Objective To investigate the value of repeat renal biopsy in the treatment and prognosis of nephrotic syndrome(NS)and acute kidney injury(AKI)following immunosuppressive therapy in patients with lupus nephritis(LN). Methods A retrospective analysis was conducted for the clinicopathological data and follow-up records of LN patients undergoing repeat renal biopsy at Peking Union Medical College Hospital from January 1,2009 to December 31,2021. Results A total of 76 patients(55 females,72.4%)were included in this study,with the mean age at the first biopsy being(29.0±10.4)years,the median inter-biopsy interval of 4.0(2.0,7.0) years,and the median total follow-up duration of 7.5(5.0,13.8)years.Pathological transformation occurred in 46(60.5%)patients,and 2 patients had comorbid diabetic nephropathy.At repeat renal biopsy,50(65.8%) patients presented NS.These patients demonstrated lower estimated glomerular filtration rate(eGFR)(P<0.001),higher chronicity index(CI)(P=0.029),and higher complement C3(P<0.001)and C4(P<0.001)levels than those with NS at the first renal biopsy(n=50).Among the 28(36.8%) patients with AKI at repeat renal biopsy,8(28.6%)experienced acute exacerbation of chronic renal insufficiency.These patients exhibited higher serum creatinine level(P=0.002),C4 level(P=0.033),CI(P=0.042),and prevalence of thrombotic microangiopathy(P=0.046)than the patients showing AKI at the first renal biopsy(n=16),while the activity index(AI)showed no significant difference(P=0.051).Over 50% of NS and AKI patients underwent treatment modifications post-repeat renal biopsy,with clinical remission rates comparable to those after the first renal biopsy(both P>0.05).Elevated CI(≥5,P=0.001)and serum creatinine(≥140 μmol/L,P<0.001)at repeat renal biopsy were identified as independent risk factors for poor prognosis.The patients with AKI at repeat renal biopsy had higher incidence of endpoint events than the non-AKI patients(P=0.015).Neither AKI at the first renal biopsy nor NS at both biopsies had significant associations with prognosis. Conclusions Repeat renal biopsy reveals not only sustained high disease activity but also accelerates chronic progression in LN patients,which underscore its critical role in guiding the therapy for severe LN post-immunosuppression.AKI,CI≥5,and serum creatinine ≥140 μmol/L at repeat renal biopsy are strongly associated with poor prognosis.
Humans ; Lupus Nephritis/drug therapy* ; Female ; Retrospective Studies ; Adult ; Male ; Prognosis ; Biopsy ; Kidney/pathology* ; Acute Kidney Injury/pathology* ; Nephrotic Syndrome/pathology* ; Glomerular Filtration Rate ; Young Adult ; Immunosuppressive Agents/therapeutic use* ; Middle Aged

BACKGROUND: It is inaccurate to reflect the level of dust exposure through working years. Furthermore, identifying a predictive indicator for lung function decline is significant for coal miners. The study aimed to explored whether club cell secretory protein (CC16) levels can reflect early lung function changes. METHODS: The cumulative respiratory dust exposure (CDE) levels of 1,461 coal miners were retrospectively assessed by constructed a job-exposure matrix to replace working years. Important factors affecting lung function and CC16 were selected by establishing random forest models. Subsequently, the potential of CC16 to reflect lung injury was explored from multiple perspectives. First, restricted cubic spline (RCS) models were used to compare the trends of changes in lung function indicators and plasma CC16 levels after dust exposure. Then mediating analysis was performed to investigate the role of CC16 in the association between dust exposure and lung function decline. Finally, the association between baseline CC16 levels and follow-up lung function was explored. RESULTS: The median CDE were 35.13 mg/m³-years. RCS models revealed a rapid decline in forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and their percentages of predicted values when CDE exceeded 25 mg/m³-years. The dust exposure level (<5 mg/m³-years) causing significant changes in CC16 was much lower than the level (25 mg/m³-years) that caused changes in lung function indicators. CC16 mediated 11.1% to 26.0% of dust-related lung function decline. Additionally, workers with low baseline CC16 levels experienced greater reductions in lung function in the future. CONCLUSIONS CC16 levels are more sensitive than lung indicators in reflecting early lung function injury and plays mediating role in lung function decline induced by dust exposure. Low baseline CC16 levels predict poor future lung function.
Uteroglobin/blood* ; Humans ; Dust/analysis* ; Occupational Exposure/analysis* ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Lung Injury/chemically induced* ; Coal Mining ; Biomarkers/blood* ; China/epidemiology* ; Air Pollutants, Occupational ; Female

OBJECTIVE: To explore the effect of bear bile powder (BBP) on acute lung injury (ALI) and the underlying mechanism. METHODS: The chemical constituents of BBP were analyzed by ultra-high-pressure liquid chromatography-mass spectrometry (UPLC-MS). After 7 days of adaptive feeding, 50 mice were randomly divided into 5 groups by a random number table (n=10): normal control (NC), lipopolysaccharide (LPS), dexamethasone (Dex), low-, and high-dose BBP groups. The dosing cycle was 9 days. On the 12th and 14th days, 20 µL of Staphylococcus aureus solution (bacterial concentration of 1 × 10^-7 CFU/mL) was given by nasal drip after 1 h of intragastric administration, and the mice in the NC group was given the same dose of phosphated buffered saline (PBS) solution. On the 16th day, after 1 h intragastric administration, 100 µL of LPS solution (1 mg/mL) was given by tracheal intubation, and the same dose of PBS solution was given to the NC group. Lung tissue was obtained to measure the myeloperoxidase (MPO) activity, the lung wet/dry weight ratio and expressions of CD14 and other related proteins. The lower lobe of the right lung was obtained for pathological examination. The concentrations of inflammatory cytokines including interleukin (IL)-6, tumour necrosis factor α (TNF-α ) and IL-1β in the bronchoalveolar lavage fluid (BALF) were detected by enzyme linked immunosorbent assay, and the number of neutrophils was counted. The colonic contents of the mice were analyzed by 16 sRNA technique and the contents of short-chain fatty acids (SCFAs) were measured by gas chromatograph-mass spectrometer (GC-MS). RESULTS: UPLC-MS revealed that the chemical components of BBP samples were mainly tauroursodeoxycholic acid and taurochenodeoxycholic acid sodium salt. BBP reduced the activity of MPO, concentrations of inflammatory cytokines, and inhibited the expression of CD14 protein, thus suppressing the activation of NF-κB pathway (P<0.05). The lung histopathological results indicated that BBP significantly reduced the degree of neutrophil infiltration, cell shedding, necrosis, and alveolar cavity depression. Moreover, BBP effectively regulated the composition of the intestinal microflora and increased the production of SCFAs, which contributed to its treatment effect (P<0.05). CONCLUSIONS BBP alleviates lung injury in ALI mouse through inhibiting activation of NF-κB pathway and decreasing expression of CD14 protein. BBP may promote recovery of ALI by improving the structure of intestinal flora and enhancing metabolic function of intestinal flora.
Animals ; Acute Lung Injury/pathology* ; Lipopolysaccharides ; Ursidae ; Gastrointestinal Microbiome/drug effects* ; Bile/chemistry* ; Lipopolysaccharide Receptors/metabolism* ; Powders ; Male ; Lung/drug effects* ; Mice ; Peroxidase/metabolism* ; Signal Transduction/drug effects* ; Cytokines/metabolism*

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.
Reperfusion Injury/drug therapy* ; Reactive Oxygen Species/metabolism* ; Reactive Nitrogen Species/metabolism* ; Humans ; Liver/drug effects* ; Animals ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVE: To evaluate the protective effects of resveratrol against acute lung injury (ALI) and investigate the potential mechanisms underlying the reactive oxygen species (ROS)-triggered thioredoxin-interacting protein (TXNIP)/NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) pathway. METHODS: C57BL/6 mice and J774A.1 cells were selected as the research subjects. Thirty Mice were randomly divided into 5 groups of 6 in each group: control with 0.9% saline, 5 mg/kg lipopolysaccharide (LPS) 24 h, 25 mg/kg resveratrol + 5 mg/kg LPS, 100 mg/kg resveratrol + 5 mg/kg LPS, and 4 mg/kg NLRP3 inhibitor CY-09 + 5 mg/kg LPS. For cell stimulation, cells were pretreated with 5 and 20 µmol/L resveratrol for 2 h, and stimulated with or without 1 µg/mL LPS and 3 mmol/L ATP for 2 h. The antioxidant N-acetyl-L-cysteine (NAC, 2 µmol/L) was used as the positive control group. Hematoxylin and eosin staining was used to evaluate the degree of lung LPS-induced tissue damage, and enzyme-linked immunosorbent assay was used to evaluate the contents of interleukin-1 β (IL-1 β) and IL-18 in the serum and cell supernatant. ROS and malondialdehyde (MDA) levels in the lung tissue were detected using the corresponding kits. Western blotting was used to detect the expressions of TXNIP, high-mobility group box 1 (HMGB1), NLRP3, as well as cysteine-aspartic acid protease 1 (caspase-1) and gasdermin D (GSDMD) along with their cleaved forms in lung tissue. Additionally, reverse transcription quantitative polymerase chain reaction was performed to analyze the expression of related inflammatory cytokines. ROS content was detected using flow cytometry and confocal laser microscopy. Mitochondrial morphological changes were observed using transmission electron microscopy, and HMGB1 expression was detected using immunofluorescence. RESULTS: Resveratrol significantly alleviated LPS-induced lung damage with reduced inflammation, interstitial edema, and leukocyte infiltration (P<0.01). It also decreased serum levels of IL-1 β and IL-18 (P<0.05), while downregulating the expressions of NLRP3, IL-6, and other inflammatory markers at both the protein and mRNA levels (P<0.05). Notably, the higher dose (100 mg/kg) demonstrated a better effect than the lower dose (25 mg/kg). In macrophages, resveratrol reduced IL-1 β and IL-18 following LPS and ATP stimulation, suppressed HMGB1 translocation, and inhibited formation and activation of the NLRP3 inflammasome (P<0.05 or P<0.01). These anti-inflammatory effects were mediated through the suppression ROS accumulation (P<0.01) and mitochondrial dysfunction. Transmission electron microscopy revealed that resveratrol preserved mitochondrial structure, preventing the mitochondrial damage seen in LPS-treated groups (P<0.01). The expressions of cleaved caspase-1, cleaved GSDMD, and cytoplasmic HMGB1 were all reduced following resveratrol treatment (P<0.01). Moreover, resveratrol inhibited dissociation of TXNIP from thioredoxin, blocking subsequent activation of NLRP3 and downstream inflammatory cytokines (P<0.01). Similarly, the higher concentration of resveratrol (20 µ mol/L) exhibited superior efficacy in vitro. CONCLUSION Resveratrol can reduce the inflammatory response following ALI and inhibit the activation of NLRP3 inflammasome and the level of HMGB1 in the cytoplasm by inhibiting ROS overproduction.
Acute Lung Injury/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Animals ; Resveratrol/pharmacology* ; Reactive Oxygen Species/metabolism* ; Inflammation/complications* ; Mice, Inbred C57BL ; Carrier Proteins/metabolism* ; Signal Transduction/drug effects* ; Lipopolysaccharides ; Thioredoxins/metabolism* ; Mice ; Lung/drug effects* ; Male ; Cell Line ; Interleukin-1beta/metabolism* ; Cell Cycle Proteins ; Stilbenes/therapeutic use*

OBJECTIVES: Hypoxia/reoxygenation (H/R) injury is a critical pathological process during liver transplantation. Kazinol B has known anti-inflammatory, anti-apoptotic, and metabolic regulatory properties, but its protective mechanism in H/R-induced liver injury remains unclear. This study aims to investigate the protective effects and underlying mechanisms of Kazinol B in H/R-induced hepatocyte injury. METHODS: An ischemia-reperfusion model was established in healthy adult male Sprague-Dawley rats, and an in vitro H/R model was created using cultured hepatocytes. Hepatocytes were treated with Kazinol B (0-100 μmol/L) to assess cytotoxicity and protective effects. Cell viability was evaluated using the cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) release assays. Expression of apoptosis-related proteins, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad), and cleaved caspase-3, was detected by Western blotting. Reactive oxygen species (ROS) levels were assessed via fluorescence probes, and inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured using enzyme-linked immunosorbent assay (ELISA). TdT-mediated nick end labeling (TUNEL) staining was performed to assess DNA damage and apoptosis. RESULTS: Kazinol B had no significant effect on hepatocyte viability at 0-50 μmol/L, but showed cytotoxicity at 100 μmol/L (P<0.05). At 0.1-20 μmol/L, Kazinol B significantly improved cell survival, reduced LDH release, decreased apoptosis, and attenuated DNA damage (all P<0.001). At 10 μmol/L, Kazinol B markedly down-regulated Bad and cleaved caspase-3 (both P<0.05), and up-regulated Bcl-2 (P<0.01). It also dose-dependently reduced ROS levels and inflammatory cytokines TNF-α and IL-1β (all P<0.01). Both in vitro and in vivo, Kazinol B inhibited activation of the c-Jun N-terminal kinase (JNK) pathway without affecting extracellular regulated protein kinase (ERK) signaling (P>0.05). TUNEL staining showed that the protective effect of Kazinol B against apoptosis was partially reversed by the JNK agonist anisomycin (P<0.01). CONCLUSIONS Kazinol B mitigates hepatocyte injury induced by H/R by inhibiting the JNK signaling pathway. Its protective effect is associated with suppression of oxidative stress and inflammation, indicating its potential as a hepatoprotective agent.
Animals ; Hepatocytes/pathology* ; Rats, Sprague-Dawley ; Male ; Rats ; Reperfusion Injury/prevention & control* ; Apoptosis/drug effects* ; Reactive Oxygen Species/metabolism* ; MAP Kinase Signaling System/drug effects* ; Cell Survival/drug effects* ; Cell Hypoxia ; Cells, Cultured

OBJECTIVES: Acute lung injury (ALI) is an acute respiratory failure syndrome characterized by impaired gas exchange. Due to the lack of effective targeted drugs, it is associated with high mortality and poor prognosis. Tripterygium wilfordii (TW) has demonstrated anti-inflammatory activity in the treatment of various diseases. This study aims to investigate the effects and underlying mechanisms of TW on myeloid-derived suppressor cells (MDSCs) in ALI, providing experimental evidence for TW as a potential adjuvant therapy for ALI. METHODS: Eighteen specific pathogen-free (SPF) C57BL/6 mice were randomly divided into normal control (NC; intranasal saline), lipopolysaccharide (LPS; 5 mg/kg intranasally to induce ALI), and LPS+TW (50 mg/kg TW by gavage on the first day of modeling, followed by 5 mg/kg LPS intranasally to induce ALI) groups (n=6 each). Lung injury and edema were assessed by histopathological scoring and wet-to-dry weight ratio. Cytokine levels [interleukin (IL)-1β, IL-6, IL-18, tumor necrosis factor-α (TNF-α)] in lung tissue lavage fluid were measured by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to assess the proportions of MDSCs, polymorphonuclear MDSCs (PMN-MDSCs), and monocytic MDSCs (M-MDSCs) in bone marrow, spleen, peripheral blood, and lung tissue, as well as reactive oxygen species (ROS) levels in lung tissues. Messenger RNA (mRNA) expression levels of inducible nitric oxide synthase (iNOS) and arginase-1 (ARG-1) in lung tissues were determined by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). PMN-MDSCs sorted from the lungs of LPS-treated mice were co-cultured with splenic CD3⁺ T cells and divided into NC, triptolide (TPL)-L, and TPL-H groups, with bovine serum albumin, 25 nmol/L TPL, and 50 nmol/L TPL, respectively. Flow cytometry was used to detect the effect of PMN-MDSCs on T-cell proliferation, and RT-qPCR was used to measure iNOS and ARG-1 mRNA expression. RESULTS: Compared with the NC group, the LPS group showed marked lung pathology with significantly increased histopathological scores and wet-to-dry ratios (both P<0.001). TW treatment significantly alleviated lung injury and reduced both indices compared with the LPS group (both P<0.05). Cytokine levels were significantly decreased in the LPS+TW group compared with the LPS group (all P<0.001). The proportions of MDSCs in CD45⁺ cells from spleen, bone marrow, peripheral blood, and lung, as well as PMN-MDSCs from spleen, peripheral blood, and lung, were significantly reduced in the LPS+TW group compared with the LPS group (all P<0.05), accompanied by reduced ROS levels in lung tissues (P<0.001). iNOS and ARG-1 mRNA expression in lung tissues was significantly lower in the LPS+TW group than in the LPS group (both P<0.001). In vitro, compared with the TPL-L group, the TPL-H group showed significantly increased CD3⁺ T-cell proliferation (P<0.001), and decreased iNOS and ARG-1 mRNA expression (all P<0.05). CONCLUSIONS TW alleviates the progression of LPS-induced ALI in mice, potentially by reducing the proportion of MDSCs in lung tissues and attenuating the immunosuppressive function of PMN-MDSCs.
Animals ; Acute Lung Injury/chemically induced* ; Myeloid-Derived Suppressor Cells/cytology* ; Tripterygium/chemistry* ; Mice, Inbred C57BL ; Mice ; Cell Differentiation/drug effects* ; Male ; Lipopolysaccharides ; Nitric Oxide Synthase Type II/genetics* ; Cytokines/metabolism* ; Reactive Oxygen Species/metabolism* ; Diterpenes/pharmacology* ; Epoxy Compounds ; Phenanthrenes

OBJECTIVES: Sepsis-associated acute lung injury (S-ALI) is one of the major causes of death in intensive care unit (ICU) patients, yet its mechanisms remain incompletely understood and effective therapies are lacking. Lytic cell death of macrophages is a key driver of the inflammatory cascade in S-ALI. PANoptosis, a newly recognized form of lytic cell death characterized by PANoptosome assembly and activation, involves plasma membrane rupture (PMR) mediated by ninjurin-1 (NINJ1), a recently identified pore-forming protein. Itaconic acid is known for its anti-inflammatory effects, but its role in macrophage PANoptosis during S-ALI is unclear. This study aims to investigate the protective effect of itaconic acid on macrophage PANoptosis in S-ALI to provide new therapeutic insights. METHODS: Male specific-pathogen-free C57BL/6J mice (6-8 weeks, 18-20 g) received intraperitoneal lipopolysaccharide (LPS) to establish a classical S-ALI model. Western blotting was used to assess PANoptosome-related proteins and enzymes involved in the itaconic acid metabolic pathway, while real-time reverse transcription polymerase chain reaction and metabolomics quantified itaconic acid levels. Primary peritoneal macrophages (PMs) were pretreated with the itaconate derivative 4-octyl itaconate (4-OI) and then exposed to tumor necrosis factor alpha (TNF-α) plus interferon gamma (IFN-γ) to induce PANoptosis. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Western blotting was employed to quantify enzymes of the itaconate-metabolic pathway in PANoptotic macrophages, to evaluate the impact of 4-OI on PANoptosome-associated proteins, and to determine NINJ1 abundance in lung tissues from S-ALI mice and in PANoptotic macrophages. Fluorescent dye FM_4-64 was used to visualize 4-OI-mediated changes in PMR, whereas immunofluorescence staining mapped the effect of 4-OI on both the expression level and membrane localization of NINJ1 in PANoptotic macrophages. The effect of 4-OI on lactate dehydrogenase (LDH) release in culture supernatants and peripheal blood serum was assessed using a LDH assay kit, and non-denataring polyacylamide gel electrophoresis was used to assess the expression of NINJ1 in S-ALI mouse lung tissues and the impact of 4-OI on the expression of PANoptosis-associated NINJ1 multimeric reflected protein in macropahges. RESULTS: In S-ALI mouse lungs, PANoptosome components [NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Gasdermin D (GSDMD), Caspase-1, Z-DNA binding protein (ZBP1), and Caspase-3] and phosphorylated mixed lineage kinase domain-like protein (MLKL) S345 were significantly upregulated (all P<0.05), while metabolomics showed compensatory increases in itaconic acid and its key enzymes [aconitate decarboxylase 1 (ACOD1)/immunoresponsive gene 1 (IRG1)]. In macrophages, 4-OI obviously suppressed PANoptosome protein expression, reduced LDH release, restored plasma membrane integrity, and inhibited NINJ1 expression and oligomerization at the membrane (P<0.05). CONCLUSIONS Itaconic acid may alleviate macrophage PANoptosis in S-ALI by inhibiting NINJ1-mediated plasma membrane rupture. Targeting NINJ1 or enhancing itaconate pathways may offer a novel therapeutic strategy for S-ALI.
Animals ; Acute Lung Injury/pathology* ; Succinates/pharmacology* ; Sepsis/complications* ; Mice, Inbred C57BL ; Male ; Mice ; Macrophages/pathology* ; Cell Membrane/metabolism* ; Lipopolysaccharides ; Hydro-Lyases

OBJECTIVES: Due to prolonged exposure to cosmic radiation and meteorite impacts, lunar surface dust forms nanoscale angular particles with strong electrostatic adsorption properties. These dust particles pose potential inhalation risks, yet their pulmonary toxicological mechanisms remain unclear. Given the need for dust exposure protection in future lunar base construction and resource development, this study established an acute exposure model using lunar soil simulant (LSS) and used Earth soil (ES; Loess from Shaanxi, China) as a comparison to investigate lung injury mechanisms. METHODS: C57BL/6 mice were randomly assigned to 3 groups: Phosphate buffered saline (PBS), LSS, and ES, with 5 to 7 mice per group. Mice in the LSS and ES groups received a single intratracheal instillation to induce acute inhalation exposure. Body weight was monitored for 28 days. Mice were euthanized at days 3, 7, 14, and 28 post-exposure, and peripheral blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected. Immune cell subsets in BALF were analyzed using flow cytometry. Hematoxylin-eosin (HE) staining assessed lung structure and inflammation; periodic acid-Schiff (PAS) staining evaluated airway mucus secretion; Masson staining examined collagen deposition. Real-time reverse transcription PCR (real-time RT-PCR) was used to measure the mRNA expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and epithelial barrier genes (Occludin, Cadherin-1, and Zo-1). Lung tissues at day 7 were subjected to transcriptomic sequencing, followed by immune infiltration and pathway enrichment analyses to determine immunoregulatory mechanisms. RESULTS: Body weight in the ES group progressively declined after day 18 (all P<0.05), while the LSS group showed no significant changes compared with the control group. HE staining showed both LSS and ES induced inflammatory cell infiltration around airways and vasculature, which persisted for 28 days but gradually lessened over time. PAS staining revealed marked mucus hypersecretion in the LSS group at day 3, followed by gradual recovery; no significant mucus changes were observed in the ES group. Masson staining indicated no obvious pulmonary fibrosis in either group within 28 days. Real-time RT-PCR demonstrated significant upregulation of IL-1β and TNF-α in both LSS and ES groups, peaking on day 7, accompanied by downregulation of epithelial barrier genes (Occludin, Cadherin-1, and Zo-1)(all P<0.05). Transcriptomic analysis showed that both LSS and ES activated chemokine-related pathways and enriched leukocyte migration and neutrophil recruitment pathways. Further validation revealed upregulation of CXCL2 and MMP12 in the LSS group, whereas CXCL3 and MMP12 were predominantly elevated in the ES group. CONCLUSIONS Both LSS and ES can induce sustained lung injury and neutrophil infiltration in mice, though the underlying molecular mechanisms differ. Compared with ES, exposure to LSS additionally triggers a transient eosinophilic response, suggesting that lunar dust particles possess stronger immunostimulatory potential and higher biological toxicity.
Animals ; Mice ; Mice, Inbred C57BL ; Soil ; Lung Injury/etiology* ; Dust ; Bronchoalveolar Lavage Fluid ; Moon ; Lung/pathology* ; Inhalation Exposure/adverse effects* ; Male

Donors with a serum sodium concentration of >155 mmol/L are extended criteria donors for liver transplantation (LT). Elevated serum sodium of donors leads to an increased incidence of hepatic dysfunction in the early postoperative period of LT; however, the exact mechanism has not been reported. We constructed a Lewis rat model of 70% hepatic parenchymal area subjected to ischemia-reperfusion (I/R) with hypernatremia and a BRL-3A cell model of hypoxia-reoxygenation (H/R) with high-sodium (HS) culture medium precondition. To determine the degree of injury, biochemical analysis, histological analysis, and oxidative stress and apoptosis detection were performed. We applied specific inhibitors of the epithelial sodium channel (ENaC) and Na⁺/Ca²⁺ exchanger (NCX) in vivo and in vitro to verify their roles in injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels and the area of hepatic necrosis were significantly elevated in the HS+I/R group. Increased reactive oxygen species (ROS) production, myeloperoxidase (MPO)‍-positive cells, and aggravated cellular apoptosis were detected in the HS+I/R group. The HS+H/R group of BRL-3A cells showed significantly increased cellular apoptosis and ROS production compared to the H/R group. The application of amiloride (Amil), a specific inhibitor of ENaC, reduced ischemia-reperfusion injury (IRI) aggravated by HS both in vivo and in vitro, as evidenced by decreased serum transaminases, inflammatory cytokines, apoptosis, and oxidative stress. SN-6, a specific inhibitor of NCX, had a similar effect to Amil. In summary, hypernatremia aggravates hepatic IRI, which can be attenuated by pharmacological inhibition of ENaC or NCX.
Animals ; Reperfusion Injury/drug therapy* ; Hypernatremia/complications* ; Rats ; Liver/metabolism* ; Rats, Inbred Lew ; Male ; Apoptosis ; Sodium-Calcium Exchanger/antagonists & inhibitors* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Epithelial Sodium Channel Blockers/pharmacology* ; Epithelial Sodium Channels ; Cell Line ; Liver Transplantation