H2O2 Levels Research Articles

Polyethylene Microplastic modulates the toxicity of Pentachlorophenol to the microalgae Isochrysis galbana, clone t-ISO.

Pentachlorophenol (PCP) and polyethylene microplastic (PE-MP) have been designated as emerging and persistent pollutants, respectively. The combined effects of those pollutants are still unknown, especially to organisms like phytoplankton that may adsorb to their surface. Therefore, the purpose of this study was to investigate for the first time the effects of PE-MP alone and in combination with PCP on the microalgae Isochrysis galbana, clone t-ISO following 72 h of exposure. Photosynthetic pigments amounts, carotenoid, protein, carbohydrate and fatty acids have been assessed. Acute toxicity test showed that the 72 h median inhibition concentration (72 h-EC50) was 148.2, 0.66 and 087 mg L-1 for PE-MP, PCP and their mixture. The utmost effects in growth inhibition rates were noted with 0.5 and 1.25 mg L-1 PCP (23% and 85%, respectively), and 200 and 300 mg L-1 PE-MP (49% and 64%, respectively). Moreover, it was found that those concentrations had a major impact on the photosynthetic pigments, protein, carbohydrate, and fatty acids amounts in algal cells. Furthermore, levels of H2O2 and Malondialdehyde (MDA), as well as the activities of catalase (CAT), superoxide dismutase (SOD), and ascorbate peroxidase (APX), indicated the induction of an oxidative stress in algal cells. It appears that adding PE-MP at a no-effect concentration (25 mg L-1) reduces the toxicity caused by PCP due to its adsorption to polyethylene microplastics.

Effects of nickel, lead, and copper stress on the growth and biochemical responses of Aegilops tauschii seedlings

Heavy metal pollution causes severe abiotic stress in cereal crops around the world. This study investigated the effects of different concentrations (0, 100, 200, and 300 mg·kg–1) of nickel, lead, and copper stress on the growth and biochemical responses of Aegilops tauschii seedlings, to provide a reference for research on the mechanism of invasion and screening potential sources of wheat tolerance genes. The results showed that nickel, lead, and copper stress caused a significant decrease in the contents of chlorophyll a, chlorophyll b, and chlorophyll (a + b) in A. tauschii, thereby inhibiting photosynthesis to different degrees and hindering seedling growth, which was reflected in significant reductions in plant height and root length, with the most notable effect observed under stress by 300 mg·kg–1 lead. As the concentration of heavy metals increased, the activities of antioxidant enzymes (SOD, POD, and APX), non-enzymatic antioxidants (GSH and AsA), and the contents of osmotic regulatory substances (proline and soluble proteins) in A. tauschii significantly increased. Additionally, heavy metal stress increased H2O2 and TBARS levels. However, when the nickel, lead, and copper concentrations reached 300 mg·kg–1, no significant differences were found in H2O2 or TBARS levels compared to those in the CK group. To summarize, A. tauschii can mitigate the accumulation of ROS and membrane lipid peroxidation caused by heavy metal stress through self-regulation, thus exhibiting a certain degree of tolerance to stress caused by different concentrations of nickel, lead, and copper. Finally, the evaluation using the membership function method revealed that among the three heavy metals, A. tauschii exhibited the strongest adaptation to Cu, followed by Ni and Pb.

Metabolomic analysis of the browning and browning inhibition pulp of Fuji apple at different ripening stages

Apples at different ripening stages display distinct processing properties and browning characteristics in products. This study aimed to identify differential metabolites and metabolic pathways of browning pulp and browning inhibition pulp of Fuji apple across four ripening stages (M1–M4), corresponding to days after full bloom (DAFB: 148, 155, 162, and 171). We investigated the physicochemical characteristics, browning-related enzyme activities, and metabolomic profiles of apples at the four stages, revealing defensive metabolic changes associated with browning throughout ripening. Specifically, the browning rate in apples increased with ripening, peaking before declining in the late stages, and exhibited positive correlations with activities of polyphenol oxidase (PPO), peroxidase (POD), and catalase (CAT), and negative correlations with superoxide dismutase (SOD), phenylalanine ammonia-lyase (PAL), and H2O2 levels. Metabolomic profiling identified 315, 393, and 243 distinct metabolites in fresh control (FC), browning pulp (BR), and browning-inhibited pulps (CM) of apple at the four ripening stages, respectively. KEGG enrichment analysis revealed that FC and BR of the four ripening apples were differentiated by phenylpropanoid biosynthesis, while CM was featured by flavonoid biosynthesis. The characterized differential metabolites in BR were changed to α-linolenic acid metabolism with ripening, while those in CM were from flavonoid and phenylpropanoid biosynthesis. Furthermore, the in-depth analysis revealed 40 significantly differential metabolites associated with amino acid, nucleotide, coenzyme, and vitamin metabolism, potentially modulating the stress-responsive cellular redox balance. This research provides critical insights for browning prevention in the processing of fruits at various ripening stages.

Cerium Oxide Nanoparticles (CeO2 NPs) Enhance Salt Tolerance in Spearmint (Mentha spicata L.) by Boosting the Antioxidant System and Increasing Essential Oil Composition

Salinity represents a considerable environmental risk, exerting deleterious effects on horticultural crops. Nanotechnology has recently emerged as a promising avenue for enhancing plant tolerance to abiotic stress. Among nanoparticles, cerium oxide nanoparticles (CeO2 NPs) have been demonstrated to mitigate certain stress effects, including salinity. In the present study, the impact of CeO2 NPs (0, 25, and 100 mg L−1) on various morphological traits, photosynthetic pigments, biochemical parameters, and the essential oil profile of spearmint plants under moderate (50 mM NaCl) and severe (100 mM NaCl) salinity stress conditions was examined. As expected, salinity reduced morphological parameters, including plant height, number of leaves, fresh and dry weight of leaves and shoots, as well as photosynthetic pigments, in comparison to control. Conversely, it led to an increase in the content of proline, total phenols, malondialdehyde (MDA), hydrogen peroxide (H2O2), and antioxidant enzyme activities. In terms of CeO2 NP applications, they improved the salinity tolerance of spearmint plants by increasing chlorophyll and carotenoid content, enhancing antioxidant enzyme activities, and lowering MDA and H2O2 levels. However, CeO2 NPs at 100 mg L−1 had adverse effects on certain physiological parameters, highlighting the need for careful consideration of the applied concentration of CeO2 NPs. Considering the response of essential oil compounds, combination of salinity stress and CeO2 treatments led to an increase in the concentrations of L-menthone, pulegone, and 1,8-cineole, which are the predominant compounds in spearmint essential oil. In summary, foliar application of CeO2 NPs strengthened the resilience of spearmint plants against salinity stress, offering new insights into the potential use of CeO2 NP treatments to enhance crop stress tolerance.

OsNAL11 and OsGASR9 Regulate the Low-Temperature Germination of Rice Seeds by Affecting GA Content

Low temperatures cause serious threat to rice seed emergence, which has become one of the main limiting factors in the production of direct seeding rice. It is of great importance to study the genes controlling low-temperature tolerance during seed germination and to mine the possible regulatory mechanism for developing new rice varieties with immense low-temperature germination ability. In the current research study, two types of mutants of nal11 and gasr9, derived from the WT (wild type) ZH11, were used for the analysis of low-temperature germinability. The results showed that the nal11 and gasr9 mutants displayed no significant difference in germination rate with ZH11 at room temperature, but the mutants showed significantly lower germination rates, germination potential and germination index, and slowed seedling growth in the simulated direct seeding experiments at low temperatures compared to ZH11. Additionally, the activity of POD, SOD, CAT, and anti-superoxide anion radial activity were significantly reduced, but the levels of MDA and H2O2 were significantly higher in the nal11 and gasr9 mutant seeds that were germinated at low temperatures compared to ZH11. Further analysis revealed that the levels of total active GA, especially GA4 and GA7, were significantly lower in the nal11 and gasr9 mutants than that in ZH11 during low-temperature germination. Based on qRT-PCR analysis, the expression levels of some GA synthesis-related genes were higher, whereas some were lower in the nal11 and gasr9 mutants than those in ZH11, however, the GA metabolism-related genes OsGA2ox8 and OsGA2ox10 and the GA signaling negative regulator gene SLR1 were significantly up-regulated in both nal11 and gasr9 mutants at several time points during low-temperature germination. This may explain the lower GA levels in the nal11 and gasr9 mutants. Furthermore, the interaction between the OsNAL11 and OsGASR9 proteins was confirmed by Y2H, LUC, and Co-IP assays. This study provides preliminary insights into the regulatory mechanism of the OsNAL11 and OsGASR9 genes, which control the low-temperature germination of rice seeds by affecting the GA pathway. Our study will provide the basis for further mining the molecular mechanisms of low-temperature germination in rice and valuable theoretical reference for breeding varieties with strong low-temperature germinability.

A highly permeable nanoplatform based on functionalized carbon dots for synergistic reactive oxygen/nitrogen species tumor therapy

Reactive oxygen species (ROS)-based antitumor strategies, particularly chemodynamic therapy, have garnered considerable attention. However, challenges such as difficulties in achieving deep penetration, relatively low H2O2 levels in the tumor microenvironment, the requirement for low pH by the Fenton reaction, and their short lifespan have impeded satisfactory therapeutic outcomes. Hence, we have developed a nanoplatform with enhanced permeability that not only generates significant amounts of ROS but also converts them into longer-lasting reactive nitrogen species (RNS), thereby improving tumor therapy efficacy. In our study, carbon dots were functionalized by doping with gold atoms and grafting nitrosoglutathione (GSNO) to form ACN, which exhibits glucose oxidase-like properties and enables laser-responsive NO release. ACN and indocyanine green (ICG) were then loaded onto MnO2 nanoflowers to form MnO2@AI. Upon arrival at the tumor site, MnO2 reacts with H2O2 and GSH, leading to its degradation and the subsequent release of ACN, which is characterized by three permeation-promoting properties: ultra-small size, positive charge, and NO content. In addition, ACN promotes H2O2 production through glucose metabolism and reduces pH, both of which enhance the Fenton-like reaction of MnO2, thereby amplifying ROS generation. The ICG in MnO2@AI enhances its photothermal properties, leading to the responsive release of NO from GSNO grafted onto ACN, which then reacts with the increased ROS to generate more toxic RNS. Collectively, the approach described herein offers substantial potential for advancing the treatment of malignant tumors.

Radish and Spinach Seedling Production and Early Growth in Response to Struvite Use as a Phosphorus Source.

To sustain the increasing needs of a rapidly growing population, agriculture has relied on the use of synthetic fertilizers to intensify its production. However, the economical, environmental and health impacts associated with their use have raised significant concerns, especially given the scarcity of phosphorus. Utilizing nutrient-recovered materials like struvite can enhance circularity in agriculture and reduce its reliance on synthetic fertilizers. The objective of this study was to assess the implementation of struvite as a complete substitute to triple superphosphate, for radish and spinach seedling production and early growth, with or without supplementary fertigation. In addition, two rates of struvite were examined (0.68 and 1.37 g L-1 substrate) to evaluate its solubility. In the germination of radish, struvite had similar performance with conventional fertilization, while in spinach, the use of struvite decreased mean germination times. Both plants maintained comparable growth, chlorophyll content and antioxidant capacity when struvite was used, in comparison to conventional fertilizers. However, higher struvite rates under un-fertigated conditions significantly increased the chlorophyll b and total chlorophylls in the spinach, while phenolics and flavonoids decreased, contingent on the fertigation applications. In the radish, struvite maintained similar MDA and H2O2 levels to conventional fertilization, while decreases occurred in the spinach, with the application of ST1 under un-fertigated conditions, compared with conventional fertilization. The P and N contents of the plants were also affected, though these effects varied depending on the plant species, fertigation applications and struvite rates. This variance can be attributed to the characteristics of struvite, the plant species and the cultivation practices. The results of this study suggest that struvite can be successfully implemented in seedling production, establishing significant prospects for its commercialization and use in nurseries.

Choline supplementation reduces cadmium uptake and alleviates cadmium toxicity in Solanum lycopersicum seedlings

Sustainable plant production in soil polluted with heavy metals requires that novel strategies are developed for the benefit of humans and other living things. Cadmium (Cd) is a common heavy metal pollutant for plants, and there is limited information on the use of exogenous bio-regulators to reduce the accumulation and toxic effects of Cd pollution in plants. Choline is an endogenous quertarnary amine that is known to improve stress tolerance in plants, while its mechanism of action in certain conditions is yet to be determined. This study investigated the effects of foliar choline supplementation (10 mM) on Solanum lycopersicum seedlings exposed to Cd application (50 mg/L in soil). The seedlings were randomized to five groups: Control (E1), Cd stress (E2), Choline supplementation after Cd stress (E3), Choline (E4), and Choline supplementation before Cd stress (E5). Following the applications, the Cd content, growth and development parameters (chlorophyll content, fresh and dry weight), oxidative stress parameters (H2O2 and MDA contents), as well as antioxidative defense system (SOD, GSH, AsA, and TPC contents) were analyzed. Choline supplementation after Cd stress reduced the enhanced Cd content in roots by 38% but did not alter it in leaves (p > 0.05) compared to the Cd group. Choline supplementation before Cd stress decreased Cd content both in roots by 87.5% and in leaves by 50%. Choline supplementation after and before Cd stress increased fresh and dry weights in both roots and leaves. While the Cd group (E2) increased the H2O2 level and SOD activity, no remarkable change was observed in H2O2 levels in all choline supplementations (E3, E4, E5). Therefore, lipid peroxidation (MDA) was not observed in choline supplementation before Cd stress (E5), however, when the choline was applied after Cd stress (E3) MDA content was reduced by 40% compared with the Cd stress group (E2). Choline supplementations after and before Cd stress (E3, E5) increased AsA content by 30%, while the Cd group (E2) decreased it by 60% compared with the control group (E1). Choline supplementations before Cd stress (E5) increased TPC by 33%, while the Cd group (E2) decreased it by 18%, moreover, when choline was applied after Cd stress (E3), no change was observed compared to the control group. These data suggest that choline prevents inhibition of plant growth due to Cd toxicity by reducing Cd uptake. The results provided in the present study are likely to enhance the quality and efficiency of crop production in heavy metal-polluted areas.

Redox-Inducible Radiomimetic Photosensitizers Selectively Suppress Cancer Cell Proliferation by Damaging DNA through Radical Cation Chemistry.

Radiotherapy leverages ionizing radiation to kill cancer cells through direct and indirect effects, and direct effects are considered to play an equal or greater role. Several photosensitizers have been developed to mimic the direct effects of radiotherapy, generating radical cations in DNA models, but none has been applied in cellular studies. Here, we design a radiomimetic photosensitizer, producing DNA radical cations in cells for the first time. To reduce adverse effects, several redox-inducible precursors are prepared as cancer cells have elevated levels of GSH and H2O2. These precursors respond to GSH or H2O2, releasing the active photosensitizer that captures DNA abasic (AP) sites and generates DNA radical cations upon photolysis, without disrupting the redox state of cells. DNA radical cations migrate freely and are eventually trapped by H2O and O2 to yield DNA lesions, thus triggering DNA damage response. Our study suggests that direct effects of radiotherapy suppress cancer cell proliferation mainly by inducing G2/M phase cell cycle arrest, rather than promoting apoptosis. Synergistic effects of the precursor and chemotherapeutic agents are also observed in combination phototherapy. Beyond highlighting an alternative strategy for phototherapy, this proof-of-concept study affords a facile cellular platform to study the direct effects of radiotherapy.

Redox‐Inducible Radiomimetic Photosensitizers Selectively Suppress Cancer Cell Proliferation by Damaging DNA through Radical Cation Chemistry

AbstractRadiotherapy leverages ionizing radiation to kill cancer cells through direct and indirect effects, and direct effects are considered to play an equal or greater role. Several photosensitizers have been developed to mimic the direct effects of radiotherapy, generating radical cations in DNA models, but none has been applied in cellular studies. Here, we design a radiomimetic photosensitizer, producing DNA radical cations in cells for the first time. To reduce adverse effects, several redox‐inducible precursors are prepared as cancer cells have elevated levels of GSH and H2O2. These precursors respond to GSH or H2O2, releasing the active photosensitizer that captures DNA abasic (AP) sites and generates DNA radical cations upon photolysis, without disrupting the redox state of cells. DNA radical cations migrate freely and are eventually trapped by H2O and O2 to yield DNA lesions, thus triggering DNA damage response. Our study suggests that direct effects of radiotherapy suppress cancer cell proliferation mainly by inducing G2/M phase cell cycle arrest, rather than promoting apoptosis. Synergistic effects of the precursor and chemotherapeutic agents are also observed in combination phototherapy. Beyond highlighting an alternative strategy for phototherapy, this proof‐of‐concept study affords a facile cellular platform to study the direct effects of radiotherapy.

Exploring the synergistic benefits of biochar and gibberellic acid in alleviating cadmium toxicity

Cadmium (Cd) toxicity significantly threatens agricultural productivity and food safety. Developing effective strategies to enhance plant tolerance to Cd stress is essential. This study investigates the synergistic effects of biochar (BC) and gibberellic acid (GA3) on mitigating Cd toxicity in maize (Zea mays), focusing on their impact on oxidative stress markers and antioxidant enzyme activities. Soil samples were collected from the Cholistan Institute of Desert Studies (CIDS) and analyzed for trace metal ions and other properties. Biochar was produced from fruit and vegetable waste, washed, washed, deashed, and mixed with 10 ppm GA3. FH-1036 hybrid maize seeds were sterilized and planted in pots containing soil with varying Cd levels (0, 8, and 16 mg Cd/kg soil). Twelve treatments were established, including control, GA3, BC, and their combinations under different Cd stress levels. Plants were irrigated to maintain 60% field capacity and harvested at the V10 growth stage. Hydrogen peroxide (H2O2) contents and activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) were measured in roots, stems, and leaves. Statistical analysis was performed using OriginPro 2021, with ANOVA and Fisher’s LSD test used to determine significant differences. GA3 and BC treatments significantly reduced H2O2 levels in maize roots, stems and leaves under Cd stress. The combined treatment of GA3 + BC showed the most significant reduction in H2O2 levels across all plant parts, reducing root H2O2 by 50%, stem H2O2 by 55%, and leaf H2O2 by 53% under severe Cd stress (16 mg Cd/kg). SOD activity increased under non-stress conditions but decreased under Cd stress, with the highest activity observed in the combined treatment. POD activity followed a similar pattern, with GA3 + BC treatment resulting in the most significant increases under non-stress conditions and the least reductions under Cd stress. CAT activity showed substantial increases with GA3 + BC treatment, particularly under severe Cd stress, with a notable rise over the control. APX activity also exhibited enhancements with GA3 and BC treatments, especially in the combined treatment under various Cd stress levels. This study highlights the potential of combined BC and GA3 treatments in improving Cd stress tolerance in maize. Future research should focus on field trials and the long-term impacts of these treatments on crop productivity and soil health.

Responses of Intestinal Antioxidant Capacity, Morphology, Barrier Function, Immunity, and Microbial Diversity to Chlorogenic Acid in Late-Peak Laying Hens.

This study examined the influence of chlorogenic acid (CGA) on gut antioxidant status, morphology, barrier function, immunity, and cecal microbiota in late-peak laying hens. A total of 240 Hy-Line Brown hens, aged 43 weeks, were randomly assigned to four groups, the basal diet +0, 400, 600, and 800 mg/kg CGA, for 12 weeks. The results revealed that CGA significantly reduced ileal H2O2 and malondialdehyde levels; increased duodenal height, ileal villus height, and villus height-to-crypt depth ratio; while decreasing jejunal crypt depth. The 600 and 800 mg/kg CGA significantly upregulated the duodenal, jejunal, and ileal ZO-1 and occludin gene expression; increased IgG levels in serum and ileum; and upregulated ileal IgA gene expression. The 600 mg/kg CGA significantly upregulated CD3D and CD4 gene expression, while downregulating IL-1β gene expression in duodenum, jejunum, and ileum. Moreover, CGA changed the gut microbiota structure. The SCFA-producing bacteria unclassified_f__Peptostreptococcaceae, unclassified_f_Oscillospiraceae, Pseudoflavonifractor, Lachnospiraceae_FCS020_group, Oscillospira, Elusimicrobium, Eubacterium_ventriosum_group, Intestinimonas, and norank_f_Coriobacteriales_Incertae_Sedis were significantly enriched in the 400, 600, and/or 800 mg/kg CGA groups. The bacteria Lactobacillus, Bacillus, and Akkermansia were significantly enriched in the 600 mg/kg CGA group. Conclusively, dietary CGA (600-800 mg/kg) improved intestinal antioxidant status, morphology, barrier and immune function, and beneficial microbiota growth in late-peak laying hens.

CsNAC17 enhances resistance to Colletotrichum gloeosporioides by interacting with CsbHLH62 in Camellia sinensis

Abstract The pathogen Colletotrichum gloeosporioides causes anthracnose, a serious threat to tea trees around the world, particularly in warm and humid regions. RNA-Seq data have previously indicated NAC transcription factors are involved in anthracnose resistance, but underlying mechanisms remain unclear. The BiFC, Split-LUC, and Co-IP assays validated the interaction between CsbHLH62 and CsNAC17 identified through yeast two-hybrid (Y2H) screening. CsNAC17 or CsbHLH62 overexpression enhanced anthracnose resistance, as well as enhanced levels of H2O2, hypersensitivity, and cell death in Nicotiana benthamiana. The NBS-LRR gene CsRPM1 is regulated by CsNAC17 by binding directly to its promoter (i.e., CACG, CATGTG), while CsbHLH62 facilitates CsNAC17’s binding and increases trascriptional activity of CsRPM1. Additionally, transient silencing of CsNAC17 and CsbHLH62 in tea plant leaves using the virus-induced gene silencing (VIGS) system resulted in decreased resistance to anthracnose. Conversely, transient overexpression of CsNAC17 and CsbHLH62 in tea leaves significantly enhanced the resistance against anthracnose. Based on these results, it appears that CsbHLH62 facilitates the activity of CsNAC17 on CsRPM1, contributing to increased anthracnose resistance.

HERBAL-INFUSED EGYPTIAN BEE HONEY: A BOON OR A CURSE? ITS IMPACT ON SENSORIAL, PHYSICOCHEMICAL, & ANTIBACTERIAL PROPERTIES

Herbal honey mixture remedies are well known for their therapeutic benefits in traditional medicine. This research aspired to assess melissopalynological, sensorial, physicochemical, & antibacterial activity for three types of honey (clover, citrus, and cucurbits) and their mixtures with black seed, date palm pollen, & wheat germ at 1, 2.5, & 5%. The best mixtures were chosen according to overall acceptability. Consumer’s preference was given to raw honey. However, some mixtures were as acceptable as raw honey. Honey’s naturalness is characterized by a predominance of fructose over glucose, as revealed by melissopalynological analysis. Herbs infused with discrete kinds of honey typically exhibited higher electrical conductivity, free acidity, ash, H2O2, and HMF levels, but lower pH. The type of honey herb may affect the physicochemical characteristics of honey in different ways. Honey, whether used alone or in combination with the three herbs, demonstrated the same significant antibacterial effect for Staphylococcus aureus and MRSA. Inhibition zones of honey and its mixtures were lower than the control for Pseudomonas aeruginosa. Most undiluted samples created larger bacterial inhibition zones than their 50% diluted counterparts.

Mesoporous cerium oxide nanoenzyme for Efficacious impeding tumor and metastasis via Conferring resistance to anoikis

Tumor cells can survive when detached from the extracellular matrix or lose cell-to-cell connections, leading to a phenomenon known as anoikis resistance (AR). AR is closely associated with the metastasis and proliferation of tumor cells, enabling them to disseminate, migrate, and invade after detachment. Here, we have investigated a novel composite nanoenzyme comprising mesoporous silica/nano-cerium oxide (MSN-Ce@SP/PEG). This nanoenzyme exhibited satisfactory catalase (CAT) activity, efficiently converting high levels of H2O2 within tumor cells into O2, effectively alleviating tumor hypoxia. Furthermore, MSN-Ce@SP/PEG nanoenzyme demonstrated high peroxidase (POD) activity, elevating reactive oxygen species (ROS) levels and attenuating AR in hepatocellular carcinoma (HCC) cells. The MSN-Ce@SP/PEG nanoenzyme exhibited satisfactory dual bioactivity in CAT and POD and was significantly enhanced under favorable photothermal conditions. Through the synergistic effects of these capabilities, the nanoenzyme disrupted the epithelial-mesenchymal transition (EMT) process in detached HCC cells, ultimately inhibiting the recurrence and metastasis potential of anoikis-resistant HCC cells. This study represents the first report of a novel nanoenzyme based on mesoporous silica/nano-cerium oxide for treating AR in HCC cells, thereby suppressing HCC recurrence and metastasis. The findings of this work offer a pioneering perspective for the development of innovative strategies to prevent the recurrence and metastasis of HCC.

Brain Abnormalities in Young Single- and Double-Heterozygote Mice for Both Nkx2-1- and Pax8-Null Mutations.

In humans and mice, Nkx2-1 and Pax8 are crucial morphogenic transcription factors defining the early development of the thyroid and specific extrathyroidal tissues. By using 3-month-old single or double heterozygotes for Nkx2-1- and Pax8-null mutations (DHTP) mice, we studied brain abnormalities under different human-like dysthyroidisms, focusing on putative alterations of specific neurotransmitter systems, expression of markers of pre- and post-synaptic function and, given the physio-pathological role mitochondria have in controlling the bioenergetic status of neurons, of mitochondrial dynamics and oxidative balance. Compared to Wt controls, DHTP mice, bearing both systemic and brain hypothyroidism, showed altered expression of synaptic markers, generic and cholinergic (corroborated by immunohistochemistry in caudate, putamen, hippocampus, and basal forebrain) and glutamatergic ones, and reduced expression of key proteins of synaptic plasticity potency and several isoforms of glutamate receptors. The brain of DHTP mice was characterized by lower levels of H2O2 and imbalanced mitochondrial dynamics. Nkx2-1 + / - mice showed dopaminergic neuron-specific alterations, morphologically, more evident in the substantia nigra of DHTP mice. Nkx2-1 + / - mice also showed enhanced mitochondrial biogenesis and oxidative capacity likely as a global response of the brain to Nkx2-1 haploinsufficiency and/or to their elevated T3 circulating levels. Reduced transcription of both tyrosine hydroxylase and dopamine transporter was observed in Pax8 + / - euthyroid mice, suggesting a dopaminergic dysfunction, albeit likely at an early stage, but consistent with the deregulated glucose homeostasis observed in such animals. Overall, new information was obtained on the impact of haploinsufficiency of Pax8 and NKx2-1 on several brain neuroanatomical, molecular, and neurochemical aspects, thus opening the way for future targeting brain dysfunctions in the management of both overt and subclinical thyroid dysfunctions.

Tumour reoxygenation after intratumoural hydrogen peroxide (KORTUC) injection: a novel approach to enhance radiosensitivity

BackgroundKORTUC (0.5% hydrogen peroxide (H2O2) in 1% sodium-hyaluronate) releases cytotoxic levels of H2O2 in tissues after intratumoural injection. High levels of tumour control after radiotherapy plus KORTUC are reported in breast cancer patients. Here, we use human xenograft models to test the hypothesis that oxygen microbubbles released post-KORTUC are effective in modifying the hypoxic tumour microenvironment.Methods and materialsPimonidazole and Image-iT™ Red (live hypoxia marker) were utilised to assess dose-dependent changes in hypoxia post-H2O2 in HCT116 and LICR-LON-HN5 spheroids. Using a dual 2-nitroimidazole-marker technique and phospho-ATM we evaluated changes in hypoxia and reactive oxygen species (ROS) respectively, in HCT116 and LICR-LON-HN5 xenografts following intratumoural KORTUC.ResultsA significant reduction in Image-iT™ Red fluorescence was observed in spheroids 1 h post-H2O2 at ≥1.2 mM, maintained at 24 h. Ultrasound demonstrated sustained release of oxygen microbubbles within tumours, 1 h post-KORTUC. Hypoxia markers demonstrated significant tissue reoxygenation in both models post-KORTUC and significantly increased phospho-ATM foci reflecting increased ROS production.ConclusionIntratumoural KORTUC represents a novel oxygen delivery method, which can be exploited to enhance radiation response. If efficacy is confirmed in the ongoing phase 2 breast trial it could improve treatment of several tumour types where hypoxia is known to affect radiotherapy outcomes.

Dual-responsive natural killer cell nano-engagers for cancer immunotherapy via inhibiting IL-6/JAK2/STAT3 pathway

Natural killer (NK) cell-based immunotherapy is a promising approach for treating solid tumors and hematological malignancies. However, its therapeutic efficacy is limited by poor tumor infiltration and suppressive tumor microenvironment. Here, we introduce a rapid, simple, and efficient solution: bovine serum albumin-stabilized ultra-small (4 nm) NK cell nano-engagers, termed Bi2Se3@BSA nanodots (Nds). These Nds, responsive to high H2O2 levels in tumor cell environments, enhance near-infrared (NIR)-II photothermic immunotherapy. In vitro and in vivo experiments demonstrate their effectiveness in activating photothermal therapy (PTT)-induced immunogenic cell death (ICD), initiating immune cascade reactions, and stimulating immune response activation. By upregulating NKG2D, RAE-1, and secreting cytokines such as IFN-γ and TNF-α, targeted NK cell infiltration is achieved, reversing the immunosuppressive tumor microenvironment and optimizing NK cell cytotoxicity. Transcriptomic analysis confirms the association of immune response activation with the IL-6/JAK2/STAT3 signaling pathway. Notably, combining these nano-engagers with immune checkpoint inhibitors (aPD-1) significantly enhances therapeutic efficacy, facilitating tumor eradication and reducing recurrence risk. Taken together, NK cell nano-engagers inhibit the IL-6/JAK2/STAT3 signaling pathway, target NK cell activation, stimulate immune functions, and improve the immunosuppressive microenvironment. This study presents an alternative strategy for NK cell-based immunotherapy and highlights this promising tool for cancer immunotherapy.

Protective effects of Khaya senegalensis stem bark extracts against acetaminophen-induced oxidative damage, dyslipidaemia, and hepatotoxicity in rats

Background Free radical attacks have been implicated in the aetiology of many diseases and several plants are used traditionally for the management of many oxidative-stress related diseases. Khaya senegalensis is used traditionally for the management diseases such as diabetes and for the treatment of infections. However, mechanisms underlying actions of K. senegalensis are poorly understood. Purpose This study aimed at the preliminary determination of the phytochemical constituents and investigation of the antioxidative and hepatoprotective actions of K. senegalensis in acetaminophen-treated rats. Method Aqueous extracts of K. senegalensis were screened for the presence of key phytochemicals. Total flavonoid and phenolic contents were quantified. Wistar albino rats were pre-treated with saline (control) or graded concentrations of K. senegalensis (50 – 200mg/kgbw) for 10 days prior to acetaminophen (2g/kg body weight) administration. Serum levels of vitamin C, thiobarbituric reactive substances, catalase activities, enzyme markers of liver function were assessed. Cholesterol-phospholipid ratio in treated-rats were determined. Results K. senegalensis extract showed the presence of saponins, tannins, cardiac glycosides, alkaloids, flavonoids and phenolic compounds. Total phenolic and total flavonoid contents were determined as 57.14±0.85mgQE/g and 51.72±0.77mgGE/g. Acetaminophen (2g/kg bw) raised serum TBARS (4.7-fold, P<0.001), H2O2 levels (2.3-fold, P<0.001), AST (5.9-fold, P<0.001), ALT (6.6-fold, P<0.001) and ALP (4.2-fold, P<0.001) and reduced serum levels of vitamin C (54%, P<0.001) and catalase activity (74.6%, P<0.001). Treatment of K. senegalensis extracts inhibited effects of acetaminophen on TBARS (18.2% - 46.4%, P<0.05 – 0.001), vitamin C (1.4 – 1.8-fold, P<0.001 – 0.05), H2O2 levels (19.1 – 50.1%, P<0.001-0.05), catalase activities (1.4 – 3.1-fold, P<0.001 – 0.05), AST (27.7 – 62.8%, P<0.001 – 0.05), ALT (35.6 – 57.5%, P<0.001 – 0.05) and ALP (15.9 – 46.2%, P<0.01 – 0.05). The extract reduced cholesterol-phospholipid ratio (21 – 31%, P<0.05). Conclusion These results motivate further development of the therapeutic potential of K. senegalensis

Glucose-fueled cationic nanomotors for promoting the healing of infected diabetic wounds

Hyperglycemia-promoted bacterial infection will seriously exacerbate diabetic wounds, and its current clinical treatments are suffering from the adverse effects associated with off-target, bacterial resistance, and glycemic fluctuation. Herein, we present a kind of glucose-fueled cationic nanomotors capable of remarkably enhancing antibacterial efficacy, and thus expediting diabetic wound healing. The nanomotors have positively charged surfaces, and consist of mesoporous bowl-shaped polydopamine nanoparticles grafted with quaternized polymer brushes and coupled with glucose oxidase (GOx) and catalase (CAT). Stemming from the GOx-CAT cascade reaction in diabetic wound microenvironment, they can perform robust chemotactic motion towards both high glucose regions, where bacteria proliferation predominantly occurs, and elevated H2O2 levels, which bacterial metabolism produced. This enables the nanomotors to facilitate targeted migration towards bacteria-rich regions and simultaneous downregulation of glycemic levels, as well as to significantly enhance the electrostatic interaction between antibacterial components and bacteria. Consequently, the nanomotors exhibit amplified contact-killing effects of their attached cationic molecules, leading to an almost 10-fold enhancement in antibacterial efficacy compared to previous counterparts. The in vivo experiments approved that the nanomotors demonstrated the accelerated healing of infected diabetic wounds by S. aureus and biosafety. The results herein provide an insight into the clinical treatment of infected diabetic wounds.