Search Results (82)

Soil contamination with lead (Pb) and cadmium (Cd) poses a severe threat to agricultural safety. This study explored the marine bacterium Bacillus velezensis Hao 2023 for bioremediation potential and EPS yield enhancement. Soil filtrate tests under metal stress revealed high tolerance to Pb²⁺ (250 mg/L) and Cd²⁺ (2.5 mg/L), with distinct mechanisms: Cd²⁺ removal was strongly correlated with significant pH increase (up to 8.10), suggesting that immobilization likely occurred through precipitation, while Pb²⁺ was sequestered via EPS synthesis, achieving a yield of 1.62 g/L under stress. To decouple production from metal stress, fermentation was optimized using single-factor and response surface methodology. Key conditions (sucrose, ammonium sulfate, 45 g/L sea salt, 35 °C, pH 6.0, 8% inoculum, 150 rpm) achieved 1.081 g/L EPS under metal-free conditions. These results demonstrate strain Hao 2023’s metal-specific resistance and provide a scalable process for soil remediation agent development. Full article

Conventional wastewater treatment methods often rely on energy-intensive physical and chemical processes that are costly and may generate secondary pollution. These limitations have prompted the exploration of more sustainable alternatives. Among them, phycoremediation, particularly using microalgae, has emerged as a promising strategy for mitigating environmental pollution. Microalgae possess unique capabilities to sequester heavy metals, assimilate nutrients, and degrade emerging contaminants while simultaneously producing valuable biomass. The efficacy of microalgal bioremediation can be enhanced through omics-based approaches, which enable these biological agents to convert toxic compounds into non-toxic forms and improve ecosystem health. Additionally, forming microalgae–microorganism consortia can enhance process efficiency and cost-effectiveness. This review highlights multi-pronged strategies for pollutant mitigation in wastewater, focusing on environmentally and economically viable microalgal cultivation systems. It also identifies research gaps and discusses the potential for biomass valorization into economically important products. Full article

An inorganic–organic hybrid nano-adsorbent was prepared by chemical immobilisation of an organic Schiff base Cu (II) ion receptor, DHB ((E)-N-(1-(2-hydroxy-6-methyl-4-oxo-4H-pyran-3-yl) ethylidene) benzohydrazide), a selective dehydroacetic acid-based chemosensor, onto a mesoporous silica support. In order to prepare the sorbent, the silylating agent was anchored onto the silica. During this procedure, 3-Chloropropyl trimethoxy silane (CPTS) was attached to the surface, increasing hydrophobicity. By immobilising DHB onto the CPTS platform, the silica surface was activated, and as a result the coordination chemistry of the Schiff base generated a hybrid adsorbent with the capability to rapidly sequestrate Cu (II) ions from wastewater, as an answer to combat growing Waste Electrical and Electronic Equipment (WEEE) contamination in water supplies, in the wake of a prolonged consumerism mentality and boom in cryptocurrency mining. The produced hybrid materials were characterised by FTIR, proximate and ultimate analysis, nitrogen physisorption, PXRD, SEM, and TEM. The parameters influencing the removal efficiency of the sorbent, including pH, initial metal ion concentration, contact time, and adsorbent dosage, were optimised to achieve enhanced removal efficiency. Under optimal conditions (pH 7.0, adsorbent dosage 3 mg, contact time of 70 min, and 25 °C), Cu (II) ions were quantitatively sequestered from the sample solution; 93.1% of Cu (II) was removed under these conditions. The adsorption was found to follow pseudo-second-order kinetics, and Langmuir model fitting affirmed the monolayer adsorption. Full article

This review synthesizes research on nuclear factor erythroid 2-related factor 2 (Nrf2) in intestinal health across human, livestock, and mouse models. The Nrf2 signaling pathway serves as a master regulator of cellular antioxidant defenses and a key therapeutic target for intestinal inflammatory disorders, including ulcerative colitis and Crohn’s disease. The interplay between oxidative stress, Nrf2 signaling, and NF-κB inflammatory cascades represents a critical axis in the pathogenesis and resolution of intestinal inflammation. Under normal physiological conditions, Nrf2 remains sequestered in the cytoplasm by Kelch-like ECH-associated protein 1 (Keap1), which facilitates its ubiquitination and proteasomal degradation. However, during oxidative stress, reactive oxygen species (ROS) and electrophilic compounds modify critical cysteine residues on Keap1, disrupting the Keap1-Nrf2 interaction and enabling Nrf2 nuclear translocation. Once in the nucleus, Nrf2 binds to antioxidant response elements (ARE) in the promoter regions of genes encoding phase II detoxifying enzymes and antioxidant proteins, including heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and glutamate-cysteine ligase. This comprehensive review synthesizes current evidence demonstrating that activation of Nrf2 signaling confers protection against intestinal inflammation through multiple interconnected mechanisms: suppression of NF-κB-mediated pro-inflammatory cascades, enhancement of cellular antioxidant capacity, restoration of intestinal barrier integrity, modulation of immune cell function, and favorable alteration of gut microbiota composition. We systematically examine a diverse array of therapeutic agents targeting Nrf2 signaling, including bioactive peptides, natural polyphenols, flavonoids, terpenoids, alkaloids, polysaccharides, probiotics, and synthetic compounds. The mechanistic insights and therapeutic evidence presented underscore the translational potential of Nrf2 pathway modulation as a multi-targeted strategy for managing intestinal inflammatory conditions and restoring mucosal homeostasis. Full article

Celiac disease (CeD) is a chronic, immune-mediated enteropathy triggered by dietary gluten in genetically susceptible individuals, with environmental and epigenetic factors also contributing to its pathogenesis. Once considered a rare pediatric malabsorptive disorder, CeD is now recognized as a systemic condition that can manifest with both gastrointestinal and extraintestinal symptoms across the lifespan. Although strict adherence to a gluten-free diet (GFD) remains the cornerstone of treatment, up to 30–40% of patients experience persistent symptoms and/or ongoing mucosal injury despite reported compliance. This therapeutic gap, combined with advances in molecular understanding of disease mechanisms, has driven the development of novel strategies targeting key pathogenic pathways. Intraluminal interventions include gluten-degrading enzymes and gluten-sequestering agents, while other approaches target tissue transglutaminase 2, induce antigen-specific immune tolerance, or modulate cytokine-driven inflammation, with particular emphasis on interleukin-15 (IL-15) signaling. Additional strategies aim to inhibit lymphocyte trafficking to the intestinal mucosa and enhance intestinal barrier function through zonulin modulation. Adjunctive therapies under investigation include nutraceuticals, microbiota-targeted interventions, and vaccine-based approaches. More recently, advanced experimental and computational platforms, such as human intestinal organoids, organ-on-chip systems, and machine learning–driven analytics, are being leveraged in efforts to accelerate translational research and support the rational design of precision medicine approaches. This narrative review synthesizes current evidence for therapies beyond the GFD, examines challenges in clinical implementation, and discusses how technological innovations may reshape the future therapeutic landscape of CeD. Full article

Expansion of d(GGGGC)_n repeat in the C9ORF72 gene is causal for Amyotrophic Lateral Sclerosis (ALS) and Frontal Temporal Dementia (FTD). Proposed mechanisms include Repeat-Associated Non-AUG translation or the formation of G-quadruplexes (GQ) that disrupt translation, induce protein aggregation, sequester RNA processing factors, or alter RNA editing. Here, I show, using AlphaFold V3 (AF3) modeling, that the TAR DNA-binding protein (TDP-43) docks to a complex of GQ and hemin. TDP-43 methionines lie over hemin and likely squelch the generation of superoxide by the porphyrin-bound Fe. These TDP-43 methionines are frequently altered in ALS patients. Tau protein, a variant of which causes ALS, also binds to GQ and heme and positions methionines to detoxify peroxides. Full-length Tau, which is often considered prone to aggregation and a prion-like disease agent, can bind to an array composed of multiple GQs as a fully folded protein. In ALS and FTD, loss-of-function variants cause an uncompensated surplus of superoxide, which sparks neuronal cell death. In Alzheimer’s Disease (AD) patients, GQ and heme complexes bound by β-amyloid 42 (Aβ4) are also likely to generate superoxides. Collectively, these neuropathologies have proven difficult to treat. The current synthesis provides a framework for designing future therapeutics. Full article

Bacterial biofilms are critical contributors to chronic infections and antimicrobial resistance. Among the diverse extracellular matrix components, extracellular DNA (eDNA) and amyloid proteins have recently emerged as pivotal structural and functional molecules. Both individually contribute to biofilm stability and antibiotic tolerance, yet their cooperative roles remain underappreciated. This review aims to summarize current knowledge on the origins and functions of eDNA and amyloid proteins in biofilms, to highlight their molecular interactions, and to discuss how their synergistic effects promote biofilm-mediated resistance to antimicrobial agents. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases up to September 2025. Keywords included “biofilm”, “extracellular DNA”, “amyloid proteins”, “matrix”, and “antimicrobial resistance”. Relevant original research and review articles were systematically screened and critically analyzed to integrate emerging evidence on eDNA–amyloid interactions in bacterial biofilms. Current studies demonstrate that eDNA originates primarily from autolysis, active secretion, and host-derived DNA, while amyloid proteins are produced by multiple bacterial species, including Escherichia coli (curli), Pseudomonas aeruginosa (Fap), Bacillus subtilis (TasA), and Staphylococcus aureus (phenol-soluble modulins). Both molecules independently strengthen biofilm integrity and provide protective functions against antimicrobial agents. Importantly, recent evidence shows that eDNA can act as a nucleation template for amyloid fibrillation, while amyloid fibers stabilize and protect eDNA from degradation, creating a dense extracellular network. This synergistic eDNA–amyloid assembly enhances biofilm robustness, impedes antibiotic penetration, sequesters antimicrobial peptides, protects persister cells, and facilitates horizontal gene transfer of resistance determinants. The interplay between eDNA and amyloid proteins represents a central but underexplored mechanism driving biofilm-mediated antimicrobial resistance. Understanding this cooperative network not only deepens our mechanistic insights into bacterial pathogenesis but also highlights novel therapeutic targets. Strategies that disrupt eDNA–amyloid interactions may offer promising avenues for combating persistent biofilm-associated infections. Full article

The lysosome is no longer viewed as a simple degradative “trash can” of the cell. The lysosome is not only degradative; its acidic, redox-active lumen also serves as a chemical “microreactor” that can modulate anticancer drug disposition and activation. This review examines how the distinctive chemical features of the lysosome, including its acidic pH (~4.5–5), strong redox gradients, limited thiol-reducing capacity, generation of reactive oxygen (ROS), diverse acid hydrolases, and reservoirs of metal ions, converge to influence the fate and activity of anticancer drugs. The acidic lumen promotes sequestration of weak-base drugs, which can reduce efficacy by trapping agents within a protective “safe house,” yet can also be harnessed for pH-responsive drug release. Lysosomal redox chemistry, driven by intralysosomal iron and copper, catalyzes Fenton-type ROS generation that contributes to oxidative damage and ferroptosis. The lysosome’s broad enzyme repertoire enables selective prodrug activation, such as through protease-cleavable linkers in antibody–drug conjugates, while its membrane transporters, particularly P-glycoprotein (Pgp), can sequester chemotherapies and promote multidrug resistance. Emerging therapeutic strategies exploit these processes by designing lysosomotropic drug conjugates, pH- and redox-sensitive delivery systems, and combinations that trigger lysosomal membrane permeabilization (LMP) to release trapped drugs. Acridine–thiosemicarbazone hybrids exemplify this approach by combining lysosomal accumulation with metal-based redox activity to overcome Pgp-mediated resistance. Advances in chemical biology, including fluorescent probes for pH, redox state, metals, and enzymes, are providing new insights into lysosomal function. Reframing the lysosome as a chemical reactor rather than a passive recycling compartment opens new opportunities to manipulate subcellular pharmacokinetics, improve drug targeting, and overcome therapeutic resistance in cancer. Overall, this review translates the chemical principles of the lysosome into design rules for next-generation, more selective anticancer strategies. Full article

Substance use disorders (SUDs) remain a major global health challenge with limited treatment options and high relapse rates. Vaccines that induce drug-sequestering antibodies have shown promise, but their efficacy is hindered by the poor immunogenicity of small-molecule haptens. Adjuvants, substances that enhance immune responses, are critical for overcoming this limitation and improving vaccine efficacy. This review synthesizes over two decades of preclinical and clinical research to guide rational adjuvant design for SUD vaccines. Five major adjuvant classes are examined: aluminum-salt adjuvants, emulsion adjuvants, toll-like receptor (TLR) agonists, protein immunopotentiators, and cytokine modulators. Their physicochemical properties, innate immune activation profiles, and applications in nicotine, stimulant, and opioid vaccines are discussed. Comparative analyses reveal pronounced drug-specific and carrier-specific variability. Case studies illustrate the superior performance of a complementary TLR-agonist pair in a nicotine nanovaccine versus its limited effect in oxycodone vaccines. They also reveal the differential efficacy of an oil-in-water emulsion adjuvant across antigen types. Four principles emerge: (i) no adjuvant is universally optimal; (ii) drug pharmacology influences immune signaling; (iii) adjuvant-carrier compatibility is important; (iv) complementary adjuvant pairings often outperform single agents. These insights support a precision-vaccinology paradigm that tailors adjuvant strategies to each drug class and the delivery vehicle, advancing the development of next-generation SUD vaccines. Full article

Background: As of 2022, 80% of all documented microbial infections are biofilm-associated: communities of microorganisms adhered to a surface and enclosed in a complex extracellular polymeric substance (EPS). The EPS acts as a physical barrier protecting the bacteria from antimicrobial agents and host immune responses. To combat this hurdle, the application of glycoside hydrolases (GH) has been investigated due to their ability to cleave particular structural polysaccharides within the EPS, thus breaking down the protective barrier and improving antibiotic clearance. While various studies demonstrate the capacity of GHs to improve antibiotic efficacy against biofilms in combination, there is clear differential success between these treatments depending on the GH and antibiotic chosen. Due to the overlap of GH targets and antibiotic structures, it is imperative to ensure that the antibiotics in combinatorial treatments are not degraded by the GH. Methods: This study aimed to screen the GH α-amylase produced from Aspergillus oryzae (AO) and Bacillus subtilis (BS), combined with various antibiotics from different classes, charges, and mode of actions by determining MICs. against the bacterium Pseudomonas aeruginosa (PA) of 6 antibiotics with or without α-amylase and treat 2-day PA biofilms with antibiotics with or without GHs. Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) stability assays and Differential Scanning Fluorimetry (DSF) were conducted to determine antibiotic and GH degradation as well as antibiotic sequestration. Results: Increased MICs in the presence of GHs as well as decreased antibiotic clearance against 2-day biofilms were suggestive of antibiotic degradation. LC-MS/MS stability assays of tetracycline and ciprofloxacin in the presence and absence of α-amylase further demonstrated the α-amylase-mediated antibiotic sequestration. Differential scanning fluorimetry (DSF) assays confirmed α-amylase-antibiotic interactions. Conclusions: This study suggests that α-amylase is capable of degrading and sequestering a variety of antibiotics, and the degree to which these phenomena occur varies depending upon the source of the GH. As a potential treatment for biofilm-associated infections, it is imperative that the GH + antibiotic combinations are determined compatible prior to clinical use. Full article

Celiac disease (CeD) is a chronic autoimmune enteropathy triggered by dietary gluten in genetically predisposed individuals. Along with other disorders such as non-celiac gluten/wheat sensitivity and gluten allergy, adherence to a strict gluten-free diet (GFD) is required as the only effective treatment for CeD. To this end, and partially due to the burdensome nature and limited efficacy in some patients of a GFD, significant research into alternative therapies has been catalyzed. This review gives a perspective on current and emerging treatment strategies targeting different aspects of CeD pathogenesis. These include gluten-degrading enzymes (e.g., AN-PEP, Latiglutenase, Zamaglutenase), gluten-sequestering agents (e.g., AGY-010, BL-7010), modulators of intestinal permeability (e.g., Larazotide acetate, IMU-856), immune-modulating agents (e.g., ZED1227, AMG 714, EQ102), and strategies for immune tolerization (e.g., TAK-101, KAN-101, Nexvax2). Newer approaches are also targeting probiotics to modulate the gut microbiota (e.g., VSL#3, Lactobacillus plantarum HEAL9), nutraceuticals (e.g., polyphenols, vitamins), or food modifications to remove the gluten from naturally gluten-containing foodstuffs (e.g., gluten transamidation, Gluten Friendly™ technology). Despite encouraging results in preclinical and clinical trials, no treatment has yet been conclusively proven to serve as an effective alternative to the GFD. Continued research is essential to validate efficacy, optimize dosing, and ensure safety in broader patient populations. Here, we provide a comprehensive overview of the therapeutic landscape for CeD, analyze the main strengths and limitations of each treatment and highlight promising directions for future management of CeD, altogether evidencing the urgent need to develop effective alternatives for these patients. Full article

Neurodegeneration is increasingly recognized not as a linear trajectory of protein accumulation, but as a multidimensional collapse of biological organization—spanning intracellular signaling, transcriptional identity, proteostatic integrity, organelle communication, and network-level computation. This review intends to synthesize emerging frameworks that reposition neurodegenerative diseases (ND) as progressive breakdowns of interpretive cellular logic, rather than mere terminal consequences of protein aggregation or synaptic attrition. The discussion aims to provide a detailed mapping of how critical signaling pathways—including PI3K–AKT–mTOR, MAPK, Wnt/β-catenin, and integrated stress response cascades—undergo spatial and temporal disintegration. Special attention is directed toward the roles of RNA-binding proteins (e.g., TDP-43, FUS, ELAVL2), m6A epitranscriptomic modifiers (METTL3, YTHDF1, IGF2BP1), and non-canonical post-translational modifications (SUMOylation, crotonylation) in disrupting translation fidelity, proteostasis, and subcellular targeting. At the organelle level, the review seeks to highlight how the failure of ribosome-associated quality control (RQC), autophagosome–lysosome fusion machinery (STX17, SNAP29), and mitochondrial import/export systems (TIM/TOM complexes) generates cumulative stress and impairs neuronal triage. These dysfunctions are compounded by mitochondrial protease overload (LONP1, CLPP), UPR maladaptation, and phase-transitioned stress granules that sequester nucleocytoplasmic transport proteins and ribosomal subunits, especially in ALS and FTD contexts. Synaptic disassembly is treated not only as a downstream event, but as an early tipping point, driven by impaired PSD scaffolding, aberrant endosomal recycling (Rab5, Rab11), complement-mediated pruning (C1q/C3–CR3 axis), and excitatory–inhibitory imbalance linked to parvalbumin interneuron decay. Using insights from single-cell and spatial transcriptomics, the review illustrates how regional vulnerability to proteostatic and metabolic stress converges with signaling noise to produce entropic attractor collapse within core networks such as the DMN, SN, and FPCN. By framing neurodegeneration as an active loss of cellular and network “meaning-making”—a collapse of coordinated signal interpretation, triage prioritization, and adaptive response—the review aims to support a more integrative conceptual model. In this context, therapeutic direction may shift from damage containment toward restoring high-dimensional neuronal agency, via strategies that include the following elements: reprogrammable proteome-targeting agents (e.g., PROTACs), engineered autophagy adaptors, CRISPR-based BDNF enhancers, mitochondrial gatekeeping stabilizers, and glial-exosome neuroengineering. This synthesis intends to offer a translational scaffold for viewing neurodegeneration as not only a disorder of accumulation but as a systems-level failure of cellular reasoning—a perspective that may inform future efforts in resilience-based intervention and precision neurorestoration. Full article

The interactions of Fe³⁺ with some ligands (Tranexamic (TXA⁻), Indole-3-acetic (IAA⁻), and Aminomethylphosphonic (AMPA²⁻) acids) of biological and environmental interest were studied. The speciation studies were performed in NaNO_3(aq) and NaCl_(aq) using potentiometric and, only for IAA⁻, spectrophotometric titrations at T = 298.15 K and 0.01 ≤ I/mol dm⁻³ ≤ 1.0. The proposed speciation models are as follows: Fe(TXA)H³⁺, Fe(TXA)₂⁺, Fe(TXA)(OH)⁺, and Fe(TXA)(OH)_2(aq) for TXA⁻; Fe(IAA)²⁺ for IAA⁻; and Fe(AMPA)H₂³⁺, Fe(AMPA)H²⁺, and Fe(AMPA)⁺ for AMPA²⁻. A comparison of logβ for the common FeL species gives logβ_FeIAA = 6.56 and logβ_FeAMPA = 14.84 (at I = 1.00 mol dm⁻³ and T = 298.15 K), suggesting that AMPA²⁻ has a higher complexing ability towards Fe³⁺ than IAA⁻. The dependence on the ionic strength of the formation constants was modeled by means of a Debye–Hückel type equation and the SIT model, whilst the sequestering ability of the investigated ligands towards Fe³⁺ was quantified at various pHs, ionic strengths, and in the different supporting electrolytes by means of an empirical pL_0.5 parameter. To complete this study of the behavior of the different Fe³⁺/ligand systems, various simulations in biological fluids and natural waters were conducted. Full article

Essential oils have enormous versatility as sources of natural fragrances and as active agents in the cosmetic industry. Therefore, the chemical composition and antimicrobial and antioxidant activities of the essential oil from the fresh leaves of Siparuna guianensis A. DC. for cosmetic purposes were analyzed. The GC/MS technique was used to analyze the essential oil and the major constituents found were the sesquiterpenes bicyclogermacrene (32.52%), germacrene D (21.60%), and germacrene B (6.84%) and the monoterpene myrcene (3.66%). The antioxidant activity of the essential oil was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical sequestering method and the assay based on the oxidation of 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS). The antioxidant potential of the essential oil was not evidenced in both tests. In vitro tests showed that the studied essential oil, when combined with the antibiotic ampicillin, demonstrated a synergistic effect against clinically resistant Staphylococcus aureus and XDR S. epidermidis strains and an additive effect against S. pseudointermedius and MDR S. epidermidis. On the other hand, the combination of essential oil with gentamicin resulted in synergism when tested against S. epidermidis and an additive effect when evaluated against XDR S. epidermidis. Topical products formulated on the basis of these results exhibited activity against resistant S. epidermidis, demonstrating that the essential oil can act as a valuable ingredient to restore the efficacy of antibiotics against multidrug-resistant bacteria, in addition to improving the olfactory characteristics of the final product. Full article

Foodborne diseases are one of the most serious problems the food sector has to confront, while questions have been raised concerning the effects of several antimicrobial additives on consumer health. Nisin is a peptide produced primarily by Lactococcus lactis with antimicrobial properties mostly against Gram-positive bacteria. It is generally recognized as safe (GRAS) for use in a wide range of food categories. However, its interaction with components of the food matrix, its susceptibility to proteolytic degradation, or the competitive presence of other components may limit its activity. To enhance its effectiveness against Gram-negative bacteria, its combination with essential oils or other antimicrobial components has been investigated. In addition, its encapsulation in several types of nano-delivery systems has been used to protect nisin from food matrix sequestering while regulating its release. In this review, we present how nisin is utilized, alone or in combination with other antimicrobial agents in a range of emulsion types, as well as the standard techniques for the physicochemical characterization of these systems. Full article