bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glutathione Therapy in Diseases: Challenges and Potential
Solutions for Therapeutic Advancement
Authors: Dehkordi Hossein Tahmasebi , Ghasemi Sorayya 
Published: August 2023

:
An endogenous antioxidant, reduced glutathione (GSH), is found at high
concentrations in nearly all typical cells. GSH synthesis is a controlled process, and any
disruption in the process of GSH synthesis could result in GSH depletion. Cellular
oxidative damage results from GSH depletion. Various pathological conditions such as
aging, cardiovascular disease (CVD), psychiatric disorders, neurological disorders, liver
disorders, and diabetes mellitus are more affected by this stress. There are various
reasons for GSH reduction, but replenishing it can help to improve this condition.
However, there are challenges in this field. Low bioavailability and poor stability of GSH
limit its delivery to tissues, mainly brain tissue. Today, new approaches are used for the
optimal amount and efficiency of drugs and alternative substances such as GSH. The
use of nano-materials and liposomes are effective methods for improving the treatment
effects of GSH. The difficulties of GSH decrease and its connection to the most
important associated disorders are reviewed for the first time in this essay. The other
major concerns are the molecular mechanisms involved in them; the impact of treatment
with replacement GSH; the signaling pathways impacted; and the issues with alternative
therapies. The utilization of nano-materials and liposomes as potential new approaches
to solving these issues is being considered.
Coriandrum sativum and Aloysia triphylla can Protect the Development of Cancer: An in Vivo Study using Mouse Painting Assay
Authors: Khabour Omar F. , Abuhammad Sawsan , Alzoubi Karem H. , Alkofahi Ahmad S. 
Published: August 2023

Aim:
The aim of this study is to examine the protective properties of Coriandrum sativum
and Aloysia triphylla against the development of skin cancer

Method:
The skin cancer balb/c mouse model was utilized in the study. Plant extracts were administered
to animals using oral gavage. In addition, skin cancer was induced using 7,12-dimethylbenz(
a) anthracene (DMBA).

Results:
The study found that A. triphylla extract reduced both tumor incidence (P<0.01) and papilloma
frequency (P<0.001) and delayed the onset of tumor development (P<0.001). The A. triphylla
extract did not affect tumor size in animals. C. sativum leaf extract reduced the number of tumors
per animal, the incidence of tumors, and the frequency of papilloma (P<0.05). In addition, it
delayed (P<0.01) the onset of tumors. Treatment of animals with C. sativum seed extract reduced
the frequency of papilloma (P<0.05) and delayed the onset of tumors (P<0.05). However, the examined
plant extracts did not impact the size of tumors induced by DMBA (P>0.05).

Conclusion:
The findings of this study revealed that C. sativum and A. triphylla could protect
against cancer development as indicated using the animal model of skin painting assay.
COL10A1 as a Prognostic Biomarker in Association with Immune Infiltration
in Prostate Cancer
Authors: Wang Chenyang , Wang Jirong , Chen Siyu , Li Kunpeng , Wan Shun , Yang Li 
Published: August 2023

Background:
The collagen type X alpha 1 (COL10A1) has recently been found to play an important role in the development and progression of cancer. However, the link between COL10A1 and the tumor immune microenvironment remains understood scantily.

Methods:
In the current study, the pan-cancer data of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were used to investigate the expression mode, the clinical prognostic and diagnostic value of COL10A1 in different tumors. We used TCGA data to assess the correlations between COL10A1 and clinical symptoms of prostate cancer. The R packages "edgR" and "clusterProfiler" were used for differential expression gene and enrichment analysis of COL10A1. Immunohistochemistry was further employed to corroborate the expression of COL10A1 gene in prostate cancer. After that, we used TIMER to evaluate the pertinence of COL10A1 expression to immune infiltration level in prostate cancer.

Results:
On the whole, COL10A1 was expressed at significantly higher levels in a variety of tumor tissues than in the corresponding normal tissues. Besides, significant correlations with tumor prognosis and relative exactitude in predicting tumors show that COL10A1 may be a probable prognostic and diagnostic biomarker of prostate cancer. In addition, the evidence indicates a significant correlation between COL10A1 and clinical symptoms of prostate cancer. Furthermore, the main molecular functions of COL10A1 included humoral immune response, complement activation, immunoglobulin, regulation of complement activation, and regulation of humoral immune response. Finally, we found that COL10A1 expression is positively correlated with enhanced macrophage and M2 macrophage infiltration in prostate cancer.

Conclusion:
The study indicates that COL10A1 might participate in M2 macrophage polarization in prostate cancer. COL10A1 might be an innovative biomarker to evaluate tumor microenvironment immune cell infiltration and prognosis in prostate cancer.
mirna-383-5p Functions as an Anti-oncogene in Glioma through the
Akt/mTOR Signaling Pathway by Targeting VEGFA
Authors: Liu Yan , Wang Zhen , Tang Zhi , Fu Yao , Wang Lei 
Published: August 2023

Background:
Previously, we have screened 59 differentially expressed miRNAs and 419
mRNAs in the glioblastoma samples that have been compared to the peritumoral tissues using bioinformatics
analyses, which included miRNA-383-5p and vascular endothelial growth factor A (VEGFA).
miRNA-383-5p and VEGFA/Akt/mTOR pathway play important regulatory roles in the malignant
biological behavior of glioma.

Methods:
Glioma cell lines, U87 and U251, were collected for in vitro experiments. miRNA-383-5p
and VEGFA expression levels were detected with qRT-PCR and WB. The protein expressions of Akt,
mTOR, and VEGFR in U87 and U251 were detected with WB. The effect of miRNA-383-5p on the
VEGFA activity was verified by dual-luciferase reporter assay. CCK-8 was used to examine the U87
and U251 cells’ inhibition. Flow cytometry and transwell assays were used to detect cell apoptosis and
invasion, respectively.

Results:
Our research data indicated overexpression of miRNA-383-5p to suppress malignant biological
behavior, which was manifested as promoting the apoptosis of U87 and U251 cells and inhibiting
invasion, proliferation, and metastasis. VEGFA is one of the downstream target genes of miRNA-383-
5p. miRNA-383-5p could inhibit the expression of VEGFA and Akt/mTOR signaling pathways.
Overexpression of VEGFA can reverse the inhibitory effect of miRNA-383-5p and reactivate the
Akt/mTOR signaling pathway.

Conclusion:
Our results indicate that miRNA-383-5p functions as an anti-oncogene by inhibiting the
VEGFA/Akt/mTOR signaling pathway in glioma cells. These data provide potential therapeutic targets
for glioblastoma.
EZH2-regulated PARP-1 Expression is a Likely Mechanism for the
Chemoresistance of Gliomas to Temozolomide
Authors: Liang Qiang , Wang Bing , Zhang Chenran , Song Chaoli , Wang Junyu , Sun Wei , Jiang Lei , Lin Jing 
Published: August 2023

Background:
Chemoresistance in gliomas accounts for the major cause of tumor progress
and recurrence during comprehensive treatment with alkylating agents including temozolomide
(TMZ). The oncogenic role of Enhancer of zeste homolog 2 (EZH2) has been identified in many solid
malignancies including gliomas, though the accurate effect of EZH2 on chemotherapy resistance of
gliomas has been elusive.

Objective:
To elucidate the role of EHZ2 on TMZ resistance of gliomas and the molecular mechanisms.

Methods:
Immunohistochemistry (IHC) and Reverse transcription-quantitative (RT-q) PCR, and western
blot assay were performed for expressional analysis. Cell Counting Kit-8 (CCK-8) assay was applied
to determine the TMZ sensitivity. EZH2-silencing lentivirus was generated for mechanic study.

Results:
EZH2 was overexpressed in gliomas both at the transcriptional and protein levels. EZH2 level
in glioma cell lines was positively correlated with resistance to TMZ, represented by the 50% inhibition
rate (IC50). Moreover, there was increased TMZ sensitivity in EZH2-inhibited glioma cells than in
the control cells. Furthermore, we determined that PARP1 was a common molecule among the downregulated
DNA repair proteins in both U251 and U87 glioma cell lines after EZH2 inhibition. Specifically,
we observed a spontaneous increase of PARP1 expression with TMZ treatment and interestingly,
the increase of PARP1 could be also reduced by EZH2 inhibition in the glioma cells. Finally, combined
treatment with lentivirus-induced EZH2 inhibition and a PARP1 inhibitor dramatically enhanced
TMZ cytotoxicity compared with either one alone.

Conclusion:
EZH2-PARP-1 signaling axis is possibly responsible for the chemoresistance of gliomas
to TMZ. Simultaneously inhibiting these two genes may improve the outcome of TMZ chemotherapy.
Synthesis and Anti-bacterial Activity Evaluation against Mycobacterium
tuberculosis of New Quinoline Derivatives Coupled with the Camphor
Nucleus
Authors: de Andrade Gabriel F. , da Silva Emerson T. , Lourenço Maria C.S. , Wardell Solange M.S.V. , Wardell James L. , de Souza Marcus V.N. 
Published: August 2023

Abstract:
Tuberculosis is a serious infectious disease caused by Mycobacterium tuberculosis (Mtb), also
known as Koch’s bacillus. The involvement of latent forms and resistant strains has aggravated the situation,
making the disease a serious public health problem.

:
The objective of the study was to synthesize and evaluate ten new compounds containing camphor nucleus
coupled to quinolinic derivatives as probable inhibitors of sensitive and resistant strains of Mtb
growth.

:
The synthesis of the final compounds, 3a-e and 4a-e, was based on the use of intermediates previously
obtained, in which the coupling of the camphor nucleus to quinoline derivatives was carried out via a
convergent route, which resulted in good yields (50-80%). All the final compounds were fully characterized,
and the 3-dimensional molecular structure of compound 4c was determined. The antimycobacterial
activities of all compounds against Mtb strains were evaluated and the cytotoxicity test
was conducted using the in vitro microplate procedure with broth microdilution assay (MTT).

:
Compound 3e was the most active against sensitive and resistant strains, with a minimal inhibitory concentration
(MIC) of 9.5 μM similar to ethambutol, a first-line drug used against the tuberculosis. The
most active compound 3e was selected for the potential activity against Vero cells and it displayed no
cytotoxicity at a concentration near the MIC value.

:
The final compounds were obtained in good yields, with derivative 3e being the most promising with
high activity and low cytotoxicity. Such findings open new perspectives for drug development based on
the incorporation of camphor nucleus in selected compounds.
Study of Interactions of Nucleoside Anticancer Drugs, Capecitabine and
Gemcitabine, with SWNT and BNNT using Molecular and Quantum
Mechanical Calculations
Authors: Moosavi Fatemeh , Hasanzadeh Neda , Yahyaei Hooriye , Rayatzadeh Aye 
Published: August 2023

Abstract:
Using single-wall carbon nanotubes (SWCNTs) and boron nitride nanotubes (BNNTs), this
study evaluated the interactions between Capecitabine (CAP) and Gemcitabine (GEM). Molecular mechanics
and quantum mechanics were used in the analysis.

:
The interaction between CP and GM with SWCNTs and BNNTs under various solvents was analyzed
using the self-consistent reaction field (SCRF) as a model and DFT as the analytical method. Additionally,
the effect of temperature on the stability of the molecule interactions during the experiment was
examined. The thermodynamic properties of the title compounds were analyzed based on theoretical
calculations. It included the calculation of Frontier Molecular Orbitals (FMOs) and Total Density of
States (DOS). In addition to studying the ionization potential (I), we also examined the other molecular
properties of the structures, such as electrophilicity (ω), electron affinity (A), chemical hardness (η), and
electronic chemical potential (μ). To investigate the interaction between CAP and GEM with SWCNTs
and BNNTs, molecular mechanics methods (MM) including AMBER, OPLS, CHARMM, and MM+
force fields, were employed. Monte Carlo simulation techniques were used to calculate the results at
different temperatures.

:
The effects of the liquid phase and mixed solvent media with varying dielectric constants (Water,
DMSO, Methanol, and Ethanol) on the interaction between CAP and GEM using the force fields described
above were examined in this study. The correlation between data generated by Monte Carlo,
Quantum Mechanics, and Molecular Mechanics was demonstrated. There was a striking similarity in
the thermodynamic properties and conformer populations of all three materials.
Physicochemical, ADMET Properties, and Molecular Docking Studies of N-benzoyl-N’-naphtylthiourea Derivatives for Anti-breast Cancer Activity
Authors: Megawati Dewi Sinta , Ekowati Juni , Siswodihardjo Siswandono 
Published: August 2023

Background:
N-benzoyl-N'-naphthylthiourea (BNTU) is a thiourea-derived compound that is
predicted to have anti-breast cancer activity. However, their physicochemical properties, ADMET, and
receptor-specific targets for their anti-breast cancer activity have not been reported.

Objective:
This study aimed to predict the physicochemical properties, ADMET, and anti-breast cancer
activity of BNTU and its derivatives by in silico approach.

Methods:
The physicochemical and ADMET properties were predicted using the pkCSM online program
and ProTox-II online tool. While the anti-breast cancer activity was predicted using the molecular docking
method through the Molegro Virtual Docker (MVD) program on the HER-2 receptor. The parameter
observed in the molecular docking method was the bond energy value or rerank score (RS). Compounds
with small RS values were predicted to have a great activity.

Results:
Most BNTU derivatives had lower RS values than BNTU, especially 4TBBNTU, and
4CFBNTU, although their RS values were still higher than lapatinib and TAK-285. As for the reference
ligand hydroxyurea, the RS value of BNTU and its derivatives was much lower. The physicochemical and
pharmacokinetic properties (ADMET) of lapatinib and TAK-285 were not better than that of BNTU and
its derivatives.

Conclusion:
Five compounds that deserve to be synthesized and tested for anti-breast cancer activity in
vitro and in vivo are 4TBBNTU, 3CFBNTU, 4CFBNTU, 4OCBNTU, and the lead compound BNTU.
The 3D-QSAR Study, Molecular Docking, and ADMET Analysis of Darunavir Derivatives of HIV-1 Protease Inhibitors
Authors: Fang Rui-Jing , Zhang Yan-Jun , Wang Wei-Xian , Wu Tian-Le , Zhang Shuai-Jun , He Yi-Yang , Xiong Fei , Wang Zhong-Hua 
Published: August 2023

Background:
Acquired Immunodeficiency Syndrome (AIDS) is one of most prevalent infectious diseases in the world , and HIV-1 protease (PR) is a vital target of drug design. Nowadays, three-dimensional quantitative structure-activity relationships (3D-QSAR) are applied to help design new protease inhibitions (PIs).

Objective:
The primary objective of this study is to apply the 3D-QSAR study to a series of 42 derivatives of Darunavir (DRV) and to design new molecules possessing high antivirus activity.

Methods:
Partial Least Squares (PLS) were used to cross-validate the dataset of compounds, and the optimal number of principal components (ONC), cross-validate coefficient (q²), standard error of estimate (SEE), non-cross-validated correlation coefficient (R²) and fisher test value (F) were calculated to assess model robustness. In this study, the CoMSIA-DAH model (q²=0.754, r²= 0.988, rpred2=0.57) possessed the highest predicted activity. Newly designed molecules were analyzed by docking studies with compound 25 taken as a template.

Results:
Within eight newly designed drugs, compound N02 possessed the highest antivirus activity (IC50=0.00461 nM) predicted by the CoMSIA-DAH model. The Surflex-Dock module of SYBYL-X 2.0 was used to affirm the predicted anti-PR activity of the newly designed compounds and the results of docking complex structure could be visualized. All newly designed molecules were in agreement with CSore above four and the docking study revealed that Asp29, Asp30, Ile50, Asp124, Asp128, Asp129 and Ile149 were critical residues in the process of inhibiting PR.

Conclusion:
One of the main aspects of this study is the successful design of a series of molecules with excellent investigatory values, which elucidates explicit quantitative structure-activity relationships of DRV derivatives and will provide significant suggestions for future pharmaceutical research.
In silico Investigation of Caged Xanthone Compounds Isolated from
Cratoxylum sumatranum Stem Bark against Entamoeba histolytica Enzymes
Authors: Hafid Achmad Fuad , Sari Defi Kartika , Wardana Fendi Yoga , Pratama Mohammad Rizki Fadhil , Tumewu Lidya , Ilmi Hilkatul , Permanasari Adita Ayu , Nisa Hanifah Khairun , Widyawaruyanti Aty 
Published: August 2023

Background:
Amoebiasis is caused by Entamoeba histolytica, a pathogenic species living on human colon tissues. Metronidazole is currently used for the treatment of amoebiasis, but resistance of E. histolytica to the use of such treatment has been reported. Therefore, the development of new anti-amoebic drugs is still very much needed for clinical treatment. Preliminary research on extract and fractions from Cratoxylum sumatranum stem bark has shown their anti-amoebic activity. Two compounds from the cage xanthone groups, cochinchinoxanthone and cochinchinone D, have been isolated from the active fraction of C. sumatranum stem bark.

Objective:
This study aimed to investigate the anti-amoebic activity of the two known compounds against E. histolytica.

Methods:
The in silico method used was molecular docking with several receptors, including thioredoxin reductase, triose phosphate isomerase, pyruvate ferredoxin oxidoreductase, Giardia fructose-1,6-bisphosphate aldolase, serine acetyltransferase, and phosphoserine phosphatase. The prediction of ADMET properties was also carried out for both the compounds.

Results:
The results showed cochinchinone D to have a higher binding affinity to thioredoxin reductase, pyruvate ferredoxin oxidoreductase, and Giardia fructose-1,6-bisphosphate aldolase receptors than cochinchinoxanthone. In contrast, cochinchinoxanthone bound better to the triose phosphate isomerase and phosphoserine phosphatase receptors, while both exhibited the same affinity for serine acetyltransferase. In general, the two compounds were also found to have similar ADMET profiles.

Conclusion:
In conclusion, caged xanthone compounds from C. sumatranum have the potential to be developed as anti-amoebic agents against E. histolytica through the mechanism of inhibition of these enzymes.
c-Jun N-terminal Kinase (JNK), p38, and Caspases: Promising Therapeutic
Targets for the Regulation of Apoptosis in Cancer Cells by Phytochemicals
Authors: Kumar Manish , Kaur Satwinderjeet , Kaur Sandeep 
Published: August 2023

Abstract:
Carcinogenesis is a process in which uncontrolled cell proliferation forms preneoplastic
nodules which precede the appearance of cancer. In normal cells, growth and proliferation are regulated
by certain growth and hormonal stimulation, while mutational alterations in these signals render
the cells independent and resistant to these signals. In cancer, the critical homeostatic balance between
cell growth and apoptosis is lost and the cells continue to survive beyond their normal life
span. The activation of c-Jun N-terminal kinase (JNK), p38 and caspases are involved in potential
proapoptotic signaling pathways. JNK, p38 MAPK pathway and caspases play a crucial role in the
control of apoptosis in response to stress. The most recent and up-to-date literature was evaluated in
this study, which describes the role of JNK, p38 MAPK pathway and caspases as therapeutic target in
cancer. Chemotherapy uses drugs that are cytotoxic to highly proliferating tumor cells but also kills
the non-tumor rapidly proliferating cells in the hair, skin and gastrointestinal tract epithelium, thereby
accounting the side effects of these types of treatments. Recently, chemopreventive modalities derived
from phytoconstituents present in plants provide a broad-spectrum strategy to overcome the
incidence of cancer. Non-toxic, safe and affordable bioavailabilities of chemopreventive agents provide
credence support in the field of cancer research compared to conventional therapies that cause
serious consequences. Chemoprevention envisages the basic mechanisms like modulating the activity
of xenobiotic-metabolizing enzymes, induction of apoptosis, immune system activation, suppressing
angiogenesis and the formation of metastasis, antioxidant and anti-inflammatory properties. The present
review highlighted the role of phytoconstituents derived from food, vegetables and medicinal
plants in the induction of apoptosis in cancer cells, which in turn is mediated by the activation of
JNK, p38 MAPK pathways, and caspases.
A Case Series of Appendicitis and Pseudo-appendicitis in a Paediatric Intensive Care Unit
Authors: Hon Kam L. , Leung Alexander K.C. , Lee Yan T.K. , Tsang Stephanie , Leung Karen K.Y. , Hui Wun F.A. , Cheung Wing L. , Leung Wai Y.M. 
Published: August 2023

Introduction:
Appendicitis is a common childhood condition that can be diagnostically challenging. Severe cases may necessitate support in the critical or intensive care unit. These “criti-cal appendicitis diagnoses” have rarely been described.

Case Description:
We retrospectively reviewed the Paediatric Intensive Care Unit (PICU) database of the Hong Kong Children’s Hospital and identified cases of suspected and confirmed appendicitis. Clinical features, radiologic findings and final diagnosis of each case were summarized and report-ed in this case series. We review six anonymized cases of appendicitis managed in a PICU to illus-trate the different age spectrum and clinical manifestations of the condition. Rupture of the inflamed appendix, peritonitis and pancreatitis were some of the complications encountered. Crohn’s disease was found in one case as an underlying diagnosis. Also, one girl clinically diagnosed with appendi-citis was found to be a case of ruptured hepatoblastoma with no appendicitis (i.e., pseudo-appendicitis).

Conclusion:
Prompt diagnosis, surgical removal of the inflamed appendix, and use of appropriate antimicrobials when indicated are essential in reducing mortality and morbidity associated with se-vere appendicitis. Significant premorbid conditions such as acute myeloid leukemia, Mitochondrial Encephalopathy Lactic Acidosis Syndrome (MELAS), inflammatory bowel disease and complica-tions may be present in patients needing intensive care as is illustrated in the present cases. Pseudo-appendicitis is an important differential diagnosis. Imaging is crucial and useful in establishing and confirming the diagnosis of appendicitis and pseudo-appendicitis in these PICU cases.