Ying Xie

Arsenic-induced myocardial injury (AIMI) is a cardiovascular consequence of arsenic exposure. Astragaloside IV (AS-IV), a primary bioactive compound from Astragalus membranaceus, is known for its cardioprotective properties, yet its efficacy against AIMI remains unexplored. This study combined network toxicology, molecular docking, molecular dynamics simulations, and in vivo experiments to assess AS-IV’s protective effects and potential mechanisms in AIMI. We identified 101 overlapping targets between AS-IV and AIMI. Functional enrichment implicated apoptosis-related processes and inflammatory pathways in AS-IV’s actions. Five hub genes—LGALS3, MMP9, IL2, AR, and BCL2L1—were identified. Docking and simulations predicted potential interactions of AS-IV with MMP-9 and galectin-3 (encoded by MMP9 and LGALS3). In vivo, AS-IV ameliorated arsenic-induced histopathological damage and reduced cTnI levels. Arsenic exposure decreased myocardial GSH-Px activity but increased T-SOD activity, whereas MDA levels showed no statistically significant changes across groups. AS-IV restored GSH-Px activity and further increased T-SOD activity without significantly altering MDA levels. In addition, AS-IV attenuated cardiomyocyte apoptosis, as evidenced by reduced TUNEL positivity and cleaved caspase-3 expression. Notably, arsenic upregulated galectin-3, which AS-IV dose-dependently reduced, while MMP-9 remained unchanged in this early-stage model, consistent with minimal fibrosis. Further bioinformatic analyses linked galectin-3 to early immune-inflammatory and extracellular matrix remodeling signals. In conclusion, AS-IV attenuated arsenic-induced myocardial injury and cardiomyocyte apoptosis in mice. The protective effects were accompanied by changes in oxidative stress-related enzyme activities and reduced myocardial Galectin-3 expression. These findings suggest that galectin-3 may represent a candidate target associated with AS-IV treatment, although its causal involvement in the cardioprotective effects of AS-IV requires further investigation.

Ferroptosis contributes to ultraviolet (UV)-induced epidermal injury, but whether circadian state modifies keratinocyte susceptibility remains unclear. We integrated human epidermal transcriptomic analyses with functional experiments in HaCaT keratinocytes to compare UVA- and UVB-induced ferroptosis-associated responses and assess their temporal regulation. Both wavelengths reduced cell viability and increased reactive oxygen species, lipid peroxidation, and intracellular Fe²⁺ accumulation; ferrostatin-1 provided partial protection. UVB reduced xCT and GPX4 and showed a proteasome-sensitive component of GPX4 loss, whereas UVA predominantly reduced GPX4 without detectably altering xCT. Human epidermal transcriptomes showed heterogeneous cross-sectional associations among circadian, oxidative-stress, and ferroptosis-related genes, while longitudinal profiles revealed positive temporal coupling between NR1D1-associated signals and GPX4. In synchronized HaCaT cells, ARNTL and NR1D1 displayed 24 h rhythmicity, whereas GPX4 and SLC7A11 did not meet the prespecified rhythmicity criterion. Nevertheless, UVA-induced cytotoxicity, oxidative stress, lipid peroxidation, and GPX4 loss varied across post-synchronization time points and were greatest at 24 h. SR8278 partially preserved GPX4 abundance and attenuated UVA-induced loss of viability, reactive oxygen species accumulation, and lipid peroxidation, without significantly affecting Fe²⁺ accumulation. These findings associate circadian state with temporal variation in UVA-induced ferroptosis susceptibility and implicate the broader clock-redox system rather than rhythmic expression of individual ferroptosis effectors.

Ultraviolet A (UVA) intensity in daily life is a significant risk factor for skin photoaging. Ginkgo biloba extract (GBE), a plant‐derived natural extract widely used in clinical practice, has been reported to reduce oxidative damage under various pathological conditions, including diabetes, ischemic injury, and neurodegeneration. These findings suggest that GBE may also protect the skin against UVA‐induced oxidative damage and photoaging. In this study, a UVA‐induced photoaging model was established by applying 1% 8‐methoxypsoralen (8‐MOP) to the dorsal skin of mice two hours before each UVA exposure to enhance photosensitivity. The mice were then exposed to UVA radiation for seven consecutive days with a cumulative dose of 110 J/cm ² , while GBE was administered orally (100 mg/kg/day) prior to and during UVA irradiation. Skin oxidative stress markers, collagen degradation, and plasma inflammatory cytokines (TNF‐α, IL‐1β, COX‐2, IL‐6) were analyzed, and Western blotting was used to assess MAPK pathway activation (ERK, JNK, p38), NF‐κB nuclear translocation, and the expression of c‐Jun, c‐Fos, and matrix metalloproteinases (MMP‐1, MMP‐3, MMP‐9). UVA/8‐MOP exposure significantly enhanced oxidative stress, inflammatory responses, and MMP expression, activating MAPK and NF‐κB pathways, whereas GBE treatment markedly alleviated these effects and preserved collagen structure. These findings suggest that GBE exerts protective potential against UVA/8‐MOP‐induced skin photoaging by mitigating oxidative stress, enhancing endogenous defense mechanisms, reducing free radical damage to biomolecules such as DNA and proteins, and suppressing inflammation, supporting its possible application as a therapeutic candidate for anti‐photoaging interventions.

This study explores the roles of ubiquitin-like modification genes in pan-cancer, focusing on their regulatory mechanisms, prognostic implications, and drug sensitivity. Data on five key neddylation pathway genes (RBX1, NEDD8, NAE1, UBA3, UBE2M) were collected from TCGA and GTEx databases, covering mRNA expression, DNA methylation, SNVs, and CNVs. Gene expression differences between normal and cancer tissues, along with associations with genetic alterations, methylation, and cancer-related pathways, were analyzed. Drug sensitivity correlations were assessed using GDSC and CTRP databases. Neddylation pathway genes exhibit hypomethylation and overexpression across various cancers, correlating with poor prognosis. SNVs are predominantly missense mutations, while CNVs are mostly heterozygous deletions and amplifications. These genes regulate several key cancer-related pathways, such as DNA damage repair, cell cycle modulation, and inhibition of RTK/RAS/MAPK pathways. Ubiquitin-like modification genes are associated with poor prognosis due to their low methylation and high expression in cancers. Their genetic alterations impact cancer pathways, underscoring their potential as therapeutic targets and prognostic biomarkers.

Circadian rhythms, the internal timekeeping systems governing physiological processes, significantly influence skin health, particularly in response to ultraviolet radiation (UVR). Disruptions in circadian rhythms can exacerbate UVR-induced skin damage and increase the risk of skin aging and cancer. This review explores how circadian rhythms affect various aspects of skin physiology and pathology, with a special focus on DNA repair. Circadian regulation ensures optimal DNA repair following UVR-induced damage, reducing mutation accumulation, and enhancing genomic stability. The circadian control over cell proliferation and apoptosis further contributes to skin regeneration and response to UVR. Oxidative stress management is another critical area where circadian rhythms exert influence. Key circadian genes like brain and muscle ARNT-like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) modulate the activity of antioxidant enzymes and signaling pathways to protect cells from oxidative stress. Circadian rhythms also affect inflammatory and immune responses by modulating the inflammatory response and the activity of Langerhans cells and other immune cells in the skin. In summary, circadian rhythms form a complex defense network that manages UVR-induced damage through the precise regulation of DNA damage repair, cell proliferation, apoptosis, inflammatory response, oxidative stress, and hormonal signaling. Understanding these mechanisms provides insights into developing targeted skin protection and improving skin cancer prevention.

Cisplatin (DDP)‐based chemotherapy is a preferred treatment for a broad spectrum of cancers, but the precise mechanisms of its hepatotoxicity are not yet clear. Recently, the role of voltage‐dependent anion channel protein 1 (VDAC1) in mitochondrial activity and cell apoptosis has attracted much attention. Our aim was to investigate the effects of mitochondrial outer membrane protein VDAC1 oligomerization in DDP‐induced hepatocyte apoptosis. L‐02 hepatocytes were divided into 4 groups: (a) control group, (b) 4,4'diisothiocyanate‐2,2'‐disulfonic acid (DIDS; 40 μm) group, (c) DDP (5 μm) group, and (d) DDP and DIDS combination group. Cell apoptosis was tested by Annexin V/FITC assay, protein expression of caspase‐3, γH2AX and NDUFB6 were observed by western blot assay, reactive oxygen species (ROS), and mitochondrial superoxide anion radical (O₂^•−) were detected by DCFH‐DA and MitoSOX probe, and DNA damage was assessed by comet assay. Moreover, the activity of mitochondrial respiratory chain complex I was determined by the colorimetry method. Compared with the control group, apoptosis rate and activated cleaved‐caspase‐3 protein, ROS and O₂^•− generation, DNA damage marker comet tail length, and γH2AX protein level increased in the DDP treatment group (P < 0.05). Activity of mitochondrial COXI decreased after DDP treatment (P < 0.05). DIDS, as a VDAC1 oligomerization inhibitor, antagonized DDP‐induced apoptosis by diminishing oxidative stress and DNA damage and protecting mitochondrial complex protein. These results show that VDAC1 oligomerization may play an important role in DDP‐induced hepatocyte apoptosis by increasing ROS and mtDNA leakage from VDAC1 pores, exacerbating oxidative stress and mtDNA damage.

Background: Workers in fireworks production are mainly at risk for explosion injury. However, there are few reports on the consequences of methanol poisoning in fireworks laborers.Case Presentation: We report on three patients with visual loss caused by inhalation exposure to high concentrations of methanol, who were engaged in the granulation process of the fireworks manufacturing industry. They presented with severe metabolic acidosis and visual impairments, accompanied by headache, chest tightness, shortness of breath, dizziness, and vomiting. All were diagnosed with acute methanol poisoning. One patient developed bilateral blindness and two patients improved after timely hemodialysis treatment.Conclusions: These case reports emphasize the risk of methanol poisoning in the fireworks industry or other factories using commercial alcohol with high methanol content. Early hemodialysis intervention and metabolic acidosis correction are crucial for rescuing visual impairment caused by methanol exposure. Awareness and supervision of commercial alcohol use are indispensable for similar industrial processes.