The investigation of cytotoxic and apoptotic activity of Cl-amidine on the human U-87 MG glioma cell line.

BACKGROUND: Peptidyl (protein) arginine deiminases (PADs) provide the transformation of peptidyl arginine to peptidyl citrulline in the presence of calcium with posttranslational modification. The dysregulated PAD activity plays an important role on too many diseases including also the cancer. In this study, it has been aimed to determine the potential cytotoxic and apoptotic activity of chlorine-amidine (Cl-amidine) which is a PAD inhibitor and whose effectiveness has been shown in vitro and in vivo studies recently on human glioblastoma cell line Uppsala 87 malignant glioma (U-87 MG) forming an in vitro model for the glioblastoma multiforme (GBM) which is the most aggressive and has the highest mortality among the brain tumors. METHODS: In the study, the antiproliferative and apoptotic effects of Cl-amidine on GBM cancer model were investigated. The antiproliferative effects of Cl-amidine on U-87 MG cells were determined by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate method at the 24th and 48th hours. The apoptotic effects were analyzed by Annexin V and Propidium iodide staining, caspase-3 activation, and mitochondrial membrane polarization (5,5', 6,6'-tetrachloro-1,1', 3,3' tetraethyl benzimidazolyl carbocyanine iodide) methods in the flow cytometry. RESULTS: It has been determined that Cl-amidine exhibits notable antiproliferative properties on U-87 MG cell line in a time and concentration-dependent manner, as determined through the 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate assay. Assessment of apoptotic effects via Annexin V and Propidium iodide staining and 5,5', 6,6'-tetrachloro-1,1', 3,3' tetraethyl benzimidazolyl carbocyanine iodide methods has revealed significant efficacy, particularly following a 24-hour exposure period. It has been observed that Cl-amidine induces apoptosis in cells by enhancing mitochondrial depolarization, independently of caspase-3 activation. Furthermore, regarding its impact on healthy cells, it has been demonstrated that Cl-amidine shows lower cytotoxic effects when compared to carmustine, an important therapeutic agent for glioblastoma. CONCLUSION: The findings of this study have shown that Cl-amidine exhibits significant potential as an anticancer agent in the treatment of GBM. This conclusion is based on its noteworthy antiproliferative and apoptotic effects observed in U-87 MG cells, as well as its reduced cytotoxicity toward healthy cells in comparison to existing treatments. We propose that the antineoplastic properties of Cl-amidine should be further investigated through a broader spectrum of cancer cell types. Moreover, we believe that investigating the synergistic interactions of Cl-amidine with single or combination therapies holds promise for the discovery of novel anticancer agents.

Should we reconsider blocking the thyroid for 123 I-Ioflupane studies in elderly patients: quantifying radiation dose to the unblocked thyroid and implications for clinical practice.

OBJECTIVES: To measure the absorbed dose to the thyroid in patients injected with 123 I-Ioflupane where the thyroid was not blocked with prophylaxis to investigate whether thyroid blocking should be limited to younger patients. This risk from the additional absorbed dose to the thyroid was then compared to the risk from iodine overdose through ingestion of the iodide prophylaxis, resulting in iodine-induced hyper/hypothyroidism (IIH). METHODS: A cohort of patients (n = 30) who did not receive thyroid prophylaxis underwent static thyroid imaging 3 h after 123 I-Ioflupane administration. The measured thyroidal uptake of free 123 I was then extrapolated to peak uptake time (24 h post-administration). This value was used to calculate cumulated activity in the thyroid and thus thyroid-thyroid absorbed dose D(rthy←rthy ) using the relevant S-value in the MIRD method. RESULTS: Mean D(rthy←rthy ) was found to be 13.6 mGy with an SD of 8.8 mGy; this would contribute an additional 0.5 mSv to the effective dose. CONCLUSION: ARSAC recommends in its Notes for Guidance prophylactic thyroid blocking if the absorbed dose to the thyroid is >50 mGy; the maximum thyroid dose in this study cohort was 36.3 mGy. With risk from IIH and its associated cardiac complications increasing with age, this study suggests that iodide prophylaxis with 123 I-Ioflupane should be reconsidered for elderly patient.

Inactivation of planktonic cells and inhibitory effect on post-treatment biofilm formation of methicillin-resistant Staphylococcus aureus by photodynamic treatment with IR780 iodide loaded mesoporous silica nanoparticles and near infrared light.

The rapid spread of antimicrobial resistance is one of the biggest threats to global health. In the search for new treatment approaches that can eradicate pathogens without inducing drug-resistant strains, photodynamic therapy stands as a promising one. The aim of this study was to investigate the antimicrobial photodynamic potential of mesoporous silica nanoparticles (MSN) loaded with IR780 iodide on one of the most common multidrug-resistant bacteria both in hospitals and in the community, which is methicillin-resistant Staphylococcus aureus (MRSA). Mesoporous silica nanoparticles loaded with IR780 iodide were synthesized, their photodynamic and photothermal properties were examined, and their antimicrobial photodynamic potential against one methicillin-susceptible Staphylococcus aureus (MSSA), and one MRSA strain was investigated. Irradiation was achieved via a 785 nm diode laser (500 mW/cm2, 5 min). Viable bacterial cells were counted by serial dilution method. The post-treatment biofilm recurring ability of MRSA was assessed 24 h post-PDT treatment using Crystal Violet assay. Scanning Electron Microscopy (SEM) of post-treatment biofilms was acquired. Data were analyzed by ANOVA followed by Tukey's test (p ≤ 0.05). Results revealed that mesoporous silica nanoparticles loaded with IR780 iodide-mediated photodynamic therapy were effective in killing both tested strains. The antimicrobial effect was stronger on MRSA, in which 99.97% of photokilling (3.54 log reduction) was observed. The killing was mainly due to the photodynamic action of the nanoparticles. Post-treatment biofilm recurring ability of MRSA was much less in the treated group than that of the control group (50% inhibition), as confirmed by both optical density at 570 nm (OD570) measurement, and Scanning Electron Microscope (SEM) imaging.

High-Throughput Screening of ToxCast PFAS Chemical Library for Potential Inhibitors of the Human Sodium Iodide Symporter.

Over the past decade, there has been increased concern for environmental chemicals that can target various sites within the hypothalamic-pituitary-thyroid axis to potentially disrupt thyroid synthesis, transport, metabolism, and/or function. One well-known thyroid target in both humans and wildlife is the sodium iodide symporter (NIS) that regulates iodide uptake into the thyroid gland, the first step of thyroid hormone synthesis. Our laboratory previously developed and validated a radioactive iodide uptake (RAIU) high-throughput assay in a stably transduced human NIS cell line (hNIS-HEK293T-EPA) to identify chemicals with potential for NIS inhibition. So far, we have tested over 2000 chemicals (US EPA's ToxCast chemical libraries PI_v2, PII, and e1K) and discovered a subset of chemicals that significantly inhibit iodide uptake in the hNIS assay. Here, we utilized this screening assay to test a set of 149 unique per- and polyfluoroalkyl substances (PFAS) (ToxCast PFAS library) for potential NIS inhibition. For this evaluation, the 149 blinded samples were screened in a tiered approach, first in an initial single-concentration (≤100 µM) RAIU assay and subsequent evaluation of the chemicals that produced ≥20% inhibition using multiconcentration (MC) response (0.001-100 µM) testing in parallel RAIU and cell viability assays. Of this set, 38 of the PFAS chemicals inhibited iodide uptake ≥20% in the MC testing with 25 displaying inhibition ≥50%. To prioritize the most potent PFAS NIS inhibitors in this set, chemicals were ranked based on outcomes of both iodide uptake and cytotoxicity and normalized to perchlorate, a known positive control. Consistent with previous findings, PFOS and PFHxS were again found to be potent NIS inhibitors, yet significant inhibition was also observed for several other screened PFAS chemicals. Although further studies are clearly warranted, this initial screening effort identifies NIS as a molecular target for potential thyroid disruption by this persistent and structurally diverse class of chemicals.

Importance of diet in amphibian metamorphosis-based studies designed to assess the risk of thyroid active substances.

The present study evaluated the hypothesis that dietary quality used in historical studies may impact the effects of chemical stressors on premetamorphic development and metamorphosis due to suboptimal nutritional quality. A modified Amphibian Metamorphosis Assay (AMA) was performed in which Nieuwkoop and Faber (NF) Stage 47 tadpoles of Xenopus laevis were exposed for 32 days to iodide (I- )-deficient FETAX solution supplemented with <0.025, 0.17, 0.52, 1.58, and 4.80 µg I- /L (measured concentrations 0.061, 0.220, 0.614, 1.65, and 4.73 µg I- /L) and fed a pureed Frog Brittle (FB) diet. An AMA guideline benchmark group (four replicates) exposed to dechlorinated tap water and fed standard Sera Micron Nature® (SMN) diet was evaluated concurrently. Developmental delay, observed as changes in stage distribution or median developmental stage, occurred in FB treatments with 0.061, 0.220, and 0.614 µg/L I- , respectively. Developmental rates and hind limb length of the 1.65 and 4.73 µg/L I- groups were similar to each other, but both treatments fell short of the developmental rate achieved by the SMN benchmark. Iodide supplementation also had no impact on nonthyroidal growth endpoints, which were markedly reduced in FB-fed frogs compared with their SMN-fed counterparts. All larvae that received the FB diet had mildly to severely hypoplastic/atrophic thyroids, a condition for which iodine supplementation had little if any ameliorative effect. Collectively, these results suggested that nutritional deficiencies in the FB diet negatively affected both growth and metamorphic development, the latter of which was only compensated to a limited extent by iodine supplementation.

Perchlorate, nitrate, and thiocyanate: Environmental relevant NIS-inhibitors pollutants and their impact on thyroid function and human health.

Thyroid disruptors are found in food, atmosphere, soil, and water. These contaminants interfere with the thyroid function through the impairment of thyroid hormone synthesis, plasma transport, peripheral metabolism, transport into the target cells, and thyroid hormone action. It is well known that iodide uptake mediated by the sodium-iodide symporter (NIS) is the first limiting step involved in thyroid hormones production. Therefore, it has been described that several thyroid disruptors interfere with the thyroid function through the regulation of NIS expression and/or activity. Perchlorate, nitrate, and thiocyanate competitively inhibit the NIS-mediated iodide uptake. These contaminants are mainly found in food, water and in the smoke of cigarettes. Although the impact of the human exposure to these anions is highly controversial, some studies indicated their deleterious effects in the thyroid function, especially in individuals living in iodine deficient areas. Considering the critical role of thyroid function and the production of thyroid hormones for growth, metabolism, and development, this review summarizes the impact of the exposure to these NIS-inhibitors on thyroid function and their consequences for human health.

Antimicrobial Photodynamic Effect of Cross-Kingdom Microorganisms with Toluidine Blue O and Potassium Iodide.

Streptococcus mutans (S. mutans) and Candida albicans (C. albicans) are prominent microbes associated with rapid and aggressive caries. In the present study, we investigated the antimicrobial efficacy, cytotoxicity, and mechanism of toluidine blue O (TBO)-mediated antimicrobial photodynamic therapy (aPDT) and potassium iodide (KI). The dependence of KI concentration, TBO concentration and light dose on the antimicrobial effect of aPDT plus KI was determined. The cytotoxicity of TBO-mediated aPDT plus KI was analyzed by cell counting kit-8 (CCK-8) assay. A singlet oxygen (1O2) probe test, time-resolved 1O2 detection, and a 1O2 quencher experiment were performed to evaluate the role of 1O2 during aPDT plus KI. The generation of iodine and hydrogen peroxide (H2O2) were analyzed by an iodine starch test and Amplex red assay. The anti-biofilm effect of TBO-mediated aPDT plus KI was also evaluated by counting forming unit (CFU) assay. KI could potentiate TBO-mediated aPDT against S. mutans and C. albicans in planktonic and biofilm states, which was safe for human dental pulp cells. 1O2 measurement showed that KI could quench 1O2 signals, implicating that 1O2 may act as a principal mediator to oxidize excess iodide ions to form iodine and H2O2. KI could highly potentiate TBO-mediated aPDT in eradicating S. mutans and C. albicans due to the synergistic effect of molecular iodine and H2O2.

ROS/JNK-mediated lysosomal injury in rat intestinal epithelial-6 cells during heat stress.

Injury to the intestinal epithelial cells and loss of the intestinal barrier are critical to heatstroke. To reveal the mechanism through which heatstroke leads to intestinal epithelial injury, the relationship between reactive oxygen species (ROS), c-Jun NH2-terminal kinase (JNK), and lysosomes were studied in intestinal epithelial cells subjected to heat stress. Cells of heat stress groups were incubated at 43 °C for 1 h, then incubated at 37 °C as indicated. Control group cells were incubated at 37 °C. Cell-counting kit-8 assay was used to assess cell viability. Cells were labeled with 2'-7'dichlorofluorescin diacetate and acridine orange (AO) staining, respectively, the total ROS and AO were detected by confocal laser scanning microscopy and flow cytometry. Apoptosis was analyzed by flow cytometry using annexin V-fluorescein isothiocyanate/prodium iodide staining, the expressions of mitogen-activated protein kinases were detected by western blotting. Heat stress induced apoptosis and inhibited cell viability, the production of ROS, and lysosomal injury in IEC-6 cells. After pretreatment with the lysosomal cathepsin inhibitor E64, the JNK inhibitor SP600125, or the ROS scavenger NAC, the effect of heat stress on apoptosis or lysosomal injury was significantly attenuated. In conclusion, heat stress induced apoptosis, lysosomal injury, and the accumulation of ROS in IEC-6 cells; mechanistically, this occurred through the ROS-induced activation of JNK signaling, which mediated the lysosomal injury and ultimately apoptosis.

Dentin Discoloration and Pulpal Ion Concentrations Following Silver Diamine Fluoride and Potassium Iodide Treatment.

OBJECTIVE: The objective of this in vitro study was to evaluate the effects of potassium iodide on dentin discoloration and ion penetration into the pulp chamber after application of silver diamine fluoride (SDF). METHODS: Proximal surfaces of extracted one-rooted sound human teeth were polished to obtain flat dentin and treated with 17% EDTA for two minutes. Each tooth was then fixed to a test tube. The specimens were distributed into five groups according to the treatment: SDF (Advantage Arrest, Elevate Oral Care); SDF-KI (SSKI, Upsher-Smith); RV-SDF (Riva Star, SDI); and RV-SDFKI. The CIE L*a*b* color value for each proximal dentin was assessed using a colorimeter (CR200, Konica-Minolta) at baseline, after two minutes, 10 minutes, and 24 hours, and ΔE compared to baseline was calculated. Subsequently, the water-filled tube was inverted to collect the ions that had penetrated from the tooth surface into the pulp chamber. Silver, iodide, and fluoride in the pulp were measured using trace element analysis (ISMat) and fluoride ion-selective electrode (Orion, Thermo Scientific) at days 1, 2, 7, and 14. RESULTS: Dentin in both SDF-KI groups showed no visual change in color whereas the groups using only SDF exhibited gradual staining. The time, the treatment and their interaction had a significant effect on ΔE (p<0.001). The fluoride concentrations at day 1 and day 14 for group SDF and KI were significantly lower compared to SDF (p=0.044). There was a difference between control groups and other groups in silver and iodine (p<0.05), whereas there was no significant difference among groups with treatment after 14 days (p>0.05). CONCLUSION: The application of KI after SDF treatment could significantly reduce the dentin staining. The pulpal fluoride concentration in the groups using SDF-KI was lower compared to the ones using SDF only, whereas there was no difference observed in iodide and silver among the groups with treatment.

Synthesis of oxymatrine hydrazone and its preventive action against sevoflurane induced neuron damage through ERK pathway up-regulation.

Exposure of patients undergoing multiple surgeries to anesthetic compounds leads to harmful side effects such as memory loss and impaired cognition. The current study was aimed to synthesize and investigate the effect of oxymatrine hydrazone on neuronal toxicity induced by sevoflurane in rats. Incubation with oxymatrine hydrazone was followed by exposure to sevoflurane for 48 h and determination of proliferation by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. Apoptosis was detected by flow cytometry using Annexin V­FITC and propydium iodide staining. Western blot analysis was used for determination of changes in protein expression. Sevoflurane exposure significantly (P<0.05) reduced proliferation of neurons by activation of cell apoptosis. However, pretreatment of neurons with oxymatrine hydrazone prevented reduction of proliferative potential induced on exposure with sevoflurane. Pre-treatment of neurons with 5.0 µM doses of oxymatrine hydrazone significantly prevented apoptosis induction by sevoflurane. Moreover, oxymatrine hydrazone pretreatment inhibited BCL2 Associated-X (BAX) and cleaved caspase-3 levels induced by sevoflurane exposure in neurons. Phosphorylation of extracellular signal­regulated protein kinase (ERK1/2) and expression of BCL-2 in neurons exposed to sevoflurane were markedly promoted on pretreatment with oxymatrine hydrazone. Additionally, U0126 (ERK ½ activation inhibitor) treatment of sevoflurane exposed neurons inhibited promotion of ERK1/2 phosphorylation by oxymatrine hydrazone pre-treatment. In summary, cytotoxicity of sevoflurane in neurons was prevented on pretreatment with oxymatrine hydrazone. Pretreatment of sevoflurane exposed neurons with oxymatrine hydrazone inhibited apoptosis, suppressed BAX/caspase-3 and elevated BCL-2. Moreover, oxymatrine hydrazone pre-treatment promoted ERK1/2 phosphorylation in sevoflurane exposed neurons. Therefore, oxymatrine hydrazone has a great potential for prevention of neurotoxicity induced by sevoflurane.

Bioactivity and antibacterial activity of iodine-containing calcium titanate against implant-associated infection.

Developing antimicrobial biomaterials is a major challenge in the fields of orthopaedic and dental implants. In this study, we evaluated the bone-bonding ability and antibacterial activity of a novel biomaterial for preventing implant-associated infections. We have previously reported that NaOH heat treatment improved the bone-bonding ability of titanium, which was later modified to release target ions from the calcium titanate surface. Iodine, an essential nutrient, exhibits broad-spectrum antimicrobial activity; hence, we designed a calcium titanate that releases iodine ions (Ca-I-Ti). The material was prepared from a simple solution using heat treatments as well as inexpensive devices and chemical agents. MC3T3-E1 cells seeded on Ca-I-Ti displayed high degrees of bioactivity and viability, and Ca-I-Ti exhibited antibacterial activity against methicillin-susceptible Staphylococcus aureus. In vivo biomechanical and histological experiments showed that Ca-I-Ti had excellent bone-bonding ability at 8 weeks after implantation. In a subcutaneous infection model in rats, methicillin-susceptible Staphylococcus aureus on the implant was reduced by approximately 95% compared to that on commercially pure titanium, indicating that Ca-I-Ti has antibacterial effects in vivo. In addition, no local or systemic complications were observed, and active infection in the surrounding tissues was histologically inhibited. Thus, iodine-containing calcium titanate is a safe biomaterial with excellent bioactivity and antibacterial properties, indicating its potential in preventing implant-associated infections.

Enzymatic synthesis and characterization of aryl iodides of some phenolic acids with enhanced antibacterial properties.

Phenolic acids represent a class of drugs with mild antibacterial properties. We have synthesized iodinated gallic and ferulic acids and together with commercially available iodinated forms of salicylic acids studied their cytotoxicity, bacteriostatic and anti-virulence action. Out of these, iodogallic acid had lowest minimal inhibitory concentration (MIC) against Staphylococcus aureus (MIC = 0.4 mM/118.8 µg/ml). Yet, it had strong effect on erythrocyte membrane lipid ordering and on α-hemolysin secretion by the bacteria at lower non-bacteriostatic and non-cytotoxic concentrations (<0.1 mM). Iodogallic acid formed static complexes with α-hemolysin in solutions (logKb = 4.69 ± 0.07) and inhibited its nano-pore conduction in artificial lipid bilayers (IC50 = 37.9 ± 5.3 µM). These effects of iodogallic acid converged on prevention of hemolysis induced by α-hemolysin (IC50 = 41.5 ± 4.2 µM) and pointed to enhanced and diverse anti-virulence properties of some aryl iodides. The analysis of molecular surface electrostatic charge distribution, molecular hydrophilicity, electronegativity, and dipole moment of studied compounds suggested the importance of the number of hydroxyl groups and their proximity to iodine in anti-virulence activity manifestation. In iodogallic acid, charge redistribution resulted in higher hydrophilicity without concomitant change in overall molecular electronegativity and dipole moment compared to non-iodinated gallic acid. This study shows new directions for the development of antibacterial/antivirulence therapeutics.

Apelin-13 attenuates depressive-like behaviors induced by chronic unpredictable mild stress via activating AMPK/PGC-1α/FNDC5/BDNF pathway.

Chronic stress induces neuronal death and impairs hippocampal neurogenesis, thus leading to cognitive deficits and depressive-like behaviors. Our previous studies found that apelin-13, a novel neuropeptide, and its receptors can improve cognitive impairment and depressive-like behaviors in rats, but its mechanism remains unknown. The study aims to evaluate the underlying mechanism of apelin-13 on cognitive impairment and depressive-like behaviors. A 4-week chronic unpredictable mild stress (CUMS) is used to establish a rat model of depression. Apelin-13(2 ug/day) is administered daily to the rats during the last 1 week. Depressive-like behaviors, including tail suspension test (TST) and sucrose preference test (SPT), are performed. The cognitive functions are established by identify index of novel objects recognition test (NORT) and the number of crossing hidden platform in morris water maze (MWM). The neuronal death is measured by popidium iodide (PI) and flow cytometry. The activity of superoxide dismutase (SOD) and glutathione-peroxidase (GSH-PX) in the hippocampus are determined. The protein expressions of p-AMPK, AMPK, BDNF, FNDC5 and PGC-1α are examined. Golgi staining observed the spine dendritic arborization of the hippocampal cornu ammonis 1 (CA1) subregion. Results showed that apelin-13 improves cognitive impairment and ameliorates depressive-like behaviors. Moreover, apelin-13 significantly inhibits neuronal death via AMPK/PGC-1α/FNDC5/BDNF pathway. Taken together, apelin-13 could exert antidepressant effects via protecting neuron functions, which might be related to the activation of AMPK/PGC-1α/FNDC5/BDNF pathway.

Cross-species comparison of chemical inhibition of human and Xenopus iodotyrosine deiodinase.

The transition to include in vitro-based data in chemical hazard assessment has resulted in the development and implementation of screening assays to cover a diversity of biological pathways, including recently added assays to interrogate chemical disruption of proteins relevant to thyroid signaling pathways. Iodotyrosine deiodinase (IYD), the iodide recycling enzyme, is one such thyroid-relevant endpoint for which a human-based screening assay has recently been developed and used to screen large libraries of chemicals. Presented here is the development of an amphibian IYD inhibition assay and its implementation to conduct a cross-species comparison between chemical inhibition of mammalian and non-mammalian IYD enzyme activity. The successful development of an amphibian IYD inhibition assay was based on demonstration of sufficient IYD enzyme activity in several tissues collected from larval Xenopus laevis. With this new assay, 154 chemicals were tested in concentration-response to provide a basis for comparison of relative chemical potency to results obtained from the human IYD assay. Most chemicals exhibited similar inhibition in both assays, with less than 25% variation in median inhibition for 120 of 154 chemicals and 85% concordance in categorization of "active" (potential IYD inhibitor) versus "inactive". For chemicals that produced 50% or greater inhibition in both assays, rank-order potency was similar, with the majority of the IC50s varying by less than 2-fold (and all within an order of magnitude). Most differences resulted from greater maximum inhibition or higher chemical potency observed with human IYD. This strong cross-species agreement suggests that results from the human-based assay would be conservatively predictive of chemical effects on amphibian IYD.

Modeling principles of protective thyroid blocking.

PURPOSE: In the case of a nuclear incident, the release of radioiodine must be expected. Radioiodine accumulates in the thyroid and by irradiation enhances the risk of cancer. Large doses of stable (non-radioactive) iodine may inhibit radioiodine accumulation and protect the thyroid ('thyroid blocking'). Protection is based on a competition at the active carrier site in the cellular membrane and an additional temporary inhibition of the organification of iodide (Wolff-Chaikoff effect). Alternatively, other agents like e.g. perchlorate that compete with iodide for the uptake into the thyrocytes may also confer thyroidal protection against radioiodine exposure.Biokinetic models for radioiodine mostly describe exchanges between compartments by first order kinetics. This leads to correct predictions only for low (radio)iodide concentrations. These models are not suited to describe the kinetics of iodine if administered at the dosages recommended for thyroid blocking and moreover does not permit to simulate either the protective competition mechanism at the membrane or the Wolff-Chaikoff effect. Models adapted for this purpose must be used. Such models may use a mathematical relation between the serum iodide concentration and a relative uptake suppression or a dependent rate constant determining total thyroidal radioiodine accumulation. Alternatively, the thyroidal uptake rate constant may be modeled as a function of the total iodine content of the gland relative to a saturation amount. Newer models integrate a carrier-mechanism described by Michalis-Menten kinetics in the membrane and in analogy to enzyme kinetics apply the rate law for monomolecular irreversible enzyme reactions with competing substrates to model the competition mechanism. An additional total iodide uptake block, independent on competition but limited in time, is used to simulate the Wolff-Chaikoff effect. CONCLUSION: The selection of the best model depends on the issue to be studied. Most models cannot quantify the relative contributions of the competition mechanism at the membrane and the Wolff-Chaikoff effect. This makes it impossible or exceedingly difficult to simulate prolonged radioiodine exposure and the effect of repetitive administrations of stable iodine. The newer thyroid blocking models with a separate modeling of competition and Wolff-Chaikoff effect allow better quantitative mechanistic insights and offer the possibility to simulate complex radioiodine exposure scenarios and various protective dosage schemes of stable iodine relatively easily. Moreover, they permit to study the protective effects of other competitors at the membrane carrier site, like e.g. perchlorate, and to draw conclusions on their protective efficacy in comparison to stable iodine.

Design and construction of IR780- and EGCG-based and mitochondrial targeting nanoparticles and their application in tumor chemo-phototherapy.

An integration combination of phototherapy and chemotherapy to treat carcinoma, solving the inner limitation of individual-modal chemical agent-based therapy or phototherapy, emerges to be a strategy with high prospects for achieving synergistic curative effects. The dye IR780-iodide (IR780) close to infrared radiation is a phototherapy agent with high prospects. However, it is limited in its clinical applications due to poor solubility in water. While epigallocatechin-3-gallate (EGCG), naturally resourced green tea polyphenol, has been extensively proven with intrinsic antitumor activity, but it is largely restricted by its low bioavailability in vivo. Hence, novel multiple-function nanoparticles comprising hyaluronic acid (HA) and IR780 were proposed to deliver EGCG, defined as EGCG@THSI nano-scale particles (EGCG@THSI NPs), thereby rapidly solving limitations of EGCG and IR780. Amphiphilic nano-scale carrier was prepared by triphenylphosphine (TPP), hyaluronic acid (HA), cystamine, and IR780, termed as TPP-HA-SS-IR780, and EGCG was loaded into the amphiphilic copolymer by self-assembly. TPP-HA-SS-IR780 endowed the as-synthesized EGCG@THSI NPs with excellent TPP-mediated mitochondrial-targeted and glutathione-triggered rapid drug release properties. As impacted by the integration of phototherapy and chemotherapy, the EGCG@THSI NPs under NIR laser irradiation showed a prominent anti-tumor effect. Taken together, this study presented a multiple-function nano-scale carrier platform with high prospects in improving the therapeutic efficacy of anti-carcinoma drugs.

Application of Copper Iodide Nanoparticle-Doped Film and Fabric To Inactivate SARS-CoV-2 via the Virucidal Activity of Cuprous Ions (Cu+).

As a result of the novel coronavirus disease 2019 pandemic, strengthening control measures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become an urgent global issue. In addition to antiviral therapy and vaccination strategies, applying available virucidal substances for SARS-CoV-2 inactivation is also a target of research to prevent the spread of infection. Here, we evaluated the SARS-CoV-2 inactivation activity of a copper iodide (CuI) nanoparticle dispersion, which provides Cu+ ions having high virucidal activity, and its mode of actions. In addition, the utility of CuI-doped film and fabric for SARS-CoV-2 inactivation was evaluated. The CuI dispersion exhibited time-dependent rapid virucidal activity. Analyses of the modes of action of CuI performed by Western blotting and real-time reverse transcription-PCR targeting viral proteins and the genome revealed that CuI treatment induced the destruction of these viral components. In this setting, the indirect action of CuI-derived reactive oxygen species contributed to the destruction of viral protein. Moreover, the CuI-doped film and fabric demonstrated rapid inactivation of the SARS-CoV-2 solution in which the viral titer was high. These findings indicated the utility of the CuI-doped film and fabric as anti-SARS-CoV-2 materials for the protection of high-touch environmental surfaces and surgical masks/protective clothes. Throughout this study, we demonstrated the effectiveness of CuI nanoparticles for inactivating SARS-CoV-2 and revealed a part of its virucidal mechanism of action. IMPORTANCE The COVID-19 pandemic has caused an unprecedented number of infections and deaths. As the spread of the disease is rapid and the risk of infection is severe, hand and environmental hygiene may contribute to suppressing contact transmission of SARS-CoV-2. Here, we evaluated the SARS-CoV-2 inactivation activity of CuI nanoparticles, which provide the Cu+ ion as an antiviral agent, and we provided advanced findings of the virucidal mechanisms of action of Cu+. Our results showed that the CuI dispersion, as well as CuI-doped film and fabric, rapidly inactivated SARS-CoV-2 with a high viral titer. We also demonstrated the CuI's virucidal mechanisms of action, specifically the destruction of viral proteins and the genome by CuI treatment. Protein destruction largely depended on CuI-derived reactive oxygen species. This study provides novel information about the utility and mechanisms of action of promising virucidal material against SARS-CoV-2.

Iodide Analogs of Arsenoplatins-Potential Drug Candidates for Triple Negative Breast Cancers.

Patients with triple negative breast cancers (TNBCs)-highly aggressive tumors that do not express estrogen, progesterone, and human epidermal growth factor 2 receptors-have limited treatment options. Fewer than 30% of women with metastatic TNBC survive five years after their diagnosis, with a mortality rate within three months after a recurrence of 75%. Although TNBCs show a higher response to platinum therapy compared to other breast cancers, drug resistance remains a major obstacle; thus, platinum drugs with novel mechanisms are urgently needed. Arsenoplatins (APs) represent a novel class of anticancer agents designed to contain the pharmacophores of the two FDA approved drugs cisplatin and arsenic trioxide (As2O3) as one molecular entity. Here, we present the syntheses, crystal structures, DFT calculations, and antiproliferative activity of iodide analogs of AP-1 and AP-2, i.e., AP-5 and AP-4, respectively. Antiproliferative studies in TNBC cell lines reveal that all AP family members are more potent than cisplatin and As2O3 alone. DFT calculations demonstrate there is a low energy barrier for hydrolysis of the platinum-halide bonds in arsenoplatins, possibly contributing to their higher cytotoxicities compared to cisplatin.

Functionalization of nanocellulose to quaternized nanocellulose tri-iodide and its evaluation as an antimicrobial agent.

The reported research involves formation of quaternized nanocellulose triiodide for use as an agent for controlled release of iodine. Nanocellulose was extracted from bagasse and the extracted cellulose nanofibers (CNFs) were quaternized with 3-chloro-2-hydroxypropyltrimethyl ammonium chloride (CHPTAC) in NaOH/urea solution. This was followed by exchange of Cl- with I3- by reaction with KI/I2. Nanofibers having I3- anions were characterized by SEM, TEM, XRD, XRF and FTIR spectroscopy. The iodine content was estimated to be 33.42% and the fibers showed no leaching of molecular I2 in detectable amounts. The fibers showed a maximum activity of 94.73% and 99.86% against E. coli and S. aureus, respectively. These are capable of sustaining 100% antimicrobial activity over a period of six months. These fibers can thus find potential applications as a disinfectant agent in biomedical and water purification processes.

Evaluation of potential toxicity of Steriplant©N aerosolization toward human alveolar cells A459 in vitro.

Protection of patients against hospital-acquired infections is of major importance. Disinfection of magnetic resonance imaging suites is, due to their unique properties and environment particularly, difficult to implement. We developed an OPTI-JET CS MD 2ZE aerosolizator for disinfection of a magnetic resonance imaging suite using the electrolyzed oxidizing water biocide Steriplant©N. The disinfection of the magnetic resonance imaging suite with this system reduced from the number of colony formed unit/m3 air by 87% and 96% in 6 and 15 min of disinfection, respectively. It is well known that exposure of personnel or patients to aerosols may represent risk to the respiratory system; therefore, the aim of this study was to assess potential cytotoxicity and genotoxicity of Steriplant©N aerosolization toward human alveolar cells A459 in vitro. The A459 cells were exposed to aerosol containing different concentrations (50% and 100% v/v) of Steripalnt©N for 6 min in a chamber that had been constructed to simulate the conditions in the magnetic resonance imaging suite. The cytotoxicity was evaluated by measuring iodide uptake, and the genotoxicity was determined by measuring formation of phosphorylated H2AX histones, a marker for deoxyribonucleic acid double-strand breaks, immediately after the aerosolization and after 1, 4, and 24 h postincubation. The results demonstrated that aerosolization with Steriplant©N at conditions reflecting aerosolization in a magnetic resonance imaging suite is not cytotoxic and does not exhibit genotoxic potential in vitro.