Search Results (632)

Atherosclerosis is a progressive, multifactorial disease driven by the interplay of lipid dysregulation, chronic inflammation, oxidative stress, and maladaptive vascular remodeling. Despite advances in systemic lipid-lowering and anti-inflammatory therapies, residual cardiovascular risk persists, highlighting the need for more precise interventions. Targeted drug delivery represents a transformative strategy, offering the potential to modulate key pathogenic processes within atherosclerotic plaques while minimizing systemic exposure and off-target effects. Recent innovations span a diverse array of platforms, including nanoparticles, liposomes, exosomes, polymeric carriers, and metal–organic frameworks (MOFs), engineered to engage distinct pathological features such as inflamed endothelium, dysfunctional macrophages, oxidative microenvironments, and aberrant lipid metabolism. Ligand-based, biomimetic, and stimuli-responsive delivery systems further enhance spatial and temporal precision. In parallel, advances in in-silico modeling and imaging-guided approaches are accelerating the rational design of multifunctional nanotherapeutics with theranostic capabilities. Beyond targeting lipids and inflammation, emerging strategies seek to modulate immune checkpoints, restore endothelial homeostasis, and reprogram plaque-resident macrophages. This review provides an integrated overview of the mechanistic underpinnings of atherogenesis and highlights state-of-the-art targeted delivery systems under preclinical and clinical investigation. By synthesizing recent advances, we aim to elucidate how precision-guided drug delivery is reshaping the therapeutic landscape of atherosclerosis and to chart future directions toward clinical translation and personalized vascular medicine. Full article

Three previously synthesized ketene dithioacetals were used as intermediates to obtain four nucleophiles to synthesize ten tetra-substituted pyrazoles (11–20). This was achieved through microwave irradiation in ethanol as the solvent, yielding superb results ranging from 68.4% to 90.1%, in agreement with some of the principles of green chemistry. The proposed structures were determined using various spectroscopic techniques, including infrared spectroscopy and hydrogen and carbon-13 nuclear magnetic resonance. Furthermore, the compounds underwent in-silico evaluations using CLC-Pred and AdmetSAR software to predict the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. This was combined with molecular docking calculations for four main cancer-related targets for pyrazole core, to facilitate screening for subsequent biological assessments. Based on the data generated from these analyses, it was identified two pyrazoles (11 and 18) likely to exhibit anti-tumor activity, while also demonstrating low toxicity levels. Upon selection, these two pyrazoles were subjected to toxicity assessments using the Artemia salina method and evaluated for their effects on the viability of Jurkat cancer cells with a potency of 45.05 and 14.85 µM to 11 and 18, respectively, and with a potency of above 100 µM for the non-carcinogenic cells HEK 293. Overall, the findings from these studies indicate pyrazole derivatives as potential anti-tumor candidates. Full article

Infectious laryngotracheitis (ILT) is a severe upper respiratory disease highly contagious in chickens that causes a huge economic impact on the poultry industry all over the world. The current study aimed to design a multi-epitope-based vaccine candidate using envelope glycoprotein B and glycoprotein D of the ILT virus using an immune informatics approach. The glycoproteins B and D are crucial for attachment as well as entry of ILT virus inside the cell, which makes them a potential option for designing vaccine candidates. The prediction of epitopes, viz. helper T lymphocyte, cytotoxic T lymphocyte and interferon-gamma producing epitopes, was performed and high-scoring predicted epitopes were joined in an organized manner using suitable linkers to design the final vaccine candidate. The avian beta-defensin 1 was included as an adjuvant in the amino-terminal of the vaccine design that possesses antimicrobial activity and histidine residues at the carboxy-terminal for the purpose of purification. The final vaccine candidate was evaluated for its physicochemical characteristics, solubility, antigenicity, stability, and allergenicity and validated for its modeling. Molecular docking, binding affinity, and interacting residues between the vaccine candidate and immune receptors, viz. TLR 3, MHC Class I and Class II were assessed. Further, to assess the immune response profile generated by the final vaccine design, an insilico immune simulation study was also performed. The findings of this study revealed that the final vaccine candidate was antigenic, nonallergenic, stable, interacted with immune receptors, and able to produce antibodies as well as cellular immune responses against ILTV infection. Full article

Breast, colon, and ovarian cancers are among the most prevalent malignancies worldwide, with distinct clinical features. This study aims to identify key proteins as common biomarkers for breast, colon, and ovarian cancer through protein analysis, molecular mechanisms, and patient sample validation. Data mining from curated databases identified 483 proteins for breast cancer, 521 for colon cancer, and 223 for ovarian cancer. Interaction network analysis revealed shared clusters involved in cancer progression, DNA repair, and cell proliferation. A core set of 27 proteins was found to be common across all three cancer types, participating in key biological processes such as DNA damage response, cell proliferation, and apoptosis. Notably, these proteins are implicated in KEGG pathways linked to multiple cancers. Differential gene expression analysis revealed significant alterations in the expressions of MSH2 and KIT across the three cancers, suggesting their potential as common biomarkers. The high expression of these proteins was associated with better survival outcomes, highlighting their potential as common biomarkers for breast, colon, and ovarian cancers. The in-silico methodology integrated various bioinformatic tools—including cluster identification, gene expression profiling, protein network visualization, and biomarker prediction—enhancing the understanding of shared molecular mechanisms and potential therapeutic targets. Full article

Background/Objectives: Highly pathogenic coronaviruses (CoVs), including SARS-CoV, MERS-CoV, and SARS-CoV-2, continue to pose a significant threat to global public health. Therefore, this situation highlights the urgent need for effective broad-spectrum antiviral agents. Curcumin, a naturally occurring polyphenol known for its antiviral and anti-inflammatory properties, faces limitations such as poor bioavailability and rapid metabolic degradation, restricting its practical therapeutic application. Methods: To address these limitations, this study introduces a novel design strategy aimed at 42 new curcumin derivatives with improved pharmacokinetic profiles, specifically targeting the conserved coronavirus enzyme papain-like protease (PLpro). A comprehensive in silico evaluation was performed, including ADMET (Absorption, Distribution, Metabolism, Elimination, and Toxicity) analysis, molecular docking, molecular dynamics (MD) simulations, and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) calculations. Results: Extensive pharmacokinetic and toxicological assessments (ADMET analyses) identified 19 derivatives exhibiting optimal drug-like characteristics according to Lipinski’s Rule of Five (Ro5). Molecular docking analyses demonstrated that these novel derivatives possess significantly enhanced binding affinities to PLpro enzymes from SARS-CoV, MERS-CoV, and SARS-CoV-2 compared to standard antiviral agents and natural curcumin. Further validation through MD simulations and MM/PBSA calculations confirmed the structural stability and robust interactions of the most promising derivatives within the SARS-CoV PLpro active site. Conclusions: The results of this study provide essential structural and functional insights, reinforcing the potential of these newly developed curcumin derivatives as potent, broad-spectrum antiviral agents effective against current and future coronavirus threats. Full article

Psychosis constitutes a cardinal component of schizophrenia and affects nearly fifty percent of those with bipolar disorder. We sought to molecularly characterize psychosis segregating in consanguineous families. Participants from eight multiplex families were evaluated using standardized testing tools. DNA was subjected to exome sequencing followed by Sanger sequencing. Effects of variants were modeled using in-silico tools, while cDNA from a patient’s blood sample was analyzed to evaluate the effect of a splice-site variant. Twelve patients in six families were diagnosed with schizophrenia, whereas four patients from two families had psychotic bipolar disorder. Two homozygous rare deleterious variants in INSR (c.2232-7T>G) and NFXL1 (c.1322G>A; p.Cys441Tyr) were identified, which segregated with severe treatment-resistant psychosis/schizophrenia in two families. There were none, or ambiguous findings in the other six families. The predicted deleterious missense variant affected a conserved amino acid, while the intronic variant was predicted to affect splicing. However, cDNA analysis from a patient’s blood sample did not reveal an aberrant transcript. Our results indicate that INSR and NFXL1 variants may have a role in psychosis that requires to be investigated further. Lack of molecular diagnosis in some patients suggests the need for genome sequencing to pinpoint the genetic causes. Full article

Background/Objectives: Chronic pancreatitis (CP) is a progressive inflammatory condition of the pancreas that leads to irreversible changes in pancreatic structure. The pancreatic α and β cells secrete hormones such as insulin and glucagon into the bloodstream. The pancreatic acinar cells secrete digestive enzymes that break down macromolecules. When these digestive enzymes do not function properly, maldigestion, malabsorption, and malnutrition may result. Presented here is a case study of an individual newly diagnosed with chronic pancreatitis, along with a genetic analysis of his son and an in-silico analysis of two of the variant proteins. Methods: This study was conducted using human subjects, namely, the proband (father) and his son. Medical genetic testing of the proband (father) identified the presence of two variants in the cystic fibrosis transmembrane receptor gene (CFTR): variant rs213950, resulting in a single amino acid change (p. Val470Met), and variant rs74767530, a nonsense variant (Arg1162Ter) with known pathogenicity for cystic fibrosis. Medical testing also revealed an additional missense variant, rs515726209 (Ala73Thr), in the CTRC gene. Cheek cell DNA was collected from both the proband and his son to determine the inheritance pattern and identify any additional variants. A variant in the human leukocyte antigen (rs7454108), which results in the HLA-DQ8 haplotype, was examined in both the proband and his son due to its known association with autoimmune disease, a condition also linked to chronic pancreatitis. In silico tools were subsequently used to examine the impact of the identified variants on protein function. Results: Heterozygosity for all variants originally identified through medical genetic testing was confirmed in the proband and was absent in the son. Both the proband and his son were found to have the DRB1*0301 (common) haplotype for the HLA locus. However, the proband was also found to carry a linked noncoding variant, rs2647088, which was absent in the son. In silico analysis of variant rs213950 (Val470Met) in CFTR and rs515726209 (Ala73Thr) in CTRC revealed distinct changes in predicted ligand binding for both proteins, which may affect protein function and contribute to the development of CP. Conclusions: This case study of a proband and his son provides additional evidence for a polygenic inheritance pattern in CP. The results also highlight new information on the role of the variants on protein function, suggesting additional testing of ligand binding for these variants should be done to confirm the functional impairments. Full article

The growing threat of antimicrobial resistance has intensified the search for new bioactive compounds, particularly in extreme environments such as Antarctica. Streptomyces fildesensis So13.3, isolated from Antarctic soil, harbours a biosynthetic gene cluster (BGC) associated with actinomycin D production, an antibiotic with biomedical relevance. This study investigates the regulatory role of TetR/AcrR transcription factors encoded within this biosynthetic gene cluster (BGC), focusing on their structural features and expression under different nutritional conditions. Additionally, we propose that repressing an active pathway could lead to the activation of silent biosynthetic routes, and our in-silico analysis provides a foundation for selecting key mutations and experimentally validating this strategy. Expression analysis revealed that TetR-279, in particular, was upregulated in ISP4 and IMA media, suggesting its participation in nutrient-dependent BGC regulation. Structural modelling identified key differences between TetR-206 and TetR-279, with the latter containing a tetracycline-repressor-like domain. Molecular dynamics simulations confirmed TetR-279’s structural stability but showed that the S166P CRISPy-web-guided mutation considerably affected its flexibility, while V167A and V167I had modest effects. These results underscore the importance of integrating omics, structural prediction, and gene editing to evaluate and manipulate transcriptional regulation in non-model bacteria. Targeted disruption of TetR-279 may derepress actinomycin biosynthesis, enabling access to silent or cryptic secondary metabolites with potential pharmaceutical applications. Full article

Hydrogels are pivotal in advanced materials, driving innovations in medical fields, such as targeted drug delivery, regenerative medicine, and skin repair. This systematic review explores the transformative impact of in-silico design on hydrogel development, leveraging computational tools such as molecular dynamics, finite element modeling, and artificial intelligence to optimize synthesis, characterization, and performance. We analyze cutting-edge strategies for tailoring the physicochemical properties of hydrogels, including their mechanical strength, biocompatibility, and stimulus responsiveness, to meet the needs of next-generation biomedical applications. By integrating machine learning and computational modeling with experimental validation, this review highlights how in silico approaches accelerate material innovation, addressing challenges and outlining future directions for scalable, personalized hydrogel solutions in regenerative medicine and beyond. Full article

Bacterial cellulose (BC) is a highly pure and crystalline cellulose produced via bacterial fermentation. However, due to its chemical structure made of strong hydrogen bonds and its high molecular weight, BC can neither be melted nor dissolved by common solvents. Therefore, processing BC implies the use of very strong, often toxic and dangerous chemicals. In this study, we proved a green method to produce electrospun BC fibers by testing different ionic liquids (ILs), namely, 1-butyl-3-methylimidazolium acetate (BmimAc), 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (EmimTFSI) and 1-ethyl-3-methylimidazolium dicyanamide (EmimDCA), either individually or as binary mixtures. Moreover, γ-valerolactone (GVL) was tested as a co-solvent derived from renewable sources to replace dimethyl sulfoxide (DMSO), aimed at making the viscosity of the cellulose solutions suitable for electrospinning. A BmimAc and BmimAc/EmimTFSI (1:1 w/w) mixture could dissolve BC up to 3 w%. GVL was successfully applied in combination with BmimAc as an alternative to DMSO. By optimizing the electrospinning parameters, meshes of continuous BC fibers, with average diameters ~0.5 μm, were produced, showing well-defined pore structures and higher water absorption capacity than pristine BC. The results demonstrated that BC could be dissolved and electrospun via a BmimAc/GVL solvent system, obtaining ultrafine fibers with defined morphology, thus suggesting possible greener methods for cellulose processing. Full article

Background/Objectives: Low-frequency alternating current (LFAC) has been shown to induce nerve conduction block (LFACb). However, the effects of LFAC on conduction delay prior to block remain unclear. This study investigates the impact of LFACb on conduction velocity and blocking thresholds in myelinated and unmyelinated fibers using experimental and computational models. Methods: Four models were employed to analyze LFACb effects: (1) in-vivo experiments in earthworms examined conduction delays across nerve bundles with distinct conduction velocities; (2) ex-vivo experiments in canine vagus nerves assessed the upstream and downstream effects of LFAC waveforms ranging from 50 mHz to 500 mHz; (3) in-silico simulations using the Horn, Yoshida, and Schild (HYS) model for unmyelinated fibers explored size-dependent conduction delays and blocking thresholds; and (4) in-silico simulations using the McIntyre, Richardson, and Grill (MRG) model extended to 504 Nodes of Ranvier characterized myelination effects, localized nodal interactions, and diameter-dependent thresholds. Results: LFAC-induced conduction delays were independent of LFAC frequency but strongly influenced by fiber diameter and conduction velocity. Larger fibers exhibited lower block thresholds and shorter delays before block onset. In contrast, smaller fibers demonstrated prolonged subthreshold conduction delays before achieving full block. Conclusions: These findings suggest that LFACb could serve as a neuromodulation tool for selectively blocking larger fibers while preserving smaller fiber function. This has potential applications in functional electrical stimulation (FES) and temporary, non-destructive nerve blocks for clinical and research applications. Full article

Heavy metal contamination in soils is a growing concern due to anthropogenic activities, and Allium sativum (garlic) has shown tolerance to mercury pollution. We analyzed the physiological and molecular responses of garlic cloves exposed to HgCl₂ at 0, 5000, 23,000, and 46,000 mg/kg for 2, 3, and 4 h. The germination percentage was lower than 46,000 mg/kg Hg for 4 h. We also analyzed the expression levels of NAC transcription factors and found that AsNAC11 had higher expression at 46,000 mg/kg at 2 h; AsNAC17 was underexpressed and the maximum was at 2 h at 23,000 mg/kg. AsNAC20 had the highest expression (30 times more than the control) at 3 and 4 h with 23,000 mg/Kg. AsNAC27 showed the highest expression at 3 h with 23,000 mg/kg. The tissues exhibited a maximum Hg bioconcentration factor of 0.037 at 23,000 mg/kg, indicating moderate mercury absorption. However, at a concentration of 46,000 mg/kg, the BCF decreased to 0.023. Our in-silico analysis revealed that the analyzed AsNACs are associated with various abiotic stress responses. This study provides valuable insights into genes that could be utilized for genetic improvement to enhance crop resistance to mercury soil contamination. Full article

Introduction: The third step in histidine degradation is catalysed by imidazolonepropionase. It catalyses the conversion of 4-imidazolone-5-propionic acid to produce N-formimino-L-glutamic acid by hydrolyzing the carbon-nitrogen bonds. The histidine is a very expensive amino acid inside the cell and its degradation is a very conserved process. To date, very few reports are there regarding the structure of bacterial imidazolonepropionase but no reports have been published regarding the comparative structure and sequence analysis of this enzyme from bacterial sources. Methods: An in-silico study has been done to characterize the imidazolonepropionase from gram-positive Bacillus subtilis and gram-negative Agrobacterium fabrum. Results: The sequence analysis revealed that a higher amount of charged residues are present in Bacillus subtilis. These charged residues help in the increment of polarity and hydrophilicity of Bacillus subtilis. The formation of intra-protein interactions was also high in gram-positive species. Interestingly, both species have almost equal abundance of aromatic amino acids in their sequences, but the formation of aromatic-aromatic interactions was high in Bacillus subtilis. Finally, the molecular dynamics simulation study revealed that imidazolonepropionase from Bacillus subtilis was more stable and compact than Agrobacterium fabrum. Conclusions: The imidazolonepropionase from Bacillus subtilis was more stable than Agrobacterium fabrum. Due to the presence of higher stable imidazolonepropionase in Bacillus subtilis, it can use histidine more efficiently. Full article

In recent years, inulin enzymatic hydrolysis has become a very promising alternative for producing fructose on a large scale. Genetically modified chicory was used to extract inulin of industrial quality. By using an adequate kinetic model from the literature, this study aimed to determine the optimal operating alternatives of a batch (BR) or fed-batch (FBR) reactor used for the hydrolysis of inulin to fructose. The operation of the FBR with a constant or variable/dynamic feeding was compared to that of the BR to determine which best maximizes reactor production while minimizing enzyme consumption. Multi-objective optimal solutions were also investigated by using the Pareto-optimal front technique. Our in-silico analysis reveals that, for this enzymatic process, the best alternative is the FBR operated with a constant control variable but using the set-point given by the (breakpoint) of the Pareto optimal front under the imposed technological constraints. This set point reported the best performances, regarding all the considered opposite economic objectives. Also, the FBR with a constant, but NLP optimal feeding, reported fairly good performances. Full article