Search Results (2,502)

Eurasian aspen (Populus tremula L.) is a tree species with recognised ecological and economic importance for both natural and plantation forests. For the fast cloning of selected aspen genotypes, the method of plant propagation through in vitro culture (micropropagation) is often recommended. The efficiency of this method is related to the use of shoot-inducing chemical growth regulators, among which cytokinins, a type of plant hormone, dominate. Although cytokinins can inhibit rooting, this effect is avoided by using cytokinin-free media. This study sought to identify concentrations and combinations of growth regulators that would stimulate one type of P. tremula organogenesis (either shoot or root formation) without inhibiting the other. The investigated growth regulators included cytokinin 6-benzylaminopurine (BAP), auxin transport inhibitor 2,3,5-triiodobenzoic acid (TIBA), auxins indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA), gibberellin biosynthesis inhibitor paclobutrazol (PBZ), and a gibberellin mixture (GA₄/₇). Both BAP and TIBA increased shoot number per P. tremula explant and decreased the number of adventitious roots, but TIBA, in contrast to BAP, did not inhibit lateral root formation. However, for the maintenance of both adventitious shoot and root formation above the control level, the combination of PBZ and GA_4/7 was shown to be especially promising. Full article

The rise of multidrug-resistant Pseudomonas aeruginosa underscores the need for novel therapeutic targets beyond conventional peptidoglycan biosynthesis. Some bacterial strains bypass MurA inhibition by fosfomycin via a cell wall salvage pathway. This study targeted P. aeruginosa AmgK (PaAmgK) and MurU (PaMurU) to identify inhibitors that could complement fosfomycin therapy. A malachite-green-based dual-enzyme assay enabled efficient activity measurements and high-throughput chemical screening. Screening 232 compounds identified Congo red and CTAB as potent PaMurU inhibitors. A targeted mass spectrometric analysis confirmed the selective inhibition of PaMurU relative to that of PaAmgK. Molecular docking simulations indicate that Congo red preferentially interacts with PaMurU through electrostatic contacts, primarily involving the residues Arg28 and Arg202. The binding of Congo red to PaMurU was corroborated further using SUPR-differential scanning fluorimetry (SUPR-DSF), which revealed ligand-induced thermal destabilization. Ongoing X-ray crystallographic studies, in conjunction with site-directed mutagenesis and enzyme kinetic analyses, aim to elucidate the binding mode at an atomic resolution. Full article

Background/Objectives: In the last few decades, the dengue virus, a prevalent flavivirus, has demonstrated various epidemiological, economic, and health impacts around the world. Dengue virus serotype 2 (DENV2) plays a vital role in dengue-associated mortality. The RNA-dependent RNA polymerase (RdRp) of DENV2 is a charming druggable target owing to its crucial function in viral reproduction. In recent years, streptomycetes natural products (NPs) have attracted considerable attention as a potential source of antiviral drugs. Methods: Seeking prospective inhibitors that inhibit the DENV2 RdRp allosteric site, in silico mining of the Streptome database was executed. AutoDock4.2.6 software performance in predicting docking poses of the inspected inhibitors was initially conducted according to existing experimental data. Upon the assessed docking parameters, the Streptome database was virtually screened against DENV2 RdRp allosteric site. The streptomycetes NPs with docking scores less than the positive control (68T; calc. −35.6 kJ.mol⁻¹) were advanced for molecular dynamics simulations (MDS), and their binding affinities were computed by employing the MM/GBSA approach. Results: SDB9818 and SDB4806 unveiled superior inhibitor activities against DENV2 RdRp upon MM/GBSA//300 ns MDS than 68T with ΔG_binding values of −246.4, −242.3, and −150.6 kJ.mol⁻¹, respectively. A great consistency was found in both the energetic and structural analyses of the identified inhibitors within the DENV2 RdRp allosteric site. Furthermore, the physicochemical characteristics of the identified inhibitors demonstrated good oral bioavailability. Eventually, quantum mechanical computations were carried out to evaluate the chemical reactivity of the identified inhibitors. Conclusions: As determined by in silico computations, the identified streptomycetes NPs may act as DENV2 RdRp allosteric inhibitors and mandate further experimental assays. Full article

The transition to sustainable energy sources has intensified interest in lignocellulosic biomass (LCB) as a feedstock for second-generation biofuels. However, the inherent structural recalcitrance of LCB requires the utilization of an effective pretreatment to enhance enzymatic hydrolysis and subsequent fermentation yields. This manuscript presents a novel, single-step, and optimized nitrogen explosive decompression system (NED 3.0) designed to address the critical limitations of earlier NED versions by enabling the in situ removal of inhibitory compounds from biomass slurry and fermentation inefficiency at elevated temperatures, thereby reducing or eliminating the need for post-treatment detoxification. Aspen wood (Populus tremula) was pretreated by NED 3.0 at 200 °C, followed by enzymatic hydrolysis and fermentation. The analytical results confirmed substantial reductions in common fermentation inhibitors, such as acetic acid (up to 2.18 g/100 g dry biomass) and furfural (0.18 g/100 g dry biomass), during early filtrate recovery. Hydrolysate analysis revealed a glucose yield of 26.41 g/100 g dry biomass, corresponding to a hydrolysis efficiency of 41.3%. Fermentation yielded up to 8.05 g ethanol/100 g dry biomass and achieved a fermentation efficiency of 59.8%. Inhibitor concentrations in both hydrolysate and fermentation broth remained within tolerable limits, allowing for effective glucose release and sustained fermentation performance. Compared with earlier NED configurations, the optimized system improved sugar recovery and ethanol production. These findings confirm the operational advantages of NED 3.0, including reduced inhibitory stress, simplified process integration, and chemical-free operation, underscoring its potential for scalability in line with the EU Green Deal for bioethanol production from woody biomass. Full article

Cynara cardunculus L. subsp. cardunculus (Cynara cardunculus L. var. sylvestris (Lam.) Fiori), the wild cardoon, is known for its culinary applications and potential health benefits. Due to this, and given the growing interest in circular economies, deepening our under-standing of the effects of wild cardoon leaf waste on angiogenesis and collagenase activity represents a valuable opportunity to valorise agricultural byproducts as health-promoting ingredients. In this study, the waste product of wild cardoon leaves was extracted to examine its chemical composition and biological activities. Analytical techniques identified several bioactive compounds, including flavonoids, hydroxycinnamic acids such as dicaffeoyl-succinoylquinic acids, and luteolin-7-O-rutinoside. In vivo tests in zebrafish embryos and the chick chorioallantoic membrane demonstrated dose-dependent antiangiogenic effects, particularly enhanced by the complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD). Considering the link between angiogenesis and collagenase, the potential effects of the extract on collagenase activity was investigated. The extract alone inhibited collagenase with an IC₅₀ value comparable to that of the standard inhibitor while its complexed form exhibited a 4.5-fold greater inhibitory activity. A molecular docking study examined the interaction between the main compounds and collagenase. In conclusion, wild cardoon leaves can represent a valuable source of bioactive compounds. This study demonstrated that the complexation of the extract with cyclodextrin determines an increase in its biological activity. Full article

Some studies performed in our laboratory on pyrrole and its derivatives pointed towards the enrichment of the evaluations of these promising chemical structures for the potential treatment of neurodegenerative conditions in general and Parkinson’s disease in particular. A classical Paal-Knorr cyclization approach is applied to synthesize the basic hydrazine used for the formation of the designed series of hydrazones (15a–15g). The potential neurotoxic and neuroprotective effects of the newly synthesized derivatives were investigated in vitro using different models of induced oxidative stress at three subcellular levels (rat brain synaptosomes, mitochondria, and microsomes). The results identified as the least neurotoxic molecules, 15a, 15d, and 15f applied at a concentration of 100 µM to the isolated fractions. In addition, the highest statistically significant neuroprotection was observed for 15a and 15d at a concentration of 100 µM using three different injury models on subcellular fractions, including 6-hydroxydopamine in rat brain synaptosomes, tert-butyl hydroperoxide in brain mitochondria, and non-enzyme-induced lipid peroxidation in brain microsomes. The hMAOA/MAOB inhibitory activity of the new compounds was studied at a concentration of 1 µM. The lack of a statistically significant hMAOA inhibitory effect was observed for all tested compounds, except for 15f, which showed 40% inhibitory activity. The most prominent statistically significant hMAOB inhibitory effect was determined for 15a, 15d, and 15f, comparable to that of selegiline. The corresponding selectivity index defined 15f as a non-selective MAO inhibitor and all other new hydrazones as selective hMAOB inhibitors, with 15d indicating the highest selectivity index of >471. The most active and least toxic representative (15d) was evaluated in vivo on Rotenone based model of Parkinson’s disease. The results revealed no microscopically visible alterations in the ganglion and glial cells in the animals treated with rotenone in combination with 15d. Full article

The shikimate pathway is the fundamental metabolic route for aromatic amino acid biosynthesis in bacteria, plants, and fungi, but is absent in mammals. This review explores how multi-enzyme synergy and allosteric regulation coordinate metabolic flux through this pathway by focusing on three key enzymes: 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase, chorismate mutase, and tryptophan synthase. We examine the structural diversity and distribution of these enzymes across evolutionary domains, highlighting conserved catalytic mechanisms alongside species-specific regulatory adaptations. The review covers directed evolution strategies that have transformed naturally regulated enzymes into standalone biocatalysts with enhanced activity and expanded substrate scope, enabling synthesis of non-canonical amino acids and complex organic molecules. Industrial applications demonstrate the pathway’s potential for sustainable production of pharmaceuticals, polymer precursors, and specialty chemicals through engineered microbial platforms. Additionally, we discuss the therapeutic potential of inhibitors targeting pathogenic organisms, particularly their mechanisms of action and antimicrobial efficacy. This comprehensive review establishes the shikimate pathway as a paradigmatic system where understanding allosteric networks enables the rational design of biocatalytic platforms, providing blueprints for biotechnological innovation and demonstrating how evolutionary constraints can be overcome through protein engineering to create superior industrial biocatalysts. Full article

Experimental and theoretical studies were applied to investigate the adsorption properties of testagen (KEDG) peptide on copper surfaces in sodium chloride solution and, implicitly, its inhibition efficiency (IE) on metal corrosion. The tetrapeptide synthesized from the amino acids lysine (Lys), glutamic acid (Glu), aspartic acid (Asp), and glycine (Gly), named as H-Lys-Glu-Asp-Gly-OH, achieved an inhibition efficiency of around 86% calculated from electrochemical measurements, making KEDG a promising new copper corrosion inhibitor. The experimental data were best fitted to the Freundlich adsorption isotherm. The standard free energy of adsorption ($\mathsf{\Delta }{\mathrm{G}}_{\mathrm{a}\mathrm{d}\mathrm{s}}^{\mathrm{o}}$) reached the value of −30.86 kJ mol⁻¹, which revealed a mixed action mechanism of tetrapeptide, namely, chemical and physical spontaneous adsorption. The copper surface characterization was performed using optical microscopy and SEM/EDS analysis. In the KEDG presence, post-corrosion, SEM images showed a network surface morphology including microdeposits with an acicular appearance, and EDS analysis highlighted an upper surface layer consisting of KEDG, sodium chloride, and copper corrosion compounds. The computational study based on DFT and Monte Carlo simulation confirmed the experimental results and concluded that the spontaneous adsorption equilibrium establishment was the consequence of the contribution of noncovalent (electrostatic, van der Waals) interactions and covalent bonds. Full article

Background/Objectives: As novel synergistic strategy for heart failure (HF), this study explores the formulation and characterization of liposomal systems co-loaded with SGLT2 inhibitors (dapagliflozin—DAPA and empagliflozin—EMPA) and curcumin (Cur). Methods: To enhance liposomal membrane stability and achieve sustained, controlled drug release, oleanolic acid (OA) was incorporated into the lipid bilayer, while the liposomal surface was coated with polyvinylpyrrolidone (PVP). Results: The resulting liposomes exhibited favorable physico-chemical properties (particle size ~170 nm, low PDI, negative zeta potential), high encapsulation efficiencies (up to 97%), and spherical morphology as confirmed by STEM. XRD and DSC analyses indicated successful API incorporation and amorphization within the lipid matrix, while PVP coating provided slight improvements in thermal stability. Trehalose proved to be an effective cryoprotectant, preserving liposome integrity after freeze-drying. In vitro release studies demonstrated sustained and delayed drug release, especially in PVP-coated and OA-containing formulations. Conclusions: All these findings highlight the promise of PVP-coated, OA-stabilized liposomal formulations co-loaded with SGLT2 inhibitors and Cur as biocompatible, multifunctional platforms for targeted HF therapy. Full article

Wax deposition, driven by the crystallization of long-chain n-alkanes, poses severe challenges across industries such as petroleum, oil and natural gas, food processing, and chemical manufacturing. This phenomenon compromises flow efficiency, increases energy demands, and necessitates costly maintenance interventions. Wax inhibitors, designed to mitigate these issues, operate by altering wax crystallization, aggregation, and adhesion over the pipelines. Classic wax inhibitors, comprising synthetic polymers and natural compounds, have been widely utilized due to their established efficiency and scalability. However, synthetic inhibitors face environmental concerns, while natural inhibitors exhibit reduced performance under extreme conditions. The advent of nano-based wax inhibitors has revolutionized wax management strategies. These advanced materials, including nanoparticles, nanoemulsions, and nanocomposites, leverage their high surface area and tunable interfacial properties to enhance efficiency, particularly in harsh environments. While offering superior performance, nano-based inhibitors are constrained by high production costs, scalability challenges, and potential environmental risks. In parallel, the development of “green” wax inhibitors derived from renewable resources such as vegetable oils addresses sustainability demands. These eco-friendly formulations introduce functionalities that reinforce inhibitory interactions with wax crystals, enabling effective deposition control while reducing reliance on synthetic components. This review provides a comprehensive analysis of the mechanisms, applications, and comparative performance of classic and nano-based wax inhibitors. It highlights the growing integration of sustainable and hybrid approaches that combine the reliability of classic inhibitors with the advanced capabilities of nano-based systems. Future directions emphasize the need for cost-effective, eco-friendly solutions through innovations in material science, computational modeling, and biotechnology. Full article

Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target pharmacology, including interactions with cannabinoid receptors, Peroxisome Proliferator-Activated Receptors (PPARs), Transient Receptor Potential (TRP) channels, and potentially SGLT2. Objective: To evaluate the potential of phytocannabinoids as novel modulators of renal glucose reabsorption via SGLT2 and to compare their efficacy, safety, and pharmacological profiles with synthetic SGLT2 inhibitors. Methods: We performed a narrative review encompassing the following: (1) the molecular and physiological roles of SGLT2; (2) chemical classification, natural sources, and pharmacokinetics/pharmacodynamics of major phytocannabinoids (Δ⁹-Tetrahydrocannabinol or Δ⁹-THC, Cannabidiol or CBD, Cannabigerol or CBG, Cannabichromene or CBC, Tetrahydrocannabivarin or THCV, and β-caryophyllene); (3) in silico docking and drug-likeness assessments; (4) in vitro assays of receptor binding, TRP channel modulation, and glucose transport; (5) in vivo rodent models evaluating glycemic control, weight change, and organ protection; (6) pilot clinical studies of THCV and case reports of CBD/BCP; (7) comparative analysis with established synthetic inhibitors. Results: In silico studies identify high-affinity binding of several phytocannabinoids within the SGLT2 substrate pocket. In vitro, CBG and THCV modulate SGLT2-related pathways indirectly via TRP channels and CB receptors; direct IC₅₀ values for SGLT2 remain to be determined. In vivo, THCV and CBD demonstrate glucose-lowering, insulin-sensitizing, weight-reducing, anti-inflammatory, and organ-protective effects. Pilot clinical data (n = 62) show that THCV decreases fasting glucose, enhances β-cell function, and lacks psychoactive side effects. Compared to synthetic inhibitors, phytocannabinoids offer pleiotropic benefits but face challenges of low oral bioavailability, polypharmacology, inter-individual variability, and limited large-scale trials. Discussion: While preclinical and early clinical data highlight phytocannabinoids’ potential in SGLT2 modulation and broader metabolic improvement, their translation is impeded by significant challenges. These include low oral bioavailability, inconsistent pharmacokinetic profiles, and the absence of standardized formulations, necessitating advanced delivery system development. Furthermore, the inherent polypharmacology of these compounds, while beneficial, demands comprehensive safety assessments for potential off-target effects and drug interactions. The scarcity of large-scale, well-controlled clinical trials and the need for clear regulatory frameworks remain critical hurdles. Addressing these aspects is paramount to fully realize the therapeutic utility of phytocannabinoids as a comprehensive approach to T2DM management. Conclusion: Phytocannabinoids represent promising multi-target agents for T2DM through potential SGLT2 modulation and complementary metabolic effects. Future work should focus on pharmacokinetic optimization, precise quantification of SGLT2 inhibition, and robust clinical trials to establish efficacy and safety profiles relative to synthetic inhibitors. Full article

Goosegrass (Eleusine indica) is a major weed in Brazilian soybean, corn, and cotton systems, infesting over 60% of grain-producing areas and potentially reducing yields by more than 50%. Its competitiveness is due to its rapid emergence, fast tillering, C4 metabolism, and adaptability to various environmental conditions. A critical challenge relates to its widespread resistance to multiple herbicide modes of action, notably glyphosate and acetyl-CoA carboxylate (ACCase) inhibitors. Resistance mechanisms include 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) target-site mutations, gene amplification, reduced translocation, glyphosate detoxification, and mainly ACCase target-site mutations. This literature review summarizes the current knowledge on herbicide resistance in goosegrass and its management in Brazil, with an emphasis on integrating chemical and non-chemical strategies. Mechanical and physical controls are effective in early or local infestations but must be combined with chemical methods for lasting control. Herbicides applied post-emergence of weeds, especially systemic ACCase inhibitors and glyphosate, remain important tools, although widespread resistance limits their effectiveness. Sequential applications and mixtures with contact herbicides such as glufosinate and protoporphyrinogen oxidase (PPO) inhibitors can improve control. Pre-emergence herbicides are effective when used before or immediately after planting, with adequate soil moisture being essential for their activation and effectiveness. Given the complexity of resistance mechanisms, chemical control alone is not enough. Integrated weed management programs, combining diverse herbicides, sequential treatments, and local resistance monitoring, are essential for sustainable goosegrass management. Full article

Background: Reducing postprandial blood glucose (PBG) is a crucial strategy for treating diabetes and minimizing the risk of complications. Developing efficient and safe α-glycosidase inhibitors from natural products to lower PBG has attracted much attention. Silphium perfoliatum L. (SP), a traditional herbal medicine of North American Indigenous tribes, has efficacy of treating metabolic diseases, but its hypoglycemic activity and bioactive components have not been fully studied. Methods: In vitro α-glucosidase inhibition and in vivo sucrose/maltose/starch tolerance assays were performed to assess the hypoglycemic effects of SP extracts, and UPLC-Triple-TOF-MS/MS analysis was used to tentatively identify its chemical structure composition. In vitro enzyme inhibition and molecular docking were used to verify the effective ingredients. Results: In vitro hypoglycemic activities of four extracts of SP (SP-10/SP-40/SP-60/SP-C) showed that SP-10 exhibited strong α-glucosidase (sucrase and maltase) inhibitory effects with IC₅₀ of 67.81 μg/mL and 62.99 μg/mL, respectively. Carbohydrate tolerance assays demonstrated that SP-10 could significantly reduce the PBG levels of diabetic mice, with a significant hypoglycemic effect at a dosage of 20 mg/kg. A total of 26 constituents, including 11 caffeoylquinic acids (CQAs) and 15 flavonol glycosides, were tentatively identified by mainly analyzing secondary MS fragmentation. Moreover, three CQAs rich in SP-10, namely chlorogenic acid (CGA), neochlorogenic acid (NCGA), and cryptochlorogenic acid (CCGA), may be the main hypoglycemic substances, as evidenced by their inhibitory effects on sucrase and maltase. Conclusions: The α-glucosidase inhibitory effects of SP extract both in vitro and in vivo and its active ingredients were systematically studied for the first time. Results indicated that SP extract, rich in CQAs, had significant hypoglycemic activity, supporting the considerable potential of SP as hypoglycemic functional food or cost-effective therapeutic agents for diabetes treatment. Full article

Tumor immunotherapy has revolutionized cancer treatment by harnessing the immune system to recognize and eliminate malignant cells, with immune checkpoint inhibitors targeting programmed death receptor 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) demonstrating remarkable clinical success. However, challenges such as treatment resistance, immune-related adverse effects, and high costs highlight the need for novel therapeutic approaches. Aptamers, short, single-stranded oligonucleotides with high specificity and affinity for target molecules, have emerged as promising alternatives to conventional antibody-based therapies. This review provides a comprehensive analysis of aptamer-based strategies targeting immune checkpoints, with a particular focus on PD-1/PD-L1 and CTLA-4. We summarize recent advances in aptamer design, including bispecific and multifunctional aptamers, and explore their potential in overcoming immune resistance and improving therapeutic efficacy. Additionally, we discuss strategies to enhance aptamer stability, bioavailability, and tumor penetration through chemical modifications and nanoparticle conjugation. Preclinical and early clinical studies have demonstrated that aptamers can effectively block immune checkpoint pathways, restore T-cell activity, and synergize with other immunotherapeutic agents to achieve superior anti-tumor responses. By systematically reviewing the current research landscape and identifying key challenges, this review aims to provide valuable insights into the future directions of aptamer-based cancer immunotherapy, paving the way for more effective and personalized treatment strategies. Full article

Cardiovascular diseases (CVD), such as myocardial hypertrophy, heart failure, atherosclerosis, and myocardial ischemia/reperfusion (I/R) injury, are among the major threats to human health worldwide. Post-translational modifications alter the function of proteins through dynamic chemical modification after synthesis. This mechanism not only plays an important role in maintaining homeostasis and plays a crucial role in maintaining normal cardiovascular function, but is also closely related to the pathological state of various diseases. Histone deacetylases (HDACs) play an important role in the epigenetic regulation of gene expression, and play important roles in post-translational modification by catalyzing the deacetylation of key lysine residues in nucleosomal histones, which are closely associated with the occurrence and development of cardiovascular diseases. Recent studies indicate that HDAC inhibitors (HDACis) may represent a new class of drugs for the treatment of cardiovascular diseases by influencing post-translational modifications. In this review, we systematically summarize the mechanism of action of HDACs and HDACis in post-translational modifications related to common cardiovascular diseases, providing new ideas for the treatment of CVD, and explore possible future research directions on the relationship between HDAC and HDACi in post-translational modifications and cardiovascular diseases. Full article