Excessive Reactive Oxygen Species Research Articles

Can Rice Growth Substrate Substitute Rapeseed Growth Substrate in Rapeseed Blanket Seedling Technology? Lesson from Reactive Oxygen Species Production and Scavenging Analysis.

Rapeseed (Brassica napus L.) seedlings suffering from inappropriate growth substrate stress will present poor seedling quality. However, the regulatory mechanism for the production and scavenging of reactive oxygen species (ROS) caused by this type of stress remains unclear. In the current study, a split plot experiment design was implemented with two crop growth substrates-a rice growth substrate (RIS) and rapeseed growth substrate (RAS)-as the main plot and two genotypes-a hybrid and an open-pollinated variety (Zheyouza 1510 and Zheyou 51, respectively)-as the sub-plot. The seedling quality was assessed, and the ROS production/scavenging capacity was evaluated. Enzymatic and non-enzymatic systems, including ascorbic acid and glutathione metabolism, and RNA-seq data were analyzed under the two growth substrate treatments. The results revealed that rapeseed seedling quality decreased under RIS, with the plant height, maximum leaf length and width, and aboveground dry matter being reduced by 187.7%, 64.6%, 73.2%, and 63.8% on average, respectively, as compared to RAS. The main type of ROS accumulated in rapeseed plants was hydrogen peroxide, which was 47.8% and 14.1% higher under RIS than under RAS in the two genotypes, respectively. The scavenging of hydrogen peroxide in Zheyouza 1510 was the result of a combination of enzymatic systems, with significantly higher peroxidase (POD) and catalase (CAT) activity as well as glutathione metabolism, with significantly higher reduced glutathione (GSH) content, under RAS, while higher oxidized glutathione (GSSH) was observed under RIS. However, the scavenging of hydrogen peroxide in Zheyou 51 was the result of a combination of elevated oxidized ascorbic acid (DHA) under RIS and higher GSH content under RAS. The identified gene expression levels were in accordance with the observed enzyme expression levels. The results suggest that the cost of substituting RAS with RIS is a reduction in rapeseed seedling quality contributing to excessive ROS production and a reduction in ROS scavenging capacity.

Effects of Vibrio harveyi infection on the biochemistry, histology and transcriptome in the hepatopancreas of ivory shell (Babylonia areolata)

The ivory shell (Babylonia areolata) is one of the most promising high quality marine products. However, ivory shell is susceptible to Vibrio harveyi infection during the culture period. In this study, we investigated the biochemical indicators, histological changes and transcriptomic response in the hepatopancreas of ivory shells from the PBS control group (PC) and infection group (A3) with 1 × 109 CFU/mL V. harveyi after 24 h. Results showed that compared to the PC group, biochemical indicators, including malondialdehyde (MDA), reactive oxygen species (ROS), acid phosphatase (ACP), and Caspase 3 (Casp-3) were significantly increased (p < 0.05) in A3 group after V. harveyi infection for 24 h. Compared with the PC group, the hepatopancreas of A3 group were seriously damaged, the columnar epithelial cells of the tissue were enlarged, the space of digestive cells was increased, and vacuolar cavities appeared. A total of 95,581 unigenes were obtained and 2949 (1787 up-regulated and 1162 down-regulated) differential expressed genes (DEGs) were identified in the A3 group. GO and KEGG enrichment analysis showed that DEGs were mainly enriched in immune system process (GO:0002376), antioxidant activity (GO:0016209), lysosome (ko04142), toll and IMD signaling pathway (ko04624), and etc. These biological functions and pathways are associated with immune and inflammatory responses and apoptosis. 12 DEGs were randomly selected for real-time quantitative PCR (RT-qPCR) validation, and the expression profiles of these DEGs were consistent with the transcriptome data, confirming the accuracy and reliability of the transcriptome results. In summary, V. harveyi infection of ivory shells inducing oxidative stress, leading to severe hepatopancreatic damage, stimulating glutathione production to neutralize excessive ROS, and stimulating antimicrobial peptides production to counteract the deleterious effects of bacterial infection, which in turn modifying the immune and inflammatory response, ultimately resulting in apoptosis. This study provided valuable information to explore the immune regulation mechanism after V. harveyi infection and established molecular basis to support the prevention of V. harveyi infection.

Inhibition of Caspase-1-dependent pyroptosis alleviates myocardial ischemia/reperfusion injury during cardiopulmonary bypass (CPB) in type 2 diabetic rats

Cardiovascular complications pose a significant burden in type 2 diabetes mellitus (T2DM), driven by the intricate interplay of chronic hyperglycemia, insulin resistance, and lipid metabolism disturbances. Myocardial ischemia/reperfusion (MI/R) injury during cardiopulmonary bypass (CPB) exacerbates cardiac vulnerability. This study aims to probe the role of Caspase-1-dependent pyroptosis in global ischemia/reperfusion injury among T2DM rats undergoing CPB, elucidating the mechanisms underlying heightened myocardial injury in T2DM. This study established a rat model of T2DM and compared Mean arterial pressure (MAP), heart rate (HR), and hematocrit (Hct) between T2DM and normal rats. Myocardial cell morphology, infarction area, mitochondrial ROS and caspase-1 levels, NLRP3, pro-caspase-1, caspase-1 p10, GSDMD expressions, plasma CK-MB, cTnI, IL-1β, and IL-18 levels were assessed after reperfusion in both T2DM and normal rats. The role of Caspase-1-dependent pyroptosis in myocardial ischemia/reperfusion injury during CPB in T2DM rats was examined using the caspase-1 inhibitor VX-765 and the ROS scavenger NAC. T2DM rats demonstrated impaired glucose tolerance but stable hemodynamics during CPB, while showing heightened vulnerability to MI/R injury. This was marked by substantial lipid deposition, disrupted myocardial fibers, and intensified cellular apoptosis. The activation of caspase-1-mediated pyroptosis and increased reactive oxygen species (ROS) production further contributed to tissue damage and the ensuing inflammatory response. Notably, myocardial injury was mitigated by inhibiting caspase-1 through VX-765, which also attenuated the inflammatory cascade. Likewise, NAC treatment reduced oxidative stress and partially suppressed ROS-mediated caspase-1 activation, resulting in diminished myocardial injury. This study proved that Caspase-1-dependent pyroptosis significantly contributes to the inflammation and injury stemming from global MI/R in T2DM rats under CPB, which correlate with the surplus ROS generated by oxidative stress during reperfusion.

Multi-responsive sodium hyaluronate/tannic acid hydrogels with ROS scavenging ability promote the healing of diabetic wounds

Oxidative stress caused by excessive reactive oxygen species (ROS) accumulation significantly hinders wound healing in patients with diabetes. Scavenging ROS and reducing inflammation are crucial for rapid healing. In this work, a multi-responsive sodium hyaluronate (HA)/tannic acid (TA) hydrogel was developed based on boronate ester bonds. Sodium hyaluronate with 3-aminophenyl boronic acid modification (HA-APBA) was mixed and crosslinked with TA to form HA-APBA/TA hydrogels. These hydrogels are injectable, self-healing, and biocompatible. The HA-APBA/TA hydrogels could release free TA through the collapse of the structure at low pH, high H2O2 concentration, and high glucose concentration, thus possessing good ROS scavenging ability. In full-thickness skin wounds of db/db mice, the HA-APBA/TA hydrogels promoted wound healing, collagen deposition, and significant angiogenesis. Furthermore, they have been shown to effectively reduce the levels of inflammatory factors in wounds and lower the expression of CD86, a pro-inflammatory macrophage surface marker. This resulted in a more effective transition of wound healing from the inflammatory phase to the proliferative phase. This study provides an optional strategy for alleviating oxidative stress and controlling excessive inflammation, thereby promoting diabetic wound healing.

Self-adaptive bioactive scaffolds orchestrate diabetic microenvironment remodeling and vascularized bone regeneration

The repair of diabetic bone defects is still challenging as the innate healing process is impaired by adverse microenvironments such as excessive reactive oxygen species (ROS) and insufficient angiogenesis and osteogenesis. Herein, a self-adaptive biocomposite scaffold that can orchestrate sequential regulation of diabetic microenvironment and vascularized bone regeneration was developed for efficient diabetic bone defect repair. The therapeutic scaffold system was meticulously constructed through the incorporation of hydrogel and 3D-printed architecture. In response to the multiple diabetic microenvironment (high level of glucose and ROS), the hydrogel consisting of Vitamin C-loaded phenylboric acid-grafted poly (glutamic acid)/poly (vinyl alcohol) showed adaptive degradation and antioxidative properties by scavenging the intracellular ROS, as well as promoting M2 polarization of macrophages. Furthermore, the copper-doped bioactive glass-contained 3D-printed polycaprolactone within the scaffold system was demonstrated to enhance the mechanical strength and stimulate the in vitro angiogenic and osteogenic performance by releasing copper and silicon ions. Moreover, in a diabetic rat femoral defect model, the biocomposite scaffold showed better angiogenesis and bone regeneration by following diabetic microenvironment remodeling. Therefore, the designed self-adaptive biocomposite scaffold can promote diabetic bone regeneration by sequentially regulating pathological and regenerative cues. This study offers vital insight into the design of a self-adaptive bioactive scaffold for the treatment of diabetic bone defects.

Mechanistic Interrogation on Wound Healing and Scar Removing by the Mo4/3B2-x Nanoscaffold Revealed Regulated Amino Acid and Purine Metabolism.

Wound rehabilitation is invariably time-consuming, scar formation further weakens therapeutic efficacy, and detailed mechanisms at the molecular level remain unclear. In this work, a Mo4/3B2-x nanoscaffold was fabricated and utilized for wound healing and scar removing in a mice model, while metabolomics was used to study the metabolic reprogramming of metabolome during therapy at the molecular level. The results showed that transition metal borides, called Mo4/3B2-x nanoscaffolds, could mimic superoxide dismutase and glutathione peroxidase to eliminate excess reactive oxygen species (ROS) in the wound microenvironment. During the therapeutic process, the Mo4/3B2-x nanoscaffold could facilitate the regeneration of wounds and removal of scars by regulating the biosynthesis of collagen, fibers, and blood vessels at the pathological, imaging, and molecular levels. Subsequent metabolomics study revealed that the Mo4/3B2-x nanoscaffold effectively ameliorated metabolic disorders in both wound and scar microenvironments through regulating ROS-related pathways including the amino acid metabolic process (including glycine and serine metabolism and glutamate metabolism) and the purine metabolic process. This study is anticipated to illuminate the potential clinical application of the Mo4/3B2-x nanoscaffold as an effective therapeutic agent in traumatic diseases and provide insights into the development of analytical methodology for interrogating wound healing and scar removal-related metabolic mechanisms.

Sea Cucumber Viscera Processed by Protease Hydrolysis Combined with Cordyceps militaris Fermentation Protect Caco-2 Cells against Oxidative Damage via Enhancing Antioxidant Capacity, Activating Nrf2/HO-1 Pathway and Improving Cell Metabolism.

Excessive reactive oxygen species (ROS) may lead to oxidative damage and metabolic disorder. The pathogenesis of human bowel inflammation is closely related to oxidative damage of intestinal epithelial cells caused by ROS. This study aimed to explore the high-value utilization of the byproducts of sea cucumber in antioxidant food for colitis prevention. The technology of protease hydrolysis combined with Cordyceps militaris fermentation was used to obtain fermented sea cucumber viscera protease hydrolysates (FSVHs). The results revealed that FSVH could enhance antioxidant capacity and alleviate oxidative damage and apoptosis by activating the Nrf2/HO-1 pathway and triggering the self-protection immune mechanisms. Moreover, the FSVH supplementation could upregulate antioxidant-related metabolic pathways of Caco-2 cells such as glutathione metabolism, confirming the enhanced antioxidant capacity of damaged cells. In summary, FSVH could exert protective effects on Caco-2 cells in response to oxidative damage, providing a promising prospect for sea cucumber resource utilization and colitis prevention.

Enhanced therapeutic efficacy of SERCA2a gene-modified adipose-derived mesenchymal stem cell exosomes in doxorubicin-induced cardiomyopathy in male albino rats.

Worldwide, cancer is still the primary cause of death, and one of the most widely used anthracyclines for treating cancer is doxorubicin (DOX). But a major worry is DOX-induced cardiomyopathy, which is primarily resulted from an excess of reactive oxygen species. Heart sarcoplasmic reticulum calcium ion ATPase2a (SERCA2a) controls the amount of calcium ions stored in the sarcoplasmic reticulum (SR). This study aims to evaluate and compare the efficacy of SERCA2a gene modified adipose mesenchymal stem cell-derived exosomes (AMSCs-dE) to nontransfected AMSCs-dE, in DOX induced cardiomyopathy in adult male albino rat. Thirty one adult male albino rats were randomly divided into control group and DOX group that further subdivided into three DOX, AMSCs-dE and SERCA2a AMSCs-dE subgroups. AMSCs-dE were administered intravenously (IV). The levels of serum creatine kinase MB (CK-MB) were assessed after DOX injection and before sacrifice. Cardiac muscle samples were taken for histological analysis using Masson's trichrome and hematoxylin and eosin stains two months after the experiment. Proliferating cell nuclear antigen (PCNA) and connexin 43 were stained using immunohistochemistry. The expression of TNF and SERCA2a genes and proteins was measured by real-time polymerase chain reaction (PCR) and Western blot (Wb) analysis, respectively. Fluorescent microscopy demonstrated non-transfected and transfected exosomes labeled with PKH26 and GFP, respectively, in culture and cardiac muscle. DOX induced myocarditis progressing to degenerative and fibrotic changes in cardiac muscle that regressed in response to AMSCs-dE therapy. However, SERCA2a gene modified AMSCs-dE treatment reversed the mentioned parameters to nearly its normal level. These findings suggest that SERCA2a gene modification enhances the therapeutic efficacy of AMSCs-dE in treating DOX-induced cardiomyopathy.

Baicalin derivative dynamically cross-linked natural polysaccharide hydrogel for diabetic wound healing

Diabetes is a chronic disease affects nearly 10% of the global population, the prolonged metabolic abnormalities and the complex microenvironment in diabetic wounds often leading to impaired healing. To address the typical characteristics of diabetic wounds, such as hyperglycemia, low pH, excessive reactive oxygen species (ROS) production, and chronic inflammation, this study designed a baicalin derivative dynamically cross-linked natural polysaccharide hydrogel (CFPB) and explored its potential to promote diabetic wound healing. The framework of CFPB utilized chitosan and modified with dextran to introduce aldehyde groups via mild grafting, and crosslinked with the modified active substance baicalin to effectively extend the drug delivery time. A series of characterizations demonstrated that CFPB hydrogel possesses excellent mechanical properties, self-healing ability, and responsive release capability. Subsequently, multi-level biological experiments validated the promoting effect of CFPB hydrogel on diabetic wound healing in vitro and in vivo. This study not only offers a potential candidate for the local therapy of diabetic wounds, but also provides new insights for the development of advanced wound dressings.

Neutrophil membrane-derived nanoparticles protect traumatic brain injury via inhibiting calcium overload and scavenging ROS

The secondary injury is more serious after traumatic brain injury (TBI) compared with primary injury. Release of excessive reactive oxygen species (ROS) and Ca2+ influx at the damaged site trigger the secondary injury. Herein, a neutrophil-like cell membrane-functionalized nanoparticle was developed to prevent ROS-associated secondary injury. NCM@MP was composed of three parts: (1) Differentiated neutrophil-like cell membrane (NCM) was synthesized, with inflammation-responsive ability to achieve effective targeting and to increase the retention time of Mn3O4 and nimodipine (MP) in deep injury brain tissue via C-X-C chemokine receptor type 4, integrin beta 1 and macrophage antigen-1. (2) Nimodipine was used to inhibit Ca2+ influx, eliminating the ROS at source. (3) Mn3O4 further eradicated the existing ROS. In addition, NCM@MP also exhibited desirable properties for T1 enhanced imaging and low toxicity which may serve as promising multifunctional nanoplatforms for precise therapies. In our study, NCM@MP obviously alleviated oxidative stress response, reduced neuroinflammation, protected blood–brain barrier integrity, relieved brain edema, promoted the regeneration of neurons, and improved the cognition of TBI mice. This study provides a promising TBI management to relieve the secondary spread of damage.Graphical

A chitosan-based light-curing hydrogel dressing for accelerated healing of infected wounds

Bacterial infections, excessive reactive oxygen species (ROS) accumulation and a persistent inflammatory response severely impede the wound healing process. In this study, we developed a novel multifunctional hydrogel dressing (LCPN) based on lipoic acid modified chitosan (LAMC), polypyrrole nanoparticles (PPy NPs) and nicotinamide mononucleotide (NMN) for accelerated healing of infected wounds. The synthesized LCPN hydrogel has several properties. Modification of lipoic acid significantly enhances the water solubility of chitosan making it easier to dissolve and absorb wound secretions. Interestingly, owing to the breaking and restructuring of disulfide bonds, LCPN hydrogel can be quickly bonded under UV light without relying on photoinitiators. In addition, the incorporation of PPy NPs not only enhances the electrical conductivity of LCPN hydrogel, but also confers photothermal antimicrobial capability to LCPN hydrogel. More importantly, the sustained release of NMN in LCPN hydrogel can significantly enhance cell proliferation, migration and antioxidant capacity, which is conducive to accelerated wound healing. In vitro and in vivo experiments have shown that LCPN hydrogel has excellent biocompatibility and the ability to promote wound healing. Therefore, the prepared multifunctional hydrogel is expected to be used as a novel dressing to accelerate wound healing.

Cost-effective and natural-inspired lotus root/GelMA scaffolds enhanced wound healing via ROS scavenging, angiogenesis and reepithelialization

Skin wounds, prevalent and fraught with complications, significantly impact individuals and society. Wound healing encounters numerous obstacles, such as excessive reactive oxygen species (ROS) production and impaired angiogenesis, thus promoting the development of chronic wound. Traditional clinical interventions like hemostasis, debridement, and surgery face considerable challenges, including the risk of secondary infections. While therapies designed to scavenge excess ROS and enhance proangiogenic properties have shown effectiveness in wound healing, their clinical adoption is hindered by high costs, complex manufacturing processes, and the potential for allergic reactions. Lotus root, distinguished by its natural micro and macro porous architecture, exhibits significant promise as a tissue engineering scaffold. This study introduced a novel scaffold based on hybridization of lotus root-inspired and Gelatin Methacryloyl (GelMA), verified with satisfactory physicochemical properties, biocompatibility, antioxidative capabilities and proangiogenic abilities. In vivo tests employing a full-thickness wound model revealed that these scaffolds notably enhanced micro vessel formation and collagen remodeling within the wound bed, thus accelerating the healing process. Given the straightforward accessibility of lotus roots and the cost-effective production of the scaffolds, the novel scaffolds with ROS scavenging, pro-angiogenesis and re-epithelialization abilities are anticipated to have clinical applicability for various chronic wounds.

Nano-Fe3O4: Enhancing the tolerance of Elymus nutans to Cd stress through regulating programmed cell death

Cadmium (Cd) poses a significant threat to plant growth and the environment. Nano-Fe3O4 is effective in alleviating Cd stress in plants. Elymus nutans Griseb. is an important fodder crop on the Qinghai-Tibetan Plateau (QTP). However, the potential mechanism by which nano-Fe3O4 alleviates Cd stress in E. nutans is not well understood. E. nutans were subjected to single Cd, single nano-Fe3O4, and co-treatment with nano-Fe3O4 and Cd, and the effects on morphology, Cd uptake, antioxidant enzyme activity, reactive oxygen species (ROS) levels and programmed cell death (PCD) were studied to clarify the regulatory mechanism of nano-Fe3O4. The results showed that Cd stress significantly decreased the germination percentage and biomass of E. nutans. The photosynthetic pigment content decreased significantly under Cd stress. Cd stress also caused oxidative stress and lipid peroxidation, accumulation of excessive ROS, resulting in PCD, but the effect of nano-Fe3O4 was different. Seed germination, seedling growth, and physiological processes were analyzed to elucidate the regulatory role of nano-Fe3O4 nanoparticles in promoting photosynthesis, reducing Cd accumulation, scavenging ROS, and regulating PCD, to promote seed germination and seedling growth in E. nutans. This report provides a scientific basis for improving the tolerance of Elymus to Cd stress by using nano-Fe3O4.

Fabrication of multifunctional ZnO@tannic acid nanoparticles embedded in chitosan and polyvinyl alcohol blend packaging film

The current study explores biodegradable packaging materials that have high food quality assurance, as food deterioration is mostly caused by UV degradation and oxidation, which can result in bad flavor and nutrition shortages. Thus, new multifunctional zinc oxide nanoparticles/tannic acid (ZnO@TA) with antioxidant and antibacterial activities were incorporated into polyvinyl alcohol/chitosan (PVA/CH) composite films with different ratios (1%, 3%, and 5% based on the total dry weight of the film) via a solution blending method in a neutral aqueous solution. Additionally, ZnO nanoparticles have unique antibacterial mechanisms through the generation of excessive reactive oxygen species (ROS) that may lead to intensify pathogen resistance to conventional antibacterial agents. Thus, minimizing the negative effects caused by excessive levels of ROS may be possible by developing unique, multifunctional ZnO nanoparticles with antioxidant potential via coordination bond between tannic acid and ZnO nanoparticles (ZnO@TA). ZnO@TA nanoparticles were examined using Fourier-transform infrared (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The effect of the incorporation of ZnO@TA nanoparticles on the barrier, mechanical, thermal, antioxidant, antimicrobial, and UV blocking characteristics of chitosan/polyvinyl alcohol (ZnO@TA@CH/PVA) films was investigated. The lowest water vapor and oxygen permeability and the maximum antioxidant capacity% are 31.98 ± 1.68 g mm/m2 kPa day, 0.144 ± 5.03 × 10–2 c.c/m2.day, and 69.35 ± 1.6%, respectively, which are related to ZnO@TA(50)@CH/PVA. Furthermore, ZnO@TA(50)@CH/PVA film exhibits the maximum UV shielding capacity of UVB (99.994). ZnO@TA(50) @PVA/CH films displayed better tensile strength and Young`s modulus of 48.72 ± 0.23 MPa and 2163.46 ± 61.4 MPa, respectively, than the other film formulations. However, elongation % at break exhibited the most reduced value of 19.62 ± 2.3%. ZnO@TA@CH/PVA film exhibits the largest inhibition zones of 11 ± 1.0, 12.3 ± 0.57, and 13.6 ± 0.57 mm against Staphylococcus aureus, Aspergillus flavus, and Candida albicans, respectively. In accordance with these results, ZnO@TA@CH/PVA films could be utilized for food preservation for the long-term.

Saikosaponin D potentiates the antineoplastic effects of doxorubicin in drug-resistant breast cancer through perturbing NQO1-mediated intracellular redox balance

BackgroundDrug resistance to doxorubicin (DOX) significantly limits its therapeutic efficacy in breast cancer (BC) patients. Saikosaponin D (SSD), a triterpene saponin derived from the traditional herb Radix Bupleuri, has shown promise as a chemotherapeutic sensitizer in preclinical studies due to its notable antitumor activity. However, the role and mechanism of SSD in DOX-resistant BC cells remain largely unexplored. PurposeThis study aimed to investigate the chemosensitizing effect of SSD on DOX-resistant BC and the underlying molecular mechanisms both in vitro and in vivo. MethodsIn vitro assays, including cell viability, clone formation, three-dimensional tumor spheroid growth, and apoptosis analysis, were conducted to evaluate the synergistic effect of SSD and DOX on resistant BC cells. Reactive oxygen species (ROS), GSH/GSSG, NADPH/NADP+, and NADH/NAD+ detections were employed to assess the impact of SSD on cellular redox homeostasis. Western blotting, cell cycle distribution assay, and DOX uptake assay were performed to further elucidate the possible antineoplastic mechanism of SSD. Finally, a subcutaneous MCF7/DOX cell xenografted model in nude mice was established to identify the in vivo anticarcinogenic effect of SSD combined with DOX. ResultsSSD significantly inhibited cell viability, proliferation, and clone formation, enhancing DOX's anticancer efficacy in vitro and in vivo. Mechanistically, SSD reduced STAT1, NQO1, and PGC-1α protein levels, leading to cellular redox imbalance, excessive ROS generation, and depletion of GSH, NADPH, and NADH. SSD induced DNA damage by disrupting redox homeostasis, resulting in G0/G1 phase cell cycle arrest. Additionally, SSD increased DOX accumulation in BC cells via inhibiting P-gp protein expression and efflux activity. ConclusionWe demonstrated for the first time that SSD enhances the sensitivity of chemoresistant BC cells to DOX by disrupting cellular redox homeostasis through inactivation of the STAT1/NQO1/PGC-1α signaling pathway. This study provides evidence for SSD as an adjuvant agent in drug-resistant BC treatment.

The transcription factor LBD10 sustains pollen tube growth and integrity by modulating reactive oxygen species homeostasis via the regulation of flavonol biosynthesis in Arabidopsis.

Reproduction in angiosperms relies on the precise growth of pollen tubes, facilitating the delivery of sperm cells to the ovule for double fertilization. LATERAL ORGAN BOUNDARIES DOMAIN10 (LBD10), a plant-specific transcription factor, plays a pivotal role in Arabidopsis pollen development. Here, we uncovered LBD10's function in sustaining pollen tube growth and integrity. The lbd10 mutant exhibited elevated levels of reactive oxygen species (ROS) and hydrogen peroxide (H2O2) in both pollen grains and tubes, leading to compromised pollen tube growth. The inhibition of ROS synthesis and scavenging of excess ROS with an antioxidant treatment each alleviated these defects in lbd10. The lbd10 mutant displayed reduced flavonol accumulation in both pollen grains and tubes. All the altered phenotypes of lbd10 were complemented by expressing LBD10 under its native promoter. Exogenous application of flavonoids recused the defects in pollen tube growth and integrity in lbd10, along with reducing the excess levels of ROS and H2O2. LBD10 directly binds the promoters of key flavonol biosynthesis genes in chromatin and promotes reporter gene expression in Arabidopsis mesophyll protoplasts. Our findings indicate that LBD10 modulates ROS homeostasis by transcriptionally activating genes crucial for flavonol biosynthesis, thereby maintaining pollen tube growth and integrity.

Spatiotemporal delivery of microenvironment responsive hydrogel incorporated with stem cells-loaded porous microspheres for abdominal wall repair

Healing the wounds of abdominal wall defects characterised by severe complications represents a significant clinical challenge. Mesenchymal stem cells (MSC)-based therapies have emerged as a promising strategy for tissue regeneration. However, the low engraftment and survival rates limit their application owing to the complicated wound microenvironment and large wound areas in abdominal wall defects. Inspired by focal biointerfaces, the present research engineered a spatiotemporal delivery microenvironment-responsive therapeutic platform, termed MSC-GSM@HG, for abdominal wall repair. The constructed platform proved capable of dissolving HA-PBA/Gel-DA (HG) hydrogels in response to in vivo inflammatory responses and subsequently releasing MSC-laden gelatine and silk fibroin microspheres (GSMs). Meanwhile, the HG hydrogels can not only protect the MSCs from excessive reactive oxygen species but also exhibit haemostatic and anti-inflammatory properties. Strikingly, this microsphere-releasing hydrogel platform actively enhanced the repair of abdominal wall defects in vivo, by reducing inflammatory response, facilitating angiogenesis and promoting collagen deposition. Therefore, the microenvironment-responsive platform represents a promising strategy for MSC-based therapies for abdominal wall defects through spatiotemporal delivery mechanisms.

Highly BBB-permeable nanomedicine reverses neuroapoptosis and neuroinflammation to treat Alzheimer's disease

The prevalence of Alzheimer's disease (AD) is increasing globally due to population aging. However, effective clinical treatment strategies for AD still remain elusive. The mechanisms underlying AD onset and the interplay between its pathological factors have so far been unclear. Evidence indicates that AD progression is ultimately driven by neuronal loss, which in turn is caused by neuroapoptosis and neuroinflammation. Therefore, the inhibition of neuroapoptosis and neuroinflammation could be a useful anti-AD strategy. Nonetheless, the delivery of active drug agents into the brain parenchyma is hindered by the blood-brain barrier (BBB). To address this challenge, we fabricated a black phosphorus nanosheet (BP)-based methylene blue (MB) delivery system (BP-MB) for AD therapy. After confirming the successful preparation of BP-MB, we proved that its BBB-crossing ability was enhanced under near-infrared light irradiation. In vitro pharmacodynamics analysis revealed that BP and MB could synergistically scavenge excessive reactive oxygen species (ROS) in okadaic acid (OA)-treated PC12 cells and lipopolysaccharide (LPS)-treated BV2 cells, thus efficiently reversing neuroapoptosis and neuroinflammation. To study in vivo pharmacodynamics, we established a mouse model of AD mice, and behavioral tests confirmed that BP-MB treatment could successfully improve cognitive function in these animals. Notably, the results of pathological evaluation were consistent with those of the in vitro assays. The findings demonstrated that BP-MB could scavenge excessive ROS and inhibit Tau hyperphosphorylation, thereby alleviating downstream neuroapoptosis and regulating the polarization of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Overall, this study highlights the therapeutic potential of a smart nanomedicine with the capability of reversing neuroapoptosis and neuroinflammation for AD treatment.

Ultrasmall Cu2I2 nanoclusters trigger metabolic-epigenetic reprogramming and endogenous antioxidant systems for alleviating osteoarthritis

Temporomandibular joint (TMJ) osteoarthritis (OA) affects millions of people worldwide, characterized by imbalance metabolism, excess reactive oxygen species (ROS), aberrant epigenetic alterations and so on. Currently, analgesics and anti-inflammatory drugs are mainly used for treatment, but they only alleviate symptoms. Here, we designed a ultrasmall copper-based nanoclusters agent (copper iodide coordination, Cu2I2), which exhibited remarkable ROS-scavenging activities. And the antioxidant properties of Cu2I2 nanoclusters (Cu2I2 NCs) were achieved by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Excitingly, Cu2I2 NCs exhibited excellent metabolic-epigenetic regulation property via reprogramming energy metabolism to inhibit S-adenosylmethionine (SAM)-production metabolic pathway and contributing to the global hypomethylation mediated by Dnmt3a. Then, the expression of anti-osteoclastogenic genes was upregulated. Consistent with in vitro observations, Cu2I2 NCs efficiently alleviated subchondral bone destruction of TMJ OA in rats. Altogether, this study not only provides a novel nanoclusters agent for TMJ OA treatment that can activate endogenous antioxidant systems, but also reveals the significance and feasibility of therapeutic strategies to break the bridge between metabolic and epigenetic regulation.

Dual-functional fluorescent probe for imaging ROS and hypoxia dynamic in cancer cells

Hypoxia is able to induce the overexpression of nitroreductase (NTR) in cancer cells. Moreover, there is still the controversy about reactive oxygen species (ROS) change under the hypoxic condition. Herein, we designed and synthesized a fluorescent probe WNO that could simultaneously visualize the fluctuation changes of NTR and ROS in hypoxic HeLa cells. WNO consists of 4-nitro-1,8-naphthalimide group and 2,3,3-trimethyl indolium salt. In buffer 4-nitro-1,8-naphthalimide group could selectively response to NTR in the presence of nicotinamide adenine dinucleotide phosphate (NADH), resulting in a strong green fluorescence. However, upon LED light irradiation 2,3,3-trimethyl indolium salt moiety could efficiently convert into Cy3 emitting a red fluorescence. Furthermore, the monitoring for NTR and photoconversion of WNO in hypoxic HeLa cells were investigated in detail by confocal fluorescence imaging through green and red channels, respectively. It was found that WNO could image the intracellular NTR or hypoxia level. Meanwhile, the WNO photoconversion was accelerated largely in hypoxic cells, which resulted from the production of excessive ROS. WNO and/or its photoconversion product mainly accumulated into the mitochondria. Moreover, MTT assay indicated that LED irradiation or hypoxia treatment made the cytotoxicity of WNO increase by 50 %. Additionally, based on ROS-stimulated the photoconversion of WNO, the intracellular ROS and NTR changes in mitochondrial dysfunction and oxidative stress were also investigated. It indicated that WNO was capable of sensitive and rapid imaging the intracellular ROS and NTR levels under both conditions. These findings would provide an excellent foundation for cancer diagnosis and therapy.