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This study aimed to investigate the protective effects of ginsenoside Rg1 on high-altitude hypoxia-induced acute lung injury (ALI) and elucidated its molecular targets and related pathways, specifically its association with the fluid shear stress pathway. Using a combination of bioinformatics analysis and both in vivo and in vitro experiments, we assessed the role of ginsenoside Rg1 in mitigating physiological and biochemical disturbances induced by hypoxia. In the in vivo experiments, we measured arterial blood gas parameters, levels of inflammatory cells and cytokines, erythrocyte and platelet parameters, and conducted histological analysis in rats. The in vitro experiments utilized human pulmonary microvascular endothelial cells (HPMECs) and A549 cells to examine cell viability, intracellular reactive oxygen species (ROS) and Ca2⁺ levels, and mitochondrial function. The results of the in vivo experiments demonstrate that ginsenoside Rg1 significantly increased arterial blood oxygen partial pressure and saturation, elevated arterial blood glucose levels, and stabilized respiratory and metabolic functions in rats. It also reduced inflammatory cells and cytokines, such as tumor necrosis factor-α and interleukin-6, and improved erythrocyte and platelet abnormalities, supporting its protective role through the regulation of the fluid shear stress pathway. Histological and ultrastructural analyses revealed that Rg1 significantly protected lung tissue structure and organelles. In vitro experiments further confirmed that Rg1 improved cell viability in HPMEC and A549 cells under hypoxic conditions, decreased intracellular ROS and Ca2⁺ levels, and enhanced mitochondrial function. These findings collectively demonstrate that ginsenoside Rg1 exerts significant protective effects against high-altitude hypoxia-induced ALI by enhancing oxygen delivery and utilization, reducing inflammatory responses, and maintaining cellular metabolism and vascular function. Notably, the protective effects of Rg1 are closely associated with the regulation of the fluid shear stress pathway, suggesting its potential for treating high-altitude hypoxia-related diseases. [ABSTRACT FROM AUTHOR]

Radiation-induced intestinal injury is a common complication of radiotherapy for abdominal and pelvic malignancies. Due to its rapid proliferation, the small intestine is particularly sensitive to radiation, making it a critical factor limiting treatment. Ferulic acid (FA), a derivative of cinnamic acid, exhibits antioxidant, anti-inflammatory, and anti-radiation properties. In this study, we established a mouse model of radiation-induced intestinal injury using a dose of 11 Gy at a rate of 96.62 cGy/min. Our findings indicate that FA's protective effects against radiation-induced intestinal injury may be mediated through the parkinsonism-associated deglycase (DJ-1) nuclear factor erythroid 2-related factor 2 (Nrf2) and silent mating type information regulation 2 homolog 1 (Sirt1) nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) NOD-like receptor family, pyrin domain containing 3 (NLRP3). FA was found to mitigate changes in oxidative stress indices and inflammatory factors induced by radiation, as well as to attenuate radiation-induced pathological alterations in the small intestine. Furthermore, FA enhanced the expression of DJ-1 and Nrf2 at both the transcriptional and protein levels, inhibited NLRP3 protein fluorescence intensity, and reduced the expression of NLRP3, interleukin-18 (IL-18), and interleukin-1 beta (IL-1β). Additionally, FA suppressed the transcription and translation of NF-κB, NLRP3, cysteine-aspartic acid protease-1 (Caspase-1), IL-18, and IL-1β by upregulating Sirt1, thereby alleviating radiation-induced inflammatory injury in the small intestine. Thus, FA holds promise as an effective therapeutic agent for ameliorating radiation-induced intestinal injury. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the damage caused to HaCaT cells by 60Co γ-rays at different doses and the underlying mechanism and to establish a cell model of radiation-induced skin injury. HaCaT cells were irradiated with a single dose of 60Co γ-rays (the radiation source was 3 m away from the cells, and the dose rate was 100.68 cGy/min). The cell activity was detected using the CCK-8 method, the vitality of superoxide dismutase (SOD) was measured using the water soluble tetrazolium salt staining method, the malondialdehyde (MDA) level was determined using the thiobarbituric acid method, the apoptosis rate was monitored through flow cytometry, and the expression of the apoptosis- and inflammation-related proteins was detected via western blotting. After irradiation with 60Co γ-rays at 18 Gy for 24 h, the morphology of HaCaT cells changed significantly, cell activity decreased to 57.5%, MDA level increased to 66.28 µmol/mg, inhibition rate of SOD increased to 32.12%, apoptosis rate increased to 18.05%, and expression of inflammatory factors increased. After incubation for 24 h at an absorbed dose of 18 Gy, the cellular models of radiation-induced skin injury were established. The mechanism of cell injury may be related to cell oxidative damage, apoptosis, and inflammatory reaction.

Wistar rats were irradiated with different doses of 60Co γ rays to establish models of radioactive dermatitis to exploring the development of their characteristics and rules. Twenty-six Wistar rats were randomly divided into three groups: normal control (NC) (n=6) , rad 30 Gy (n=10), and rad 45 Gy (n=10) groups. The rad 30 Gy and 45 Gy groups received a single dose of local irradiation to the buttocks, respectively. Changes in irradiated skin, body weights, and skin blood flow were observed on the 7 th, 14 th, 21 st, 28 th, 35 th, 45 th, and 60 th day after irradiation. Irradiated skin tissue samples were collected for H&E staining on the 60 th day to analyze the resultant pathological changes. Compared to the NC group, the rad group suffered distinct degrees of skin injury, which were severe on the 21 st day, followed by gradual recovery. Skin blood flow of the buttocks in erythematous hyperemia and early healing were increased, whereas its decrease in ulcers necrose and late healing. H&E staining demonstrated epidermal thickening and increase in the number of squamous epithelial cells in the rad 30 Gy group and marked epidermal thicking and dermal inflammatory cell infiltration in the rad 45 Gy group. Better model of radioactive dermatitis may be obtained by using rad 45 Gy 60Co γ rays on the skin of the buttock of Wistar rats for a singe dose of local radiation.

Daytime dysfunction, including symptoms like sleepiness, poor memory, and reduced responsiveness, is not well researched. It is crucial to develop animal models and study the biological mechanisms involved. We simulated sleep disorders through sleep deprivation, and stressful stimuli were used to establish daytime functional animal models. We used tests like the sodium pentobarbital sleep synergy test and the DSI telemetry system to measure sleep duration and structure. We also used tests like the Morris water maze, open field test, grip test, and baton twirling test to assess mental and physical fatigue. To assess the intrinsic biological mechanisms, we measured sleep–wake-related neurotransmitters and related receptor proteins, circadian rhythm-related proteins and cognition-related proteins in hypothalamus tissue, and oxidative stress, inflammatory factors, S100β, and HPA axis-related indexes in serum. Multi-factor sleep deprivation resulted in the disruption of sleep–wakefulness structure, memory–cognitive function degradation, decreased grip coordination, and other manifestations of decreased energetic and physical strength. The intrinsic biological mechanisms were related to the disturbed expression of sleep–wake, circadian rhythm, memory–cognition-related proteins, as well as the significant elevation of inflammatory factors, oxidative stress, the HPA axis, and other related indicators. Intrinsically related biological mechanisms and reduced sirt1 expression can lead to disruption of circadian rhythms; resulting in disruption of their sleep–wake-related neurotransmitter content and receptor expression. Meanwhile, the reduced expression of sirt1 also resulted in reduced expression of synapse-associated proteins. This study prepared an animal model of daytime dysfunction by means of multi-factor sleep deprivation. With sirt1 as a core target, the relevant biological mechanisms of neurological disorders were modulated. [ABSTRACT FROM AUTHOR]

The disruption of hematopoietic and immune functions is a significant consequence of the long-term effects of radiation exposure. This study investigated the potential mechanisms by which ferulic acid (FA) acts as a radioprotective agent in mitigating radiation-induced immune damage. C57BL/6J mice were exposed to a dose of 6.0 Gy of 60Co γ irradiation. FA was administered at doses of 25, 50, and 100 mg/kg/d for 7 days before and 30 days following irradiation. We evaluated changes in peripheral blood cells, T and B lymphocytes, natural killer cells in the spleen, and hematopoietic stem/progenitor cells in the bone marrow (BM). Whole-genome transcriptome sequencing of BM was performed to explore potential mechanisms. FA administration resulted in a significant reduction in malonaldehyde levels (p < 0.0001), an increase in catalase and beta-nicotinamide adenine dinucleotide levels in serum (p < 0.05), and enhanced multipotent progenitors (p < 0.01) and common lymphoid progenitors (p < 0.05) in the BM. Additionally, there was an elevation in white blood cell levels, red blood cell levels, and hemoglobin levels in peripheral blood (p < 0.01). Transcriptome analysis indicated that FA reversed the radiation-induced expression of genes related to immunity and inflammation. Enzyme-linked immunosorbent assay experiments further demonstrated that FA reduced interleukin-6 levels in the BM and decreased JAK1, JAK2, and STAT3 protein content (p < 0.01). In conclusion, FA might mitigate hematopoietic and immune damage by modulating the JAK/STAT signaling pathway. [ABSTRACT FROM AUTHOR]

Low-dose radiation has been extensively employed in clinical practice, including tumor immunotherapy, chronic inflammation treatment and nidus screening. However, the damage on the spleen caused by low-dose radiation significantly increases the risk of late infection-related mortality, and there is currently no corresponding protective strategy. In the present study, a novel compound preparation named CB001 mainly constituted of Acanthopanax senticosus (AS) and Oldenlandia diffusa (OD) was developed to alleviate splenic injury caused by fractionated low-dose exposures. As our results show that, white pulp atrophy and the excessive apoptosis in spleen tissue induced by radiation exposure were significantly ameliorated by CB001. Mechanistically, BAX-caspase-3 signaling and nucleotide-binding domain and leucine-rich-repeat-containing family pyrin 3 (NLRP3) inflammasome signaling were demonstrated to be involved in the radio-protective activity of CB001 with the selective activators. Furthermore, the crosstalk between apoptosis signaling and NLRP3 inflammasome signaling in mediating the radio-protective activity of CB001 was clarified, in which the pro-apoptotic protein BAX but not the anti-apoptotic protein Bcl2 was found to be downstream of NLRP3. Our study demonstrated that the use of a novel drug product CB001 can potentially facilitate the alleviation of radiation-induced splenic injury for patients receiving medical imaging diagnosis or fractionated radiation therapy. [ABSTRACT FROM AUTHOR]

Traditional Chinese Medicine (TCM) has been commonly used in clinical practice for thousands of years and has made enormous contributions to public health in China. However, the adverse effects on the cardiac system or TCM-induced cardiovascular diseases have emerged frequently in recent years, resulting in growing attention to the safety of TCM. Generally, TCM with adverse cardiac effects has typical therapeutic or toxic effects, which are based on specific material basis for efficacy/toxicity, specific clinical symptoms and toxic mechanisms. However, improper strategies adopted for research on the cardiotoxicity of TCM simply follow the basic principles of conventional toxicology and cause exaggerative or incorrect interpretations in the toxicity of TCM. In this review, we aim to present the classification and possible toxic mechanisms for TCM with cardiotoxicity based on the material basis for toxicity to rethink the existing problems in toxicity studies for TCM and provide new perspectives for research on the potential cardiotoxicity of TCM. We hope that this study can offer important theoretical support and scientific advice for the toxicity study and clinical rational use of TCM having cardiotoxicity. [ABSTRACT FROM AUTHOR]