Search Results (281)

Volatile sulfur compounds (VSCs) are a subgroup of plant volatile organic compounds (VOCs) that are chemically reactive and sensory-active. In tomato (Solanum lycopersicum), sulfur-containing volatiles such as methanethiol, dimethyl sulfide, dimethyl disulfide, dimethyl trisulfide, volatile thiols, and heterocyclic sulfur compounds are of particular relevance due to their extremely low odor thresholds and strong influence on aroma perception. Beyond their sensory importance, VSCs have been shown to be involved in plant defense mechanisms, stress responses, redox homeostasis, and multitrophic interactions with microorganisms, herbivores, and neighboring plants. The formation of these structures is governed by complex interactions between sulfur assimilation pathways, lipid peroxidation processes, environmental factors, and both enzymatic and non-enzymatic reactions. The accurate characterization of VSCs remains challenging due to the following factors: their high reactivity; their low abundance; their chemical instability; and their susceptibility to oxidation. Despite the significant enhancement in detection of VSC capabilities brought about by modern analytical approaches, such as gas chromatography coupled with sulfur-selective detection and high-resolution mass spectrometry, significant methodological limitations remain. This review summarizes the current state of knowledge on the analytical challenges of VSCs in tomato plants, their biosynthesis and biological functions, mainly in the context of plant defense. Full article

Background and Objectives: Sarcoidosis is a multisystem inflammatory disorder associated with significant oxidative stress. This study aimed to evaluate dynamic thiol-disulfide homeostasis (TDH)-a systemic redox status indicator-in patients with sarcoidosis. Materials and Methods: This cross-sectional study enrolled 58 sarcoidosis patients (diagnosed via ATS/ERS/WASOG criteria) and 53 healthy controls. Concentrations of native thiol (NT) and total thiol (TT) were determined utilizing an automated spectrophotometric technique. Disulfide (DS) levels and proportional indices were calculated, and the association of TDH parameters with the presence of sarcoidosis (patients vs. healthy controls) was examined using receiver operating characteristic (ROC) and Cohen’s d analysis. Results: Patients exhibited significantly reduced serum NT and TT levels compared to the control group (p = 0.003 and p = 0.009, respectively), whereas DS and the DS/NT ratio were elevated (p = 0.011 and p < 0.001). All parameters showed medium effect sizes. ROC analysis indicated that TDH parameters demonstrate an association with the presence of sarcoidosis, with AUC values ranging from 0.625 to 0.664. Among these, the DS/NT ratio showed the highest observed association with the disease group (AUC = 0.664), yielding 75.8% sensitivity and 60.3% specificity at a 5.7% cut-off. Conclusions: Our findings indicate that TDH is significantly altered in sarcoidosis, reflecting a systemic shift toward an oxidative state. These parameters appear to be exploratory biochemical indicators of systemic redox imbalance. To better understand their involvement in disease pathophysiology, future large-scale, prospective clinical trials might provide further insights. Full article

Ferulic acid (FA) is a phenolic acid mainly present in wheat bran. It has beneficial health effects, but may affect gluten network formation and the processing quality of wheat-based products. This study investigated the interaction mechanisms between FA and glutenin/gliadin in dough and simulated dough systems. The results show that FA’s effects on both proteins were dose and system dependent. In dough, low-dose FA (≤0.3 g) promoted structural loosening of glutenin, as suggested by β-sheet conversion to β-turns/random coil structures, increased t-g-t disulfide and free thiols, and reduced particle size, whereas high doses promoted reaggregation via microenvironment reshaping, hydrophobic enhancement, cross-linking, and subunit rearrangement. For gliadin, low-dose FA may have altered local charge and hydrogen-bonding environments, while high-dose FA increased the hydrogen-bonding proportion by 45.71% and g-g-g conformation by 60.85%, suggesting enhanced molecular aggregation. In simulated dough, FA promoted stronger structural loosening of glutenin but favored gliadin aggregation, indicating that starch, lipids, water distribution, and other dough components may redirect FA–protein interactions. Molecular docking, as a complementary approach, predicted the preferential binding of FA to gliadin, LMW-GS and HMW-GS at different sites. These findings provide a theoretical basis for regulating phenolic acid–gluten interactions in whole-wheat and functional wheat-based products. Full article

Anthraquinone-based intercalating compounds, such as doxorubicin and mitoxantrone, have long been used clinically due to their ability to induce DNA damage. More recently, heteroarene-fused anthraquinones have been developed to further enhance their anticancer activity. Among these compounds, 4,11-bis(2-(2-chloroacetamidine)ethylamino)anthra[2,3-b]thiophene-5,10-dione dihydrochloride (designated as derivative a) was identified as a potent apoptotic inducer. Based on this scaffold, two additional derivatives were synthesized by replacing the sulfur atom within the heterocyclic ring with nitrogen (derivative b) or oxygen (derivative c). Building upon our previous identification of ENOX2 as the primary target of this scaffold, the present study investigated the antiproliferative effects and underlying mechanisms of these derivatives in colon cancer cells with varying p53 statuses. Derivatives a and b effectively induced apoptosis and suppressed proliferation in p53 wild-type HCT116 cells, which was concomitantly accompanied by significant ENOX2 downregulation and the activation of intrinsic apoptotic signaling. In contrast, p53-null HCT116 cells exhibited reduced sensitivity, attenuated apoptotic responses, and minimal ENOX2 downregulation. Notably, derivative c primarily induced G2/M arrest rather than apoptosis regardless of p53 status, indicating a predominantly cytostatic mechanism. Collectively, these findings suggest that the degree of ENOX2 modulation is linked to the distinct anti-proliferative responses induced by heteroarene-fused anthraquinones, and that p53 status serves as a critical molecular switch influencing the transition between cytostatic growth arrest and apoptotic cell death. Full article

Background/Objectives: Fine-needle aspiration biopsy (FNAB) is the primary diagnostic procedure for the evaluation of thyroid nodules. Although considered safe and minimally invasive, its immediate systemic biochemical effects, particularly those related to oxidative stress and mechanical tissue injury, remain insufficiently characterized. This study aimed to evaluate the acute systemic impact of FNAB on oxidative stress parameters and to determine whether these changes correlate with cytological malignancy risk. Methods: A total of 208 patients undergoing ultrasound-guided FNAB for a solitary thyroid nodule were prospectively included. Venous blood samples were collected in the supine position immediately before and within 1 min after the procedure. Thiol–disulfide homeostasis parameters were measured using an automated spectrophotometric method, and ischemia-modified albumin (IMA) levels were analyzed concurrently. Pre- and post-procedural values were compared using the Wilcoxon signed-rank test. Associations between oxidative stress markers and Bethesda cytological categories were assessed using Spearman’s correlation analysis. Results: Native thiol and IMA levels demonstrated statistically significant changes following FNAB, whereas total thiol, disulfide levels, and derived thiol–disulfide ratios remained unchanged. The reduction in IMA levels was predominantly observed in lower-risk cytological categories. No significant correlations were identified between oxidative stress parameters and Bethesda-based malignancy risk. Conclusions: FNAB induces only minor and transient alterations in selected systemic oxidative stress markers, which are clinically inconsequential. The observed changes in native thiol and IMA levels appear to reflect short-term procedural effects rather than malignancy-associated redox alterations. These findings support the systemic safety of FNAB and emphasize the need for careful temporal standardization when interpreting circulating oxidative biomarkers in thyroid nodule research. Full article

Oral mucosal repair is a redox-regulated process that may be impaired by diabetes, chronic inflammation, infection, and chemotherapy- or radiotherapy-induced oral mucositis. Reactive oxygen species (ROS) support host defense, epithelial migration, angiogenesis, extracellular matrix remodeling, and adaptive repair when their production is transient and compartmentalized. In contrast, persistent ROS promote lipid, protein, and DNA oxidation, mitochondrial dysfunction, and extracellular matrix damage. Photobiomodulation (PBM) is increasingly used to support oral tissue repair, but its effects should be interpreted as dose- and context-dependent redox modulation rather than as simple antioxidant activity. This narrative review synthesizes oxidative stress biomarkers and redox-sensitive pathways relevant to oral mucosal repair and PBM, including oxidant–antioxidant balance, lipid and protein oxidation, oxidative DNA damage, antioxidant defense, thiol/disulfide homeostasis, mitochondrial and NADPH oxidase-derived ROS, Nrf2/HO-1, NF-κB, HIF-1α/VEGF, MAPK/ERK, PI3K/Akt, and MMP/TIMP signaling. The review emphasizes the distinction between transient mitochondrial ROS/nitric oxide signaling and sustained NADPH oxidase-driven oxi-inflammatory stress. It proposes a practical redox-guided framework for biomarker selection, PBM response interpretation, and future study design, while noting that this framework remains conceptual and is not yet a validated clinical decision algorithm. Full article

Sponge spicules have emerged as promising biomaterial scaffolds due to their biocompatibility and unique structural properties; however, achieving stable and bioactive functionalization remains a key challenge. The tripeptide GHK is known to promote collagen synthesis and wound repair, yet its therapeutic efficacy is often limited by rapid diffusion and instability. Here, we report ALTUM, a thiol-functionalized sponge spicule composite in which GHK is covalently conjugated via disulfide linkage to enable controlled and redox-responsive peptide delivery. ALTUM exhibited sustained GHK retention under physiological and storage conditions, while exposure to reduced glutathione (GSH) selectively accelerated peptide release through disulfide bond cleavage. This dual release behavior—long-term stability combined with reduction-triggered activation—distinguishes ALTUM from conventional delivery systems. The composite also demonstrated structural stability under thermal, cyclic, and photostability conditions. In an artificial human skin model, ALTUM enhanced dermal penetration of GHK and significantly increased collagen deposition in the dermal layer, demonstrating its capacity to promote collagen production within deeper skin tissue, compared to simple spicule–peptide mixtures. ALTUM was fabricated at an optimized spicule-to-peptide ratio of 3% (w/w), preserving the needle-shaped spicule morphology after surface modification. In vitro, ALTUM exhibited a sustained release profile, with GHK release markedly accelerated in the presence of 10 mM glutathione (GSH) compared with non-reductive conditions, reaching approximately 60% cumulative release over 35 days. In the bioprinted artificial human skin model, ALTUM delivered 9.72 ng/cm² of GHK, more than five-fold higher than the physical mixture of spicules and free GHK (1.9 ng/cm²), and significantly increased type I collagen expression in human dermal fibroblasts. Mechanistically, ALTUM-mediated delivery was associated with increased TGF-β expression and engagement of the SMAD signaling pathway, as indicated by increased phosphorylation of SMAD2/3, consistent with involvement of the TGF-β–SMAD axis in the observed collagen induction. Collectively, these findings establish ALTUM as a structurally stable, redox-responsive dermal delivery platform that enhances collagen synthesis and skin regeneration. Full article

Reactivity of non-aromatic 2,5-dichloro-2H-pyrroles toward S-nucleophiles was investigated. It was found that these non-aromatic derivatives exhibit both oxidative and electrophilic properties. Their reaction with thiols and xanthates proceeds as redox process to form disulfides and 5-chlorinated pyrroles as a result of 2,5-dichloro-2H-pyrroles reduction. However, the reaction with ammonium thiocyanate afforded the corresponding 5-thiocyanated 1H-pyrroles. Based on these findings, a novel one-pot method for the thiocyanation of 2,3,4-trisubstituted pyrroles was developed. The protocol involves the in situ generation of highly reactive 2,5-dichloro-2H-pyrroles via dearomative chlorination of the corresponding pyrroles using trichloroisocyanuric acid (TCCA). Subsequent addition of ammonium thiocyanate leads to regioselective incorporation of a thiocyanate group at the C5 position and rearomatization of the pyrrole core. A broad scope of pyrrole-5-thiocyanates was obtained in yields up to 82%. Furthermore, these derivatives were efficiently transformed into 5-trifluoromethylthiolated pyrroles using Ruppert’s reagent in up to 94% yield. This reaction sequence provides a cost-effective way to obtain 5-trifluoromethylthiolated pyrroles, avoiding the need for high-cost electrophilic reagents. The synthetic utility of these novel sulfur-containing pyrrole derivatives was also demonstrated. Full article

Background: Response to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) varies considerably, and oxidative stress may modulate radiosensitivity. This study evaluated ischemia-modified albumin (IMA) and thiol–disulfide homeostasis as potential biochemical predictors of pathological tumor regression. Methods: A prospective observational cohort study was conducted to assess pre- and post-treatment oxidative stress biomarkers in patients with LARC receiving capecitabine-based long-course CRT. Serum IMA, native thiol, total thiol, and disulfide levels were quantified spectrophotometrically. Pathologic regression was graded according to the Modified Ryan system as good (TRG 0–1) or poor (TRG 2–3). Receiver operating characteristic (ROC) analyses, Firth-penalized logistic regression, and internal validation using cross-validation, calibration, and decision-curve analyses were performed. Results: Of 38 screened patients, 31 met eligibility criteria and completed CRT, alongside 31 matched healthy controls. Compared with controls, patients had higher baseline disulfide (15.7 ± 5.2 vs. 11.9 ± 3.1 µmol/L; p = 0.012) and IMA levels (0.886 ± 0.062 vs. 0.798 ± 0.048 ABSU; p = 0.006). Poor responders exhibited higher pre-treatment IMA (0.927 ± 0.045 vs. 0.842 ± 0.050 ABSU; p = 0.020) and disulfide levels (18.4 ± 5.2 vs. 13.0 ± 3.8 µmol/L; p = 0.012). Pre-treatment IMA demonstrated the highest predictive accuracy for poor tumor regression (AUC = 0.872; 95% CI 0.751–0.993). In multivariable Firth-penalized logistic regression, elevated baseline IMA was independently associated with poor pathological response (OR = 3.63; 95% CI 1.22–16.20; p = 0.043), whereas negative circumferential resection margin (CRM) status was independently associated with favorable regression (OR = 0.21; 95% CI 0.02–0.71; p = 0.003). The internally validated model demonstrated excellent discrimination (AUC = 0.948; 95% CI 0.866–0.966) and good calibration. Conclusions: Baseline IMA and CRM status were independently associated with pathological response after CRT in LARC. These findings suggest that oxidative-stress biomarkers may have potential value for response stratification; however, the results should be considered exploratory and require external validation in larger independent cohorts before clinical application. Full article

While the pathological impact of reactive oxygen species (ROS) in the aetiology of human infertility has received much attention, this review explores the counterproposal that these highly reactive metabolites play a positive role in mediating reproductive success. The physiological importance of ROS in biological systems can be distilled into three main categories of influence: (1) ROS can oxidize thiols to generate either the corresponding sulfenic acid or disulfide bridges. This oxidizing capacity is critical for several reproductive processes, including the cross linking of sperm chromatin during epididymal maturation, formation of the mitochondrial sheath, and the activation of proteolytic zymogens involved in such processes as ovulation, menstruation, implantation, and parturition. Thiol oxidation is also involved in the suppression of phosphatase activity and the resulting promotion of phosphorylation-dependent signal transduction pathways, which are involved in virtually every aspect of reproduction from sperm capacitation to parturition; (2) The destructive properties of ROS are also biologically significant in the defence against genital tract infections and in mediating such processes as autophagy, apoptosis, and ferroptosis, which are fundamental to the reproductive process; (3) Finally, ROS are involved in controlling the redox status of transition metals (particularly iron and copper) in the active site of many enzymes that are of fundamental importance to reproduction. Given the biological importance of ROS to procreation, we should use antioxidants with care in managing both male and female infertility and avoid the induction of reductive stress. Full article

Background: This pilot study examined whether oxidative–nitrosative stress is associated with clinical status in amyotrophic lateral sclerosis (ALS). We analyzed associations between plasma markers of oxidative–nitrosative imbalance and ALSFRS–R, disease duration, survival, and routine biochemical parameters. Methods: Twenty-nine ALS patients fulfilling the Gold Coast diagnostic criteria were enrolled. Plasma levels of 3-nitrotyrosine (3–NT), 8-oxo-2′-deoxyguanosine (8–oxodG), malondialdehyde (MDA), glutathione (GSH), non-protein thiols (NP–SH), and non-protein disulfides (NP–SS–NP), as well as creatinine, urea, uric acid and BMI, were measured. Associations with ALSFRS–R and disease duration were evaluated using non-parametric correlation analyses and second-order polynomial regression (adjusted R²), while survival was explored using Kaplan–Meier analysis and multivariable Cox regression. Given the modest sample, we considered statistical power and applied Benjamini–Hochberg false discovery rate (FDR) correction within marker families. Results: At the uncorrected significance level, 3–NT showed a positive correlation with ALSFRS–R and a negative correlation with disease duration, and NP–SH correlated negatively with disease duration; however, these associations did not remain significant after FDR correction (FDR-adjusted p ≥ 0.099). Other oxidative–nitrosative markers and biochemical parameters showed no robust relationships with clinical measures. In Cox models, 3–NT was not significantly associated with survival (HR 3.44 per 1 nM, 95% CI 0.25–47.97, p = 0.358), whereas older age predicted higher mortality (HR 1.05 per year, 95% CI 1.00–1.10, p = 0.036). Conclusions: 3–NT and NP–SH exhibited the strongest trends among the investigated markers, but their clinical associations in this small cross-sectional cohort remain exploratory and require confirmation in larger longitudinal studies. Full article

Infertility is a global health problem, with male factors contributing to nearly half of all cases. Up to 30% of male infertility is classified as idiopathic, in part because routine semen analysis does not assess sperm fertilizing competence. Capacitation is a complex process that endows spermatozoa with the competence to fertilize the oocyte, and it depends on oxidant-driven phosphorylation events. These events include increased PKA substrate and tyrosine phosphorylation, which promote hyperactivated motility and the acrosome reaction. These pathways are normally restrained by decapacitation factors that must be relieved in the female reproductive tract before capacitation can proceed. Protein CoAlation is an antioxidant modification of protein thiols through a disulfide bond with coenzyme A (CoASH). We previously detected protein CoAlation in human spermatozoa and observed that its levels decline during capacitation, but its function was unknown. We hypothesized that protein CoAlation functions as a decapacitation mechanism that prevents redox signalling, enabling oxidative activation of phosphorylation events during capacitation. Using spermatozoa from healthy human donors, we leveraged subcellular fractionation, immunocytochemistry, computer-assisted sperm analysis (CASA), and immunoblotting to determine the sperm protein CoAlation profile, assess CoASH biosynthetic enzymes, and test how pharmacological modulation of CoAlation levels influences capacitation. CoAlated proteins were distributed across intracellular sperm compartments, and spermatozoa possess the CoASH biosynthetic enzymes PANK2 and CoASY, indicating an intrinsic capacity for CoAlation. Inhibition of CoASH biosynthesis reduced CoAlation and enhanced PKA substrate phosphorylation, tyrosine phosphorylation, hyperactivated motility, and the progesterone-induced acrosome reaction under capacitating conditions. Pantothenic acid supplementation increased CoAlation and suppressed these processes without impairing viability or baseline motility. These findings indicate that high levels of protein CoAlation in several protein bands are a pre-existing feature of the non-capacitated state that restrains the redox-regulated events of capacitation and that its decline is required to permit sperm capacitation. CoAlation levels may emerge as a biomarker of sperm capacitation and fertilizing competence. Full article

Refined wheat staple foods are widely criticized for low dietary fiber and high postprandial glycemic response, making soluble dietary fiber fortification a promising strategy for cereal improvement. This study investigated how resistant dextrin (RD) modulates wheat starch, gluten, dough, and bread quality through multiscale interactions. In wheat starch, 6% RD gave the best overall balance, reducing 14-day retrogradation from 57.2% to 48.6%, delaying gelatinization, and restricting amylose diffusion, with hydrogen bonding identified as a major contributing interaction. In gluten, RD increased water-holding capacity but weakened network integrity, as evidenced by reduced moduli, a shift in thiol–disulfide balance, secondary-structure redistribution (increased β-sheet, decreased α-helix/β-turn), and suppressed glutenin polymerization, yielding a looser microstructure. In dough, SEM and rheological results suggested that moderate RD (4–6%) may form a hydrated, polysaccharide-rich phase that fills structural voids and improves matrix continuity, partially offsetting gluten weakening and enhancing viscoelasticity. Overall, this study establishes a quantitative relationship between RD addition level, multiscale macromolecular interactions in wheat matrices, and the processing performance and quality of bakery products. Full article

Muco-obstructive lung diseases, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and bronchiectasis, are characterized by the accumulation of highly viscoelastic mucus that compromises mucociliary clearance and fosters infection and inflammation. Mucoactive therapy, encompassing both true mucolytics and non-cleaving agents, seeks to restore airway patency by altering mucus structure, hydration, and transport properties, yet its clinical impact remains variable. This narrative review provides a critical reappraisal of the pharmacological actions and therapeutic outcomes of the main mucolytic agents: N-acetylcysteine (NAC), erdosteine, carbocisteine, bromhexine, ambroxol, and dornase alfa. Beyond their classical role in reducing mucus viscosity, these drugs exhibit pleiotropic effects, including antioxidant, anti-inflammatory, and immunomodulatory activities. Specifically, for thiol-based compounds, the action consists of breaking the disulfide bonds that stabilize the mucin network; for carbocisteine, it lies in modulating mucin glycosylation and chloride transport. Ambroxol and bromhexine act by stimulating surfactant secretion and enhancing mucociliary clearance. Finally, dornase alfa exerts an enzymatic effect on extracellular DNA, a key contributor to the tenacity of mucus in cystic fibrosis. Clinical evidence indicates that NAC and erdosteine can reduce exacerbation rates in COPD, carbocisteine shows benefit with prolonged administration, and dornase alfa remains a cornerstone in CF management. However, therapeutic efficacy is constrained by heterogeneous mucus composition, pharmacokinetic limitations, and disease-specific variability. A key interpretative message is that clinical benefit appears greatest when the dominant biophysical determinant of mucus pathology is specifically targeted, supporting a transition from broad disease-label prescribing to mechanism-informed, phenotype-aware mucolytic therapy. Emerging strategies, such as agents targeting mucin–DNA interactions and advanced inhalation delivery systems, promise improved specificity and durability. By integrating mechanistic insights with clinical data, this review underscores the need for personalized mucolytic therapy and innovative approaches to overcome current challenges in managing muco-obstructive lung diseases. Full article

Antiretroviral therapy (ART) effectively controls Human Immunodeficiency Virus Type-1 (HIV-1) infection in people with HIV-1 (PWH), preventing the progression of their infections to AIDS. However, as PWH age, they experience lifestyle- and age-related diseases, notably various types of cancer beyond those traditionally associated with AIDS, with greater incidence and mortality than their non-HIV-1-positive counterparts, despite effective arrest of HIV-1 infection by ART. Dysregulation of redox enzymes presents an underexplored linkage between HIV-1 infection and cancer comorbidity, impacting reactive oxygen/nitrogen species (RONS) management, inflammation, immune function, and mitochondrial function. Chronic HIV-1 infection increases both RONS production and RONS neutralization responses, accelerating development of a sustained RONS-rich environment that still possesses sufficient dampening to prevent outright cytotoxic effects. Such an environment promotes both tumor proliferation and resistance adaptations to chemo- and radiotherapies. This review considers the effects of chronic HIV-1 infection on redox enzyme function and links these effects to tumorigenic mechanisms as potentially shared pathways. We then examine current methods of modulating redox function, consider how these could potentially impact both HIV-1 infection and cancer progression, and lastly propose future methods of co-treatment that could be explored. Full article