{"title":"Association of organ iron levels with type 2 diabetes mellitus and glycemic traits: A bidirectional two-sample Mendelian randomization study","authors":"Akshaya Vasudevan , Padmanaban Venkatesan","doi":"10.1016/j.jtemb.2024.127586","DOIUrl":"10.1016/j.jtemb.2024.127586","url":null,"abstract":"<div><h3>Introduction</h3><div>Observational studies have found that higher iron levels are associated with an increased risk of diabetes mellitus. Given the limitations of causal inferences from observational studies and the expensive and time-consuming nature of randomized controlled trials, Mendelian randomization analysis presents a reasonable alternative to study causal relationships. Previous MR analyses studying iron levels and diabetes have used indirect markers of iron levels, such as serum ferritin, and found conflicting results. In this study, we performed bidirectional Mendelian Randomization analyses using organ iron (liver, spleen, and pancreas) levels, which are more direct markers of iron status, to study the causal association of iron levels with type 2 diabetes mellitus and glycaemic traits.</div></div><div><h3>Methods</h3><div>Two sample MR analyses were employed bi-directionally to study the causal effect of liver, spleen, and pancreas iron levels on type 2 diabetes and glycaemic traits and the causal effect of type 2 diabetes on organ iron levels, using summary data from genome-wide association studies (UK-Biobank, DIAGRAM, and MAGIC consortia). SNPs associated with organ iron levels with a cut-off of P < 5 × 10<sup>−7</sup> were used as instrumental variables for the MR analyses of the effect of organ iron levels on type 2 diabetes/glycaemic traits, and SNPs associated with diabetes mellitus with a cut-off of P < 5 × 10<sup>−8</sup> were used as instrumental variables for the MR analyses of the causal effect of type 2 diabetes on organ iron levels. Serum ferritin (GWAS meta-analysis of deCODE, UK INTERVAL, and Denmark studies) and haemoglobin (Blood Cell consortium) were used as positive controls for the MR analysis with liver iron as the exposure. Primary analyses used the inverse variance weighted means of Wald’s ratio. Sensitivity analyses included inverse variance weighted median, weighted mode, and MR-Egger methods.</div></div><div><h3>Results</h3><div>Our findings reveal no causal association between liver and pancreas iron levels with type 2 diabetes (Liver iron: OR = 1.02, P = 0.1, Pancreas iron: OR = 1.11, P = 0.5). This also holds for glycaemic traits, except for the negative causal effect of liver iron levels on HbA1c (OR = 0.93, P = 0.001). Spleen iron levels had a negative causal effect on type 2 diabetes (OR = 0.94, P = 0.049). However, these exceptions are likely due to possible pleiotropy, as these associations can be explained by the effect of the genetic variants on factors that falsely decrease HbA1c levels. No causal association was found for the effect of type 2 diabetes on organ iron levels.</div></div><div><h3>Conclusion</h3><div>Organ iron levels, which are relatively more direct indicators of iron status, showed no causal association with type 2 diabetes in the European population.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"87 ","pages":"Article 127586"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928947","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}
Yuting Zeng , Yalong Wang , Yanan He , Qinyang Li , Ruiqin Chen , Cuiping Wu , Na Li , Xinya Cheng , Yuhui Du , Fangfang Yu , Yue Ba , Guoyu Zhou
{"title":"Association between maternal serum zinc and birth weight is modified by neonatal SOD2 polymorphism and promoter methylation","authors":"Yuting Zeng , Yalong Wang , Yanan He , Qinyang Li , Ruiqin Chen , Cuiping Wu , Na Li , Xinya Cheng , Yuhui Du , Fangfang Yu , Yue Ba , Guoyu Zhou","doi":"10.1016/j.jtemb.2025.127595","DOIUrl":"10.1016/j.jtemb.2025.127595","url":null,"abstract":"<div><h3>Background</h3><div>Conflicting findings exist regarding the association between maternal serum zinc and neonatal birth weight. This study aimed to explore the association between maternal serum zinc and birth weight, and whether this association was modified by neonatal <em>SOD2</em> polymorphism and promoter methylation.</div></div><div><h3>Methods</h3><div>We recruited 464 mother-newborn pairs at Houzhai Center Hospital from January 2010 to January 2012. Maternal serum zinc concentration was determined using atomic absorption spectrophotometry. Neonatal <em>SOD2</em> polymorphism and promoter methylation were measured by TaqMan probe assay and real-time quantitative methylation-specific PCR (QMSP), respectively. Relationships among maternal serum zinc, neonatal <em>SOD2</em> promoter methylation, and birth weight were analyzed by generalized linear model (GLM). Stratified and interaction analyses were conducted to explore the modification of neonatal <em>SOD2</em> polymorphism and promoter methylation on the association between maternal serum zinc and birth weight.</div></div><div><h3>Results</h3><div>Our findings revealed that higher maternal zinc concentrations were associated with decreased birth weight (<em>P</em>-trend < 0.05). Each 1 μmol/L increment in maternal zinc level was associated with a 9.553 g (95 % <em>CI</em>: −16.370, −2.735) decrease in birth weight. A significant interaction between <em>SOD2</em> promoter methylation and maternal serum zinc in relation to birth weight was observed in the AG+GG group (<em>P</em>-interaction < 0.05). Newborns carrying AA genotype were more sensitive to maternal serum zinc in the lower <em>SOD2</em> group (<em>P</em>-interaction < 0.05).</div></div><div><h3>Conclusions</h3><div>Maternal serum zinc was inversely associated with birth weight, and this association was modified by neonatal <em>SOD2</em> polymorphism and promoter methylation. These findings suggest that <em>SOD2</em> polymorphism and promoter methylation may influence the relationship between maternal zinc status and fetal growth.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"87 ","pages":"Article 127595"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019002","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}
Adnan Mohammad Massadeh , Kawthar Zeyad Alzarieni , Hebah Ziyad Alzaghol , Mahmoud Mustafa Smadi
{"title":"Occurrence and health risk assessment of selected metals in commercially available infant formulas in Jordan","authors":"Adnan Mohammad Massadeh , Kawthar Zeyad Alzarieni , Hebah Ziyad Alzaghol , Mahmoud Mustafa Smadi","doi":"10.1016/j.jtemb.2024.127585","DOIUrl":"10.1016/j.jtemb.2024.127585","url":null,"abstract":"<div><h3>Background</h3><div>Infant formulas are the primary source of nutrition for infants and babies when breastfeeding is unavailable, as they are enriched with a variety of macro- and micronutrients to improve their nutritional value and satisfy the different needs of babies. Recently, there has been a rising concern about toxic metal levels in infant formulas, as highlighted by various studies. However, there are currently no sufficient studies focusing on toxic metal levels of infant formulas in Jordan. The current study aims to determine the levels of 25 metals, including Na, Mg, K, Ca, Cr, Fe, Mn, Co, Ni, Cu, Zn, Li, Ti, V, Ga, Sr, Ag, Ba, Bi, Th, U, Al, Cd, In, and Pb, in infant formulas (starter infant formula, follow-on formula, and growing-up formula) using inductively coupled plasma mass spectrometry (ICP-MS) and evaluate their safety and quality.</div></div><div><h3>Methods</h3><div>The metal compositions of 37 infant formula samples collected from different Jordanian pharmacies were determined using inductively coupled plasma-mass spectrometry (ICP-MS) after digesting the samples with 9 mL of HNO<sub>3</sub> (70 %) and 3 mL of H<sub>2</sub>O<sub>2</sub> (30 %) using the microwave-assisted digestion technique. The possible health risks associated with the exposure to Cd, Pb, Al, and Ni in infant formulas were evaluated using estimated daily intake, target hazard quotient, and hazard index calculations. Also, method validation, including accuracy, precision, limit of detection, and limit of quantification, was performed.</div></div><div><h3>Results</h3><div>The results revealed that follow-on formula (intended for 7–12-month-old babies) had the highest mean concentration of all studied metals, except for zinc, which had the highest mean concentration in starter infant formula (intended for less than 6-month-old babies). Also, 72.97 % and 89.20 % of the tested samples had Pb and Cd levels that exceeded the European permissible limit, respectively. Regarding the estimated daily intake (EDI), babies aged 7–12 months were found to be the most exposed to Cd and Pb toxicity, while babies aged less than 6 months were found to be the most exposed to Ni toxicity. Unfortunately, the overall non-carcinogenic negative adverse effects (hazard index HI) of Cd and Pb for babies aged 7–12 months exceeded the acceptable threshold of 1.</div></div><div><h3>Conclusion</h3><div>Based on the results, the consumption of infant formulas sold in Jordan may pose serious health risks to babies, with Cd and Pb levels in follow-on formulas (posing the highest risk). The source of contamination in infant formulas may be contaminated raw materials, the manufacturing process, packaging, or storage. So, strict regulations ought to be established to safeguard the health of babies.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"87 ","pages":"Article 127585"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928949","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}
Aleksandra Naziębło , Olga Bemowska-Kałabun , Małgorzata Wierzbicka , Maksymilian Zienkiewicz
{"title":"Foliar application of nitrates limits lead uptake by Cucumis sativus L. plants","authors":"Aleksandra Naziębło , Olga Bemowska-Kałabun , Małgorzata Wierzbicka , Maksymilian Zienkiewicz","doi":"10.1016/j.jtemb.2025.127592","DOIUrl":"10.1016/j.jtemb.2025.127592","url":null,"abstract":"<div><div>Lead is a toxic heavy metal, which accumulates in the soil and is readily absorbed by plant roots. The uptake of toxic elements by crops is a serious threat to human health. For this reason, it is important to prevent the incorporation of heavy metals into the food chain. Our previous study showed that foliar application of calcium nitrate reduces the intensity of lead uptake by different plant species. A significant decrease in metal concentration was observed both in the roots and in the shoots of three crops: tomato, cucumber, and flax. The present research investigated the mechanism for limiting lead accumulation in plant tissues. The experiments were conducted on <em>Cucumis sativus</em> L. seedlings, grown in hydroponic conditions. To compare the role of Ca<sup>2 +</sup> and NO<sub>3</sub><sup>-</sup> ions in the restriction of lead uptake three different calcium salts (nitrate, chloride, and formate), and two nitrates (calcium and potassium) were applied foliarly to plants. The results show that Ca(NO<sub>3</sub>)<sub>2</sub> is more efficient in decreasing lead accumulation in tissues than other calcium salts which suggests an important role of NO<sub>3</sub><sup>-</sup> ions in the process. In addition, the study demonstrated that the exogenous supply of nitrates helps compensate for nitrogen deficiency caused by lead action and supports the mineral balance. The reduction in lead toxicity to plants after foliar application of nitrates may be due to the stimulation of the biosynthesis of nitric oxide – a key molecule responsible for stress response.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"87 ","pages":"Article 127592"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974086","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}
Dongdong Yu , Yinyin He , Hongsen He , Zhengyan Hu , Yun Huang , Jun Tang
{"title":"Serum iodine concentration in pregnant women and its association with thyroid function","authors":"Dongdong Yu , Yinyin He , Hongsen He , Zhengyan Hu , Yun Huang , Jun Tang","doi":"10.1016/j.jtemb.2024.127584","DOIUrl":"10.1016/j.jtemb.2024.127584","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to investigate the association of serum iodine concentration (SIC) with thyroid function-associated parameters in pregnant women in mild iodine deficient area, and explore its potential to predict individual iodine nutrition status in pregnant women.</div></div><div><h3>Methods</h3><div>A total of 741 pregnant women undergoing prenatal examinations in their second trimester at the Women's Hospital, Zhejiang University School of Medicine, from March 2021 to May 2022 were finally recruited into the study. Venous blood and morning urine were collected. Serum free triiodothyronine (FT3), free thyroxine (FT4), thyro-stimulating hormone (TSH), total thyroxine (TT4), total triiodothyronine (TT3), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), UIC (urinary iodine concentration) and SIC were measured.</div></div><div><h3>Results</h3><div>The median SIC was 54.44 μg/L. SIC was linearly and positively associated with concentrations of FT4 [ β = 0.10, 95 % CI: (0.07, 0.12), TT4 [ β = 0.29, 95 % CI: (0.26, 0.33), TT3 [ β = 0.14, 95 % CI: (0.09, 0.18). There was an inverted \"U\" shaped relationship between SIC and FT3. The associations between SIC and thyroid hormones remained robust when participants taking specific drug were excluded.</div></div><div><h3>Conclusions</h3><div>SIC is associated with thyroid function-related parameters in pregnant women in their second trimester, indicating that the SIC may have the potential to predict individual iodine nutrition status in pregnant women.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"87 ","pages":"Article 127584"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018956","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}
Catrin Herpich , Sophia Walter , Christiane Ott , Ulrike Haß , Tilman Grune , Ursula Müller-Werdan , Kristina Norman
{"title":"Pro-inflammatory diet affects markers of iron metabolism in healthy older adults","authors":"Catrin Herpich , Sophia Walter , Christiane Ott , Ulrike Haß , Tilman Grune , Ursula Müller-Werdan , Kristina Norman","doi":"10.1016/j.jtemb.2024.127583","DOIUrl":"10.1016/j.jtemb.2024.127583","url":null,"abstract":"<div><h3>Background</h3><div>Inflammation and inadequate nutrition are common in older age and known to affect iron homeostasis. However, it is not known whether a pro-inflammatory diet affects iron status in older adults. We investigated the diet quality of healthy older adults considering markers of iron homeostasis and inflammation compared to a younger control.</div></div><div><h3>Methods</h3><div>Serum markers of iron metabolism (iron, transferrin, ferritin, hepcidin, soluble transferrin receptor [sTfR]) and inflammation (interleukin-6 [IL-6], IL-10 high-sensitive C- reactive protein [hsCRP]) were quantified using immunosorbent assays. Insulin resistance was determined by calculating the homeostasis model assessment index (HOMA-IR). The Dietary Inflammatory Index® (DII) was computed based on dietary intake and inflammatory (ID) or less inflammatory diet (LID) groups were created by using median DII score specific to age group and sex.</div></div><div><h3>Results</h3><div>DII did not differ by age (p = 0.668, n = 80, F: 75 %, >65 years, n = 60, F: 72 %, ≤35 years). Iron and inflammation status were different between age groups in terms of higher transferrin saturation, sTfR, ferritin and IL-6 concentrations in the old (all p ≤ 0.001). Only in older adults, BMI, HOMA-IR, hsCRP, ferritin and hepcidin concentrations were significantly higher in ID compared to LID (all p < 0.01). In addition, a risk-factor adjusted regression analysis showed that ID was independently associated with higher ferritin and hepcidin concentrations in older adults.</div></div><div><h3>Conclusion</h3><div>In older age, a pro-inflammatory diet is associated with systemic inflammation and disturbed iron homeostasis.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"87 ","pages":"Article 127583"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aghogho Oyibo , Adesewa C. Adebayo , Odunayo A. Taiwo , Omolaja Osoniyi
{"title":"Ameliorative role of Tetrapleura tetraptera (Schum. & Thonn.) taub in cadmium chloride-induced oxidative stress in Drosophila melanogaster using in vivo and computational approaches","authors":"Aghogho Oyibo , Adesewa C. Adebayo , Odunayo A. Taiwo , Omolaja Osoniyi","doi":"10.1016/j.jtemb.2024.127571","DOIUrl":"10.1016/j.jtemb.2024.127571","url":null,"abstract":"<div><h3>Background</h3><div>Cadmium (Cd) is a naturally occurring transition metal associated with oxidative stress in living organisms. Whereas <em>Tetrapleura tetraptera (Tt),</em> an ethnomedicinal plant is said to possess high antioxidant activity and used to treat various human diseases locally. Therefore, the study aimed to investigate the biological activity of the ethanolic pod extract of <em>T. tetraptera</em> in cadmium chloride-induced toxicity in <em>Drosophila melanogaster</em>.</div></div><div><h3>Methods</h3><div>Six groups of adults (1–3 days old) <em>D. melanogaster</em> as shown: Control, Tt 2.5 mg/10 g diet, Tt 5 mg/10 g diet, CdCl<sub>2</sub>, CdCl<sub>2</sub>+ Tt 2.5 mg/10 diet and CdCl<sub>2</sub>+Tt 5 mg/10 g diet were exposed via diet for 7 days consisting of 50 flies per vial and 5 replicate per group. Thereafter, we evaluated markers for free radical generation, antioxidant, non-antioxidant activities, and emergence rates of the flies. The active compounds of Tt extract were molecularly docked against glutathione-S-transferase II.</div></div><div><h3>Results</h3><div>The results indicated that CdCl<sub>2</sub> significantly induced oxidative stress by increasing the levels of lipid peroxidation (LPO), hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)<sub>,</sub> nitric oxide (NO) and decreasing the activity of GST without an effect on total thiol (T-SH) and non-protein thiols (NP-SHs) levels. However, co-treatment with <em>T. tetraptera</em> (2.5 mg/10 g diet) significantly decreased levels of LPO, H<sub>2</sub>O<sub>2,</sub> but increased GST activity. Also, co-treatment with <em>T. tetraptera</em> (5 mg/10 g diet) increased NPSH and T-SH levels by 18.6 % and 35.8 %. Furthermore, Co-treatment (5 mg/10 g diet) increased the rate of offspring emergence.</div></div><div><h3>Conclusion</h3><div><em>T. tetraptera</em> ameliorated cadmium chloride-induced oxidative stress in <em>Drosophila melanogaster</em> and increased offspring hatching rate. <em>T. tetraptera</em> may therefore serve as a good regimen for the treatment of oxidative stress-related diseases induced by cadmium.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"87 ","pages":"Article 127571"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788239","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":"Exploring the role of boron-containing compounds in biological systems: Potential applications and key challenges","authors":"Haseeb Khaliq","doi":"10.1016/j.jtemb.2025.127594","DOIUrl":"10.1016/j.jtemb.2025.127594","url":null,"abstract":"<div><h3>Background</h3><div>Boron, a naturally abundant trace element, plays a crucial role in various biological processes and influences important physiological functions such as bone health, immune response, and cellular metabolism. Its applications span diverse scientific fields including anatomy, pharmacology, reproduction, medicine, and agriculture.</div></div><div><h3>Objectives</h3><div>This review examines the diverse functions of boron-compounds in biological systems and highlights their therapeutic potential, challenges associated with toxicity, and mechanisms underlying their biological interactions.</div></div><div><h3>Methods</h3><div>In this paper, the literature on boron action was reviewed, paying special attention to studies that examined the effects of boron on health and its therapeutic applications in multiple areas.</div></div><div><h3>Results</h3><div>Boron exhibits broad therapeutic potential by affecting several pathways. However, excessive consumption can cause toxicity and negatively impact health. Current research only partially elucidates the mechanisms of boron's biological effects, so further studies are needed.</div></div><div><h3>Conclusion</h3><div>Understanding boron's interactions in biological systems is critical to optimizing its application in healthcare and ensuring safety. Future research will improve our knowledge of boron's biological effects and promote innovative therapeutic applications.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"87 ","pages":"Article 127594"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019019","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}
Akrity Anand , Susanta Sengupta , Dušan Galusek , Ana M. Beltrán , Dagmar Galusková , Aldo R. Boccaccini
{"title":"A new approach to overcome cytotoxic effects of Cu by delivering dual therapeutic ions (Sr, Cu)","authors":"Akrity Anand , Susanta Sengupta , Dušan Galusek , Ana M. Beltrán , Dagmar Galusková , Aldo R. Boccaccini","doi":"10.1016/j.jtemb.2024.127565","DOIUrl":"10.1016/j.jtemb.2024.127565","url":null,"abstract":"<div><h3>Introduction</h3><div>The incorporation of trace elements such as strontium (Sr) and copper (Cu) in the composition of mesoporous bioactive glass (MBG) is widely known to enhance its biological functionality for bone tissue regeneration</div></div><div><h3>Methods</h3><div>Two MBG powders with the composition 80SiO<sub>2</sub>-11CaO-5P<sub>2</sub>O<sub>5</sub>-xCuO/SrO, one doped with 4 mol.% of CuO, the second with 4 mol.% of SrO were blended in the weight ratios of Cu-MBG: Sr-MBG; 100:0, 70: 30, 50: 50, 30: 70 and 0:100 aiming at minimizing Cu to minimize the cytotoxicity of Cu while preserving its antimicrobial activity. The synergistic effects of Sr and Cu ions on bioactivity, cytotoxicity, and antimicrobial activity were studied.</div></div><div><h3>Results</h3><div>Transmission electron microscopy (TEM) examination of Cu-MBG and Sr-MBG showed fringes related to the development of a mesoporous structure. The specific surface area values of the Cu-MBG and Sr-MBG powders were 287 and 349 m<sup>2</sup>/g, respectively. A characteristic compact layer consisting of particles with platelet-like morphology commonly associated with HAp crystals was confirmed after 7 days soaking in simulated body fluid (SBF). Mouse preosteoblast cells (MC3T3-E1) exhibited higher cell viability when exposed to a 1 % w/v eluate from blended Cu-MBG powders compared to pure Cu-MBG. Notably, the Cu-MBG: Sr-MBG ratio of 30:70 exhibited cell viability of around 85 % at this concentration. A higher cell viability (above 100 %) towards MC3T3-E1 cells was observed for all powders when tested with the 0.1 % w/v eluate. With progressive increase in the amount of Cu-MBG in the blended system the bacterial inhibitory effects were more pronounced. The Cu ions released from Cu-MBG generate hydroxyl ions and increase the pH leading to disruption of the cellular membrane of microbes, resulting in enhanced antimicrobial activity.</div></div><div><h3>Conclusion</h3><div>This newly developed blended system composed of Cu and Sr doped MBGs is expected to be more effective as bioactive filler in comparison to single ion doped MBGs for bone tissue engineering applications.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"87 ","pages":"Article 127565"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831562","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}
Yuanyuan Wang , Lei Qi , Sihong Guo , Yuehui Jia , Ruixiang Wang , Cunqi Lv , Qingyu Zeng , Ying Gao , Tong Wang , Qi Li
{"title":"Sodium selenite inhibits the growth of cervical cancer cells through the PI3K/AKT pathway","authors":"Yuanyuan Wang , Lei Qi , Sihong Guo , Yuehui Jia , Ruixiang Wang , Cunqi Lv , Qingyu Zeng , Ying Gao , Tong Wang , Qi Li","doi":"10.1016/j.jtemb.2024.127582","DOIUrl":"10.1016/j.jtemb.2024.127582","url":null,"abstract":"<div><h3>Background</h3><div>Selenium can inhibit cervical cancers, but the specific mechanism of anti-cervical cancer is not fully understood.</div></div><div><h3>Methods</h3><div>In this study, we investigated the anti-cervical cancer effect of sodium selenite (SS) in vivo and in vitro to reveal the role of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway in terms of the mechanism. In vivo experiments, HeLa cell xenografts were constructed in BALB/c female nude mice, and then intraperitoneally injected with 3 mg/kg sodium selenite (SS) for 14 days. In vitro experiments, we detected cell viability by MTT assay and apoptosis by Annexin V-FITC/PI staining. The levels of PI3K, AKT, phosphorylated PI3K (p-PI3K), and phosphorylated Akt (p-AKT) were measured by Western Blot.</div></div><div><h3>Results</h3><div>HeLa cell xenografts in female nude mice showed delayed tumor growth and no apparent toxicity in the liver or kidney. SS reduced the viability and increased apoptosis of HeLa and SiHa cells. SS did not affect PI3K and AKT levels and decreased p-PI3K and p-AKT levels. In addition, the results also revealed that the SS combined with LY294002, a specific PI3K inhibitor, enhanced the inhibitory effect of SS on the PI3K/AKT signaling pathway, further inhibiting cervical cancer cell viability and increased apoptosis.</div></div><div><h3>Conclusions</h3><div>SS exerted its anti-cervical cancer effects by inhibiting cell proliferation, promoting apoptosis, and inhibiting the PI3K/AKT signaling pathway.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"87 ","pages":"Article 127582"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873752","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}