Search Results (13,537)

Background: Neglected tropical diseases (NTDs) significantly impact global health, particularly affecting impoverished communities. Among these diseases, leishmaniasis, caused by protozoan parasites of the genus Leishmania and transmitted through sandfly vectors, remains a challenge due to limited therapeutic options. Current treatments often suffer from significant limitations, such as high toxicity, limited efficacy, and the emergence of drug resistance. Objectives: This study investigates the potential antileishmanial mechanism of action of nitroindazole derivatives, specifically evaluating the compound VATR131, a molecule with notable selectivity and potency against Leishmania infantum. Methods: We employed computational methodologies, including target fishing, molecular docking, and atomistic molecular dynamics simulations, to identify and characterize potential molecular targets of VATR131. Results: The analysis revealed cysteine peptidase A as a promising target potentially mediating the antileishmanial activity of VATR131. Molecular dynamics simulations suggest critical hydrophobic interactions and hydrogen bonds between the compound and its most likely receptor, thus offering deeper insights into its potential mechanism of action. Conclusions: These findings contribute to the development of novel and effective therapies for leishmaniasis, highlighting the need for experimental validation and continued investigation of nitroindazole derivatives as promising therapeutic candidates. Full article

Due to the rising atmospheric carbon dioxide levels driven by human activity, extensive scientific efforts have been dedicated to developing methods aimed at reducing its concentration in the atmosphere. A novel approach involves using hydrates as a long-lasting reservoir of CO₂ sequestration. This review provides an initial overview of hydrate characteristics, their formation mechanisms, and the experimental techniques commonly employed for their characterization, including X-ray, Raman spectroscopy, cryoSEM, DSC, and molecular dynamic simulation. One of the main challenges in CO₂ sequestration via hydrates is the requirement of high pressures and low temperatures to stabilize CO₂ molecules within the hydrate crystalline cavities. However, deviations from classical temperature-pressure phase diagrams observed in natural and engineered environments can be explained by considering that hydrate stability and formation are primarily governed by chemical potentials, not just temperature and pressure. Activity, which reflects concentration and non-ideal interactions, greatly influences chemical potentials, emphasizing the importance of solution composition, salinity, and additives. In this context the role of promoters and inhibitors in facilitating or hindering hydrate formation is discussed. Furthermore, the review presents an overview of the impact of marine sediments and naturally occurring compounds on CO₂ hydrate formation, along with the sampling methodologies used in sediments to determine the composition of these natural compounds. Special attention is given to the effect and chemical characterization of dissolved organic matter (DOM) in marine aquatic environments. The focus is placed on the key roles of various natural occurring molecules, such as amino acids, protein derivatives, and humic substances, along with the analytical techniques employed for their chemical characterization, highlighting their central importance in the CO₂ gas hydrates formation. Full article

Cellular senescence is a state of irreversible growth arrest characterized by a pro-inflammatory phenotype, playing dual roles in development. In the fetal intestine, the regulation of senescent cells is critical for maintaining tissue homeostasis. Human breast milk (HBM), known for its rich composition of bioactive molecules, may play a role in modulating senescence, although its effects on senescent intestinal cells remain unexplored. This study investigated whether HBM selectively eliminates senescent cells in the FHs74Int fetal intestinal epithelial cell line. Senescence was assessed via β-galactosidase activity and expression of p16 and p21. The model cell line was treated with HBM, infant formula, and milk fractions, and outcomes included cell recovery, senescence markers, apoptosis, and mitochondrial potential. Total free fatty acids (FFA) were quantified and correlated with senolytic activity. HBM reduced senescent cell recovery without affecting non-senescent cells, correlating with decreased β-galactosidase activity, reduced phospho-p38 and γH2AX expression, mitochondrial depolarization, and caspase activation. Only the lipid fraction retained senolytic activity, which was associated with elevated FFA levels. Incubation of HBM at 37 °C increased FFA content and conferred senolytic activity. These findings are consistent with the idea that HBM exerts selective senolytic effects via FFA, revealing a novel mechanism by which breast milk could contribute to intestinal homeostasis. Full article

The exponential increase in environmental pollutants due to industrialization, urbanization, and agricultural intensification has underscored the urgent need for sensitive, selective, and real-time monitoring technologies. Among emerging analytical tools, organic fluorescent sensors have demonstrated exceptional potential for detecting a wide range of pollutants in water, air, and soil, with a limit of detection (LOD) in the pM–µM range. This review critically examines recent advances in organic fluorescent sensors, focusing on their photophysical properties, molecular structures, sensing mechanisms, and environmental applications. Key categories of organic sensors, including small molecules, polymeric materials, and nanoparticle-based systems, are discussed, highlighting their advantages, such as biocompatibility, tunability, and cost-effectiveness. Comparative insights into inorganic fluorescent sensors, including quantum dots, are also provided, emphasizing their superior photostability and wide operating range (in some cases from pg/mL up to mg/mL) but limited biodegradability and higher toxicity. The integration of nanomaterials and microfluidic systems is presented as a promising route for developing portable, on-site sensing platforms. Finally, the review outlines current challenges and future perspectives, suggesting that fluorescent sensors, particularly organic ones, represent a crucial strategy toward sustainable environmental monitoring and pollutant management. Full article

Human cytomegalovirus (HCMV) establishes lifelong latency following primary infection, residing within myeloid progenitor cells and monocytes. To achieve this, the virus employs multiple immune evasion strategies. It suppresses innate immune signaling by inhibiting Toll-like receptor and cGAS-STING pathways. In addition, the virus suppresses major histocompatibility complex (MHC)-dependent antigen presentation to evade T cell recognition. As the downregulation of MHC molecules may trigger NK cell activation, the virus compensates for this by expressing proteins such as UL40 and IL-10, which engage inhibitory NK cell receptors and block activating signals, thereby suppressing NK cell immune surveillance. Viral proteins like UL36 and UL37 block host cell apoptosis and necroptosis, allowing HCMV to persist undetected and avoid clearance. In settings of profound immunosuppression, such as after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or solid organ transplantation, slow immune reconstitution creates a window for viral reactivation. Likewise, immunosenescence and chronic low-grade inflammation during aging increases the risk of reactivation. Once reactivated, HCMV triggers programmed cell death, releasing viral PAMPs (pathogen-associated molecular patterns) and host-derived DAMPs (damage-associated molecular patterns). This release fuels a potent inflammatory response, promoting further viral reactivation and exacerbating tissue damage, creating a vicious cycle. This cycle of inflammation and reactivation contributes to both transplant-related complications and the decline of antiviral immunity in the elderly. Therefore, understanding the immune regulatory mechanisms that govern the switch from latency to reactivation is critical, especially within the unique immune landscapes of transplantation and aging. Elucidating these pathways is essential for developing strategies to prevent and treat HCMV-related disease in these high-risk populations. Full article

Plant-based extracts and elicitors (signaling molecules that activate the fruit’s innate defense responses) have emerged as promising and sustainable alternatives to synthetic chemicals for preserving postharvest fruit quality and extending shelf life. This review provides a comprehensive analysis, uniquely complemented by a bibliometric assessment of the research landscape from 2005 to 2025, to identify key trends and effective solutions. This review systematically examined the efficacy of various natural compounds including essential oils (complex volatile compounds with potent antimicrobial activity such as lemongrass and thyme), phenolic-rich botanical extracts like neem and aloe vera, and plant-derived elicitors such as methyl jasmonate and salicylic acid. Their preservative mechanisms are multifaceted, involving direct antimicrobial activity by disrupting microbial membranes, potent antioxidant effects that scavenge free radicals, and the induction of a fruit’s innate defense systems, enhancing the activity of enzymes like superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD). Applications of edible coatings of chitosan or aloe vera gel, nano-emulsions, and pre- or postharvest treatments effectively reduce decay by Botrytis cinerea and Penicillium spp.), delay ripening by suppressing ethylene production, minimize water loss, and alleviate chilling injury. Despite their potential, challenges such as sensory changes, batch-to-batch variability, regulatory hurdles, and scaling production costs limit widespread commercialization. Future prospects hinge on innovative technologies like nano-encapsulation to improve stability and mask flavors, hurdle technology combining treatments synergistically, and optimizing elicitor application protocols. This review demonstrates the potential of continued research and advanced formulation to create plant-based preservatives, that can become integral components of an eco-friendly postharvest management strategy, effectively reducing losses and meeting consumer demands for safe, high-quality fruit. Full article

RNA-targeting techniques have emerged as powerful tools in cancer research and therapeutics, offering precise and programmable control over gene expression at the post-transcriptional level. Once viewed as passive intermediates in the central dogma, RNA molecules are now recognized as dynamic regulators of cellular function, capable of influencing transcription, translation, and epigenetic regulation. Advances in high-throughput sequencing technologies, transcriptomics, and structural RNA biology have uncovered a diverse landscape of coding and non-coding RNAs involved in oncogenesis, drug resistance, and tumor progression. In response, several RNA-targeting strategies have been developed to modulate these transcripts, including antisense oligonucleotides (ASOs), RNA interference (RNAi), CRISPR-Cas13 systems, small molecules, and aptamers. This review provides a comparative analysis of these technologies, highlighting their molecular mechanisms, therapeutic potential, and current limitations. Emphasis is placed on the translational progress of RNA-targeting agents, including recent FDA approvals and ongoing clinical trials for cancer indications. Through a critical comparison of these strategies, this review underscores the growing significance of RNA-targeting technologies as a foundation for next-generation cancer therapeutics and precision oncology. Full article

β-Hydroxy-β-methylbutyrate (HMB), a natural metabolite derived from the essential amino acid leucine, is primarily recognised for its anabolic and anti-catabolic effects on skeletal muscle tissue. Recent studies indicate that HMB may also play a role in influencing the structural organisation of extracellular matrix (ECM) components, particularly collagen, which is crucial for maintaining the mechanical integrity of connective tissues. In this investigation, bovine type I collagen was polymerised in the presence of two concentrations of HMB (0.025 M and 0.25 M) to explore its potential function as a molecular modulator of fibrillogenesis. The morphology of the resulting collagen fibres and their molecular architecture were examined using atomic force microscopy (AFM) and Fourier-transform infrared (FTIR) spectroscopy. The findings demonstrated that lower levels of HMB facilitated the formation of more regular and well-organised fibrillar structures, exhibiting increased D-band periodicity and enhanced stabilisation of the native collagen triple helix, as indicated by Amide I and III band profiles. Conversely, higher concentrations of HMB led to significant disruption of fibril morphology and alterations in secondary structure, suggesting that HMB interferes with the self-assembly of collagen monomers. These structural changes are consistent with a non-covalent influence on interchain interactions and fibril organisation, to which hydrogen bonding and short-range electrostatics may contribute. Collectively, the results highlight the potential of HMB as a small-molecule regulator for soft-tissue matrix engineering, extending its consideration beyond metabolic supplementation towards controllable, materials-oriented modulation of ECM structure. Full article

Hydrogen bonding, a prevalent molecular interaction in nature, is crucial in biological and chemical processes. The emergence of single-molecule techniques has enhanced our microscopic understanding of hydrogen bonding. However, it is still challenging to track the dynamic behaviour of hydrogen bonding in solution, particularly under physiological conditions where interactions are significantly weakened. Here, we present a nanoscale-confined, functionalised quantum mechanical tunnelling (QMT) probe that enables continuous monitoring of electrical fingerprints of single-molecule hydrogen bonding interactions for over tens of minutes in diverse solvents, including polar physiological solutions, which reveal reproducible multi-level conductance distributions. Moreover, the functionalised QMT probes have successfully discriminated between L(+)- and D(−)-tartaric acid enantiomers by resolving the conductance difference. This work uncovers dynamic single-molecule hydrogen bonding processes within confined nanoscale spaces under physiological conditions, establishing a new paradigm for probing molecular hydrogen-bonding networks in supramolecular chemistry and biology. Full article

Although methotrexate (MTX) is a magnificent cure for cancerous neoplasms and inflammatory disorders, its usage is bound due to associated hazards, especially nephrotoxicity. The present study investigated the possible therapeutic impact of alogliptin (ALO), prescribed for managing type 2 diabetes, on renal injury caused by MTX and explored the mechanisms that could illustrate this suggested protective effect. Four rat groups were involved: control, ALO (20 mg/kg/d, intragastrically (I.G.)) for ten days, MTX, and MTX + ALO groups. The latter two groups were given MTX (20 mg/kg, I.P.) on the 7th day, while the MTX + ALO group was administered ten days of 20 mg/kg of ALO. A significant impairment in renal function, catalase activity, reduced glutathione content, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) expressions, coupled with an increase in kidney injury molecule-1 (KIM-1), malondialdehyde, tumor necrosis factor-alpha (TNF-α), and cleaved caspase-3 (c-caspase-3) expressions, was observed in MTX-intoxicated rats, evidenced by remarkable deterioration in renal construction. Conversely, ALO improved renal function and architecture. Moreover, ALO retrieved the oxidative balance, the attenuated Nrf2/HO-1 expression, and the elevated KIM-1, TNF-α, and c-caspase-3 expression. In conclusion, ALO might abrogate MTX-elicited kidney damage by rectifying the deviation in oxidative status, apoptotic and inflammatory pathways, paving the way for managing MTX-induced nephrotoxicity. Full article

Plants have evolved a complex, multilayered immune system that integrates molecular recognition, signaling pathways, epigenetic regulation, and small RNA-mediated control. Recent studies have shown that DNA-level regulatory mechanisms, such as RNA-directed DNA methylation (RdDM), histone modifications, and chromatin remodeling, are critical for modulating immune gene expression, allowing for rapid and accurate pathogen-defense responses. The epigenetic landscape not only maintains immunological homeostasis but also promotes stress-responsive transcription via stable chromatin modifications. These changes contribute to immunological priming, a process in which earlier exposure to pathogens or abiotic stress causes a heightened state of preparedness for future encounters. Small RNAs, including siRNAs, miRNAs, and phasiRNAs, are essential for gene silencing before and after transcription, fine-tuning immune responses, and inhibiting negative regulators. These RNA molecules interact closely with chromatin features, influencing histone acetylation/methylation (e.g., H3K4me3, H3K27me3) and guiding DNA methylation patterns. Epigenetically encoded immune memory can be stable across multiple generations, resulting in the transgenerational inheritance of stress resilience. Such memory effects have been observed in rice, tomato, maize, and Arabidopsis. This review summarizes new findings on short RNA biology, chromatin-level immunological control, and epigenetic memory in plant defense. Emerging technologies, such as ATAC-seq (Assay for Transposase-Accessible Chromatin using Sequencing), ChIP-seq (Chromatin Immunoprecipitation followed by Sequencing), bisulfite sequencing, and CRISPR/dCas9-based epigenome editing, are helping researchers comprehend these pathways. These developments hold an opportunity for establishing epigenetic breeding strategies that target the production of non-GMO, stress-resistant crops for sustainable agriculture. Full article

The impact of gluten on human health has been the subject of intense study. Gluten proteins are implicated in a range of adverse health effects, such as allergy, celiac disease, and non-celiac gluten sensitivity in predisposed individuals. However, beyond their potential to trigger adverse reactions, gluten proteins also harbor sequences that, upon digestion or fermentation, can release bioactive peptides with health-promoting properties. These peptides have been reported to exhibit antioxidant, antihypertensive, and immunomodulatory activities, suggesting that gluten-derived products may contribute positively to human health. This review aims to explore the dual nature of gluten proteins, examining their role as both potential health hazards and sources of beneficial molecules. By dissecting the molecular mechanisms underlying gluten-related disorders and the functional properties of gluten-derived peptides, we seek to provide a balanced view of gluten’s complex role in nutrition and health. Full article

The voltage-gated proton channel (H_v1) selectively transports protons (H⁺) across biological membranes in response to membrane potential changes. H_v1 is assembled as a dimer, and unlike most voltage-gated ion channels, it lacks a traditional central pore domain; instead, the voltage-sensing domain (VSD) of each monomer facilitates proton conduction via a hydrogen-bond network. H_v1 is widely expressed in various human cell types (e.g., immune cells, sperm, etc.) including tumor cells. In tumor cells, the accumulation of acidic intermediates generated by glycolysis under hypoxic conditions or ROS production leads to significant cytosolic acidification. H_v1 can remove protons from the cytosol rapidly, contributing to the adaptation of the cells to the tumor microenvironment, which may have significant consequences in tumor cell survival, proliferation, and progression. Therefore, H_v1 may be very promising not only as a tumor marker but also as a potential therapeutic target in oncology. Molecules that modulate the proton flux through H_v1 can be divided into two broad groups: inhibitors and activators. H_v1 inhibitors can be simple ions, small molecules, lipids, and peptides. In contrast, fewer H_v1 activators are known, including albumin, NH29, quercetin, and arachidonic acid. The mechanism of action of some inhibitors is well described, but not all. H_v1 modulation has profound effects on cellular physiology, especially under stress or pathological conditions, like cancer and inflammation. The therapeutic application of selective H_v1 inhibitors or activators could be a very promising strategy in the treatment of several serious diseases. Full article

Lignocellulosic agricultural residues represent a rich source of potential feedstock for biorefinery applications, but their valorization remains challenging. The white-rot fungus Irpex lacteus J2 exhibited a promising degradation effect, but its molecular mechanisms of lignocellulose degradation remained largely uncharacterized. Here, we performed high-quality whole-genome sequencing and untargeted metabolomic profiling of I. lacteus J2 during the degradation of corn straw as the sole carbon source. The assembled I. lacteus J2 genome contained 14,647 protein-coding genes, revealing a rich genetic repertoire for biomass degradation and secondary metabolite synthesis. Comparative genomics showed high synteny (mean amino acid sequence identity 92.28%) with I. lacteus Irplac1. Untargeted metabolomic analysis unveiled a dynamic metabolic landscape during corn straw fermentation. Dominant metabolite classes included organic acids and derivatives (27.32%) and lipids and lipid-like molecules (25.40%), as well as heterocyclic compounds (20.41%). KEGG pathway-enrichment analysis highlighted significant activation of core metabolic pathways, with prominent enrichment in global metabolism (160 metabolites), amino acid metabolism (99 metabolites), carbohydrate metabolism (24 metabolites), and lipid metabolism (19 metabolites). Fermentation profiles at 3 and 15 days demonstrated substantial metabolic reprogramming, with up to 210 upregulated and 166 downregulated metabolites. Correlation analyses further revealed complex metabolic interdependencies and potential regulatory roles of key compounds. These integrated multi-omics insights significantly expand our understanding of the genetic basis and metabolic versatility, enabling I. lacteus J2 to efficiently utilize lignocellulose. Our findings position I. lacteus J2 as a robust model strain and provide a valuable foundation for developing advanced fungus-based strategies for sustainable bioprocessing and valorization of agricultural residues. Full article

Current standard treatments for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), a urological disorder with anxiety as a major comorbidity, are limited in success rates. Recent findings revealed the anti-inflammatory and neuroprotective effects of CO-releasing molecules (CO-RMs), but there is a gap in the knowledge on its effects in CP/CPPS. Therefore, the objective of our study was to investigate the potential therapeutic effects of CORM-A1 on the scrotal pain threshold and anxiety-related behaviors in experimental model of CP/CPPS. Adult Wistar albino male rats were randomized to Sham (intraprostatic saline) or CP/CPPS (intraprostatic λ-carrageenan) groups (n = 12). Half received CORM-A1 (2 mg/kg/day, i.p., days 1–7), others PBS, forming four subgroups (n = 6). The pain threshold (by an electronic von Frey esthesiometer) and anxiety-like behavior (by an open field, elevated plus maze and light/dark test) were assessed; prostates were histologically examined. Carrageenan-induced CP/CPPS caused significant mechanical pain hypersensitivity (p < 0.001), anxiety-like behaviors (p < 0.001–0.05), and histological prostate damage when compared to corresponding Sham groups. CORM-A1 treatment increased pain thresholds (p < 0.001) and improved behavioral outcomes (p < 0.001–0.01) in all ethological tests. These findings indicate that CORM-A1 exerts analgesic and anxiolytic effects in an experimental model of CP/CPPS in rats. Full article