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Scientific Reports Jun 2024In honey bees, circulation of blood (hemolymph) is driven by the peristaltic contraction of the heart vessel located in the dorsal part of the abdomen....
In honey bees, circulation of blood (hemolymph) is driven by the peristaltic contraction of the heart vessel located in the dorsal part of the abdomen. Chlorantraniliprole (CHL) is an insecticide of the anthranilic diamide class which main mode of action is to alter the function of intracellular Ca release channels (known as RyRs, for ryanodine receptors). In the honey bee, it was recently found to be more toxic when applied on the dorsal part of the abdomen, suggesting a direct cardiotoxicity. In the present study, a short-term exposure of semi-isolated bee hearts to CHL (0.1-10 µM) induces alterations of cardiac contraction. These alterations range from a slow-down of systole and diastole kinetics, to bradycardia and cardiac arrest. The bees heart wall is made of a single layer of semi-circular cardiomyocytes arranged concentrically all along the long axis of tube lumen. Since the heart tube is suspended to the cuticle through long tubular muscles fibers (so-called alary muscle cells), the CHL effects in ex-vivo heart preparations could result from the modulation of RyRs present in these skeletal muscle fibers as well as cardiomyocytes RyRs themselves. In order to specifically assess effects of CHL on cardiomyocytes, for the first time, intact heart cells were enzymatically dissociated from bees. Exposure of cardiomyocytes to CHL induces an increase in cytoplasmic calcium, cell contraction at the highest concentrations and depletion of intracellular stores. Electrophysiological properties of isolated cardiomyocytes were described, with a focus on voltage-gated Ca channels responsible for the cardiac action potentials depolarization phase. Two types of Ca currents were measured under voltage-clamp. Exposure to CHL was accompanied by a decrease in voltage-activated Ca currents densities. Altogether, these results show that chlorantraniliprole can cause cardiac defects in honey bees.
Topics: Animals; Bees; ortho-Aminobenzoates; Myocytes, Cardiac; Insecticides; Cardiotoxicity; Calcium; Myocardial Contraction; Heart; Ryanodine Receptor Calcium Release Channel; Diamide
PubMed: 38942905
DOI: 10.1038/s41598-024-65007-2 -
Molecules (Basel, Switzerland) Jun 2024Organic arsenic compounds such as -aminophenylarsine oxide (-APAO) are easier for structural optimization to improve drug-like properties such as pharmacokinetic...
Organic arsenic compounds such as -aminophenylarsine oxide (-APAO) are easier for structural optimization to improve drug-like properties such as pharmacokinetic properties, therapeutic efficacy, and target selectivity. In order to strengthen the selectivity of 4-(1,3,2-dithiarsinan-2-yl) aniline 7 to tumor cell, a thiourea moiety was used to strengthen the anticancer activity. To avoid forming a mixture of α/β anomers, the strategy of 2-acetyl's neighboring group participation was used to lock the configuration of 2,3,4,6-tetra--acetyl-β-d-glucopyranosyl isothiocyanate from 2,3,4,6-tetra--acetyl-α-d-glucopyranosyl bromide. 1-(4-(1,3,2-dithiarsinan-2-yl) aniline)-2-N-(2,3,4,6-tetra--acetyl-β-d-glucopyranos-1-yl)-thiourea 2 can increase the selectivity of human colon cancer cells HCT-116 (0.82 ± 0.06 μM vs. 1.82 ± 0.07 μM) to human embryonic kidney 293T cells (1.38 ± 0.01 μM vs. 1.22 ± 0.06 μM) from 0.67 to 1.68, suggesting a feasible approach to improve the therapeutic index of arsenic-containing compounds as chemotherapeutic agents.
Topics: Humans; Thiourea; Antineoplastic Agents; Drug Design; Glucose; Cell Line, Tumor; Cell Proliferation; HCT116 Cells; Molecular Structure; Arsenicals; Structure-Activity Relationship
PubMed: 38930915
DOI: 10.3390/molecules29122850 -
Methods in Molecular Biology (Clifton,... 2024Redox modulation is a common posttranslational modification to regulate protein activity. The targets of oxidizing agents are cysteine residues (Cys), which have to be...
Redox modulation is a common posttranslational modification to regulate protein activity. The targets of oxidizing agents are cysteine residues (Cys), which have to be exposed at the surface of the proteins and are characterized by an environment that favors redox modulation. This includes their protonation state and the neighboring amino acids. The Cys redox state can be assessed experimentally by redox titrations to determine the midpoint redox potential in the protein. Exposed cysteine residues and putative intramolecular disulfide bonds can be predicted by alignments with structural data using dedicated software tools and information on conserved cysteine residues. Labeling with light and heavy reagents, such as N-ethylmaleimide (NEM), followed by mass spectrometric analysis, allows for the experimental determination of redox-responsive cysteine residues. This type of thiol redox proteomics is a powerful approach to assessing the redox state of the cell, e.g., in dependence on environmental conditions and, in particular, under abiotic stress.
Topics: Cysteine; Oxidation-Reduction; Proteomics; Sulfhydryl Compounds; Stress, Physiological; Protein Processing, Post-Translational; Mass Spectrometry; Proteins
PubMed: 38869790
DOI: 10.1007/978-1-0716-3973-3_7 -
Analytical Chemistry Jun 2024Rapid tissue differentiation at the molecular level is a prerequisite for precise surgical resection, which is of special value for the treatment of malignant tumors,...
Rapid tissue differentiation at the molecular level is a prerequisite for precise surgical resection, which is of special value for the treatment of malignant tumors, such as glioblastoma (GBM). Herein, a SERS-active microneedle is prepared by modifying glutathione (GSH)-responsive molecules, 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), on the surface of Au@Ag substrates for the distinction of different GBM tissues. Since the Raman signals on the surface of the DTNB@Au@Ag microneedle can be collected by both portable and benchtop Raman spectrometers, the distribution of GSH in different tissues at centimeter scale can be displayed through Raman spectroscopy and Raman imaging, and the entire analysis process can be accomplished within 12 min. Accordingly, in vivo brain tissues of orthotopic GBM xenograft mice and ex vivo tissues of GBM patients are accurately differentiated with the microneedle, and the results are well consistent with tissue staining and postoperative pathological reports. In addition, the outline of tumor, peritumoral, and normal tissues can be indicated by the DTNB@Au@Ag microneedle for at least 56 days. Considering that the tumor tissues are quickly discriminated at the molecular level without the restriction of depth, the DTNB@Au@Ag microneedle is promising to be a powerful intraoperative diagnostic tool for surgery navigation.
Topics: Glioblastoma; Spectrum Analysis, Raman; Animals; Humans; Glutathione; Gold; Mice; Brain Neoplasms; Needles; Silver; Mice, Nude; Dithionitrobenzoic Acid; Cell Line, Tumor; Metal Nanoparticles
PubMed: 38867357
DOI: 10.1021/acs.analchem.4c00483 -
Optics Express May 2024In this paper, a highly integrated terahertz (THz) biosensor is proposed and implemented, which pioneered the preparation of low-temperature gallium arsenide (LT-GaAs)...
In this paper, a highly integrated terahertz (THz) biosensor is proposed and implemented, which pioneered the preparation of low-temperature gallium arsenide (LT-GaAs) thin film photoconductive antenna (PCA) on the sensor for direct generation and detection of THz waves, simplifying complex terahertz time-domain spectroscopy (THz-TDS) systems. A latch type metasurface is deposited in the detection region to produce a resonance absorption peak at 0.6 THz that is independent of polarisation. Microfluidics is utilised and automatic injection is incorporated to mitigate the experimental effects of hydrogen bond absorption of THz waves in aqueous-based environment. Additionally, cell damage is minimised by regulating the cell flow rate. The biosensor was utilised to detect the concentration of three distinct sizes of bacteria with successful results. The assay was executed as a proof of concept to detect two distinct types of breast cancer cells. Based on the experimental findings, it has been observed that the amplitude and blueshift of the resonance absorption peaks have the ability to identify and differentiate various cancer cell types. The findings of this study introduce a novel approach for developing microfluidic THz metasurface biosensors that possess exceptional levels of integration, sensitivity, and rapid label-free detection capabilities.
Topics: Gallium; Arsenicals; Biosensing Techniques; Terahertz Spectroscopy; Humans; Equipment Design; Microfluidics
PubMed: 38858883
DOI: 10.1364/OE.518638 -
PeerJ 2024To investigate the effects of arsenic trioxide (ATO) on human colorectal cancer cells (HCT116) growth and the role of transient receptor potential melastatin 4 (TRPM4)...
BACKGROUND
To investigate the effects of arsenic trioxide (ATO) on human colorectal cancer cells (HCT116) growth and the role of transient receptor potential melastatin 4 (TRPM4) channel in this process.
METHODS
The viability of HCT116 cells was assessed using the CCK-8 assay. Western blot analysis was employed to examine the protein expression of TRPM4. The apoptosis of HCT116 cells was determined using TUNEL and Flow cytometry. Cell migration was assessed through the cell scratch recovery assay and Transwell cell migration assay. Additionally, Transwell cell invasion assay was performed to determine the invasion ability of HCT116 cells.
RESULTS
ATO suppressed the viability of HCT116 cells in a dose-dependent manner, accompanied by a decline in cell migration and invasion, and an increase in apoptosis. 9-phenanthroline (9-Ph), a specific inhibitor of TRPM4, abrogated the ATO-induced upregulation of TRPM4 expression. Additionally, blocking TRPM4 reversed the effects of ATO on HCT116 cells proliferation, including restoration of cell viability, migration and invasion, as well as the inhibition of apoptosis.
CONCLUSION
ATO inhibits CRC cell growth by inducing TRPM4 expression, our findings indicate that ATO is a promising therapeutic strategy and TRPM4 may be a novel target for the treatment of CRC.
Topics: Humans; TRPM Cation Channels; Arsenic Trioxide; Colorectal Neoplasms; HCT116 Cells; Cell Movement; Apoptosis; Cell Proliferation; Cell Survival; Oxides; Antineoplastic Agents; Neoplasm Invasiveness; Arsenicals
PubMed: 38854798
DOI: 10.7717/peerj.17559 -
Immunopharmacology and Immunotoxicology Jun 2024Myelodysplastic syndrome (MDS) is a prevalent hematological neoplastic disorder in clinics and its immunopathogenesis has garnered growing interest. Oral and intravenous... (Comparative Study)
Comparative Study
BACKGROUND
Myelodysplastic syndrome (MDS) is a prevalent hematological neoplastic disorder in clinics and its immunopathogenesis has garnered growing interest. Oral and intravenous arsenic agents have long been used to treat hematological malignancies. The main component of oral arsenic is realgar (arsenic disulfide), while arsenic trioxide is the main component of intravenous arsenic.
METHODS
This study aimed to assess the effects of ATO and Realgar on the enhancement of peripheral blood, drug safety, and T cell immune status in the NUP98-HOXD13 (NHD13) mice model of MDS, specifically in the peripheral blood, spleen, and liver.
RESULTS
The study findings indicate that realgar and arsenic trioxide (ATO) can improve peripheral hemogram in mice, whereas realgar promotes higher peripheral blood cell production than ATO. Furthermore, the clinical administration method and dose did not cause significant toxicity or side effects and thus can be considered safe. Coexistence and interconversion of hyperimmune function and immunosuppression in mice were also observed in this study. In addition, there were interactions between immune cells in the peripheral blood, spleen, and liver to regulate the immune balance of the body and activate immunity T-cell activation.
CONCLUSION
In summary, oral and intravenous arsenic agents are beneficial in improving peripheral hemogram and immunity in mice.
Topics: Animals; Arsenic Trioxide; Arsenicals; Mice; Disease Models, Animal; Myelodysplastic Syndromes; Sulfides; Disulfides; T-Lymphocytes; Spleen
PubMed: 38816179
DOI: 10.1080/08923973.2024.2344158 -
Journal of Colloid and Interface Science Oct 2024With the advancement of wearable and implantable medical devices, hydrogel flexible bioelectronic devices have attracted significant interest due to exhibiting...
With the advancement of wearable and implantable medical devices, hydrogel flexible bioelectronic devices have attracted significant interest due to exhibiting tissue-like mechanical compliance, biocompatibility, and low electrical resistance. In this study, the development and comprehensive performance evaluation of poly(acrylic acid)/ N,N'-bis(acryloyl) cystamine/ 1-butyl-3-ethenylimidazol-1-ium:bromide (PAA/NB/IL) hydrogels designed for flexible sensor applications are introduced. Engineered through a combination of physical and chemical cross-linking strategies, these hydrogels exhibit strong mechanical properties, high biocompatibility, and effective sensing capabilities. At 95 % strain, the compressive modulus of PAA/NB/IL 100 reach up to 3.66 MPa, with the loading-unloading process showing no significant hysteresis loop, indicating strong mechanical stability and elasticity. An increase in the IL content was observed to enlarge the porosity of the hydrogels, thereby influencing their swelling behavior and sensing functionality. Biocompatibility assessments revealed that the hemolysis rate was below 5 %, ensuring their suitability for biomedical applications. Upon implantation in rats, a minimal acute inflammatory response was observed, comparable to that of the biocompatibility control poly(ethylene glycol) diacrylate (PEGDA). These results suggest that PAA/NB/IL hydrogels hold promise as biomaterials for biosensors, offering a balance of mechanical integrity, physiological compatibility, and sensing sensitivity, thereby facilitating advanced healthcare monitoring solutions.
Topics: Hydrogels; Biosensing Techniques; Animals; Rats; Biocompatible Materials; Acrylic Resins; Humans; Surface Properties; Cystamine; Particle Size; Imidazoles; Hemolysis
PubMed: 38815387
DOI: 10.1016/j.jcis.2024.05.142 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... May 2024This study employed knowledge graph technology to analyze the research status and hot spots of Realgar and provide guidance for clinical application and further research...
This study employed knowledge graph technology to analyze the research status and hot spots of Realgar and provide guidance for clinical application and further research of this drug. The research articles both in English and Chinese involving Realgar were retrieved from five databases including CNKI, Wanfang, VIP, SinoMed, and Web of Science. And NoteExpress, a literature management software was used to screen literature. CiteSpace was utilized for visualized analysis and presentations of the authors, institutions, and keywords. 2 879 articles in Chinese and 194 articles in English were included. China Journal of Chinese Materia Medica and Journal of Ethnopharmacology were the top Chinese and English journals in terms of publication volume. Realgar is widely used in the treatment of skin diseases, blood diseases, and cancer. JIANG Hong was the author who have published more articles in Chinese and English working with teams. School of Public Health of China Medical University and China Academy of Chinese Medical Sciences published the most articles in Chinese and English. The research on Realgar mainly focuses on clinical application, mechanism of action, reduction of toxicity, and enhancement of efficacy. The authors and institutions of Realgar research are mainly concentrated in China. The study on the mechanism of treating hematological diseases and cancer with Realgar, as well as the research on its effects of reducing toxicity and enhancing efficacy, are the current research hotspots. The mechanism of "same treatment for different diseases" in Realgar needs to be further explored. It is urgent to carry out interdisciplinary research on Realgar. This study can provide a refe-rence for the clinical application of Realgar and provide ideas for further research on Realgar.
Topics: Humans; Arsenicals; China; Sulfides; Drugs, Chinese Herbal; Biomedical Research
PubMed: 38812149
DOI: 10.19540/j.cnki.cjcmm.20240207.501 -
Redox Biology Jul 2024Intracellular redox homeostasis in the airway epithelium is closely regulated through adaptive signaling and metabolic pathways. However, inhalational exposure to...
Intracellular redox homeostasis in the airway epithelium is closely regulated through adaptive signaling and metabolic pathways. However, inhalational exposure to xenobiotic stressors such as secondary organic aerosols (SOA) can alter intracellular redox homeostasis. Isoprene hydroxy hydroperoxide (ISOPOOH), a ubiquitous volatile organic compound derived from the atmospheric photooxidation of biogenic isoprene, is a major contributor to SOA. We have previously demonstrated that exposure of human airway epithelial cells (HAEC) to ISOPOOH induces oxidative stress through multiple mechanisms including lipid peroxidation, glutathione oxidation, and alterations of glycolytic metabolism. Using dimedone-based reagents and copper catalyzed azo-alkynyl cycloaddition to tag intracellular protein thiol oxidation, we demonstrate that exposure of HAEC to micromolar levels of ISOPOOH induces reversible oxidation of cysteinyl thiols in multiple intracellular proteins, including GAPDH, that was accompanied by a dose-dependent loss of GAPDH enzymatic activity. These results demonstrate that ISOPOOH induces an oxidative modification of intracellular proteins that results in loss of GAPDH activity, which ultimately impacts the dynamic regulation of the intracellular redox homeostatic landscape in HAEC.
Topics: Humans; Oxidation-Reduction; Epithelial Cells; Sulfhydryl Compounds; Oxidative Stress; Glyceraldehyde-3-Phosphate Dehydrogenases; Hemiterpenes; Peroxides
PubMed: 38810423
DOI: 10.1016/j.redox.2024.103199