Cytotoxic effects of imidazolium ionic liquids on fish and human cell lines

Ionic liquids bring a promise of a wide range of "green" applications that could replace conventional volatile solvents. However, before these applications become large-scale, their toxicity needs to be investigated in order to predict the impact on human health and environment. In this study we assessed the cytotoxicity of imidazolium ionic liquids (in the concentrations between 0.1 mmol L-1 and 10 mmol L-1) in the ovarian fish cell line CCO and the human tumour cell line HeLa using the MTT cell viability assay. Our results showed that the most cytotoxic ionic liquid was 1-n-butyl-3-methylimidazolium bis(trifluoro methylsulphonyl)imide, [BMIM][Tf2N], followed by 1-n-butyl-3-methylimidazolium tetrafluoroborate [BMIM][BF4], 1-n-butyl-3-methylimidazolium hexafluorophosphate [BMIM][PF6], and 1,3-dimethylimidazolium hexafluorophosphate [MMIM][PF6]. Generally, the effects were concentration-dependent. They also depended on the type of anion and the n-alkyl chain length. The comparison between the fish CCO and human HeLa cell lines suggests that CCO cells provide a good biological system for initial toxicity testing of ionic liquids that could replace in vivo bioassays.     

Next Wave of Targets in the Treatment of Advanced Renal Cell Carcinoma

While surgical resection has remained the mainstay of treatment in early-stage renal cell carcinoma (RCC), therapeutic options in the advanced setting have remarkably expanded over the last 20 years. Tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptor (VEGF-TKIs) and anti-programmed cell death 1 (PD-1)/anti-programmed death-ligand 1 (PD-L1)-based immune checkpoint inhibitors (ICIs) have become globally accepted options in the upfront metastatic setting, with different ICI-based combination strategies improving overall survival compared to single-agent Sunitinib. Although some patients benefit from long-term responses, most eventually develop disease progression. Ongoing efforts to better understand the biology of RCC and the different mechanisms of acquired resistance have led to the identification of promising therapeutic targets. Belzutifan, a novel agent targeting the angiogenic pathway involving hypoxia-inducible factors (HIFs), has already been approved for the treatment of early-stage tumors associated with VHL disease and represents a very promising therapy in advanced RCC. Other putative targets include epigenetic regulation enzymes, as well as several metabolites such as adenosine, glutaminase and tryptophan, which are critical players in cancer cell metabolism and in the tumor microenvironment. Different methods of immune regulation are also being investigated, including CAR-T cell therapy and modulation of the gut microbiome, in addition to novel agents targeting the interleukin-2 (IL-2) pathway. This review aims to highlight the emergent novel therapies for RCC and their respective completed and ongoing clinical trials.     

Early respiratory and ocular involvement in X-linked hypohidrotic ectodermal dysplasia

X-linked hypohidrotic ectodermal dysplasia (XLHED; ectodysplasin deficiency) has been classically described as affecting hair, sweat glands, and dentition. What may be underappreciated is the effect ectodysplasin deficiency has on glands surrounding the airways and eyes and the resulting chronic health issues. In this study, 12 male children (age range 6–13 years) and 14 male adults with XLHED (18–58 years of age) were investigated by pulmonary function tests, measurement of fractional exhaled nitric oxide, and by ophthalmologic assessments. Twelve healthy individuals (six children, six adults) served as controls. Signs of airway constriction and inflammation were detected in eight children with XLHED, including the youngest subject, and in ten adult XLHED patients. Increased tear osmolarity, reduced tear film break-up time, and other ocular abnormalities were also present at an early age. Five of 12 XLHED subjects not reporting a history of asthma and 7 of the 12 patients not reporting a history of dry eye issues showed at least two abnormal test results in the respective organ system. The presence of residual sweat ducts, suggestive of partial ectodysplasin gene expression, correlated with milder disease in two XLHED subjects with mutations affecting the collagen-like domain of ectodysplasin. Conclusion: The high prevalence of asthma-like symptoms in XLHED patients as young as 6 years and a similar prevalence of dry eye problems indicate that screening evaluation, regular monitoring, and consideration of therapeutic intervention should begin in early childhood.     

Behavioural response in paired food choice experiments with Oniscus asellus (Crustacea, Isopoda) as an indicator of different food quality

This paper describes a study of behavioural response in terrestrial isopod Oniscus asellus when offered two food pellets of different quality. One group had a choice of sterilised food and food pellets covered with mould. The other group had a choice of uncontaminated and cadmium-dosed food. During the behavioural test, the animals were monitored by a video camera and each visit to food pellets and time spent around it was counted. The results show that animals spent significantly less time near sterilised and cadmium-dosed food than with uncontaminated or mould-covered food. Discrimination between offered food pellets showed that avoidance behaviour can be used as an indicator of different food quality.     

Chemical and Electrochemical Synthesis of Some Substituted N,N′-Diacyl-p-phenylenediamines

Some N,N′-diacyl-p-phenylenediamines substituted with halogens ( 2a - c ) were prepared. Their polarographic reduction in N,N-dimethylformamide with Et₄NClO₄ was performed and discussed. The mechanism of the electrochemical reduction is stated. Large-scale electrolytic reductions of 2a - b to 3a - b were performed.     

Higher sensitivity of CA1 synapses to aglycemia in streptozotocin-diabetic rats is age-dependent

We studied conduction velocity in peripheral nerves and the block of synaptic transmission produced by lack of glucose in hippocampal slices from 4- and 12-month-old streptozotocin-induced diabetic rats and their age-matched controls. In sural nerves of young and old diabetic rats, the conduction velocity was reduced by 30–35%. In slices from young diabetics, CA1 synaptic transmission was more sensitive to aglycemia than in control slices. However, all slices from older rats showed comparable increases in CA1 synaptic sensitivity to aglycemia. We conclude that the cerebral adaptation to diabetic hyperglycemia apparent in the hippocampus of young rats is masked in older rats by an age-dependent increase in sensitivity to lack of glucose.