Sodium perchlorate 200mg/2ml solution for injection ampoules

Perchlorate is a strong chaotropic agent that causes macromolecule denaturation, DNA damage, and oxidative stress. However, perchlorate deliquescence is thought to promote the formation of liquid salt brines, even at hyper-arid and cold environments, such as the Martian regolith. For that reason, the detection of high levels of perchlorate at different locations on the Martian surface led to hypotheses about the existence of Martian microenvironments compatible with life, especially with those organisms tolerant to hyper-salinity and perchlorate. Extreme halophilic archaea have been proposed as the best candidates to inhabit those environments not only due to their high tolerance to salinity and perchlorate, but also because of their resistance to a wide variety of stress conditions. Since specific perchlorate responses remain largely unknown, in this work, we have analyzed the molecular mechanisms of perchlorate tolerance exhibited by the model extreme halophilic archaeon Haloferax volcanii using a transcriptomic approach. We report that perchlorate produced transcriptional effects opposite to those of salinity, and we propose that the "salt-in" strategy could promote high perchlorate tolerance in extreme halophilic archaea due to the intracellular accumulation of KCl, which may shield the chaotropic activity of perchlorate. This natural adaptation would be enhanced by changes in other stress responses like DNA repair, refolding and turnover of damaged proteins, removal of oxidative species, and tRNA modifications, among others. These results may help to understand how life could survive on Mars, now or in the past, and highlight the importance of extreme halophiles in the development of in situ resource utilization systems.IMPORTANCEPerchlorate is a toxic chlorinated compound that promotes the formation of liquid salt brines, even at hyper-arid and cold environments. For the past two decades, different probes have reported high levels of perchlorate salts at multiple locations on the Martian surface, which could facilitate the presence of potentially habitable environments by specific microorganisms capable of tolerating both hyper-salinity and high perchlorate concentrations. Therefore, the significance of this research was to investigate the molecular mechanisms for perchlorate tolerance using the extreme haloarchaeon Haloferax volcanii as a model organism. This analysis leads to the identification of critical genes and pathways involved in perchlorate tolerance and supports that certain molecular adaptations specific to extreme haloarchaea may be responsible for the high levels of perchlorate tolerance exhibited by these microorganisms, serving as a valuable resource for Mars exploration.

Abstract licence: CC BY

Perchlorate, a widespread environmental contaminant originating from various industrial applications, agricultural practices, and natural sources, poses potential risks to ecosystems and human health. While previous studies have highlighted its influence on the thyroid endocrine system and its impact on gonadal maturation, reproduction, and sex hormone synthesis, the specific interplay between thyroid and steroid hormones, in this context, remains largely unexplored. Therefore, this study was undertaken to investigate the adverse effects and underlying mechanisms triggered by exposure to sodium perchlorate (SP) on reproductive endocrine activity in zebrafish. For 21 d, the fish were exposed to test SP concentrations (0, 3, 30, 300 mg/L), which were determined based on the exposure concentrations that induced various toxic effects in the fish, considering naturally occurring concentrations. Exposure to SP, except at 3 mg/L in males, significantly decreased the production of thyroid hormone (TH) in both female and male zebrafish. Moreover, gonadal steroid levels were markedly reduced in both sexes. The expression of hepatic vitellogenin (VTG) mRNA in female zebrafish was significantly decreased, whereas aromatase activity in male zebrafish was significantly elevated in the SP exposure groups. The reduced levels of THs and gonadal steroid hormones were strongly correlated. Abnormal responses to SP exposure led to reduced reproductive success in the 300 mg/L SP exposure group. These findings indicate that prolonged and continuous exposure to a specific concentration of SP may lead to long-term reproductive problems in zebrafish, primarily through hormonal imbalances and suppression of hepatic VTG mRNA expression.

Abstract licence: CC BY-NC-ND

Studying the survival of terrestrial microorganisms under Martian conditions, particularly in the presence of perchlorates, provides crucial insights for astrobiology. This research investigates the resilience of the extremophile black fungus Rhinocladiella similis to magnesium perchlorate and UV-C radiation. Results show R. similis, known for its tolerance to acidic conditions, exhibits remarkable resistance to UV-C radiation combined with perchlorate, as well as to high concentrations of magnesium perchlorate, surpassing Exophiala sp. strain 15Lv1, a eukaryotic model organism for Mars-like conditions. Growth curve analyses revealed both strains can thrive in perchlorate concentrations mimicking Martian perchlorate-rich environments, with R. similis adapting better to higher concentrations. Morphological and protein production changes were investigated, and mass spectrometry identified perchlorate-induced proteins, advancing molecular understanding of potential microbial life on Mars. These findings advance knowledge of extremophile capabilities, contributing to the search for life beyond Earth and informing the design of future Martian rovers equipped for biosignature detection.

Abstract licence: CC BY-NC-ND

The sodium iodide symporter (NIS) mediates iodide uptake into thyroid follicular cells, providing the basis for radioiodine (RAI) imaging and therapy of differentiated thyroid cancer (DTC). Loss of functional NIS expression leads to RAI-refractory disease. Restoration of RAI uptake via NIS delivery into tumors using mesenchymal stem cells (MSCs) represents a therapeutic strategy for RAI-refractory DTC. This study exploits transforming growth factor β (TGF-β) biology in RAI-refractory BRAFV600E-mutant papillary thyroid cancer (PTC) to selectively drive NIS transgene expression in engineered MSCs using a synthetic TGF-β1-inducible SMAD-responsive promoter (SMAD-NIS-MSCs) to reestablish RAI accumulation. The 125I uptake assay confirmed stimulation of functional NIS expression in SMAD-NIS-MSCs through TGF-β1 released from BRAFV600E-mutant PTC cell lines (BCPAP, K1) from co-culture or by incubation with tumor-conditioned medium. Chemotaxis assays showed directed chemotaxis of MSCs toward BCPAP- and K1-tumor-conditioned medium. SMAD-NIS-MSCs applied intravenously to mice harboring BCPAP or K1 xenografts followed by 123I scintigraphy demonstrated tumor-specific MSC recruitment and RAI accumulation. Application of SMAD-NIS-MSCs followed by 131I demonstrated a significant delay in tumor growth with prolonged survival. We demonstrate re-establishment of NIS-mediated RAI therapy in RAI-refractory BRAFV600E-mutant PTC tumors using MSC-mediated NIS gene delivery driven by their TGF-β1 biology.

Abstract licence: CC BY

Environmental pollution is recognized as a critical contributor to pregnancy loss. However, there is currently a paucity of evidence concerning the potential impact of perchlorate, thiocyanate and nitrate, which are known as sodium iodine symporter inhibitors. This study was therefore designed to investigate the potential association between urinary perchlorate, thiocyanate and nitrate concentration and the risk of pregnancy loss. Based on the National Health and Nutrition Examination Survey 2001-2002 and 2005-2020 cycles, a total of 3249 reproductive-aged women were enrolled, of whom 1729 (53.22 %) had a history of pregnancy loss encompassing miscarriages, stillbirths, ectopic pregnancies, or abortions. Logistic regression analyses revealed that urinary perchlorate levels were significantly associated with increased pregnancy loss prevalence. In the weighted quantile sum and Bayesian kernel machine regression models, co-exposure to three anions were also significantly associated with higher pregnancy loss odds, with perchlorate identified as the primary contributor. Additionally, the mediation analysis suggested that insulin resistance, represented by the triglyceride-glucose index, accounted for 6.08 % of the perchlorate-associated risk. In summary, our study revealed a potential role of perchlorate exposure in pregnancy loss. Further prospective studies are needed to confirm our findings and elucidate the underlying causative mechanistic links.

Abstract licence: CC BY