Journal of Trace Elements in Medicine and Biology最新文献

{"title":"Osteogenic and angiogenic potential of molybdenum-containing mesoporous bioactive glass nanoparticles: An ionic approach to bone tissue engineering","authors":"","doi":"10.1016/j.jtemb.2024.127518","DOIUrl":"10.1016/j.jtemb.2024.127518","url":null,"abstract":"<div><p>Biomaterials intended for application in bone tissue engineering (BTE) ideally stimulate osteogenesis and angiogenesis simultaneously, as both mechanisms are of critical importance for successful bone regeneration. Mesoporous bioactive glass nanoparticles (MBGNs) can be tailored towards specific biological needs, for example by addition of ions like Molybdenum (Mo). While Mo has been shown to enhance osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (BMSCs) as well as their ability to form and mature a primitive osseous extracellular matrix (ECM), there are contradictory findings regarding its impact on angiogenesis. In this study, the effects of Mo-MBGNs (mol%: 70 SiO₂, 25 CaO, 5 MoO₃) on viability, proliferation, osteogenic differentiation, ECM formation and angiogenic response of BMSCs were compared to undoped MBGNs (in mol%: 70 SiO₂, 30 CaO) and a control group of BMSCs. Furthermore, a human umbilical vein endothelial cells tube formation assay and a chorioallantoic membrane-assay using fertilized chicken eggs were used to analyze angiogenic properties. Mo-MBGNs were cytocompatible and promoted the proliferation of BMSCs. Furthermore, Mo-MBGNs showed promising osteogenic properties as they enhanced osteogenic differentiation, ECM formation and maturation as well as the gene expression and protein production of relevant osteogenic factors in BMSCs. However, despite the promising outcome on osteogenic properties, the addition of Mo to MBGNs resulted in anti-angiogenic effects. Due to the high relevance of vascularization in-vivo, the anti-angiogenic properties of Mo-MBGNs might hamper their osteogenic properties and therefore might restrict their performance in BTE applications. These limitations can be overcome by the addition of ions with distinct pro-angiogenic properties to the Mo-MBGNs-composition. Due to their promising osteogenic properties, Mo-MBGNs constitute a suitable basis for further research in the field of ionic (growth factor free) BTE.</p></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0946672X2400138X/pdfft?md5=3b2be0b6cb9abd899bd3d33371fdfb56&pid=1-s2.0-S0946672X2400138X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142136606","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}

{"title":"Investigation of the concentration and isotopic composition of Cu, Fe and Zn in human biofluids in the context of Alzheimer’s disease via tandem and multi-collector inductively coupled plasma-mass spectrometry","authors":"","doi":"10.1016/j.jtemb.2024.127515","DOIUrl":"10.1016/j.jtemb.2024.127515","url":null,"abstract":"<div><p>Studies on essential trace elements in the context of Alzheimer’s disease (AD) concluded that Cu, Fe and Zn interact with amyloid-β, accelerating plaque formation in the brain. Additionally, Cu and Fe in the vicinity of plaques produce reactive oxygen species (ROS) resulting in oxidative stress, whereas Zn plays a role in the antioxidant defence as a co-factor for antioxidants. In this work, the Cu, Fe and Zn concentrations and isotope ratios were determined in whole blood, blood serum and cerebrospinal fluid of 10 patients diagnosed with AD and 8 control individuals, using tandem (ICP-MS/MS) and multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS), respectively. In whole blood and blood serum of AD patients, a heavier Cu isotopic composition was observed (significant for whole blood only) compared to controls. Albumin levels in cerebrospinal fluid tend to increase with age, which could indicate an increased leakiness of the blood-brain barrier. In cerebrospinal fluid, a large variability was observed for the Cu and Fe isotope ratios, potentially resulting from that leakiness at the blood-brain barrier. Therefore, potential effects of AD on the concentration and isotopic composition of essential elements in cerebrospinal fluid related to amyloid-β formation could be hidden. Finally, in blood serum, Zn, urea and creatinine concentrations showed an increase with age and showed a significant difference between sexes.</p></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147228","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":"Associations of maternal serum concentration of iron-related indicators with gestational diabetes mellitus in Chinese: A pilot prospective cohort study","authors":"","doi":"10.1016/j.jtemb.2024.127514","DOIUrl":"10.1016/j.jtemb.2024.127514","url":null,"abstract":"<div><h3>Background</h3><p>We aimed to provide a comprehensive understanding of the associations between iron metabolism and gestational diabetes mellitus (GDM) by examining multiple iron-related indicators.</p></div><div><h3>Methods</h3><p>We conducted a prospective study involving 907 Chinese pregnant women. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum concentrations of iron-related indicators during the first trimester (≤ 14 weeks of gestation). GDM outcomes were measured through oral glucose tolerance tests (OGTT) conducted between weeks 24 and 28 of gestation.</p></div><div><h3>Results</h3><p>Subjects with iron-related indicators below the 10th percentile (except for serum iron and soluble transferrin receptor) had a higher risk of GDM compared to normal subjects (10th-90th percentiles). The ORs (95 %CI; p-value) were 1.88 (1.10, 3.20; P=0.020) for ferritin, 1.88 (1.10, 3.19; P=0.020) for hepcidin. Higher levels of ferritin (&gt; 90th percentile) were associated with a higher risk of abnormal fasting blood glucose, while lower levels (&lt; 10th percentile) of ferritin, hepcidin, and transferrin were associated with a higher risk of one-hour postprandial glucose ≥ 8.6 mmol/L in the OGTT.</p></div><div><h3>Conclusions</h3><p>Lower levels (&lt; 10th percentiles) of several iron-related indicators (ferritin, hepcidin, and transferrin) were associated with a higher risk of GDM and abnormal blood glucose compared to normal subjects.</p></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096619","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":"Effects of tauroursodeoxycholate on arsenic-induced hepatic injury in mice: A comparative transcriptomic analysis","authors":"","doi":"10.1016/j.jtemb.2024.127512","DOIUrl":"10.1016/j.jtemb.2024.127512","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Prolonged exposure to excessive arsenic (As) and its compounds can cause damage to multiple systems, including respiratory, cardiovascular, immune, nervous, and endocrine systems. Manifestations include changes in skin pigmentation, excessive keratosis on palms and soles, gastrointestinal symptoms, and anemia. The liver as an important detoxification organ of the body, is a significant target organ for arsenic toxicity, and liver diseases are common. So far, the molecular mechanism has not been fully elucidated. Evidence suggests that taurodeoxycholic acid (TUDCA) has a protective role in arsenic-induced liver injury. This study aims to reveal potential target genes at the transcriptional level following TUDCA intervention, providing insights for the intervention of arsenic-induced liver injury.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;The TUDCA intervention model of arsenic liver injury in C57BL/6 N mice was established. The experiment was divided into two phases and lasted for 24 weeks. The phase I trial (12 weeks) was divided into control, low, middle and high groups according to the dose of As. The phaseⅡtrial (12 weeks) was administered in combination with 10 mg/L sodium arsenite (the first stage high arsenic group) and TUDCA, so subsequent groups was named with H indicating high arsenic. Divide into four groups: control group(C), TUDCA solvent control group(H-Vehicle), TUDCA combined with As group(H-TUDCA), arsenic group (As). As was ingested through free water and TUDCA was administered to mice by gavage at a dose of 0.1 mL/10 g.b.w (100 mg/kg) once a day for 12 weeks. The differential expression gene (DEG) profile was obtained from the second batch of mouse liver tissues by RNA sequencing technology. Comparative transcriptomic analysis methods were used to identify co-varying DEGs between arsenic induction and TUDCA intervention, along with their associated pathways. QRT-PCR was utilized for validation.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Transcriptome results showed that 487 DEGs were identified after arsenic induction. TUDCA intervention identified 231 DEGs (p-values &lt; 0.05 and | log2(fold change) | &gt; 1). The comparison of \"AS vs C\" and \"H_TUDCA vs AS\" identified 65 covariant DEGs, and further screened the TUDCA pathways and related genes among these genes，six pathways and 11 genes (&lt;em&gt;Ccl21a, Ccr7, Mdm2, Slc2a4, Akr1b7, Pnpla3, Dusp8, Hspa1a, Cyp7a1, Cybrd1, Trpm6&lt;/em&gt;) were obtained. Next, we screened for covariant DEGs among the top 50 potential hub genes in arsenic-induced DEGS, and obtained 7 (&lt;em&gt;Hbb-bs, Hspa1a, Mdm2, Slc2a4, Ptk6, Egr1, and Dusp8&lt;/em&gt;). Finally, the intersection of Hub gene and pathway gene was selected as the target genes &lt;em&gt;Dusp8, Hspa1a, Mdm2 and Slc2a4.&lt;/em&gt; The sequencing results showed that the mRNA expressions of &lt;em&gt;Dusp8, Hspa1a&lt;/em&gt; and &lt;em&gt;Mdm2&lt;/em&gt; were significantly increased after arsenic induction, while the expression of &lt;em&gt;Slc2a4&lt;/em&gt; was significantly decreased (P&lt;0.0","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130069","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":"Linalool may have a therapeutic effect on cadmium-induced nephrotoxicity by regulating NF-κB/TNF and GRP78/CHOP signaling pathways","authors":"","doi":"10.1016/j.jtemb.2024.127510","DOIUrl":"10.1016/j.jtemb.2024.127510","url":null,"abstract":"<div><p>Cadmium (Cd) is an environmental pollutant heavy metal with nephrotoxic effect. One of the primary constituents of essential oils is Linalool (Lin), a monoterpene having a variety of pharmacological properties including antimicrobial, anti-inflammatory, and antioxidant effects. The purpose of this study was to ascertain how Lin affected endoplasmic reticulum stress (ERS) and pro-inflammatory mediators in Cd-induced nephrotoxicity. In the experiment, 28 male rats were randomly divided into four equal groups as control (no application), Cd (Cd at a dose of 3 mg/kg for the first 7 days), Cd+Lin (Cd at a dose of 3 mg/kg for the first 7 days and 100 mg/kg/day Lin) and Lin (100 mg/kg/day Lin) (n=7). The experiment was completed on the 15th day after all treatments were performed. Blood serum and kidney tissue samples were used for analyses. Cd-induced histopathological changes, inflammation, oxidative stress, and apoptosis were determined to increase in kidney tissue. However, it was observed that Cd-induced adverse effects in kidney tissue were mainly eliminated by Lin treatment. In conclusion, Lin demonstrated anti-inflammatory, anti-oxidant and anti-apoptotic effects in Cd-induced nephrotoxicity. Therefore, we believe that Lin may represent a high potential therapeutic strategy against renal tissue damage.</p></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096621","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":"Molecular and immunohistochemical alterations in fluoride-induced neurological impediment in adult rats","authors":"","doi":"10.1016/j.jtemb.2024.127511","DOIUrl":"10.1016/j.jtemb.2024.127511","url":null,"abstract":"<div><h3>Summary</h3><p>This study highlights the potential neurotoxic and impaired behavioral effects associated with high fluoride concentrations in drinking water.</p></div><div><h3>Purpose</h3><p>Fluoride is known to cause neurotoxicity, evinced by lower I.Q. levels in children from high-fluoride regions as compared to those in low-fluoride regions. Thus, the present study was designed to investigate the molecular mechanism behind the neurological and behavioural changes induced by sodium fluoride in Wistar rats.</p></div><div><h3>Material and methods</h3><p>A total of 24 female Wistar rats, aged six weeks and weighing approximately 150–220 g, were randomly divided into three groups: Group I (control) received reverse osmosis (R.O.) water, Group II received Sodium Fluoride (NaF) at 10 ppm, and Group III received NaF at 50 ppm in their drinking water for 60 days. The animals underwent behavioural tests including the Forced Swim Test (F.S.T.), Open Field Test (OFT), and Novel Object Recognition Test (N.O.R.T.), to assess any alterations in behaviour. After 60 days, the animals were euthanized, and their blood and brain samples were analysed to evaluate biochemical changes by Western Blot/I.H.C. analysis of B.A.X., Bcl2, LC3B, TLR4, PARP1, p53, Caspase, α-Synuclein, PARKIN, NeuN, KI67, DNM-1, and M.F.N. for assessing molecular pathways for toxicity.</p></div><div><h3>Results</h3><p>Impaired locomotion, memory impairment, and behaviour resembling depression in the animals were evinced by reduced mobility index in the F.S.T., discrimination index in the N.O.R.T., and reduced locomotor activity in the open field test results. Additionally, alterations in antioxidant levels and oxidative stress parameters were observed in the brain. The expression levels of various apoptotic and inflammatory biomarkers (B.A.X., Bcl2, TLR4, PARP1, p53, and Caspase) showed apoptosis in neurons. The confocal studies showed increased expression of inflammatory (α-Synuclein, PARKIN), apoptotic (LC3B, B.A.X., p53, KI67), and mitochondrial dysfunction (NeuN, DNM-1, M.F.N.) markers in fluoride-treated animals. Toxicity was more prominent in 50 ppm of fluoride-treated animals.</p></div><div><h3>Conclusion</h3><p>Fluoride showed potent neuronal toxicity as evidenced by alterations of various molecular markers.</p></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096519","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":"Serum and urinary cadmium and zinc profiles in breast cancer patients and their association with estrogen and HER-2 receptors, and redox status","authors":"","doi":"10.1016/j.jtemb.2024.127513","DOIUrl":"10.1016/j.jtemb.2024.127513","url":null,"abstract":"<div><h3>Background</h3><p>Cadmium, a metal implicated in environmental toxicity, is linked to tumor growth and cancer. On the other hand, zinc plays an essential function in oxidative stress and can counteract cadmium toxicity and carcinogenicity. This research aims to evaluate the urine and serum values of cadmium and zinc in breast cancer (BC) patients and their association with estrogen (ER) and HER-2 receptors, and redox status.</p></div><div><h3>Methods</h3><p>Forty BC patients and thirty healthy subjects participated in this study. Cadmium and zinc levels were measured in serum and urine samples by atomic absorption spectrophotometer. Redox status markers were determined by colorimetric methods.</p></div><div><h3>Results</h3><p>The amount of cadmium in the BC patients was substantially greater than in the healthy subjects. Zinc levels were significantly lower in patients with BC compared to controls. Breast cancer patients with ER-positive tumors had significantly higher urinary cadmium concentrations (U-Cd) compared to patients with ER-negative tumors. There was no significant difference between the parameters of redox status and the value of cadmium and zinc between patients with BC in the HER-2 subgroup. Malondialdehyde levels in the serum were substantially greater in BC patients than in healthy subjects. Total thiol level and catalase and superoxide dismutase activity in serum were considerably lower in BC patients than in healthy subjects.</p></div><div><h3>Conclusions</h3><p>The etiology of BC may be due to a disturbance in redox status and levels of elements. Increasing U-Cd and lowering zinc levels in the serum could be the risk factors for BC.</p></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142040977","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":"Deciphering the associations of selenium distribution in serum GPx-3 and selenoprotein P with cardiovascular risk factors in a healthy population with moderate levels of selenium: The ATTICA study","authors":"","doi":"10.1016/j.jtemb.2024.127509","DOIUrl":"10.1016/j.jtemb.2024.127509","url":null,"abstract":"<div><h3>Background</h3><p>Selenium (Se) is an essential micronutrient, important for human health. The relationship of Se with cardiovascular risk factors is still inconclusive, especially regarding the role of different selenoproteins. The present study evaluated the relation of total serum Se as well as its distribution in plasma selenoproteins, namely glutathione peroxidase 3 (GPx3) and selenoprotein P (SelP) with cardiovascular risk factors in a sex-specific manner, in a healthy population with moderate levels of Se. Methods: A sub-sample from the ATTICA Study’s database, consisting of 398 participants (160 females and 238 males) with data on Se and selenoproteins levels, was considered. GPx3, SelP and the main non-specific serum selenium containing protein, selenoalbumin (SeAlb) were simultaneously determined in human plasma by high-performance liquid chromatography (HPLC) coupled with inductively coupled plasma mass spectrometry (ICP-MS) at baseline. Results: Participants that belong to the highest tertiles of GPx3 and SelP presented the lowest blood pressure. Homocysteine was inversely associated with SelP and its ratio SelP/TSe in both sexes. In males, the lowest tertile of GPx3 showed lower adiponectin levels (0.66 ± 0.21 μg/mL) in comparison to the 2nd tertile of GPx3 (p=0.002), SelP was inversely associated with visceral adipose index (VAI) (-2.29 ± 0.81, p=0.005). Particularly, in males, the middle tertile of SelP had the lowest VAI values. Regarding females, lower Lp(a) concentration by 11.96 ± 5.84 mg/dL was observed in low SelP levels while higher leptin concentration by 2.30 ± 0.73 μg/L and lower fibrinogen concentration by 27.32 ± 13.30 mg/dL was detected in low GPx3 levels. Conclusion: Circulating selenoproteins exert differentiated effects on cardiovascular risk factors, some of them in a sex-specific manner.</p></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142076919","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":"Copper-induced pro-apoptotic response and its alleviation by Quercetin through autophagic modulation in HEPG2 cells","authors":"","doi":"10.1016/j.jtemb.2024.127508","DOIUrl":"10.1016/j.jtemb.2024.127508","url":null,"abstract":"<div><h3>Background</h3><p>Recent studies indicated that the liver is susceptible to Cu-induced stress as it stores and distributes the metal to other cellular organelles. To counteract the hepatocytic damage, a known polyphenol, quercetin, was employed for its remarkable antioxidant properties. Thus, the study aimed to assess quercetin’s potency against Cu-induced toxicity in HEPG2 cells.</p></div><div><h3>Methods</h3><p>The cellular viability of HEPG2 cells was carried out by MTT assay. All the cellular experiments were divided into control, Cu 100 µM, Cu 100 µM (with Q μM), Cu 300 µM, Cu 300 µM (with Q 50 nM), and only quercetin (50 nM). Following this, reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were evaluated in co-exposure studies. Moreover, rhodamine-123, Hoechst stain, monodansylcadaverine (MDC), and acridine orange (AO) stain were used to visualize the morphological changes under bright field and fluorescent microscopy. Subsequently, western blotting was adopted to determine the expression level of apoptotic and autophagic marker proteins.</p></div><div><h3>Results</h3><p>Copper increased intracellular ROS, resulted in morphological abnormalities, nuclear condensation, and disrupted MMP. Moreover, Cu caused apoptotic cell deaths characterized by overexpressed pro-apoptotic proteins such as poly (ADP-ribose) polymerase (PARP), cysteine-dependent aspartate-specific proteases 3 (Caspase 3), and Bcl-2-associated X protein (Bax) and downregulated anti-apoptotic proteins such as B-cell lymphoma 2 (Bcl-2), respectively. However, quercetin restored overexpressed pro-apoptotic proteins and induced autophagosome-bound microtubule-associated protein light chain-3 (LC3II) conversion from LC3I. Furthermore, Cu-modulated autophagy marker proteins, including sequestosome-1 (p62), heat shock cognate proteins (Hsc 70, Hsc 90), lysosome-associated membrane protein (LAMP-2A), and AMP-associated protein kinase (AMPK).</p></div><div><h3>Conclusion</h3><p>This study promotes the nutraceutical ability of quercetin to combat Cu-induced hepatotoxicity by understanding the intricate biological signaling pathways within cells.</p></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142040979","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":"Arsenic-induced disruption of circadian rhythms and glutamine anaplerosis in human urothelial carcinoma","authors":"","doi":"10.1016/j.jtemb.2024.127507","DOIUrl":"10.1016/j.jtemb.2024.127507","url":null,"abstract":"<div><p>Inorganic arsenic (iAs)-induced urothelial carcinoma (UC) develops into a poor-prognosis malignancy. Arsenic-induced oxidative stress contributes to circadian rhythm disruption altered metabolism. Glutamine anaplerosis is a common metabolic feature of rapidly proliferating malignant cells, in which glutaminase (GLS) is a key enzyme in this process. Therefore, this study intends to determine if arsenic-induced oxidative stress can alter circadian rhythms and promote glutamine anaplerosis. Exonic expression of core circadian molecules (<em>CLOCK</em>, <em>ARNTL</em>, and <em>NR1D1</em>) and <em>GLS</em> in varying grades of UC were assessed using 423 bladder cancer samples from the TCGA Urothelial Bladder Cancer (BLCA) dataset. The levels of circadian proteins and metabolic markers in 44 UC patients from non-black foot disease (BFD) and BFD areas were detected by immunohistochemistry. In vitro and in vivo experiments elucidated the regulatory mechanisms of arsenic-mediated circadian disturbance and metabolic alteration. Public database analysis showed that <em>ARNTL</em>, <em>NR1D1</em>, and <em>GLS</em> exhibited greater expression in more high-grade UC. Strong immunoreactivity for BMAL1, GLS, and low levels of NR1D1 were found in malignant urothelial lesions, especially in arsenic-exposed UC. Arsenic-induced overexpression of BMAL1 and GLS involves activation of NADH: quinone oxidoreductase 1 (NQO1), continuously altering the NADH oscillations to promote glutamate metabolism in SV-HUC-1, T24 and BFTC-905 cells. These phenomenon were also demonstrated in the urothelium of arsenic-exposed animals. The present findings highlight the potential clinical significance of BMAL1 and GLS in UC in the BFD region. Furthermore, these results suggest that arsenic interferes with circadian rhythm and glutamine anaplerosis by NADH oscillatory imbalance in urothelial cells and urothelial cancer cells, predisposing them to malignant development.</p></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977584","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}