The high-osmolarity glycerol (HOG) signalling pathway, comprising Ste11/Ssk2/Ssk22 (MAPKKK), Pbs2 (MAPKK), and Hog1 (MAPK), is an important and conserved pathway in fungi. However, the functions and downstream regulatory factors of Hog1 in nematode-trapping (NT) fungi remain poorly understood. Here, three proteins (AoNmd5, AoPyp1, and AoPtp) interacting with Hog1 were screened in a representative NT fungus Arthrobotrys oligospora using yeast screening library and verified using yeast two-hybrid (Y2H) assay. The function of AoNmd5 was furtherly characterized by phenotypic comparison, staining technique, and multi-omics analyses. AoNmd5 was essential for vegetative growth, conidial development, trap morphogenesis, and nematode predation ability. In addition, AoNmd5 played crucial roles in endocytosis, lipid metabolism, reactive oxygen species, stress response, autophagy, and other metabolic processes. Furthermore, we constructed an AoNmd5 interaction network based on transcriptomic analysis and Y2H, revealing its significant role in the respiratory chain and redox processes as well as its interaction with the small GTPase Ran1, which mediates Hog1 nucleocytoplasmic shuttling. These findings suggest that the Hog1-Nmd5 signalling pathway has pleiotropic roles in A. oligospora. This study deepens our understanding of the HOG pathway and its interaction with importins in NT fungi.

In areas impacted by mining activities, waste rich in heavy metals can contaminate water bodies and aquatic biota. Metal contamination is related to several pathological triggers in key organ such as the liver. The objective of the work was to evaluate the effects of mining waste on the liver of fish species Psalidodon rivularis. For this, 57 specimens were collected in a reference stream (S1), without contamination by mining waste, and an impacted stream (S2), located downstream iron ore mines and six associated tailings dams, southeastern Brazil. Liver samples were collected and subjected to morphological, immunohistochemistry, TUNEL assay and Western blotting techniques. Water and sediment samples were collected to evaluate metal concentrations (Al, Cd, Fe, Pb, Mn, Hg). Compared to S1, Fe, Al and Mn concentrations were significantly higher in S2. In fish from S2, liver presented histopathologies such as cell and tissue alterations, hyperemia, inflammatory infiltrate, apoptosis, necrosis and fibrosis, and histopathological alteration index (HAI) significantly higher. TUNEL-positive cells were more frequent in fish at S2, and hepatocytes showing ferroptosis morphological characteristics were detected in this site. CYP1A, metallothionein (MT-1), superoxide dismutase (SOD1), glutathione peroxidase (GPx1) and catalase (CAT) were identified in the cytoplasm of hepatocytes from both sites, but MT-1 and SOD1 was also localized in the nucleus in S2. The expression of these proteins was significantly higher in S2. We concluded that exposure to mining waste rich in heavy metals induced oxidative stress, cell death and severe histopathology in the liver of chronically exposed fish.

A previous study demonstrated that a tetrapeptide FFDR derived from coix seed possesses antioxidant properties. In continuation of the study, Density Functional Theory (DFT) was employed to investigate the molecular-level complexation behaviour of FFDR with Ca2+, Cu2+, and Mg2+. DFT predictions were validated using spectroscopy and cellular model. The electronic properties revealed that Mg-FFDR, with its lower energy gap (1.733 eV), exhibits higher reactivity compared to Ca-FFDR which displayed higher stability (8.180 eV). The Quantum Theory of Atoms in Molecules (QTAIM) showed positive Laplacian values for all metal‑oxygen bonds, indicating the presence of coordination bonds characteristic of closed-shell interactions. Results from 1H NMR spectra revealed J-coupling patterns consistent with metal coordination for Mg and Ca-peptide complexes. FTIR spectra displayed distinct changes in the vibrational frequencies of functional groups involved in metal binding for all complexes. Both Mg-FFDR and Ca-FFDR demonstrated significant ROS scavenging activities, and enhanced SOD and CAT activities in HepG2 cells. These findings serve as a baseline for the rational design of metal-peptide complexes as functional foods or nutraceuticals.

Paddy fields are major sources of atmospheric methane and are at risk of cadmium (Cd) contamination. Aerobic methanotrophs, which serve as biological methane sinks, play a key role in methane cycling, but their responses to Cd stress remain poorly understood. Here, we examined the relationship between Cd pollution levels and aerobic methane oxidation potential in paddy soils. We evaluated methanotrophic enrichments under Cd exposure, applied metagenomic sequencing to identify functional microbes, and investigated Cd tolerance mechanisms in pure culture. Aerobic methane oxidation rates were positively correlated with Cd levels in paddy soils from South China, with Methylocystis and Methylomonas emerging as dominant genera possessing diverse Cd tolerance genes. Notably, interspecific differences in Cd tolerance were observed among methanotrophic strains. The faster-growing Methylomonas sp., endowed with more robust antioxidant defenses and extracellular polymeric substances synthesis genes, exhibited Cd resistance through markedly enhanced loosely bound extracellular polymeric substances production, in contrast to the Cd-sensitive Methylobacter sp. Gene knockout experiments confirmed the essential roles of glutathione synthase, glutathione peroxidase, and exosortase in exopolysaccharide extrusion for Cd detoxification. These findings advance our understanding of the methane cycle in Cd-contaminated rice paddies and suggest potential strategies to mitigate methane emissions while addressing Cd detoxification.

Cisplatin, the pioneering heavy metal compound, stands out as a potent drug for the treatment of various solid tumors. However, its clinical utility is hampered by notable toxicity and adverse effects, particularly nephrotoxicity. The potency of rutecarpine, a phytochemical, in mitigating cisplatin-induced nephrotoxicity was assessed in the present study. In this experimental setup, healthy male Wistar rats were grouped into four and Group I rats served as the control group, receiving only vehicle control. Group II rats were subjected to cisplatin treatment alone, administered intraperitoneally at a dosage of 7 mg/kg body weight on the 19th, 20th, and 21st days. Group III and IV rats were orally administered with rutecarpine at doses of 10 and 20 mg/kg body weight, respectively, starting from Day 1 and continuing daily for 21 days. Additionally, they were injected intraperitoneally with cisplatin at the same dosage and schedule as Group II. Relative kidney weight and renal biochemical markers blood urea nitrogen, lactate dehydrogenase, serum urea, and creatinine were measured to assess rutecarpine inhibitory potency against cisplatin toxicity. Markers of oxidative damage and antioxidants levels were quantified in the ruteacarpine- and cisplatin-treated rats. The study investigated the anti-inflammatory property of rutecarpine in cisplatin-induced nephrotoxicity by analyzing inflammatory cytokines. Renal tissue levels of monocyte chemoattractant protein-1, intercellular adhesion molecule-1, high-mobility group box 1, and nuclear factor kappa B, key markers of nephrotoxicity, were quantified to assess rutecarpine's potential to mitigate cisplatin-triggered damage. Histopathological examinations were performed to confirm the impact of rutecarpine against cisplatin-induced nephrotoxicity. Treatment with rutecarpine notably reduced renal biochemical markers, prevented renal edema, and attenuated oxidative stress-induced damage in cisplatin-treated rats. Both inflammatory and nephrotoxicity markers showed significant decreases in rats treated with rutecarpine along with cisplatin. Histological analysis affirmed that rutecarpine pretreatment effectively prevented cisplatin-induced nephrotoxicity. The study findings demonstrate that rutecarpine ameliorates cisplatin-triggered nephrotoxicity through its antioxidant and anti-inflammatory properties, suggesting that rutecarpine supplementation alongside cisplatin treatment could potentially reduce nephrotoxicity in cancer patients.

In recent years, the marked augment of antibiotic resistance hampered the development of antibacterial agent. Nanozymes by their in situ ROS production capability oxidize cellular substances of bacterial cell and eliminate MDR bacteria. Therefore, synthesis of effective nanozymes from green precursors is rarely reported, so the prime objective of this study was to synthesize Cu-Mn3O4 nanozymes from aqueous extracts of medicinal plant Azadirachta indica via co-precipitation approach and to endorse their biomedical applications. The synthesized materials were characterized by X-ray diffraction (XRD), Fourier Transform Infrared spectrometer (FTIR), Scanning Electron Images (SEM), and Field-Emission Scanning Electron Microscopy (FESEM) images. X-ray Diffraction (XRD) patterns revealed the formation of hausmannite Mn3O4 crystal system. Fourier Transform Infrared spectrometer (FTIR) spectra revealed functional groups on the surface nanoparticles for their stabilization. Energy-Dispersive X-ray spectroscopy (EDAX) profile confirmed the existence of desired elements in the synthesized nanozymes. B1 mimics oxidase enzyme most effectively with Km = 0.175 mM and Vmax = 10.34 µM/min. The low Km and high Vmax indicates the strong binding affinity and high catalytic activity. From the agar diffusion antibacterial assay, it can be concluded that B3 is the most potent antibacterial agent specifically against Gram-positive bacteria Bacillus subtilis with inhibition zone of 27 mm at 250 µg/mL. Their cytotoxic activities on neuroblastoma (SHSY5) cell line were investigated for the first time. The data revealed that synthesized nanooctahedrons possess a significant cytotoxicity against cancer cell lines SHSY5Y (IC50 = 137.47 ± 14.11 µg/mL) and SKOV3 (IC50 = 72.72 ± 9.33 µg/mL). Overall, with increasing Cu amount, the percentage growth inhibition of Mn3O4 crystal system enhanced. The improved antibacterial activity and cytotoxicity is due to synergy between metal and phytochemicals. Radical scavenging activity of synthesized nanozymes is comparatively lower than their green source and the comparatively lower IC50 values of B1, 234.12 ± 15.13 and 220.12 ± 10.37 respectively, which indicates that it is more active in scavenging DPPH and ABTS radical. B2 (IC50 = 310.56 ± 5.92 µg/mL) and B3 (IC50 = 43.56 ± 3.03 µg/mL) scavenge superoxide radicals and FRAP more effectively. It is noticed that synthesized nanozymes have greater antibacterial and anticancer activity but low scavenging ability compared to green extract. Thus, Cu-Mn3O4 NPs from Azadirachta indica leaf extract could be utilized as a replacement of potential antibiotic drug candidate against MDR bacteria and in cancer avenues.

Heat shock factors (HSFs) play a central role in regulating the responses of plants to various stresses. However, the function and regulation of HSFs in pumpkins remains largely unknown. In this study, an HSF, CmHSF30 was identified in Cucurbiamoschata, which belongs to the HSFA subfamily. The expression level of CmHSF30 was significantly upregulated in response to heat stress and exogenous phytohormone treatments, including ABA, GA, IAA, and SA. The CmHSF30 was localized in the nucleus and functions as a transcriptional activator. By overexpressing CmHSF30 in Arabidopsis and pumpkin, the function and regulation of CmHSF30 in response to heat stress were studied. The overexpression of CmHSF30 in Arabidopsis enhanced plant thermotolerance by increased germination rate and survival rate under heat stress, as evidenced by the elevated of contents chlorophyll and GSH, and SOD activity, and decreased contents of H2O2 and MDA. Furthermore, the overexpression of CmHSF30 in pumpkins also enhanced the thermotolerance of transgenic pumpkins by reducing cell death. In contrast, CRISPR/Cas9 mediated knockout of CmHSF30 decreased pumpkin thermotolerance. Besides, RT-qPCR analysis revealed that CmHSF30 plays a positive role in regulating the expression of stress-related genes, including AtHSP18.2, AtHSP20, AtHSP70, AtPP2C, and AtMYB82 from Arabidopsis and CmHSP18.2, CmHSP20, CmHSP70, CmPP2C, and CmMYB46 from pumpkin. Yeast two-hybrid showed that CmHSF30 interacts with CmMYB46. The results indicate that CmHSF30 functions as a positive regulator, enhancing plant thermotolerance by regulating target genes and reducing ROS accumulation.

Medical or surgical interventions are commonly used to alleviate the clinical symptoms of individuals suffering from ischemic heart disease (IHD), but global morbidity and mortality remain high. This is due to the complexity of disease progression and the pathological basis of IHD, which primarily includes myocardial infarction (MI), myocardial ischemia-reperfusion injury (IRI), and heart failure (HF), as well as underlying mechanisms, such as mitochondrial damage, inflammation, oxidative stress, and cardiomyocyte death. However, many drugs have limitations, such as poor stability and low bioavailability, and surgical strategies are often ineffective in preventing disease recurrence. To overcome these problems, it is necessary to develop effective drug delivery systems and technologies. Due to their advantages in enhancing drug utilization, nanomaterials are being used to control drug biodistribution and achieve targeted accumulation, addressing the therapeutic needs of IHD. In this work, we first described the clinical aspects of MI, IRI, and HF in the context of IHD as well as their shared pathological origins. Next, clinical interventional procedures for IHD are summarized. Finally, recent developments in the use of nanomaterials for the treatment of MI, IRI, and HF are highlighted, along with potential directions for future research.

Polygonum multiflorum Thunb. (PM) is a traditional Chinese medicine with pharmacological activities such as anti-inflammatory, anti-oxidation and anti-aging. An increasing number of reports have documented liver injury associated with PM both domestically and internationally. In our previous study, we found that dianthrones from PM showed strong hepatotoxicity in the zebrafish model and may be potential toxicity markers. However, the in vitro hepatotoxicity and molecular mechanisms of dianthrones remain to be elucidated.

Trans-emodin dianthrones is a dianthrones compound isolated from PM. In this study, we focused on the hepatotoxicity and molecular mechanism of the trans-emodin dianthrones.

HepG2 cells were used to evaluate hepatotoxicity and study the molecular mechanism of trans-emodin dianthrones in vitro. After administration of trans-emodin dianthrones, CCK-8 was used to detect cell viability, biochemical method was used to detect hepatotoxicity and antioxidant levels, reactive oxygen species (ROS) content and mitochondrial membrane potential (MMP) were analyzed by flow cytometry, the expression levels of JNK/Bax signaling pathway, PI3K/AKT/mTOR signaling pathway and apoptosis-related proteins were detected by Western blotting. Redox and mitochondria-related gene expression levels were detected by qPCR.

Trans-emodin dianthrones reduced cell viability and activated apoptosis and the process was regulated by JNK/Bax and PI3K/AKT/mTOR pathways. Trans-emodin dianthrones activates JNK and AKT, thereby initiating the ROS-driven apoptosis cascade and increasing ROS-mediated cell damage, highlighting the importance of ROS stress in PM-induced hepatotoxicity.

Trans-emodin dianthrones exhibited significant hepatotoxicity at the level of HepG2 cells, and its mechanism is related to inhibiting the antioxidant system, causing mitochondrial dysfunction and inducing apoptosis induced by JNK/Bax and PI3K/AKT/mTOR pathways.

Red radish microgreens (RRM) have gained considerable attention for their promising therapeutic potential. However, the molecular mechanisms underlying their bioactivity remain inadequately characterized. This study explores the anti-inflammatory, antioxidant, and anticancer properties of RRM extract using in silico and in vivo Drosophila model analyses. The metabolite profile of the RRM extract was characterized using comprehensive metabolomics techniques, including Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography High-Resolution Mass Spectrometry (LC-HRMS). Furthermore, in silico analysis utilizing network pharmacology identified target proteins of RRM compounds associated with cancer, inflammation, and oxidative stress. Concurrently, in vivo experiments with Drosophila melanogaster PGRP-LBΔ (Dm PGRP-LBΔ) larvae was conducted to assess the extract's impact on immune and oxidative stress pathways. In silico analysis revealed that RRM compounds interacted with key proteins (AKT1, ESR1, MAPK1, SRC, TP53), modulating pathways related to cancer, inflammation, and oxidative stress. Molecular dynamics simulations reinforced the docking results by confirming robust binding of kaempferitrin to AKT1. In vivo studies showed that RRM extract suppressed immune-related genes (dptA, totA) through the NFκB and JAK-STAT pathways, reduced ROS levels, and selectively regulated antioxidant gene expression by enhancing sod1 while decreasing sod2 and cat. These results suggest RRM extract as a functional food for managing oxidative stress, inflammation, and cancer. Further research in higher organisms and clinical settings is needed.

Oxidative stress and chronic inflammation are important drivers in the pathogenesis and progression of many chronic diseases, such as cancers of the breast, kidney, lung, and others, autoimmune diseases (rheumatoid arthritis), cardiovascular diseases (hypertension, atherosclerosis, arrhythmia), neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease), mental disorders (depression, schizophrenia, bipolar disorder), gastrointestinal disorders (inflammatory bowel disease, colorectal cancer), and other disorders. With the increasing demand for less toxic and more tolerable therapies, flavonoids have the potential to effectively modulate the responsiveness to conventional therapy and radiotherapy. Flavonoids are polyphenolic compounds found in fruits, vegetables, grains, and plant-derived beverages. Six of the twelve structurally different flavonoid subgroups are of dietary significance and include anthocyanidins (e.g. pelargonidin, cyanidin), flavan-3-ols (e.g. epicatechin, epigallocatechin), flavonols (e.g. quercetin, kaempferol), flavones (e.g. luteolin, baicalein), flavanones (e.g. hesperetin, naringenin), and isoflavones (daidzein, genistein). The health benefits of flavonoids are related to their structural characteristics, such as the number and position of hydroxyl groups and the presence of C2C3 double bonds, which predetermine their ability to chelate metal ions, terminate ROS (e.g. hydroxyl radicals formed by the Fenton reaction), and interact with biological targets to trigger a biological response. Based on these structural characteristics, flavonoids can exert both antioxidant or prooxidant properties, modulate the activity of ROS-scavenging enzymes and the expression and activation of proinflammatory cytokines (e.g., interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α)), induce apoptosis and autophagy, and target key signaling pathways, such as the nuclear factor erythroid 2-related factor 2 (Nrf2) and Bcl-2 family of proteins. This review aims to briefly discuss the mutually interconnected aspects of oxidative and inflammatory mechanisms, such as lipid peroxidation, protein oxidation, DNA damage, and the mechanism and resolution of inflammation. The major part of this article discusses the role of flavonoids in alleviating oxidative stress and inflammation, two common components of many human diseases. The results of epidemiological studies on flavonoids are also presented.

Despite the undeniable role of chemotherapeutics in cancer treatment, their administration may be associated with various side effects. Cardiac injury is among the most crucial side effects related to the induction of chemotherapeutic agents. Since the heart is a vital organ, cardiotoxicity often prevents clinicians from continuing chemotherapy. Hesperidin and hesperetin, flavonoids derived from citrus fruits, possess several pharmaceutical properties. This study firstly explores the cardioprotective effects of hesperidin and hesperetin against chemotherapy-induced cardiotoxicity mechanisms, emphasizing their potential as adjunctive therapies. Key literature gaps are identified, and further mechanistic studies will be proposed. The findings underscore the translational potential of these flavonoids, advocating for rigorous preclinical optimization and clinical trials to validate their efficacy and safety. This review lays a foundation for integrating natural compounds into cardioprotective strategies in oncology. A systematic search was conducted in databases (PubMed, Scopus, ISI) until May 2025, according to PRISMA principles. The search terms were chosen according to our research objective and queried in the title and abstract. Following the screening of 82 papers, twelve articles were selected based on our inclusion and exclusion criteria. Based on the evaluated results, chemotherapy adversely affects cardiac tissue, leading to elevated risks of morbidity and mortality. Co-administration of hesperidin and hesperetin with chemotherapy prevents heart injury and preserves cardiac function, maintaining it almost like a normal heart. The protective role of hesperidin and hesperetin is based on their ability to fight free radicals, reduce inflammation, and stop cell death. Nonclinical investigations indicate that hesperidin and hesperetin ameliorate chemotherapy-induced cardiotoxicity. Nonetheless, they may influence the efficacy of anticancer medications, which primarily function by elevating oxidants, inflammation, and apoptosis. This indicates that meticulously designed trials are necessary to evaluate the efficacy and safety of this combination along with the synergistic potential of them in preventing chemotherapy-induced cardiotoxicity while maintaining anticancer effectiveness.

Liupao tea is known for its anti-inflammatory antioxidant and regulation of gut microecological balance properties. This study aims to investigate the therapeutic effects of Liupao tea aqueous extract (LPTAE) on ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in rats. The rats were randomly divided into five groups: the Normal group, the DSS group, the LPTL group, the LPTM group, and the LPTH group. Throughout the experiment, the rats' activity levels, stool consistency, and body weights were observed and recorded daily. After the experiment, colon length was measured, and colon tissues were collected for pathological analysis. Additionally, the colon contents were analyzed for gut microbiota composition and short-chain fatty acid (SCFA) level, while serum samples were collected to determine inflammatory and oxidative factors. The results indicated that treatment with low, medium, and high doses of LPTAE significantly inhibited weight loss, alleviated rectal bleeding, and reduced colon shortening compared to the DSS group. It also decreased the disease activity index and histopathological activity index scores in the rats. Furthermore, LPTAE reduced the levels of inflammatory cytokines such as IL-1β, IL-6, TNF-α, and malondialdehyde, while simultaneously increasing the levels of superoxide dismutase and SCFAs, including acetic acid, propionic acid, and butyric acid. 16S rDNA gene sequencing of the gut microbiota revealed that all doses of LPTAE reversed the decrease in both α and β diversities caused by UC, increased the relative abundance of beneficial bacteria such as Lactobacillus, Muribaculaceae, Alloprevotella, and Blautia, and decreased the levels of harmful bacteria such as Prevotella, Romboutsia, and Bacteroides. In summary, within the tested doses (100, 150, 250 mg/kg), LPTAE alleviated DSS-induced colitis by modulating the gut microbiota and correcting the metabolic imbalance of SCFAs.

Reactive oxygen species (ROS), regulators of cellular behaviors ranging from signaling to cell death, have complex production and control mechanisms to maintain a dynamic redox balance under physiological conditions. Redox imbalance is frequently observed in tumor cells, where ROS within tolerable limits promote oncogenic transformation, while excessive ROS induce a range of regulated cell death (RCD). As such, targeting ROS-mediated regulated cell death as a vulnerability in cancer. However, the precise regulatory networks governing ROS-mediated cancer cell death and their therapeutic applications remain inadequately characterized. In this Review, we first provide a comprehensive overview of the mechanisms underlying ROS production and control within cells, highlighting their dynamic balance. Next, we discuss the paradoxical nature of the redox system in tumor cells, where ROS can promote tumor growth or suppress it, depending on the context. We also systematically explored the role of ROS in tumor signaling pathways and revealed the complex ROS-mediated cross-linking networks in cancer cells. Following this, we focus on the intricate regulation of ROS in RCD and its current applications in cancer therapy. We further summarize the potential of ROS-induced RCD-based therapies, particularly those mediated by drugs targeting specific redox balance mechanisms. Finally, we address the measurement of ROS and oxidative damage in research, discussing existing challenges and future prospects of targeting ROS-mediated RCD in cancer therapy. We hope this review will offer promise for the clinical application of targeting oxidative stress-mediated regulated cell death in cancer therapy.

The accumulation of reactive oxygen species (ROS) in the skin following UVB exposure is a key contributor to ultraviolet-induced skin photodamage. Orientin, a bioactive flavonoid, has demonstrated antioxidant properties in previous studies. However, its efficacy in treating skin photodamage remains inadequately understood. This study investigates the effects of orientin in preventing UVB-induced immortalized human keratinocytes (HaCaT cells) and BALB/c mouse skin photodamage by activating the AMPK/Nrf2 axis. Results show that orientin protects HaCaT cell viability after UVB exposure, reduces ROS levels, and upregulates antioxidant enzymes, including SOD1, HO-1, and NQO-1, while concurrently suppressing the expression of inflammatory mediators such as COX-2, IL-6, and IL-8. Additionally, orientin promotes AMPK phosphorylation, which facilitates Nrf2 nuclear translocation, thereby enhancing the antioxidant defense of cells. This effect is diminished upon inhibition of AMPK or Nrf2. In the BALB/c mouse model of photodamage, topical application of orientin alleviates symptoms like skin roughness, scaling, and erythema induced by UVB irradiation, while also elevating antioxidant enzyme expression in skin tissues. These findings suggest that orientin mitigates ultraviolet-induced skin photodamage both in vitro and in vivo, boosts cellular antioxidant capacity, and diminishes inflammatory responses, suggesting its potential for further exploration in skin photodamage management.

Holothuria scabra (H. scabra), a marine organism traditionally known for its health benefits, has been utilized in both food and medicine. Our previous studies indicated that 2-butoxytetrahydrofuran (2-BTHF), which is isolated from H. scabra, possesses the potential to alleviate amyloid-β and α-synuclein accumulations associated with Alzheimer's and Parkinson's diseases (AD and PD), respectively. However, the mechanisms through which 2-BTHF mitigates PD-related neurotoxicity remain unclear. In this study, we investigated the effects of 2-BTHF on a 6-hydroxydopamine (6-OHDA)-induced Caenorhabditis elegans (C. elegans) model. Our results demonstrated that 2-BTHF recovered dopaminergic (DAergic) neurons from degeneration and restored dopamine-related behaviors. Furthermore, 2-BTHF reduced reactive oxygen species (ROS) production, preserved mitochondrial fluorescence, and decreased both mitochondrial and cytoplasmic unfolded protein responses (UPRmt and UPRcyto) activation. Transcriptome sequencing analysis revealed the critical roles of various systems, including the immune system, nervous system, glutathione (GSH) metabolism, xenobiotics, terpenoids, energy metabolism, cell growth and death, and aging-related longevity pathways. Additionally, 2-BTHF showed potential interactions with stress resistance and detoxification transcription factors, promoting the nuclear translocation of DAF-16 and SKN-1, which in turn activated their targets, including SOD-3, CTL-2, GCS-1, and GST-4. Moreover, 2-BTHF increased total GSH levels and reduced the ced-3-related cascade. This study demonstrates that 2-BTHF holds promise as a therapeutic agent for treating 6-OHDA-induced DAergic neurodegeneration in the C. elegans model.

This study investigated the preventive effects and mechanisms of Paeonia lactiflora pall stem and leaf extract (PLE) on oxidative stress-induced diarrhea in broilers, using a Diquat (DQ)-induced model. Results indicated that PLE significantly improved growth performance, increased average daily gain (ADG), reduced feed-to-gain ratio (F/G), and enhanced liver and kidney indices. PLE alleviated DQ-induced oxidative stress diarrhea by reducing the diarrhea rate by 63.84%, upregulating mRNA expression of MUC2, Claudin-1, ZO-1, and Occludin, and decreasing AST and ALT activities in serum. Additionally, PLE increased levels of CAT, SOD, GSH-Px, and GSH while reducing PCO and MDA levels in serum, intestine, and liver tissues. Furthermore, PLE increased acetic acid content and decreased propionic acid, butyric acid, and isobutyric acid contents. PLE also altered gut microbiota by up-regulated Bacteroidetes and Barnesiella and down-regulated Firmicutes and unclassified_o__Eubacteriales. Network pharmacology suggested that PLE acts via the PI3K-Akt-Nrf2 pathway, confirmed by up-regulated mRNA expression of PI3K, AKT, Nrf2, NQO1, and HO-1, and down-regulated Keap1 in intestinal and liver tissues. Correlation analysis revealed significant associations between Barnesiella and unclassified_o__Eubacteriales with short-chain fatty acids and PI3K-Akt-Nrf2 pathway-related genes. Thus, PLE prevents and alleviates oxidative stress-induced diarrhea in broilers by modulating the PI3K-Akt-Nrf2 pathway, regulating gut microbiota, and influencing short-chain fatty acids.

Synucleinopathies and amyloidogenic disorders are the two most prevalent neurodegenerative conditions, characterized by progressive loss of neurons and aggregation of proteins in the central nervous system. Emerging evidence suggests that despite their distinct pathological hallmarks: α-synuclein in Parkinson's disease (PD) and amyloid-β in Alzheimer's disease (AD), both disorders share common molecular pathways, including oxidative stress, neuroinflammation, misfolding/aggregation of proteins and mitochondrial dysfunction. This review explores the molecular intersections between synucleinopathies and amyloidogenesis. Furthermore, this review highlights how these pathways drive neuronal loss and suggest that targeting them could provide broad therapeutic benefits. By elucidating the shared mechanisms between PD and AD, the multi-targeted therapies could address the underlying molecular disruptions common to both disorders, offering new avenues for effective disease-modifying treatments in neurodegenerative diseases.

Alkali and drought stresses are two common abiotic factors affecting plants growth and development. Auxin signal also regulates plant responses to abiotic stresses. Especially, auxin early response genes can quickly respond after sensing auxin signal. However, auxin early response genes related to alkali and drought stresses are rarely reported in Leymus chinensis. In this study, LcSAUR1 (small auxin-up RNA) was isolated from the difference expression analysis of the transcriptome data in Leymus chinensis under alkali and drought stresses. And LcSAUR1 exhibited inhibitory expression under alkali and drought stresses. Further research showed that LcSAUR1 was localized in the nucleus, cell membrane, and chloroplast, suggesting that it might has special biofunction. Overexpression of LcSAUR1 led to shorter root lengths in LcSAUR1-transgenic Arabidopsis and rice. Under alkali and drought stresses, the OE-LcSAUR1-Col lines showed delayed germination and larger stomatal aperture, and the OE-LcSAUR1-NIP lines had lower survival rates. The determination of physiological indicators including hydrogen peroxide (H2O2), malondialdehyde (MDA), catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), the contents of proline (PRO), and the staining of nitro-blue tetrazolium (NBT) and Diaminobenzidine (DAB) indicated that the overexpressed LcSAUR1-transgenic Arabidopsis and rice produced more reactive oxygen species (ROS). In addition, for the genes related to abiotic stresses, the expression of AtSnRK2.6, AtNCEB3, AtCAT2, and AtAPX1 in the OE-LcSAUR1-Col lines, and OsLEA3-2, OsABF1, OsCAT2, and OsAPX2 in the OE-LcSAUR1-NIP lines were all lower than their WT under alkali and drought stresses, suggesting that LcSAUR1 regulates alkali and drought tolerances might through those abiotic-related genes. The study suggests that the LcSAUR1 negatively regulates alkali and drought stresses, providing a novel insight into auxin signal and abiotic stresses.

Alcoholic Liver Disease (ALD), a chronic condition caused by long-term heavy alcohol consumption, can progress to cirrhosis or liver failure. HuGan Tablets (HGT) is a compound preparation made of six Chinese herbs, which is used in clinic for the treatment of chronic hepatitis, with studies demonstrating its efficacy in alleviating alcohol-induced liver injury in rats. However, the active components and therapeutic targets of HGT remain unclear and require further investigation.

The aim of this study was to develop a systematic pipeline based on the SPR fishing strategy to identify effective components and therapeutic targets in Chinese formulas, using HGT as a representative case.

HRMS was employed to analyze HGT ingredients absorbed in rat blood, while network pharmacology, molecular docking and literature mining were utilized to identify potential targets of HGT for ALD alleviation. A systematic SPR-based fishing system was developed by evaluating protein target coupling efficiency, sample recovery rate, specificity of target-small molecule binding, and LOD, and candidate components screened and identified using this system were further screened by SPR affinity tests. Additionally, therapeutic efficacy of the selected compounds was validated in vitro using an ethanol-induced AML12 model and further confirmed in vivo using a mouse model of ALD by assessing markers such as ALT, AST, and oxidative stress indicators.

A total of 128 compounds were identified in HGT, with 29 metabolites detected in rat blood. MFN2, SOD2, mTOR, RXRA, and GSTP1 were identified as anti-ALD targets of HGT through integrated network pharmacology, molecular docking, and literature analysis. An SPR-based active component fishing system was successfully developed, capturing 15 candidate compounds. SPR affinity analysis revealed strong binding (KD: 3.41-221.7 μM) between (R,S)-goitrin, chlorogenic acid, saikosaponin B2, schisandrin, schisandrol B, schisandrin A, schisandrin C, and schisantherin A and the target proteins. Except for (R,S)-goitrin, the other seven compounds significantly reduced ALT, AST, TG, ROS, and MDA levels while enhancing SOD and GSH activities in cellular models, with comparable therapeutic effects observed in ALD mice.

This study scientifically established an integrated SPR-based pipeline to systematically characterize active ingredients and therapeutic targets in herbal formulations, which was successfully applied to reveal key therapeutic targets and pharmacodynamic components of HGT for ALD. This study provides a valuable framework for SPR-based screening of bioactive components in traditional formulas, as well as for understanding the material basis and mechanism of action of HGT in the treatment of ALD.

Most DNA damage caused by oxidative metabolism consists of single lesions that can accumulate in tissues. This review focuses on two classes of lesions: the two 8-oxopurine (8-oxo-Pu) lesions that are repaired by the base excision repair (BER) enzyme and the four 5',8-cyclopurine (cPu) lesions that are repaired exclusively by the nucleotide excision repair (NER) enzyme. The aim is to correlate the simultaneous quantification of these two classes of lesions in the context of neurological disorders. The first half is a summary of reactive oxygen species (ROS) with particular attention to the pathways of hydroxyl radical (HO•) formation, followed by a summary of protocols for the quantification of six lesions and the biomimetic chemistry of the HO• radical with double-stranded oligonucleotides (ds-ODN) and calf thymus DNA (ct-DNA). The second half addresses two neurodegenerative diseases: xeroderma pigmentosum (XP) and Cockayne syndrome (CS). The quantitative data on the six lesions obtained from genomic and/or mitochondrial DNA extracts across several XP and CS cell lines are discussed. Oxidative stress contributes to oxidative DNA damage by resulting in the accumulation of cPu and 8-oxo-Pu in DNA. The formation of cPu is the postulated culprit inducing neurological symptoms associated with XP and CS.

With the growing human interest in space exploration, understanding the oxidative damage effects of microgravity on somatic and germ cells and their underlying mechanisms has become a pivotal scientific challenge for ensuring reproductive health during long-term space missions. In this review, we comprehensively summarize the molecular mechanisms of microgravity-induced oxidative stress, advanced detection methods, and potential protective strategies for germ cells. The evidence demonstrates that microgravity substantially compromises germ cell viability and embryonic developmental potential by disrupting mitochondrial function, increasing reactive oxygen species (ROS) production, and impairing antioxidant defenses. These alterations result in DNA damage, lipid peroxidation, and protein oxidation, thereby affecting cellular integrity and functionality. Furthermore, we discuss how cells respond to microgravity-induced oxidative stress through adaptive mechanisms, such as autophagy, apoptosis, and antioxidant systems, although these responses can have both beneficial and detrimental effects on cellular homeostasis. Additionally, this paper highlights the utility of fluorescent probes for detecting ROS levels under microgravity conditions, which are convenient and practical, but may require further optimization to improve sensitivity and specificity. To counteract these challenges, interventions such as antioxidants and artificial gravity systems show promise but need rigorous validation in prolonged microgravity environments. Finally, future research should integrate multi-omics approaches to unravel the oxidative damage network, advance space-adapted reproductive technologies, and provide essential theoretical insights and technical support for maintaining human reproductive health beyond Earth.

Cadmium (Cd) pollution leads to reduced crop yields and poses a threat to human health, making it an important environmental and agricultural safety issue. Selenium [Se(IV)] has been shown to alleviate Cd stress in plants; however, the mechanisms underlying Se-mediated protection against Cd toxicity remain largely unclear. In this study, we investigated the physiological and molecular mechanisms of Se(IV)-alleviated Cd toxicity in strawberry plants through physio-biochemical and transcriptomic analyses. Our results showed that foliar spraying with Se(IV) increased photosynthetic efficiency, reduced Cd-induced oxidative damage by enhancing antioxidant enzyme activities and soluble sugar contents, thereby improving Cd stress tolerance. Transcriptomic profiling revealed 477 common differentially accumulated transcripts (DATs), predominantly enriched in transporter activity, oxidoreductase function, and antioxidant-related processes. Notably, seven key genes involved in Cd efflux, chelation, secondary metabolite transport and nutrient uptake (FvPCR9-like, FvCBP-like, FvWAT1-like, FvMOT1, FvYW_6g02140, FvNRT2.1 and FvZIP8) exhibited opposite expression patterns under Se(IV) and Cd treatments. Supplementation with Se(IV) also modulated phytohormone signaling, nitrogen metabolism and carbon metabolism pathways, providing a multi-dimensional approach to mitigating Cd-induced physiological disruptions. This study provides novel insights into Se(IV)-mediated Cd stress adaptation, and offers promising strategies for developing low-Cd-accumulating crops, addressing critical environmental and agricultural challenges associated with heavy metal contamination.

To clarify the microRNA (miRNA)-target gene axis is involved in response to pathogen-associated molecular pattern (PAMP)-induced oxidative stress in shellfish, the full-length cDNA of a novel mitogen-activated protein kinase-interacting kinase 1 (MNK1) homolog gene from the scallop Patinopecten yessoensis (PyMNK1) was cloned and characterized. The interaction between miR-1985 and PyMNK1 was verified, and then the responses and possible molecular function of miR-1985, PyMNK1, and miR-1985/PyMNK1 axis to poly(I:C) (a classic virus-related PAMP) stimulation in P. yessoensis were explored and preliminarily dissected. The results indicate: 1) The full-length cDNA of PyMNK1 was 5354 bp, with a high level of sequence conservation across mollusks. 2) MiR-1985 bound to the 3'-UTR of PyMNK1 and negatively regulated the expression of PyMNK1. 3) PyMNK1 may repress the relative expression of superoxide dismutase (SOD) by binding its promoter. 4) Both PyMNK1 silencing and miR-1985 overexpression promoted the expression and enzymatic activity of SOD. 5) The miR-1985/PyMNK1 axis may be involved in the response to poly(I:C) stimulation by elevating the activity of the SOD/catalase axis. To summarize, all observations from this study indicated that P. yessoensis may enhance its redox capability via the miR-1985/PyMNK1/SOD/CAT cascade and thereby alleviate PAMP-induced oxidative stress.

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two neurodegenerative disorders that share common genes and pathomechanisms and are referred to as the ALS-FTD spectrum. A hallmark of ALS-FTD pathology is the abnormal aggregation of proteins, including Cu/Zn superoxide dismutase (SOD1), transactive response DNA-binding protein 43 (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS/TLS), and dipeptide repeat proteins resulting from C9orf72 hexanucleotide expansions. Genetic mutations linked to ALS-FTD disrupt protein stability, phase separation, and interaction networks, promoting misfolding and insolubility. This review explores the molecular mechanisms underlying protein aggregation in ALS-FTD, with a particular focus on TDP-43, as it represents the main aggregated species inside pathological inclusions and can also aggregate in its wild-type form. Moreover, this review describes the protective mechanisms activated by the cells to prevent protein aggregation, including molecular chaperones and post-translational modifications (PTMs). Understanding these regulatory pathways could offer new insights into targeted interventions aimed at mitigating cell toxicity and restoring cellular function.

The increasing pollution of polystyrene (PS) and polymethyl methacrylate (PMMA) microplastics (MPs) has become a global marine environmental problem. Diatoms contribute nearly 40% of marine primary productivity and shape the nitrogen cycle in the oceans. However, the persistence of the phytotoxicity of MPs on diatoms, especially nitrogen assimilation, remains largely unknown. To examine the persistence of PS and PMMA toxicity in diatoms, two subexperiments (a 96 h exposure followed by a recovery phase) were conducted on Thalassiosira pseudonana at concentrations ranging from 0.001 to 1 mg/L. The results showed that PS and PMMA inhibited algal growth by 3.76-6.49% and 4.44-8.37%; increased oxidative stress by 10.06-30.51% and 30.46-38.12%; and caused ultrastructural damage by 14.24-25.56% and 12.28-20%, respectively, consistent with the downregulation of glyoxylate, dicarboxylate metabolism, and glutathione metabolism. At the recovery stage, the algal density induced by PS was significantly recoverable at 0.001 and 0.01 mg/L, consistent with the enhanced carbohydrate metabolisms. After recovery, the cell permeability and reactive oxygen species (ROS) levels induced by PS and PMMA were significantly decreased at 1 mg/L, respectively, which was closely related to the downregulation of glycine, serine, and threonine metabolism and the upregulation of pantothenate and coenzyme A biosynthesis. Moreover, the inhibition of nitrogen assimilation enzymic activities induced by PS and PMMA was significantly recovered at 1 mg/L despite the downregulation of nitrogen metabolism. This study highlights the phenomena and mechanisms of phytotoxicity and recovery, and provides new insights for comprehensive understanding and evaluation of environmental risks of MPs.

Propranolol is a beta-blocker psychoactive drug used for the management of high blood pressure, tremors, atrial fibrillation, and migraine headaches. This study investigated the effect of propranolol on behavior, acetylcholinesterase, lipid peroxidation, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in the brain of African Sharptooth Catfish Clarias gariepinus juveniles.

A total of 180 African Sharptooth Catfish were exposed to 7.00-, 9.00-, 11.00-, 13.00-, and 15.00-mg/L acute propranolol concentrations and a control (0.00 mg/L) for 24, 48, 72, and 96 h, and the 96-h LC50 value was 9.48 mg/L. For sublethal study, 120 juvenile African Sharptooth Catfish were divided into four groups of 30 fish each and exposed to 1.90-, 0.95-, and 0.47-mg/L propranolol concentrations and a control for 21 d and allowed to recover for 7 d. All the treatment groups and control were set in triplicates, with 10 fish in each. The behavioral changes due to propranolol exposure were monitored by direct observation and scoring during the exposure and withdrawal period. The brains of fish were sampled every week for 4 weeks in order to evaluate the effects of propranolol on acetylcholinesterase, lipid peroxidation, and oxidative stress parameters.

Behavioral changes were evidenced by alterations in swimming rates, air gulping activities, and opercula beats in the propranolol-exposed fish during the acute exposure. Sublethal exposure resulted in a significant decrease in superoxide dismutase and catalase but increase in glutathione peroxidase and reductase values. Significant increase in lipid peroxidation and acetylcholinesterase enzyme levels were observed as exposure duration increased from day 7 compared with the control. The effects of propranolol on the observed parameters appeared to wane after fish withdrawal from the drug for 7 d.

The drug propranolol, as demonstrated by these alterations, may negatively impact nontarget aquatic species and may have ecological consequences.

ABSTRACTBased on the well-documented hazards of microplastics and the importance and typicality of Saccharomyces cerevisiae (S. cerevisiae) in the environment, in this study, the influencing mechanisms of functional group, particle size and dosage of polystyrene microplastics (PS MPs) on S. cerevisiae were studied systematically. The results showed that compared with the bigger particle size and lower concentration of carboxylated PS MPs, the smaller particle size and higher concentration of aminated PS MPs had the most serious inhibition of the growth of S. cerevisiae, and their cell morphology was more abnormal, the more PS MPs attached to the yeast cells. The results of orthogonal experiment showed that the inhibitory effects of PS MPs on S. cerevisiae followed the order: functional groups > concentrations > particle sizes. Through the analysis of the antioxidant properties of S. cerevisiae, it was found that the activities of superoxide dismutase and catalase were first stimulated and then inhibited, and the concentrations of superoxide dismutase enzymes in the environment with bigger particle size and lower concentration of PS MPs was higher than that in the environment with smaller particle size and higher concentrations of PS MPs. catalase enzyme showed an opposite trend in particle sizes and a similar trend in concentrations. The concentrations of malondialdehyde increased with the increase of PS MPs concentrations and the decrease of particle sizes, indicating that PS MPs could induce S. cerevisiae to produce a large amount of reactive oxygen species, resulting in severe oxidative damage to S. cerevisiae.

Inflammation is a multifaceted biological response of the immune system against various harmful stimuli, including pathogens (such as bacteria and viruses), cellular damage, toxins, and natural/synthetic irritants. This protective mechanism is essential for eliminating the cause of injury, removing damaged cells, and initiating the repair process. While inflammation is a fundamental component of the body's defense and healing process, its dysregulation can lead to pathological consequences, contributing to various acute and chronic diseases, such as autoimmune disorders, cancer, metabolic syndromes, cardiovascular diseases, neurodegenerative conditions, and other systemic complications. Generally, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease-modifying anti-rheumatic drugs (DMARDs), antihistamines, biologics, and colchicine are used as pharmacological agents in the management of inflammatory diseases. However, these conventional treatments often have limitations, including adverse side effects, long-term toxicity, and drug resistance. In contrast, enzyme-based therapeutics have emerged as a promising alternative due to their high specificity, catalytic efficiency, and ability to modulate inflammatory pathways with reduced side effects. These enzymes function by scavenging reactive oxygen species (ROS), inhibiting cytokine transcription, degrading circulating cytokines, and blocking cytokine release by targeting exocytosis-related receptors. Additionally, their role in tissue repair and regeneration further enhances their therapeutic potential. Most natural anti-inflammatory enzymes belong to the oxidoreductase class, including catalase and superoxide dismutase, as well as hydrolases such as trypsin, chymotrypsin, nattokinase, bromelain, papain, serratiopeptidase, collagenase, hyaluronidase, and lysozyme. Engineered enzymes, such as Tobacco Etch Virus (TEV) protease and botulinum neurotoxin type A (BoNT/A), have also demonstrated significant potential in targeted anti-inflammatory therapies. Recent advancements in enzyme engineering, nanotechnology-based enzyme delivery, and biopharmaceutical formulations have further expanded their applicability in treating inflammatory diseases. This review provides a comprehensive overview of both natural and engineered enzymes, along with their formulations, used as anti-inflammatory therapeutics. It highlights improvements in stability, efficacy, and specificity, as well as minimized immunogenicity, while discussing their mechanisms of action and clinical applications and potential future developments in enzyme-based biomedical therapeutics.

In the present study, the effects of emerging and legacy pollutants such as hazardous microplastics (hMP) and toxic elements (As, Cd, Hg and Pb) were investigated in wild Mediterranean mussel Mytilus galloprovincialis (n = 40) from three estuaries with different anthropogenic uses in the Asturias region (SW Bay of Biscay). The expression levels of six candidate genes related with oxidative stress and/or heavy metal detoxification (sod1, sod2, cat, hsp70, mt10 & mt20) were measured using qPCR. The relationship between their expression levels, the Condition Index (CI), and the concentration of these concurrent pollutants was assessed through linear mixed models (LMM). PERMANOVA revealed significant differences between polluted and clean locations for both pollutants and gene expression levels in mussels. However, no differences were found between Nalón and Sella estuaries despite their distinct historical uses and pollution levels, suggesting recovery in post-mining times. Overall, the expression of the antioxidant gene sod2 and the detoxification genes mt10 and mt20 were upregulated in mussels from the most industrialized and heavy metal polluted estuary of Avilés, with Cd and Pb significantly predicting mt10 and mt20 increase. Hg and the hMP content significantly explained the expression patterns of sod1 and sod2 genes. To the best of our knowledge, this is the first study examining the combined molecular effects of legacy and emerging pollutants on wild populations of the bioindicator Mediterranean mussel. Additionally, it represents the first application of this molecular approach to monitor the ecological status of estuaries in the region that could be applied elsewhere.

Konjac glucomannan (KGM) is a polysaccharide with potential medical and functional properties. Here, the antioxidant and cytoprotective effects of sulfated and differently sized KGM fractions were investigated using various in vitro assays. The sulfated KGMs (SKGMs) were prepared via a relay strategy. First, Vitamin C (Vc)-H2O2 degradation was employed to obtain three soluble KGM fractions with different molecular weights. Second, nine KGM derivatives with varying sulfate content were obtained by the sulfur trioxide-pyridine method. The scavenging of DPPH, superoxide, and hydroxyl radicals was measured in vitro. The antioxidant activity of SKGM correlated positively with sulfate content. SKGM-I-2 displayed the most potent radical scavenging activity. Its purification by cellulose DEAE-52 column chromatography yielded four homogeneous fractions (SKGM-I-2a, SKGM-I-2b, SKGM-I-2c, and SKGM-I-2d). Pretreatment with SKGM-I-2d increased the viability of RAW264.7 cells exposed to H2O2. Moreover, SKGM-I-2d significantly increased the activity of superoxide dismutase and catalase, as well as the levels of glutathione, while regulating the expression of Keap1, Nrf2, and HO-1 in RAW264.7 cells. The present study suggests that SKGM-I-2d protects RAW264.7 cells against H2O2-induced oxidative injury through the activation of the Nrf2/Keap1 signaling pathway. These results provide a scientific basis for future studies linking the structural and functional features of KGM.

Heat stress is a critical challenge in the poultry industry. It arises when birds are exposed to elevated ambient temperatures beyond their thermoneutral zone, often exacerbated by high humidity and inadequate ventilation. This condition disrupts the birds' ability to maintain thermal homeostasis, leading to physiological and behavioral changes such as increased panting, reduced feed intake, and elevated water consumption. These responses aim to dissipate heat but often result in energy imbalances, oxidative stress, and impaired immune function. Green tea polyphenols (GTPs) mitigate heat stress in poultry birds by modulating oxidative stress pathways, primarily by scavenging reactive oxygen species (ROS) and enhancing antioxidant defense mechanisms. These pathways play a pivotal role in neutralizing ROS generated during oxidative stress, inflammation, and exposure to electrophilic compounds. This action helps restore cellular balance and enhances overall antioxidant defense mechanisms by converting harmful free radicals into less reactive molecules, such as water and oxygen. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) plays a significant character in the activation of the enzymatic antioxidants network. It translocates to the nucleus upon activation, binds to antioxidant response elements (AREs) in the promoter regions of target genes, and upregulates the expression of key antioxidant enzymes. Therefore, the regulation of Nrf2 is considered a critical molecular marker in mitigating the effects of heat stress, as its activation enhances the expression of antioxidant and detoxification enzymes, protecting against oxidative damage and inflammation induced by elevated temperatures. This exploratory review summarizes the antioxidant mechanisms and anti-oxidative stress effects of GTPs in mitigating heat stress in poultry. It highlights the cytoprotective molecular basis of epigallocatechin-3-gallate (EGCG), particularly its role in modulating Nrf2-mediated cellular pathways, which enhance antioxidant defense systems and protect against oxidative damage.

Zinc (Zn) is an essential trace element for cellular processes such as oxidative stress regulation. Research on the relationship between Zn and the corpus luteum (CL) is limited, showing contradictory findings. Zinc supplementation before artificial insemination (AI) increases bovine CL size and progesterone (P4) levels. In mice, in vitro experiments suggest that Zn may reduce P4 production. This study aimed to evaluate the role of Zn in bovine luteal cell function by assessing 1) the effect of parenteral Zn supplementation (400 mg) 7 days after AI on CL size and plasma P4 levels in vivo, and 2) the impact of Zn supplementation (0, 0.8 and 1.2 μg/ml) on P4 production, reactive oxygen species (ROS) levels and luteal cell viability in vitro. In vivo, Zn supplementation increased CL size but reduced plasma P4 levels. In vitro, 0.8 μg/ml Zn decreased P4 synthesis and ROS levels while enhancing cell viability, whereas 1.2 μg/ml Zn had no significant effect compared to the control. These findings indicate that Zn modulates luteal function in a dose-dependent manner, reducing oxidative stress while impairing P4 production. Further studies are needed to optimize Zn supplementation strategies during assisted reproductive technologies and clarify Zn mechanisms of action.

Conditional manipulation of gene expression is essential in plant biology, yet a simple stimuli-based inducible system for regulating any plant gene is lacking. Here, we present an innovative stress-inducible CRISPR/dCas9-based gene-regulatory toolkit tailored for intentional gene regulation in solanaceous plants. We have translationally fused the transmembrane domain of a tomato membrane-bound NAC transcription factor with dCas9 to utilize the reversible-tethering-based activation mechanism. This system sequesters dCas9 to the plasma membrane under normal conditions and allows membrane detachment in response to heat induction and NLS-mediated nuclear transfer, enabling stress-inducible gene regulation. Transient assays with tomato codon-optimized dCas9-assisted inducible CRISPR activation and interference systems confirmed their superior ability on transcriptional control, rapid induction, and reversibility after stimulus withdrawal in solanaceous plants. The transformative potential of the toolkit was exemplified by enhancing tomato immunity against bacterial speck disease under elevated temperatures by precisely regulating crucial salicylic acid signalling components, SlCBP60g and SlSARD1. Additionally, it was instrumental in engineering heat-stress tolerance in tomato plants through multiplex activation of heat-responsive transcription factors, SlNAC2 and SlHSFA6b. These findings demonstrate the unprecedented temporal control offered by this novel stress-inducible toolkit over gene-expression dynamics, paving the way for favourable manipulation of complex traits in environmentally-challenged crops.

Endocrine-disrupting chemicals (EDCs) are ubiquitous emerging environmental contaminants. However, the comprehensive impact of EDCs on soil ecosystems, particularly on the model organism Eisenia fetida, remains inadequately understood due to disparate experimental and assessment methods. A meta-analysis was conducted to analyze the effects of EDCs on earthworm functional traits, including survival, behavior, growth, reproduction, and cellular responses. The analysis revealed that EDCs significantly impaired earthworm survival (-17.5%, p < 0.05), behavior (-62.2%, p < 0.001), growth (-11.5%, p < 0.001), and reproduction (-36.7%, p < 0.001). EDCs induced substantial oxidative stress, evidenced by a 36.5% (p < 0.001) increase in reactive oxygen species (ROS) production and elevated oxidative damage. The antioxidant defense system showed compensatory activation, with enhanced superoxide dismutase (10.0%) and catalase (8.90%) activities and glutathione levels (23.3%) (p < 0.001). The present study found chemical-specific toxicity patterns with heavy metals causing the most severe effects on behavior and reproduction. Toxicity profiles varied with exposure concentration and duration, revealing complex dose-response and temporal relationships. These findings provide crucial insights for the ecological risk assessment of EDCs and establish a foundation for developing targeted mitigation strategies. Furthermore, the findings highlight the importance of taking multiple endpoints into account when evaluating the toxicity of EDCs and suggest possible directions for future research.

Oxidative stress plays a crucial role in the pathogenesis of ulcerative colitis (UC), contributing to mucosal damage and inflammation. Zataria multiflora possesses antioxidant properties, yet clinical evidence regarding its effects in UC remains limited. This study aimed to evaluate the impact of Z. multiflora extract on oxidative stress markers and disease severity in UC patients.

In this triple-blind, randomized, placebo-controlled trial, 92 patients with mild-to-moderate UC were randomly assigned to receive either Z. multiflora extract (6 mg/kg/day) or a placebo for two months. Oxidative stress markers, including malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD), and thiol groups (SH), were measured before and after treatment. Disease severity was assessed using the Partial Simple Clinical Colitis Activity Index (P-SCCAI).

Z. multiflora supplementation significantly increased TAC (p = 0.01), SOD (p = 0.02), and SH (p = 0.01) levels, indicating enhanced antioxidant defenses. However, MDA levels did not significantly decrease (p = 0.06). Clinically, the Z. multiflora group exhibited significant improvements in bowel frequency (p < 0.001), urgency of defecation (p < 0.001), general well-being (p < 0.001), and final P-SCCAI scores (p < 0.001) compared to the placebo group.

Z. multiflora supplementation improved antioxidant markers and alleviated UC symptoms, though MDA levels remained unchanged. These findings suggest its potential as a complementary therapy for UC. Further large-scale, long-term studies are warranted to confirm its efficacy and optimize dosing.

Renal ischemia/reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). It can progress to chronic injury and subsequently to chronic kidney disease (CKD) via the renal fibrosis pathway. Luteolin is one of the most commonly occurring flavonoids and exhibits potential therapeutic activity against various pathophysiological processes. In this study, we investigated the protective role of luteolin in counteracting renal I/R injury and its potential mechanisms through systematic network pharmacology, molecular docking, and in vivo experimental studies. Using network pharmacology, we constructed and analyzed a luteolin-renal I/R injury target network. We assessed the relationship between luteolin and renal I/R injury targets using molecular docking analysis. Subsequently, we established a rat model of AKI to CKD transition using unilateral ischemia/reperfusion injury (UIRI), and detected changes in the expression of related proteins using biochemical indices. Network pharmacological analysis and molecular docking showed that luteolin affected renal I/R injury through multiple targets and pathways. As demonstrated by in vivo experiments, luteolin significantly attenuated renal I/R-induced oxidative injury by inhibiting renal lipid peroxidation in rats through the modulation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Luteolin attenuated the levels of relevant inflammatory markers, significantly upregulated the synthesis of apoptosis-related proteins, and downregulated the expression of anti-apoptotic proteins. Our results suggest that luteolin effectively inhibited oxidative damage, inflammation, apoptosis, and fibrosis caused by renal I/R injury, thus exerting a nephroprotective effect. The antioxidant effects of luteolin may be related to the regulation of Nrf2/HO-1 signaling.

Platelet-rich plasma (PRP) is a pioneering therapy widely used in various medical fields, showing promising outcomes. However, its impact on human sperm quality remains poorly explored among emerging therapies. This study aims to investigate the effect of autologous PRP supplementation on oxidative stress levels and mitochondrial activity in human sperm. PRP was freshly prepared from venous blood and added to each ejaculated semen sample at different concentrations of 2%, 5%, and 10%. Reactive oxygen species (ROS) in spermatozoa were measured after 24 hours of incubation at 37° (5% CO2), using nitro-blue tetrazolium (NBT) test. The MTT test was used to measure the mitochondrial succinate deshydrogenase activity. A total of 180 semen samples were obtained from 15 patients. The supplementation with PRP significantly reduced the reactive oxidative species levels and improved mitochondrial activity in spermatozoa. The level of oxidative stress in sperm was significantly decreased after 24h of incubation with PRP at 2% (p = 0.001), 5% (p = 0.001) and 10% (p = 0.001) when compared to the control group. The succinate dehydrogenase activity was enhanced in the three groups when compared to the control group. It increased from 0.667 ± 0.313 to 0.952 ± 0.499 (p = 0.018), 1.201 ± 0.657 (p = 0.002) and 1.159 ± 0.607 (p = 0.001) after incubation with 2%, 5% and 10% of PRP, respectively. This study has shown that PRP supplementation could be a promising tool to enhance sperm quality against oxidative stress and mitochondrial dysfunction. These findings could be a starting point to investigate the usefulness of PRP in ART procedures.

Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) is a globally recognized energetic material that widely used in industrial, mining, and military fields. Like hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and other nitramine compounds, HMX has also been reported to exhibit neurotoxicity. However, the molecular mechanisms underlying the toxic effects of HMX remain poorly understood. Therefore, this study aims to investigate the neurotoxicity induced by HMX by adopting PC12 cells. The results show that HMX treatment decreased cell viability and upregulated the intracellular free calcium ions (Ca2+) in PC12 cells. Furthermore, HMX caused aggravated oxidative stress in PC12 cells, as evidenced by the upregulations of reactive oxygen species (ROS) and malondialdehyde (MDA). Intracellular biochemical assays demonstrated that HMX induced loss of mitochondrial membrane potential in PC12 cells. Notably, altered expression of brain-derived neurotrophic factor (BDNF) and ionotropic glutamate receptors (iGluRs), as well as an abnormal transcription profile, were also observed in PC12 cells treated by HMX. These findings suggest that HMX exerts toxic effects on PC12 cells, involved in oxidative stress, and disturbances in Ca2+ and BDNF, accompanied by aberrant iGluRs. Overall, the present study helps us better understand the health hazards associated with HMX and provides valuable insights for developing the health protection standards related to HMX exposure.

Rotator cuff tears (RCTs) commonly lead to muscle atrophy, fatty infiltration, and fibrosis, resulting in pain, weakness, and impaired shoulder mobility. These pathological changes are often irreversible and pose substantial treatment challenges. The aim of this study was to evaluate the therapeutic potential of muscle-derived mitochondria (Mito) in mitigating muscle degeneration and fibrosis following RCTs.

Sprague Dawley rats were assigned to 3 groups: sham surgery, RCTs treated with Mito, or RCTs treated with phosphate-buffered saline solution (PBS). Following RCTs, in vivo Mito or PBS treatments were administered to the supraspinatus muscles (SSPs) of the rats immediately and then biweekly for 12 weeks. Data were collected on muscle morphology, fibrosis, fatty infiltration, oxidative stress, mitochondrial function, macrophage phenotypes, and serum inflammatory cytokines. In vitro experiments included mitochondria tracking in bone marrow-derived macrophages (BMDMs), characterization of macrophage polarization, and inflammatory cytokine profiling.

Isolated mitochondria preserved their morphology and function. Mito treatment improved muscle wet weight (p < 0.0001) and fiber cross-sectional area (p < 0.0001) while reducing fibrosis (p < 0.0001) and fatty infiltration (p < 0.0001). It upregulated mitochondrial markers cytochrome c oxidase (COX IV) and translocase of outer mitochondrial membrane 20 (TOMM20) (p < 0.0001) and enhanced antioxidative activity, as shown by increased superoxide dismutase (SOD) activity (p < 0.0001), elevated glutathione peroxidase (GSH-PX) levels (p = 0.038), and decreased malondialdehyde (MDA) levels (p = 0.0002). Mitochondrial density and morphology were restored in SSPs after Mito treatment. Additionally, Mito treatment induced an anti-inflammatory macrophage phenotype and reduced pro-inflammatory cytokines in vivo and in vitro.

Mito treatment mitigated muscle degeneration, improved mitochondrial function, and fostered an anti-inflammatory environment through macrophage modulation, demonstrating its potential as a cell-free therapeutic strategy for RCT-related muscle pathologies.

Although this is a preclinical study, its approach offers a novel avenue for improving RCT treatment outcomes. However, further validation in large animal models is needed to address the translational applicability of these findings, given the inherent regenerative capacity of rodent muscles.

Cardiovascular disease (CVD) is one of the most critical diseases which is the predominant cause of death in the world. Early screening and diagnosis of the disease and effective treatment after diagnosis play an important role in the patient's recovery. Metal-organic frameworks (MOFs), a kind of hybrid ordered micro or meso-porous materials, constructed by metal nodes or clusters with organic ligands, due to their special features like high porosity and specific surface area, open metal sites, or ligand tunability, are widely used in various areas including gas storage, catalysis, sensors, biomedicine. Recently, advances in MOFs are bringing new developments and opportunities for the healthcare industry including the theranostic of CVD. In this review, the applications of MOFs are illustrated in the diagnosis and therapy of CVD, including biomarker detection, imaging, drug delivery systems, therapeutic gas delivery platforms, and nanomedicine. Also, the toxicity and biocompatibility of MOFs are discussed. By providing a comprehensive summary of the role played by MOFs in the diagnosis and treatment of CVDs, it is hoped to promote the future applications of MOFs in disease theranostics, especially in CVDs.