Beni-Suef University Journal of Basic and Applied Sciences最新文献

Background

Atherosclerosis remains a leading cause of cardiovascular morbidity and mortality despite advances in lipid-lowering therapy. The proprotein convertase subtilisin/kexin type 9 protein (PCSK9) was originally characterized for promoting degradation of the low-density lipoprotein receptor and raising circulating low-density lipoprotein cholesterol, but growing evidence shows that PCSK9 also participates directly in vascular inflammation and oxidative stress, bridging lipid dysregulation and immune activation.

Main body

PCSK9 amplifies vascular inflammation through several linked mechanisms. PCSK9 augments toll-like receptor 4/nuclear factor kappa B signaling, raising transcription and release of cytokines such as tumor necrosis factor alpha, and increasing adhesion molecule expression that promotes leukocyte recruitment. PCSK9 upregulates scavenger receptors, notably lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), and CD36, which enhances uptake of oxidized lipoprotein, foam cell formation and activation of the NLRP3 inflammasome. PCSK9 also promotes reactive oxygen species generation via NADPH oxidase and impairs nitric oxide biology, worsening endothelial dysfunction. Together these pathways form a self-amplifying loop in which oxidized lipoprotein and cytokines further increase PCSK9 expression. Clinical and preclinical data indicate that PCSK9 inhibitors markedly lower low-density lipoprotein cholesterol and can reduce some markers of plaque inflammation and oxidative stress, but its full therapeutic potential remains a subject of ongoing investigation.

Conclusion

PCSK9 functions as a molecular bridge between dyslipidemia and vascular inflammation; defining the precise molecular interactions and how different modes of PCSK9 inhibition affect these pathways may enable targeted anti-inflammatory strategies to complement lipid lowering and reduce residual cardiovascular risk.

Background

This study develops and characterizes biphasic Janus nanoparticles (JNPs) for the co-delivery of miconazole nitrate (MCN) and berberine hydrochloride (BER), aiming to enhance antifungal efficacy through combinatorial therapy against superficial fungal infections.

Methods

JNPs were synthesized using single-phase emulsion (O/W-S) and double-phase emulsion (W/O/W) methods, and their physicochemical properties were characterized, including size distribution, polydispersity, surface charge, and encapsulation efficiency. In vitro drug release profiles of MCN and BER from JNPs were evaluated, along with a hydrogel (HG) formulation incorporating optimized JNPs for topical application. Solubility assessments, Fourier transform infrared (FT-IR) spectroscopy for compatibility analysis, and antifungal activity testing against Candida albicans using the agar well diffusion method were also performed.

Results

JNPs exhibited a unique dumbbell-shaped morphology, achieving encapsulation efficiencies of 90.32% for MCN and 71.13% for BER in the W/O/W method. In vitro drug release studies showed cumulative releases of 97.52% for MCN and 90.23% for BER over 24 h in the JNP-HG formulation. The hydrogel, with a pH of 6.75 ± 0.13 and exhibiting non-Newtonian pseudoplastic behaviour, demonstrated excellent spreadability. Antifungal tests revealed significant efficacy of the co-loaded JNPs in the hydrogel, showing larger inhibition zones compared to individual drugs due to synergism.

Conclusion

This research introduces a novel platform employing JNPs for the combinatorial delivery of hydrophilic and hydrophobic drugs, facilitating sustained release and offering promising therapeutic potential for antifungal agents. Future studies should evaluate its in vivo performance and explore diverse combinatorial therapies.

Background

Spontaneous abortion, affecting over 20% of pregnancies, presents significant physical and psychological burdens. While chromosomal aneuploidy and environmental factors contribute to its etiology, the role of maternal genetic and psychiatric factors remains underexplored. Emerging evidence links psychiatric disorders, particularly bipolar disorder, to increased spontaneous abortion risk, potentially via immune or neuroendocrine dysregulation. This research examines the causal link between bipolar disorder and spontaneous abortion using mendelian randomization (MR) and delves into molecular mechanisms via bioinformatics analysis.

Results

Initial MR analysis revealed no direct causal association between bipolar disorder and spontaneous abortion (odds ratio (OR) = 1.05, 95% Confidence Interval (CI): 0.99–1.12). However, single-nucleotide-polymorphism-level analysis identified rs1054442 as a potential mediator, linked to reduced expression of DDN, a gene implicated in neurodevelopment and immune modulation. Microarray data demonstrated significant downregulation of DDN in endometrial tissue from spontaneous abortion patients (logFold Change (logFC) = − 1.21, p = 0.004). Concurrently, immune checkpoint genes—CTLA4, IGSF8, ITPRIPL1, and TIGIT—exhibited altered expression patterns, suggesting disrupted immune tolerance at the maternal–fetal interface.

Conclusions

Although bipolar disorder does not directly elevate spontaneous abortion risk, genetic variants associated with the disorder may contribute to immune dysfunction via DDN dysregulation, indirectly predisposing to spontaneous abortion. These discoveries point to the potential influence of maternal immune modulation in the origins of spontaneous abortion and indicate therapeutic targets for those at risk. Further studies are needed to validate these mechanisms and explore clinical interventions targeting immune checkpoint pathways.

We obtain new results regarding the existence, uniqueness, and stability of solutions for a class of fractional Caputo sequential coupled hybrid system which are investigated by applying fixed-point theorems such as Banach’s contraction mapping principle and Leray–Schauder’s alternative. Also, the stability of the mentioned fractional sequential hybrid system is defined and studied. Lastly, we demonstrate some numerical examples in order to confirm our results.

Background

Breast cancer is the major cause of cancer-related deaths globally. This public health emergency is further worsened by challenges of drug resistance and toxicities of the current medications. Hence, the search for novel drugs has become very necessary.

Methods

In this study, some cytotoxic 1, 3-diphenyl-1H-pyrazole derivatives were virtually screened against estrogen receptor alpha (ERα) of breast cancer to identify promising ligands from the dataset of molecules. Afterward, the bioactive ligands were subjected to QSAR modeling and the validated model was used to design more potent analogs of the most active member of the dataset selected as lead/template molecule (Tm). Subsequently, the binding affinity of the designed ligands against the active sites of ERα was investigated with the aid of molecular docking and molecular mechanics generalized born surface area (MM/GBSA) calculations. Furthermore, density functional theory (DFT) calculation and molecular dynamics simulations were used to study the electronic properties and thermodynamic stability of the most promising ligands and their complexes with the receptor, respectively. Finally, the pharmacokinetic and toxicity profiles of the ligands were also investigated.

Results

The validated penta-parametric QSAR model (R²_train = 0.896; R²_adj = 0.875; Q²_CV = 0.816; and R²_test = 0.703) used for designing new bioactive ligands hinted the predominant influence of molecular size, shape, and symmetry on the observed cytotoxic effects of the investigated 1, 3-diphenyl-1H-pyrazole derivatives on breast cancer cells (MCF-7). The designed ligands; DP-1, DP-2, DP-3, DP-4, and DP-5 which bind to the ERα target with Gibbs free energy change (∆G_Total) of − 41.57, − 42.06, − 42.16, − 41.64, and − 41.91 kcal/mol, respectively, appear more potent than Tm with ∆G_Total value of − 34.89 kcal/mol and tamoxifen (∆G_Total = − 34.89 kcal/mol), an approved drug used herein as positive control. Moreover, the excellent cytotoxic potentials of the new drug candidates against MCF-7 cells were supported by both quantum mechanical calculations and molecular dynamic simulations. In addition, the ligands display sound pharmacokinetic profiles.

Conclusion

The designed ligands could be excellent sources of novel drug candidates against estrogen receptor positive breast cancer. Hence, further in vitro and in vivo investigations on the bioactive molecules are recommended.

Background

The occurrence of malaria, filariasis, yellow fever, West Nile virus, chikungunya, Zika, and dengue diseases causes significant morbidity and mortality in underdeveloped countries due to the emergence of virulent strains and the development of drug resistance. Nanotechnology, a potent tool, can mitigate the mosquito’s emergence and larvae breeding sources effectively. Nanocomposites, an amalgamation of metals/metal oxide/polymer, will target the specific mosquitoes and can suppress their growth and development. Therefore, our objective is to explore the larvicidal potency of nanocomposites in the larvae of Aedes aegypti, Culex quinquefasciatus, Anopheles stephensi, and Culex pipiens and to address the possible use of nanocomposites as insecticides in Integrated Pest Management.

Main body

Nanocomposites have diverse applications in biological sectors due to the distinctive optical and physical chemical properties. These tailored composites can tackle virulent strains, and mosquitoes can’t develop resistance. Nanocomposites act against larvae of various developmental stages (1st–4th instar) in Ae.aegypti, Cx. quinquefasciatus, An.stephensi, and Cx. pipiens with significant LC₅₀ values. The larvicidal effect of the nanocomposite is influenced by species-specific, size and shape, surface coating, and others. The nanocomposites induce reactive oxygen species (ROS), triggering oxidative stress and activating apoptosis mechanisms in the larvae. From the available literature studies, nanocomposites are effective against Ae. aegypti > Cx. quinquefasciatus > Cx. pipiens > An. stephensi mosquitoes.

Conclusion

The nanocomposites are effective against all stages of mosquito larvae and can be further formulated as an insecticide to control the mosquito menace. Thus, the nanocomposites are a novel material for the eradication of juvenile mosquitoes with higher efficacy and efficiency.

Background

Epilepsy is a chronic neurological disorder affecting millions globally, with a significant portion of patients remaining pharmacoresistant. Acupuncture, particularly transcutaneous auricular vagus nerve stimulation (taVNS), has gained attention for its potential in epilepsy management. This study conducts a comprehensive bibliometric analysis of global research trends in acupuncture for epilepsy from 2000 to 2024 to assess publication trends, key research themes, influential articles, and research hotspots.

Methods

A systematic search was conducted using the Web of Science Core Collection (WoSCC) database for articles published between 2000 and 2025. Bibliometrix and VOSviewer were used for bibliometric and thematic analysis, mapping research trends, co-occurrence networks, and thematic evolution.

Results

A steady increase in publications was observed, with notable contributions from China and institutions like Fudan University. Key research themes include vagus nerve stimulation (VNS), electroacupuncture, and neuroinflammation, highlighting the shift toward neuromodulation. Citation impact was highest in journals such as Evidence-Based Complementary and Alternative Medicine. Emerging trends point to taVNS and neuroprotection as significant research areas, with clinical studies increasingly focusing on the biological mechanisms behind acupuncture’s anticonvulsant effects.

Conclusions

Acupuncture for epilepsy has grown in global recognition, especially in VNS and electroacupuncture. However, further high-quality clinical trials and standardized protocols are required to establish acupuncture’s efficacy in clinical epilepsy treatment, particularly in pharmacoresistant cases.

Background

Clostridium perfringens, a bacterium associated with various animal and human diseases, could produce several toxins, such as epsilon toxin (ETX). The economic importance of ETX is related to its ability to cause enterotoxemia in domestic ruminants, which causes sudden death. This neurotoxin is also a unique environmental triggering agent for multiple sclerosis (MS). Antibodies against the TGVSLTTSYSFANTN peptide of ETX had been found in clinically definite multiple sclerosis (CDMS). However, no similarity with human proteins was found by the conducted basic local alignment search tool (BLAST) search. Several studies revealed that similar epitopes shared between the infectious microorganisms and the human proteome could trigger autoimmune responses. Although several ETX-based antigens had been designed, this issue was not considered in the designs.

Methods

In the current study, the ETX sequence was analyzed to find any shared peptides with more than 5 residues in length in the human proteome. Then, a vaccine construct was designed based on specific peptides of ETX with no similarity to the human proteome. The obtained construct was analyzed regarding its antigenic and structural properties.

Results

No match was discovered for peptides longer than 7-meric. Hepta- and 6-meric peptides matched to a total of 4 and 83 identical peptides in the human proteome, respectively. A construct with a length of 110 amino acids (approximately 13 kDa with the estimated pI of 8.75) was obtained. This construct contains both alpha helical and extended regions linked by coiled regions. The extended and coiled regions were more frequent than the helical regions. The AlphaFold 3D model was consistent with the results obtained from the secondary structure prediction. The molecular dynamic (MD) simulation demonstrated that the designed construct maintains its structural compactness during the simulation, and after 50 ns of MD, the designed construct achieves an equilibrium and stabilized state.

Conclusions

A novel antigen was designed based on safe epitopes of epsilon toxin by which potential molecular mimicry involved in autoimmune responses could be avoided. The current study results require experimental verification in future investigations.

Background

This study investigates the antiviral potential of turmeric-derived compounds, particularly curcuminoids, against the Egyptian strain of Potato Virus Y (PVY^N-Egypt) using in silico molecular docking simulations. The binding interactions of five key compounds—curcumin, bisdemethoxycurcumin, demethoxycurcumin, isorhamnetin, and ribavirin (as a control)—were evaluated against three essential viral proteins: P1 protease, helper component proteinase (HCPro), and coat protein, to assess their therapeutic viability.

Results

Molecular docking results revealed that isorhamnetin exhibited the strongest binding affinity toward P1 protease. Curcumin and bisdemethoxycurcumin showed favorable binding to both HCPro and CP. ADMET profiling demonstrated that most tested ligands, except for curcuminol and ribavirin, had good oral bioavailability and favorable gastrointestinal absorption. Polar surface area (PSA), a key factor in membrane permeability and drug-likeness, was also considered—compounds with lower PSA values generally show better bioavailability. However, potential toxicity concerns were identified for curcuminol and ribavirin. Among the compounds, curcumin and its derivatives—particularly isorhamnetin—emerged as promising antiviral candidates, while bisdemethoxycurcumin showed potential to inhibit viral replication. Ribavirin displayed moderate binding but fewer favorable interactions compared to curcumin-based ligands.

Conclusion

This study provides new insights into the development of antiviral agents targeting PVY. The findings support the potential of curcumin derivatives, especially isorhamnetin and bisdemethoxycurcumin, as effective antiviral agents. Further experimental validation is recommended to explore their applications in agriculture and pharmaceutical biotechnology.

Background

Luteolin is a natural polyphenolic flavonoid (C₆–C₃–C₆ structure) found in various medicinal herbs. It exhibits significant antioxidant, anti-inflammatory, and anti-fibrotic properties, making it a promising therapeutic compound for fibrotic illnesses, including pulmonary fibrosis. The condition is distinguished by excessive extracellular matrix formation in lung tissue, resulting in stiffness and reduced respiratory performance. Current treatments, limited to nintedanib and pirfenidone, merely slow disease progression, highlighting the need for more effective therapeutic options.

Main body

Luteolin exerts its effects by modulating key signaling pathways, including transforming growth factor-beta/small mothers against decapentaplegic (TGF-β/SMAD), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), nuclear factor erythroid 2–related factor 2 (NRF2), signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase (MAPK), and NOD-like receptor family pyrin domain-containing 3 (NLRP3), thereby reducing oxidative stress, inflammation, and fibrosis. In vitro and pre-clinical studies also support its therapeutic potential. Furthermore, network pharmacology has identified multiple hub targets of luteolin and highlighted its synergistic interactions with other bioactive compounds. These interactions contribute to enhanced biological outcomes such as cell cycle deceleration, apoptosis induction, and angiogenesis inhibition in inflammatory conditions and cancers. However, poor bioavailability and targeted delivery challenges limit luteolin’s clinical utility. To overcome these issues, nanoparticle-based delivery systems, including nanosuspensions, solid lipid nanoparticles, and polymeric nanoparticles, have been developed to enhance their lung-targeted delivery and therapeutic efficacy.

Conclusion

This narrative review outlines luteolin’s multiple molecular targets, pathways, and mechanisms in modulating fibrotic diseases, especially lung fibrosis, and emphasizes the gap between current formulation strategies and clinical translation. Advanced delivery technologies hold promise for enhancing luteolin’s therapeutic value. Hence, additional investigation is needed to establish its effectiveness as well as its safety in clinical settings and develop luteolin as a viable treatment option for chronic respiratory diseases, particularly pulmonary fibrosis.