Coenzyme Q10 is a lipid-soluble antioxidant essential for the mitochondrial electron transport chain. Its concentration in the body decreases with age. The biosynthesis of coenzyme Q10 involves enzymes coq1 (PDSS1, PDSS2) through coq9, though the regulatory mechanisms of their gene expression and enzyme activities are unknown. SIRT1, an anti-aging gene, regulates various transcription factors. This study investigates the impact of SIRT1 knockdown on the gene expression of coenzyme Q10 biosynthetic enzymes and coenzyme Q10 levels in MDA-MB-231 and HepG2 cells. SIRT1 knockdown significantly increased coq4 gene expression in MDA-MB-231 cells, while coq6 and coq7 expression decreased. In HepG2 cells, coq4 expression also increased, but coq6 and coq7 expression remained unchanged. Coenzyme Q10 levels increased in both cell lines. Further experi­ments with PGC-1α and NRF1 knockdown, downstream factors of SIRT1, in MDA-MB-231 cells showed no change in coq4 expression, while coq6 and coq7 expression decreased, and coenzyme Q10 levels remained unchanged. These findings suggest that the increase in coenzyme Q10 levels following SIRT1 knockdown may be attributed to coq4, indicating a pathway distinct from PGC-1α and NRF1.

Cancer cachexia affects approximately 80% of patients with advanced cancer, leading to anorexia, weight loss, and severe muscle wasting that negatively impacts survival. Despite its clinical significance, no effective therapies have been approved worldwide. Inflammatory cytokines, particularly interleukin-6 (IL-6), are known to play a key role in the pathogenesis of cachexia and represent promising therapeutic targets. In this study, we explored the role of intestinal oxidative stress in regulating systemic inflammation associated with cancer cachexia. We orally administered antioxidant polymer nanoparticles (siSMAPo^TN), designed to localize in the intestinal lumen and selectively scavenge reactive oxygen species (ROS), to tumor-bearing cancer cachexia model mice. As a result, siSMAPo^TN treatment suppressed plasma IL-6 elevation, mitigated muscle protein degradation signaling, and effectively prevented muscle atrophy. Notably, the intestinally localized action of antioxidant nanoparticles led to systemic therapeutic effects, thereby signifi­cantly alleviating cancer cachexia. These findings highlight that increased oxidative stress contributes to the systemic inflam­matory cascade of cachexia, and demonstrate the therapeutic potential of intestinally acting antioxidant nanoparticles as a novel non-invasive strategy for cancer cachexia management.

Dysfunction of sirtuins (SIRTs), a family of NAD⁺-dependent histone deacetylases involved in epigenetic modulation of protein function and gene expression, is associated with both age-related metabolic diseases and cancers in mammals, and SIRT modulators are consid­ered attractive therapeutic targets. However, although various SIRT detection methodologies have been developed, especially focusing on other enzymatic activities of SIRTs, such as long chain defatty-acylase activity, there has been little progress in developing methodologies capable of quantitatively evaluating SIRT activity. Herein, we present the first Förster resonance energy transfer (FRET)-based ratiometric fluorescence probes for SIRT1, containing fluorescein isothiocyanate (FITC) as a FRET acceptor, coumarin as a FRET donor and an H3K9 SIRT recognition peptide sequence. Cleavage by SIRT of firstly designed probe released the coumarin fluorophore and structural modification of the latter units yielded compounds with high SIRT1 selectivity and reactivity. We con­firmed that these probes enabled the quantitative measurement of ‍SIRT1 enzyme activity. They are expected to be useful tools in ‍studies of epigenetic regulation mechanisms, and in high-throughput screening for drug discovery targeting SIRT.

Hemorrhagic shock/reperfusion (HS/R) injury is associated with high global mortality, and intestinal injury plays a pivotal role in ‍driving systemic complications. This study examined the therapeutic potential of Ginsenoside Rg2 (G-Rg2) in mitigating HS/R intestinal injury and elucidated its relationship involving leukocyte immunoglobulin-like receptor B4 (Lilrb4). Using an established rat HS/R model and hypoxia/reoxygenation (H/R) IEC-6 cells, we evaluated the effects of G-Rg2 on intestinal barrier integrity, inflammatory responses, oxidative stress, and apoptosis. The results indicated that G-Rg2 treatment significantly alleviates intestinal mucosal damage, inhibits epithelial apoptosis, and restores tight junction proteins (Occludin, ZO-1). In vitro experi­ments revealed that G-Rg2 enhances cell viability, suppresses reactive oxygen species (ROS) overproduction, and reduces pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β). Mechanistically, G-‍Rg2 upregulated Lilrb4 expression, and supressed NF-κB pathway activation. Collectively, these findings suggested that G-Rg2 alleviates HS/R-induced intestinal injury by the upregulation of Lilrb4 and the inhibition of the NF-κB pathway.

Acute kidney injury (AKI) is a critical condition with high morbidity and mortality, often caused by ischemia/reperfusion (I/R) injury. Morroniside (MOR), derived from Cornus officinalis, has anti-inflammatory and antioxidant properties. This study investigates its effects on AKI induced by hypoxia/reoxygenation (H/R) in renal tubular epithelial cells. H/R-induced HK-2 cells were treated with MOR (0.5, 1.0, and 2.0 ‍‍μM). Cell viability was assessed using CCK-8, and oxidative stress was evaluated via reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) levels. Ferroptosis was examined through GPX4 and ACSL4 expression. The Nrf2/HO-1 signaling pathway was analyzed by Western blotting. Results show that MOR alleviates H/R-induced cell damage and oxidative stress by increasing cell viability, reducing lactate dehydrogenase (LDH) release, ROS, and MDA levels, while enhancing SOD and GSH activities. It also inhibits ferroptosis by upregulating GPX4 and downregulating ACSL4. Additionally, MOR activates the Nrf2/HO-1 signaling pathway. These findings suggest that MOR protects renal tubular epithelial cells from H/R injury by reducing oxidative damage and inhibiting ferroptosis, poten­tially through the Nrf2/HO-1 pathway.

High-sugar food intake is linked with elevated lung cancer (LC) risk. Accelerated biological senescence is a risk factor for various diseases. This study probes the role of senescence indicators in the genetic causality between high-sugar food intake and LC risk. Using GWAS data and Mendelian randomization, we found that the intake of sugar added in tea exhibited a significant positive causal association with overall LC risk (OR = 1.310, 95% CI: 1.024–1.675, p = 0.031) and lung squamous cell carcinoma risk (OR = 1.616, 95% CI: 1.089–2.398, p = 0.017). Artificial sweetener intake in cereals was positively linked with small cell lung cancer risk (OR = 4.042, 95% CI: 1.153–14.170, p = 0.029). GrimAge acceleration was significantly correlated with LC risk (p = 0.047), and Hannum age acceleration showed a positive linkage with small cell lung cancer risk (p = 0.002). The intake of sugar added to tea was positively causally linked to both GrimAge (p = 0.045) and Hannum age acceleration (p = 0.025). Mediation analysis indicated that GrimAge acceleration mediated 9.64% of the effect of sugar added to tea on LC risk. In conclusion, high-sugar food intake exhibits a genetic causal linkage with LC risk, partially mediated by biological senescence.

Dense tumor-associated macrophage infiltration correlates with poor prognosis in esophageal cancer (EC), yet the underlying molecular mechanisms remain undefined. An EC cell-macrophage co-culture system was established. M2 polarization was evaluated by flow cytometry and ELISA. qPCR and Western blot were employed to detect mRNA and protein levels. MeRIP-PCR assessed CXCR4 m6A methylation. Colony formation, wound-healing, and ‍apoptosis assays measured EC cell proliferation, migration, and apoptosis. Compared with macrophages co-cultured with normal esophageal epithelial cells, those co-cultured with EC cells exhibited increased IL-10 and TGF-β secretion, accompanied by up-regulation of CD206, CD163, CXCR4, and METTL3. METTL3 up-regulated CXCR4 by mediating CXCR4 m6A methylation. METTL3-overexpressing macrophages elevated CD206/CD163 levels and IL-10/TGF-β secretion, whereas CXCR4 knockdown reversed these effects. Moreover, METTL3-high macrophages promoted EC cell proliferation and migration, up-regulated PD-L1, and inhibited apoptosis. METTL3 is up-regulated in EC-associated macrophages, promotes M2 polarization via m6A modification of CXCR4, and thereby accelerates EC malignant progression.

Oxidative stress serves as both a precursor to and consequence of numerous pathological conditions; however, its assessment remains technically challenging and often imprecise. In the current investi­gation, we established a rapid high-performance liquid chroma­tography (HPLC)-based method for quantifying serum oxidized albumin in a murine model of chronic kidney disease (CKD). We optimized the HPLC protocol specifically for measuring oxidized albumin in mice. To validate our methodology, C57BL/6J mice underwent 5/6 nephrectomy (5/6Nx) and were randomly allocated to one of three dietary regimens: standard diet, high-salt diet, or ‍high-salt diet supplemented with Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), a superoxide dismutase mimetic. Following an 8-week intervention period, serum oxidized albumin levels were quantitatively assessed. The key findings were as follows: (i) Our optimized oxidized albumin assay demonstrates excellent intra-day and inter-day reproducibility with a rapid analysis time of 9.5 ‍‍min; (ii) Oxidized albumin concentrations were significantly increased in high-salt diet-fed animals relative to normal-diet controls, an effect that was attenuated by Tempol administration; (iii) Significant positive correlations were observed between oxidized albumin levels and both urinary protein excretion and 8-isoprostane concentrations. Collectively, we have developed a robust and efficient HPLC-based analytical approach for measuring oxidized albumin in murine serum. This method­ology demonstrates both rapid processing capabilities and comparable performance compared to conventional techniques, suggesting substantial utility for investigating oxidative stress in animal models.

Reactive oxygen species (ROS) are deeply involved in aging and ‍the onset of various diseases, and enhancing the body’s antioxidant capacity is considered effective for prevention. This study investigated the effects of ultrasound (US) exposure as a novel non-invasive intervention on the body’s antioxidant capacity. First, a single US exposure to the rat back transiently increased the scavenging activities of multiple radicals, including hydroxyl radical (^•OH), superoxide radical (O₂^•−), and singlet oxygen (¹O₂). Next, upon performing cyclic US exposure, the increase in antioxidant capacity persisted for over 24 ‍‍h, with the most multifaceted and pronounced effects observed at medium intensity (I_SPTA = 0.11 ‍‍W/cm²). Furthermore, long-term exposure for approximately one month revealed that biological antioxidant capacity was maintained at a high level. These results suggest that US exposure induces an oxidative stress response similar to exercise stimulation and may promote long-term adaptations such ‍as antioxidant enzyme expression. This study is the first in the world to demonstrate enhanced antioxidant capacity in vivo through non-invasive intervention using US.

Chronic atrophic gastritis is a precancerous condition in the gastric carcinogenesis cascade, in which persistent inflammation plays a central role. This study aimed to evaluate the protective effects of Icariside II, a bioactive flavonoid derived from Epimedium, against inflammation-associated gastric mucosal injury. A composite mouse model was established by oral inoculation with Helicobacter pylori, administration of N-methyl-N-nitrosourea in drinking water, and a high-salt diet. Mice were randomly assigned to a model control group, an Icariside II treatment group receiving 20 milligrams per kilogram per day by gavage, or an eradication therapy group. Icariside II alleviated gastric glandular atrophy and hyperplasia and ‍significantly reduced interleukin-6, interleukin-1β, and tumor necrosis factor α levels in both serum and gastric tissue homogenates. In human gastric cancer cells exposed to an inflammatory stimulus with tumor necrosis factor α, Icariside II reduced cell proliferation and migration, promoted apoptosis, and decreased the release of pro-inflammatory cytokines. Mechanistic analyses showed that Icariside II suppressed inflammation-related signaling activity by reducing phosphorylation and nuclear trans­location of key transcriptional regulators, leading to decreased expression of genes involved in inflammation, cell survival, and invasion. These findings indicate that Icariside II may represent a ‍potential natural compound for preventing or delaying the progression of chronic atrophic gastritis.