Search Results (11,267)

Implementation of novel antiviral coatings and textiles, which can be utilised in the production of personal protective equipment, has the potential to enhance public health security against future pandemic outbreaks. Respiratory viruses, particularly SARS-CoV-2, responsible for COVID-19, have emerged as a major global concern due to their rapid transmission and high mortality rates, leading to nearly seven million deaths worldwide between 2020 and 2025. This statistic underscores the necessity for the development and implementation of advanced antiviral materials to prevent viral infections. This research focused on the in vitro evaluation of the antiviral properties of three antibacterial compounds containing silver (Ag) that were functionalized with coatings. We assessed onsite synthesised Ag powder in comparison to commercially available antibacterial additives, which included nanosilver on colloidal silica (AgSiO₂) and silver sodium hydrogen zirconium phosphate (AgNaOPZr), as potential antiviral agents in coatings against human coronavirus (HCoV). Antiviral assessments revealed that coatings containing Ag at higher concentrations (2.5 and 5%) exhibited limited antiviral effectiveness, with a titer reduction in log < 2. In contrast, the functionalization of AgSiO₂ on coatings significantly suppressed viral replication resulting in a notable reduction in virus titer of log ≥ 2 for all tested concentrations. Full article

Reactions of benzoquinone with amines can potentially lead to the formation of coupled merocyanine or merocyanine/polymethine systems. In this study, several diamino-substituted 1,4-benzoquinones were synthesized. The crystal structures for three derivatives bearing 2-hydroxyethylamino or 2-(2-hydroxyethoxy)ethyl)amino substituents were determined using single-crystal X-ray crystallographic analysis. A characteristic feature of all molecular structures is the presence of an extensive network of intermolecular interactions, significantly stabilized by hydrogen bonding. Additionally, changes in the optical behavior of the synthesized compounds were monitored by UV-Vis spectroscopy in the presence of Cu²⁺ and Zn²⁺ ions, followed by the addition of primary, secondary or biogenic (butane-1,4-diamine) amines. Full article

Objectives: Shengji Yuhong Ointment (SJYHO) is a classic Traditional Chinese Medicine prescription used for refractory wounds, yet its systemic pharmacological mechanisms remain unclear. This study aimed to identify its key active compounds and develop a simplified, effective topical formulation. Methods: We employed an integrated approach, combining network pharmacology and machine learning to screen the key constituents and core targets of SJYHO. The lead compound, glycyrrhizic acid, was formulated into a hydrogel (GA-Gel). Its therapeutic efficacy was evaluated in a full-thickness excisional wound model in Sprague-Dawley rats over 21 days, assessing healing kinetics, histology, and pain behavior. The interaction between glycyrrhizic acid and the identified target PPIA, along with its immunomodulatory effects, was validated through molecular docking, molecular dynamics simulation, and RT-qPCR. Results: Our integrated analysis identified PPIA as the core target and glycyrrhizic acid as a key bioactive component of SJYHO. Animal experiments demonstrated that GA-Gel significantly accelerated wound closure, which was driven by its multi-faceted actions: reducing inflammation, promoting collagen deposition, alleviating pain, and modulating late-stage angiogenesis. Mechanistically, we confirmed that glycyrrhizic acid stably binds to PPIA. Furthermore, GA-Gel treatment mediated wound immune infiltration by specifically regulating CD8⁺ T cells, neutrophils, and memory B cells, an effect that was dependent on PPIA targeting. Conclusions: This study demonstrates that glycyrrhizic acid, formulated as GA-Gel, recapitulates the wound-healing benefits of SJYHO by specifically targeting PPIA and modulating the immune microenvironment. Our findings not only elucidate a key mechanistic pathway but also present GA-Gel as a rationally designed, clinically translatable therapy for acute and chronic wounds. Full article

Background/Objectives: In the Brazilian Amazon, which accounts for over 99% of national malaria cases, 34,260 cases were reported as of August 2025, predominantly caused by Plasmodium vivax, responsible for 86.69% of the infections. The increasing resistance of the parasite to conventional therapies highlights the urgent need for novel control strategies, with essential oils and plant-derived substances emerging as promising alternatives. Methods: In this context, we evaluated the anti-Plasmodium potential of Piper alatipetiolatum essential oil and its major constituent 6-ishwarone against P. vivax, including cytotoxicity in Vero and PBMCs, molecular docking on dihydrofolate reductase (DHFR) and lactate dehydrogenase (LDH), and in silico pharmacokinetic profiling. Results: Both the oil and 6-ishwarone inhibited P. vivax dose-dependently (2.1 ± 1 to 100%), with IC₅₀ values of 9.25 µg/mL and 3.93 µg/mL, respectively. Importantly, no cytotoxic effects were observed at 24 h, with cell viability ranging from 94.7% to 98.3%, highlighting the selectivity of these compounds towards the parasite over mammalian cells. Docking studies indicated selective binding of 6-ishwarone to DHFR (−7.7 kcal/mol; Ki = 2.27 µM) with key interactions (Trp816, Lys820, Tyr819, Asn823, Thr865), whereas binding to LDH was weaker (−6.2 kcal/mol; Ki = 28.10 µM), suggesting DHFR as the primary molecular target. In silico ADMET predictions and experimental data indicated favorable drug-like properties: TPSA = 20.23 Ų, moderate lipophilicity (LogP = 3.37), soluble (ESOL Log S = −3.58; Ali Log S = −3.89; Silicos-IT Log S = −2.84), high gastrointestinal absorption, BBB permeability (0.985), not a P-glycoprotein substrate (0.11), and low likelihood of CYP inhibition. Toxicity predictions showed non-mutagenic and non-hepatotoxic effects, low cardiotoxicity (hERG inhibition risk 0.08–0.32), low reproductive toxicity (0.03), moderate neurotoxicity (0.28), low acute toxicity (oral LD₅₀ = 2.061 mol/kg), and low chronic toxicity (LOAEL = 1.995 log mg/kg/day). Conclusions: Together, these findings demonstrate that essential oil and 6-ishwarone of P. alatipetiolatum are selective, bioavailable, and promising natural leads for antimalarial drug development. Full article

Although low-silicon Al-Si alloys have been extensively studied, further improvement in their mechanical performance remains a critical challenge. This study examines the synergistic effects of scandium (Sc) and zirconium (Zr) additions on the solidification behavior, microstructural evolution, and mechanical properties of Al-5Si-Cu-Mg alloys. The Sc/Zr additions refine the α-Al grains and modify the eutectic Si morphology, with the most uniform microstructure obtained at 0.5 wt.% due to the formation of coherent Al₃(Sc,Zr) dispersoids. These additions also suppress the formation of needle-like β-Al₅FeSi phases and promote the transformation to compact α-Al₁₅(Fe,Mn)₃(Si,Zr,Sc)₂ intermetallics, optimizing the solidification process. The yield strength increases with Sc/Zr content owing to grain-boundary and precipitation strengthening. However, the alloy without Sc/Zr exhibits the highest ultimate tensile strength and elongation, likely due to its finer secondary dendrite arm spacing and the absence of casting-induced cracks in this investigation. Although Sc/Zr additions of 0.25–0.5 wt.% contribute to microstructural refinement, the concurrent formation of porosity and coarse intermetallic compounds leads to a deterioration in ductility. Excessive Sc/Zr additions further coarsen grains and degrade the overall mechanical integrity. Full article

A comprehensive study of the structural–phase transformations and hydrogen desorption kinetics in the Mg₅₆Al₄₄ system was conducted using a multistage approach combining thermodynamic modeling CALPHAD, Thermo-Calc 2025a, mechanical synthesis (MS), spark plasma sintering (SPS), and subsequent dispersion treatment. Thermodynamic modeling revealed a stable existence region of the intermetallic compound Mg₁₇Al₁₂, exhibiting Cp-T anomalies at 303 and 351 °C that closely corresponded to the experimental DSC/TGA results. Microstructural analysis showed that varying the ball-to-powder ratio BPR 20:1 and BPR 30:1 determines the defect density, crystallite size 25–45 nm, and lattice strain 1.5–3.0 × 10⁻³, all of which directly influence the hydrogen desorption kinetics. For the samples synthesized at BPR 30:1, the onset temperature of hydrogen release decreased to 180–200 °C while maintaining a hydrogen storage capacity of 4.9 wt.%, accompanied by a reduction in the apparent activation energy of desorption from 92 to 74 kJ·mol⁻¹ according to the Kissinger method. The dispersion stage partially disrupted and redistributed the surface MgO layer, leading to a reduction in its overall contribution and improvement in structural homogeneity, rather than complete oxide removal. The combined MS-SPS-dispersion processing route enabled controlled nanostructure formation, reduced the hydrogen desorption temperature by approximately 100 °C compared to conventional MgH₂-based materials, and significantly enhanced the thermokinetic performance. These findings demonstrate that Mg-Al alloys are promising candidates for solid-state hydrogen storage systems with improved desorption kinetics and reduced activation barriers. Full article

Cardiovascular disease (CVD) encompasses ischemic conditions of the heart, brain, and bodily tissues, primarily resulting from hyperlipidemia, atherosclerosis (AS), hypertension, and other related factors. CVD accounts for over 40% of global non-communicable disease mortality, making it the leading cause of death and a significant medical burden worldwide. AS, the principal pathological basis for most cardiovascular diseases, is characterized as a chronic, sterile inflammatory condition triggered by lipid overload and various other factors. In recent years, natural bioactive compounds have gained prominence in the treatment of human diseases. Among these, curcumin (Cur) has garnered considerable attention due to its anti-inflammatory, lipid-lowering, antihypertensive, and endothelial protective properties. This review examines traditional pharmacological approaches for treating AS, with particular emphasis on the critical mechanisms through which Cur exerts its therapeutic effects. Additionally, it introduces novel nanoformulations designed to address the inherent limitations of Cur, providing valuable insights for researchers investigating its application in AS therapy. Full article

Breast cancer is one of the most prevalent malignancies affecting women worldwide. Among environmental risk factors, increasing attention has been given to endocrine-disrupting chemicals (EDCs), which can interfere with hormonal signaling pathways. Chronic exposure to these compounds, even at low doses, may lead to molecular changes that initiate carcinogenesis or promote tumor progression. Owing to EDCs’ resistance to degradation and ability to bioaccumulate in organisms and the environment, they pose a growing concern for human health. They can mimic or block natural hormones by binding to receptors, such as estrogen, progesterone, aryl hydrocarbon, or thyroid-stimulating receptors, disrupting hormone synthesis, secretion, and metabolism. They have shown the ability to initiate carcinogenic changes in breast tissue or accelerate cancer progression. This review focuses on the relationship between EDC exposure and breast cancer, examining both their mechanisms of action and long-term health effects. Compounds such as polychlorinated biphenyls, parabens, phenols, 2,3,7,8-tetrachlorodibenzo-p-dioxin, diethylhexyl phthalate, and bisphenol A, which are frequently encountered in everyday products, are discussed in detail. By presenting European Union guidelines and exploring EDCs’ biological activity and pathways of endocrine disruption, we aimed to raise awareness of their potential risks and emphasize the need for further research. Full article

Sirtuin 1 (SIRT1) is an NAD⁺-dependent deacetylase implicated in various physiological and pathological processes, including cardiovascular diseases. The lead compound for SIRT1, resveratrol (1), as well as natural-derived and synthetic SIRT1-activating compounds demonstrated to exert cardioprotective effects. In the present work, we evaluated a small series of diarylimidazoles, of which 4 emerged, in in vitro enzymatic assays, as an activator of SIRT1 endowed with a similar potency compared with that of 1. Therefore, 4 was subjected to pharmacological investigation, where it was proven to reduce myocardial damage induced by ischemia/reperfusion injury in isolated rat hearts, thus demonstrating its cardioprotective properties. An in silico study suggested the binding mode of this derivative within SIRT1 in the presence of the p53-AMC-peptide. These promising results could pave the way to further expand and optimize this chemical class of new SIRT1 activators as potential cardioprotective agents. Full article

Extracellular glutathione (GSH) is degraded on the cell surface, in which the γ-glutamyl residue is removed to generate cysteine–glycine (Cys–Gly) dipeptides that are subsequently transported to the cytoplasm. Carnosine dipeptidase 2 (CNDP2) is a cytoplasmic enzyme that hydrolyzes Cys–Gly and plays an important role in maintaining intracellular cysteine (Cys) homeostasis. CNDP2-mediated hydrolysis of Cys–Gly promotes Cys mobilization and contributes to the replenishment of intracellular GSH levels. CNDP2 is frequently overexpressed in various cancers and has been implicated in tumor cell proliferation and progression. This mechanism may enhance cancer cell survival by causing resistance to oxidative stress, which indicates that CNDP2 is a potential therapeutic target for cancer treatment. Although bestatin (BES) has been identified as a CNDP2 inhibitor, its limited specificity and suboptimal drug-like properties have limited its therapeutic potential. In this study, we performed an in silico screen of a small-molecule compound library and identified KKL-35 as a novel CNDP2-binding molecule. Molecular dynamics (MD) simulations suggested that KKL-35 interacts within the catalytic pocket. Biochemical assays confirmed that it inhibits CNDP2 enzymatic activity, albeit with lower potency compared with BES. Despite its modest intrinsic activity, KKL-35 exhibits favorable physicochemical and pharmacokinetic properties, which are characterized by a low topological polar surface area (TPSA), reduced molecular flexibility, and well-balanced lipophilicity. This positions it as an attractive and tractable starting point for lead optimization. Taken together, these findings establish KKL-35 as a validated CNDP2 inhibitor and a promising lead compound for the development of more selective therapeutics targeting CNDP2-mediated cancer cell metabolism. Full article

Bioactive ingredients are compounds, typically derived from natural sources, that provide specific health benefits or perform certain beneficial functions. Although they can play a role in maintaining good health, their effects can vary widely based on a person’s specific genotype and phenotype, leading to situations where certain ingredients induce beneficial responses for some individuals but not others. Herein, we report a method for the rapid discovery of relationships between genes, bioactive ingredients, and physiological effects. First, RNA-Seq was performed after applying 6 plant-derived ingredients to a three-dimensional skin model. After determining expression changes for each ingredient, these changes were ranked and visualized using score-based prediction models. Based on our analysis, we were able to quickly determine and visualize the effect (or lack thereof) of the ingredients on gene expression. Our findings demonstrate the utility of combining RNA-Seq with score-based models and visualizations for screening bioactive ingredients by gene expression, visualizing their impact based on ingredient or physiological effect, and the applicability of this method to any bioactive ingredient for rapid determination of potential ingredients relevant to maintaining health and wellness. Full article

Gunshot injuries are challenging conditions because of the unique characteristics of the wounding agents producing soft tissue damage that may be compounded by the formation of an expanding temporary cavity (cavitation). Variations in ballistic performance leading to higher energy transfer by the projectile, including bullet tumbling, deformation, and fragmentation, cause increased soft tissue injury and may also lead to more extensive bone comminution compromising local blood supply. Once life-threatening injuries have been excluded or properly addressed, the emergency management of localized trauma from bullets and shotgun pellets may be complicated due to progressive tissue necrosis within the zone of injury. Additionally, the risk of infection should be tackled, especially in high energy bone injuries. War experience suggests a baseline separation between wounds with limited tissue destruction which can routinely be managed as simple penetrating injuries and those resulting from high energy transfer to the tissues involving a substantial amount of necrotic elements surrounding the wound channel which call for a more aggressive surgical approach. A further justification for such a distinction is the need for antibiotic therapy, which varies according to most studies depending on the wounding mechanism, the nature of the wound, and the extent of tissue injury. The emergency physician should also be aware of the possibility of “bizarre” bullet paths resulting in occult injuries of important anatomic structures. Full article

Bacterial canker of kiwifruit, caused by Pseudomonas syringae pv. actinidiae (Psa), poses a serious threat to the global kiwifruit industry. Although flavonoids are widely recognized as natural antibacterial compounds, the transcriptional regulatory networks controlling their synthesis in kiwifruit and their relationship with production of downstream antibacterial metabolites remain poorly understood. In this study, we identified the transcription factor AcMYB5 as a key mediator of salicylic acid (SA) signaling that activates flavonoid biosynthesis and enhances resistance to Psa. Comparative analysis between the resistant cultivar ‘Jinkui’ and the susceptible cultivar ‘Hongyang’ revealed that Psa infection induced a rapid accumulation of endogenous SA, accompanied by a decrease in jasmonic acid (JA) levels in ‘Jinkui’. From a pool of SA-induced candidate genes, we identified AcMYB5, which is rapidly up-regulated by SA and encodes a nuclear localization protein. Overexpression of AcMYB5 in susceptible kiwifruit significantly enhanced resistance to Psa. Mechanistically, AcMYB5 directly binds to and activates the promoter of the chalcone isomerase (AcCHI), a key structural gene in the flavonoid pathway, leading to a marked increase in total flavonoid content. Notably, AcMYB5 did not activate any other genes in the flavonoid synthesis pathway in our assays, underscoring its target specificity. Our findings reveals a novel AcMYB5-AcCHI module that finely tunes flavonoid-mediated defense responses, offering valuable genetic targets and strategic insights for kiwifruit-resistant breeding. Full article

Pulmonary arterial hypertension (PAH) is a devastating cardiovascular disorder caused by right heart failure leading to premature death. The TGFBR2 and BMPR-II receptors, which are members of the TGF-β receptor family, are considered promising targets for developing novel drugs in PAH. Lupeol and ψ-taraxasterol, naturally occurring triterpene molecules with proven anti-inflammatory, anti-cancer, and cardioprotective activities, hold considerable potential in the treatment of PAH. Hence, the present study aimed to evaluate the impacts of lupeol and ψ-taraxasterol isolated from Cirsium sintenisii Freyn on the TGF-β and BMP pathways, aiming to determine their therapeutic values in PAH. The effects of the compounds were extensively investigated using both in silico and wet lab experiments, including reporter assays, RT-PCR/QPCR, Western blots, and cell proliferations assays. Both lupeol and ψ-taraxasterol demonstrated interactions with the majority of components of these signaling pathways, including the TGFBR2 and BMPR-II receptors, suggesting that both compounds were capable of modulating the BMP and TGF-β pathways. Data derived from reporter assays, RT-PCR/QPCR, and Western blots demonstrated that lupeol and ψ-taraxasterol inhibited the TGF-β signaling pathway by reducing the phosphorylation of the SMAD3 protein and the expression of pai-1 transcripts. Additionally, ψ-taraxasterol enhanced BMP signaling via regulating the phosphorylation of SMAD1/5 proteins and upregulated the expression of id-1 transcripts. Finally, lupeol and ψ-taraxasterol inhibited abnormal proliferation of mutant-type (bmpr2^R899X+/-) PAMSCs stimulated with the TGF-β1 ligand with no discernible effects on wild-type cells. This is the first comprehensive report outlining the potential therapeutic effects of lupeol and ψ-taraxasterol in PAH, which may have immediate experimental and clinical applications not only in PAH but also other BMP- and TGF-β-associated disorders. Full article

Background/Objectives: Neglected tropical diseases (NTDs) caused by protozoan parasites such as Trypanosoma cruzi, Trypanosoma brucei, Leishmania spp., and Plasmodium falciparum remain a global health challenge due to limited therapies and increasing drug resistance. Natural products provide diverse scaffolds for antiparasitic drug discovery. This study aimed to investigate the multitarget inhibitory potential of alkaloids isolated from Croton linearis Jacq. against validated protozoan enzymes. Methods: Eighteen alkaloids were virtually screened against 17 molecular targets relevant to protozoan parasites. Protein–ligand docking simulations were performed using crystallographic structures of enzymes, including Cyp51, DHFR-TS, PTR1, AD-kinase, and DHODH. Predicted interactions were analyzed to identify hydrogen bonds, hydrophobic contacts, and π–π stacking with key residues in the active sites. Results: Several alkaloids exhibited high binding affinities, in some cases surpassing co-crystallized ligands. Reticuline, norsalutaridine, laudanosine, and jacularine consistently showed the strongest activity, with docking scores ranging from −8.0 to −9.3 kcal/mol across multiple targets. Notably, norsalutaridine displayed the highest predicted affinity for L. infantum Cyp51, while reticuline showed strong binding to T. cruzi DHFR-TS and L. major PTR1. Conclusions: The study highlights the potential of C. linearis alkaloids as multitarget inhibitors against protozoan parasites. These compounds represent promising lead candidates for the development of antiparasitic agents, while emphasizing the value of natural product scaffolds for neglected disease drug discovery. The findings also support the future exploration of semisynthetic derivatives to optimize activity and selectivity. Full article