Thyroid disruption is an increasingly recognized issue in the use and development of chemicals and new drugs, especially to help toxicologist to complement the reproductive and developmental toxicology information of chemicals. Still, adequate assessment methods are scarce and often suffer a trade-off between physiological relevance and labor- and cost-intensive assays. Here, we present a tiered approach for a medium-throughput screening of chemicals to identify their thyroid disrupting potential in zebrafish embryos as a New Approach Methodology (NAM). After identifying the maximum tolerated concentrations, we exposed zebrafish larvae to sub-adverse effect levels of the reference compounds benzophenone-2, bisphenol A, phenylthiourea, potassium perchlorate, propylthiouracil, and phloroglucinol to exclude any systemic toxicity. Applying the transgenic zebrafish line that carries a gene for the red fluorescence protein (Tg(tg:mCherry)) under the thyroglobulin promoter, we could identify the thyroid disrupting effects of the chemicals by a time and cost-effective image analysis measuring the fluorescence levels in the thyroid glands. Our observations could be confirmed by altered expression patterns of genes involved in the hypothalamus-pituitary-thyroid (HPT) axis. Finally, to anchor the observed thyroid disruption, we determined some changes in the Thyroid hormone levels of triiodothyronine (T3) and Thyroxine (T4) using a newly developed liquid chromatography mass spectrometric (LCMS) method. The presented approach carries the potential to extend the toolbox for legislative authorities and chemical producers for the assessment of thyroid-specific endocrine disruption and to overcome current challenges in the evaluation of endocrine disruptors.

2023-01-02·Expert review of endocrinology & metabolism

Non-thionamide antithyroid drug options in Graves’ hyperthyroidism

Review

作者: Ruslan, Aliya ; Okosieme, Onyebuchi E

INTRODUCTION:

The thionamide anti-thyroid drugs namely carbimazole, methimazole, and propylthiouracil, have been the predominant therapy modality for Graves' hyperthyroidism for over 60 years. Although these agents have proven efficacy and favorable side-effect profiles, non-thionamide alternatives are occasionally indicated in patients who are intolerant or unresponsive to thionamides alone. This review examines the available non-thionamide drug options for the control of Graves' hyperthyroidism and summarizes their clinical utility, efficacy, and limitations.

AREAS COVERED:

We reviewed existing literature on mechanisms, therapeutic utility, and side-effect profiles of non-thionamide anti-thyroid drugs. Established non-thionamide agents act on various phases of the synthesis, release, and metabolism of thyroid hormones and comprise historical agents such as iodine compounds and potassium perchlorate as well as drug repurposing candidates like lithium, glucocorticoids, beta-blockers, and cholestyramine. Novel experimental agents in development target key players in Graves' disease pathogenesis including B-cell depletors (Rituximab), CD40 blockers (Iscalimab), TSH-receptor antagonists, blocking antibodies, and immune-modifying peptides.

EXPERT OPINION:

Non-thionamide anti-thyroid drugs are useful alternatives in Graves' hyperthyroidism and more clinical trials are needed to establish their safety and long-term efficacy in hyperthyroidism control. Ultimately, the promise for a cure will lie in novel approaches that target the well-established immunopathogenesis of Graves' disease.

2022-10-01·Aquatic toxicology (Amsterdam, Netherlands)

Potassium perchlorate effects on primordial germ cells of developing medaka larvae

Article

作者: Reh, Beh ; Wang, Xuegeng ; Bhandari, Ramji K ; Feng, Yashi

Perchlorate is a chemical compound commonly used in military artillery and equipment. It has been detected in drinking water, air, soil, and breast milk. Exposure of humans to perchlorate can occur in the theater of war and areas adjacent to military training grounds. A high concentration of perchlorate has been found to affect reproduction in vertebrates, including fish. However, whether environmental concentrations of perchlorate can affect primordial germ cells (PGCs), the founders of sperm and eggs, is not clearly understood. In the present study, we examined the effects of 0, 10, 100, and 1000 μg/L potassium perchlorate exposure on the embryonic development of medaka and their PGCs. Perchlorate exposure delayed hatching time, reduced heartbeat, inhibited migration of PGCs, and increased developmental deformities in the larvae. The 10 and 20 mg/L concentrations of perchlorate were lethal to embryos, whereas vitamin C co-treatment (1 mg/L) completely blocked perchlorate-induced mortality. RNA-seq analysis of isolated PGCs showed a non-linear pattern in expression profiles of differentially altered genes. Significantly upregulated genes were found in PGCs from the 10 and 1000 μg/L groups, whereas the 100 μg/L groups showed the highest number of significantly downregulated genes. Gene ontology analysis predicted differentially expressed genes to be involved in proteolysis, metabolic processes, peptides activity, hydrolase activity, and hormone activity. Among the cellular components, extracellular, intracellular, sarcoplasmic, and 6-phosphofructokinase and membrane-bounded processes were affected. Ingenuity Pathway Analysis of PGC transcriptomes revealed thyroid hormone signaling to be affected by all concentrations of perchlorate. The present results suggested that perchlorate affected the development of medaka larvae and vitamin C was able to ameliorate perchlorate-induced embryo mortality. Additionally, perchlorate altered the global transcriptional network in PGCs in a non-linear fashion suggesting its potential effects on developing germ cells and fertility.

项与过氯酸钾相关的新闻（医药）

2023-04-26

·Science Daily

New findings indicate gene-edited rice might survive in Martian soil

New research suggests future Martian botanists may be able to grow gene-edited rice on Mars. Andy Weir's bestselling 2011 book, The Martian, features botanist Mark Watney's efforts to grow food on Mars after he becomes stranded there. While Watney's initial efforts focus on growing potatoes, new research presented at the 54th Lunar and Planetary Science Conference by a team of interdisciplinary researchers from the U of A suggests future Martian botanists like Watney may have a better option: growing rice. As outlined in the team's abstract, Rice Can Grow and Survive in Martian Regolith with Challenges That Could be Overcome Through Control of Stress-Related Genes, one of the biggest challenges to growing food on Mars is the presence of perchlorate salts, which have been detected in the planet's soil and are generally considered to be toxic for plants. The team was able to simulate Martian soil using basaltic rich soil mined from the Mojave Desert, called the Mojave Mars Simulant, or MMS, which was developed by scientists from NASA and the Jet Propulsion Laboratory. The teams then grew three varieties of rice, including one wild-type and two gene-edited lines with genetic mutations that better enable them to respond to stress, such as drought, sugar starvation or salinity. These varieties were grown in the MMS, as well as a regular potted mix and a hybrid of the two. While plants were able to grow in the Martian simulant, they were not as developed as those grown in the potting soil and hybrid mix. Replacing just a quarter of the Martian simulant with potting soil resulted in improved development. The team also experimented with the amount of perchlorate in the soil, finding that 3 grams per kilogram was the threshold beyond which nothing would grow, while mutant strains could still root in 1 gram per kilogram. Their findings suggest that there might be a way forward for genetically modified rice to find purchase in Martian soil. Next steps will include experimenting with a newer Martian soil simulant called the Mars Global Simulant, as well as other rice strains that have increased tolerance for higher salt concentrations. An important part of the research will be determining to what degree perchlorate may be leeching into the plant from the soil. Farther down the road, the researchers would like to introduce rice into a closed habitat chamber and place it in a Mars simulation chamber that replicates the temperature and atmosphere of the planet. Whether humans ever colonize Mars, the team's research could have applications here on Earth. Second author on the abstract, Abhilash Ramachandran, a post-doctoral fellow at the Arkansas Center for Space and Planetary Sciences, noted that he spoke with an Australian researcher from an area where the soil had high salinity, and saw their work as a potential way to grow food there. He added, "We could use Earth as a terrestrial analog before the seeds ever get sent to Mars." First author on the abstract, Peter James Gann, a doctoral student in cell and molecular biology, said that the project began when he met Ramachandran for coffee in the student union. "He was new here at the university, and we shared the things we were doing in our respective laboratories. Since he works on planetary science, and I specialize in cell and molecular biology, we decided to try out plants." They were joined by co-authors Yheni Dwiningsih, a post-doctoral associate in plant sciences; Dominic Dharwadker, an undergraduate student in the Honors College; and Vibha Srivastava, a professor in the Department of Crop, Soil and Environmental Sciences who has a joint appointment with the U of A System Division of Agriculture. Gann, for one, is pleased with how his initial conversation with Ramachandran has turned out. "Relevant and interesting research can emanate from talking to strangers over a cup of coffee or a glass of beer," he said, before adding: "Ain't that cool?"

2023-03-22

·Science Daily

The devil is in the details: Re-imagining fertilizer precursor synthesis

Researchers have improved the Faradaic efficiency of the nitrogen reduction reaction into ammonia by straightforward optimization of chemical process parameters. They found that trace water was the probable source of the high selectivity by facilitating incorporation of lithium oxide into the solid electrolyte interphase. These findings will also aid optimization of other analogous reactions, and thus help the chemicals industry optimize the sustainability of one of the most carbon-intensive reactions globally. The Haber-Bosch reaction helps feed the world by converting nitrogen into ammonia, a fertilizer precursor. However, its carbon footprint is huge: this one reaction is the source of nearly 2% of global carbon emissions. Now, in a study recently published in ACS Energy Letters, researchers from Osaka University have helped re-imagine this reaction to improve the sustainability of the chemical industry. Replacing the Haber-Bosch reaction with a more sustainable alternative has been an active area of research for many years. These efforts have led to a globally well-established electrochemical reaction for ammonia synthesis. However, efforts at optimizing this reaction are hindered by insufficient understanding of how it proceeds. A general consensus is the need to minimize the water concentration in the reaction as much as possible. Revisiting this consensus -- with the goal of providing chemical reaction details that will be useful for optimizing ammonia production -- is the problem that the researchers sought to address. "There are various creative ways to improve the Faradaic efficiency by increasing the nitrogen partial pressure or solubility," explains Yu Katayama. "We have complemented these studies by showing that trace water can facilitate the reaction progress." The researchers report a trace water concentration (ca. 36 millimolar) and a lithium perchlorate concentration (0.8 molar) that results in a Faradaic efficiency of ca. 28% at atmospheric pressure. This selectivity is the highest reported to date at ambient pressure, without using a gas diffusion electrode. "X-ray photoelectron spectroscopy experiments indicate that the selectivity is attributable in part to the trace water facilitating lithium oxide incorporation into the solid electrolyte interphase," says Katayama. "Higher water concentrations might facilitate hydrogen evolution, an undesired side reaction." "This surprising result can only be found with help and discussion with researchers from ICL. I believe the outcome emphasizes the importance of research collaboration." This work succeeded in improving the Faradaic efficiency of nitrogen reduction into ammonia at ambient pressure by straightforward means and uncovering the chemistry that leads to this result. Fine-tuning chemical process parameters dramatically improved the output of this reaction. Thus, there are many previously discounted electrochemical systems that might be worthwhile revisiting for future research efforts that investigate their detailed mechanisms. Researchers are now closer to optimizing fertilizer precursor synthesis in industry and minimizing the carbon footprint of its production.

2022-07-11

·Science Daily

Future smart homes could be powered with electronics built on stones

What if you could power the smart thermostats, speakers and lights in your home with a kitchen countertop? Stones, such as marble and granite, are natural, eco-friendly materials that many people building or renovating houses already use. Now, in a step toward integrating energy storage with these materials, researchers have fabricated microsupercapacitors onto the surface of stone tiles. The devices are durable and easily scaled up for customizable 3D power supplies. What if you could power the smart thermostats, speakers and lights in your home with a kitchen countertop? Stones, such as marble and granite, are natural, eco-friendly materials that many people building or renovating houses already use. Now, in a step toward integrating energy storage with these materials, researchers have fabricated microsupercapacitors onto the surface of stone tiles. The devices, reported in ACS Nano, are durable and easily scaled up for customizable 3D power supplies. It would be convenient if the surfaces in rooms could charge smart home devices or other small electronics without being connected to the electrical grid. And although stone is a widely used material for floors, countertops and decorative backsplashes, it hasn't been integrated with energy storage devices, such as batteries and capacitors. But stones, even those that are polished and seem smooth, have microscopic bumps and divots, making it difficult to adhere electrical components to them. Researchers have recently figured out how to place microsupercapacitors, which have fast charging and discharging rates and excellent power supply storage, onto irregular surfaces with lasers. So, Bongchul Kang and colleagues wanted to adapt this approach to build microsupercapacitors on marble. The researchers patterned a copper oxide nanoparticle solution on a marble tile into two comb-like sides whose prongs were interspersed. They pointed a near-infrared laser on the nanoparticles, producing pure copper electrodes that were porous, highly conductive and strongly attached to the stone's surface. To form the microsupercapacitor, the researchers deposited iron oxide onto one of the electrodes to form a cathode, and manganese oxide on the other to form an anode. The electrolyte layer connecting the electrodes was made from a lithium perchlorate and polymer solution. In tests, the device maintained a high energy storage capacity even after 4,000 charge-discharge cycles. When multiple microenergy devices were strung together in a three-by-three array, enough energy was stored to light an LED. In addition, the stone energy storage devices were exceptionally durable against harsh impacts and could be quickly recycled. The researchers say that stone microenergy devices could provide high-performance, customizable and conveniently accessible power from natural building materials. The authors acknowledge funding from the National Research Foundation of Korea.

100 项与过氯酸钾相关的药物交易

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