Nickel refining fumes (Ni) are recognized occupational pollutants that adversely affect workers' respiratory health; however, the specific molecular mechanisms underlying their induction of lung injury remain poorly understood. Chrysin, a flavonoid compound with established anticancer and antioxidant properties, has uncertain therapeutic effects on lung injury. This study aims to investigate the effects of chronic low-dose exposure to Ni on human bronchial epithelial cells (Beas-2B cells). After 180 days of continuous low-dose Ni treatment, the test cells exhibited pronounced characteristics of malignant transformation compared to the control group. Transcriptomic analysis indicated significant activation of hypoxia signaling pathways in the transformed cells (2B-Ni cells). Both cellular and animal experiments confirmed the presence of abnormal ferroptosis-related markers and a suppression of the ferroptosis process. Chrysin significantly suppresses 2B-Ni cell activity by inhibiting proliferation, invasion, and migration capabilities while inducing ferroptosis. Further studies demonstrate that Ni regulates the prolyl hydroxylase domain protein 1 (PHD1)/hypoxia-inducible factor-1α (HIF-1α)/microRNA-210 (miR-210)/angiopoietin-like protein 4 (ANGPTL4) pathway, facilitating escape from ferroptosis in Beas-2B cells and subsequent malignant transformation. Conversely, Chrysin regulates PHD1/HIF-1α-induced ferroptosis, resulting in increased intracellular MDA, total iron content, and lipid peroxidation levels. The addition of DMOG or CoCl2 can reverse this effect. In summary, this study confirms that the PHD1/HIF-1α/miR-210/ANGPTL4 pathway mediates Ni-induced suppression of ferroptosis, thereby promoting malignant transformation in Beas-2B cells. Conversely, chrysin mitigates Ni-induced lung injury by regulating PHD1/HIF-1α-induced ferroptosis in 2B-Ni cells. These findings offer essential theoretical support and potential targets for evaluating Ni's carcinogenic risk and developing ferroptosis-targeted anti-tumor therapies.

NiNPs pose a persistent occupational hazard to the lung. However, it remains unclear whether mitochondrial lipid metabolismcentered on mitochondrial deacetylase Sirt3can be mechanistically modulated to mitigate NiNPs-induced epithelial injury. Here, we integrated GBD contextualization, network toxicology, structure-based docking/molecular dynamics, and mechanistic studies in human lung epithelial cells with Sirt3 gain- and loss-of-function. Acute NiNPs exposure reduced viability, increased ROS, dissipated mitochondrial membrane potential, increased Drp1 and decreased MFN1/MFN2, and suppressed Sirt3. Concomitantly, lipid metabolism-related markers suggested increased lipid synthesis and uptake, reduced expression of the β-oxidation-associated enzyme ACOX1, lipid droplet accumulation, and apoptosis. Sirt3 knockdown exacerbated redox collapse and lipid imbalance, whereas Sirt3 overexpression partially improved mitochondrial and lipid metabolism-related readouts, with reduced apoptosis. In silico analyses suggested stable binding of Sch B to Sirt3, and Sch B treatment was associated with increased Sirt3 expression, dampened inflammatory/profibrotic signaling, partially rescued ACOX1, and alleviated apoptosis. Collectively, these results support a Sirt3-associated mitochondrial-redox and lipid marker axis as a key contributing mechanism in epithelial injury under NiNPs suspension exposure conditions, and Sch B treatment is associated with phenotypic improvement accompanied by increased Sirt3 levels.

Occupational exposure to nickel refining fumes (NiRF) represents a critical risk factor for respiratory diseases; however, the molecular mechanisms governing NiRF-induced epithelial-mesenchymal transition (EMT) in bronchial epithelial cells remain incompletely elucidated. In vitro experiments using the human bronchial epithelial cell line Beas-2B as a model demonstrated that NiRF exposure robustly activated the hypoxia-inducible factor-1α (HIF-1α)/Notch signaling pathway, while concomitantly triggering glutamine metabolic reprogramming. This reprogramming phenotype was characterized by the upregulated expression of the glutamine transporter SLC1A5 and enhanced expression of glutaminase 1 (GLS1). Functional validation assays revealed that small interfering RNA (siRNA)-mediated silencing of HIF-1α (siHIF-1α) or Notch1 (siNotch1) significantly downregulated GLS1 expression, and reversed NiRF-induced glutamine metabolic activation. Furthermore, pharmacological inhibition of glutamine metabolism via treatment with a GLS1 inhibitor effectively abrogated the EMT process in Beas-2B cells, as evidenced by the upregulated expression of the epithelial marker E-cadherin and the downregulated expression of the mesenchymal markers N-cadherin and vimentin. In vivo experiments further confirmed that NiRF promoted EMT in lung tissue cells in a dose-dependent manner, accompanied by activation of the HIF-1α/Notch signaling pathway and enhanced glutamine metabolism (as reflected by the upregulated expression of both SLC1A5 and GLS1). Collectively, these findings verify that glutamine metabolic activation, mediated by the HIF-1α/Notch pathway, constitutes the core mechanism underlying NiRF-driven EMT in Beas-2B cells. This study provides novel theoretical insights and potential therapeutic targets for elucidating the pathogenesis of occupational NiRF-associated respiratory injury and developing targeted intervention strategies.

Di(2-ethylhexyl) phthalate (DEHP), a common plasticizer, exhibits environmental persistence and multisystem toxicity. With plastic production continually rising, China's annual output exceeded 77 million tons in 2024, reflecting a 2.9 % year-on-year increase (Ministry of Industry and Information Technology). This reflects largescale consumption and increasing environmental pressure. However, its toxic mechanisms on the intestine, a key organ for defense and metabolism, remain poorly understood. This study indicated that DEHP exposure causes damage to zebrafish intestinal tissue, resulting in a reduction in commensal bacteria such as Fusobacterium and Cetobacterium, and enrichment of Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium and Pseudomona. The analysis suggested that the expression of Toll-like receptor pathways, NOD-like receptor signaling pathways, and MAPK signaling pathways related to immunity and metabolism was upregulated. In addition,genes such as tlr4, myd88, nf-kappa b, and il10 were significantly upregulated. Together, these findings show that DEHP may raise the risk of intestinal immune injury via the TLR4/MyD88/NF-kappa B pathway and dysbiosis of the intestinal microbiota. This study contributes to the assessment and control of health risks associated with DEHP contamination in water.

Nickel nanoparticles (NiNPs) are extensively used in nanotechnology, electronics, and biomedical fields, raising concerns about their pulmonary toxicity and potential role in inducing lung adenocarcinoma (LUAD). While heavy metals, like arsenic and cadmium, are well-known to drive LUAD through metabolic reprogramming, the molecular mechanism linking NiNPs to LUAD-particularly their impact on fatty acid metabolism (FAM)-remains unclear. This study is the first to explore whether NiNPs promote LUAD progression via the CDK1/STAT3/FASN axis, a key regulator of FAM, and to evaluate the natural compound apigenin (API) as a potential inhibitory agent. When human (A549) and mouse (LLC) LUAD cells were exposed to NiNPs, assessments of cell function and protein expression revealed increased malignant phenotypes, including enhanced proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), along with activation of the CDK1/STAT3/FASN axis and upregulation of FAM-related markers. Genetic silencing of either CDK1 or FASN reversed the dysregulation of FAM and reduced the malignant characteristics of the cells. Molecular docking analysis confirmed that API binds strongly to CDK1, and further experiments demonstrated that API suppresses NiNP-induced tumor growth both in laboratory cell models and in living organisms, while also blocking the activity of the CDK1/STAT3/FASN axis.

BackgroundLung adenocarcinoma (LUAD) is one of the most common malignant tumors globally, characterized by poor prognosis and high mortality. Abnormal fatty acid metabolism plays a crucial role in LUAD progression. This study aims to develop a prognostic model based on fatty acid metabolism to improve the overall prognosis of LUAD.Materials and methodsBioinformatics analyses were performed using TCGA and GEO datasets, supplemented by cell experiments. A total of 309 fatty acid metabolism-related genes were identified from MsigDB. Differentially expressed genes were analyzed using the ‘limma’ R package. A prognostic model was constructed using LASSO regression and validated with survival analyses via the ‘survminer’, ‘survival’, and ‘pROC’ R packages. The analysis included somatic mutations, tumor mutation burden, clinical correlations, stemness analysis, cytokine correlations, and enrichment analysis. Protein interaction networks were constructed using STRING and Cytoscape, while immune cell infiltration and immunotherapy responses were evaluated with the ‘oncoPredict’ R package. Results were validated through cell experiments and immunohistochemistry staining of lung tissues.ResultsWe identified 125 differentially expressed genes related to fatty acid metabolism, with 33 genes significantly associated with prognosis. Patients in the high-risk group had poorer overall survival and progression-free survival, and the risk score correlated with gender, N stage, clinical stage, and T stage. The risk score was also associated with cancer stem cells, with a significantly higher mRNAsi index in the high-risk group. Additionally, the risk score correlated with various cytokine expressions and showed significant enrichment in cell cycle pathways. Key genes like CDK1 were highly expressed in LUAD cell lines and validated in clinical samples. The low-risk group showed better responses to immune checkpoint inhibitors, with the risk score correlating with immune checkpoint gene expression.ConclusionThis study successfully established a novel prognostic model based on fatty acid metabolism, which provides valuable insights for the treatment of LUAD.

MiRNA-based therapeutics represent a promising approach for treating multiple diseases, yet the key regulatory miRNAs in chronic cerebral hypoperfusion (CCH)-related cognitive impairment remains unclear. Here, we identify miR-153 as consistently upregulated in both male and female mild cognitive impairment (MCI) and late-stage of Alzheimer's disease (AD) patients, as well as in the basal forebrain of both male and female postmortem AD specimens and male CCH rats. Knockdown of miR-153 in the basal forebrain alleviated CCH-induced cognitive deficits. Mechanistically, miR-153 directly targeted Karyopherin alpha 5 (KPNA5), a nuclear transport protein that facilitates nuclear factor erythroid 2-related factor 2 (NRF2) nuclear translocation. miR-153 suppressed KPNA5 via two binding sites in its 3'UTR, impairing NRF2-mediated antioxidant responses and promoting oxidative stress, and KPNA5 bound to three nuclear localization sequences of NRF2 through protein interaction. Restoration of the miR-153-KPNA5-NRF2 axis in the basal forebrain alleviated oxidative stress damage in male CCH rats, while no such effect was observed in the hippocampus. These findings reveal a potential role of the miR-153-KPNA5-NRF2 axis in CCH-related cognitive decline.

Background and aims: Acrylamide (ACR) induces hepatotoxicity, yet its underlying mechanisms remain incompletely understood. Our prior proteomic analysis of serum from occupationally ACR-exposed individuals identified significantly elevated levels of eukaryotic elongation factor 2 (eEF2). Given that eEF2 activity is regulated by its phosphorylation status, which is solely mediated by eukaryotic elongation factor 2 kinase (eEF2K), we investigated the role of eEF2K in ACR-induced hepatic injury. Methods: eEF2K gene knockout (eEF2K-/-) mice were used to assess the impact of eEF2K ablation on ACR-induced hepatotoxicity. Downstream mechanisms were explored by liver metabolomics and Western blot analysis. Results: ACR exposure significantly increased hepatic eEF2K expression and eEF2 phosphorylation (P < 0.05). eEF2K knockout (KO) significantly attenuated ACR-induced hepatic injury, indicated by improved histopathology, reduced serum ALT/AST levels, and restored liver coefficients (P < 0.05). Metabolomics revealed that eEF2K ablation counteracted ACR-induced perturbations in sphingolipid metabolism. Mechanistically, eEF2K deficiency normalized sphingolipid metabolism and prevented MAPK signaling dysregulation induced by ACR. Conclusions: This study identifies eEF2K as a key regulator in ACR-induced hepatic injury. ACR exposure promotes MAPK signaling hyperactivation via eEF2K-dependent dysregulation of sphingolipid metabolism, contributing to hepatic injury. Inhibition of eEF2K attenuates ACR-induced hepatic injury. Inhibition of eEF2K represents a novel therapeutic strategy for mitigating ACR-associated hepatic injury.

Nickel exposure increases the risk of lung cancer; however, the mechanisms underlying nickel-induced oncogenic cell death remain unclear. While ferroptosis is linked to lung cancer, its role in nickel-induced malignant transformation is not well understood. We simulated long-term exposure of human bronchial epithelial cells (Beas-2B cells) to nickel-refining fumes (NiRF) from a smelter and found that NiRF exposure induced their malignant transformation. Ferroptosis was inhibited in these transformed cells (2B-NiRF cells), a phenomenon also observed in NiRF-exposed mouse lung tissue. Treatment of 2B-NiRF cells with ferroptosis inducers and inhibitors indicated that ferroptosis suppresses their malignant phenotype. Transcriptome analysis of 2B-NiRF cells revealed enrichment in hypoxia and HIF-1 signaling pathways. Mechanistically, the NiRF-induced hypoxic microenvironment inactivates prolyl hydroxylase domain protein 1 (PHD1), stabilizing hypoxia-inducible factor-1α (HIF-1α), which coordinates the transcriptional program to maintain 2B-NiRF cells in a ferroptosis-resistant state. Overexpression of PHD1 inhibits HIF-1α and its downstream angiopoietin-like protein 4 (ANGPTL4)/janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway, thereby restoring sensitivity to ferroptosis in 2B-NiRF cells; knockdown of ANGPTL4 similarly modulates sensitivity to ferroptosis. This underscores the crucial role of the PHD1/HIF-1α/ANGPTL4/JAK2/STAT3 axis in ferroptosis-mediated NiRF-induced malignant transformation. The NiRF-exposed mouse model further confirms that in vivo expression of the PHD1/HIF-1α/ANGPTL4/JAK2/STAT3 axis is dysregulated. In conclusion, this study reveals a novel regulatory cascade in which NiRF inhibits cellular ferroptosis via the PHD1/HIF-1α/ANGPTL4/JAK2/STAT3 axis, thereby inducing malignant transformation of cells, providing potential targets for occupational lung cancer risk management against ferroptosis.

Background The impact of acrylamide (ACR) on learning and memory has garnered considerable attention. However, the targets and mechanisms are still unclear. Results Elongation factor 2 (eEF2) was significantly upregulated in the results of serum proteomics. Results from in vitro and in vivo experiments indicated a notable upregulation of Eukaryotic elongation factor 2 kinase (eEF2K), the sole kinase responsible for eEF2 phosphorylation, following exposure to ACR (P < 0.05). Subsequent in vitro experiments using eEF2K siRNA and in vivo experiments with eEF2K-knockout mice demonstrated significant improvements in abnormal indicators related to ACR-induced learning and memory deficits (P < 0.05). Proteomic analysis of the hippocampus revealed Lpcat1 as a crucial downstream protein regulated by eEF2K. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that eEF2K may play a role in the process of ACR-induced learning and memory impairment by affecting ether lipid metabolism. Conclusions In summary, eEF2K as a pivotal treatment target in the mechanisms underlying ACR-induced learning and memory impairment, and studies have shown that it provides robust evidence for potential clinical interventions targeting ACR-induced impairments.

Nickel (Ni), a ductile and hard silver-white transition metal, is commonly found in occupational environments and can harm the human body. Since it is a toxic compound, long-term Ni exposure can cause pneumonia, rhinitis, and other types of respiratory inflammatory diseases. Resveratrol (Res) is a plant antitoxin polyphenol, which also has anti-cancer and anti-inflammatory properties. In this report, the toxicity of Ni-refining fumes on the human lung bronchial epithelial (BEAS-2B) cells, as well as the protective effects of Res were investigated in vitro, and the specific mechanism of its anti-inflammatory effect was explained. The experimental observations of this study revealed that Ni-refining fumes induce BEAS-2B cell damage, increase reactive oxygen species (ROS) content, activate NLRP3 (LRR-, NOD-, and pyrin domain-containing 3) inflammasome, and promote the secretion of the cytokine Interleukin (IL)-1β, leading to cellular inflammation and reducing cell activity. Resveratrol (20 μmol/L) activated sirtuin 1 (SIRT1) in BEAS-2B cells to increase protein and mRNA expression. SIRT1 was observed to inhibit the transcriptional activity of nuclear factor-kappaB (NF-κB), reduced the expression of NLRP3 protein and mRNA, and inhibited NLRP3 inflammation. The level of inflammasome activation and IL-1β overexpression could reduce the inflammatory damage caused by the Ni-refining fume particles on the BEAS-2B cells and exert anti-inflammatory protective effects. In vivo experiments further confirmed that resveratrol could effectively alleviate the acute inflammatory injuries caused due to exposure to the Ni-refining fume particles in the lung tissues of the Wistar rats, and verified that resveratrol could exert its anti-inflammatory impact through the SIRT1-NF-κB-NLRP3 pathway. These results provide an important theoretical basis for developing novel protective drugs and investigating the mechanism of action for inflammatory injury in occupational populations caused by exposure to nickel and other heavy metals.

Background: hnRNPAB, a member of the hnRNP protein family, is involved in mRNA cytoplasmic localization, transport, and the regulation of transcription, metabolism, and splicing. It is associated with malignant progression and metastasis in liver cancer and lung adenocarcinoma. However, a systematic pan-cancer analysis exploring its role in diagnosis, prognosis, and immune prediction is lacking. Methods: This study evaluated hnRNPAB expression across 33 cancers and its association with immune infiltration using UCSC Xena, TIMER, GEPIA, BioGPS, and ARCHS4 databases. Methylation levels were analyzed using UALCAN and MethSurv. Survival analysis was performed with GEPIA and MethSurv platforms, and mutation analysis was conducted via cBioPortal. Protein interaction networks were constructed using STRING and Cytoscape, and functional enrichment analyses were performed with KEGG and GSVA. Immune infiltration was assessed using TIMER, CIBERSORT, and quanTIseq, and the relationship between hnRNPAB and cancer-associated fibroblasts (CAFs) was analyzed using TIMER2.0. Results: hnRNPAB was significantly overexpressed in various cancers, with high expression correlating with poor prognosis. Mutation analysis revealed that amplification mutations of hnRNPAB were associated with worse survival rates. Low methylation of hnRNPAB was linked to cancer progression. Additionally, hnRNPAB was involved in cell cycle regulation, mTORC1, and PI3K-AKT signaling pathways. Immune cell infiltration analysis demonstrated a significant association between hnRNPAB and CAF infiltration, affecting immune therapy outcomes. Conclusion: This study highlights the association between hnRNPAB overexpression and poor prognosis across multiple cancers, particularly in kidney and liver cancers. hnRNPAB promotes tumor growth and metastasis by regulating immune cell infiltration and CAF activity. The study also explores its mutations and methylation status, suggesting its potential as a therapeutic target or biomarker in cancer metabolism reprogramming and immune evasion.

目的 探讨高尔基体磷蛋白3(golgiosomal phosphoprotein 3,GOLPH3)调控JAK2/STAT3信号通路在镍精炼烟尘致人支气管上皮细胞(Beas-2B)炎性损伤中的作用.方法 采用不同浓度镍精炼烟尘(0.00、12.50、25.00、50.00 μg/ml)处理Beas-2B细胞24 h,使用CCK8法检测细胞存活率;采用蛋白免疫印迹(Western blot,WB)法检测GOLPH3及JAK2/STAT3信号通路蛋白JAK2、p-JAK2、STAT3、p-STAT3和炎性效应蛋白NLRP3、白细胞介素-18(IL-18)、肿瘤坏死因子-α(TNF-α)表达水平.使用siRNA转染沉默GOLPH3,采用WB法检测GOLPH3、JAK2、p-JAK2、STAT3、p-STAT3、NLRP3、IL-18、TNF-α 蛋白表达水平;使用 JAK2/STAT3 通路抑制剂AG490抑制该信号通路,采用WB法检测JAK2、p-JAK2、STAT3、p-STAT3及NLRP3、IL-18、TNF-α蛋白表达水平.结果 随着镍精炼烟尘染毒浓度增加,Beas-2B细胞存活率显著降低(P＜0.05);GOLPH3、p-JAK2、p-STAT3、NLRP3、IL-18、TNF-α蛋白表达水平呈逐渐升高趋势(P＜0.05);与si-对照组相比,si-GOLPH3组Beas-2B细胞中GOLPH3、p-JAK2、p-STAT3 和 NLRP3、IL-18、TNF-α 表达均降低(P＜0.05);与二甲基亚砜(dimethyl sulfoxide,DMSO)组相比较,AG490 组 Beas-2B 细胞中 p-JAK2、p-STAT3 和 NLRP3、IL-18、TNF-α 表达均降低(P＜0.05).结论 镍精炼烟尘可通过激活GOLPH3调控JAK2/STAT3信号通路,诱导Beas-2B细胞发生炎性损伤.

IntroductionThe aim of this study is to establish a prognostic risk model based on ferroptosis to prognosticate the severity of Alzheimer’s disease (AD) through gene expression changes.MethodsThe GSE138260 dataset was initially downloaded from the Gene expression Omnibus database. The ssGSEA algorithm was used to evaluate the immune infiltration of 28 kinds of immune cells in 36 samples. The up-regulated immune cells were divided into Cluster 1 group and Cluster 2 group, and the differences were analyzed. The LASSO regression analysis was used to establish the optimal scoring model. Cell Counting Kit-8 and Real Time Quantitative PCR were used to verify the effect of different concentrations of Aβ1–42 on the expression profile of representative genes in vitro.ResultsBased on the differential expression analysis, there were 14 up-regulated genes and 18 down-regulated genes between the control group and Cluster 1 group. Cluster 1 and Cluster 2 groups were differentially analyzed, and 50 up-regulated genes and 101 down-regulated genes were obtained. Finally, nine common differential genes were selected to establish the optimal scoring model. In vitro, CCK-8 experiments showed that the survival rate of cells decreased significantly with the increase of Aβ1–42 concentration compared with the control group. Moreover, RT-qPCR showed that with the increase of Aβ1–42 concentration, the expression of POR decreased first and then increased; RUFY3 was firstly increased and then decreased.DiscussionThe establishment of this research model can help clinicians make decisions on the severity of AD, thus providing better guidance for the clinical treatment of Alzheimer’s disease.

Abstract Aims and Methods To construct a scientific and reasonable competency model for occupational health post to provide a reference standard for the education and training of occupational health-related personnel. A purposive sampling method was used to select the investigation subjects. Thirty-seven experts from Prevention and Treatment Center for Occupational Diseases, Centre for Disease Control and Prevention, university research organization, occupational health services and Institute of Public Health Supervision in multiple locations were selected to develop a questionnaire for occupational health post competency through literature reading and semi-structured expert interview methods. Two rounds of consultation were conducted and SPSS 21.0 was applied for statistical analysis of the data. Results The occupational health post competency indication system with 5 primary indicators and 25 secondary indicators was determined. And the competency was stratified from inside to outside with reference to the "onion model", then the occupational health post competency model was completed. Conclusion The final constructed competency model for occupational health post was divided into three layers, with the innermost layer being professionalism, the middle layer being professional skills, general competence and work and development, and the outer layer being basic knowledge. The use of the model can be promoted to improve the post competency evaluation mechanism and clarify the positioning of occupational health-related personnel at different stages of their personal career development.

Acrylamide is widely found in a variety of fried foods and cigarettes and is not only neurotoxic and carcinogenic, but also has many potential toxic effects. The current assessment of acrylamide intake through dietary questionnaires is confounded by a variety of factors, which poses limitations to safety assessment. In this review, we focus on the levels of AAMA, the urinary metabolite of acrylamide in humans, and its association with other diseases, and discuss the current research gaps in AAMA and the future needs. We reviewed a total of 25 studies from eight countries. In the general population, urinary AAMA levels were higher in smokers than in non-smokers, and higher in children than in adults; the highest levels of AAMA were found in the population from Spain, compared with the general population from other countries. In addition, AAMA is associated with several diseases, especially cardiovascular system diseases. Therefore, AAMA, as a biomarker of internal human exposure, can reflect acrylamide intake in the short term, which is of great significance for tracing acrylamide-containing foods and setting the allowable intake of acrylamide in foods.

Abstract Recent studies have shown that phosphoglycerate kinase 1 (PGK1) may improve neurodegeneration. However, the role of PGK1 in acrylamide(ACR)-induced neuronal damage is not yet clear. In this study, SD rats were treated with 6 mg/kg and 18 mg/kg of ACR, and PC12 cells were treated with 1.25 mM and 2.5 mM of ACR, and PC12 cells were transfected with PGK1 siRNA. Behavioral responses and histopathological changes in the rats were monitored, and transmission electron microscopy was used to observe changes in neurons and internal organelles in the hippocampal tissues of the various groups. Western blot and RT-qPCR were used to detect changes in the expression of neuronal-related proteins BDNF, Syn1, Nrf2 signaling pathway-related proteins and PGK1 in the hippocampal tissues of the rats and PC12 cells. Immunohistochemistry and immunofluorescence were used to analyze PGK1 expression in the hippocampal tissues of the rats. The results showed that after ACR treatment, obvious hindlimb clasping effect was observed in rats, hippocampal tissue pathology occurred, neuronal boundaries became blurred, mitochondria swelled, and organelles became sparse. BDNF and Syn1 mRNA expression and protein levels decreased both in vivo and in vitro, while Nrf2 and PGK1 mRNA expression and protein levels increased both in vivo and in vitro. In PC12 cells, inhibition of PGK1 can alleviate cell damage, and increase the expression of BDNF and Syn1 while Nrf2 expression is suppressed. These results suggest that inhibiting the expression of PGK1 can protect nerve cell damage induced by ACR.

Long intergenic non-protein coding RNA 1547 (LINC01547) presents a notable relationship with prognosis in patients with ovarian cancer. Herein, we examined the expression of LINC01547 in non-small cell lung cancer (NSCLC) to ascertain its clinical significance. We also explored the detailed functions of LINC01547 in regulating the aggressive phenotype of NSCLC and the molecular mechanism of action underlying its carcinogenic activities events in NSCLC. Furthermore, we applied the data acquired from the tissue specimens and the Cancer Genome Atlas (TCGA) database to analyze the level of LINC01547 in NSCLC and conducted functional assays to address the regulatory effect of LINC01547. Further, we examined the mechanistic interaction among LINC01547, microRNA-195-5p (miR-195-5p), and homeobox C8 (HOXC8) using bioinformatics prediction and luciferase reporter assay. LINC01547 was noticeably overexpressed, as affirmed by data from TCGA and our own cohort; moreover, poor prognosis was associated with increased LINC01547 levels in patients with NSCLC. LINC01547 regulates cell proliferation, colony-forming, migration, and invasion, and its absence produced tumor-repressing effects in NSCLC. Mechanistically, as a competitive endogenous RNA, LINC01547 decoyed miR-195-5p and consequently resulted in the overexpression of HOXC8 in NSCLC cells. Using rescue experiments, we found that the regulatory activities of LINC01547 deficient in repressing the malignant properties of NSCLC cells could be counteracted by hindering miR-195-5p or overexpressing HOXC8. Conclusively, LINC01547 serves as a crucial component to worsen the oncogenicity of NSCLC cells by controlling the miR-195-5p/HOXC8 axis. Thus, the newly identified competing endogenous RNA pathway may potentially be an attractive therapeutic for NSCLC management.

Sphingosine kinase 1 (SphK1) is an important signaling molecule for cell proliferation and survival. However, the role of SphK1 in acrylamide (ACR)-induced nerve injury remains unclear. The purpose of this study was to investigate the role and potential mechanism of SphK1 in ACR-induced nerve injury. Liquid chromatography triple quadrupole tandem mass spectrometry (LC-MS/MS) and reverse transcription-quantitative PCR (RT-qPCR) were used to detect sphingosine 1-phosphate (S1P) content in serum and SphK1 content in whole blood from an occupational work group exposed to ACR compared to a non-exposed group. For in vitro experiments, SphK1 in human SH-SY5Y neuroblastoma cells was activated using SphK1-specific activator phorbol 12-myristate 13-acetate (PMA). Our research also utilized cell viability assays, flow cytometry, western blots, RT-qPCR and related protein detection to assess activity of the mitogen activated protein kinase (MAPK) signaling pathway. The results of the population study showed that the contents of SphK1 and S1P in the ACR-exposed occupational contact group were lower than in the non-exposed group. The results of in vitro experiments showed that expression of SphK1 decreased with the increase in ACR concentration. Activating SphK1 improved the survival rate of SH-SY5Y cells and decreased the apoptosis rate. Activating SphK1 in SH-SY5Y cells also regulated MAPK signaling, including enhancing the phosphorylation of extracellular signal-regulated protein kinases (ERK) and inhibiting the phosphorylation of c-Jun N-terminal kinase (JNK) and p38. These results suggest that activating SphK1 can protect against nerve cell damage caused by ACR.