Oxidative Damage Research Articles

Astaxanthin‐S‐Allyl Cysteine Ester Protects Pancreatic β‐Cell From Glucolipotoxicity by Suppressing Oxidative Stress, Endoplasmic Reticulum Stress and mTOR Pathway Dysregulation

ABSTRACTGlucolipotoxicity (GLT) has emerged as established mechanism in the progression of diabetes. Identifying compounds that mitigate GLT‐induced deleterious effect on β‐cells are considered important strategy to overcome diabetes. Hence, in the present study, astaxanthin‐s‐allyl cysteine (AST‐SAC) diester was studied against GLT in β‐cells. Mus musculus pancreatic β‐cell line (βTC‐tet) was treated with high glucose (25 mM; HG) and 95 μM palmitate (PA) for 24 h to induce GLT. AST‐SAC at various concentrations (5, 10, and 15 μg/ml) were treated to understand the protective effect against HG + PA exposure in β‐cells. Under HG + PA exposure conditions oxidative stress, deregulation of mTOR pathway and endoplasmic reticulum (ER) stress are witnessed. AST‐SAC treatment eased oxidative stress, mitochondrial depolarization, DNA damage, calcium overload and accumulation of autophagosome against HG + PA exposure conditions thereby protected the cell viability of β‐cells. AST‐SAC maintained the level of proteins involved in mTOR pathway under HG + PA exposure conditions. Also, AST‐SAC treatment has mitigated the increased expression of genes and proteins such as IRE1 and PERK involved in ER stress‐mediated unfolded protein response (UPR) signaling pathways. In correspondence to it, the expression of genes involved in insulin secretion was preserved by AST‐SAC. Due to these protective effects of AST‐SAC the insulin secretion was well‐maintained in β‐cells under HG + PA exposure conditions. AST‐SAC through normalizing antioxidant status and mTOR axis as well as preventing the harmful effect of ER‐stress mediated UPR pathway has promoted the β‐cell survival and insulin secretion against GLT. Simultaneously targeting oxidative stress/mTOR axis/ER stress is required to efficiently overcome GLT in β‐cells.

Abstract A017: HER2 overexpression initiates breast tumorigenesis non-cell-autonomously by altering energy metabolism in the tissue microenvironment

Abstract Breast cancer is the most common cancer globally, with approximately 70% of pre-malignant breast tumors, known as ductal carcinoma in situ (DCIS), and 20% of invasive breast tumors overexpressing human epidermal growth factor receptor 2 (HER2). While the biological role of HER2 in invasive breast cancer has been extensively studied, its impact on breast cancer stem cells (BCSCs) and early-stage tumorigenesis, particularly within the tumor microenvironment, remains unclear. Here, we explore the role of HER2 overexpression in driving cellular events within the tumor microenvironment during the premalignant stage of breast tumorigenesis, using in vitro, in vivo, and ex vivo models. We conducted multi-omics analyses on mammary ducts from a HER2+ breast cancer mouse model at the pre-cancerous stage. Our results showed that HER2/Neu overexpression alters glucose and lipid metabolism and pentose phosphate pathway in mammary epithelial cells. Ex vivo organ culture of mammary ducts confirmed that these metabolic changes lead to increased reactive oxygen species (ROS) levels within the tumor microenvironment suggesting that oxidative stress and subsequent DNA damage are early events in HER2-driven tumorigenesis. Immunostaining of histological sections from mouse mammary glands further revealed that elevated oxidative stress and DNA damage not only in HER2+ cells but also in neighboring HER2- cells. Moreover, whole genome sequencing of tumor cells confirmed that both HER2+ and HER2- tumor cells have similar mutational burden. This suggests a non-cell-autonomous effect, where HER2 overexpression in one cell population affects the tumor microenvironment and adjacent cells, contributing to early-stage cancer development. To investigate the involvement of BCSCs during tumor initiation, we performed mammosphere assays on primary cells from HER2+ mouse models and clinical DCIS samples. Our findings showed that neither BCSCs nor their cells of origin express HER2 in both DCIS samples and murine mammary glands and tumors. This suggests that HER2 overexpression may not directly drive BCSC formation but rather creates a genotoxic microenvironment that facilitates the transformation of HER2- cell populations through a non-cell-autonomous mechanism. In summary, our findings indicate that HER2 overexpression contributes to the creation of a genotoxic tumor microenvironment by altering cellular energy metabolism and increasing ROS levels. This, in turn, may lead to the transformation of BCSCs in HER2- cell populations during early breast tumorigenesis. Understanding the role of HER2 overexpression in shaping the tumor microenvironment could provide new insights into therapeutic and preventive strategies against breast cancer. Citation Format: Sevim B. Gurler, Oliver Wagstaff, Lili Dimitrova, Fuhui Chen, Robert Pedley, William Weston, Ian J. Donaldson, Brian A. Telfer, David Novo, Kyriaki Pavlou, George Taylor, Yaqing Ou, Kaye Williams, Andrew Gilmore, Keith Brennan, Ahmet Ucar. HER2 overexpression initiates breast tumorigenesis non-cell-autonomously by altering energy metabolism in the tissue microenvironment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr A017.

Studies on the Oxidative Damage of the Wobble 5-Methylcarboxymethyl-2-Thiouridine in the tRNA of Eukaryotic Cells with Disturbed Homeostasis of the Antioxidant System

We have previously shown that 2-thiouridine (S2U), either as a single nucleoside or as an element of RNA chain, is effectively desulfurized under applied in vitro oxidative conditions. The chemically induced desulfuration of S2U resulted in two products: 4-pyrimidinone nucleoside (H2U) and uridine (U). Recently, we investigated whether the desulfuration of S2U is a natural process that also occurs in the cells exposed to oxidative stress or whether it only occurs in the test tube during chemical reactions with oxidants at high concentrations. Using different types of eukaryotic cells, such as baker’s yeast, human cancer cells, or modified HEK293 cells with an impaired antioxidant system, we confirmed that 5-substituted 2-thiouridines are oxidatively desulfurized in the wobble position of the anticodon of some tRNAs. The quantitative LC-MS/MS-MRMhr analysis of the nucleoside mixtures obtained from the hydrolyzed tRNA revealed the presence of the desulfuration products of mcm5S2U: mcm5H2U and mcm5U modifications. We also observed some amounts of immature cm5S2U, cm5H2U and cm5U products, which may have indicated a disruption of the enzymatic modification pathway at the C5 position of 2-thiouridine. The observed process, which was triggered by oxidative stress in the living cells, could impair the function of 2-thiouridine-containing tRNAs and alter the translation of genetic information.

Benefits of Astaxanthin supplementation: selected issues

INTRODUCTION: Astaxanthin, a carotenoid compound belonging to the xanthophyll group, occurs naturally in algae, yeast, and marine organisms such as shrimp, trout, lobster, and krill. Renowned for its antioxidant prowess, astaxanthin shields mitochondria from harm caused by reactive oxygen species (ROS). Its exceptional antioxidant potency is noteworthy, surpassing that of α-tocopherol (Vitamin E) by 100-fold and eclipsing over 600 other recognized natural carotenoids. REVIEW METHODS: The article was complied by analyzing data from PubMed and Google Scholar data regarding the benefits of astaxanthin supplementation. THE STATE OF KNOWLEDGE: Astaxanthin, offers a range of health benefits. It modulates immune responses, inhibits cancer cell growth, reduces bacterial presence and gastric inflammation. With potent antioxidant properties, it also serves as a neuroprotective agent by combating neuroinflammation. Additionally, astaxanthin shows promise in preventing and treating liver diseases, thanks to its antioxidant, anti-inflammatory, and signaling pathway regulation properties. Overall, antioxidants like astaxanthin, whether from diet or supplements, help combat lipid and protein oxidation, thereby slowing down the progression of atherosclerosis. CONCLUSION: Astaxanthin emerges as a promising candidate for treating various pathological conditions linked to oxidative damage and impaired mitochondria function. These conditions span across cardiovascular diseases, neurodegenerative disorders and liver diseases. It could also help healthy people like athletes in enhancement of overall quality of life.

Changing dynamics in daily rhythms of oxidative stress indicators in SCN and extra-SCN brain regions with aging in male Wistar rats.

The suprachiasmatic nucleus (SCN) in the hypothalamus regulates circadian timing system (CTS) by co-ordinating peripheral tissue clocks and extra-SCN oscillators in the brain. Aging disrupts the CTS, impairing physiological functions and reducing antioxidant defences, which contribute to neurodegeneration. The brain is vulnerable to oxidative damage due to its high metabolic activity, oxygen consumption, and levels of iron and lipids. Antioxidant enzymes, such as catalase (CAT), glutathione S-transferase (GST), superoxide dismutase (SOD), and lipid peroxidation (LPO), help against oxidative damage. In this study, we examined the temporal patterns of these antioxidant stress indicators in the SCN and extra-SCN brain regions (frontal cortex, cerebellum, and hippocampus) at various time points in male Wistar rats 3, 12, and 24months. The rhythmicity of GST and LPO levels persisted across brain regions with aging, while CAT rhythmicity was lost in the SCN and hippocampus of older rats. SOD rhythmicity persisted in cortex, cerebellum, and hippocampus but was lost in the SCN. The daily rhythm parameters of CAT were affected most significantly, followed by SOD, GST, and LPO. Our findings demonstrate that aging leads to desynchronization of oxidative stress indicators potentially contributing to neurodegeneration and circadian dysfunction with varying effects across different brain tissues.

Redox Imbalance and Antioxidant Defenses Dysfunction: Key Contributors to Early Aging in Childhood Cancer Survivors

Survival rates for childhood cancer survivors (CCS) have improved, although they display a risk for early frailty due to the long-term effects of chemo/radiotherapy, including early aging. This study investigates antioxidant defenses and oxidative damage in mononuclear cells (MNCs) from CCS, comparing them with those from age-matched and elderly healthy individuals. Results show impaired antioxidant responses and increased oxidative stress in CCS MNCs, which exhibited uncoupled oxidative phosphorylation, leading to higher production of reactive oxygen species, similar to metabolic issues seen in elderly individuals. Key antioxidant enzymes, namely glucose-6-phosphate dehydrogenase, hexose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, catalase, and superoxide dismutase, showed reduced activity, likely due to lower expression of nuclear factor erythroid 2–related factor 2 (Nrf2). This imbalance caused significant damage to lipids, proteins, and DNA, potentially contributing to cellular dysfunction and a higher risk of cancer recurrence. These oxidative and metabolic dysfunctions persist over time, regardless of cancer type or treatment. However, treatment with N-acetylcysteine improved Nrf2 expression, boosted antioxidant defenses, reduced oxidative damage, and restored oxidative phosphorylation efficiency, suggesting that targeting the redox imbalance could enhance long-term CCS health.

Photosynthetic efficiency and water retention in okra (Abelmoschus esculentus) contribute to tolerance to single and combined effects of drought and heat stress.

The co-occurrence of drought and heat significantly hampers plant productivity. Although their impacts are well studied, these studies have been based on the effects of individual stressors rather than their combined influence. Okra is crucial for food and nutritional security and livelihoods in many regions, yet it remains under-researched and unimproved. Okra has been proven to be sensitive to both drought and heat stress. This study employed a cost-effective phenotyping method to assess key traits characterising the diversity of okra morphophysiological responses to independent and interactive heat-drought stresses. This study aimed to understand okra responses to stress, identify stress-resilient traits, and characterise okra genotypes. We also addressed the need to examine interactive stress effects, which mirror real-world scenarios more accurately than single-stress studies. Sixty-three okra genotypes were subjected to heat, drought, or concurrent heat-drought stress at the seedling stage in improvised climate-controlled chambers. The germplasm exhibited significant variations in response to the various stresses. The broad-sense heritability was high (> 0.60) for traits such as chlorophyll content, plant biomass, performance indices, electrolyte leakage, and total leaf area. Drought stress alone had a more pronounced effect than heat stress alone, and the adverse impact was worsened under combined heat and drought stress. The interactive impact of drought and heat was more likely additive than antagonistic or synergistic. A positive and strong relationship was observed between photosynthetic efficiency parameters such as the Fv/Fm ratio, chlorophyll content, relative water index, and biomass parameters such as dry shoot weight. The 63 okra genotypes were classified into three distinct clusters, suggesting potential for future breeding efforts. Okra genotype considered to be tolerant or climate resilient (such as GH170, V1060831, GH174, V1060874, and GH106) to drought and heat, maintained enhanced photosynthetic efficiency and high internal water potential, possibly reducing osmotic and oxidative damage. This study revealed some mechanisms underlying the adaptation of okra genotypes to independent and combined heat and drought stress. The results provide a basis for breeding efforts to develop climate-resilient okra varieties.

X-ray fluorescence mapping of brain tissue reveals the profound extent of trace element dysregulation in stroke pathophysiology.

The brain is a privileged organ with regards to its trace element composition and maintains a robust barrier system to sequester this specialized environment from the rest of the body and the vascular system. Stroke is caused by loss of adequate blood flow to a region of the brain. Without adequate blood flow ischemic changes begin almost immediately, triggering an ischemic cascade, characterized by ion dysregulation, loss of function, oxidative damage, cellular degradation, and break down of the barrier that helps maintain this environment. Ion dysregulation is a hallmark of stroke pathophysiology and we observe that most elements in the brain are dysregulated after stroke. X-ray fluorescence-based detection of physiological changes in the neurometallome after stroke reveals profound ion dysregulation within the lesion and surrounding tissue. Not only are most elements significantly dysregulated after stroke, but the level of dysregulation cannot be predicted from a cell-level description of dysregulation. X-ray fluorescence imaging reveals that the stroke lesion retains<25% of essential K+ after stroke, but this element is not concomitantly elevated elsewhere in the organ. Moreover, elements like Na+, Ca2+, and Cl- are vastly elevated above levels available in normal brain tissue (>400%, >200%, and>150%, respectively). We hypothesize that weakening of the blood-brain-barrier after stroke allows elements to freely diffuse down their concentration gradient so that the stroke lesion is in equilibrium with blood (and the compartments containing brain interstitial fluid and cerebrospinal fluid). The changes observed for the neurometallome likely has consequences for the potential to rescue infarcted tissue, but also presents specific targets for treatment.

A multi-scale integrative approach to study the impact of a common pesticide, the dimethoate, on a mangrove fiddler crab Tubuca urvillei.

At land-sea interface, mangroves are likely to be exposed to pesticides due to agricultural run-offs. In Mayotte Island (Comoros archipelago, Mozambique Channel), dimethoate (DMT) is found in high concentrations in tomatoes, but no data confirm its presence in mangroves. We aimed at screening the presence of DMT in three mangroves of Mayotte at different levels (highest point above crops, village, upstream mangrove, downstream mangrove) and assessing the impact of DMT coupled with reduced salinity on mangrove crab physiology. To do so, we performed 24-h exposures at sublethal concentrations (10 and 100µg L-1) corresponding to 100 × and 1000 × the environmental standard (no data exist on environmental concentrations), in seawater (SW) and diluted SW (dSW). We exposed male fiddler crab Tubuca urvillei, one of the most common fiddler crabs living in mangrove areas regularly flooded and exposed to agricultural run-offs. Different physiological endpoints were considered: behaviour, acetylcholinesterase (AChE) activity, muscle energy metabolism, DNA oxidative damage and osmoregulatory capacity using hemolymph samples, posterior gills and claw muscle. We confirmed the presence of DMT in one mangrove and the effect of pesticide exposure at the different endpoints. Changes in behavioural and physiological parameters highlighted in this study could warn us of recent pesticide use upstream and help us understand past or future community-level changes in mangrove ecosystems affected by pesticide inputs.

Saussurea involucrata SiLEA5 Enhances Tolerance to Drought Stress in Solanum lycopersicum

Drought adversely affects plant growth, which leads to reduced crop yields and exacerbates food insecurity. Late embryogenesis abundant (LEA) proteins are crucial for plants’ responses to abiotic stresses. This research further investigates the role of SiLEA5 by utilizing transgenic tomatoes under drought stress. The expression of SiLEA5 was upregulated under drought and abscisic acid (ABA) treatment, resulting in decreased electrolyte leakage and malondialdehyde content, alongside increased levels of osmotic regulators and antioxidant enzyme activity. These biochemical alterations reduce oxidative damage and enhance drought resistance. qRT-PCR analysis revealed the upregulation of ABA signaling genes and key enzymes involved in proline biosynthesis (P5CS) and dehydrin (DHN) synthesis under drought stress. Additionally, overexpression of SiLEA5 increased the net photosynthetic rate (Pn) and fruit yield of tomatoes by regulating stomatal density and aperture. These findings suggest that SiLEA5 may be a potential target for improving drought tolerance in tomatoes and other crops.

Evidence of Oxidative Stress as a Mechanism of Pharmaceutical-Induced Toxicity in Amphibians

Amphibians, which are essential components of ecosystems, are susceptible to pharmaceutical contamination, a phenomenon of increasing concern owing to the widespread consumption and detection of pharmaceutical compounds in environmental matrices. This review investigates oxidative stress (OS) as the primary mechanism of drug toxicity in these organisms. The evidence gathered reveals that various pharmaceuticals, from antibiotics to anesthetics, induce OS by altering biomarkers of oxidative damage and antioxidant defense. These findings underscore the deleterious effects of pharmaceuticals on amphibian health and development and emphasize the necessity of incorporating OS biomarkers into ecotoxicological risk assessments. Although further studies on diverse amphibian species, drug mixtures, and field studies are required, OS biomarkers offer valuable tools for identifying sublethal risks. Furthermore, the development of more refined OS biomarkers will facilitate the early detection of adverse effects, which are crucial for protecting amphibians and their ecosystems. Ultimately, this review calls for continued research and mitigation strategies to safeguard biodiversity from pharmaceutical contamination.

β-cryptoxanthin suppresses oxidative stress via activation of the Nrf2/HO-1 signaling pathway in diabetic kidney disease

ObjectivesThis study aims to explore the role and investigate mechanisms of β-Cryptoxanthin (BCX) in high glucose (HG)-induced podocyte injury and renal dysfunction.MethodsIn this study, db/db mice were orally treated with BCX. Blood glucose, body weight, urinary albumin creatinine ratio (ACR) were recorded to evaluate the mice renal function. The H&amp;amp;E, PAS staining, and transmission electron microscopy (TEM) were utilized to examine the effect of BCX on the morphological changes of glomeruli in db/db mice. In addition, reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP) level, ATP level, and SA-β-gal staining were used to assess the podocyte oxidative damage, mitochondrial dysfunction and senescence. Furthermore, the effects of BCX on Nrf2/HO-1 signaling pathway were evaluated in vivo and in vitro through Western blotting, immunohistochemistry and immunofluorescence analysis.ResultsIn vivo, BCX reversed glomerular mesangial matrix expansion and reduced proteinuria in db/db mice, as well as decreased glomerular oxidative stress and kidney aging. Similarly, in vitro study showed that BCX effectively alleviated the oxidative stress, mitochondrial dysfunction, and senescence induced by HG in podocytes. Furthermore, we identified that the antioxidative effects of BCX are associated with the activation of Nrf2/HO-1 signaling pathway, and that Nrf2 knockdown partially abrogated the protective effects of BCX in vitro.ConclusionOur study demonstrated for the first time that BCX alleviates podocyte injury in DKD by promoting Nrf2/HO-1 signaling pathways. BCX may be a potential candidate compound for preventing Diabetic kidney disease (DKD).

Metabolic-driven analytics of traumatic brain injury and neuroprotection by ethyl pyruvate.

Research on traumatic brain injury (TBI) highlights the significance of counteracting its metabolic impact via exogenous fuels to support metabolism and diminish cellular damage. While ethyl pyruvate (EP) treatment shows promise in normalizing cellular metabolism and providing neuroprotection, there is a gap in understanding the precise metabolic pathways involved. Metabolomic analysis of the acute post-injury metabolic effects, with and without EP treatment, aims to deepen our knowledge by identifying and comparing the metabolite profiles, thereby illuminating the injury's effects and EP's therapeutic potential. In the current study, an untargeted metabolomics approach was used to reveal brain metabolism changes in rats 24h after a controlled cortical impact (CCI) injury, with or without EP treatment. Using principal component analysis (PCA), volcano plots, Random Forest and pathway analysis we differentiated the brain metabolomes of CCI and sham injured animals treated with saline (Veh) or EP, identifying key metabolites and pathways affected by injury. Additionally, the effect of EP on the non-injured brain was also explored. PCA showed a clear separation of the four study groups (sham-Veh, CCI-Veh, sham-EP, CCI-EP) based on injury. Following CCI injury (CCI-Veh), 109 metabolites belonging to the amino acid, carbohydrate, lipid, nucleotide, and xenobiotic families exhibited a twofold change at 24h compared to the sham-Veh group, with 93 of these significantly increasing and 16 significantly decreasing (p < 0.05). CCI animals were treated with EP (CCI-EP) showed only 5 metabolites in the carbohydrate, amino acids, peptides, nucleotides, lipids, and xenobiotics super families that exhibited a twofold change, compared to the CCI-Veh group (p < 0.05). In the non-injured brain, EP treatment (sham-EP) resulted in a twofold change in 6 metabolites within the amino acid, peptide, nucleotide, and lipid super families compared to saline treated sham animals (sham-Veh, p < 0.05). This study delineates the unique metabolic signatures resulting from a CCI injury and those related to EP treatment in both the injured and non-injured brain, underscoring the metabolic adaptations to brain injury and the effects of EP. Our analysis uncovers significant shifts in metabolites associated with inflammation, energy metabolism, and neuroprotection after injury, and demonstrates how EP intervention after injury alters metabolites associated with mitigating inflammation and oxidative damage.

Antioxidant supplementation boosts the advantages of CrossFit workouts on oxidative and muscle damage markers in obese males.

Supplementing with antioxidants may be one of the most efficient means of minimizing oxidative stress during workouts in obese individuals. The aim of this study is to identify the results after twelve weeks of CrossFit workouts combined with Spinach thylakoid extract on the levels of insulin resistance (insulin and Homeostatic Model Assessment of Insulin Resistance [HOMA-IR]), fasting blood sugar (FBS), malondialdehyde (MDA), creatine kinase (CK), lactate dehydrogenase (LDH), total antioxidant capacity (TAC), and superoxide dismutase (SOD), glutathione peroxidase (GPx) in obese males. Sixty-eight males with an average age of 27 ± 8 yrs and a BMI of 32.6 ± 2.6kg.m- 2 were randomly split into four groups each consisting of seventeen individuals. : control group (CG), supplement group (SG), training group (TG), and training + supplement group (TSG). After initial assessments, the two training groups (TG and TSG) started on a 12 weeks of the CrossFit workouts program involving three sessions per week each lasting up to 60min. Participants in supplement groups ingested 30min before lunch, 5 gof Spinach thylakoid extract per day or one sachet of raw corn starch in the control group. Baseline and post-intervention measurements were performed 48h pre- and post-last session, respectively. The findings revealed noteworthy relationships between the exercise groups and timefor TAC, SOD, GPx, MDA, CK, and LDH (p < 0.001, ES: 0.88, 0.88, 0.8, 0.4, 0.7, and 0.7, respectively). In addition, there were statistically significant differences among study groups after attending the intervention program in TAC (ES: 0.88), SOD (ES: 0.92), GPX (ES: 0.85), MDA (ES: 0.5), CK (ES: 0.7) and LDH (ES: 0.8). The effect sizes of insulin (0.77), glucose (0.21), and HOMA-IR (0.44) varied significantly (p < 0.05) among the groups. The results demonstrated that CrossFit workouts for 12 weeks combined with Spinach thylakoid extract in men with obesity may prevent oxidative damage caused by obesity and CrossFit workouts.

Iron-based MOF with Catalase-like activity improves the synergistic therapeutic effect of PDT/ferroptosis/starvation therapy by reversing the tumor hypoxic microenvironment.

Reversing the hypoxic microenvironment of tumors is an important method to enhance the synergistic effect of tumor treatment. In this work, we developed the nanoparticles called Ce6@HGMOF, which consists of a photosensitizer (Ce6), glucose oxidase (GOX), chemotherapy drugs (HCPT) and an iron-based metal-organic framework (MOF). Ce6@HGMOF can consume glucose in tumor cells through "starvation therapy", cut off their nutrition source, and produce gluconic acid and hydrogen peroxide (H2O2). Utilizing this feature, Ce6@HGMOF can produce oxygen through catalase-like catalytic activity, thereby reversing the hypoxic microenvironment of tumors. This strategy of changing the hypoxic environment can help to slow down the growth of tumor blood vessels and improve the drug-resistant microenvironment to some extent. Meanwhile, increasing the supply of oxygen can enhance the effect of photodynamic therapy (PDT) and enhance the oxidative stress damage caused by reactive oxygen species (ROS) in tumor cells. On the other hand, cancer cells usually produce higher levels of glutathione (GSH) to adapt to high oxidative stress and protect themselves. The Ce6@HGMOF we designed can also consume GSH and induce ferroptosis of tumor cells through Fenton reaction with H2O2, while enhancing the effect of PDT. This innovative synergistic strategy, the combination of PDT/ferroptosis /starvation therapy, can complement each other and enhance each other. It has great potential as a powerful new anti-tumor paradigm in the future.

SNP alleviates ferric and salt stress in Phaseolus vulgaris seeds

Seed germination and early development are delicate events often influenced by various environmental factors. Among these factors, the accumulation of salts and heavy metals in the soil is noteworthy. This study aimed to observe the effect of priming with solutions of sodium nitroprusside, polyethylene glycol 6000, and potassium nitrate on the germination of Phaseolus vulgaris seeds exposed to toxic conditions of iron and sodium chloride. Seeds were germinated on plates placed in a growth chamber at a constant temperature of 25°C and a 12-hour photoperiod. The percentage of germination, germination speed, root and shoot lengths, catalase, peroxidase activities, and malondialdehyde content were evaluated. Exposure to high concentrations of sodium chloride and iron reduced germination percentage, germination speed, root and shoot lengths of treated plants. Only sodium nitroprusside treatment mitigated the effects of stressors. No increase in malondialdehyde content was observed in any treatment, suggesting no lipid peroxidation of membranes. However, all treatments showed increased catalase activity, possibly indicating oxidative stress and metabolic damage. Sodium nitroprusside stands out as a stress alleviator for sodium chloride and iron accumulation during the germination phase.

Harnessing the therapeutic potential of exercise in extracellular vesicle-based therapy in metabolic disease associated cardiovascular complications.

Cardiovascular disease (CVD) is a leading cause of mortality, affecting ∼18 million individuals each year. Obesity and type 2 diabetes mellitus in particular, both chronic metabolic disorders, are risk factors for CVD. The salutary effects of physical activity in preventing and ameliorating CVD have long been acknowledged, as it improves glucose and lipid homeostasis, alongside attenuating oxidative damage, increasing mitochondrial function, and ultimately improving cardiac function. Exercise serves as a catalyst for the secretion of extracellular vesicles (EVs), facilitating inter-tissue communication, by which tissues can deliver important signals from one tissue to another. In recent years, an increasing number of studies have focused on the cargo encapsulated within exercise-derived EVs, as well as the orchestration of inter-tissue crosstalk aimed at modulating metabolism and tissue function in CVDs. The precise mechanisms underpinning the cardioprotective properties of exercise-derived EVs, however, remains only partially elucidated. This review explores novel EV based therapeutic options in CVD and, in particular, EVs derived from models of exercise to alter metabolism and enhance cardiovascular outcomes.

Exploring the Updated Roles of Ferroptosis in Liver Diseases: Mechanisms, Regulators, and Therapeutic Implications.

Ferroptosis, a newly discovered mode of cell death, is a type of iron-dependent regulated cell death characterized by intracellular excessive lipid peroxidation and imbalanced redox. As the liver is susceptible to oxidative damage and the abnormal iron accumulation is a major feature of most liver diseases, studies on ferroptosis in the field of liver diseases are of great interest. Studies show that targeting the key regulators of ferroptosis can effectively alleviate or even reverse the deterioration process of liver diseases. System Xc- and glutathione peroxidase 4 are the main defense regulators of ferroptosis, while acyl-CoA synthetase long chain family member 4 is a key enzyme causing peroxidation in ferroptosis. Generally speaking, ferroptosis should be suppressed in alcoholic liver disease, non-alcoholic fatty liver disease, and drug-induced liver injury, while it should be induced in liver fibrosis and hepatocellular carcinoma. In this review, we summarize the main regulators involved in ferroptosis and then the mechanisms of ferroptosis in different liver diseases. Treatment options of drugs targeting ferroptosis are further concluded. Determining different triggers of ferroptosis can clarify the mechanism of ferroptosis occurs at both physiological and pathological levels.

Age-associated metabolic and epigenetic barriers during direct reprogramming of mouse fibroblasts into induced cardiomyocytes.

Heart disease is the leading cause of mortality in developed countries, and novel regenerative procedures are warranted. Direct cardiac conversion (DCC) of adult fibroblasts can create induced cardiomyocytes (iCMs) for gene and cell-based heart therapy, and in addition to holding great promise, still lacks effectiveness as metabolic and age-associated barriers remain elusive. Here, by employing MGT (Mef2c, Gata4, Tbx5) transduction of mouse embryonic fibroblasts (MEFs) and adult (dermal and cardiac) fibroblasts from animals of different ages, we provide evidence that the direct reprogramming of fibroblasts into iCMs decreases with age. Analyses of histone posttranslational modifications and ChIP-qPCR revealed age-dependent alterations in the epigenetic landscape of DCC. Moreover, DCC is accompanied by profound mitochondrial metabolic adaptations, including a lower abundance of anabolic metabolites, network remodeling, and reliance on mitochondrial respiration. Invitro metabolic modulation and dietary manipulation invivo improve DCC efficiency and are accompanied by significant alterations in histone marks and mitochondrial homeostasis. Importantly, adult-derived iCMs exhibit increased accumulation of oxidative stress in the mitochondria and activation of mitophagy or dietary lipids; they improve DCC and revert mitochondrial oxidative damage. Our study provides evidence that metaboloepigenetics plays a direct role in cell fate transitions driving DCC, highlighting the potential use of metabolic modulation to improve cardiac regenerative strategies.

Effects of oxidative stress on the changes of viability of Paeonia lactiflora seeds with different water content before and after cryopreservation.

Cryopreservation in liquid nitrogen (LN) is an efficient long - term seed preservation strategy and water content is one of the main factors affecting seed viability after cryopreservation. In this study, Paeonia lactiflora seeds with varying water content were used as materials to determine changes in the antioxidant system before and after cryopreservation. When the water content of P. lactiflora seeds was 15.96% - 10.12%, the viability of P. lactiflora seeds decreased significantly compared with that of the seeds without cryopreservation, but at the water content of 8.14% - 7.56% there were no significant differences. However, when the water content of P. lactiflora seeds decreased to 6.01% - 5.19% the viability was slightly increased compared to the seeds without cryopreservation. The content of superoxide anion (O2-), hydroxyl radical (·OH), hydrogen peroxide (H2O2), malondialdehyde (MDA) and protein carbonyl group (PCO) of seeds with high water content (15.96% - 10.12%) were significantly increased after cryopreservation. However, superoxide anion (O2-), hydroxyl radical (·OH) and hydrogen peroxide (H2O2) did not change significantly in seeds with low water content (6.01% - 5.19%) after cryopreservation, while oxidative stress indexes MDA and PCO decreased. These three substances were significantly negatively correlated with seed viability. In terms of antioxidant substances, the contents of catalase (CAT), ascorbic acid (AsA) and glutathione (GSH) decreased and the activities of glutathione reductase (GR) and dehydroascorbate reductase (DHAR) increased during the cryopreserved process of seeds with varying water content. These changes were significantly correlated with ROS content and the changes of MDA and PCO, among which AsA content, GSH content and CAT activity were positively correlated with seed viability. The changes of GR and DHAR activity were negatively correlated with seed viability. In summary, when the water content of the seeds ranged from 8.14% - 5.19%, ROS content did not increase significantly after cryopreservation compared with that of before preservation. The changes of MDA and PCO contents before and after cryopreservation, it was inferred that no obvious oxidative damage occurred in seeds, so the viability of seeds did not decrease compared with that of before cryopreservation. Therefore, the optimum water content of P. lactiflora seeds for cryopreservation is 8.14% - 5.19%.