Insulin resistance and pancreatic β-cell dysfunction are the main pathogenesis of type 2 diabetes mellitus (T2DM). However, insulin therapy and diabetes medications do not effectively solve the two problems simultaneously. In this study, a biomimetic oral hydrogen nanogenerator that leverages the benefits of edible plant-derived exosomes and hydrogen therapy was constructed to overcome this dilemma by modulating gut microbiota and ameliorating oxidative stress and inflammatory responses. Hollow mesoporous silica (HMS) nanoparticles encapsulating ammonia borane (A) were used to overcome the inefficiency of H2 delivery in traditional hydrogen therapy, and exosomes originating from ginger (GE) were employed to enhance biocompatibility and regulate intestinal flora. Our study showed that HMS/A@GE not only considerably ameliorated insulin resistance and liver steatosis, but inhibited the dedifferentiation of islet β-cell and enhanced pancreatic β-cell proportion in T2DM model mice. In addition to its antioxidant and anti-inflammatory effects, HMS/A@GE augmented the abundance of Lactobacilli spp. and tryptophan metabolites, such as indole and indole acetic acid, which further activated the AhR/IL-22 pathway to improve intestinal-barrier function and metabolic impairments. This study offers a potentially viable strategy for addressing the current limitations of diabetes treatment by integrating gut-microbiota remodelling with antioxidant therapies.

Oxidative damage contributes to age-related macular degeneration. Irigenin possesses diverse pharmacologic properties, including antioxidative and antiapoptotic effects. Our in vivo experiments indicated that irigenin mitigates UVB-induced histopathologic changes and oxidative DNA damage. Histologic analyses and TUNEL staining revealed that this compound dose-dependently ameliorated UVB-induced retinal damage and apoptosis. Furthermore, irigenin substantially reduced the level of 8-hydroxyguanosine, a biomarker of UVB-induced oxidative DNA damage. We further explored the molecular mechanisms that mediate the protective effects of irigenin. Our findings suggested that UVB-induced generation of ROS disrupts the stability of the mitochondrial membrane, activating intrinsic apoptotic pathways; the underlying mechanisms include the release of cytochrome c, activation of caspase-9 and caspase-3, and subsequent degradation of PARP-1. Notably, irigenin reversed mitochondrial disruption and apoptosis. It also modulated the Bax and Bcl-2 expression but influenced the mitochondrial apoptotic pathways. Our study highlights the role of the Nrf2 pathway in mitigating the effects of oxidative stress. We found that UVB exposure downregulated, but irigenin treatment upregulated the expression of Nrf2 and antioxidant enzymes. Therefore, irigenin activates the Nrf2 pathway to address oxidative stress. In conclusion, irigenin exhibits protective effects against UVB-induced ocular damage, evidenced by the diminution of histological alterations. It mitigates oxidative DNA damage and apoptosis in the retinal tissues by modulating the intrinsic apoptotic pathways and the AIF mechanisms. Furthermore, irigenin effectively reduces lipid peroxidation, enhancing the activity of antioxidant enzymes by stimulating the Nrf2 pathway. This protective mechanism underscores the potential benefit of irigenin in combating UVB-mediated ocular damage.

There is increasing evidence that exposure to weak electromagnetic fields (EMFs) generated by modern telecommunications or household appliances has physiological consequences, including reports of electromagnetic field hypersensitivity (EHS) leading to adverse health effects. Although symptoms can be serious, no underlying mechanism for EHS is known and there is no general cure or effective therapy. Here, we present the case study of a self-reported EHS patient whose symptoms include severe headaches, generalized fatigue, cardiac arrhythmia, attention and memory deficit, and generalized systemic pain within minutes of exposure to telecommunications (Wifi, cellular phones), high tension lines and electronic devices. Tests for cerebral, cardiovascular, and other physiological anomalies proved negative, as did serological tests for inflammation, allergies, infections, auto-immune conditions, and hormonal imbalance. However, further investigation revealed deficits in cellular anti-oxidants and increased radical scavenging enzymes, indicative of systemic oxidative stress. Significantly, there was a large increase in circulating antibodies for oxidized Low-Density Lipoprotein (LDLox), byproducts of oxidative stress accumulating in membranes of vascular cells. Because a known primary effect of EMF exposure is to increase the concentration of cellular oxidants, we propose that pathology in this patient may be causally related to a resulting increase in LDLox synthesis. This in turn could trigger an exaggerated auto-immune response consistent with EHS symptoms. This case report thereby provides a testable mechanistic framework for EHS pathology with therapeutic implications for this debilitating and poorly understood condition.

Inflammatory bowel disease (IBD) is a chronic immune-mediated condition that affects the digestive system and includes Crohn\'s disease (CD) and ulcerative colitis (UC). Although the exact etiology of IBD remains uncertain, dysfunctional immunoregulation of the gut is believed to be the main culprit. Amongst the immunoregulatory factors, reactive oxygen species (ROS) and reactive nitrogen species (RNS), components of the oxidative stress event, are produced at abnormally high levels in IBD. Their destructive effects may contribute to the disease\'s initiation and propagation, as they damage the gut lining and activate inflammatory signaling pathways, further exacerbating the inflammation. Oxidative stress markers, such as malondialdehyde (MDA), 8-hydroxy-2\'-deoxyguanosine (8-OHdG), and serum-free thiols (R-SH), can be measured in the blood and stool of patients with IBD. These markers are elevated in patients with IBD, and their levels correlate with the severity of the disease. Thus, oxidative stress markers can be used not only in IBD diagnosis but also in monitoring the response to treatment. It can also be targeted in IBD treatment through the use of antioxidants, including vitamin C, vitamin E, glutathione, and N-acetylcysteine. In this review, we summarize the role of oxidative stress in the pathophysiology of IBD, its diagnostic targets, and the potential application of antioxidant therapies to manage and treat IBD.

Reactive oxygen species (ROS), as metabolic byproducts, play pivotal role in physiological and pathological processes. Recently, studies on the regulation of ROS levels for disease treatments have attracted extensive attention, mainly involving the ROS-induced toxicity therapy mediated by ROS producers and antioxidant therapy by ROS scavengers. Nanotechnology advancements have led to the development of numerous nanomaterials with ROS-modulating capabilities, among which carbon dots (CDs) standing out as noteworthy ROS-modulating nanomedicines own their distinctive physicochemical properties, high stability, and excellent biocompatibility. Despite progress in treating ROS-related diseases based on CDs, critical issues such as rational design principles for their regulation remain underexplored. The primary cause of these issues may stem from the intricate amalgamation of core structure, defects, and surface states, inherent to CDs, which poses challenges in establishing a consistent generalization. This review succinctly summarizes the recently progress of ROS-modulated approaches using CDs in disease treatment. Specifically, it investigates established therapeutic strategies based on CDs-regulated ROS, emphasizing the interplay between intrinsic structure and ROS generation or scavenging ability. The conclusion raises several unresolved key scientific issues and prominent technological bottlenecks, and explores future perspectives for the comprehensive development of CDs-based ROS-modulating therapy.

The prevalence of retinal neovascular diseases necessitates novel treatments beyond current therapies like laser surgery or anti-VEGF treatments, which often carry significant side effects. A novel therapeutic approach is introduced using copper-containing layered double hydroxides (Cu-LDH) nanozymes integrated with nitric oxide-releasing molecules (GSHNO), forming Cu-LDH@GSHNO aimed at combating oxidative stress within the retinal vascular system. Combination of synthetic chemistry and biological testing, Cu-LDH@GSHNO are synthesized, characterized, and assessed for curative effect in HUVECs and an oxygen-induced retinopathy (OIR) mouse model. The results indicate that Cu-LDH@GSHNO demonstrates SOD-CAT cascade catalytic ability, accompanied with GSH and nitric oxide-releasing capabilities, which significantly reduces oxidative cell damage and restores vascular function, presenting a dual-function strategy that enhances treatment efficacy and safety for retinal vascular diseases. The findings encourage further development and clinical exploration of nanozyme-based therapies, promising a new horizon in therapeutic approaches for managing retinal diseases driven by oxidative stress.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection inhibits mitochondrial oxidative phosphorylation (OXPHOS) and elevates mitochondrial reactive oxygen species (ROS, mROS) which activates hypoxia-inducible factor-1alpha (HIF-1α), shifting metabolism toward glycolysis to drive viral biogenesis but also causing the release of mitochondrial DNA (mtDNA) and activation of innate immunity. To determine whether mitochondrially targeted antioxidants could mitigate these viral effects, we challenged mice expressing human angiotensin-converting enzyme 2 (ACE2) with SARS-CoV-2 and intervened using transgenic and pharmacological mitochondrially targeted catalytic antioxidants. Transgenic expression of mitochondrially targeted catalase (mCAT) or systemic treatment with EUK8 decreased weight loss, clinical severity, and circulating levels of mtDNA; as well as reduced lung levels of HIF-1α, viral proteins, and inflammatory cytokines. RNA-sequencing of infected lungs revealed that mCAT and Eukarion 8 (EUK8) up-regulated OXPHOS gene expression and down-regulated HIF-1α and its target genes as well as innate immune gene expression. These data demonstrate that SARS-CoV-2 pathology can be mitigated by catalytically reducing mROS, potentially providing a unique host-directed pharmacological therapy for COVID-19 which is not subject to viral mutational resistance.

Acute pancreatitis (AP) is a common inflammatory disorder of the exocrine pancreas that causes severe morbidity and mortality. Although the pathophysiology of AP is poorly understood, a substantial body of evidence suggests some critical events for this disease, such as dysregulation of digestive enzyme production, cytoplasmic vacuolization, acinar cell death, edema formation, and inflammatory cell infiltration into the pancreas. Oxidative stress plays a role in the acute inflammatory response. The present review clarified the role of oxidative stress in the occurrence and development of AP by introducing oxidative stress to disrupt cellular Ca2+ balance and stimulating transcription factor activation and excessive release of inflammatory mediators for the application of antioxidant adjuvant therapy in the treatment of AP.

UNASSIGNED: To identify the impact of redox imbalance on the clinical evolution of patients with polycystic ovary syndrome and carry out a qualitative and quantitative projection of the benefits of vitamin D supplementation.
UNASSIGNED: Combinations of the keywords polycystic ovary syndrome, vitamin D, oxidative stress, reactive oxygen species, antioxidant, and free radicals were used in PubMed, Cochrane Library, LILACS, EMBASE, and Web of Science databases. The last search was conducted on August 22, 2023.Selection of studies: Based on the inclusion and exclusion criteria, studies were selected considering a low risk of bias, published in the last 5 years in English, which investigated the effects of vitamin D supplementation in women with PCOS, focusing on oxidative stress markers. Of the 136 articles retrieved, 6 intervention studies (445 women) were included.
UNASSIGNED: The risk of bias in included studies was assessed using the Jadad scale, and analysis and visualization of continuous data were performed using Review Manager 5.4.1, summarized as standardized mean differences (SMD) with confidence intervals (CI) of 95%.
UNASSIGNED: Vitamin D effectively reduced malondialdehyde (P=0.002) and total testosterone (P=0.0004) levels and increased total antioxidant capacity levels (P=0.01). Although possible improvements in the modified Ferriman-Gallwey hirsutism score, levels of sex hormone-binding globulin, and free androgen index were identified and the results were not statistically significant.
UNASSIGNED: Vitamin D is a promising alternative for the treatment of PCOS with a positive influence on the oxidative, metabolic, and endocrine disorders of this syndrome.

Chronic hypertension is a major risk factor for preeclampsia (PE), associated with significant maternal and neonatal morbidity. We previously demonstrated that pregnant stroke-prone spontaneously hypertensive rats (SHRSP) display a spontaneous PE-like phenotype with distinct placental, fetal, and maternal features. Here, we hypothesized that supplementation with alpha lipoic acid (ALA), a potent antioxidant, during early pregnancy could ameliorate the PE phenotype in this model. To test this hypothesis, timed pregnancies were established using 10 to 12-week-old SHRSP females (n = 19-16/group), which were assigned to two treatment groups: ALA (injected intraperitoneally with 25 mg/kg body weight ALA on gestation day (GD1, GD8, and GD12) or control, receiving saline following the same protocol. Our analysis of maternal signs showed that ALA prevented the pregnancy-dependent maternal blood pressure rise (GD14 blood pressure control 169.3 ± 19.4 mmHg vs. 146.1 ± 13.4 mmHg, p = 0.0001) and ameliorated renal function, as noted by the increased creatinine clearance and improved glomerular histology in treated dams. Treatment also improved the fetal growth restriction (FGR) phenotype, leading to increased fetal weights (ALA 2.19 ± 0.5 g vs. control 1.98 ± 0.3 g, p = 0.0074) and decreased cephalization indexes, indicating a more symmetric fetal growth pattern. This was associated with improved placental efficiency, decreased oxidative stress marker expression on GD14, and serum soluble fms-like tyrosine kinase 1 (sFlt1) levels on GD20. In conclusion, ALA supplementation mitigated maternal signs and improved placental function and fetal growth in SHRSP pregnancies, emerging as a promising therapy in pregnancies at high risk for PE.