bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro Antibacterial Activity of a Novel Acid-Activated Antimicrobial
Peptide against Streptococcus mutans
Authors: Lin Haixing , Zhou Runhong , Zhang Minna , Huang Ruifeng , Fan Cuiqiong , Zhou Shaofen , Qiu Jingnan , He Jian
Published: August 2023

Background:

Dental caries is an oral disease associated with infection by microbial biofilm.
The metabolic activity of cariogenic bacteria results in a pH decrease in the plaque biofilm,
causing tooth demineralization. This acidic environment favors the growth of cariogenic bacteria
that are highly resistant to strong acids, which, in turn, produce more acid resulting in a further decrease
in the pH of the plaque biofilm. Therefore, the strategy of utilizing the acidic dental plaque
microenvironment to prevent and treat dental caries has become a hot research topic in recent
years, such as the development of pH-sensitive drug delivery systems.

Aims:

Design of a new acid-activated antibacterial peptide.

Objective:

To design and synthesis an acid targeted antimicrobial peptide with the GWHHFFHFFHFF
sequence.

Methods:

Minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC)
testing confirmed its antibacterial activity. Propidium iodide (PI) staining was used to detect nucleic
acid leakage. Determination of anti-biofilm activity by biofilm inhibition assay. A phototoxicity
study confirmed the phototoxicity of PPIX-P12.

Results:

MIC and MBC testing confirmed that P12 possessed acid-activated anti-Streptococcus mutans
activity. Bactericidal kinetic experiments and propidium iodide (PI) staining experiments
showed that P12 killed planktonic S. mutans UA159 cells leading to the leakage of nucleic acids in
the acidic medium. Moreover, P12 showed acid-activated anti-biofilms at the early and mature biofilm
stages. P12 was conjugated with the phototherapeutic agent protoporphyrin IX (PpIX) to construct
the protoporphyrin derivative PpIX-P12. In vitro experiments revealed that PpIX-P12 displayed
better antibacterial activity in pH 5.5 medium than in pH 7.2 medium.

Conclusion:

In conclusion, we designed an acid-activated AMP, which had no antimicrobial activity
at neutral pH, but had antimicrobial activity at an acidic pH.
Bio-Functional Mesoporous Silica Nanoparticles as Nano-Structured
Carriers in Cancer Theranostic Review on Recent Advancements
Authors: Gevariya Darshan , Priya Lipika , Mehta Smit , Patel Vishwas , Bhuva Dhara , Panjwani Drishti , Patel Shruti , Ahlawat Priyanka , Dharamsi Abhay , Patel Asha
Published: August 2023

Background:

Cancer is a life-threatening disease worldwide, but proper treatment has
not yet been developed. Many therapies are available to treat cancer disorders, like chemotherapy,
surgery, hormone therapy, and immunotherapy. Chemotherapy often relies on a combination of
harmful, highly toxic platinum-based compounds. Also, there are chances of poor distribution of
chemotherapeutic agents and cytotoxic to most cells which leads to damage to other healthy cells,
also, there are chances of resistance.

Objective:

The main objective of this study is the development of mesoporous silica nanoparticles.
Mesoporous silica nanoparticles are recognized as carriers with high drug loading capacity and significant
functionalized surface area for targeted drug delivery. Mesoporous silica nanoparticles
have shape, particle size, pore volume, higher surface area, and the possibility of surface modification.
Hence results in thermally and chemically stable nanomaterials. For targeted drug delivery,
MSN is conjugated with a variety of ligands, including monoclonal antibodies, hyaluronic acid,
transferrin, folic acid, etc., that have a particular affinity for the receptors that are overexpressed on
the surface of malignant cells, so using this nanocarrier reducing the dose related toxicity of normal
cell.

Methods:

This review focuses on different methods for synthesizing mesoporous silica nanoparticles.
Sol-gel method and modified stobber method were used for the synthesis of this nanoparticle.

Results:

Successfully synthesized mesoporous silica nanoparticle with particle size around 50-200
nm and drug loading efficiency was found to be around 71%.

Conclusion:

Mesoporous silica nanoparticles are great carriers for intracellular and targeted drug
delivery systems.
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

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

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

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.
Food Safety Knowledge, Attitudes, and Practices Among Food Handlers in
Jeddah, Saudi Arabia
Authors: Alghafari Wejdan
Published: August 2023

Background:

Several outbreaks of foodborne illness have recently occurred in Saudi Arabia, posing a public health concern, especially considering the increasing trend of food consumption at restaurants.

Objectives:

This study evaluates the food safety knowledge, attitudes, and self-reported practices among food handlers in Jeddah, Saudi Arabia, and their association with the food handlers’ sociodemographic characteristics.

Methods:

A cross-sectional study was performed for a convenience sample of 80 food handlers (15–65 years old), followed by face-to-face interviews. A validated questionnaire with 65 questions across four sections (sociodemographic characteristics, knowledge, attitudes, and practice related to food safety) was utilized for data collection. Data entry and analysis were conducted using the SPSS version 26 software.

Results:

Most of the participants exhibited moderate levels of food safety knowledge and practices and a high level of food safety attitudes. Food safety knowledge was significantly greater among the oldest participants (>45 years old), those holding valid health cards, and those who had attended training courses (p<0.05). However, no significant differences in food safety attitudes and practices were found based on the sociodemographic characteristics of the participants (p>0.05). Food safety knowledge was found to be significantly correlated with the food safety attitudes of the participants (r= 0.379, p= 0.001), and food safety attitudes were significantly correlated with practices (r= 0.264, p= 0.018).

Conclusion:

This study revealed that continuous implementation of food safety educational and training programs is necessary to improve the knowledge of food handlers and transform it into appropriate attitudes and practices.
The Diagnostic Features of Peripheral Blood Biomarkers in Identifying
Osteoarthritis Individuals: Machine Learning Strategies and Clinical Evidence
Authors: Zhou Qiao , Liu Jian , Xin Ling , Hu Yuedi , Qi Yajun
Published: August 2023

Background:

People with osteoarthritis place a huge burden on society. Early diagnosis
is essential to prevent disease progression and to select the best treatment strategy more effectively.
In this study, the aim was to examine the diagnostic features and clinical value of peripheral
blood biomarkers for osteoarthritis.

Objective:

The goal of this project was to investigate the diagnostic features of peripheral blood
and immune cell infiltration in osteoarthritis (OA).

Methods:

Two eligible datasets (GSE63359 and GSE48556) were obtained from the GEO database
to discern differentially expressed genes (DEGs). The machine learning strategy was employed
to filtrate diagnostic biomarkers for OA. Additional verification was implemented by collecting
clinical samples of OA. The CIBERSORT website estimated relative subsets of RNA transcripts
to evaluate the immune-inflammatory states of OA. The link between specific DEGs and
clinical immune-inflammatory markers was found by correlation analysis.

Results:

Overall, 67 robust DEGs were identified. The nuclear receptor subfamily 2 group C
member 2 (NR2C2), transcription factor 4 (TCF4), stromal antigen 1 (STAG1), and interleukin 18
receptor accessory protein (IL18RAP) were identified as effective diagnostic markers of OA in
peripheral blood. All four diagnostic markers showed significant increases in expression in OA.
Analysis of immune cell infiltration revealed that macrophages are involved in the occurrence of
OA. Candidate diagnostic markers were correlated with clinical immune-inflammatory indicators
of OA patients.

Conclusion:

We highlight that DEGs associated with immune inflammation (NR2C2, TCF4,
STAG1, and IL18RAP) may be potential biomarkers for peripheral blood in OA, which are also
associated with clinical immune-inflammatory indicators.
The Potential Roles of Ficus carica Extract in the Management of COVID-19
Viral Infections: A Computer-aided Drug Design Study
Authors: Hamed Mahmoud , Khalifa Maha , El Hassab Mahmoud A. , Abourehab Mohammed A. S. , Al Kamaly Omkulthom , Alanazi Ashwag S. , Eldehna Wagdy M. , Mansour Fotouh R.
Published: August 2023

Introduction:

The conventional processes of drug discovery are too expensive, timeconsuming
and the success rate is limited. Searching for alternatives that have evident safety and
potential efficacy could save money, time and improve the current therapeutic regimen outcomes.

Method:

Clinical phytotherapy implies the use of extracts of natural origin for prophylaxis,
treatment, or management of human disorders. In this work, the potential role of common Fig (Ficus
carica) in the management of COVID-19 infections has been explored. The antiviral effects
of Cyanidin 3-rhamnoglucoside which is abundant in common Figs have been illustrated on COVID-19 targets. The immunomodulatory effect and the ability to ameliorate the cytokine storm
associated with coronavirus infections have also been highlighted. This work involves various
computational studies to investigate the potential roles of common figs in the management of
COVID-19 viral infections.

Results:

Two molecular docking studies of all active ingredients in common Figs were conducted
starting with MOE to provide initial insights, followed by Autodock Vina for further confirmation
of the results of the top five compounds with the best docking score.

Conclusion:

Finally, Molecular dynamic simulation alongside MMPBSA calculations were conducted
using GROMACS to endorse and validate the entire work.
DeepEpi: Deep Learning Model for Predicting Gene Expression Regulation
Based on Epigenetic Histone Modifications
Authors: Hamdy Rania , Omar Yasser , Maghraby Fahima
Published: August 2023

Background:

Histone modification is a vital element in gene expression regulation. The way
in which these proteins bind to the DNA impacts whether or not a gene may be expressed. Although
those factors cannot influence DNA construction, they can influence how it is transcribed.

Objective:

Each spatial location in DNA has its function, so the spatial arrangement of chromatin modifications
affects how the gene can express. Also, gene regulation is affected by the type of histone modification
combinations that are present on the gene and depends on the spatial distributional pattern of
these modifications and how long these modifications read on a gene region. So, this study aims to
know how to model Long-range spatial genome data and model complex dependencies among Histone
reads.

Methods:

The Convolution Neural Network (CNN) is used to model all data features in this paper. It
can detect patterns in histones signals and preserve the spatial information of these patterns. It also uses
the concept of memory in long short-term memory (LSTM), using vanilla LSTM, Bi-Directional
LSTM, or Stacked LSTM to preserve long-range histones signals. Additionally, it tries to combine
these methods using ConvLSTM or uses them together with the aid of a self-attention.

Results:

Based on the results, the combination of CNN, LSTM with the self-attention mechanism obtained
an Area under the Curve (AUC) score of 88.87% over 56 cell types.

Conclusion:

The result outperforms the present state-of-the-art model and provides insight into how
combinatorial interactions between histone modification marks can control gene expression. The source
code is available at https://github.com/RaniaHamdy/DeepEpi.
Prevention of Preterm Labor by Isosorbide Dinitrate and Nitroglycerin Patch
Authors: Ghafarzadeh Masoumeh , Shakarami Amir , Yari Fatemeh
Published: August 2023

Background:

Preterm labor is one of the most important causes of hospitalization during
pregnancy and can lead to serious complications in neonates.

Objective:

This study aims to compare the effect of transdermal nitroglycerin (TNG) patches and
sublingual tablets of Isosorbide dinitrate (ISD) for the prevention of preterm delivery.

Methods:

A total of 110 healthy pregnant women aged 18-35 years with a healthy and alive fetus
and gestational age between 24-34 weeks who had at least 8 regular uterine contractions per hour
were included in this single-blinded clinical trial. After exclusion, the women were randomly divided
into TNG (n = 50) and ISD (n = 49) groups. After the first dose of medication (TNG or ISD),
patients who developed complications such as hypotension, headache, or both, were also excluded
from the study.

Results:

A total of 58 patients completed the treatment course (29 patients in each group). A significant
difference in delayed preterm labor and recovery time was reported between the TNG and ISD
groups.

Conclusion:

Complications and the number of contractions were not statistically different in the two
groups. We concluded that the TNG patch is more effective than ISD in delaying labor. Both drugs
are likely to have a similar incidence of side effects.
Effect of Curcumin-containing Nanofibrous Gelatin-hydroxyapatite
Scaffold on Proliferation and Early Osteogenic Differentiation of Dental
Pulp Stem Cells
Authors: Dizaj Solmaz Maleki , Rezaei Yashar , Namaki Fatemeh , Sharifi Simin , Abdolahinia Elaheh Dalir
Published: August 2023

Background:

In recent years, the electrospinning method has received attention because of
its usage in producing a mimetic nanocomposite scaffold for tissue regeneration. Hydroxyapatite and
gelatin are suitable materials for producing scaffolds, and curcumin has the osteogenesis induction effect.

Aims:

This study aimed to evaluate the toxicity and early osteogenic differentiation stimulation of nanofibrous
gelatin-hydroxyapatite scaffold containing curcumin on dental pulp stem cells (DPSCs).

Objective:

The objective of the present investigation was the evaluation of the proliferative effect and
primary osteogenic stimulation of DPSCs with a nanofibrous gelatin-hydroxyapatite scaffold containing
curcumin. Hydroxyapatite and gelatin were used as suitable and biocompatible materials to make a scaffold
suitable for stimulating osteogenesis. Curcumin was added to the scaffold as an osteogenic differentiation-
enhancing agent.

Methods:

The nanofibrous gelatin-hydroxyapatite scaffold containing curcumin significantly increased
the proliferation and the ALP activity of DPSCs (P<0.05). The proliferative effect was insignificant in
the first 2 days, but the scaffold increased cell proliferation by more than 40% in the fourth and sixth
days. The prepared scaffold increased the activity of the ALP of DPSCs by 60% compared with the control
after 14 days (p<0.05).

Results:

The nanofibrous gelatin-hydroxyapatite scaffold containing curcumin significantly increased
the proliferation and the ALP activity of DPSCs (P<0.05). The proliferative effect was insignificant in
the first 2 days, but the scaffold increased cell proliferation by more than 40% in the fourth and sixth
days. The prepared scaffold increased the activity of the ALP of DPSCs by 60% compared with the control
after 14 days (p<0.05).

Conclusion:

The produced nanofibrous gelatin-hydroxyapatite scaffold containing curcumin can be utilized
as a potential candidate in tissue engineering and regeneration of bone and tooth.

Future Prospects:

The prepared scaffold in the present study could be a beneficial biomaterial for tissue
engineering and the regeneration of bone and tooth soon.
Preparation, Characterization, and Evaluation of the Anticancer Effect of
Mesoporous Silica Nanoparticles Containing Rutin and Curcumin
Authors: Dizaj Solmaz Maleki , Kouhsoltani Maryam , Pourreza Kosar , Sharifi Simin , Abdolahinia Elaheh Dalir
Published: August 2023

Aims and Objective:

The aim of this study was the preparation of mesoporous silica nanoparticles
co-loaded with rutin and curcumin (Rut-Cur-MSNs) and the assessment of its physicochemical
properties as well as its cytotoxicity on the head and neck cancer cells (HN5). Besides, ROS generation
of HN5 cells exposed to Rut-Cur-MSNs was evaluated.

:

Several investigations showed that rutin and curcumin have potential effects as anticancer phytochemicals;
however, their low aqueous solubility and poor bioavailability limited their applications.

:

The assessment of physicochemical properties and anticancer effect of prepared nanoparticles was the
objective of this study.

Methods:

The physicochemical properties of produced nanoparticles were evaluated. The toxicity of Rut-Cur-MSNs on HN5 cells was assessed. In addition, the ROS production in cells treated with Rut-Cur-MSNs was assessed compared to control untreated cells.

Results:

The results showed that Rut-Cur-MSNs have mesoporous structure, nanometer size and negative surface charge. The X-ray diffraction pattern showed that the prepared nanoparticles belong to the family of silicates named MCM-41. The cytotoxicity of Rut-Cur-MSNs at 24 h was significantly higher than that of rutin-loaded MSNs (Rut-MSNs) and curcumin-loaded MSNs (Cur-MSNs) (p<0.05).

Conclusion:

The achieved results recommend that the prepared mesoporous silica nanoparticles containing
rutin and curcumin can be a useful nanoformulation for the treatment of cancer.

:

The produced nanomaterial in this study can be helpful for cancer therapy.
Time-varying Reliability Analysis of Contact Fatigue Strength for
Nutation Face Gear Transmission
Authors: Zhu Lili , Shen Yuting , Liang Xu , Wu Bo
Published: August 2023

Background:

Nutation face gear transmission is a patent about a new type of transmission
based on meshing between two face gears. It replaces spur gear with internal face gear to form a “faceface”
meshing gear pair and actualizes its deceleration function by combining the nutation principle,
which has the advantages of both face gear and nutation drive.

Objective:

The purpose of this paper is to establish the time-varying reliability calculation model of contact
fatigue strength based on fractal contact theory, so as to improve the reliability, safe service and further
optimization design of the nutation face gear transmission.

Methods:

The time-varying uncertainties of the contact stress and the allowable contact stress of the face
gear teeth are analyzed respectively, and then the time-varying reliability model of the contact fatigue
strength is established. Finally, the drift rate and fluctuation rate of each random variable are simulated
using the Monte Carlo simulation method to obtain the time-varying reliability of the contact fatigue
strength for the nutation face gear drive.

Results:

The results show that the general trend of geometric Brownian motion locus of each random
variable is consistent with the actual situation.

Conclusion:

For the given example of the nutation face gear transmission device, the reliability of the
contact fatigue strength of the planetary face gear meshing with the fixed face gear and the rotating face
gear within one year is calculated to be 0.9912 and 0.9856 respectively, and the maximum vibration noise
is about 68dB, which meets the expected value.
The Molecular Dynamics Simulation of Thermal Properties of R290 for
Auto-cascade Refrigeration System
Authors: Feng Haocheng , Liu Zhenzhen , Wang Zilong , Zhang Hua
Published: August 2023

Background:

Hydrocarbons are increasingly being considered as potential fourth-generation refrigerants due to their environmentally-friendly properties. However, accurate prediction and calculation of their thermal properties are essential for their industrial application.

Objective:

In this study, molecular dynamics simulations were performed to calculate the density, self-diffusion coefficient, viscosity and thermal conductivity of R290 at various operating temperatures of 200-240 K and pressures of 0.15 and 0.20 MPa, and 270-390 K and pressures of 1.5 and 2.0 MPa to verify the feasibility of the methods.

Methods:

The equilibrium molecular dynamics simulation (EMD) approach was utilised. The soundness of the model and force field were verified by calculating the density of the system during the relaxation phase. In the output stage, the self-diffusion coefficient was calculated using the Einstein relation, while the viscosity and thermal conductivity were calculated using the Green-Kubo method. The simulation results were compared with the NIST data values, and the errors were analysed.

Results:

 Results: The density simulation results for R290 in the relaxation phase yielded an overall average absolute relative deviation (AARD) value of 3.97%. In the output stage, the simulation results for the transport coefficients of R290 showed AARD values of 7.68%, 6.60% and 11.04% for the self-diffusion coefficient, viscosity, and thermal conductivity, respectively, compared to the NIST data values.

Conclusion:

These results indicate the feasibility of using molecular dynamics simulations to study the transport properties of hydrocarbon refrigerants. The findings also provide a foundation for future research on hydrocarbon refrigerant mixtures.

Patent:

The research presented in this work could serve as a valuable reference for future patent applications and technological innovations related to hydrocarbon refrigerants, particularly R290. This includes, but is not limited to, delivery pipelines, connectors, storage containers, control and detection systems, and the preparation and application of R290 and other refrigerant mixtures.
Microwave Facilitated Discovery of Substituted 1,2,4-triazaspiro[4.5]
dec-2-en-3-amines: Biological and Computational Investigations
Authors: Patel Parth P. , Patel Navin B. , Tople Manesh S. , Patel Vatsal M. , Solanki Mitesh B.
Published: August 2023

Background:

Tuberculosis is an effectual infectious disease caused by the spread of tu-bercular bacteria within the lungs via droplets of coughs and sneezes. In 2021, 1.6 million people died due totuberculosis, which is the 13th leading killer disease and 2nd leading after COVID-19 infectious disease.

Objective:

Many drugs are available as antitubercular drug, but still, requires more efficacious drug molecules with lower toxicity, side effects and small-sized molecules. To fulfill said prospective, computational study such as molecular docking and ADMET studies guides towards an ideal drug molecule with small -sized, unique spiro structures.

Methods:

Conventional and microwave-initiated Reaction of cyclohexanone, hydrazine carbothio-amide, and 2-amino-4-methoxy-6-methyl-1,3,5-triazine affords compound 1, which is subjected to the Schiff base reaction with diverse aldehydes. All structures are defined using IR, 1H NMR, 13C NMR, and mass spectroscopy. The entire series is exposed to in vitro antibacterial and antitubercu-lar and in silico molecular docking and ADMET studies.

Results:

Compounds 2c and 2b have been established to be potential antibacterial agents, whereas compounds 2d, 2e, 2j, 2k and 2l are extremely effective against tubercular strains. Furthermore, molecular docking of related molecules is performed, and compounds 2d, 2e, 2j, 2k, and 2l have higher affinities toward antitubercular proteins. ADMET parameters such as water solubility, SA score, PCaco2 value, and TPSA values are satisfactory.

Conclusion:

The microwave method has been proven to be a greener method as compared to the con-ventional heating method. Comparative results of in vitro analysis are obtained with referenced anti-bacterial drugs and antitubercular drugs. In silico observations supports their in vitro assessments. Appraisal obtained from the ADMET study leads to the formation of ideal drug molecules.