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Frontiers in Public Health 2024An increasing number of studies suggest that environmental pollution may increase the risk of vitamin D deficiency (VDD). However, less is known about arsenic (As)...
BACKGROUND
An increasing number of studies suggest that environmental pollution may increase the risk of vitamin D deficiency (VDD). However, less is known about arsenic (As) exposure and VDD, particularly in Chinese pregnant women.
OBJECTIVES
This study examines the correlations of different urinary As species with serum 25 (OH) D and VDD prevalence.
METHODS
We measured urinary arsenite (As), arsenate (As), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) levels and serum 25(OH)D, 25(OH)D, 25(OH) D levels in 391 pregnant women in Tianjin, China. The diagnosis of VDD was based on 25(OH) D serum levels. Linear relationship, Logistic regression, and Bayesian kernel machine regression (BKMR) were used to examine the associations between urinary As species and VDD.
RESULTS
Of the 391 pregnant women, 60 received a diagnosis of VDD. Baseline information showed significant differences in As, DMA, and tAs distribution between pregnant women with and without VDD. Logistic regression showed that As was significantly and positively correlated with VDD (OR: 4.65, 95% CI: 1.79, 13.32). Meanwhile, there was a marginally significant positive correlation between tAs and VDD (OR: 4.27, 95% CI: 1.01, 19.59). BKMR revealed positive correlations between As, MMA and VDD. However, negative correlations were found between As, DMA and VDD.
CONCLUSION
According to our study, there were positive correlations between iAs, especially As, MMA and VDD, but negative correlations between other As species and VDD. Further studies are needed to determine the mechanisms that exist between different As species and VDD.
Topics: Humans; Female; Vitamin D Deficiency; Pregnancy; Cross-Sectional Studies; China; Adult; Arsenic; Prevalence; Arsenicals; Vitamin D; Pregnancy Complications; Logistic Models; East Asian People
PubMed: 38694994
DOI: 10.3389/fpubh.2024.1371920 -
Carbohydrate Polymers Jul 2024The standard treatment for early-stage breast cancer involves breast-conserving surgery followed by adjuvant radiotherapy. However, approximately 20 % of patients...
The standard treatment for early-stage breast cancer involves breast-conserving surgery followed by adjuvant radiotherapy. However, approximately 20 % of patients experience distant metastasis, and adjuvant radiotherapy often leads to radiation-induced skin fibrosis (RISF). In this study, we develop an on-site injectable formulation composed of selenocystamine (SeCA) and hyaluronic acid (HyA), referred to as SeCA cross-linked HyA (SCH) agent, and investigate its potential to mitigate metastasis and prevent RISF associated with breast cancer therapy. SCH agents are synthesized using the nanoprecipitation method to modulate cell-cell tight junctions and tissue inflammation. The toxicity assessments reveal that SCH agents with a higher Se content (Se payload 17.4 μg/mL) are well tolerated by L929 cells compared to SeCA (Se payload 3.2 μg/mL). In vitro, SCH agents significantly enhance cell-cell tight junctions and effectively mitigate migration and invasion of breast cancer cells (4T1). In vivo, SCH agents mitigate distant lung metastasis. Furthermore, in animal models, SCH agents reduce RISF and promote wound repair. These findings highlight the potential of SCH agents as a novel therapeutic formulation for effectively mitigating metastasis and reducing RISF. This holds great promise for improving clinical outcomes in breast cancer patients undergoing adjuvant radiotherapy.
Topics: Hyaluronic Acid; Animals; Female; Breast Neoplasms; Mice; Fibrosis; Cell Line, Tumor; Humans; Mice, Inbred BALB C; Cystamine; Skin; Cell Movement; Injections
PubMed: 38670762
DOI: 10.1016/j.carbpol.2024.122136 -
ACS Sensors May 2024Nucleic acid-based electrochemical sensors (NBEs) use oligonucleotides as affinity reagents for the detection of a variety of targets, ranging from small-molecule... (Review)
Review
Nucleic acid-based electrochemical sensors (NBEs) use oligonucleotides as affinity reagents for the detection of a variety of targets, ranging from small-molecule therapeutics to whole viruses. Because of their versatility in molecular sensing, NBEs are being developed broadly for diagnostic and biomedical research applications. Benchmark NBEs are fabricated via self-assembly of thiol-based monolayers on gold. Although robust for rapid prototyping, thiol monolayers suffer from limitations in terms of stability under voltage modulation and in the face of competitive ligands such as thiolated molecules naturally occurring in biofluids. Additionally, gold cannot be deployed as an NBE substrate for all biomedical applications, such as in cases where molecular measurements coupled to real-time, under-the-sensor tissue imaging is needed. Seeking to overcome these limitations, the field of NBEs is pursuing alternative ligands and electrode surfaces. In this perspective, I discuss new interface fabrication strategies that have successfully achieved NBE sensing, or that have the potential to allow NBE sensing on conductive surfaces other than gold. I hope this perspective will provide the reader with a fresh view of how future NBE interfaces could be constructed and will serve as inspiration for the pursuit of collaborative developments in the field of NBEs.
Topics: Sulfhydryl Compounds; Electrochemical Techniques; Gold; Biosensing Techniques; Nucleic Acids; Electrodes; Humans
PubMed: 38661283
DOI: 10.1021/acssensors.4c00331 -
Archives of Toxicology Jul 2024Arsenic is highly toxic to the human bladder. In the present study, we established a human bladder epithelial cell line that closely mimics normal human bladder...
Arsenic is highly toxic to the human bladder. In the present study, we established a human bladder epithelial cell line that closely mimics normal human bladder epithelial cells by immortalizing primary uroplakin 1B-positive human bladder epithelial cells with human telomerase reverse transcriptase (HBladEC-T). The uroplakin 1B-positive human bladder epithelial cell line was then used to evaluate the toxicity of seven arsenicals (iAs, iAs, MMA, MMA, DMA, DMA, and DMMTA). The cellular uptake and metabolism of each arsenical was different. Trivalent arsenicals and DMMTA exhibited higher cellular uptake than pentavalent arsenicals. Except for MMA, arsenicals were transported into cells by aquaglyceroporin 9 (AQP9). In addition to AQP9, DMA and DMMTA were also taken up by glucose transporter 5. Microarray analysis demonstrated that arsenical treatment commonly activated the NRF2-mediated oxidative stress response pathway. ROS production increased with all arsenicals, except for MMA. The activating transcription factor 3 (ATF3) was commonly upregulated in response to oxidative stress in HBladEC-T cells: ATF3 is an important regulator of necroptosis, which is crucial in arsenical-induced bladder carcinogenesis. Inorganic arsenics induced apoptosis while MMA and DMA induced necroptosis. MMA, DMA, and DMMTA induced both cell death pathways. In summary, MMA exhibited the strongest cytotoxicity, followed by DMMTA, iAs, DMA, iAs, DMA, and MMA. The cytotoxicity of the tested arsenicals on HBladEC-T cells correlated with their cellular uptake and ROS generation. The ROS/NRF2/ATF3/CHOP signaling pathway emerged as a common mechanism mediating the cytotoxicity and carcinogenicity of arsenicals in HBladEC-T cells.
Topics: Humans; Epithelial Cells; Urinary Bladder; Arsenicals; Reactive Oxygen Species; Oxidative Stress; Activating Transcription Factor 3; NF-E2-Related Factor 2; Cell Line; Apoptosis; Cell Survival
PubMed: 38630284
DOI: 10.1007/s00204-024-03750-1 -
Journal of Integrative Medicine May 2024The effects of arsenic trioxide (AsO) on hepatocellular carcinoma have been documented widely. Autophagy plays dual roles in the survival and death of cancer cells....
OBJECTIVE
The effects of arsenic trioxide (AsO) on hepatocellular carcinoma have been documented widely. Autophagy plays dual roles in the survival and death of cancer cells. Therefore, we investigated the exact role of autophagy in AsO-induced apoptosis in liver cancer cells.
METHODS
The viability of hepatoma cells was determined using the MTT assay with or without fetal bovine serum. The rate of apoptosis in liver cancer cells treated with AsO was evaluated using flow cytometry, Hoechst 33258 staining, and TUNEL assays. The rate of autophagy among liver cancer cells treated with AsO was detected using immunofluorescence, Western blot assay and transmission electron microscopy.
RESULTS
Upon treatment with AsO, the viability of HepG2 and SMMC-7721 cells was decreased in a time- and dose-dependent manner. The apoptosis rates of both liver cancer cell lines increased with the concentration of AsO, as shown by flow cytometry. Apoptosis in liver cancer cells treated with AsO was also shown by the activation of the caspase cascade and the regulation of Bcl-2/Bax expression. Furthermore, AsO treatment induced autophagy in liver cancer cells; this finding was supported by Western blot, immunofluorescence of LC3-II and beclin 1, and transmission electron microscopy. In liver cancer cells, AsO inhibited the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signal pathway that plays a vital role in both apoptosis and autophagy. The PI3K activator SC-79 partially reversed AsO-induced autophagy and apoptosis. Furthermore, inhibiting autophagy with 3-methyladenine partially reversed the negative effects of AsO on cell viability. Serum starvation increased autophagy and amplified the effect of AsO on cell death.
CONCLUSION
AsO induces apoptosis and autophagy in liver cancer cells. Autophagy induced by AsO may have a proapoptotic effect that helps to reduce the viability of liver cancer cells. This study provides novel insights into the effects of AsO against liver cancer. Please cite this article as: Deng ZT, Liang SF, Huang GK, Wang YQ, Tu XY, Zhang YN, Li S, Liu T, Cheng BB. Autophagy plays a pro-apoptotic role in arsenic trioxide-induced cell death of liver cancer. J Integr Med. 2024; 22(3): 295-302.
Topics: Arsenic Trioxide; Humans; Autophagy; Arsenicals; Liver Neoplasms; Apoptosis; Oxides; Antineoplastic Agents; Cell Line, Tumor; Carcinoma, Hepatocellular; Hep G2 Cells; Cell Survival
PubMed: 38599914
DOI: 10.1016/j.joim.2024.03.011 -
Analytical Chemistry Apr 2024Cysteine (Cys) and its oxidized form, cystine (Cys2), play crucial roles in biological systems and have considerable applications in cell culture. However, Cys in cell...
Acidic Derivatization of Thiols Using Diethyl 2-Methylenemalonate: Thiol-Michael Addition Click Reaction for Simultaneous Analysis of Cysteine and Cystine in Culture Media Using LC-MS/MS.
Cysteine (Cys) and its oxidized form, cystine (Cys2), play crucial roles in biological systems and have considerable applications in cell culture. However, Cys in cell culture media is easily oxidized to Cys2, leading to solubility issues. Traditional analytical methods struggle to maintain the oxidation states of Cys and Cys2 during analysis, posing a significant challenge to accurately measuring and controlling these compounds. To effectively control the Cys and Cys2 levels, a rapid and accurate analytical method is required. Here, we screened derivatizing reagents that can react with Cys even under acidic conditions to realize a novel analytical method for simultaneously determining Cys and Cys2 levels. Diethyl 2-methylenemalonate (EMM) was found to possess the desired traits. EMM, characterized by its dual electron-withdrawing attributes, allowed for a rapid reaction with Cys under acidic conditions, preserving intact information for understanding the functions of target compounds. Combined with LC-MS/MS and an internal standard, this method provided high analytical accuracy in a short analytical time of 9 min. Using the developed method, the rapid oxidation of Cys in cell culture media was observed with the headspace of the storage container considerably influencing Cys oxidation and Cys2 precipitation rates. The developed method enabled the direct and simplified analysis of Cys behavior in practical media samples and could be used in formulating new media compositions, ensuring quality assurance, and real-time analysis of Cys and Cys2 in cell culture supernatants. This novel approach holds the potential to further enhance the media performance by enabling the timely optimal addition of Cys.
Topics: Chromatography, Liquid; Click Chemistry; Culture Media; Cysteine; Cystine; Liquid Chromatography-Mass Spectrometry; Malonates; Oxidation-Reduction; Sulfhydryl Compounds; Tandem Mass Spectrometry
PubMed: 38592893
DOI: 10.1021/acs.analchem.4c00700 -
Scientific Reports Apr 2024Phthorimaea absoluta is an invasive solanaceous plant pest with highly devastating effects on tomato plant. Heavy reliance on insecticide use to tackle the pest has been...
Phthorimaea absoluta is an invasive solanaceous plant pest with highly devastating effects on tomato plant. Heavy reliance on insecticide use to tackle the pest has been linked to insecticide resistance selection in P. absoluta populations. To underline insights on P. absoluta insecticide resistance mechanisms to diamides and avermectins, we evaluated the transcriptomic profile of parental (field-collected) and F8 (lab-reared) populations. Furthermore, to screen for the presence of organophosphate and pyrethroid resistance, we assessed the gene expression levels of acetylcholinesterase (ace1) and para-type voltage-gated sodium channel (VGSG) genes in the F1 to F8 lab-reared progeny of diamide and avermectin exposed P. absoluta field-collected populations. The VGSG gene showed up-regulation in 12.5% and down-regulation in 87.5% of the screened populations, while ace1 gene showed up-regulation in 37.5% and down-regulation in 62.5% of the screened populations. Gene ontology of the differentially expressed genes from both parental and eighth generations of diamide-sprayed P. absoluta populations revealed three genes involved in the metabolic detoxification of diamides in P. absoluta. Therefore, our study showed that the detoxification enzymes found could be responsible for P. absoluta diamide-based resistance, while behavioural resistance, which is stimulus-dependent, could be attributed to P. absoluta avermectin resistance.
Topics: Animals; Lepidoptera; Insecticides; Moths; Acetylcholinesterase; Diamide; Gene Expression Profiling; Larva; Ivermectin
PubMed: 38575641
DOI: 10.1038/s41598-024-58413-z -
Biochemistry Apr 2024Ferroptosis is a recently identified form of regulated cell death, characterized by excessive iron-dependent lipid peroxidation. Recent studies have demonstrated that...
Strong Protection by 4-Hydroxyestrone against Erastin-Induced Ferroptotic Cell Death in Estrogen Receptor-Negative Human Breast Cancer Cells: Evidence for Protein Disulfide Isomerase as a Mechanistic Target for Protection.
Ferroptosis is a recently identified form of regulated cell death, characterized by excessive iron-dependent lipid peroxidation. Recent studies have demonstrated that protein disulfide isomerase (PDI) is an important mediator of chemically induced ferroptosis and also a new target for protection against ferroptosis-associated cell death. In the present study, we identified that 4-hydroxyestrone (4-OH-E), a metabolic derivative of endogenous estrogen, is a potent small-molecule inhibitor of PDI, and can strongly protect against chemically induced ferroptotic cell death in the estrogen receptor-negative MDA-MB-231 human breast cancer cells. Pull-down and CETSA assays demonstrated that 4-OH-E can directly bind to PDI both in vitro and in intact cells. Computational modeling analysis revealed that 4-OH-E forms two hydrogen bonds with PDI His256, which is essential for its binding interaction and thus inhibition of PDI's catalytic activity. Additionally, PDI knockdown attenuates the protective effect of 4-OH-E as well as cystamine (a known PDI inhibitor) against chemically induced ferroptosis in human breast cancer cells. Importantly, inhibition of PDI by 4-OH-E and cystamine or PDI knockdown by siRNAs each markedly reduces iNOS activity and NO accumulation, which has recently been demonstrated to play an important role in erastin-induced ferroptosis. In conclusion, this study demonstrates that 4-OH-E is a novel inhibitor of PDI and can strongly inhibit ferroptosis in human breast cancer cells in an estrogen receptor-independent manner. The mechanistic understanding gained from the present study may also aid in understanding the estrogen receptor-independent cytoprotective actions of endogenous estrogen metabolites in many noncancer cell types.
Topics: Humans; Female; Protein Disulfide-Isomerases; Breast Neoplasms; Cystamine; Cell Death; Estrogens; Receptors, Estrogen; Hydroxyestrones; Piperazines
PubMed: 38569593
DOI: 10.1021/acs.biochem.3c00261 -
Journal of Hazardous Materials May 2024Arsenopyrite and pyrite often coexist in metal deposits and tailings, thus simultaneous bioleaching of both sulfides has economic (as well as environmental)...
Arsenopyrite and pyrite often coexist in metal deposits and tailings, thus simultaneous bioleaching of both sulfides has economic (as well as environmental) significance. Important targets in bio-oxidation operations are high solubilization rates and minimized accumulation of Fe(III)/As-bearing secondary products. This study investigated the role of pyrite bioleaching in the enhancement of arsenopyrite dissolution. At a pyrite to arsenopyrite mass ratio of 1:1, 93.6% of As and 93.0% of Fe were solubilized. The results show that pyrite bio-oxidation can promote arsenopyrite dissolution, enhance S bio-oxidation, and inhibit the formation of jarosites, tooeleite, and amorphous ferric arsenate. The dry weight of the pyrite & arsenopyrite residue was reduced by 95.1% after bioleaching, compared to the initial load, while only 5% weight loss was observed when pyrite was absent. A biofilm was formed on the arsenopyrite surface in the presence of pyrite, while a dense passivation layer was observed in the absence of pyrite. As(III) (as AsO) was a dominant As species in the pyrite & arsenopyrite residue. Novel and detailed findings are presented on arsenopyrite bio-dissolution in the presence of pyrite, and the presented approach could contribute to the development of novel cost-effective extractive bioprocesses. ENVIRONMENTAL IMPLICATION: The oxidation of arsenopyrite presents significant environmental hazards, as it can contribute to acid mine drainage generation and arsenic mobilization from sulfidic mine wastes. Bioleaching is a proven cost-effective and environmentally friendly extractive technology, which has been applied for decades in metal recovery from minerals or tailings. In this work, efficient extraction of arsenic from arsenopyrite bioleaching was presented through coupling the process with bio-oxidation of pyrite, resulting in lowered accumulation of hazardous and metastable Fe(III)/As-bearing secondary phases. The results could help improve current biomining operations and/or contribute to the development of novel cost-effective bioprocesses for metal extraction.
Topics: Sulfides; Iron; Arsenicals; Kinetics; Minerals; Iron Compounds; Oxidation-Reduction; Solubility; Arsenic; Biofilms; Acidithiobacillus
PubMed: 38569341
DOI: 10.1016/j.jhazmat.2024.134193 -
Journal of Medicinal Chemistry Apr 2024The success of arsenic in acute promyelocytic leukemia (APL) treatment is hardly transferred to non-APL cancers, mainly due to the low selectivity and weak binding...
The success of arsenic in acute promyelocytic leukemia (APL) treatment is hardly transferred to non-APL cancers, mainly due to the low selectivity and weak binding affinity of traditional arsenicals to oncoproteins critical for cancer survival. We present herein the reinvention of aliphatic trivalent arsenicals (As) as reversible covalent warheads of As-based targeting inhibitors toward Bruton's tyrosine kinase (BTK). The effects of As warheads' valency, thiol protection, methylation, spacer length, and size on inhibitors' activity were studied. We found that, in contrast to the bulky and rigid aromatic As warhead, the flexible aliphatic As warheads were well compatible with the well-optimized guiding group to achieve nanomolar inhibition against BTK. The optimized As inhibitors effectively blocked the BTK-mediated oncogenic signaling pathway, leading to elevated antiproliferative activities toward lymphoma cells and xenograft tumor. Our study provides a promising strategy enabling rational design of new aliphatic arsenic-based reversible covalent inhibitors toward non-APL cancer treatment.
Topics: Humans; Leukemia, Promyelocytic, Acute; Arsenicals; Arsenic; Agammaglobulinaemia Tyrosine Kinase; Signal Transduction; Protein Kinase Inhibitors
PubMed: 38556750
DOI: 10.1021/acs.jmedchem.3c02076