meng-Meng , Yu Chang-Qing , Li Li-Ping , You Zhu-Hong , Lei-Wang
Published: October 2023

Background:

LncRNA is not only involved in the regulation of the biological functions of
protein-coding genes, but its dysfunction is also associated with the occurrence and progression of
various diseases. Various studies have shown that an in-depth understanding of the mechanism of
action of lncRNA is of great significance for disease treatment. However, traditional wet testing is
time-consuming, laborious, expensive, and has many subjective factors which may affect the accuracy
of the experiment.

Objective:

Most of the methods for predicting lncRNA-protein interaction (LPI) rely on a single
feature, or there is noise in the feature. To solve this problem, we proposed a computational model,
CSALPI based on a deep neural network.

Methods:

Firstly, this model utilizes cosine similarity to extract similarity features for lncRNAlncRNA
and protein-protein, denoising similar features using the Sparse Autoencoder. Second, a
neighbor enhancement autoencoder is employed to enforce neighboring nodes to be represented
similarly by reconstructing the denoised features. Finally, a Light Gradient Boosting Machine classifier
is used to predict potential LPIs.

Results:

To demonstrate the reliability of CSALPI, multiple evaluation metrics were used under a 5-
fold cross-validation experiment, and excellent results were achieved. In the case study, the model
successfully predicted 7 out of 10 disease-associated lncRNA and protein pairs.

Conclusion:

The CSALPI can be an effective complementary method for predicting potential LPIs
from biological experiments.
Arsenic Trioxide inhibits Activation of Hedgehog Pathway in Human Neuroblastoma
Cell Line SK-N-BE(2) Independent of Itraconazole
Authors: Liu Xiaoshan , Wang Zhixuan , Xiong Xilin , Li Chunmou , Wu Yu , Su Mingwei , Yang Shu , Zeng Meilin , Weng Wenjun , Huang Ke , Zhou Dunhua , Fang Jianpei , Xu Lvhong , Li Peng , Zhu Yafeng , Qiu Kunyin , Ma Yuhan , Lei Jiaying , Li Yang
Published: October 2023

Background:

Neuroblastoma (NB) remains associated with a low overall survival rate over the long term.
Abnormal activation of the Hedgehog (HH) signaling pathway can activate the transcription of various downstream
target genes that promote NB. Both arsenic trioxide (ATO) and itraconazole (ITRA) can inhibit tumor growth.

Objective:

To determine whether ATO combined with ITRA can be used to treat NB with HH pathway activation,
we examined the effects of ATO and ITRA monotherapy or combined inhibition of the HH pathway in NB.

Methods:

Analysis of CCK8 and flow cytometry showed cell inhibition and cell cycle, respectively. Real-time
PCR analysis was conducted to assess the mRNA expression of HH pathway.

Results:

We revealed that as concentrations of ATO and ITRA increased, the killing effects of both agents on
SK-N-BE(2) cells became more apparent. During G2/M, the cell cycle was largely arrested by ATO alone and
combined with ITRA, and in the G0/G1 phase by ITRA alone. In the HH pathway, ATO inhibited the transcription
of the SHH, PTCH1, SMO and GLI2 genes, however, ITRA did not. Instead of showing synergistic effects in
a combined mode, ITRA decreased ATO inhibitory effects.

Conclusion:

We showed that ATO is an important inhibitor of HH pathway but ITRA can weaken the inhibitory
effect of ATO. This study provides an experimental evidence for the clinical use of ATO and ITRA in the treatment
of NB with HH pathway activation in cytology.
The Landscape of Randomized Clinical Trial Meta-analyses on Statins for
Aneurysmal Subarachnoid Hemorrhage: A Scoping Review
Authors: Skouras Panagiotis , Kalamatianos Theodosis , Markouli Mariam , Karagiannis Angelos , Stavrinou Lampis C.
Published: October 2023

Introduction:

Aneurysmal subarachnoid hemorrhage (aSAH) is a type of non-traumatic
SAH that can have detrimental effects on the central nervous system, resulting in severe disability or
death.

Methods:

Early nimodipine is currently the only strongly recommended pharmacological treatment
that has shown efficacy in improving neurological/functional outcomes in aSAH patients. Whether
statin treatment is of benefit to aSAH patients is an issue that has generated considerable interest and
debate. In the present scoping review, we mapped and analyzed the available literature on metaanalyses
of randomized clinical trials (RCTs) examining the effect of statins on aSAH. Seventeen
meta-analyses of RCTs, published between 2008 and 2023, were identified.

Results:

Treatments in included meta-analyses were based on various regimens of simvastatin,
pravastatin, pitavastatin or atorvastatin for up to 21 days. Eleven of the included reports indicated
some beneficial effect of statin treatment, reducing rates of at least one of the following: cerebral
vasospasm, delayed cerebral ischemia/delayed ischemic neurologic deficit, mortality or functional/
neurological outcome. In contrast, six meta-analyses, showed no such effects.

Conclusion:

The limitations reported by several meta-analyses, included low patient numbers or disproportionate
representation of patients from certain RCTs, differences in drug treatment, patient diagnostic
criteria and outcome evaluation between RCTs, as well as poor data quality or lack of RCTs
data. Knowledge of the reported limitations may aid the design of future clinical trials and/or their
meta-analyses.
Why Pharmacovigilance of Non-steroidal Anti-inflammatory Drugs is Important in India?
Authors: Dash Subhransu , Singh Preet Amol , Bajwa Neha , Choudhury Abinash , Bisht Preeti , Sharma Rajiv
Published: October 2023

Background:

Non-steroidal Anti-Inflammatory Drugs (NSAIDs) are among the drugs that are most regularly administered to manage inflammation and pain. Over-the-Counter (OTC) NSAIDs are widely accessible, particularly in developing countries like India. This casual approach to using NSAIDs may operate as a magnet for NSAID-related adverse drug reactions (ADRs) among patients.

Objectives:

As patients in India are less informed about the appropriate use of NSAIDs and consumption patttern, adverse drug reactions, and the importance of reporting ADRs, the current study's objective is to promote patient safety by using pharmacovigilance as a tool to educate patients.

Methods:

A targeted literature methodology was utilized to gather the data pertaining to NSAIDs, their ADRs and their pharmacovigilance. Different scientific databases, such as Science Direct, PubMed, Wiley Online Library, Springer, and Google Scholar, along with authentic textbooks, were explored as reference literature.

Results:

In general, NSAIDs consumption pattern depends upon the different age groups. Around 1.6 billion tablets of NSAIDs are consumed in India for ailments, such as headaches, arthritis, menstrual cramps, osteoarthritis, back pain, rheumatoid arthritis, gout, osteoporosis, tendinitis, cancer pain and chronic pain. Common ADRs of NSAIDs include nausea, vomiting, headache, gastritis, abdominal pain, and diarrhoea. Also, they can cause renal damage and cardiovascular problems if not consumed in a dose-dependent manner. However, Diclofenac and Ibuprofen have both been linked to depression and dementia. There have been reports of aplastic anaemia, agranulocytosis linked to phenylbutazone, Stevens-Johnson, and Lyell's syndrome linked to isoxicam and piroxicam, as well as the vulnerability of new-borns to Reye's syndrome after aspirin use. Lack of awareness, time constraints and unpredictability, poor training in ADRs identification, etc., are some of the reasons for the under-reporting of ADR of NSAIDs in India.

Conclusion:

In order to rationally prescribe NSAIDs, it is essential to be aware of probable ADR’s and establish prescription guidelines. Prescribers' behaviour can be changed toward excellent prescribing practices by conducting routine prescription assessments dealing with NSAIDs and providing feedback. In the near future, it will be critical to strengthen ADR data management and expand the reach of pharmacovigilance programs, ADR monitoring centers, and healthcare professionals' especially pharmacists’ training in rural locations.
The New Kernel-based Multiple Instances Learning Algorithm for Object Tracking
Authors: Zhang Hua , Wang Lijia
Published: October 2023

Background:

Visual tracking is a crucial component of computer vision systems.

Objective:

To deal with the problems of occlusion, pose variation, and illumination in long-time
tracking, we propose a new kernel-based multiple instances learning tracker.

Method:

The tracker captures five positive bags, including the occlusion bag, pose bag, illumination
bag, scale bag, and object bag, to deal with the appearance changes of an object in a complex
environment. A Gaussian kernel function is used to compute the inner product for selecting the
powerful weak classifiers, which further improves the efficiency of the tracker. Moreover, the
tracking situation is determined by using these five classifiers, and the correlating classifiers are
updated.

Results:

The experimental results show that the proposed algorithm is robust in terms of occlusion
and various appearance changes.

Conclusion:

The proposed algorithm preforms well in complex situations.
Network Anomaly Detection using Autoencoder on Various Datasets: A
Comprehensive Review
Authors: Singh Richa , Srivastava Nidhi , Kumar Ashwani
Published: October 2023

The scientific community is currently very concerned about information and communication
technology security because any assault or network anomaly can have a remarkable collision
on a number of areas, including national security, the storage of private data, social welfare,
economic concerns, and more. As a result, many strategies and approaches for this goal have
been developed over time, making the anomaly detection domain a large research subject. The
primary concern of this study is to review the most crucial elements relating to anomaly detection,
including an overview of background analysis and a core study on the most important approaches,
procedures, and systems in the field. To make the structure of this survey easier to understand,
the domain of anomaly detection was examined along with five dimensions: Detection
methods in network traffic, objectives of the paper, various datasets used, accuracy, and open issues/
gaps. The gap which has been identified after the survey can be extended as a future scope
might be helpful for the researcher.
A Review of Research on Upper Extremity Rehabilitation Robots
Authors: Liu Hongbo , Li Wenheng , Yang Xiaodong
Published: October 2023

Background:

Most of the patients with limb paralysis caused by stroke and traumatic
brain injury are unable to take care of themselves, which not only causes great physical and psychological
stress to the patients but also poses a heavy burden on their families and society. The
global population is entering the aging phase. The number and proportion of older people is increasing
in almost every country in the world. Population aging has the potential to become one of
the most important social trends of the 21st century, and almost all areas of society are affected by
it, including labor and financial markets, demand for goods and services, such as housing, transportation,
and social security, family structures, and intergenerational relationships. Rehabilitation
robotics is a research field that has emerged from this demand.

Objective:

Through the analysis of the current situation and development of upper limb rehabilitation
robots, several types of upper limb rehabilitation robots with the most widely used structures
today are extracted from the representative results, and each robot is analyzed and elaborated in
detail. It provides a reference for readers to choose the appropriate upper limb rehabilitation robots.

Methods:

We have classified the upper limb rehabilitation robots through several patents, briefly
explained and analyzed the robots grouped, summarized the advantages and disadvantages of various
robots, and provided an outlook on future development trends.

Results:

Through the research and analysis of the degree of freedom and control system of the
upper limb rehabilitation robot, it can be seen that certain upper limb rehabilitation robots have
large structures and complex systems, and their application scope is limited; most domestic rehabilitation
robots have fewer degrees of freedom and can only provide rehabilitation training for
single joints or a few degrees of freedom, especially for the shoulder, which has a small spatial
range, too low range of motion and amplitude, and a single mode of motion, and cannot complete
a wide range of motion for certain joints, as well as a compound motion for multiple joints, thus
failing to provide adequate stimulation of the central nerve.

Conclusion:

The analysis shows that the existing upper limb rehabilitation robots are poorly
adaptable and not well-suited for situations, such as for different patients and different recovery
periods of the same patient. The upper limb rehabilitation robot solution needs to be more appropriately
designed to meet all requirements in the rehabilitation movement of patients.
CYP1A2*F Polymorphism Contributes at Least Partially to the Variability
of Plasma Levels of Dehydroaripiprazole, an Active Metabolite of
Aripiprazole, in Schizophrenic Patients
Authors: Suzuki Takeshi , Nagai Goyo , Mihara Kazuo , Tomori Yoko , Kagawa Shoko , Nakamura Akifumi , Nemoto Kenji , Kondo Tsuyoshi
Published: October 2023

Aim:

The relationship between CYP1A2 polymorphisms and the steady-state plasma levels of aripiprazole and its active metabolite, dehydroaripiprazole, were investigated in Japanese schizophrenic patients.

Background:

It has been implied that cytochrome P450 (CYP) 1A2 may play a role in the metabo-lism of aripiprazole. Genetic variations in the CYP1A2 gene have been reported.

Objective:

The authors investigated the relationship between 2 CYP1A2 polymorphisms, CYP1A2*C (-3860G>A) and CYP1A2*F (-163C>A), and the steady-state plasma levels/dose (C/D) ratios of aripiprazole and dehydroaripiprazole in Japanese schizophrenic patients.

Methods:

All 89 subjects (46 males and 43 females) had been receiving 2 fixed daily doses of ari-piprazole (24 mg; n=56 and 12 mg: n=33) for more than 2 weeks. No other drugs were used except flunitrazepam and biperiden. The plasma drug levels were determined by LC/MS/MS. These CYP1A2 polymorphisms were detected using polymerase chain reaction analysis.

Results:

The mean C/D ratios of dehydroaripiprazole were significantly (P < 0.05) lower in pa-tients with the A/A allele of CYP1A2*F than in those without the allele. No differences were found in the values of aripiprazole and the combination of aripiprazole and dehydroaripiprazole among the CYP1A2*F genotype. There were no differences in the values of aripiprazole, dehydroaripipra-zole, or the combination of the 2 compounds among the CYP1A2*C genotype. The absence of the A allele of CYP1A2*F was correlated with the mean C/D ratios of dehydroaripiprazole (standardized partial correlation coefficient = 0.276, P < 0.01) by multiple regression analysis.

Conclusion:

The findings of this study suggest that the CYP1A2*F polymorphism contributes at least partially to the variability in the steady-state plasma levels of dehydroaripiprazole.
Effect of Capsule Thickness and Material Properties on the Central Optical Power of Natural Human Lens
Authors: Kakavand Reza , Komeili Amin
Published: October 2023

Background:

A thin membrane capsule covers the eye lens and links the lens and the applied forces by the ciliary muscles. The capsule converts the tension of the concentrated zonules to distributed surface tractions over the cortex surface during the lens accommodation. The gradual changes of the capsule geometry and material properties with age and its important role in the design of intraocular lens implants were the motivation of extensive researches on describing the capsule biomechanical behavior.

Aim:

The present work aimed to study the lens accommodation response to different capsule thicknesses and material properties at different ages.

Materials and Methods:

A material and geometry parametric study was performed, drawing some guidelines on the choice of lens capsule thickness and biaxial/uniaxial material parameters and exploring the response sensitivity of the finite element model at different age groups

Results:

The 16-, 35- and 48-year-old lenses were considered for lens accommodation simulation. The sensitivity of lens accommodation was studied at each age group by considering constant thickness (cnst-t) and variable thickness (var-t) capsules and biaxial (Biax) and uniaxial (Uniax) material characteristics tests. The lens was stretched through zonules, and corresponding absolute changes in central optical power (COP) were measured.

Conclusion:

After the stretch, the lens anterior and posterior curvatures increased, producing a change in COP. The Biax models underestimated the ΔCOP compared to the Uniax models. The 16-year lens model was more sensitive to material properties than thickness variation, while thickness variation was more relevant to the ΔCOP of the 35-year lens model. The 48-year model had the least sensitivity to capsule thickness and material property variations.
miRNA as an Ultimate and Emerging Diagnostic Approach for the
Detection of Alzheimer’s Disease
Authors: Jain Mukul , Agarwal Shrishti , Rana Aarzu , Tiwari Ankit , Patil Nil
Published: October 2023

Alzheimer's disease is a prevalent neurodegenerative disorder primarily affecting elderly
individuals, characterized by cognitive decline and dysfunction in the nervous system. The disease is
hallmarked by the presence of neurofibrillary tangles and amyloid-β plaques. Approximately 10.7%
of the global population aged 65 and above suffer from Alzheimer's disease, and this number is projected
to rise significantly in the foreseeable future. By the year 2050, the worldwide prevalence is
estimated to reach 139 million cases, compared to the current 55 million cases. The identification of
reliable biomarkers that can facilitate the diagnosis and prognosis of Alzheimer's disease is crucial.
MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules that play a significant role
in mRNA regulation and protein level maintenance through mRNA degradation. Over the past decade,
researchers have primarily focused on elucidating the functions and expression patterns of miRNAs
in various diseases, including Alzheimer's disease, to uncover their potential as diagnostic biomarkers.
This review emphasizes the potential of miRNAs as diagnostic biomarkers for Alzheimer's
disease and explores their roles and therapeutic possibilities. MiRNAs possess several features that
make them ideal biomarkers, including their ability to be easily detected in body fluids. Moreover,
the extraction process is minimally invasive, as miRNAs can be readily extracted. Advances in technology
have facilitated the integration of miRNAs into micro-assays, enhancing the reliability and
utility of miRNAs as diagnostic biomarkers for Alzheimer's disease.
The Antiviral Potential of Zingiber officinale (Ginger): A Comprehensive Literature Review
Authors: Amini fard Mohammad Amin , Asadi Anar Mahsa , Erabi Gisou , Nikzad Farhad , Ghasemi Mehran , Seyfi-Ghale-Jogh Mahdi , Javaherchian Fateme , baghban ladan , Jafari Amir , Olangian-Tehrani Sepehr , Nanbakhsh Sepehr , Deravi Niloofar , Tutunchian Zohreh , Mansourian Tina , Arbab Mojeni Fariba , Alizadeh Alaleh , Sheikhzadeh Farzad , Dadkhah Parisa alsadat , Chichagi Fatemeh
Published: October 2023

Herbal medicine has gained massive popularity among researchers worldwide. The
leading causes of this rapid development are lower side effects, lower prices, and higher availability
of plant extracts compared to synthetic drugs. Ginger (Zingiber officinale), from the Zingiberaceae
family, is one of the most commonly used and popular plants utilized as a dietary spice,
herbal medicine, and food preservative. Its biologically active components, such as shogaol, paradol,
zingerone, and especially gingerol, can be highly effective for the treatment of several illnesses
through various anti-inflammatory, anti-neoplastic, anti-emetic, anti-oxidant, antihyperlipidemic
and anti-hyperglycaemic activities. Ginger can also be used as an antiviral agent.
Numerous studies have been conducted to investigate the antiviral efficacy of ginger on several
viruses; for instance, severe acute respiratory syndrome 2 (SARS-COV-2), influenza, dengue,
hepatitis, herpes, Human Papilloma Virus (HPV), Human Immunodeficiency Virus (HIV), Epstein-
Barr Virus (EBV), Chikungunya virus and so on. This review summarizes the efficacy of
ginger in preventing or treating several viral diseases and its mechanism of action, emphasizing
coronavirus disease 2019 (COVID-19) due to the current high burden of disease worldwide.
Lycopene: A Powerful Nutraceutical with Diversified Health Benefits
Authors: Arora Disha , Singh Sahibpreet , Singh Jyoti
Published: October 2023

Lycopene, a tetraterpene of eight isoprene units belongs to the family of carotenoids,
abundantly found in tomatoes and its derivative products. It is non provitamin A carotenoid
which is associated with powerful antioxidant action that may trap reactive oxygen
species resulting in an increase in the overall antioxidant potential or a reduction in the
oxidative damage to proteins, lipids, and DNA, thereby decreasing the oxidative stress. Due to
this, the addition of lycopene to the diet is considered to be important. It is used as a food
colorant owing to its strong color and non-toxic nature. Recent literature reports have
highlighted the significance of lycopene in health. It exhibits many health benefits in ameliorating cancer, inflammation, diabetes mellitus, cardiovascular complications, Parkinson’s disease,
Alzheimer’s disease, and hepatic, skin, and bone diseases. In this review, we have summarized
the information regarding sources, chemistry, extraction techniques, and health benefits of
lycopene.
The progress on the Chemical Constituents and Biological Activities of Dendrobium Officinalis Caulis
Authors: Jiang Fujunrui , Yong Jianping , Lu Shaoji , Huang Ruiwen , Chen Jiancheng , Tian Danian , lu canzhong
Published: October 2023

Dendrobium Officinalis Caulis is a kind of Traditional Chinese Medicine, which has a long history of use and has been widely concerned by Chinese and foreign scholars. Much work on the chemical constituents (including polysaccharide, stilbene compound, flavonoids, alkaloids, volatile oil amino acids, etc.) together with their biological activities (including anti-oxidation, anti-tumor, enhance the body's immunity, anti-fatigue, regulate the digestive system, improve diabetes and so on) has been achieved. In this paper, we comprehensively reviewed the recent progress of its constitutents and biological activities, to provide the good reference for the researchers.