Redox Report最新文献

Peroxynitrite (ONOO^-) is a quintessential reactive oxygen species (ROS) and reactive nitrogen species (RNS), renowned for its potent oxidizing and nitrifying capabilities. Under normal physiological conditions, a baseline level of ONOO^- is present within the body. However, its production escalates significantly in response to oxidative stress. ONOO^- is highly reactive with various biomolecules in vivo, particularly proteins, lipids, and nucleic acids, thereby playing a role in a spectrum of physiological and pathological processes, such as inflammation, cancer, neurodegenerative diseases, and cardiovascular diseases. Consequently, detecting ONOO^- in vivo is of paramount importance for understanding the etiology of various diseases and facilitating early diagnosis. Fluorescent probes have become a staple in the identification of biomolecules due to their ease of use, convenience, and superior sensitivity and specificity. This review highlights the recent advancements in the development of fluorescent probes for the detection of ONOO^- in diverse disease models and provides an in-depth examination of their design and application.

Objective: Intracellular redox homeostasis is crucial for a series of physiological processes. Reactive oxygen species (ROS) play important roles in redox processes. ROS can maintain cell reproduction and survival at moderate levels while promoting the initiation and progression of tumors at high levels.

Methods: Based on a comprehensive analysis of ROS-related gene expression profiles, we established a gene signature associated with ROS to explore its influence on prognosis and immune microenvironment in gliomas.

Results: The ROS-related gene expression profile dichotomized patients into two groups with different clinicopathological features and prognoses. A 19-gene ROS-related signature was used to robustly predict prognosis in both training and validation datasets. Functional analysis indicated an association between ROS levels and the immune microenvironment. The expression of immune checkpoints and M2-type markers was upregulated in the high-risk group, which suggested the immunosuppressive function of ROS.

Conclusion: ROS-related signature is an independent prognostic factor in gliomas and could potentially exert immunosuppressive effects on the tumor microenvironment.

Objectives: To advance our knowledge of disease mechanisms and therapeutic options, understanding cell cycle regulation is critical. Recent research has highlighted the importance of reactive oxygen species (ROS) in cell cycle regulation. Although excessive ROS levels can lead to age-related pathologies, ROS also play an essential role in normal cellular functions. Many cell cycle regulatory proteins are affected by their redox status, but the precise mechanisms and conditions under which ROS promote or inhibit cell proliferation are not fully understood.Methods: This review presents data from the scientific literature and publicly available databases on changes in redox state during the cell cycle and their effects on key regulatory proteins.Results: We identified redox-sensitive targets within the cell cycle machinery and analysed different effects of ROS (type, concentration, duration of exposure) on cell cycle phases. For example, moderate levels of ROS can promote cell proliferation by activating signalling pathways involved in cell cycle progression, whereas excessive ROS levels can induce DNA damage and trigger cell cycle arrest or cell death.Discussion: Our findings encourage future research focused on identifying redox-sensitive targets in the cell cycle machinery, potentially leading to new treatments for diseases with dysregulated cell proliferation.

Emodin is a naturally occurring anthraquinone derivative with a wide range of pharmacological activities, including neuroprotective and anti-inflammatory activities. We aim to assess the anticancer activity of emodin against hepatocellular carcinoma (HCC) in rat models using the proliferation, invasion, and angiogenesis biomarkers. After induction of HCC, assessment of the liver impairment and the histopathology of liver sections were investigated. Hepatic expression of both mRNA and protein of the oxidative stress biomarkers, HO-1, Nrf2; the mitogenic activation biomarkers, ERK5, PKCδ; the tissue destruction biomarker, ADAMTS4; the tissue homeostasis biomarker, aggregan; the cellular fibrinolytic biomarker, MMP3; and of the cellular angiogenesis biomarker, VEGF were measured. Emodin increased the survival percentage and reduced the number of hepatic nodules compared to the HCC group. Besides, emodin reduced the elevated expression of both mRNA and proteins of all PKC, ERK5, ADAMTS4, MMP3, and VEGF compared with the HCC group. On the other hand, emodin increased the expression of mRNA and proteins of Nrf2, HO-1, and aggrecan compared with the HCC group. Therefore, emodin is a promising anticancer agent against HCC preventing the cancer prognosis and infiltration. It works through many mechanisms of action, such as blocking oxidative stress, proliferation, invasion, and angiogenesis.

Objectives: To observe the CISD2 expression among PCOS patients and to explore its profound impact on the follicular microenvironment. Moreover, we want to elucidate the intricate mechanistic contribution of CISD2 to the onset and progression of PCOS.

Methods: Oxidase NOX2, mitophagy-related proteins, and CISD2 were detected by WB. The changes in mitochondrial structure and quantity were observed by transmission electron microscopy. Mitochondrial and lysosome colocalization was used to detect the changes of mitophagy. MDA kit, GSH and GSSG Assay kit and ROS probe were used to detect oxidative stress damage.

Results: We found that CISD2, mitophagy and oxidase in the GCs of PCOS patients were significantly increased. Testosterone stimulation leads to the increase of oxidase, mitophagy, and CISD2 in KGN cells. CISD2 inhibition promoted the increase of mitophagy, and the activation of mitochondria-lysosome binding, while alleviating the oxidative stress.

Conclusions: Inhibition of CISD2 can improve the occurrence of oxidative stress by increasing the level of mitophagy, thus affecting the occurrence and development of PCOS diseases.

As a consequence of chronic hyperglycemia, diabetes complications and tissue damage are exacerbated. There is evidence that natural phytochemicals, including resveratrol, a bioactive polyphenol, may be able to reduce oxidative stress and improve insulin sensitivity. However, resveratrol's limited bioavailability hampers its therapeutic effectiveness. By using liposomes, resveratrol may be better delivered into the body and be more bioavailable. The objective of this study was to assess the cardioprotective potential of liposome-encapsulated resveratrol (LR) in a streptozotocin-induced (STZ) diabetic rat model. Adult male Wistar rats were categorized into five groups: control, diabetic, resveratrol-treated (40 mg/kg), liposomal resveratrol (LR)-treated (20 mg/kg) and liposomal resveratrol (LR)-treated (40 mg/kg) for a five-week study period. We compared the effects of LR to those of resveratrol (40 mg/kg) on various parameters, including serum levels of cardiac markers, tissue levels of pro-inflammatory cytokines, nuclear transcription factor, oxidative stress markers, and apoptotic markers. LR treatment in STZ-diabetic rats resulted in notable physiological improvements, including blood glucose regulation, inflammation reduction, oxidative stress mitigation, and apoptosis inhibition. LR effectively lowered oxidative stress and enhanced cardiovascular function. It also demonstrated a remarkable ability to suppress NF-kB-mediated inflammation by inhibiting the pro-inflammatory cytokines TNF-α and IL-6. Additionally, LR restored the antioxidant enzymes, catalase and glutathione peroxidase, thereby effectively counteracting oxidative stress. Notably, LR modulated apoptotic regulators, including caspase, Bcl2, and Bax, suggesting a role in regulating programmed cell death. These biochemical alterations were consistent with improved structural integrity of cardiac tissue as revealed by histological examination. In comparison, resveratrol exhibited lower efficacy at an equivalent dosage. Liposomal resveratrol shows promise in alleviating hyperglycemia-induced cardiac damage in diabetes. Further research is warranted to explore its potential as a therapeutic agent for diabetic cardiovascular complications and possible cardioprotective effects.

Objectives: Melittin, the main component of bee venom, is a natural anti-inflammatory substance, in addition to its ability to fight cancer, antiviral, and useful in diabetes treatment. This study seeks to determine whether melittin can protect renal tissue from sepsis-induced damage by preventing ferroptosis and explore the protective mechanism.

Methods: In this study, we investigated the specific protective mechanism of melittin against sepsis-induced renal injury by screening renal injury indicators and ferroptosis -related molecules and markers in animal and cellular models of sepsis.

Results: Our results showed that treatment with melittin attenuated the pathological changes in mice with lipopolysaccharide-induced acute kidney injury. Additionally, we found that melittin attenuated ferroptosis in kidney tissue by enhancing GPX4 expression, which ultimately led to the reduction of kidney tissue injury. Furthermore, we observed that melittin enhanced NRF2 nuclear translocation, which consequently upregulated GPX4 expression. our findings suggest that melittin may be a potential therapeutic agent for the treatment of sepsis-associated acute kidney injury by inhibiting ferroptosis through the GPX4/NRF2 pathway.

Conclusions: Our study reveals the protective mechanism of melittin in septic kidney injury and provides a new therapeutic direction for Sepsis-AKI.

Deficiency of TOM5, a mitochondrial protein, causes organizing pneumonia (OP) in mice. The clinical significance and mechanisms of TOM5 in the pathogenesis of OP remain elusive. We demonstrated that TOM5 was significantly increased in the lung tissues of OP patients, which was positively correlated with the collagen deposition. In a bleomycin-induced murine model of chronic OP, increased TOM5 was in line with lung fibrosis. In vitro, TOM5 regulated the mitochondrial membrane potential in alveolar epithelial cells. TOM5 reduced the proportion of early apoptotic cells and promoted cell proliferation. Our study shed light on the roles of TOM5 in OP.

Objective: The aim of this study was to clarify whether Protein kinase B (PKB)/AKT is nitrated in myocardial ischemia and reperfusion injury (MIRI) resveratrol (RSV)'s protective effect during this process.

Methods: We blocked blood flow of the left coronary artery (LAD) of mice and used H9c2 cells under an oxygen-glucose deprivation (OGD) environment as animal and cell models of MIRI. N-methyl-D-aspartic acid receptor (NMDAR) inhibitor MK801, neuronal nitric oxide synthase (nNOS) inhibitor 7-NI and RSV were used as interventions. Nitration of proteins, infarction area, cardiomyocyte apoptosis and AKT nitration sites were detected during this study.

Results: During in-vivo study, AKT nitration was induced through the NMDAR/nNOS/peroxynitrite (ONOO^-) pathway, leading to decreased phosphorylation of AKT and increased cardiomyocyte apoptosis. AKT nitration was decreased and phosphorylation was elevated when administrated with RSV, MK801 and 7-NI. In in-vitro study, AKT nitration and TUNEL positive cells was elevated when administrated with NO donor H9c2 cells after OGD/R, when administrated with RSV, MK801 and 7-NI, AKT nitration and apoptosis was deceased in H9c2 cells. Mass spectrometry revealed that nitration sites of AKT included 14 Tyrosine residues.

Discussion: RSV could inhibit AKT nitration and elevated phosphorylation through suppressing NMDAR/nNOS/ONOO^- pathway and further reduce the apoptosis of cardiomyocytes in of myocardial I/R.