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Impact of hidden hunger on pregnant women from underserved communities and its role in anaemia 隐性饥饿对服务不足社区孕妇的影响及其在贫血中的作用。
IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-30 DOI: 10.1016/j.jtemb.2025.127794
Anumesh K. Pathak , Dhruv Agarwal , Shivani Singh , Rupita Kulshresthra , Manish Raj Kulshrestha , Vandana Tiwari

Background

Micronutrient deficiencies (MiNDs) during pregnancy contribute to anemia, preeclampsia, and poor fetal outcomes. We assessed the prevalence of MiNDs and their association with anemia among pregnant women in northern India.

Methods

A prospective cross-sectional study was conducted on 322 first-trimester pregnant women from low- to middle socioeconomic backgrounds. Haematology indices were measured on an automated analyser; vitamins (A, B1, B9, B12, D3) by LC-MS/MS; and trace elements (Fe, Zn, Cu, Se, Mn) by ICP-MS.

Results

Anaemia prevalence was 46.5 %. Anemic women had significantly lower levels of manganese (50.3 %), copper (32.8 %), zinc (41.9 %), and iron (51.1 %) (p < 0.0001) and vitamins A (14.8 %), B1 (59.3 %), B9 (46.4 %), and B12 (71.3 %) (p < 0.0001). Selenium (p = 0.752) and vitamin D3 (p = 0.340) were not associated with anemia. Among anaemic women, 14 % had multiple micronutrient deficiencies.
Anemia increased the risk of low vitamin A (<900 pg/mL; OR 2.06, CI: 1.32–3.21, p = 0.001), B1 (<70 ng/mL; OR 4.30, CI: 2.68–6.89, p < 0.0001), B9 (<3 ng/mL; OR 5.91, CI: 3.64–9.59, p < 0.0001), and B12 (<200 pg/mL; OR 5.53, CI: 3.43–8.93, p < 0.0001) respectively. Similarly, the risk of low iron (<80 µg/dL; OR 8.01, 95 % CI: 4.85–13.23, p < 0.0001), zinc (<600 µg/L; OR 5.18, 95 % CI: 3.22–8.34, p < 0.0001), copper (<700 µg/L; OR 4.30, 95 % CI: 2.68–6.89, p < 0.0001), and manganese (<4.0 µg/L; OR 2.25, 95 % CI: 1.44–3.51, p = 0.004) was significantly associated with higher risk of anemia.
Univariate analysis showed significant correlations between hemoglobin and vitamins A, B1, B12, manganese; copper; and iron (p < 0.05). In multivariate analysis, B1, B9, B12, Fe, Cu, and Zn were independent predictors of Hb levels.

Conclusions

Anemia during pregnancy is strongly linked to multiple micronutrient deficiencies. Findings support antenatal strategies that extend beyond iron–folate to address multiple micronutrient deficiencies.
背景:怀孕期间微量营养素缺乏(MiNDs)会导致贫血、子痫前期和不良胎儿结局。我们评估了印度北部孕妇中MiNDs的患病率及其与贫血的关系。方法:对322名来自中低社会经济背景的妊娠早期孕妇进行前瞻性横断面研究。血液学指标在自动分析仪上测量;LC-MS/MS法测定维生素A、B1、B9、B12、D3;微量元素(Fe, Zn, Cu, Se, Mn)。结果:贫血患病率为46.5% %。贫血妇女的锰(50.3% %)、铜(32.8% %)、锌(41.9% %)和铁(51.1% %)的水平明显较低(p )。结论:怀孕期间的贫血与多种微量营养素缺乏密切相关。研究结果支持产前策略,将叶酸铁扩展到解决多种微量营养素缺乏症。
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引用次数: 0
METTL14 promotes ferroptosis during the development of cisplatin-induced kidney injury by stabilizing ERFE through IGF2BP3-dependent m6A methylation METTL14通过igf2bp3依赖的m6A甲基化来稳定ERFE,从而促进顺铂诱导肾损伤发展过程中的铁凋亡
IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-28 DOI: 10.1016/j.jtemb.2025.127793
Yan Chen , Wenlong Li , Dian Zhao , Chong Huang , Chengyun Xu

Background

Cisplatin-induced acute kidney injury (CP-AKI) is a major complication of cisplatin chemotherapy that is mechanistically linked to ferroptosis, an iron-dependent form of cell death. However, the epigenetic and post-transcriptional factors regulating ferroptosis in CP-AKI, particularly those mediated by N6-methyladenosine (m6A) RNA methylation, remain insufficiently defined. This study investigated the role of methyltransferase-like 14 (METTL14)-mediated m6A RNA methylation and its downstream targets in ferroptosis regulation during CP-AKI.

Methods

We established an in vitro model of CP-AKI using cisplatin-treated human renal proximal tubular epithelial cells (HK-2). The expressions of gene and protein were tested by qRT-PCR, western blot, and immunofluorescence. Cell viability was detected by CCK-8 assay. The total m6A methylation and ferroptosis markers were measured by the kits. MeRIP-PCR was performed to detect m6A modifications on ERFE mRNA. The binding relationship between METTL14/insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and erythroferrone (ERFE) was analyzed by RIP assay. ERFE mRNA stability was determined by Actinomycin D chase assay.

Results

Cisplatin treatment upregulated METTL14, IGF2BP3, and ERFE in HK-2 cells, coinciding with increased m6A methylation and ferroptosis induction. METTL14 knockdown attenuated cisplatin-induced ferroptosis in HK-2 cells by downregulating ERFE. Mechanistically, METTL14 stabilized ERFE mRNA through IGF2BP3-dependent m6A modification. As expected, IGF2BP3 overexpression reversed the effect of METTL14 knockdown on cisplatin-induced ferroptosis in HK-2 cells, while concomitant ERFE depletion abrogated this reversal.

Conclusion

METTL14 upregulation promotes ferroptosis in CP-AKI by stabilizing ERFE mRNA through IGF2BP3-dependent m6A modification. Targeting the METTL14/IGF2BP3/ERFE axis offers a promising strategy for mitigating cisplatin-induced kidney injury.
背景:顺铂诱导的急性肾损伤(CP-AKI)是顺铂化疗的主要并发症,与铁中毒(铁依赖性细胞死亡)有机械联系。然而,调控CP-AKI中铁下垂的表观遗传和转录后因子,特别是那些由n6 -甲基腺苷(m6A) RNA甲基化介导的因子,仍然没有得到充分的定义。本研究探讨甲基转移酶样14 (methyltransferase-like 14, METTL14)介导的m6A RNA甲基化及其下游靶点在CP-AKI中铁死亡调节中的作用。方法采用顺铂处理的人肾近端小管上皮细胞(HK-2)建立CP-AKI体外模型。采用qRT-PCR、western blot和免疫荧光检测基因和蛋白的表达。CCK-8法检测细胞活力。用试剂盒检测总m6A甲基化和铁下垂标记物。MeRIP-PCR检测ERFE mRNA上m6A的修饰。采用RIP法分析METTL14/胰岛素样生长因子2 mrna结合蛋白3 (IGF2BP3)与红细胞铁酮(ERFE)的结合关系。放线菌素D追逐法检测ERFE mRNA的稳定性。结果铂治疗上调HK-2细胞中METTL14、IGF2BP3和ERFE,与m6A甲基化增加和铁凋亡诱导一致。METTL14敲除可通过下调ERFE减轻顺铂诱导的HK-2细胞铁下垂。在机制上,METTL14通过igf2bp3依赖的m6A修饰来稳定ERFE mRNA。正如预期的那样,IGF2BP3过表达逆转了METTL14敲低对顺铂诱导的HK-2细胞铁凋亡的影响,而伴随的ERFE消耗则取消了这种逆转。结论mettl14上调通过igf2bp3依赖性m6A修饰稳定ERFE mRNA,促进CP-AKI铁凋亡。靶向METTL14/IGF2BP3/ERFE轴为减轻顺铂诱导的肾损伤提供了一种有希望的策略。
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引用次数: 0
Environmental trace metals contamination near a copper mining area from central-west region of Romania 罗马尼亚中西部地区铜矿区附近的环境痕量金属污染
IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-27 DOI: 10.1016/j.jtemb.2025.127780
Florica Emilia Morariu , Eugen Cătălin Zoican , Marinel Nicolae Horablaga , Nicolae Florin Popa , Romeo T. Cristina , Eugenia Dumitrescu , Catalin Cicerone Grigorescu , Adina Horablaga , Sorin Morariu
<div><h3>Background and objective</h3><div>The rising global demand for metals has intensified mining operations, resulting in considerable environmental pollution by heavy metals in soils and water bodies, which endangers ecosystems and human health. While heavy metals are naturally present in soils and aquatic environments, human activities such as mining and smelting have significantly disrupted their biogeochemical cycles, causing increased concentrations that pose threats to both the environment and public health. This study focuses on assessing the levels of trace and heavy metals in river water and soils in a Romanian copper mining region, as well as examining their bioaccumulation in soils, aquatic organisms, and plants. The findings aim to provide essential data to support environmental management and remediation efforts.</div></div><div><h3>Methods</h3><div>This study examines environmental metal contamination in the vicinity of a copper mining area located in the Central-West Region of Romania. Samples—including water, mud, soil, fish, and Salix alba leaves—were collected from upstream (UPS), downstream (DWS), and the confluence point (RJ) of the Aries and Abrud rivers within Alba County. Sampling sites encompassed various locations near the mining operations along the river, as well as a reference site approximately 200 km southwest (SW) in a non-mining area. All samples were analyzed using a PerkinElmer AAPinacle 900 T atomic absorption spectrometer. Additionally, concentration factors and pollution load indices for water, mud, and soil were calculated, along with bioaccumulation factors for fish and Salix alba leaves.</div></div><div><h3>Results</h3><div>Our analyses revealed elevated levels of copper (Cu), iron (Fe), and zinc (Zn) exceeding Romanian water quality standards, while mercury (Hg), cadmium (Cd), and lead (Pb) remained below standard thresholds. The contamination factor (CF) indicated higher concentrations of Cu, Zn, Fe, Hg, Cd, and Pb in the mining vicinity compared to non-mining areas, with increased CF observed downstream and at the river junction, suggesting significant pollutant dispersion. The pollution load index (PLI) corroborated these findings, showing elevated pollution levels in water, soil, and mud samples near the mining site. Bioaccumulation assessments demonstrated a bioconcentration factor (BAF) greater than one for Hg, Cd, and Pb in Salix alba leaves from all sampling points, indicating bioaccumulation, whereas Fe exhibited lower BAF values. In fish, BAFs for Cu, Zn, Hg, and Pb exceeded one across all areas, confirming accumulation, while Fe showed limited bioaccumulation. Notably, cadmium bioaccumulation was detected only upstream and at the river junction, with no accumulation downstream.</div></div><div><h3>Conclusion</h3><div>These findings highlight the impact of copper mining activities on environmental metal distribution and bioaccumulation in local biota, underscoring the need for ongoing monito
背景与目的全球对金属需求的增长加剧了采矿作业,导致土壤和水体重金属严重污染环境,危及生态系统和人类健康。虽然重金属自然存在于土壤和水生环境中,但采矿和冶炼等人类活动严重破坏了土壤和水生环境的生物地球化学循环,导致重金属浓度增加,对环境和公众健康构成威胁。本研究的重点是评估罗马尼亚铜矿矿区河水和土壤中微量和重金属的水平,以及检查它们在土壤、水生生物和植物中的生物积累。研究结果旨在为支持环境管理和补救工作提供必要的数据。方法本研究考察了罗马尼亚中西部地区铜矿区附近的环境金属污染。样本-包括水、泥、土、鱼和白柳叶-从上游(UPS)、下游(DWS)和阿尔巴县内白羊座河和阿布德河的汇合点(RJ)收集。采样地点包括沿河采矿作业附近的各个地点,以及西南约200 公里处的一个非矿区的参考地点。所有样品均使用PerkinElmer AAPinacle 900 T原子吸收光谱仪进行分析。此外,还计算了水、泥和土壤的浓度因子和污染负荷指数,以及鱼和白柳叶片的生物积累因子。结果我们的分析显示,罗马尼亚的铜(Cu)、铁(Fe)和锌(Zn)含量超过了水质标准,而汞(Hg)、镉(Cd)和铅(Pb)仍低于标准阈值。污染因子(CF)表明,与非矿区相比,矿区附近的Cu、Zn、Fe、Hg、Cd和Pb浓度较高,且下游和河流交汇处的CF增加,表明污染物扩散显著。污染负荷指数(PLI)证实了这些发现,显示矿区附近的水、土壤和泥浆样本的污染水平升高。生物积累评价表明,所有采样点的柳叶中汞、镉和铅的生物富集系数(BAF)均大于1,表明生物积累,而铁的BAF值较低。在鱼类中,Cu、Zn、Hg和Pb的baf在所有区域均超过1,证实了积累,而Fe表现出有限的生物积累。值得注意的是,镉的生物积累仅在上游和河流交界处检测到,下游没有积累。结论铜矿开采活动对环境金属分布和当地生物群生物积累的影响,强调需要持续监测和缓解策略,以保护生态和人类健康。
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引用次数: 0
Camel whey protein coated metal-organic frameworks (CWP/MOF) as a sustainable approach to treat environmental stress-induced liver toxicity by cobalt chloride in rats 骆驼乳清蛋白包覆金属有机框架(CWP/MOF)治疗环境应激性氯化钴肝毒性的研究进展
IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-27 DOI: 10.1016/j.jtemb.2025.127791
Dalia Hamad , Asmaa F.A. Dawood , Hanan M. Alharbi , Shereen Mahmoud Refaie , Marwa A. Ali , A.A. Abu-Sehly , Hanem S. Abdel –Tawab , Nermeen N. Welson , Fatma El-Zahraa A. Abd El-Aziz

Background and aim

Environmental stressors, such as heavy metal pollution, can have devastating effects on biological organisms, leading to conditions like liver toxicity. This study explored the therapeutic potential of a novel iron-based metal-organic framework (Fe-MOF) in mitigating cobalt chloride-induced liver toxicity in rats.

Methods

Utilizing a solvothermal synthesis method, CWP/MOF was created and characterized using X-ray diffraction, Fourier transform infrared spectroscopy, and transmission electron microscopy. Adult male rats were divided into four groups, each consisting of six rats. The groups were treated as follows: Group 1 (Control): Received 0.5 mL/day of distilled water only. Group 2 (CoCl₂): Treated with cobalt chloride (100 mg/kg/day) dissolved in distilled water. Group 3 (CoCl₂ + Fe-MOFs): Treated with cobalt chloride (100 mg/kg/day) and Fe-MOFs dissolved in distilled water. Group 4 (CoCl₂ + CWP/MOF): Treated with cobalt chloride (100 mg/kg/day) and CWP/MOF, dissolved in distilled water. All groups received treatment for a duration of two months.

Results

there was a one-dimensional structure and multienzyme-like activity. CWP/MOF prevented apoptosis and reduced the histopathological effect and collagen fiber percentage caused by cobalt chloride in the liver. Nanotechnology was used to increase the therapeutic efficiency of camel whey protein against the harmful effects associated with environmental stress-induced liver toxicity by cobalt chloride in rats.

Conclusions

This study highlights the potential of CWP/MOF as a groundbreaking therapeutic agent for induced liver toxicity, with promising applications in regenerative medicine and tissue engineering. By harnessing the unique properties of CWP/MOF, researchers may uncover new avenues for treating liver-related disorders and promoting overall health.
背景和目的重金属污染等环境压力因素会对生物有机体产生破坏性影响,导致肝毒性等疾病。本研究探讨了一种新型铁基金属有机框架(Fe-MOF)在减轻氯化钴诱导的大鼠肝毒性方面的治疗潜力。方法采用溶剂热合成方法制备CWP/MOF,并利用x射线衍射、傅里叶变换红外光谱和透射电镜对其进行表征。将成年雄性大鼠分为四组,每组6只。各组处理如下:1组(对照组):仅给予0.5 mL/d蒸馏水。第2组(CoCl₂):用氯化钴(100 mg/kg/天)溶解在蒸馏水中处理。第3组(CoCl₂+ Fe-MOFs):用氯化钴(100 mg/kg/天)和溶解于蒸馏水中的Fe-MOFs处理。第4组(CoCl₂+ CWP/MOF):用氯化钴(100 mg/kg/day)和CWP/MOF处理,溶解在蒸馏水中。各组均接受为期2个月的治疗。结果该蛋白具有一维结构和多酶样活性。CWP/MOF可抑制氯化钴引起的肝脏细胞凋亡,降低肝脏组织病理效应和胶原纤维百分比。利用纳米技术提高骆驼乳清蛋白对环境应激引起的氯化钴肝毒性大鼠的治疗效率。结论CWP/MOF是一种具有突破性的肝毒性治疗药物,在再生医学和组织工程领域具有广阔的应用前景。通过利用CWP/MOF的独特特性,研究人员可能会发现治疗肝脏相关疾病和促进整体健康的新途径。
{"title":"Camel whey protein coated metal-organic frameworks (CWP/MOF) as a sustainable approach to treat environmental stress-induced liver toxicity by cobalt chloride in rats","authors":"Dalia Hamad ,&nbsp;Asmaa F.A. Dawood ,&nbsp;Hanan M. Alharbi ,&nbsp;Shereen Mahmoud Refaie ,&nbsp;Marwa A. Ali ,&nbsp;A.A. Abu-Sehly ,&nbsp;Hanem S. Abdel –Tawab ,&nbsp;Nermeen N. Welson ,&nbsp;Fatma El-Zahraa A. Abd El-Aziz","doi":"10.1016/j.jtemb.2025.127791","DOIUrl":"10.1016/j.jtemb.2025.127791","url":null,"abstract":"<div><h3>Background and aim</h3><div>Environmental stressors, such as heavy metal pollution, can have devastating effects on biological organisms, leading to conditions like liver toxicity. This study explored the therapeutic potential of a novel iron-based metal-organic framework (Fe-MOF) in mitigating cobalt chloride-induced liver toxicity in rats<strong>.</strong></div></div><div><h3>Methods</h3><div>Utilizing a solvothermal synthesis method, CWP/MOF was created and characterized using X-ray diffraction, Fourier transform infrared spectroscopy, and transmission electron microscopy. Adult male rats were divided into four groups, each consisting of six rats. The groups were treated as follows: Group 1 (Control): Received 0.5 mL/day of distilled water only. Group 2 (CoCl₂): Treated with cobalt chloride (100 mg/kg/day) dissolved in distilled water. Group 3 (CoCl₂ + Fe-MOFs): Treated with cobalt chloride (100 mg/kg/day) and Fe-MOFs dissolved in distilled water. Group 4 (CoCl₂ + CWP/MOF): Treated with cobalt chloride (100 mg/kg/day) and CWP/MOF, dissolved in distilled water. All groups received treatment for a duration of two months.</div></div><div><h3>Results</h3><div>there was a one-dimensional structure and multienzyme-like activity. CWP/MOF prevented apoptosis and reduced the histopathological effect and collagen fiber percentage caused by cobalt chloride in the liver. Nanotechnology was used to increase the therapeutic efficiency of camel whey protein against the harmful effects associated with environmental stress-induced liver toxicity by cobalt chloride in rats<strong>.</strong></div></div><div><h3>Conclusions</h3><div>This study highlights the potential of CWP/MOF as a groundbreaking therapeutic agent for induced liver toxicity, with promising applications in regenerative medicine and tissue engineering. By harnessing the unique properties of CWP/MOF, researchers may uncover new avenues for treating liver-related disorders and promoting overall health.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127791"},"PeriodicalIF":3.6,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145417360","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}
引用次数: 0
Azelastine attenuates Cisplatin-induced renal and testicular injury: Involvement of Nrf2/SLC7A11-GPX4 and NCOA4-mediated ferroptosis Azelastine减轻顺铂诱导的肾脏和睾丸损伤:Nrf2/SLC7A11-GPX4和ncoa4介导的铁下垂
IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-27 DOI: 10.1016/j.jtemb.2025.127792
Salwa R. Abo El-Ela, Amal M. El Gayar, Randa A. Zaghloul

Aim

Renal and testicular toxicities are side effects of the chemotherapeutic agent cisplatin (Cis). The study aims to assess the potential repurpose of Azelastine (Az), an H1-receptor antagonist to alleviate Cis-induced toxicity.

Materials and methods

Sprague Dawley rats received Az (4 or 6 mg/kg/orally) for ten days and were challenged by a single i.p. injection of Cis (10 mg/kg) on the fifth day. Renal and testicular tissues were investigated using histopathology, immunohistochemistry, qRT-PCR, and ELISA techniques.

Results

Az (6 mg/kg) attenuated Cis-induced nephrotoxicity by reversing the elevation of serum creatinine, BUN, and urinary total protein [38.5 %, 32.3 % and 60 % (p < 0.0001)], and the decline of urinary creatinine and CrCl by 2.15- and 2.8-fold (p < 0.0001 and p < 0.01, respectively). Az (6 mg/kg) induced a significant decrease in both renal and testicular levels of MDA, tissue iron (70.9 %, 51 %, 44.5 % and 33.6 %, respectively, p < 0.0001) and TFR (27.6 %, p < 0.05 and 39 %, p < 0.0001, respectively). Moreover, Az up-regulated renal and testicular Nrf2 and GPX4 (6.9-, 15.6-, 3.9- and 4.8-fold, respectively, p < 0.0001). Both renal and testicular GSH and SLC7A11 were enhanced by Az (2.7-, 2.1-, 4.5-fold, p < 0.0001, and 3.4-fold, p < 0.01, respectively). Finally, Az induced a decrease of renal and testicular NCOA4 and FTH1 gene expressions (53.4 %, 48.6 %, 51.5 % and 41.3 %, respectively, p < 0.0001). Interestingly, Az enhanced the protein levels of NCOA4, but reduced FTH1 (44.5 %, p < 0.0001, 41 %, p < 0.001 and 1.29- and 1.33-fold p < 0.01, respectively)

Conclusion

Az mitigates Cis-induced nephrotoxicity and testicular injury by inhibiting ferroptosis.
目的:化疗药物顺铂(Cis)的副作用是肾脏和睾丸的毒性。该研究旨在评估Azelastine (Az)的潜在用途,Azelastine是一种h1受体拮抗剂,可减轻顺式诱导的毒性。材料与方法:Sprague Dawley大鼠口服4、6 mg/kg/ Az 10 d,第5天单次腹腔注射Cis(10 mg/kg)。采用组织病理学、免疫组织化学、qRT-PCR和ELISA技术对肾脏和睾丸组织进行研究。结果:Az(6 mg/kg)通过逆转血清肌酐、尿素氮和尿总蛋白升高而减轻顺式诱导的肾毒性[38.5 %,32.3 %和60 %](p
{"title":"Azelastine attenuates Cisplatin-induced renal and testicular injury: Involvement of Nrf2/SLC7A11-GPX4 and NCOA4-mediated ferroptosis","authors":"Salwa R. Abo El-Ela,&nbsp;Amal M. El Gayar,&nbsp;Randa A. Zaghloul","doi":"10.1016/j.jtemb.2025.127792","DOIUrl":"10.1016/j.jtemb.2025.127792","url":null,"abstract":"<div><h3>Aim</h3><div>Renal and testicular toxicities are side effects of the chemotherapeutic agent cisplatin (Cis). The study aims to assess the potential repurpose of Azelastine (Az), an H1-receptor antagonist to alleviate Cis-induced toxicity.</div></div><div><h3>Materials and methods</h3><div>Sprague Dawley rats received Az (4 or 6 mg/kg/orally) for ten days and were challenged by a single i.p. injection of Cis (10 mg/kg) on the fifth day. Renal and testicular tissues were investigated using histopathology, immunohistochemistry, qRT-PCR, and ELISA techniques.</div></div><div><h3>Results</h3><div>Az (6 mg/kg) attenuated Cis-induced nephrotoxicity by reversing the elevation of serum creatinine, BUN, and urinary total protein [38.5 %, 32.3 % and 60 % (<em>p</em> &lt; 0.0001)], and the decline of urinary creatinine and CrCl by 2.15- and 2.8-fold (<em>p</em> &lt; 0.0001 and p &lt; 0.01, respectively). Az (6 mg/kg) induced a significant decrease in both renal and testicular levels of MDA, tissue iron (70.9 %, 51 %, 44.5 % and 33.6 %, respectively, <em>p</em> &lt; 0.0001) and TFR (27.6 %, <em>p</em> &lt; 0.05 and 39 %, <em>p</em> &lt; 0.0001, respectively). Moreover, Az up-regulated renal and testicular Nrf2 and GPX4 (6.9-, 15.6-, 3.9- and 4.8-fold, respectively, <em>p</em> &lt; 0.0001). Both renal and testicular GSH and SLC7A11 were enhanced by Az (2.7-, 2.1-, 4.5-fold, <em>p</em> &lt; 0.0001, and 3.4-fold, <em>p</em> &lt; 0.01, respectively). Finally, Az induced a decrease of renal and testicular NCOA4 and FTH1 gene expressions (53.4 %, 48.6 %, 51.5 % and 41.3 %, respectively, <em>p</em> &lt; 0.0001). Interestingly, Az enhanced the protein levels of NCOA4, but reduced FTH1 (44.5 %, p &lt; 0.0001, 41 %, p &lt; 0.001 and 1.29- and 1.33-fold p &lt; 0.01, respectively)</div></div><div><h3>Conclusion</h3><div>Az mitigates Cis-induced nephrotoxicity and testicular injury by inhibiting ferroptosis.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127792"},"PeriodicalIF":3.6,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145411302","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}
引用次数: 0
Selective impact of zinc on human circulating CD56dim NK cells 锌对人循环CD56dim NK细胞的选择性影响
IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-27 DOI: 10.1016/j.jtemb.2025.127788
Sabrina B. Bennstein, Ronja Stöcker, Laura Heenen, Jana Jakobs, Kim Ohl, Lothar Rink

Purpose

Natural Killer (NK) cells are essential for recognizing aberrant and virus-infected cells. Adequate levels of the trace element zinc are known to be important for proper immune functionality against infections and tumor growth. So far, not many studies have analyzed the effects of zinc on NK cells. We previously observed higher levels of activated CD69+ NK cells in zinc-adequate compared to zinc-deficient donors. We therefore aimed to analyze the influence of zinc on the activation and functionality of NK cell in vitro.

Methods

Peripheral blood mononuclear cells were freshly isolated from young healthy donors. Serum zinc levels and Adjusted Zinc Diet Score (AZDS) were determined. NK cells, CD56dim NK cells, and CD56bright NK cells were analyzed ex vivo or cultivated in zinc-deficient, zinc-adequate, and zinc-supplemented media for 1 or 20 h ± specific inhibitors. CD56dim NK cell frequencies, phenotype, and functionality were analyzed via flow cytometry, qPCR, and Western blot.

Results

The frequencies of cytotoxic CD56dim NK cells positively correlated with serum zinc as well as AZDS. CD69 expression was significantly increased after 20 h of zinc supplementation on CD56dim NK cells. CD69+ CD56dim NK cells showed significant higher degranulation capacity and IFNγ production. Furthermore, NFκB inhibition upregulated CD69 expression and NFKB mRNA was significantly decreased in zinc-supplemented conditions. In addition, perforin levels were sensitive to zinc deprivation.

Conclusion

Extracellular zinc selectively activates CD56dim NK cells enhancing degranulation and IFNγ production. Zinc supplementation might be a useful tool for in vitro NK cell expansion protocols for future cellular therapies.
自然杀伤细胞(NK)是识别异常细胞和病毒感染细胞所必需的。适量的微量元素锌对于抵抗感染和肿瘤生长的正常免疫功能非常重要。到目前为止,还没有很多研究分析锌对NK细胞的影响。我们之前观察到,与锌缺乏的供者相比,锌充足的供者活化的CD69+ NK细胞水平更高。因此,我们旨在分析锌对体外NK细胞活化和功能的影响。方法从年轻健康供者新鲜分离外周血单个核细胞。测定血清锌水平和调整锌饮食评分(AZDS)。对NK细胞、CD56dim NK细胞和CD56bright NK细胞进行离体分析,或在锌缺乏、锌充足和锌补充的培养基中培养1或20 h±特异性抑制剂。通过流式细胞术、qPCR和Western blot分析CD56dim NK细胞的频率、表型和功能。结果细胞毒性CD56dim NK细胞频率与血清锌、AZDS呈正相关。补锌20 h后CD56dim NK细胞CD69表达显著升高。CD69+ CD56dim NK细胞表现出更高的脱颗粒能力和IFNγ的产生。此外,在锌补充条件下,NFκB抑制上调CD69表达,NFKB mRNA显著降低。此外,穿孔素水平对缺锌敏感。结论细胞外锌选择性激活CD56dim NK细胞,促进脱颗粒和IFNγ的产生。锌补充可能是一个有用的工具,体外NK细胞扩增方案为未来的细胞治疗。
{"title":"Selective impact of zinc on human circulating CD56dim NK cells","authors":"Sabrina B. Bennstein,&nbsp;Ronja Stöcker,&nbsp;Laura Heenen,&nbsp;Jana Jakobs,&nbsp;Kim Ohl,&nbsp;Lothar Rink","doi":"10.1016/j.jtemb.2025.127788","DOIUrl":"10.1016/j.jtemb.2025.127788","url":null,"abstract":"<div><h3>Purpose</h3><div>Natural Killer (NK) cells are essential for recognizing aberrant and virus-infected cells. Adequate levels of the trace element zinc are known to be important for proper immune functionality against infections and tumor growth. So far, not many studies have analyzed the effects of zinc on NK cells. We previously observed higher levels of activated CD69<sup>+</sup> NK cells in zinc-adequate compared to zinc-deficient donors. We therefore aimed to analyze the influence of zinc on the activation and functionality of NK cell <em>in vitro</em>.</div></div><div><h3>Methods</h3><div>Peripheral blood mononuclear cells were freshly isolated from young healthy donors. Serum zinc levels and Adjusted Zinc Diet Score (AZDS) were determined. NK cells, CD56<sup>dim</sup> NK cells, and CD56<sup>bright</sup> NK cells were analyzed <em>ex vivo</em> or cultivated in zinc-deficient, zinc-adequate, and zinc-supplemented media for 1 or 20 h ± specific inhibitors. CD56<sup>dim</sup> NK cell frequencies, phenotype, and functionality were analyzed via flow cytometry, qPCR, and Western blot.</div></div><div><h3>Results</h3><div>The frequencies of cytotoxic CD56<sup>dim</sup> NK cells positively correlated with serum zinc as well as AZDS. CD69 expression was significantly increased after 20 h of zinc supplementation on CD56<sup>dim</sup> NK cells. CD69<sup>+</sup> CD56<sup>dim</sup> NK cells showed significant higher degranulation capacity and IFNγ production. Furthermore, NFκB inhibition upregulated CD69 expression and <em>NFKB</em> mRNA was significantly decreased in zinc-supplemented conditions. In addition, perforin levels were sensitive to zinc deprivation.</div></div><div><h3>Conclusion</h3><div>Extracellular zinc selectively activates CD56<sup>dim</sup> NK cells enhancing degranulation and IFNγ production. Zinc supplementation might be a useful tool for <em>in vitro</em> NK cell expansion protocols for future cellular therapies.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127788"},"PeriodicalIF":3.6,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145417361","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}
引用次数: 0
Gallic acid mitigates cadmium-induced reproductive damage: Effects on sperm, antioxidants, and apoptosis in mice 没食子酸减轻镉诱导的生殖损伤:对小鼠精子、抗氧化剂和细胞凋亡的影响。
IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-27 DOI: 10.1016/j.jtemb.2025.127789
Sanaz Alaee , Zahra Derakhshan , Farhad Koohpeyma , Saeed Shokri , Amirreza Talaie , Hesam Kamyab
Cadmium is a well-known reproductive toxicant found in many industrial wastes. The gallic acid impact on the recovery of reproductive ability of mice exposed to cadmium was investigated. The experiment involved six groups of male mice, designated as Groups 1 through 6, each receiving specific treatments: Group 1 received distilled water, Group 2 received water containing gallic acid with a concentration of 50 mg/kg, Group 3 received water containing gallic acid with a concentration 100 mg/kg, Group 4 was treated with water containing cadmium with a concentration of 1.2 mg/kg, Group 5 received water containing cadmium and gallic acid with concentrations of 1.2 mg/kg and 50 mg/kg, respectively, and finally Group 6 received water containing 1.2 and 100 mg/kg of cadmium and gallic acid, respectively. The mice's blood samples were collected after finishing the treatment stage to evaluate testosterone levels, and the testes were excised for stereological analysis and assessment of antioxidant and apoptotic marker expression. Sperm samples extracted from the epididymis were analyzed for quantity, morphology, motility, viability, maturation, and DNA fragmentation. Results indicated significant declines in all measured parameters in mice exposed to cadmium. Additionally, high doses of gallic acid adversely affected some fertility parameters in normal mice. In cadmium-exposed mice, mRNA expression of antioxidants (Gpx1, Cat, and Sod1) and anti-apoptotic (Bcl2l1) genes was significantly reduced, while the expression of proapoptotic (Caspase3 and Bax) genes increased. Notably, 50 mg/kg of gallic acid improved all fertility parameters in these mice. It is suggested that the high concentration of antioxidants can control oxidative stress, thereby disrupting the normal physiological level of reactive oxygen species in the mice's cells. Therefore, gallic acid at the appropriate dose improves fertility parameters in mice exposed to cadmium. The results showed that the dose of 50 mg/kg of gallic acid can effectively mitigate the cadmium detrimental impacts on the health of the vital organs of the male mice reproductive system. These findings suggest the potential therapeutic application of gallic acid in combating reproductive toxicity induced by cadmium, highlighting the importance of dosage in achieving beneficial outcomes.
镉是一种众所周知的生殖毒性物质,存在于许多工业废物中。研究了没食子酸对镉暴露小鼠生殖能力恢复的影响。实验涉及六组雄性小鼠,分为第1组至第6组,每组接受特定治疗:第1组使用蒸馏水,第2组使用浓度为50 mg/kg的没食子酸水,第3组使用浓度为100 mg/kg的没食子酸水,第4组使用浓度为1.2 mg/kg的镉水,第5组使用浓度分别为1.2 mg/kg和50 mg/kg的镉和没食子酸水,最后第6组使用浓度分别为1.2和100 mg/kg的镉和没食子酸水。分别。治疗结束后采集小鼠血液样本评估睾酮水平,并切除睾丸进行体视学分析,评估抗氧化和凋亡标志物的表达。对从附睾中提取的精子样本进行数量、形态、活力、活力、成熟和DNA片段化分析。结果表明,暴露于镉的小鼠的所有测量参数都显著下降。此外,高剂量没食子酸对正常小鼠的一些生育参数有不利影响。在镉暴露小鼠中,抗氧化剂(Gpx1、Cat和Sod1)和抗凋亡基因(Bcl2l1) mRNA表达量显著降低,促凋亡基因(Caspase3和Bax) mRNA表达量升高。值得注意的是,50 mg/kg没食子酸改善了这些小鼠的所有生育参数。提示高浓度的抗氧化剂可以控制氧化应激,从而破坏小鼠细胞中正常的活性氧生理水平。因此,适当剂量的没食子酸可改善镉暴露小鼠的生育参数。结果表明,50 mg/kg剂量的没食子酸能有效减轻镉对雄性小鼠生殖系统重要器官健康的有害影响。这些发现提示没食子酸在对抗镉引起的生殖毒性方面的潜在治疗应用,强调了剂量在实现有益结果中的重要性。
{"title":"Gallic acid mitigates cadmium-induced reproductive damage: Effects on sperm, antioxidants, and apoptosis in mice","authors":"Sanaz Alaee ,&nbsp;Zahra Derakhshan ,&nbsp;Farhad Koohpeyma ,&nbsp;Saeed Shokri ,&nbsp;Amirreza Talaie ,&nbsp;Hesam Kamyab","doi":"10.1016/j.jtemb.2025.127789","DOIUrl":"10.1016/j.jtemb.2025.127789","url":null,"abstract":"<div><div>Cadmium is a well-known reproductive toxicant found in many industrial wastes. The gallic acid impact on the recovery of reproductive ability of mice exposed to cadmium was investigated. The experiment involved six groups of male mice, designated as Groups 1 through 6, each receiving specific treatments: Group 1 received distilled water, Group 2 received water containing gallic acid with a concentration of 50 mg/kg, Group 3 received water containing gallic acid with a concentration 100 mg/kg, Group 4 was treated with water containing cadmium with a concentration of 1.2 mg/kg, Group 5 received water containing cadmium and gallic acid with concentrations of 1.2 mg/kg and 50 mg/kg, respectively, and finally Group 6 received water containing 1.2 and 100 mg/kg of cadmium and gallic acid, respectively. The mice's blood samples were collected after finishing the treatment stage to evaluate testosterone levels, and the testes were excised for stereological analysis and assessment of antioxidant and apoptotic marker expression. Sperm samples extracted from the epididymis were analyzed for quantity, morphology, motility, viability, maturation, and DNA fragmentation. Results indicated significant declines in all measured parameters in mice exposed to cadmium. Additionally, high doses of gallic acid adversely affected some fertility parameters in normal mice. In cadmium-exposed mice, mRNA expression of antioxidants (<em>Gpx1</em>, <em>Cat</em>, and <em>Sod1</em>) and anti-apoptotic (<em>Bcl2l1</em>) genes was significantly reduced, while the expression of proapoptotic (<em>Caspase3</em> and <em>Bax</em>) genes increased. Notably, 50 mg/kg of gallic acid improved all fertility parameters in these mice. It is suggested that the high concentration of antioxidants can control oxidative stress, thereby disrupting the normal physiological level of reactive oxygen species in the mice's cells. Therefore, gallic acid at the appropriate dose improves fertility parameters in mice exposed to cadmium. The results showed that the dose of 50 mg/kg of gallic acid can effectively mitigate the cadmium detrimental impacts on the health of the vital organs of the male mice reproductive system. These findings suggest the potential therapeutic application of gallic acid in combating reproductive toxicity induced by cadmium, highlighting the importance of dosage in achieving beneficial outcomes.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127789"},"PeriodicalIF":3.6,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145411336","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}
引用次数: 0
Serum trace element and mineral levels and fecal microbiota in relation to cartilage damage in rheumatoid arthritis patients 类风湿关节炎患者血清微量元素和矿物质水平及粪便微生物群与软骨损伤的关系。
IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-26 DOI: 10.1016/j.jtemb.2025.127787
Anatoly V. Skalny , Tatiana V. Korobeinikova , Galina Morozova , Irina V. Menshikova , Viktor A. Gritsenko , Feng Zhang , Daria V. Mak , Xiong Guo , Tatiana I. Sotnikova , Michael Aschner , Alexey A. Tinkov
The objective of the present study was to evaluate serum trace element and mineral levels as well as taxonomic characteristics of gut microbiota and their association with cartilage damage in patients with rheumatoid arthritis (RA).

Materials and methods

Serum trace element and mineral levels in 41 healthy controls and 41 RA patients were assessed using inductively-coupled plasma mass-spectrometry. Taxonomic characteristics of fecal microbiota were assessed using 16S metagenomic sequencing. RA patients were characterized by increased cartilage oligomeric matrix protein (COMP) and complement component 3 (C3) levels, indicative of cartilage damage and inflammation.

Results

Serum Ca, Fe, Se, and Zn levels in RA patients were lower, whereas circulating Cr, Cu, and Mo concentrations exceeded the respective control values. 16S metagenomic sequencing of fecal samples revealed lower relative abundance of Firmicutes and Actinomycetota with a reduction in Firmicutes-to-Bacteroidetes ratio in RA patients. At the class level, the relative abundance of Bacilli, Coriobacteria, and Clostridia in RA patients was lower, whereas that of Bacteroidia and Negativicutes was higher compared to the control group. Tight negative association between serum Zn levels and the abundance of Bacteroidetes and Bacteroidia was observed, whereas correlation between Zn and Firmicutes-to-Bacteroidetes ratio was positive. Multiple linear regression analysis demonstrated that serum COMP level was inversely associated with serum Fe and Se levels, as well as relative abundance of Bacilli and Clostridia, being positively associated with serum Ca and C3 levels.

Conclusion

These novel findings demonstrate a multilateral relationship between trace element metabolism, gut microbiota, and cartilage damage in RA.
本研究的目的是评估血清微量元素和矿物质水平以及肠道微生物群的分类特征及其与类风湿性关节炎(RA)患者软骨损伤的关系。材料与方法:采用电感耦合等离子体质谱法测定41例健康对照者和41例RA患者血清微量元素和矿物质水平。采用16S宏基因组测序技术评估粪便微生物群的分类特征。RA患者的特点是软骨寡聚基质蛋白(COMP)和补体成分3 (C3)水平升高,表明软骨损伤和炎症。结果:RA患者血清Ca、Fe、Se和Zn水平较低,而循环Cr、Cu和Mo浓度超过各自的控制值。粪便样本的16S宏基因组测序显示RA患者中厚壁菌门和放线菌门的相对丰度较低,厚壁菌门与拟杆菌门的比例降低。在类水平上,RA患者的杆菌、Coriobacteria和Clostridia的相对丰度较低,Bacteroidia和Negativicutes的相对丰度高于对照组。血清锌水平与拟杆菌门(Bacteroidetes)和拟杆菌门(Bacteroidetes)丰度呈负相关,而与厚壁菌门与拟杆菌门(Bacteroidetes)之比呈正相关。多元线性回归分析表明,血清COMP水平与血清Fe、Se水平呈负相关,杆菌和梭状芽胞杆菌相对丰度与血清Ca、C3水平呈正相关。结论:这些新发现证明了RA中微量元素代谢、肠道微生物群和软骨损伤之间的多边关系。
{"title":"Serum trace element and mineral levels and fecal microbiota in relation to cartilage damage in rheumatoid arthritis patients","authors":"Anatoly V. Skalny ,&nbsp;Tatiana V. Korobeinikova ,&nbsp;Galina Morozova ,&nbsp;Irina V. Menshikova ,&nbsp;Viktor A. Gritsenko ,&nbsp;Feng Zhang ,&nbsp;Daria V. Mak ,&nbsp;Xiong Guo ,&nbsp;Tatiana I. Sotnikova ,&nbsp;Michael Aschner ,&nbsp;Alexey A. Tinkov","doi":"10.1016/j.jtemb.2025.127787","DOIUrl":"10.1016/j.jtemb.2025.127787","url":null,"abstract":"<div><div><strong>The objective</strong> of the present study was to evaluate serum trace element and mineral levels as well as taxonomic characteristics of gut microbiota and their association with cartilage damage in patients with rheumatoid arthritis (RA).</div></div><div><h3>Materials and methods</h3><div>Serum trace element and mineral levels in 41 healthy controls and 41 RA patients were assessed using inductively-coupled plasma mass-spectrometry. Taxonomic characteristics of fecal microbiota were assessed using 16S metagenomic sequencing. RA patients were characterized by increased cartilage oligomeric matrix protein (COMP) and complement component 3 (C3) levels, indicative of cartilage damage and inflammation.</div></div><div><h3>Results</h3><div>Serum Ca, Fe, Se, and Zn levels in RA patients were lower, whereas circulating Cr, Cu, and Mo concentrations exceeded the respective control values. 16S metagenomic sequencing of fecal samples revealed lower relative abundance of <em>Firmicutes</em> and <em>Actinomycetota</em> with a reduction in <em>Firmicutes</em>-to-<em>Bacteroidetes</em> ratio in RA patients. At the class level, the relative abundance of Bacilli, <em>Coriobacteria</em>, and <em>Clostridia</em> in RA patients was lower, whereas that of <em>Bacteroidia</em> and <em>Negativicutes</em> was higher compared to the control group. Tight negative association between serum Zn levels and the abundance of <em>Bacteroidetes</em> and <em>Bacteroidia</em> was observed, whereas correlation between Zn and <em>Firmicutes</em>-to-<em>Bacteroidetes</em> ratio was positive. Multiple linear regression analysis demonstrated that serum COMP level was inversely associated with serum Fe and Se levels, as well as relative abundance of <em>Bacilli</em> and <em>Clostridia</em>, being positively associated with serum Ca and C3 levels.</div></div><div><h3>Conclusion</h3><div>These novel findings demonstrate a multilateral relationship between trace element metabolism, gut microbiota, and cartilage damage in RA.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127787"},"PeriodicalIF":3.6,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454468","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}
引用次数: 0
Anticancer activity of the new manganese(II), iron(II), nickel(II), copper(II), and zinc(II) complexes based on 1,2,4-triazoline-3-thione derivative 基于1,2,4-三唑啉-3-硫酮衍生物的新型锰(II)、铁(II)、镍(II)、铜(II)和锌(II)配合物的抗癌活性
IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-23 DOI: 10.1016/j.jtemb.2025.127786
Agnieszka Czylkowska , Suneel Lanka , Bartłomiej Rogalewicz , Anita Raducka , Ewelina Fornal , Magdalena Iwan , Joanna Kubik , Agnieszka Korga-Plewko , Ewelina Humeniuk , Marcin Świątkowski , Monika Pitucha , Anna Gajda , Aleksandra Lis , Paweł Szymański , Marek Smoluch , Andrzej Żarczyński , Aneta Drabińska , Bruno Cury Camargo , Jacek Szczytko
In this study, we report the anticancer evaluation, synthesis, and characterization of a novel organic ligand, 4-butyl-5-((1-methyl-1H-pyrrol-2-yl)methyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione and its five metal complexes based on Mn(II), Fe(II), Ni(II), Cu(II), and Zn(II) ions. All compounds were analyzed using elemental analysis, NMR and FTIR spectroscopies, magnetic measurements, ESR, and thermogravimetric analysis. Their antioxidant properties were evaluated using the ABTS and DPPH assays, and the anticancer activity was studied in silico via molecular docking and in vitro against a panel of cancer cell lines. Notably, the Fe(II), Ni(II), and Cu(II) complexes exhibited potent anticancer activity, with IC50 values of 40.66, 45.95, and 26.51 µM against MDA-MB-231 cells. Their mechanism of action was further investigated through gene expression analysis, cell cycle analysis, apoptosis detection, thiol level evaluation, and DNA damage assessment. The results revealed that Ni(II) and Cu(II) complexes are significantly cytotoxic, while the Fe(II) complex acts as a potent cytostatic agent. Importantly, all compounds demonstrated lower activity toward normal cells than the tested cancer cells.
在这项研究中,我们报道了一种新型有机配体,4-丁基-5-((1-甲基- 1h -吡咯-2-基)甲基)-2,4-二氢- 3h -1,2,4-三唑-3-硫酮及其基于Mn(II), Fe(II), Ni(II), Cu(II)和Zn(II)离子的五种金属配合物的抗癌评价,合成和表征。所有化合物均采用元素分析、核磁共振和红外光谱、磁测量、ESR和热重分析进行分析。利用ABTS和DPPH实验评估了它们的抗氧化性能,并通过分子对接和体外对一组癌细胞研究了它们的抗癌活性。值得注意的是,Fe(II)、Ni(II)和Cu(II)配合物显示出强大的抗癌活性,对MDA-MB-231细胞的IC50值分别为40.66、45.95和26.51 µM。通过基因表达分析、细胞周期分析、细胞凋亡检测、硫醇水平评价和DNA损伤评价进一步探讨其作用机制。结果表明,Ni(II)和Cu(II)配合物具有明显的细胞毒性,而Fe(II)配合物具有强效的细胞抑制剂作用。重要的是,所有化合物对正常细胞的活性都低于测试的癌细胞。
{"title":"Anticancer activity of the new manganese(II), iron(II), nickel(II), copper(II), and zinc(II) complexes based on 1,2,4-triazoline-3-thione derivative","authors":"Agnieszka Czylkowska ,&nbsp;Suneel Lanka ,&nbsp;Bartłomiej Rogalewicz ,&nbsp;Anita Raducka ,&nbsp;Ewelina Fornal ,&nbsp;Magdalena Iwan ,&nbsp;Joanna Kubik ,&nbsp;Agnieszka Korga-Plewko ,&nbsp;Ewelina Humeniuk ,&nbsp;Marcin Świątkowski ,&nbsp;Monika Pitucha ,&nbsp;Anna Gajda ,&nbsp;Aleksandra Lis ,&nbsp;Paweł Szymański ,&nbsp;Marek Smoluch ,&nbsp;Andrzej Żarczyński ,&nbsp;Aneta Drabińska ,&nbsp;Bruno Cury Camargo ,&nbsp;Jacek Szczytko","doi":"10.1016/j.jtemb.2025.127786","DOIUrl":"10.1016/j.jtemb.2025.127786","url":null,"abstract":"<div><div>In this study, we report the anticancer evaluation, synthesis, and characterization of a novel organic ligand, 4-butyl-5-((1-methyl-1H-pyrrol-2-yl)methyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione and its five metal complexes based on Mn(II), Fe(II), Ni(II), Cu(II), and Zn(II) ions. All compounds were analyzed using elemental analysis, NMR and FTIR spectroscopies, magnetic measurements, ESR, and thermogravimetric analysis. Their antioxidant properties were evaluated using the ABTS and DPPH assays, and the anticancer activity was studied <em>in silico via</em> molecular docking and <em>in vitro</em> against a panel of cancer cell lines. Notably, the Fe(II), Ni(II), and Cu(II) complexes exhibited potent anticancer activity, with IC<sub>50</sub> values of 40.66, 45.95, and 26.51 µM against MDA-MB-231 cells. Their mechanism of action was further investigated through gene expression analysis, cell cycle analysis, apoptosis detection, thiol level evaluation, and DNA damage assessment. The results revealed that Ni(II) and Cu(II) complexes are significantly cytotoxic, while the Fe(II) complex acts as a potent cytostatic agent. Importantly, all compounds demonstrated lower activity toward normal cells than the tested cancer cells.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127786"},"PeriodicalIF":3.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519791","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}
引用次数: 0
Boric acid protects against glyphosate-induced neurotoxicity by modulating oxidative stress, inflammation, apoptosis, and autophagy pathways in the rat brain 硼酸通过调节大鼠大脑中的氧化应激、炎症、细胞凋亡和自噬途径,保护大鼠免受草甘膦诱导的神经毒性
IF 3.6 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-22 DOI: 10.1016/j.jtemb.2025.127785
Tuba Dogan , Burak Cinar , Merve Bolat , İsmail Bolat , Esra Aktas Senocak , Omercan Alat , Samet Tekin , Burak Batuhan Lacin , Ahmet Hacimuftuogli , Mesut Bunyami Halici

Background

Glyphosate (GLY) is a widely used herbicide with increasing evidence of neurotoxic effects. Boric acid (BA), a trace element, has shown potential antioxidant and anti-inflammatory properties, but its role in GLY-induced neurotoxicity remains unexplored.

Objective

This study aimed to investigate the neuroprotective effects of boric acid against glyphosate-induced brain toxicity in rats through behavioral, biochemical, molecular, and histological evaluations.

Materials and methods

Twenty-eight adult rats were divided into four groups (n = 7): Control, BA (100 mg/kg), GLY (150 mg/kg), and GLY+BA. All treatments were given orally for 7 days. Behavioral assessments were performed using the Elevated Plus Maze and Locomotor Activity Test. Oxidative stress markers (MDA, GSH, SOD, CAT, GPx), apoptotic markers (Bax, Bcl-2, Caspase-3), and inflammatory proteins (TNF-α, IL-1β, IL-6, COX-2, TLR-4, NF-κB) were analyzed. Iba-1 and GFAP were assessed by Western blot, while histopathological and immunohistochemical evaluations included 8-OHdG, TLR2, and LC3A/B.

Results

GLY exposure led to significant behavioral deficits, oxidative stress, inflammation, apoptosis, and neuronal damage. BA co-treatment significantly improved behavioral performance, restored antioxidant balance, downregulated pro-inflammatory and apoptotic markers, and reduced glial activation and histological damage.

Conclusion

Boric acid exerts neuroprotective effects against GLY-induced neurotoxicity, likely via modulation of oxidative stress, inflammation, apoptosis, and autophagy pathways, supporting its therapeutic potential in chemical-induced brain injury.
草甘膦(GLY)是一种广泛使用的除草剂,越来越多的证据表明其具有神经毒性作用。硼酸(BA)是一种微量元素,已显示出潜在的抗氧化和抗炎特性,但其在gly诱导的神经毒性中的作用仍未被探索。目的通过行为学、生化、分子和组织学评价,探讨硼酸对草甘膦致大鼠脑毒性的神经保护作用。材料与方法将成年大鼠28只分为4组(n = 7):对照组、BA(100 mg/kg)组、GLY(150 mg/kg)组和GLY+BA组。所有治疗均为口服,疗程为7 d。行为评估采用高架迷宫和运动活动测试。分析氧化应激标志物(MDA、GSH、SOD、CAT、GPx)、凋亡标志物(Bax、Bcl-2、Caspase-3)和炎症蛋白(TNF-α、IL-1β、IL-6、COX-2、TLR-4、NF-κB)。Western blot检测Iba-1和GFAP,组织病理学和免疫组化检测包括8-OHdG、TLR2和LC3A/B。结果,暴露导致显著的行为缺陷、氧化应激、炎症、细胞凋亡和神经元损伤。BA联合治疗可显著改善行为表现,恢复抗氧化平衡,下调促炎和凋亡标志物,减少神经胶质活化和组织学损伤。结论硼酸可能通过调节氧化应激、炎症、细胞凋亡和自噬通路,对gly诱导的神经毒性具有神经保护作用,支持其在化学脑损伤中的治疗潜力。
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引用次数: 0
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Journal of Trace Elements in Medicine and Biology
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