Search Results (11,903)

Background/Objectives: Ultraviolet (UV) radiation is a major environmental carcinogen responsible for skin damage through oxidative stress, DNA damage, and inflammation. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a central role in regulating cellular antioxidant defences against UV-induced damage. This scoping review aims to evaluate the potential role of sulforaphane (SFN), a known Nrf2 inducer, in protecting against UV-induced skin damage and photocarcinogenesis. Methods: A literature search was conducted in PubMed and Scopus from inception to 27 January 2026, to identify original experimental studies investigating SFN, glucoraphanin, or broccoli sprout extracts in the context of UV-induced skin damage. Eligible studies included in vitro, ex vivo, in vivo, and human models assessing outcomes related to oxidative stress, inflammation, molecular signalling pathways, and tumour development. Following screening and eligibility assessment, twelve studies were included in the qualitative synthesis. Results: The included studies suggest that SFN exerts photoprotective effects across multiple experimental models. In murine studies, SFN and SFN-rich extracts were associated with a reduction in tumour incidence, multiplicity, and volume following UV exposure. In human studies, topical SFN application reduced UV-induced erythema and induced cytoprotective enzyme expression, although clinical evidence remains limited. Mechanistically, SFN consistently activated the Nrf2 pathway, leading to increased expression of antioxidant and phase II detoxifying enzymes, and was associated with modulation of inflammatory responses and inhibition of MAPK/AP-1 signalling. Emerging evidence also indicates potential effects on UV-induced metabolic and epigenetic alterations. Conclusions: Current evidence supports a potential role for sulforaphane in mitigating UV-induced skin damage through activation of endogenous defence pathways. However, the available data are predominantly preclinical, and further well-designed clinical studies are needed to clarify its efficacy and translational relevance in humans. Full article

Metronidazole is an antibiotic used to treat Helicobacter pylori, a bacterium responsible for chronic infections in humans that cause gastric inflammation, ulcers, and cancer. However, its long-term administration is limited by toxicity and increased resistance. In the search for more effective agents against H. pylori infection, molecular hybridization has now been applied to the synthesis of the new compound 3. Its structure connects the metronidazole moiety to pectolinarigenin, the latter obtained by acid hydrolysis of glycosylated flavonoids isolated from the plant Linaria reflexa Desf. The NOE effect supported the C-7 functionalization of 3, as evidenced by the energy-minimized DFT-calculated structure. The new molecule enriches the chemical space of known metronidazole–flavonoid analogs, among which the genistein derivative 2 was reported as the most active in inhibiting bacterial strains. The computational analysis of 2 and 3 compared with metronidazole as the reference has provided favorable data for both Absorption, Distribution, Metabolism, and Excretion (ADME) predictions and the probability of anti-H. pylori activity, besides rising docking evaluation on three specific targets and dynamics simulation as inhibitors of the flavodoxin enzyme. The results are promising for further in-depth biological investigation. Full article

Salivary aldehyde dehydrogenases (ALDHs), particularly ALDH3A1, are increasingly recognized as potential contributors to oral defense against aldehyde-associated stress at the oral–environment interface. Unlike freely secreted salivary enzymes, measurable salivary ALDH activity primarily reflects intracellular and vesicle-associated enzymes derived from salivary gland epithelial cells, oral mucosal cells, immune cells, and exfoliated cellular components. Within the oral exposome, ALDHs expressed in oral epithelial and salivary gland tissues participate in the detoxification of reactive aldehydes, while salivary ALDH activity may serve as an indicator of local aldehyde-detoxification capacity and tissue redox status. Beyond aldehyde metabolism, emerging evidence suggests that ALDH-associated pathways are linked to redox regulation, epithelial stress adaptation, inflammatory signaling, and tissue repair through NAD(P)⁺-dependent processes and stress-responsive networks such as Nrf2 and SIRT1. This review provides a saliva-focused synthesis of ALDH biology, emphasizing isoform-specific functions and the potential importance of ALDH3A1 in oral epithelial defense. Altered salivary ALDH activity has been reported in association with oral conditions including periodontitis, oral lichen planus, radiation-induced salivary dysfunction, and oral squamous cell carcinoma (OSCC). Genetic factors, particularly ALDH2 polymorphisms, together with environmental exposures and microbial dysbiosis, may further influence aldehyde burden and oral disease susceptibility. Although current evidence supports the biological relevance of salivary ALDHs, their utility as clinical biomarkers or therapeutic targets remains investigational and requires further mechanistic and clinical validation. Full article

Gao-shan-hong-jing-tian (GSHJT) Oral Liquid is a phytochemical-rich preparation derived from Rhodiola, yet its anti-hypoxic active constituents and molecular mechanisms remain poorly understood. This study aimed to identify the key anti-hypoxic phytochemicals in GSHJT Oral Liquid and clarify their mechanisms of action to support its potential use in managing acute mountain sickness (AMS). We first established and validated an HPLC method for quality control, then comprehensively profiled the chemical composition using LC-MS. Network pharmacology and molecular docking were applied to predict the core anti-hypoxic components, candidate targets and signaling pathways. The primary bioactivity was further verified through an in vitro carbonic anhydrase (CA) inhibition assay. A total of 71 constituents were identified, with kaempferol and ellagic acid emerging as the primary anti-hypoxic phytochemicals. These compounds target seven core proteins (SRC, PIK3R1, ESR1, EGFR, PTK2, IGF1R, and LYN) to regulate vascular tone, inflammation, oxidative stress, blood–brain barrier integrity, and cell survival under hypoxic conditions. By modulating pathways such as HIF-1α, PI3K/AKT, FAK/PTK2, SRC, and IGF1R, these phytochemicals ultimately influence the onset and alleviation of AMS. Enzyme inhibition assays demonstrated that kaempferol and ellagic acid inhibited CA with IC₅₀ values of 34.05 μM and 119.1 μM, respectively. Molecular docking further revealed that both compounds suppressed CA activity through a combination of hydrogen bonding and hydrophobic interactions, consistent with a zinc-bound water-anchoring mechanism. This study elucidates the phytochemical basis and molecular mechanism responsible for the anti-hypoxic effects of GSHJT Oral Liquid, providing scientific support for its potential application as a natural, plant-derived intervention for preventing and alleviating acute mountain sickness, providing scientific support for its potential application and offering a reproducible paradigm for the rational development of other Rhodiola-based phytomedicines, though further in vivo validation is required to confirm the anti-hypoxic efficacy. Full article

Efficient delivery systems are essential for transporting chemotherapeutic agents to target sites, enhancing cellular uptake and reducing off-target side effects. Peptides, owing to their intrinsic biocompatibility and structural tunability, have emerged as promising carriers for delivering labile chemotherapeutics and improving pharmacokinetics and therapeutic outcomes. Along these lines, a wide variety of peptide-based delivery strategies have been developed to achieve desirable pharmaceutical properties for anticancer agents. Particularly, stimuli-responsive peptide-based nanocarriers have attracted high levels of attention due to their ability to exploit overexpressed or tumor-specific stimuli, enabling selective disassembly and controlled drug release within cancer cells. In this review, we highlight recent advances in the development of stimuli-responsive peptide nanocarriers and their applications in anticancer therapy, and discuss key challenges and future directions toward their clinical translation. Full article

Excessive chemical fertilization in maize production has reduced fertilizer-use efficiency and increased pressure on soil quality, whereas reducing fertilizer input without yield loss remains challenging. This challenge has shifted attention toward strategies that improve crop nutrient acquisition and utilization under lower fertilizer supply. Harpin protein-based enzyme complexes may provide a regulatory approach, but their field performance under reduced fertilization remains unclear. A two-year field experiment was conducted from 2023 to 2024 using two maize cultivars, Heyu236 and Fuyuan2. In 2023, the harpin protein-based enzyme complex was applied at 200-fold and 300-fold dilutions under conventional fertilization to identify effective spraying concentrations. In 2024, the same two concentrations were evaluated under conventional fertilization and 15%, 30%, and 45% fertilizer reductions. In the 2023 concentration screening trial under conventional fertilization, the enzyme complex increased kernels per ear by 5.6–9.7% and tended to increase the yield by 0.4–17.2% (not significant). In 2024, under reduced fertilization, enzyme application combined with 30% fertilizer reduction produced a stable yield response. In particular, the 300-fold dilution combined with 30% fertilizer reduction increased kernels per ear by 18.1% and 13.2% and grain yield by 16.9% and 9.5% in Fuyuan2 and Heyu 236, respectively. Soil analyses showed that the enzyme treatment mainly improved nutrient availability, as reflected by higher available P, available K, alkali-hydrolyzable N, organic matter, and available Cu, Zn, Fe, and Mn in the soil. These findings suggest that the harpin protein-based enzyme complex helped maintain maize yield under moderate fertilizer reduction by improving kernel formation and soil nutrient availability. Among the tested treatments, foliar application at 300-fold dilution combined with 30% fertilizer reduction showed the greatest potential for reducing fertilizer input while sustaining maize productivity. Full article

Mediterranean regions are forecasted to be increasingly threatened by climate change, leading to the occurrence of extreme events. One strategy to improve the resilience of agricultural systems is to introduce rotations that combine legumes and crops with high intraspecific diversity such as evolutionary populations (EPs). These cropping systems may be characterized by lower external input needs and higher buffering capacity than traditional ones. Our objective was to test if the introduction of wheat EPs impacts soil microbial functions—including microbial biomass, community structure, and enzymatic activity—and soil organic matter composition within a crop rotation framework. We conducted a two-year field experiment at two sites in Italy comparing a modern bread wheat variety to two EPs, evolved in different areas, in rotation with legumes. The composition and processes of rhizosphere microbial communities were characterized using EL-FAME and enzyme activities. In addition, rhizosphere soil organic matter signatures were measured by mid-infrared spectroscopy, and their relationships with microbial parameters were investigated using principal component analyses. The results showed that the EP–rhizosphere relationship, as well as its influence on microbial abundance and activity, is dependent both on the site of origin and local pedoclimatic conditions, although no consistent response was observed across the two sites. These effects may be buffered by the choice of the preceding crop in rotation. Full article

Cancer cells, like yeast, use fermentation despite the presence of oxygen, a phenomenon called aerobic glycolysis. The advantage is that it maintains many C-C bonds of glucose, allowing highly proliferating cells to produce the biomolecules that are necessary for cytokinesis. However, aerobic glycolysis is less energy-efficient than respiration, and it must operate at high frequency and produces large amounts of lactate, which modifies and stimulates DNA repair enzymes via lysine lactylation. This makes cancer cells resistant to radiotherapy, which requires a combination with chemotherapy using drugs that inhibit DNA repair. However, this converts healthy cells to cancer cells, indicating that research is still required regarding the relationship between glycolysis and cancer. Using yeast as a model, we discovered that the glycolytic enzymes TPI and GAPDH (Tpi1p and Tdh1-3p in yeast) interact with the DNA damage-dependent Checkpoint Rad9p (53BP1/BRCA1/MDC1 in humans). We propose that Tpi1p and Tdh1-3p override Rad9p, allowing cells with damaged DNA to proliferate. We isolated tpi and gapdh mutant strains that are deficient in DNA repair. While the tpi mutant strain has lower enzymatic activity, the gapdh mutant strains have normal enzymatic activity, confirming previous reports that GAPDH moonlights in the DNA damage response. Full article

Studies aimed at identifying genotypes tolerant to water deficit are essential for the development of superior plant materials adapted to regions with limited water availability, such as the Brazilian Semi-Arid. This study evaluated the physiological, biochemical, and enzymatic responses of Stylosanthes spp. subjected to different levels of water availability (60%, 40%, and 20% of pot capacity). The experiment was conducted using a completely randomized design using a 3 × 2 factorial scheme, comparing the accession BGF 11-001 and the cultivar BRS-Bela (cv. Bela). Physiological traits, biochemical variables, and antioxidant enzyme activity were analyzed. The accession BGF 11-001 showed resilience under water deficit, maintaining high chlorophyll content even under severe stress. This response was associated with increased accumulation of amino acids such as proline, as well as enhanced antioxidant activity, indicating a tolerance mechanism based on osmotic adjustment and cellular protection. In contrast, cv. Bela exhibited higher sensitivity to water stress, with a pronounced reduction in photosynthetic pigments and greater accumulation of compatible solutes, including total soluble proteins, reducing sugars, amino acids, and proline, without significant activation of antioxidant enzymes. Overall, the results demonstrate that the genotypes adopt distinct strategies to cope with water stress, with BGF 11-001 being more efficient in activating defense mechanisms. Therefore, BGF 11-001 has agronomic potential for cultivation in drought-prone regions and is a promising genetic resource for forage breeding programs aimed at improving drought tolerance. Full article

N-hydroxypipecolic acid (NHP) is a key mobile signal in systemic acquired resistance in plants, and its glycosylation has been proposed to regulate immune signaling. Previous studies have demonstrated that the UDP-glycosyltransferase UGT76B1, known as an SA glycosyltransferase in Arabidopsis thaliana, also catalyzes NHP glycosylation. In this study, we re-evaluated NHP glycosylation activity of UGT76B1 using an in vitro enzyme-coupled fluorescence assay that quantitatively detects UDP released during UDP-sugar-dependent glycosylation. Unexpectedly, our biochemical analyses demonstrated that UGT76B1 lacks genuine glycosylation activity toward NHP under the in vitro assay conditions tested, although this system clearly detected UGT76B1 activity toward salicylic acid (SA), as well as the activities of UGT74F1 and UGT72B1 toward SA and hydroquinone, respectively. To explore potential UGTs responsible for NHP glycosylation, we evaluated the enzymatic activities of 41 UGT candidates successfully expressed in Escherichia coli, which are selected based on transcriptomic responses to tenoxicam treatment, molecular docking simulations using AlphaFold3/AutoDock Vina, phylogenetic criteria, and previous reports. Within this selected and successfully expressed UGT panel, none exhibited authentic NHP glycosylation activity, although this does not preclude the possibility that other members of the Arabidopsis UGT family possess NHP glycosyltransferase activity. Our findings challenge the prevailing view that UGT76B1 is the primary glycosyltransferase for NHP in A. thaliana and indicate that NHP metabolism may rely on undiscovered non-canonical enzymes or distinct metabolic pathways that warrant further investigation. Full article

The sustainable production of yellow catfish (Pelteobagrus fulvidraco) fry is critical for aquaculture, yet early developmental stages face high mortality and nutritional challenges. This study evaluated the effects of dietary supplementation with broken-cell wall P. rhodozyma on growth performance, organ development, enzyme activities, and gut microbiota composition in yellow catfish fry. Dietary supplementation with broken-cell wall P. rhodozyma significantly improved fry performance, increasing survival from 12% to 52%, promoting growth, enhancing intestinal and liver development, improving digestive enzyme activities, and modulating antioxidant-related physiological responses. It also elevated beneficial Muribaculum and reduced Streptococcus in the gut, promoting microbiota stability. These results demonstrate that P. rhodozyma supplementation not only improves early growth, organ maturation, stress resistance, and intestinal health but also effectively enhances overall fry health and development, thus supporting its use as a functional feed additive in aquaculture. Full article

Background: Although prolonged inflammatory symptoms are an infrequent and problematic adverse effect of vaccination that can occur in some people, the transient activation of acute phase reactants (APRs) is expected with adjuvanted vaccines and helps to potentiate immune responses. Methods: This experiment examined the association between vaccine reactogenicity and immunogenicity in monkeys immunized with an adjuvanted recombinant protein including a receptor binding domain–human IgG1-Fc fusion protein (RBD-Fc) sequenced from the ancestral Wuhan strain of SARS-CoV-2. The acute inflammatory reaction to immunization was assessed by determining the decline in serum iron levels at 24 h and the increase in the neutrophil-to-lymphocyte ratio (NLR) as the adherent neutrophil pool trafficked into circulation. Results: Robust primary and secondary antibody responses were elicited. Larger decreases in serum iron and higher NLRs were associated with a stronger inhibition of RBD binding with angiotensin-converting enzyme (ACE2) when five early viral variants of SARS-CoV-2 were tested, including Wuhan, Alpha, Beta, Gamma and Delta. Inhibition of ACE2-RBD binding was less evident when the Omicron variant was tested. Individual variation in the APR was also predictive of the persistence of cell-mediated immunity based on the number of interferon-expressing mononuclear cells activated by viral antigen in ELISpot assays. Conclusions: Rapid antibody responses to primary immunization and large secondary responses to booster immunizations were elicited by this adjuvanted recombinant RBD-Fc vaccine, and our analysis affirmed the view that a transient APR can enhance antibody binding with antigen proteins. Full article

Sweet sorghum, a high-quality forage and energy crop, is significantly affected by drought, the primary abiotic stress impacting its growth. Melatonin (MT) has emerged as a crucial signaling molecule in plant responses to abiotic stress. This study investigates the role of melatonin in enhancing drought tolerance in sweet sorghum, specifically using the ‘Dali Shi’ variety under polyethylene glycol (PEG)-induced drought conditions. Our findings demonstrate that exogenous melatonin application significantly increased proline content (by 27.76% and 5.95% under mild and moderate drought, respectively) while decreasing malondialdehyde (MDA) levels (by 18.33% and 35.18%, respectively). Melatonin also enhanced the accumulation of photosynthetic pigments, including chlorophyll b and total chlorophyll, and improved photosynthetic fluorescence parameters (Fv/Fm and ETR). Additionally, melatonin treatment improved root vitality, stimulated carbon and nitrogen metabolism, and increased antioxidant enzyme activity. Transcriptomic analysis revealed that differentially expressed genes were enriched in pathways related to carbon fixation, glycolysis/gluconeogenesis, nitrogen metabolism, antioxidant defense, and plant hormone signaling. Notably, melatonin upregulated key genes associated with these pathways and activated bHLH and MYB transcription factors. In conclusion, this study elucidates the mechanisms by which melatonin enhances sweet sorghum’s drought tolerance, highlighting its potential as a practical approach for improving drought resistance in this crop. Full article

Nitrogen (N) fertilization is a fundamental agronomic practice that governs crop productivity, yet its effects on the molecular composition and chemical stability of soil organic carbon (SOC) remain poorly understood, especially in cereal–legume intercropping systems. Traditional studies have focused on total SOC stocks rather than molecular-level changes, and the mechanistic pathway linking N addition to SOC functional group transformation remains unclear. This study addressed these critical gaps by investigating how graded N addition (0, 180, 270, and 360 kg N ha⁻¹) reshapes SOC chemistry in a subtropical soybean–maize intercropping system. Soil physicochemical properties, inorganic N pools, N-transformation enzyme activities (urease, nitrate reductase, and glutaminase), microbial biomass indices, labile organic carbon fractions (particulate, mineral-associated, and dissolved organic carbon), and SOC functional groups characterized by Fourier transform infrared (FTIR) spectroscopy were quantified across a two-year field experiment (2024–2025). Results showed that increasing N rates significantly elevated nitrate nitrogen (NO₃⁻-N) accumulation while depressing soil pH. Nitrogen-transformation enzymes, especially nitrate reductase and glutaminase, responded strongly and positively to the N gradient. Microbial biomass carbon (MBC) and nitrogen (MBN) increased with moderate N input but exhibited saturation or decline at 360 kg N ha⁻¹, accompanied by reduced microbial carbon use efficiency (CUE) and a lower MBC/MBN ratio. Among labile carbon fractions, dissolved organic carbon (DOC) was the most responsive pool, increasing markedly with N addition and correlating strongly with NO₃⁻-N. FTIR analysis revealed that N addition shifted SOC functional group composition toward chemically recalcitrant structures: the relative abundances of aromatic C=C and carbonyl C=O groups increased significantly, whereas labile C–O groups declined. Random forest modelling identified C=C, NO₃⁻-N, and DOC as the three most influential predictors of SOC chemical composition. Structural equation modelling (SEM) demonstrated a sequential mechanistic pathway: N fertilization increased NO₃⁻-N, which stimulated glutaminase activity and enhanced DOC, ultimately promoting C=C/C=O stabilization and explaining 91.3% of the variance in SOC aromaticity. These findings reveal that N addition does not merely augment SOC quantity but fundamentally transforms its molecular architecture toward greater chemical stability through a nitrate-mediated, enzyme–labile carbon coupling mechanism. This study provides a novel spectroscopic–mechanistic framework for understanding carbon–nitrogen interactions in intercropping agroecosystems and informs precision N management strategies aimed at simultaneous crop production and long-term soil carbon sequestration. Full article

Camptotheca acuminata, the primary botanical source of camptothecin (CPT), employs this monoterpenoid indole alkaloid as a key chemical defense against herbivores in addition to its established clinical pharmaceutical importance. Given that Spodoptera frugiperda infestations pose a severe threat to C. acuminata seedlings, we examined integrated, multi-layered defense mechanisms that combine physical barriers with chemical toxins to bolster plant resistance. Physiological analyses revealed that herbivory induces antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), alongside broader metabolic reprogramming. These responses are orchestrated by differential activation of jasmonic acid (JA) and salicylic acid (SA) signaling pathways, which together drive complex defense mobilization, including a marked increase in trichome density. Concurrently, insect herbivory activates the MYB-bHLH-WD40 (MBW) transcriptional complex to promote trichome development while upregulating core CPT biosynthetic genes. In particular, two cytochrome P450 genes, Ca32236 and CaCYP81BQ18, mediate the accumulation of 10-hydroxycamptothecin (10-HCPT), a derivative that is sparingly soluble in water, which enables alkaloid transport and sequestration to specialized storage sites, including trichomes. Collectively, these stress-responsive strategies confer potent insecticidal activity against S. frugiperda and provide valuable insights for improving protection in C. acuminata seedling plantations. Full article