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Fully restoring the lost population of cardiomyocytes and heart function remains the greatest challenge in cardiac repair post myocardial infarction. In this study, a pioneered highly ROS-eliminating hydrogel was designed to enhance miR-19a/b induced cardiomyocyte proliferation by lowering the oxidative stress and continuously releasing miR-19a/b in infarcted myocardium in situ. In vivo lineage tracing revealed that â¼20.47 % of adult cardiomyocytes at the injected sites underwent cell division in MI mice. In MI pig the infarcted size was significantly reduced from 40 % to 18 %, and thereby marked improvement of cardiac function and increased muscle mass. Most importantly, our treatment solved the challenge of animal death--all the treated pigs managed to live until their hearts were harvested at day 50. Therefore, our strategy provides clinical conversion advantages and safety for healing damaged hearts and restoring heart function post MI, which will be a powerful tool to battle cardiovascular diseases in patients.
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Proliferación Celular , MicroARNs , Infarto del Miocardio , Miocitos Cardíacos , Estrés Oxidativo , Animales , MicroARNs/metabolismo , MicroARNs/genética , Miocitos Cardíacos/metabolismo , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Estrés Oxidativo/efectos de los fármacos , Ratones , Porcinos , Hidrogeles/química , Ratones Endogámicos C57BL , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Anthriscus sylvestris (L.) Hoffm has a long history of use for anti-aging, although the anti-aging properties of its decoction ingredients have been seldom explored. This study marks the first detailed examination of the in vivo anti-aging activity of A. sylvestris roots polysaccharide (AP). Structural analyses revealed that AP is a neutral heteropolysaccharide with an average molecular weight (Mw) of 34.17 kDa, comprising glucose, xylose, galactose, mannose, and arabinose, with a backbone primarily of 1,4-α-D-Glc and minor branching at 1,4,6-α-D-Man. Its advanced structure is characterized by stable triple-helical chains and nanoscale agglomerated spherical particles. Using a D-gal-induced aging mouse model, further investigation showed that AP boosts the activity of various antioxidant enzymes via the Nrf2/HO-1/NQO1 signaling pathway. Aging-related immune decline was also mitigated by an increase in lymphocyte production in thymus. Moreover, AP reduced inflammation and downregulated aging genes p53 and p21 in hippocampus and liver tissues, enhanced the cholinergic system, and improved liver functions and lipid metabolism. The collective impact of these mechanisms underscores the robust anti-aging properties of AP. These findings highlight the anti-aging and immunomodulatory potential of A. sylvestris polysaccharide, broadening the understanding of its active components.
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Mitochondria functionally degrade as neurons age. Degenerative changes cause inefficient oxidative phosphorylation (OXPHOS) and elevated electron leakage from the electron transport chain (ETC) promoting increased intramitochondrial generation of damaging reactive oxygen and reactive nitrogen species (ROS and RNS). The associated progressive accumulation of molecular damage causes an increasingly rapid decline in mitochondrial physiology contributing to aging. Melatonin, a multifunctional free radical scavenger and indirect antioxidant, is synthesized in the mitochondrial matrix of neurons. Melatonin reduces electron leakage from the ETC and elevates ATP production; it also detoxifies ROS/RNS and via the SIRT3/FOXO pathway it upregulates activities of superoxide dismutase 2 and glutathione peroxidase. Melatonin also influences glucose processing by neurons. In neurogenerative diseases, neurons often adopt Warburg-type metabolism which excludes pyruvate from the mitochondria causing reduced intramitochondrial acetyl coenzyme A production. Acetyl coenzyme A supports the citric acid cycle and OXPHOS. Additionally, acetyl coenzyme A is a required co-substrate for arylalkylamine-N-acetyl transferase, which rate limits melatonin synthesis; therefore, melatonin production is diminished in cells that experience Warburg-type metabolism making mitochondria more vulnerable to oxidative stress. Moreover, endogenously produced melatonin diminishes during aging, further increasing oxidative damage to mitochondrial components. More normal mitochondrial physiology is preserved in aging neurons with melatonin supplementation.
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Cadmium (Cd) is a toxic heavy metal that poses risks to crop production and food safety worldwide. This study evaluated whether manganese (Mn) addition could mitigate Cd toxicity and reduce Cd accumulation in barley seedlings. Hydroponically grown seedlings of Cd-tolerant (WSBZ) and Cd-sensitive (Dong17) barley cultivars were treated with 0.1 µM and 1 µM Cd as well as 0.2 mM Mn alone and in a combination with 0.1 or 1.0 µM Cd for 21 days. Cd exposure caused the dramatic alteration of growth and physiological parameters by disrupting chloroplast, and increased Cd accumulation in both genotypes. However, Mn addition markedly alleviated the negative impacts of all examined parameters caused by Cd stress. Cd addition enhanced expression of anti-oxidative enzyme related genes, including HvSOD, HvCAT, HvAPX, HvPOD in the two barley genotypes exposed to Cd stress. The expression analysis showed nearly all HvNRAMPs genes are dramatically up regulated by both Mn and Cd, with WSBZ having higher expression than Dong 17. Notably, HvNRAMP1 showed the highest expression due to Mn addition, highlighting its crucial role in Mn uptake and transportation in barley. Moreover, Cd stress and Mn addition increased and suppressed the expression of HvYSL5, HvHMA2 and HvHMA3, respectively. Conversely, the expression of HvYSL2, HvIRT1 and HvMTP8 was upregulated by both Mn and Cd treatments, with a further increase observed in the combined Cd and Mn treatments. It may be concluded that sufficient Mn supply is quite important for reducing Cd uptake and accumulation in plants.
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Probiotics are used in cheese fermentation to endow the product with unique functional properties, such as enhanced flavor and aroma development through proteolysis and lipolysis. In this study, two probiotic Lactobacillus strains, Lactobacillus plantarum A3 and Lactobacillus reuteri WQY-1, were selected to develop new probiotic cheeses in the form of single- and mixed-strain starters. The results demonstrated that the L. plantarum A3 single-strain group and the L. plantarum A3/L. reuteri WQY-1 mixed fermentation group exhibited superior product performance, particularly the release of functional hydrolysates during cheese ripening. Furthermore, Label-free quantitative proteomic analysis revealed 26 unique antioxidant peptides in the L. plantarum A3 single-strain group and 53 in the L. plantarum A3/L. reuteri WQY-1 mixed fermentation group. Among these, CMENSAEPEQSLACQCL (ß-lactoglobulin), CMENSAEPEQSLVCQCL (ß-lactoglobulin), and IQYVLSR (κ-casein) have been found to possess potential antioxidant properties both in vitro and in vivo. This confirmed that milk-derived protein peptides in cheese products exhibit potential antioxidant functions through the hydrolysis of probiotic strains.
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The objective of this study was to prepare an active packaging film using phosphorylated soy protein isolate (PPS) and Artemisia sphaerocephala Krasch. gum (ASKG) as film matrices, with the incorporation of pomegranate peel extract (PPE) to preserve fresh-cut apples. The results showed that PA-PPE (PPS/ASKG-PPE) films significantly increased thickness by 24.47â¯%, tensile strength by 58.76â¯%, and elongation at break by 30.48â¯%. Additionally, water vapor permeability and oxygen permeability decreased significantly to 6.17â¯×â¯10-13 and 0.62â¯×â¯10-13 Kgâ¢mâ¢m-2â¢s-1â¢Pa-1, respectively. FTIR, XRD, and SEM analyses confirmed the formation of intermolecular hydrogen bonds between PPS, ASKG, and polyphenols extracted from pomegranate peel, indicating excellent compatibility. Furthermore, radical scavenging activity experiments demonstrated that these films exhibited a remarkable ability to scavenge DPPH and ABTS+ radicals up to 70.44â¯% and 74.28â¯%, respectively, when the PPE content was at 3â¯wt%. Moreover, PPS could achieve a sustained release effect on polyphenols with a relatively low release rate (63.83â¯%) even after seven days' time elapsed. Finally, the PA-PPE film displayed superior performance in reducing the weight loss and browning index of fresh-cut apples within 24â¯h of storage. The development of PA-PPE film could promote sustainable resource protection and demonstrate promising prospects in the field of fresh-cut fruit packaging.
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Sensorineural hearing loss (SNHL) represents a significant clinical challenge, predominantly attributed to oxidative stress-related mechanisms. In this work, we report an innovative antioxidant strategy for mitigating SNHL, utilizing synthetically engineered allomelanin nanoparticles (AMNPs). Empirical evidence elucidates AMNPs' profound capability in free radical neutralization, substantiated by a significant decrement in reactive oxygen species (ROS) levels within HEI-OC1 auditory cells exposure to cisplatin or hydrogen peroxide (H2O2). Comparative analyses reveal that AMNPs afford protection against cisplatin-induced and noise-induced auditory impairments, mirroring the effect of dexamethasone (DEX), a standard pharmacological treatment for acute SNHL. AMNPs exhibit notable cytoprotective properties for auditory hair cells (HCs), effectively preventing ototoxicity from cisplatin or H2O2 exposure, as confirmed by both in vitro assays and cultured organ of Corti studies. Further in vivo research corroborates AMNPs' ability to reverse auditory brainstem response (ABR) threshold shifts resulting from acoustic injury, concurrently reducing HCs loss, ribbon synapse depletion, and spiral ganglion neuron degeneration. The therapeutic benefits of AMNPs are attributed to mitigating oxidative stress and inflammation within the cochlea, with transcriptome analysis indicating downregulated gene expression related to these processes post-AMNPs treatment. The pronounced antioxidative and anti-inflammatory effects of AMNPs position them as a promising alternative to DEX for SNHL treatment.
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Resveratrol (Res) has long been discovered to have antioxidant effects to prevent such as oxidation, inflammation, neurodegeneration and age-related diseases. However, its poor water solubility, low bioavailability and instability have become a barrier to its pharmaceutical application. In order to improve the neuroprotective effects and develop more potential usage of Res, three Res derivatives containing one or two glucose groups, i.e., Res-Glu1, Res-Glu2 and Res-Glu3, were designed and synthesized through click reaction. Res-Glu1, Res-Glu2 and Res-Glu3 were tested being better water solubility and stability compared to Res. Res derivatives reduced â¢OH radicals-induced DNA damage. PC12 assays indicated that glucosylated Res derivatives could alleviate H2O2-induced neurotoxicity and reduce intracellular ROS generation, demonstrating their neuroprotective effects. In addition, Res derivatives enhanced the protective effects on cerebral ischemia-reperfusion injury in rats. Res-Glu3 displayed the best neuroprotective effects among the three derivatives.
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Continuous cropping of peanuts presents significant challenges to sustainable production due to soil-borne diseases like root rot caused by Fusarium species. In this study, field inoculation experiments treatments and in vitro agar plate confrontation tests were conducted, including non-inoculated controls (CK), inoculation with Pseudomonas fluorescens (PF), Fusarium oxysporum (FO), and co-inoculation with both (PF + FO). The aim was to explore the antifungal mechanisms of Pseudomonas fluorescens in mitigating root rot and enhancing peanut yield. The results indicated that PF and PF + FO significantly enhanced peanut root activity, as well as superoxide dismutase, catalase, and glutathione S-transferase activities, while simultaneously decreasing the accumulation of reactive oxygen species and malondialdehyde contents, compared to FO treatment. Additionally, PF treatment notably increased lignin content through enhanced phenylalanine ammonia lyase, cinnamate 3-hydroxylase, and peroxidase activity compared to CK and FO treatment. Moreover, PF treatment resulted in longer roots and a higher average diameter and surface area, potentially due to increased endogenous levels of auxin and zeatin riboside, coupled with decreased abscisic acid content. PF treatment significantly elevated chlorophyll content and the maximum photochemical efficiency of PSII in the light-adapted state, the actual photochemical efficiency and the proportion of PSII reaction centers open, leading to improved photosynthetic performance. Confrontation culture assays revealed PF's notable inhibitory effects on Fusarium oxysporum growth, subsequently reducing rot disease incidence in the field. Ultimately, PF treatment led to increased peanut yield by enhancing plant numbers and pod weight compared to FO treatment, indicating its potential in mitigating Fusarium oxysporum-induced root rot disease under continuous cropping systems.
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Acetaminophen (APAP) overdose is a prevalent cause of clinical pharmacological liver injury worldwide. Artemether (ART), a first-line antimalarial drug, has demonstrated hepatoprotective activity. However, its effect on APAP-induced acute liver injury (AILI) remains unclear. In this study, we investigated whether ART can protect against AILI and examined its underlying mechanisms. In vivo, ART mitigated APAP-induced liver histological changes, including mitochondrial damage, hepatocyte necrosis, hepatocyte apoptosis, and inflammatory infiltration. Additionally, ART reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in APAP-induced mice. ART also activated the Nrf2-HO-1/GPX4 signaling pathway, exerting antioxidant effects in both in vitro and in vivo models of AILI. To confirm Nrf2 as a target of ART in vivo, we pretreated C57BL/6 mice with the Nrf2 inhibitor, ML385. The results indicated that inhibiting Nrf2 diminishes the protective effect of ART against AILI. Overall, our findings suggest that ART's protective effect against AILI is mediated through the Nrf2-related antioxidant pathway.
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Atherosclerosis is a persistent inflammatory condition of the blood vessels associated with abnormalities in lipid metabolism. Development of biomimetic nanoplatforms provides an effective strategy. Herein, inspired by the peptide CLIKKPF spontaneously coupling to phosphatidylserine (PS) on the inner leaflet of cell membranes specifically, MM@NPs were constructed by macrophage membrane spontaneous encapsulation of cyclodextrin-based nanoparticles modified with the peptide CLIKKPF and loaded with the hydrophobic compound resveratrol. MM@NPs could be specifically phagocytized by the activated endothelium with the overexpressed VCAM-1 for enhancing target delivery into the pathological lesion. Additionally, for the ApoE-/- mice, MM@NPs provide comprehensive treatment efficiency in reducing oxidant stress, alleviating the inherent inflammation, and decreasing cholesterol deposition, subsequently resulting in the atherosclerotic plaque regression. Therefore, MM@NPs could be one possible candidate for improving lipid metabolism and inflammation in atherosclerosis.
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Aim This study aims to investigate the antibacterial, antifungal, and phytochemical properties of methanolic tuber extracts from Terminalia chebula. Additionally, the study seeks to assess the in vitro anticancer effects of these extracts on an oral cancer cell line, as well as their antioxidant and anti-inflammatory activities. Materials and methods The research involves examining the antibacterial and antifungal properties of methanolic tuber extracts from Terminalia chebula. The phytochemical composition will be analyzed using standard techniques. The in vitro anticancer effects will be tested on an oral cancer cell line, while antioxidant and anti-inflammatory activities will be evaluated through appropriate assays. Results The study demonstrated that Terminalia chebula methanolic tuber extracts exhibit cytotoxic effects on the oral cancer cell line (KB-1), reducing cell viability as evidenced by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A concentration of 30 µg/mL induced notable morphological changes observed under an inverted fluorescence microscope. Antioxidant assays showed a maximum absorption of 85.3% with 50 µL of the extract, while anti-inflammatory tests revealed a 76.0% absorption. Antimicrobial activity, assessed via agar-well diffusion, indicated significant antibacterial effects, especially against Streptococcus mutans and Candida albicans at higher concentrations. The findings suggest promising therapeutic potential for Terminalia chebula extracts. Conclusion Terminalia chebula tuber extracts may treat diseases caused by studied organisms. The study suggests that methanolic extracts from Terminalia chebula tubers have potential commercial value due to their anti-inflammatory, antioxidant, and cytotoxic properties. The extracts induced apoptosis in an oral cancer cell line at 30 µg/mL after 24 hours. Further research is needed to understand the active components and underlying molecular mechanisms.
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This research was conducted to examine the impact of Wei Qi Booster (WQB) on immune parameters and anti-oxidative function in aged mice. Fifty aged mice were randomly assigned to five different groups. Group A was designated as the control group. Mice in Group B were receiving Levamisole at 10 mg/kg body weight. Each mouse in groups C, D and E received 0.1, 1, and 2% WQB, respectively. Another ten young mice, designated as group F, were fed regularly. The mice were fed according to the above methods for 28 days. Results showed that relative to the control group, the body weight and immune organs indexes experienced a substantial rise in the group with 1% WQB. In addition, 1% WQB could improve the activity of SOD and reduce the MDA levels. Expressions of CD4 and sIgA increased while CD8 decreased in the jejunum of aged mice treated with WQB. IL2 and IFN-γ levels increased in the 1% WQB group, showing no notable difference compared to the young mice group. The results demonstrated that WQB can elevate immune levels and enhance anti-oxidative functions in aged mice.
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Background: Inhibiting ROS overproduction is considered a very effective strategy for the treatment of peripheral nerve injuries, and Se has a remarkable antioxidant effect; however, since the difference between the effective concentration of Se and the toxic dose is not large, we synthesized a nanomaterial that can release Se slowly so that it can be used more effectively. Methods: Se@SiO2 NPs were synthesized using a mixture of Cu2-x Se nanocrystals, and the mechanism of action of Se@SiO2 NPs was initially explored by performing sequencing, immunofluorescence staining and Western blotting of cellular experiments. The mechanism of action of Se@SiO2 NPs was further determined by performing behavioral assays after animal experiments and by sampling the material for histological staining, immunofluorescence staining, and ELISA. The effects, mechanisms and biocompatibility of Se@SiO2 NPs for peripheral nerve regeneration were determined. Results: Porous Se@SiO2 was successfully synthesized, had good particle properties, and could release Se slowly. CCK-8 experiments revealed that the optimal experimental doses were 100 µM H2O2 and 200 µg/mL Se@SiO2, and RNA-seq revealed that porous Se@SiO2 was associated with cell proliferation, apoptosis, and the PI3K/AKT pathway. WB showed that porous Se@SiO2 could increase the expression of cell proliferation antigens (PCNA and S100) and antiapoptotic proteins (Bcl-2), decrease the expression of proapoptotic proteins (Bax), and increase the expression of antioxidative stress proteins (Nrf2, HO-1, and SOD2). EdU cell proliferation and ROS fluorescence assays showed that porous Se@SiO2 promoted cell proliferation and reduced ROS levels. The therapeutic effect of LY294002 (a PI3K/AKT pathway inhibitor) was decreased significantly and its effect was lost when it was added simultaneously with porous Se@SiO2. Animal experiments revealed that the regenerated nerve fiber density, myelin thickness, axon area, gastrocnemius muscle wet-to-weight ratio, myofiber area, sciatic nerve function index (SFI), CMAP, apoptotic cell ratio, and levels of antioxidative stress proteins and anti-inflammatory factors were increased following the administration of porous Se@SiO2. The levels of oxidative stress proteins and anti-inflammatory factors were significantly greater in the Se@SiO2 group than in the PNI group, and the effect of LY294002 was decreased significantly and was lost when it was added simultaneously with porous Se@SiO2. Conclusion: Se@SiO2 NPs are promising, economical and effective Se-releasing nanomaterials that can effectively reduce ROS production, inhibit apoptosis and promote cell proliferation after nerve injury via the PI3K/AKT pathway, ultimately accelerating nerve regeneration. These findings could be used to design new, promising drugs for the treatment of peripheral nerve injury.
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Proliferación Celular , Regeneración Nerviosa , Traumatismos de los Nervios Periféricos , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Selenio , Transducción de Señal , Dióxido de Silicio , Animales , Selenio/química , Selenio/farmacología , Dióxido de Silicio/química , Dióxido de Silicio/farmacología , Traumatismos de los Nervios Periféricos/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Regeneración Nerviosa/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ratas , Apoptosis/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/química , Nanopartículas/química , Masculino , Preparaciones de Acción Retardada/farmacología , Preparaciones de Acción Retardada/química , Ratas Sprague-Dawley , Estrés Oxidativo/efectos de los fármacos , Nervio Ciático/efectos de los fármacos , Nervio Ciático/lesiones , Células de Schwann/efectos de los fármacos , Células de Schwann/metabolismoRESUMEN
BACKGROUND: The tropical plant acerola of the genus Malpighia includes shrubs and trees with fruit that is high in nutrients and bioactive chemicals. Acerola stands out due to its exceptionally high ascorbic acid content, ranging from 1500 to 4500 mg/100 g. Vitamin C intake greatly influences gingival health. The addition of nanoparticles along with vitamin C-rich acerola exhibits high antioxidant and anti-inflammatory properties, thereby positively improving gingival health. METHOD: The antioxidant and anti-inflammatory properties of aqueous extracts of the acerola plant (Malpighia emarginata) were assessed. Silver nanoparticles (AgNPs) and copper oxide nanoparticles (CuONPs) were synthesized using the aqueous extract of acerola cherry gel by the phytogenic fabrication method. The antioxidant potential of silver and copper nanoparticles was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide, ferric reducing antioxidant power (FRAP), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and nitric oxide scavenging activities. RESULTS: Increasing concentrations of nanoparticles showed an increase in scavenging activity. Overall, CuONPs and AgNPs exhibited remarkable radical quenching efficacies. The anti-inflammatory effectiveness of CuONPs and AgNPs was monitored, showing suppression of protein denaturation as demonstrated by bovine serum albumin (BSA), egg albumin (EA), and membrane stabilization assays. The results revealed that increasing the doses of CuONPs and AgNPs had a positive impact on the anti-inflammatory activity of the nanoparticles. CONCLUSION: The present study revealed that both nanoparticles provided better antioxidant and anti-inflammatory activities. This study also elaborates on the pharmacological potential of both nanoparticles, which could be further explored for application in all healthcare sectors.
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BACKGROUND: 2-ethylhexyldiphenyl phosphate (EHDPP) was used widespread in recent years and it was reported to impair reproductive behaviors and decrease fertility in male Japanese medaka. However, whether EHDPP causes spermatogenesis disturbance remains uncertain. OBJECTIVES: We aimed to study the male reproductive toxicity of EHDPP and its related mechanism. METHODS: Human spermatocyte cell line GC-2 was treated with 10⯵M, 50⯵M or 100⯵M EHDPP for 24â¯h. Male CD-1 mice aged 6 weeks were given 1, 10, or 100â¯mg/kg/d EHDPP daily for 42 days and then euthanized to detect sperm count and motility. Proliferation, apoptosis, oxidative stress was detected in mice and cell lines. Metabolome and transcriptome were used to detect the related mechanism. Finally, anti-oxidative reagent N-Acetylcysteine was used to detect whether it could reverse the side-effect of EHDPP both in vivo and in vitro. RESULTS: Our results showed that EHDPP inhibited proliferation and induced apoptosis in mice testes and spermatocyte cell line GC-2. Metabolome and transcriptome showed that nucleotide metabolism disturbance and DNA damage was potentially involved in EHDPP-induced reproductive toxicity. Finally, we found that excessive ROS production caused DNA damage and mitochondrial dysfunction; NAC supplement reversed the side effects of EHDPP such as DNA damage, proliferation inhibition, apoptosis and decline in sperm motility. CONCLUSION: ROS-evoked DNA damage and nucleotide metabolism disturbance mediates EHDPP-induced germ cell proliferation inhibition and apoptosis, which finally induced decline of sperm motility.
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The poor implant-osseointegration under diabetic condition remains a challenge to be addressed urgently. Studies have confirmed that the diabetic pathological microenvironment is accompanied by excessive oxidative stress, imbalanced immune homeostasis, and persistent chronic inflammation, which seriously impairs the osteogenic process. Herein, a multifunctional bioactive interface with both anti-oxidative stress and immunomodulatory properties is constructed on titanium implants. Briefly, manganese dioxide nanosheets are coated onto mesoporous polydopamine nanoparticles loaded with carbon monoxide gas precursor, namely MnO2-CO@MPDA NPs, and then they are integrated on the titanium implant to obtain MCM-Ti. In the simulated diabetic microenvironment, under the action of MnO2 nanoenzymes, MCM-Ti can effectively eliminate intracellular reactive oxygen species while alleviating hypoxic state. Interestingly, the microenvironment mediates the responsive release of CO gas, which effectively drives macrophages toward M2 polarization, thereby ameliorating inflammatory response. The potential mechanism is that CO gas up-regulates the expression of heme oxygenase-1, further activating the Notch/Hes1/Stat3 signaling pathway. Furthermore, the conditioned medium derived from macrophages on MCM-Ti surface significantly enhances the osteogenic differentiation of BMSCs. In a type 2 diabetic rat model, MCM-Ti implant effectively alleviates the accompanying inflammation and enhances the osseointegration through the synergistic effects of resisting oxidative stress and remodeling immune homeostasis.
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Introduction: The research examined the antioxidative impact of astragalosides (AST) on experimental acute pancreatitis (AP) in mice. This study aims to assess the correlation between varying doses of astragalosides and superoxide dismutase (SOD) activity in an acute pancreatitis mouse model. By examining the interplay between astragaloside's protective effects and its antioxidant properties, we aim to deepen our understanding of its therapeutic potential in acute pancreatitis. Methods: The AP model in mice was induced by retrograde injection of sodium deoxycholate into the biliary and pancreatic ducts. Serum amylase activity was monitored at various time points following induction. Furthermore, 24 hours post-induction, levels of serum nitric oxide (NO), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content in pancreatic tissue were assessed. Results: The findings of this study illustrated that AST, while exhibiting a protective effect in experimental AP, could effectively lower the elevated serum NO levels, reduce MDA production, and enhance SOD activity in model mice. AST notably reduced MDA levels in the pancreatic tissue of AP mice, underscoring its ability to inhibit membrane peroxidation induced by oxygen free radicals. Furthermore, AST was observed to elevate SOD activity in scavenging oxygen free radicals in pancreatic tissue. Conclusion: These findings suggest that AST enhances recovery in an experimental acute pancreatitis mouse model by exerting antioxidative effects.
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Doxorubicin (Dox) is a broad-spectrum antineoplastic chemotherapeutic agent used in clinical settings, yet it exhibits significant cardiotoxicity, which in severe cases can lead to heart failure. Research indicates that oxidative stress plays a pivotal role in Dox -induced cardiomyocyte injury. Therefore, the application of antioxidants represents an effective strategy to mitigate the cardiotoxic effects of doxorubicin. In preliminary studies, we isolated an antioxidative peptide, PHWWEYRR (8P). This study utilizes a PCM cardiomyocyte-targeting peptide-modified liposome as a carrier to deliver 8P into cardiomyocytes, aiming to prevent Dox-induced cardiac injury through its antioxidative mechanism. The results demonstrated that we prepared the 8P-loaded and PCM-targeting peptide-modified liposome (P-P-8P), which exhibited good dispersibility, encapsulation efficiency, drug loading capacity, and in vitro release, along with myocardial targeting capability. In vitro experiments showed that P-P-8P could prevent oxidative stress injury in H9C2 cells, protect mitochondrial functions, and inhibit cell apoptosis through a mitochondria-dependent pathway. In vivo experiments indicated that P-P-8P could prevent abnormalities in serum biochemical indicators, cardiac dysfunction, and myocardial pathological changes in mice. In conclusion, P-P-8P effectively delivers 8P to cardiomyocytes, offering protection against the cardiotoxic effects of Dox, and holds potential as a future preventative or therapeutic agent for drug-induced cardiomyopathy.
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Antioxidantes , Doxorrubicina , Liposomas , Miocitos Cardíacos , Estrés Oxidativo , Doxorrubicina/administración & dosificación , Animales , Antioxidantes/farmacología , Antioxidantes/administración & dosificación , Antioxidantes/química , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Estrés Oxidativo/efectos de los fármacos , Masculino , Ratones , Línea Celular , Apoptosis/efectos de los fármacos , Cardiotoxicidad/prevención & control , Cardiotoxicidad/etiología , Ratas , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/toxicidad , Miocardio/patología , Miocardio/metabolismo , Liberación de Fármacos , Sistemas de Liberación de Medicamentos , Péptidos/administración & dosificación , Péptidos/farmacología , Péptidos/químicaRESUMEN
Both sulfur (S) supply and legume-rhizobium symbiosis can significantly contribute to enhancing the efficiency of phytoremediation of heavy metals (HMs). However, the regulatory mechanism determining the performance of legumes at lead (Pb) exposure have not been elucidated. Here, we cultivated black locust (Robinia pseudoacacia L.), a leguminous woody pioneer species at three S supply levels (i.e., deficient, moderate, and high S) with rhizobia inoculation and investigated the interaction of these treatments upon Pb exposure. Our results revealed that the root system of Robinia has a strong Pb accumulation and anti-oxidative capacity that protect the leaves from Pb toxicity. Compared with moderate S supply, high S supply significantly increased Pb accumulation in roots by promoting the synthesis of reduced S compounds (i.e., thiols, phytochelatin), and also strengthened the antioxidant system in leaves. Weakened defense at deficient S supply was indicated by enhanced oxidative damage. Rhizobia inoculation alleviated the oxidative damage of its Robinia host by immobilizing Pb to reduce its absorption by root cells. Together with enhanced Pb chelation in leaves, these mechanisms strengthen Pb detoxification in the Robinia-rhizobia symbiosis. Our results indicate that appropriate S supply can improve the defense of legume-rhizobia symbiosis against HM toxicity.