3,5-Diiodo-L-thyronine activates brown adipose tissue thermogenesis in hypothyroid rats

3,5-Diiodo-l-thyronine (T2), a thyroid hormone derivative, is capable of increasing energy expenditure, as well as preventing high fat diet-induced overweight and related metabolic dysfunction. Most studies to date on T2 have been carried out on liver and skeletal muscle. Considering the role of brown adipose tissue (BAT) in energy and metabolic homeostasis, we explored whether T2 could activate BAT thermogenesis. Using euthyroid, hypothyroid, and T2-treated hypothyroid rats (all maintained at thermoneutrality) in morphological and functional studies, we found that hypothyroidism suppresses the maximal oxidative capacity of BAT and thermogenesis, as revealed by reduced mitochondrial content and respiration, enlarged cells and lipid droplets, and increased number of unilocular cells within the tissue. In vivo administration of T2 to hypothyroid rats activated BAT thermogenesis and increased the sympathetic innervation and vascularization of tissue. Likewise, T2 increased BAT oxidative capacity in vitro when added to BAT homogenates from hypothyroid rats. In vivo administration of T2 to hypothyroid rats enhanced mitochondrial respiration. Moreover, UCP1 seems to be a molecular determinant underlying the effect of T2 on mitochondrial thermogenesis. In fact, inhibition of mitochondrial respiration by GDP and its reactivation by fatty acids were greater in mitochondria from T2-treated hypothyroid rats than untreated hypothyroid rats. In vivo administration of T2 led to an increase in PGC-1α protein levels in nuclei (transient) and mitochondria (longer lasting), suggesting a coordinate effect of T2 in these organelles that ultimately promotes net activation of mitochondrial biogenesis and BAT thermogenesis. The effect of T2 on PGC-1α is similar to that elicited by triiodothyronine. As a whole, the data reported here indicate T2 is a thyroid hormone derivative able to activate BAT thermogenesis

Does salinity variation increase synergistic effects of triclosan and carbon nanotubes on Mytilus galloprovincialis? Responses on adult tissues and sperms

The use of carbon nanotubes (CNTs) is rapidly increasing and several scientific studies have addressed their toxicological properties. However, only a very small number of publications have deal with the interaction between CNTs and other molecules. Triclosan (TCS) is an antibacterial agent used in personal care and household products. Commonly detected in aquatic ecosystems, there is a strong evidence that aquatic biota is sensitive to this compound. Aside from emergent pollutants, aquatic organisms are continuously subjected to abiotic variations including salinities. Therefore, the main goal of the present study was to better understand how physio-chemical interactions of CNTs with TCS under different salinity levels (37, 28 and 19) affect the mussel species Mytilus galloprovincialis through the evaluation of biochemical alterations on gametes (sperms) and adult tissues, providing more ecologically relevant information on organisms' responses. The results showed toxicological effects in terms of sperm metabolic activity and intracellular reactive oxygen species production as well as cellular damage and alteration of metabolic capacity at the adult's stage when exposed to both contaminants acting alone and in combination, under tested salinities. Moreover, when the mussels were exposed to the combination of both contaminants, they showed major toxic impacts on both assessed biological levels (adult tissues and sperms) especially under control salinity. This suggests that toxicity upon mixture exposure compared to single-substance exposure may impair mussels' populations, affecting reproduction success and growth.publishe

Hindering NAT8L expression in hepatocellular carcinoma increases cytosolic aspartate delivery that fosters pentose phosphate pathway and purine biosynthesis promoting cell proliferation

N-acetylaspartate (NAA) is synthesized by the mitochondrial enzyme NAT8L, which uses acetyl-CoA and aspartate as substrates. These metabolites are fundamental for bioenergetics and anabolic requirements of highly proliferating cells, thus, NAT8L modulation may impinge on the metabolic reprogramming of cancer cells. Specifically, aspartate represents a limiting amino acid for nucleotide synthesis in cancer. Here, the expression of the NAT8L enzyme was modulated to verify how it impacts the metabolic adaptations and proliferative capacity of hepatocellular carcinoma. We demonstrated that NAT8L downregulation is asso-ciated with increased proliferation of hepatocellular carcinoma cells and immortalized hepatocytes. The over -expression of NAT8L instead decreased cell growth. The pro-tumoral effect of NAT8L silencing depended on glutamine oxidation and the rewiring of glucose metabolism. Mechanistically, NAT8L downregulation triggers aspartate outflow from mitochondria via the exporter SLC25A13 to promote glucose flux into the pentose phosphate pathway, boosting purine biosynthesis. These results were corroborated by the analyses of human and mouse hepatocellular carcinoma samples revealing a decrease in NAT8L expression compared to adjacent non -tumoral tissues. Overall, this work demonstrates that NAT8L expression in liver cells limits the cytosolic avail-ability of aspartate necessary for enhancing the pentose phosphate pathway and purine biosynthesis, counter-acting cell proliferation

Chemical risk in hospital settings: Overview on monitoring strategies and international regulatory aspects

Chemical risk in hospital settings is a growing concern that health professionals and supervisory authorities must deal with daily. Exposure to chemical risk is quite different depending on the hospital department involved and might origin from multiple sources, such as the use of sterilizing agents, disinfectants, detergents, solvents, heavy metals, dangerous drugs, and anesthetic gases. Improving prevention procedures and constantly monitoring the presence and level of potentially toxic substances, both in workers (biological monitoring) and in working environments (environmental monitoring), might significantly reduce the risk of exposure and contaminations. The purpose of this article is to present an overview on this subject, which includes the current international regulations, the chemical pollutants to which medical and paramedical personnel are mainly exposed, and the strategies developed to improve safety conditions for all healthcare workers.&nbsp

Argonaute 2 drives miR-145-5p-dependent gene expression program in breast cancer cells

To perform their regulatory functions, microRNAs (miRNAs) must assemble with any of the four mammalian Argonaute (Ago) family of proteins, Ago1–4, into an effector complex known as the RNA-induced silencing complex (RISC). While the mature miRNA guides the RISC complex to its target mRNA, the Ago protein represses mRNA translation. The specific roles of the various Ago members in mediating miRNAs activity, however, haven’t been clearly established. In this study, we investigated the contribution of Ago2, the only human Ago protein endowed with nuclease activity, to the function of tumor-suppressor miR-145-5p in breast cancer (BC). We show that miR-145-5p and Ago2 protein are concomitantly downregulated in BC tissues and that restoration of miR-145-5p expression in BC cells leads to Ago2 protein induction through the loosening of Ago2 mRNA translational repression. Functionally, miR-145-5p exerts its inhibitory activity on cell migration only in presence of Ago2, while, upon Ago2 depletion, we observed increased miR-145/Ago1 complex and enhanced cell motility. Profiling by microarray of miR-145-5p target mRNAs, in BC cells depleted or not of Ago2, revealed that miR-145-5p drives Ago2-dependent and -independent activities. Our results highlight that the Ago2 protein in cancer cells strictly dictates miR-145-5p tumor suppressor activity

Effects of multi-walled carbon nanotube materials on Ruditapes philippinarum under climate changes: the case of salinity shifts

The toxicity of carbon nanotubes (CNTs) is closely related to their physico-chemical characteristics as well as the physico-chemical parameters of the media where CNTs are dispersed. In a climate change scenario, changes in seawater salinity are becoming a topic of concern particularly in estuarine and coastal areas. Nevertheless, to our knowledge no information is available on how salinity shifts may alter the sensitivity (in terms of biochemical responses) of bivalves when exposed to different CNTs. For this reason, a laboratory experiment was performed exposing the Manila clam Ruditapes philippinarum, one of the most dominant bivalves of the estuarine and coastal lagoon environments, for 28 days to unfunctionalized multi-walled carbon nanotube MWCNTs (Nf-MWCNTs) and carboxylated MWCNTs (f-MWCNTs), maintained at control salinity (28) and low salinity 21. Concentration-dependent toxicity was demonstrated in individuals exposed to both MWCNT materials and under both salinities, generating alterations of energy reserves and metabolism, oxidative status and neurotoxicity compared to non-contaminated clams. Moreover, our results showed greater toxic impacts induced in clams exposed to f-MWCNTs compared to Nf-MWCNTs. In the present study it was also demonstrated how salinity shifts altered the toxicity of both MWCNT materials as well as the sensitivity of R. philippinarum exposed to these contaminates in terms of clam metabolism, oxidative status and neurotoxicity.publishe

Synuclein expression in the lizard Anolis carolinensis

The synuclein (syn) family comprises three proteins: alpha-, beta- and gammasyn. In mammals alpha- and beta- syn are primarily expressed in the brain where they are localized in pre-synaptic terminals while gamma-syn is mainly expressed in the peripheral nervous system. In humans, syns are involved in neurodegenerative diseases with high social impact such as Parkinson’s disease and tumors. However, the normal cellular functions of the three syns have not yet been fully clarified. Members of the syn family were sequenced in representative species of all vertebrates and the comparative sequence analysis suggested that syns are evolutionary conserved, although several differences in the number of genes encoding syn proteins have been identified in different taxa. On this knowledge, non mammalian vertebrates may represent useful models to understand the evolution and the physiological role of these proteins. Our research focused on the evolution of syns with the aim of analyzing their molecular and cellular expression in the CNS of representative vertebrates. A first study was published on alpha-syn distribution in the CNS of the carp Cyprinus carpio, by using antibodies against human alpha-syn [1]. Results showed that alpha-syn proteins are expressed to different levels in the brain and spinal cord regions of the carp. Differently from mammals, neuronal expression was mainly localized in cholinergic cell populations. At intracellular level, alpha-syn expression was localized in neuronal perikarya,varicose axons and terminal varicosities, but never in the cell nucleus. Apart from the above differences, the comparison between carp and mammals also suggested similarities in the distribution at the level of definite cholinergic systems. Thus, alpha-syn possibly modulates similar molecular pathways in cholinergic systems of phylogenetically distant vertebrates as teleosts and mammals. Current model of our comparative analysis is the lizard Anolis carolinensis, given the availability of sequenced genome in this species. Three syn genes (snca, sncb and sncg) have been identified in the lizard and their expression was studied by RT-PCR and Western blot experiments. Preliminary results on syns expression in the CNS are here reported

Environmental and biological monitoring of formaldehyde inside a hospital setting: a combined approach to manage chemical risk in workplaces

Background: The safety of healthcare workers exposed to formaldehyde remains a great matter of concern for healthcare management units. This work aimed at describing the results of a combined monitoring approach (environmental and biological) to manage occupational exposure to formaldehyde in a hospital setting.Design and Methods: Environmental monitoring of working spaces and biological monitoring of urinary formaldehyde in 16 exposed healthcare workers of the Anatomic Pathology Unit of a University Hospital in Southern Italy was performed on a four-year timescale (2016-2019).Results: Values of aero-dispersed formaldehyde identified were on average low; although workers' urinary formaldehyde levels were also minimal, the statistical analysis highlighted a slight weekly accumulation.Conclusions: Our data confirm that both environmental and biological monitoring are important to identify risk situations, in particular when values of hazardous compounds are below the accepted occupational exposure levels

The influence of Climate Change on the fate and behavior of different carbon nanotubes materials and implication to estuarine invertebrates

The widespread use of Carbon nanotubes (CNTs) has been increasing exponentially, leading to a significant potential release into the environment. Nevertheless, the toxic effects of CNTs in natural aquatic systems are related to their ability to interact with abiotic compounds. Considering that salinity variations are one of the main challenges in the environment and thus may influence the behavior and toxicity of CNTs, a laboratory experiment was performed exposing the tube-building polychaete Diopatra neapolitana (Delle Chiaje 1841) for 28 days to pristine multi-walled carbon nanotube (MWCNTs) and carboxylated MWCNTs, maintained at control salinity 28 and low salinity 21. An innovative approach based on thermogravimetric analysis (TGA) was adopted for the first time to assess the presence of MWCNTs aggregates in the organisms. Both CNTs generated toxic impacts in terms of regenerative capacity, energy reserves and metabolic capacity as well as oxidative and neuro status, however greater toxic impacts were observed in polychaetes exposed to carboxylated MWCNTs. Moreover, both CNTs maintained under control salinity (28) generated higher toxic impacts in the polychaetes compared to individuals maintained under low salinity (21), indicating that exposed polychaetes tend to be more sensitive to the alteration induced by salinity variations on the chemical behavior of both MWCNTs in comparison to salt stress.publishe