bluuebunny/crossref_metadata_2025 huggingface dataset:
The Suicide Gene System Cytosine Deaminase::Uracylphosphoribosyltransferase/
5-fluorocytosine Displays a Strong Cytotoxic
Effect on Human Melanoma Cells
Authors: Bernabei-Cornejo Sofía Gala , Glikin Gerardo Claudio , Finocchiaro Liliana María Elena
Published: February 2025

Introduction:

Melanoma is considered the deadliest form of skin cancer.
While monoclonal-antibodies and molecular targets marked milestones in melanoma therapy,
more research is needed to overcome the advanced stages of this disease.

Objective:

To explore the possible use of the yeast cytosine deaminase::uracil phosphoribosyltransferase
fusion enzyme/5-fluorocytosine (CD::UPRT/5FC) suicide gene (SG) system for human
melanoma.

Methods:

In eight metastatic human melanoma cell lines, we determined: cytotoxicity, lipofection
efficiencies, colony forming capacity and bystander effects due to soluble and/or particulate
factors secreted to the conditioned media after treatments.

Results:

CD::UPRT induced cell death in a prodrug (5FC) concentration-dependent manner and
was able to eliminate the sub-population of surviving cells with clonogenic capacity. Compared
with human interferon-β gene transfer or the herpes simplex virus thymidine kinase/ganciclovir
system, at 100 μM 5FC, CD::UPRT was more efficient in inducing cell death. The strong cytotoxic
response contrasted with the low lipofection efficiencies (<5%), indicating a potent bystander
effect. We analyzed the contribution of soluble and particulate factors released by SG
lipofected cells to the conditioned media (CM) finding that they were able to deliver CD::UPRT
genetic information and/or recombinant enzyme to recipient cells. When exposed to 5FC, the
cells that received either supernatant or 12000×g pellet fractions of CM, efficiently activated the
prodrug because of the acquired CD::UPRT activity and caused cell death.

Conclusion:

This suicide gene therapy approach, amplified by the release of free 5-fluorouracil
and soluble and particulate factors containing CD::UPRT genetic information and/or enzyme,
could have a great clinical potential for malignant melanoma.
Linking Processed and Red Meat Consumption to Specific Lung Cancer
Subtypes: A Mendelian Randomization Analysis
Authors: Wen Kang , Wang Zhaoxia
Published: February 2025

Objective:

The aim of this study was to elucidate the causal relationship between the
consumption of processed and red meats (specifically pork, beef, and mutton) and susceptibility
to various lung cancer types.

Background:

Previous observational studies have indicated a potential cancer risk associated
with red and processed meat consumption. However, a clear causal relationship remains undetermined.

Purpose:

Refining the study of the association between processed and red meat and lung cancer
using a Mendelian randomization study.

Method:

We harnessed the robustness of Two-Sample Mendelian Randomization, integrating
data from the esteemed UK Biobank, capturing dietary habits with oncological datasets from the
Transdisciplinary Research In Cancer of the Lung. The analytical approach was anchored in the
inverse variance weighted (IVW) method, enriched by sensitivity analyses for result validation.

Result:

Genetic predispositions favoring processed meat consumption are linked to heightened
risks of lung cancer [IVW analysis, OR=1.8203, 95%CI [1.1115,2.9811], p=0.0173], and in
LUSC [IVW analysis, OR=2.9274, 95%CI [1.4810,5.7863], p=0.0020]. Beef was more important
in lung cancer [IVW analysis, OR=4.6739, 95% CI [2.4947, 8.7570], p=0.000001], in
LUSC [IVW analysis, OR=3.3251, 95%CI [1.2055,9.1717], p=0.0203] and in LUAD [IVW
analysis, OR=7.1480, 95%CI [3.0074,16.9893], p=0.000008]. However, no significant links
were identified between mutton or pork intake and lung cancer.

Conclusion:

Processed meat and beef consumption may elevate lung cancer risk. Additional
research is warranted to investigate potential links between mutton or pork consumption and the
risk of lung cancer.
A Valuable Target for Therapy: The Metalloproteinase ADAM10
Authors: Tripathi Siddhant , Sharma Yashika , Kumar Dileep
Published: February 2025

A special kind of posttranslational process known as proteolytic cleavage controls the
half-lives and functions of several extracellular and intracellular proteins. The metalloproteinase
ADAM10 has attracted attention because it cleaves a growing amount of protein substrates close
to the extracellular membrane leaflet. The process known as “ectodomain shedding” controls the
turnover of certain transmembrane proteins that are essential for receptor signaling and cell adhesion.
It may trigger nuclear transport, intramembrane proteolysis, and cytoplasmic domain signaling.
Additional human illnesses linked to ADAM10 include cancer, immune system malfunction,
and neurodegeneration. The difficulty in targeting proteases for medicinal reasons stems from the
many substrates that these enzymes, particularly ADAM10, have. It is usually necessary to precisely
identify the therapeutic beneficial window of use since blocking or accelerating a particular protease
activity is linked with undesirable side effects. More knowledge of the regulatory pathways
governing ADAM10 expression, subcellular localization, and activity will probably lead to the
identification of viable therapeutic targets, enabling more targeted and precise manipulation of the
enzyme's proteolytic activity.
CD1B Expression in Triple-Negative Breast Cancer: Its Implications for Prognosis and Immunotherapy Outcomes
Authors: Jin Hongwei , Wan Mengting , Pan Shuaikang , Wang Ziqi , Wang Wei , Zhang Jinguo , Han Xinghua
Published: February 2025

Introduction:

The absence of the estrogen receptor (ER), progesterone receptor (PR),
and human epidermal growth factor receptor 2 (HER2) is a hallmark of triple-negative breast cancer
(TNBC), which results in fewer treatment options and inferior clinical outcomes. The major histocompatibility
complex family includes CD1B. By exposing T cells to lipid antigens, it alters immunological
responses. Although the function of CD1B has been investigated in a number of malignancies,
its relevance in TNBC has not been fully investigated.

Method:

In this study, immunohistochemistry (IHC) analysis of tissue samples and public databases
was carried out to examine the expression of CD1B and its implications for prognosis in TNBC.

Result:

Compared to normal tissues, TNBC tissues demonstrated significantly higher levels of
CD1B expression. Better overall survival, including survival without distant metastases and survival
without recurrence, was found to be associated with higher levels. Additionally, more immune
cells, primarily memory B cells and regulatory T cells, entering the TNBC region were found to be
associated with greater levels of CD1B. It was found that the immunological microenvironment of
TNBC was significantly affected by CD1B. The association between CD1B and immune-related
pathways was also identified by examining functional enrichment. Drug sensitivity can be used to
identify potential CD1B-targeting therapies. According to these results, CD1B might be a useful
prognostic indicator and a possible target for treatment in TNBC.

Conclusion:

Nevertheless, additional experimental verification is required to verify the clinical significance
of CD1B.
In vivo and In Silico Pharmacokinetics Studies on Coumarinolignoid Cliv-92: Unraveling its Effect on Rifampicin-Induced Hepatic Damage
Authors: Kumar Ajay , Alam Sarfaraz , Tandon Sudeep , Shanker Karuna , Khan Feroz , Saikia Dharmendra
Published: February 2025

Background:

Drug-induced hepatotoxicity is a major concern and is caused by all classes
of medications, indicating a key area of research. Antitubercular drugs have a beneficial effect
but cause hepatotoxicity on prolonged use.

Aim:

The present work aimed to investigate the role of rifampicin-induced hepatic damage and the
effect of Cliv-92 on rifampicin-induced alteration in rats.

Methods:

Rats were administered with rifampicin, Cliv-92, and silymarin (standard) orally in
0.5% carboxymethyl cellulose (CMC) suspension, in doses of 100 mg/kg, once daily for fourteen
days, one hour before the administration of rifampicin. Control animals were treated with 0.5%
CMC. On the 14th day, 1hr after the last drug administration, tissue was collected, homogenized,
and various parameters, viz. SOD, CAT, GPX, and cytochromes, were estimated from rat liver
supernatant and compared with the control group. Blood serum parameters were also measured.
Simultaneously, antioxidant activity and in silico studies were performed. The constituent
isoforms of Cliv-92 and silymarin and their metabolites were analyzed for different pharmacokinetic
characteristics. Silymarin was used as a standard drug.

Result:

The result of the study suggests that the hepatoprotective potential of Cliv-92 is due to its
antioxidant property and inhibitory effect on hepatoproteins, cytochromes (CPY450). An in-silico
finding validates the safety profile of Cliv-92, its metabolites, and the standard drug silymarin and
also explains that the drug is non-mutagenic.

Conclusion:

The result of this study indicated that both Cliv-92 and silymarin could be used to
avoid drug-induced overload and hepatic damage.
Innovative Therapies: A Major Breakthrough in Combating Multi-Drugresistant Bacterial Infections Using Mixture Design and Multi-Objective
Optimization with NSGA-II Algorithm
Authors: Adouane Meriem , Kadri Nabil , Benzitoune Nourelimane , Lakhdari Chafika , Djellal Samia , Ousmer Lilla , Tahraoui Hichem , Amrane Abdeltif , Remini Hocine , Dahmoune Farid , Madani Khodir
Published: February 2025

Introduction/Objective:

The increasing resistance of pathogens to antibiotics poses a
major public health challenge. This study aims to develop an innovative approach to combat this
resistance by exploring synergies between standard antibiotics and marine metabolites.

Methods:

The methodology combines disk diffusion testing and mixture design to assess the antimicrobial
efficacy of the combinations.

Results:

The results demonstrate promising synergies between carotenoids, polyphenols, and alkaloids
with standard antibiotics, offering potential targeted use in the fight against clinical multidrug-
resistant bacteria. Specifically, Gram-negative bacteria (BGN) showed increased resistance
to antibiotics such as amoxicillin-clavulanic acid (AMC), ceftazidime, cefotaxime, tetracycline,
and cefazolin. These antibiotics, when combined with marine compounds, exhibited substantial
inhibitory effects against specific isolates, circumventing antibiotic resistance mechanisms. Similarly,
substantial synergies were observed in Gram-positive bacteria. Leveraging advanced algorithms
such as multi-objective optimization, notably the NSGA-II algorithm, we accurately predicted
minimum inhibitory concentrations (MICs) against clinically resistant bacterial isolates.
Optimal conditions against Escherichia coli, characterized by carotenoids = 0.6335, total polyphenols
= 0, indole alkaloids = 0.1723, and AMC = 0.1941, yielded a predicted MIC of 41.1126
mg/L, closely mirroring the experimental MIC of 41.66 ± 0.18 mg/L. Similarly, for Staphylococcus
aureus, optimal conditions produced a predicted MIC of 30.8304 mg/L, closely aligning with
the experimental MIC of 30.69 ± 1.80 mg/L.

Conclusion:

The consistent and reliable predictions for bacterial strains affirmed the robustness of
the applied methodology. These results not only pave the way for further exploration but also
offer valuable insights for optimizing pharmaceutical and medical interventions, presenting innovative
avenues for combating antibiotic-resistant bacterial infections.

conclusion:

The consistent and reliable MIC predictions for bacterial strains validate the robustness of the applied methodology. These findings provide a foundation for further research and potential pharmaceutical applications, offering innovative strategies to combat antibiotic-resistant bacterial infections.
Unveiling the Anticancer Potential of Phytocompounds: Pioneering Future Cancer Therapies
Authors: Chauhan Prashant , Pandey Pratibha , Ramniwas Seema , Verma Meenakshi , Ganeshan Subbulakshmi , Rajotiya Sumit , Devi Seema , Lakhanpal Sorabh , Kumar M Ravi , Pandey Shivam , Khan Fahad
Published: February 2025

Cancer epidemiological studies highlight the critical need for identifying better treatment
options against cancer. Plants have been widely studied to obtain their efficacy as potent therapeutic
agents to treat several diseases, including cancer. Interestingly, some phytocompounds, such as
flavonoids, terpenoids, alkaloids, phenolics, and organosulphur compounds [OSCs], have been
demonstrating their potential role in combating several pathologies, including the second most devasting
disease, cancer, which contributes a significant portion of annual mortality cases. Several in
vitro, in vivo, and in silico investigations have recently established remarkable properties of phytocompounds
such as antioxidant effects, induction of apoptosis, inhibition of metastasis, autophagy
modulation, cell cycle regulation, and chemosensitization that lead to cancer suppression. This underscores
the great potential of phytocompounds to contribute as an effective anticancerous drug for
the prevention of cancer cases and advancement in cancer research. Therefore, comprehending the
complicated mechanism involved in the anticancerous effects of phytocompounds against several
carcinomas is crucial to establishing novel therapeutic strategies. Thus, this review tends to summarize
the involvement of the most promising classes of phytompounds in cancer management and
highlights several clinical trial data that demonstrate significant results in managing diverse carcinomas.
Identification of a Novel HIV-1 Recombinant Form Comprising CRF01_AE and Subtype C in Hebei Province, China
Authors: Guan Yapeng , Wang Jun , Lu Xinli
Published: February 2025

Background:

Circulating recombinant form (CRF) 01_AE and subtype C are two
HIV-1 subtypes. In recent years, novel HIV-1 recombinant forms have become more and more
prevalent in China; however, new HIV-1 CRF01_AE/C recombinant forms are less prevalent
nationwide.

Objective:

Our research study aimed to investigate new recombinant forms between different
HIV-1 subtypes and evaluate their transmission risk among men who have sex with men (MSM)
in Hebei, China.

Method:

The near full-length genome (NFLG) of HIV-1 was identified using the analyses of the
phylogenetic tree and gene breakpoints.

Results:

In the present work, we have reported a novel HIV-1 recombinant form composed of
CRF01_AE and subtype C. The NFLG of this CRF01_AE/C form contained eight gene subregions,
with four subtype C gene segments inserted into the CRF01_AE backbone, consisting of I
CRF01_AE (790–1,171 nt), Ⅱ subtype C (1,172–1,840 nt), Ⅲ CRF01_AE (1,841–5,089 nt), Ⅳ
subtype C (5,090–5,666 nt), Ⅴ CRF01_AE (5,667–6,317 nt), Ⅵ subtype C (6,318–8,586 nt), Ⅶ
CRF01_AE (8,587–9,246 nt), and Ⅷ subtype C (9,247–9,409 nt). This new recombinant form
was named CRF140_0107.

Conclusion:

The study suggested that it is important to monitor HIV-1 diversity to reduce HIV-
1 transmission in China.
The Conjugation of Chlorambucil with 4-Phenylbutanoic Acid and Valproic Acid respectively for Enhancing Anti-tumor Activity
Authors: Dai Yi , Zhang Yang , Wang Xiangxiang , Zhang Yupei , Bai Juan
Published: February 2025

Background:

Nitrogen mustards exert their anticancer activity by alkylating DNA. However, except for alkylating DNA, nitrogen mustards may alkylate other bio-molecules to cause off-target effects due to their highly active functional groups. So, more exposure of DNA from chromosomes can facilitate the binding of nitrogen mustards to DNA to present stronger anticancer activity, simultaneously avoiding more side effects.

Objective:

To design and synthesize the 4-phenylbutanoic acid-chlorambucil conjugates and valproic acid-chlorambucil conjugates. Upon cellular internalization, the two conju-gates can more strongly damage the DNA of cancer cells due to the more exposure of cel-lular DNA caused by 4-phenylbutanoic acid or valproic acid.

Methods:

To validate this hypothesis, we designed and synthesized two hybrids of chlo-rambucil with 4-phenylbutanoic acid and valproic acid, denoted as compound 2a and compound 2b respectively. The antitumor activity of the aforementioned hybrids was evaluated by the MTT method, mitochondrial membrane potential analysis, apoptosis as-say, DNA damage assay, and scratch assay respectively.

Results:

Compound 2a and compound 2b were synthesized via esterification. The results of bioactivity evaluation showed compound 2a and compound 2b had stronger cytotoxici-ty against breast cancer MDA-MB-231 cells and MCF-7 cells than chlorambucil. More importantly, toward triple negative breast cancer MDA-MB-231 cells, compound 2a ex-hibited significantly greater cytotoxicity compared to both compound 2b and chlorambu-cil. Further studies were conducted on MDA-MB-231 cells, showing that compound 2a could more strongly decrease the mitochondrial membrane potential, induce cell apopto-sis, and damage cellular DNA compared to compound 2b and chlorambucil. Interestingly, in combating the migration of MDA-MB-231 cells, the results exhibited that compound 2b had a much stronger anti-migratory effect than compound 2a, inconsistent with the aforementioned in vitro cytotoxicity.

Conclusion:

These findings demonstrate that the combination of nitrogen mustards with histone deacetylase inhibitors is an effective strategy to exert synergistic anti-tumor ef-fects.
Design, Synthesis, and Biological Evaluation of Some Novel o-aminophenol Derivatives
Authors: Nguyen Dat Van , Tran Ly Duou , Vu Phuong Ngoc Uyen , Meervelt Luc Van , Nguyen Mai Ngoc Thi , Ngo Anh Lan , Duong Hoan Quoc
Published: February 2025

Background:

o-Aminophenol derivatives are of particular interest for their di-verse biological activities and potential therapeutic applications. Such as, antioxidant, an-tibacterial, and cytotoxic activities.

Objective:

This study aimed to design and synthesize a series of novel o-aminophenol de-rivatives through an efficient multi-step process, characterize them using modern spectro-scopic techniques, and evaluate their antimicrobial, antioxidant, and cytotoxic activities.

Methods:

A series of novel derivatives of o-aminophenol have been successfully synthe-sized with very high efficiency through a simple six-step process using readily available chemicals and straightforward reactions. The structures of all products were accurately de-termined using modern spectroscopic methods such as 1D and 2D NMR, as well as IR, MS spectroscopy, and X-ray methods. The antimicrobial activities of eight o-nitrophenol derivatives were assessed against Gram (-) and Gram (+) bacteria as well as fungi. In comparison, antioxidant activities were tested for two o-nitrophenol and 11 o-aminophenol derivatives using SC50 and EC50 assays. Cytotoxicity was evaluated on KB, HepG2, A549, and MCF7 cancer cell lines.

Results:

Six synthesized compounds 5b, 5c, 5g, 6b, 6c, 6g exhibited unusual doublet sig-nals in the H8 region of the 1H NMR spectrum, attributed to atropisomer formation. Eight o-nitrophenol derivatives demonstrated weak antimicrobial activity, with MIC values ranging from 100 to 200 μg/mL. Compound 5g showed activity against all tested bacterial and fungal strains. In antioxidant testing, eight o-aminophenol derivatives 6a, 6b, 6c, 6e, 6f, 6h, 6i, and 12b displayed excellent activity, with SC50 values between 18.95 and 34.26 μg/mL, approaching ascorbic acid's SC50 value of 12.60 μg/mL. Three derivatives 6d, 6g, and 12a showed superior antioxidant activity with EC50 values between 4.00 and 11.25 μg/mL, surpassing quercetin's standard of 9.8 μg/mL. Cytotoxicity assays revealed that o-aminophenol derivatives 6b, 6c, 6f, 6i, and 12b exhibited moderate inhibitory effects on KB cell lines with IC50 values from 32 to 74.94 μg/mL. Compound 6i demonstrated mod-erate cytotoxic activity against HepG2, A549, and MCF7 cell lines, with IC50 values of 29.46, 71.29, and 80.02 μg/mL, respectively.

Conclusion:

Design, synthesis, antimicrobial activity, DPPH Radical Scavenging, Cyto-toxic activity, Evaluation of H8 signal anomalies in certain compounds, and Single crystal X-ray diffraction analysis.
A Convenient one-pot Approach to the Synthesis of Novel Benzimidazole-Indole Molecular Hybrids as Benzazacamalexin Related Analogues
Authors: Stremski Yordan , Bachvarova Maria , Kirkova Desislava , Milinova Elena , Statkova-Abeghe Stela
Published: February 2025

Background:

New benzazacamalexin-related analogues are synthesized in an easily accessible one-pot approach. The method is based on the reaction of indoles with in situ formed electrophilic N-alkoxycarbonylbenzimidazolium reagents. For the first time, their application for N-alkylation of the indole nitrogen atom is announced toward novel tris-heterocyclic hybrids. The structure of newly obtained products was spectrally charac-terized by 1D and 2D-NMR, FTIR and HRMS spectral data. The current scientific re-search is based on the application of a convenient and efficient route for the preparation of various benzimidazoles. This approach is both straightforward and economical, utilizing readily accessible and affordable reagents leading to target compounds.

Objective:

The synthesis of novel benzimidazole-indole molecular hybrids as benzazaca-malexin related analogues

Methods:

A suitable in situ method has been successfully applied, using an α-amidoalkylation reaction of indoles with N,N-diacyliminium reagents derived from ben-zimidazoles and alkyl chloroformates.

Results:

The reactions led to the obtaining of ten novel compounds (5a-e, 6a-e), including bromine and iodine-containing benzo-analogues on a gram-scale scope and yields ranging from 82% to 99%. For the first time the synthesis of indole tris-heterocycles (7a, b) through the reaction of N-alkylation of the indole nitrogen atom is announced giving an-other potential synthetic application of the N,N-dialkoxycarbonyl-5,6-dimethylbenzimidazolium adducts.

Conclusion:

The structure of the newly synthesized products is spectrally analysed and proved.
In silico Identification and Computational Screening of Potential AFP Inhibitors Against Liver Cancer
Authors: Waseem Hassan Bin , Shakeel Muhammad , Hassan Faiz-ul , Yaqoob Asma , Iqbal Azhar , Khalid Amina , Akram Hafiza Nisha , Dilbar Noshaba , Qamar Saad , Tahir Rana Adnan , Sehgal Sheikh Arslan
Published: February 2025

Introduction:

Liver cancer is considered one of the most common types of cancer and a
major cause of ephemerality worldwide having a higher prevalence rate in Asia and sub-Saharan
Africa. The alpha-fetoprotein (AFP) is a serum glycoprotein that belongs to a class of oncodevelopmental
proteins and is also involved in tumor formation.

Methods:

In the current effort, a hybrid approach of virtual screening followed by pharmacophore
generation and molecular dynamic simulation analyses were performed. The screened top-ranked
10 docked compounds from the selected anti-cancer compound library were utilized to generate the
ligand-based pharmacophore. Virtual screening was performed two-dimensional similarity search
against the selected natural compound library based on their physicochemical properties. It was
observed that all the compounds from the anti-cancer compound library and natural compound
library showed similar binding resides.

Results:

Therefore, the top-ranked screened compounds that showed the least binding energy and
highest binding affinity against AFP, obtained through the anti-cancer drug library and natural
compound library were reported. The molecular docking analyses revealed that Leu-219, His-222,
Lys-242, Lys-246, His-316, Glu-318, Ala-366, Val-367, Gly-475, Ile-479, Ala-471, Asp-478 were
observed as potential residues for interaction.

Conclusion:

The observed results of virtual screening, molecular docking, and MD simulation
analyses entail noteworthy observations illustrating that NC002 was a potent inhibitor. The proposed
compound NC002 may have potential against liver cancer by targeting AFP based on MD
simulation analyses, PCA, and MM-GBSA.
The ER Stress-related Gene Prognostic Signature for Predicting Chemosensitivity and Prognosis in AML
Authors: Guo Jie , Peng Hongwei , Long Luyao , Sun Li , Yang Lin , Ren Simei
Published: February 2025

Introduction:

Acute myeloid leukemia is characterized by high heterogeneity, and
the current European Leukemia Net (ELN) risk stratification system is not universally applicable
to all AML patients, requiring approximately three weeks for testing.

Aim:

This study aimed to develop an applicable prognostic tool capable of addressing the limitations
of current methods. We selected AML patients from the clinic and TCGA database to
explore the role of ER stress in response to chemotherapy.

Methods:

Patients from the TCGA database were employed as the training cohort, and two
GEO datasets were used as external validation cohorts. Univariate/multivariate COX and LASSO
regression were exemplified to establish the prognostic model. Kaplan-Meier and timedependent
ROC were used to assess and compare the efficiency of the model with ELN stratification
and other models. In the training cohort, we selected 5 ER stress-related genes to predict
chemosensitivity and establish the ERS-5 prognostic model.

Results:

The model successfully predicted the overall survival of patients (p < 0.0001, HR =
4.86 (2.79-8.44); AUC = 0.83). It was verified in validation cohorts and could further stratify
the risk of various AML subgroups. It also enhanced the ability of ELN to predict the response
of patients with AML to main chemotherapeutic drugs. Finally, an “ERS-5” risk score was constructed
by the nomogram based on the ERS-5 model and age.

Conclusion:

Consequently, in this study, the ERS-5 model was constructed, which allowed
more rapid (about 3 hours) and accurate risk stratification and complemented the ability of ELN
to assess chemosensitivity.
Evaluation of Safety and Efficacy of Cuprum metallicum in Zebrafish and
Mouse Models as a Potential Drug Candidate for the Management of
Seizures
Authors: Sharma Mahima , Saka Vara Prasad , Kumar Godlaveti Vijay Narasimha , Behera Sangita , Regar Rajkumar , Gupta Pankaj , Narula Ritika H
Published: February 2025

Background:

In an alternative medicinal system, Cuprum metallicum (CM) is used for
the management of seizure-like conditions. However, there is a lack of scientific evidence regarding its effect.

Objective:

The present study aimed to evaluate the effect of CM against Pentylenetetrazoleinduced seizures in zebrafish and mice.

Methods:

Zebrafish were exposed to CM-6C, CM-30C, and valproic acid for 1 Hr then fish were
exposed to pentylenetetrazole to record seizure score and locomotor pattern using ANY maze video tracking software. Mice were pretreated with CM-6C, CM-30C, and valproic acid for 10 days.
After 30 min of the last dose, pentylenetetrazole was administered intraperitoneally. Observations
during the next 30 min were recorded to detect latency to first myoclonic jerk (FMJ), tonic-clonic
seizures, and the severity of seizure and survival protection after 24 Hrs.

Results:

PTZ exposure significantly decreased the latency from score-1 to score-5, which CM-6C
and 30C significantly increased. Furthermore, CM-6C and 30C normalized the locomotor activity
affected by PTZ exposure. Among the animals treated with the CM-6C and 30C, significantly increased latency to FMJ, tonic-clonic seizures, and survival protection compared to the PTZ group
of Cuprum met.

Conclusion:

The results of the study indicate that CM 6C and 30C have the potential to work
against seizures as they attenuated the PTZ-induced seizures in Zebrafish and BALB/c mice. It
could be presumed that CM-6C and 30C could be a beneficial alternative drug candidate for the
treatment of epilepsy
Advances in Neuromorphic Computing Devices: Insights on Both Conventional and Unconventional Architectures
Authors: Decastri Davide , Borghi Francesca
Published: February 2025

Neuromorphic circuits and devices have been introduced in the last decades as elements
of a key strategy for developing of new paradigms of computation, inspired by the intent to mimic
elementary neuron structure and biological mechanisms, for the overcoming of energy and timeconsuming
bottlenecks achieved by digital computing (DC) technologies. Although the term “neuromorphic”
is in common use, its meaning is often misunderstood and indistinctly associated with
many different technologies, based on both conventional and unconventional electronic components
and architectures. Here an overview of the different technological strategies used for developing
neuromorphic computing systems is proposed, with an insight on the neuromorphic features they
implement and a special focus on the technological strategies and patents that exploit unconventional
computing paradigms.
Precision Formulation of Ocular Films for Eye Infections Using Innovative Quality by Design Optimization
Authors: Maddileti Repollu , Chinthaginjala Haranath
Published: February 2025

Aim:

The current study focused on formulating ocular films embedded with levofloxacin for the treatment of conjunctivitis by employing the solvent-casting technique.

Methods:

These films were formulated with gelatin, Aloe barbadensis leaves mucilage (ABLM), and HPMC K4M to enhance the therapeutic effectiveness of levofloxacin. Various evaluations were carried out to confirm the quality and stability of the films, including as-sessments of thickness, weight uniformity, uniformity in LFX, % loss of moisture, and perme-ation. In vitro drug release studies were conducted to simulate ocular environments and ana-lyze the precise release of LFX.

Results:

The films exhibited uniform thickness (0.15–0.19 mm) and weight (61.85–65.54 mg) with a consistent film area (0.502 cm²). LFX content ranged from 85.66% to 97.03%, with T-6 being the most uniform. Moisture loss was found to be 7.98–9.55%, and absorption (highest in T-6, i.e., 18.05%) increased with gelatin. LFX permeation peaked at 97.03% (T-6) in 24-h dif-fusion studies. T-8 demonstrated exceptional mucoadhesion (>10 h), and ANOVA confirmed the important influence of gelatin, ABLM, and HPMC K4M on LFX content (F-value: 129.91, p=0.0010).

Conclusion:

The study concluded that combining ABLM with HPMC K4M enabled con-sistent, diffusion-controlled release of LFX, offering an effective and sustained formulation for treating conjunctivitis.
Knowledge, Attitudes, and Practice about Teeth Bleaching Among Subpopulation in Saudi Arabia: A Cross-sectional Study
Authors: Algharbi Muteb , Alenezi Yousef E , Alshammari Fahad F , Alkhalaf Salem A , Siddiqui Ammar A
Published: February 2025

Background

One of the most popular cosmetic dental procedures is teeth whitening. The public's comprehension of its safety and appropriate use, however, is still lacking. The purpose of this study is to assess knowledge, attitudes, and practices about teeth whitening among the population in Saudi Arabia.

Methods

Using a validated questionnaire, 500 persons in Saudi Arabia participated in a cross-sectional survey. The survey evaluated participant knowledge, opinions, and teeth-whitening behaviors in addition to demographic information. SPSS was used to analyze the data, and a significance level of p < 0.05 was considered significant.

Results

Most participants (88%, n=440) understood that getting a dental consultation was necessary before getting teeth whitening. On the other hand, only 29.2% (n=146) thought the bleaching was safe, while 53.6% (n=268) were unsure. Better attitudes and understanding about teeth whitening were substantially correlated with higher educational attainment (p < 0.001). While most people knew that smoking causes tooth discoloration (94.8%, n=474), fewer people knew that other factors, such as too much fluoride, can also cause it (59%, n=295).

Conclusion

Most people in Saudi Arabia understand how important it is to get professional advice before bleaching their teeth. However, there are still false beliefs about its safety, especially among the less educated. It is advised to implement focused educational programs to raise public awareness and encourage safer teeth-whitening procedures.
Factors Influencing Japanese Nursery School Teachers’ Practical Skills in Pediatric Basic Life Support (PBLS)
Authors: Yamada Keiko , Sumiyoshi Tomoko
Published: February 2025

Aim

This study aimed to identify factors related to practical Pediatric Basic Life Support (PBLS) skills among nursery school teachers in regional Japanese cities.

Background

Reducing the mortality rate of infants and young children owing to unintentional injuries is a critical issue in every country. Nursery school teachers, caring for preschool children should possess accurate knowledge and confidence in their responses to emergencies. However, their practical skills in this area have yet to be investigated.

Methods

This study was conducted with 608 nursery school teachers from 45 nursery schools in Niigata Prefecture, Japan. Data were collected using the PBLS practical skills questionnaire created by the authors and the Utrecht Work Engagement Scale-Japanese version (UWESJ17). Multiple regression analysis extracted factors related to PBLS practical skills. Analysis was conducted using SPSS Statistics version 29.0, with the significance level set at less than 5%.

Results

Among participants, 57.8% were in their 40s or older, and 61.8% had over 10 years of nursery school teaching experience. Multiple regression analysis resulted in a model with six predictors, including experience taking a PBLS course, UWESJ17 score, and regular PBLS training at nursery school.

Conclusion

Factors related to the PBLS practical skills of nursery school teachers included personal and facility factors. Employers should establish regular and effective PBLS training programs, mandatory for all nursery school teachers. Injury prevention and response manuals should be distributed to all schools, ensuring consistency and preparedness. This study focused on one region of Japan; therefore, further research in diverse contexts is needed.
Computational Screening of Clinical Drug Libraries for Neurofibromin Inhibition: A Molecular Docking and Dynamics Study for Neurofibromatosis Therapy
Authors: Patel Esha , Nair Ajay , Sharma Sameer , Bhalla Diya , Shyam Keerthana , Dinesh Susha
Published: February 2025

Introduction:

Neurofibromatosis type 1 (NF1) is a genetic disorder characterized
by the development of benign tumors due to mutations in the NF1 gene, which encodes
the tumor suppressor neurofibromin. This study aimed to identify novel inhibitors
of neurofibromin through drug repurposing of clinical trial compounds from the Zinc15
database.

Method:

Utilizing advanced in silico techniques, we conducted molecular docking via
PyRx and molecular dynamics simulations with GROMACS. Among the compounds
analyzed, ZINC000261527152 (Tetrodotoxin) emerged as a promising candidate due to
its binding affinity to NF1. Tetrodotoxin formed stable conventional and carbon-hydrogen
bonds with key residues, including GLU 981, GLY 984, GLN 985, SER 1030, SER 1561,
and ASN 1563. Molecular dynamics simulations confirmed the stability of the Tetrodotoxin-
NF1 complex, with favorable RMSD, RMSF, radius of gyration (Rg), and solvent-
accessible surface area (SASA) values over a 100 ns simulation period.

Result:

These results suggest that Tetrodotoxin could effectively inhibit neurofibromin,
presenting a novel therapeutic approach for neurofibromatosis. However, despite the
promising computational findings, further experimental validation through in vitro and in
vivo studies is essential to confirm the efficacy and safety of Tetrodotoxin as a treatment
for NF1.

Conclusion:

This research underscores the utility of computational drug repurposing
methodologies and their role in accelerating the discovery of novel treatments for genetic
disorders, particularly neurofibromatosis, thereby potentially improving patient outcomes
and quality of life.
Early Detection of Oral Squamous Cell Carcinoma by Image Analysis Using Artificial Intelligence and Nano-diagnostics
Authors: Balasamy Sesuraj , Sundramoorthy Ashok K.
Published: February 2025

Background:

Artificial Intelligence (AI) combined with nanotechnology could detect
oral cancer development in an earlier stage by using various advanced techniques such as biosensors,
Raman scattering, bio-imaging, smartphones, and AI applications.

Objective:

This study aimed to review the latest developments in sophisticated early oral cancer diagnosis
using AI techniques combined with nanotechnologies such as Raman scattering and Oral
Squamous Cell Carcinoma (OSCC) imaging models.

Methods:

Machine learning includes Gabor filters, Resnet 50 for feature extraction, and nanotechnologies
such as Raman scattering. An AI smartphone-based image module helped to detect oral
cancers such as high-risk OSCC.

Results:

AI systems enhance oral cancer identification. Nano-biosensors and Raman scattering aid
in precise detection. AI models, like CNNs, accurately classify oral lesions. Integrating AI, IoT, and
smartphones enables remote screening in underserved communities.

Discussion:

Artificial intelligence enhances ML and DL accuracy for oral cancer diagnosis. The
hybrid Gabor filter, Resnet 50, and nano-based methods impact treatment.

Conclusion:

Artificial intelligence and nano-based oral cancer detection, using ML and DL, offer
precise diagnosis. These technological advancements enable early detection and improve treatment
outcomes.
Perspective on Tau Hypothesis in Alzheimer’s Disease: Traversing the Therapeutic Potential of Flavonoids
Authors: kumari Dipender , Choudhary Manjusha , Bamrah Prabhjeet Kaur , Malan Aditya , Nitesh
Published: February 2025

Tau protein is found in abundance in brain. It is responsible for structural stabilization of
neurons. It is a substrate of numerous protein kinases like glycogen synthase kinase-3 (GSK-3β),
cyclin dependent protein kinase-5 (CDK5), and protein kinase A (PKA), which impel the deformation
of its structure. In Alzheimer’s disease (AD), tau hyperphosphorylation entails the way to
build-up neurofibrillary tangles (NFTs) inside the neurons. Lamentably, there are no such treatments
that can reverse or halter the course of AD. The drugs approved by FDA, donepezil, galantamine,
rivastigmine (cholinesterase inhibitors) and memantine (N-methyl D-aspartate receptors antagonists),
provide only symptomatic relief from AD. An extensive literature survey from several databases like
PubChem, Science Direct, and Web of Science was performed and it was concluded that naturally
derived phytoconstituents can be a reliable alternative for AD treatment. The diverse spectrum of
activity of the naturally occurring flavonoids may make them especially useful for preventing tau
hyperphosphorylation by inhibiting the activity of various protein kinases like glycogen synthase
kinase-3, cyclin-dependent protein kinase-5, and mitogen-activated protein kinases. The present review
aims to identify the mechanisms of action and highlight the therapeutic benefits of different
flavonoids in AD intervention.
Anticancer and Cisplatin Sensitizing Activities against Oesophageal Squamous Cell Carcinoma KYSE-150 Cells and Antioxidant Activity of Ethanolic and Methanolic Ulva sp. Extracts
Authors: Brianna Brianna , Mohamed Naaif , Wu Yuan Seng , Tan Sang Loon , Yow Yoon-Yen , Appalaraju Velaga , Anwar Ayaz , Afzal Shehryar
Published: February 2025

Introduction:

Green macroalgae have exhibited potent anticancer and antioxidant properties
against oesophageal squamous cell carcinoma (ESCC). While cisplatin is used widely for ESSC
treatment, it has low efficacy and induces chemoresistance.

Methods:

This study aimed to investigate the anticancer and cisplatin chemosensitising potentials of
two polar Ulva sp. extracts in chemoresistant ESCC KYSE-150 cells and their antioxidant activity.
Following phytochemical screening, cell viability, apoptosis, reactive oxygen species (ROS) assays
were performed on Ulva sp. treated KYSE-150 along with chemosensitising effects and in silico
molecular docking of phytochemicals against tumour-related protein targets.

Results:

Screening indicated the presence of glycosides (G-glycoside), tannins, terpenoids, carbohydrates,
lipids, proteins and flavonoids, while absence of alkaloids. Both ethanolic (IC50 = 237.2
μg/ml) and methanolic (IC50=165.6 μg/ml) extracts induced higher cytotoxicity through caspase 3/7
activation of apoptosis. Besides, both extracts demonstrated potent antioxidant properties with methanolic
extract showing better scavenging activity compared to ethanolic extract. In silico molecular
docking revealed the ligands have high binding affinity towards B-cell lymphoma-extra-large with
the predicted binding energies (-5.1 to -11.1 kcal/mol), where β-carotene displayed the highest binding
affinity (-11.1 kcal/mol).

Conclusion:

While both extracts did not enhance the cisplatin-sensitivity of KYSE-150 cells, they
exhibited significant antioxidant properties, signifying their potential as a treatment for ESSC.
A Hybrid Deep-Learning based Security Enhancement Framework for Intrusion Detection in WSNs
Authors: Reddy Nalavala Ramanjaneya , Sudarsanam P , Yathish Nirmala , MJ Pavithra , Kalyani Kapula , Asif Shaik , Reddy Pundru Chandra Shaker
Published: February 2025

Aims and background:

Cybersecurity issues have grown as technology rapidly extends
the digital landscape. Intrusion-Detection Systems (IDSs) are essential for detecting malicious
network traffic. Hardware or software can power these systems. Traditional IDS approaches generally
fail to protect data privacy and detect complicated, unique intrusions, principally in WSNs.

Objectives and Methods:

A hybrid model for WSN intrusion detection utilizing the Convolutional
Neural Network and Bidirectional Long-Short-Term-Memory (CNN-BiLSTM) model to overcome
these constraints is proposed. Federated-Learning(FL) improves intrusion recognition and privacy
in this approach. The FL-based CNN-BiLSTM model is unusual in that numerous sensor nodes
can train a central model without revealing private data, addressing privacy issues. By carefully
studying local and temporal network links, the CNN-BiLSTM model detects sophisticated and undiscovered
cyber threats using deep learning. The WSN-DS and CIC-IDS2017 datasets were used
to create the model to detect and classify DoS attacks.

Results:

Experimental results showed that the FL-CNN-BiLSTM model outperformed existing
IDS models in detecting complex and unknown assaults. On both datasets, the model had 99.9%
precision and recall, decreasing false positives and negatives. FL and deep-learning (DL) can improve
WSN security and privacy, according to our research.

Conclusion:

The FL-CNN-BiLSTM architecture helps identify complex cyber threats and shows
how deep learning may improve intrusion detection systems while protecting user data.
MicroRNAs in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review of Clinical Studies
Authors: Antoniou Eleni , Oikonomou Evangelos , Theofilis Panagiotis , Lambadiari Vaia , Kassi Eva , Chasikidis Christos , Zisimos Konstantinos , Andreou Konstantinos , Kalogera Vasiliki , Katsarou Ourania , Foti Elena , Kleopa Eva , Striki Athanasia , Siasos Gerasimos
Published: February 2025

Introduction:

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is
a major contributor to global morbidity and mortality. As diagnostic tools for MASLD remain
limited, microRNAs (miRs) have garnered attention as promising biomarkers due to their roles
in regulating metabolic pathways and reflecting disease states. Method: This systematic review
of clinical studies explores the association between miRNAs and the spectrum of MASLD-related
pathologies, including steatosis, fibrosis, and Hepatocellular Carcinoma (HCC). A comprehensive
literature search was conducted using PRISMA guidelines, resulting in 44 peer-reviewed
studies being included. The review identifies several key miRs, such as miR-122, miR-34a, and
miR-193-5p, which are linked to lipid metabolism, insulin resistance, and MASLD severity. Results:
Additionally, miR-214 and miR-193-5p are highlighted as potential biomarkers for fibrosis,
while miR-21 and miR-34a are implicated in the progression of HCC. These miRs were found in
various tissues, including serum, liver, visceral adipose tissue, and ascitic fluid, demonstrating
their utility as diagnostic and prognostic tools across the MASLD spectrum. Conclusion: While
miR panels are being developed for clinical assessment, further research is required to confirm
their roles in diagnosis and treatment, as well as their integration into routine clinical practice.
Excavator Cab Layout Optimization Design based on Whale Optimization Algorithm
Authors: Su Nina , Yan Xinyu , Bai Wei , Lv Shuyi , Xin Yunsheng
Published: February 2025

Background:

During excavator operation, drivers often need to work continuously for a
long period of time, and this work pattern can greatly reduce work efficiency. In addition, drivers
maintain a fixed posture for a long time to operate the excavator, which can cause the phenomenon
of muscle fatigue and joint discomfort, and even cause muscle strains and other injuries.

Objective:

In order to protect the driver's health and work efficiency, the excavator cab is optimized
and designed to reduce the harm to the human body through reasonable improvement for long time
work, so as to improve the work efficiency.

Method:

Inspired by the patent, 16 muscles of human body were selected to conduct muscle fatigue
analysis experiments on 11 operation processes of excavator to obtain the optimisation indexes, followed
by the establishment of biomechanical model of human upper limbs and lower limbs according
to the experimental results, and the construction of optimization model based on the value of the
minimum joint moments, and finally, the optimized layout of excavator cab was re-optimized by
using the whale optimization algorithm.

Results:

After 600 iterations of the algorithm, the total joint torque decreases from 395N*m to
348.2N*m.In the optimised excavator, the driver's total RULA score decreases from 4 to 3 when
performing the right turn, left turn and backward action, while the total RULA score decreases from
5 to 4 when performing the lowering arm, extending arm, shovel unloading and left rotation action.

Conclusion:

The driver is more likely to cause muscle fatigue when controlling the excavator to
perform forward movement and lower arm movement, the optimization of joystick position and
length, pedal position, and seat height using whale algorithm improves the driver's comfort during
operation and reduces the fatigue during operation accordingly. The findings of this study can provide
a reference for related patent research and development.