Journal of Trace Elements in Medicine and Biology最新文献

{"title":"Comprehensive analysis of 44 elements in the lung cancer tissues of smokers: A comparative study with control lung tissues","authors":"Ljubinko Đenić ,&nbsp;Jovana Jagodić ,&nbsp;Katarina Kozlica ,&nbsp;Aleksandar Lukač ,&nbsp;Aleksandar Ristanović ,&nbsp;Janez Ščančar ,&nbsp;Aleksandar Stojsavljević","doi":"10.1016/j.jtemb.2025.127760","DOIUrl":"10.1016/j.jtemb.2025.127760","url":null,"abstract":"<div><div>Lung cancer remains one of the leading causes of morbidity and mortality worldwide, yet the baseline status of trace elements in healthy/control lung tissues is largely unresolved, with no comprehensive elemental profile established for lung cancer. This study aimed to characterize baseline concentrations of 44 elements in healthy lung tissues (n = 92) and investigate changes in elemental composition in cancerous lung tissues (n = 92). The second aim was to observe possible differences in elemental concentrations in healthy and cancerous lung tissues based on age and sex. Additionally, this study aimed to identify trace elements potentially involved in lung cancer pathophysiology. Through detailed elemental analysis, this study revealed significant differences between healthy and cancerous lung tissues. Specifically, concentrations of Mn, Co, Ni, Cd, and U were significantly higher in healthy lung tissues, while Cu, Tl, Pb, Rh, Pd, and Bi were significantly higher in cancerous lung tissues. Age-related analysis of the control tissue group showed that healthy lung tissue from older individuals (above 64 years) had lower concentrations of elements Mn, Zn, Be, Al, Sb, Ba, Tl, Ga, Rb, Y, Re, Eu, Tb, Dy, Ho, Er, Yb, La, and Bi than healthy tissues from younger individuals (below 64 years). In cancerous lung tissues, those from females (n = 40) exhibited significantly lower concentrations of Cr, Cu, As, and Pb but higher Pt concentrations than cancerous lung tissues from males (n = 52). Furthermore, in cancerous lung tissues, those from younger patients displayed lower concentrations of As, Sb, and Au compared to equivalent tissues from older individuals. These findings offer valuable insights into the elemental composition of lung cancer tissue, enhancing the understanding of how trace elements could influence lung cancer pathophysiology.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127760"},"PeriodicalIF":3.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of lead (Pb)-induced neurotoxicity on protein synthesis and cellular stress responses in LUHMES cells","authors":"Tsunehiko Hongen ,&nbsp;Tomohiro Ito ,&nbsp;Xian-Yang Qin ,&nbsp;Hideko Sone","doi":"10.1016/j.jtemb.2025.127759","DOIUrl":"10.1016/j.jtemb.2025.127759","url":null,"abstract":"<div><div>Exposure to lead (Pb) poses significant risks to human brain development. This study investigates the molecular mechanisms underlying Pb acetate-induced neurotoxicity in LUHMES cells, which represent a human fetal-derived dopaminergic neuronal precursor model particularly suited for studies of neurotoxicity and Parkinson’s disease. Morphological analyses revealed that Pb acetate exposure at concentrations exceeding 10 µM induced cytotoxicity and disrupted neurite outgrowth. Distinct gene expression changes associated with Pb exposure were determined through RNA-sequencing. Principal component analysis highlighted significant alterations in gene expression at higher Pb concentrations (10 µM) compared with lower Pb concentrations (1 µM) and controls. Notably, Pb acetate exposure impaired ribosomal function, Spliceosome and protein processing in the endoplasmic reticulum (ER) pathways. Furthermore, these three pathways related that Pb acetate exposure resulted in the upregulation of genes related to ER-associated degradation and apoptosis, whereas the ubiquitin ligase complex was disrupted, suggesting compromised protein homeostasis. These findings underscore the potential of ribosomal processes and ER stress pathways as biomarkers of Pb acetate exposure. This study provides advanced mechanistic insights into the toxicological effects of lead (Pb) as a heavy metal, with a specific emphasis on its influence on cellular processes related to proteostasis and stress response pathways. Our findings further highlight the importance of LUHMES cells as a human-derived neuronal model for elucidating neurodevelopmental toxicity and identifying molecular biomarkers of Pb exposure, particularly those associated with dysregulation in ribosomal function and endoplasmic reticulum (ER) stress signaling.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127759"},"PeriodicalIF":3.6,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between serum cobalt concentration and thyroid function in pregnant women: A cross-sectional study","authors":"Xia Chai ,&nbsp;Zhen Wang ,&nbsp;Yujie Li ,&nbsp;Jinlin Lei ,&nbsp;Chong Guo ,&nbsp;Weiwei Gu ,&nbsp;Biyun Zhang ,&nbsp;Huailan Guo","doi":"10.1016/j.jtemb.2025.127762","DOIUrl":"10.1016/j.jtemb.2025.127762","url":null,"abstract":"<div><h3>Background</h3><div>Maintaining normal thyroid function during pregnancy is crucial for maternal health as well as fetal growth and development. Exposure to environmental trace elements may influence thyroid function in pregnant women, but the specific role of cobalt remains unclear. This study aimed to systematically assess the relationship between serum cobalt concentration and thyroid function in pregnant women. Additionally, it explored cobalt’s role within trace element mixtures to further elucidate its potential effects on thyroid function and provide theoretical and experimental foundations for future research.</div></div><div><h3>Methods</h3><div>This cross-sectional study included 293 pregnant women with valid trace element and thyroid function data from an initial 303 recruits. Measurements included serum cobalt, other trace elements (chromium, manganese, aluminum, vanadium, nickel), and thyroid indicators (Tg, TSH, FT3, FT4, TPOAb, TgAb).The relationships between serum cobalt and thyroid function, including potential non-linear effects, were analyzed using multiple linear regression, Bayesian kernel machine regression (BKMR), and restricted cubic spline (RCS) models. Additionally, interactions between cobalt and other trace elements were examined.</div></div><div><h3>Results</h3><div>Higher cobalt exposure was significantly negatively correlated with FT3 and FT4 levels. The linear trend test (P for trend &lt; 0.001) further supported this exposure-response relationship. BKMR analysis indicated that cobalt had the most significant effect on thyroid function among all the trace metals studied, with no significant interactions observed between trace elements. RCS analysis further revealed a non-linear correlation between cobalt and FT4, as well as a linear negative correlation with FT3. Spearman correlation analysis showed a positive correlation between cobalt and chromium, manganese, aluminum, and vanadium.</div></div><div><h3>Conclusion</h3><div>Elevated serum cobalt concentration was significantly associated with lower FT3 and FT4 levels in pregnant women. The findings suggest that cobalt may affect FT3 and FT4 through different mechanisms, with FT4 exhibiting a non-linear response, while FT3 declines in a stable linear manner. Cobalt was positively correlated with several trace elements; however, no significant interactions were observed among them. This suggests that cobalt’s effect on thyroid function in pregnant women may be independent.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127762"},"PeriodicalIF":3.6,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship between heavy metals and miRNAs in pancreatic ductal adenocarcinoma","authors":"Andrea Pisano ,&nbsp;Angela Sabalic ,&nbsp;Giovanni Forte ,&nbsp;Grazia Fenu ,&nbsp;Beatrice Bocca ,&nbsp;Federica Etzi ,&nbsp;Davide Tutedde ,&nbsp;Claudia Trignano ,&nbsp;Giovanni Fiorito ,&nbsp;Peter Massányi ,&nbsp;Roberto Madeddu","doi":"10.1016/j.jtemb.2025.127754","DOIUrl":"10.1016/j.jtemb.2025.127754","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, characterized by poor prognosis due to the late diagnosis and chemotherapy resistance. Both genetic and environmental factors, including heavy metals exposure are involved in PDAC development. In this study, we evaluated the association between a panel of miRNAs and metals with PDAC, and subsequently assessed their correlation using Spearman’s test to investigate potential biological links. miRNA expression was analysed in the serum of PDAC patients (n = 37) compared to healthy controls (n = 20), as well as in tumour biopsies (n = 23) versus adjacent healthy tissue (n = 21). For metals, whole blood and tumour biopsies were examined and compared with their respective healthy counterparts. The metals considered were cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), manganese (Mn), lead (Pb), nickel (Ni), iron (Fe), zinc (Zn), and selenium (Se); the analysed miRNAs included miR-361–3p, miR-320d, miR-20b–5p, miR-4486, miR-216a–5p, miR-216b–5p, miR-324–5p, miR-125a–5p. Our results showed that miR-320d, miR-20b–5p, miR-4486, miR-216a–5p and miR-216b–5p were significantly overexpressed in PDAC serum samples compared to controls as well as PDAC patients showed high concentration of Cr and Cu. On the other hand, no significant differences were reported between PDAC biopsies and healthy counterpart. However, higher concentration of Cu, Fe, Se, and Zn were observed in tumour samples. Spearman's Rank Correlation analysis revealed a positive correlation between miR-216a-5p and Mn, Cd and Zn and negative correlation with miR-320d and miR-361–3p in tissue samples. While in serum, miR-361–3p was positively correlated with Cu, suggesting a potential link between oxidative stress regulation and PDAC development. This study suggests that specific miRNAs correlate with metals in PDAC, such as miR-361–3p with Cu and miR-216a-5p with Mn, hinting at a potential role of metal homeostasis in tumour-related pathways. However, these findings warrant further validation and functional studies, and may provide novel insights for biomarker development and therapeutic strategies in PDAC.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127754"},"PeriodicalIF":3.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Magnesium Depletion Score with all-cause and cardiovascular mortality in adults with diabetes","authors":"Yi Lin ,&nbsp;Yimei Wu ,&nbsp;Haihui Zhu ,&nbsp;Laizan Zheng","doi":"10.1016/j.jtemb.2025.127761","DOIUrl":"10.1016/j.jtemb.2025.127761","url":null,"abstract":"<div><h3>Background</h3><div>This study was to investigate the associations between Magnesium Depletion Score (MDS) and all-cause and cardiovascular disease (CVD) mortality in American adults with diabetes.</div></div><div><h3>Materials and methods</h3><div>Data was gathered from NHANES between 1999 and 2018 and utilized together with the National Death Index to track deaths. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs) of MDS for all-cause and CVD mortality. Kaplan–Meier survival analyses were performed using log-rank tests. Subgroup analyses were conducted while accounting for confounding variables.</div></div><div><h3>Results</h3><div>A total of 7078 adults with diabetes were included in this study. This study observed a total of 1904 all-cause deaths and 542 deaths due to CVD over a median follow-up period of 88 months. After adjusting for all relevant factors, HR of MDS ≥ 3 was 1.47 (95 % CI: 1.21–1.77) for all-cause mortality and 1.89 (95 % CI: 1.31–2.72) for CVD mortality compared to MDS = 0 (P for trend &lt; 0.001). The HRs were 1.13 (95 % CI: 1.07–1.19) for all-cause mortality and 1.24 (95 % CI: 1.13–1.37) for CVD mortality. The strength of the correlation was significantly affected by age (p for interaction = 0.003) and hypertension (p for interaction = 0.001). The subgroup analysis findings demonstrated the constant association between MDS and CVD mortality across various subgroups (all p for interaction &gt; 0.05).</div></div><div><h3>Conclusion</h3><div>The findings of this study suggest that individuals with diabetes who have a high MDS may have an increased risk of all-cause and CVD mortality. Timely interventions, particularly in those with an MDS of 3 or higher, could potentially mitigate this risk.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127761"},"PeriodicalIF":3.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of spinacetin against cadmium-exacerbated hepatic ischemia/reperfusion injury via regulating AMPK/SIRT1/PGC-1α and NF-κB pathway","authors":"Aqsa Bibi ,&nbsp;Hong-xing Zhang ,&nbsp;Muhammad Faisal Hayat ,&nbsp;Khalid J. Alzahrani ,&nbsp;Khalaf F. Alsharif ,&nbsp;Fuad M. Alzahrani","doi":"10.1016/j.jtemb.2025.127757","DOIUrl":"10.1016/j.jtemb.2025.127757","url":null,"abstract":"<div><h3>Background</h3><div>Cadmium (Cd) is a potent environmental toxicant that affect different body organs including the liver. Spinacetin (SPI) is a plant-derived polyphenolic compound with diverse biological activities.</div></div><div><h3>Objective</h3><div>The current investigation assessed the palliative potential of SPI against Cd-exacerbated hepatic ischemic/reperfusion (I/R) injury in rats.</div></div><div><h3>Methodology</h3><div>Forty male albino rats were apportioned into five groups including the sham, I/R induced, I/R + Cd (5 mg/kg), I/R + Cd (5 mg/kg) + SPI (50 mg/kg), and I/R + SPI (50 mg/kg) treated group. Gene expressions were quantified using qRT PCR. Biochemical assessments were performed using ELISA technique and standard assays. Results were cross validated through molecular simulation and molecular docking analysis.</div></div><div><h3>Findings</h3><div>It was revealed that Cd intoxication in I/R group downregulated the gene expression of silent information regulator sirtuin-1 (SIRT1), adenosine monophosphate-activated protein kinase (AMPK), mitochondrial transcription factor-A (TFAM), peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α), and Estrogen-Related Receptor Alpha (ERRα) while upregulating the mRNA expressions of COX-2, TNF-α, IL-6, IL-1β, and NF-κB. Enzymatic potential of glutathione reductase (GSR), superoxide dismutase (SOD), glutathione reductase (GSR), catalase (CAT), heme-oxygenase-1 (HO-1), glutathione peroxidase (GPx), and concentration of glutathione (GSH) were suppressed while the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were upregulated following the Cd intoxication in I/R induced group. Cd intoxication in IR group escalated the levels of ALT, AST, ALP, and GGT while reducing the intensity of albumin and total protein. Moreover, I/R-induced and IR + Cd group showed upregulation in Bax, Caspase-3 and Caspase-9 while reducing the levels of Bcl-2. Severe histological impairments were observed in I/R as well as I/R + Cd treated group. Nonetheless, SPI therapy showed significant protection of hepatic tissues against I/R and I/R + Cd intoxication via regulating mitochondrial biogenesis, oxidative stress, inflammation, apoptosis and histological impairments.</div></div><div><h3>Conclusion</h3><div>Cd intoxication escalates the hepatic ischemic injury via upregulating oxidative injury, inflammation and other key regulatory pathways. Spinacetin reversed I/R-mediated hepatic damage, demonstrating its potential hepatoprotective efficacy.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127757"},"PeriodicalIF":3.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145097809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the quantitative performance of different spectroscopic techniques for multielemental analysis of nail and hair samples: A comparative study","authors":"João Silva ,&nbsp;Eva Marguí ,&nbsp;Romain Guillemaut ,&nbsp;Jasna Jablan ,&nbsp;Alessandro Migliori ,&nbsp;Paula Kasprzyk ,&nbsp;Joaquim J. Ferreira ,&nbsp;Sofia Pessanha","doi":"10.1016/j.jtemb.2025.127751","DOIUrl":"10.1016/j.jtemb.2025.127751","url":null,"abstract":"<div><h3>Background</h3><div>The accurate detection and quantification of elemental content in skin appendages, such as, hair and nails are pivotal in biomedical research, including disease diagnostics, environmental exposure monitoring, and forensic investigations.</div></div><div><h3>Methods</h3><div>This study evaluates and compares the suitability of different sample treatments and four spectroscopic techniques—Energy Dispersive X-ray Fluorescence (EDXRF), Total Reflection X-ray Fluorescence (TXRF), Inductively Coupled Plasma Mass Spectrometry (ICP-MS), and Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) for multielemental analysis of these biological tissues. Making use of different Certified Reference Materials (CRMs), the performance of the developed methods was assessed based on their sensitivity, precision, range of detectable elements, and the extent of sample preparation required.</div></div><div><h3>Results</h3><div>EDXRF method is suited for rapid and non-destructive determination of light elements present at relatively high concentrations – Sulfur (S), Chlorine (Cl), Potassium (K) and Calcium (Ca) – in hair and nail samples. TXRF provides information of most of the elements present in the target samples, including Bromine (Br), but the determination of light element (i.e, Phosphorus (P), S, Cl) is not feasible. Finally, the proposed ICP-OES/ICP-MS method is useful for the determination of major, minor and trace elements, except chlorine.</div></div><div><h3>Conclusion</h3><div>This comparative study reveals the distinct strengths, range of elements and suitable applications of each technique, providing a valuable framework for selecting appropriate methods based on specific analytical needs.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127751"},"PeriodicalIF":3.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145097746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting FOXO3a, TLR2/MyD88/NF-κB cascade, and ferroptosis by theaflavin ameliorates iron-elicited liver toxicity","authors":"Afnan Bakhsh ,&nbsp;Samir A. Salama ,&nbsp;Musaad M. Althobaiti ,&nbsp;Shuruq E. Alsufyani ,&nbsp;Abdullah M. Almalki ,&nbsp;Samyah T. Alanazi","doi":"10.1016/j.jtemb.2025.127758","DOIUrl":"10.1016/j.jtemb.2025.127758","url":null,"abstract":"<div><h3>Background</h3><div>While iron is essential in trace amounts, elevated level represents a serious health problem. Elevated iron level arises as a secondary consequence to hemochromatosis and anemias that necessitate frequent blood transfusions, leading to organ toxicity, particularly liver toxicity.</div></div><div><h3>Methods</h3><div>The current study investigated the potential ameliorating impact of theaflavin against the iron-elicited liver toxicity. A model of iron intoxication was established in male Wistar rats, and theaflavin was given over a 10-day period. Blood and liver specimens were collected and subjected to histopathological, ELISA, biochemical, and Western blotting investigations.</div></div><div><h3>Results</h3><div>Theaflavin suppressed the iron-evoked liver injury as indicated by a significant decrease in activity of the hepatocellular enzymes in sera and improved hepatic histopathological architecture. Theaflavin activated the antioxidant transcription factor FOXO3a with upregulation of its responsive antioxidant gene products including thioredoxin reductase, superoxide dismutase, and catalase, along with reduced DNA oxidative modification. Equally important, theaflavin suppressed TLR2 inflammatory cascade as evidenced by a significant downregulation in protein expression of TLR2 and its adaptor protein MyD88, and inhibition of phosphorylation and nuclear translocation of its downstream inflammatory transcription factor NF-κB. In the same context, theaflavin markedly reduced levels of NF-κB-responsive cytokines TNF-α and IL-6. Interestingly, theaflavin repressed the iron-elicited hepatocellular ferroptosis as indicated by modulation of its biomarkers GPx4 and COX-2 protein expression, and levels of lipid hydroperoxides and hepatocellular iron load.</div></div><div><h3>Conclusion</h3><div>These findings emphasize the ameliorating impact of theaflavin against the iron-elicited liver toxicity and shed light on FOXO3a, TLR2/MyD88/NF-κB cascade, and ferroptosis as possible molecular targets.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127758"},"PeriodicalIF":3.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liraglutide orchestrates ferroptosis defense against murine cisplatin acute kidney injury: NRF2 activation via both KEAP1-dependent and -independent mechanisms is essential for SLC7A11/GPX4 renoprotection","authors":"Nermeen S. Abdel Razek ,&nbsp;Noha N. Nassar ,&nbsp;Rabab H. Sayed ,&nbsp;Ayman E. El-Sahar ,&nbsp;Dalaal M. Abdallah","doi":"10.1016/j.jtemb.2025.127755","DOIUrl":"10.1016/j.jtemb.2025.127755","url":null,"abstract":"<div><h3>Objective</h3><div>Acute kidney injury (AKI) induced by oxidative stress, and recently associated with ferroptosis, represents a major complication of the chemotherapeutic cisplatin that often necessitates treatment cessation. The glucagon-like peptide 1 receptor (GLP1R) agonist liraglutide possesses reno-protective potential via its antioxidant character in different kidney injury settings while reducing iron overload in other models. Hence, we investigated the potential protective role of liraglutide in cisplatin-induced AKI targeting KEAP1-dependent and -independent ferroptosis pathways.</div></div><div><h3>Methods</h3><div>Rats were assigned to one of four groups: vehicle control, liraglutide control, cisplatin-induced AKI, and liraglutide-pretreated AKI. Renal function markers and histopathological changes were assessed. SLC7A11, NRF2, and KEAP1-canonical and non-canonical hubs were analyzed to elucidate the drug’s molecular mechanisms on ferroptosis.</div></div><div><h3>Results</h3><div>Liraglutide significantly improved renal function, evidenced by the reduction of serum cystatin C, creatinine, and BUN, along with renal histological improvements. In the kidney, liraglutide activated/phosphorylated AKT, mTOR, and P62 to reduce KEAP1 and inactivated GSK3β to enhance NRF2-mediated GPX4 and SLC7A11 formation, thus inhibiting cisplatin-ferroptosis-triggered renal injury.</div></div><div><h3>Conclusion</h3><div>Therefore, liraglutide is a promising treatment candidate for attenuating cisplatin-induced AKI by SLC7A11/GPX4 trajectory through upregulating the AKT/mTOR/P62/KEAP1/NRF2 and AKT/GSK3β/NRF2 signaling pathways to increase GPX4 alongside with SLC7A11. Indeed, the GLP1R-mediated AKT activation acts as a potential target for Liraglutide reno-protective actions; hence, the GLP1R can be considered a therapeutic entity in such a renal injurious paradigm.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127755"},"PeriodicalIF":3.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective efficacy of royal jelly and propolis against cadmium-induced dysregulation of neurogenesis and neurotransmitters in the brain of rats: Molecular mechanisms and ultrastructure investigations","authors":"Norhan S. El-Sayed ,&nbsp;Eman M. Omar ,&nbsp;Esraa S. Habiba ,&nbsp;Sahar A. Harby ,&nbsp;Amany Attaallah ,&nbsp;Maria Augustyniak ,&nbsp;Abeer El Wakil ,&nbsp;Lamia M. El-Samad ,&nbsp;Mohamed A. Hassan","doi":"10.1016/j.jtemb.2025.127756","DOIUrl":"10.1016/j.jtemb.2025.127756","url":null,"abstract":"<div><div>This study seeks to evaluate the neuroprotective efficacy of royal jelly (RJ) and propolis (P) against cadmium-induced dysregulation of neurogenesis and neurotransmitters in the brains of <em>Wistar</em> male rats and decipher implicated underlying mechanisms. We probed oxidative stress, inflammatory, neurotransmitter, and neurogenesis biomarkers, along with histopathological and ultrastructural attributes. Energy dispersive x-ray (EDX) microanalysis revealed that RJ and P administration diminished the cadmium (Cd) ratio in the brain compared with the Cd-administered rats. Accordingly, Cd triggered a noticeable disturbance in recognition, which was counterbalanced by RJ and P therapies. Additionally, Cd-administered rats demonstrated lessened superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST) activities with increased malondialdehyde (MDA) level. Furthermore, Cd treatment led to substantial rises in nuclear factor kappa B (NF-κB), Indoleamine 2,3-dioxygenase (IDO), and tumor necrosis factor alpha (TNF-α) concentrations, with a dwindled tissue inhibitor of metalloproteinase 3 (TIMP3) level. These deregulations were significantly rectified by RJ and P therapies. Crucially, Cd accumulation disrupted levels of neurotransmitters, including dopamine (DA), serotonin (SRO), and amyloid beta 1–42 (Aβ1–42), and acetylcholinesterase (AChE) activity, along with a notable diminution in neurogenesis biomarkers, involving brain-derived neurotrophic factor (BDNF) level and doublecortin (DCX) mRNA expression. Notably, RJ and P counteracted these interferences and reinstated levels of major factors to those in the control group. Interestingly, glial fibrillary acidic protein (GFAP) immunohistochemistry, histological, and ultrastructure investigations disclosed salient correlations with biochemical findings. Altogether, our results substantiate the effective and better utilization of RJ than P to counterbalance the pernicious Cd consequences.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127756"},"PeriodicalIF":3.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}