Vitamin D is a steroid hormone classically involved in the calcium metabolism and bone homeostasis. Recently, new and interesting aspects of vitamin D metabolism has been elucidated, namely the special role of the skin, the metabolic control of liver hydroxylase CYP2R1, the specificity of 1α-hydroxylase in different tissues and cell types and the genomic, non-genomic and epigenomic effects of vitamin D receptor, which will be addressed in the present review. Moreover, in the last decades, several extraskeletal effects which can be attributed to vitamin D have been shown. These beneficial effects will be here summarized, focusing on the immune system and cardiovascular system.

3-iodothyronamine (T1AM) is a novel relative of thyroid hormone, able to interact with specific G protein-coupled receptors, known as trace amine-associated receptors. Significant functional effects are produced by exogenous T1AM, including a negative inotropic and chronotropic effect in cardiac preparations. This work was aimed at estimating endogenous T1AM concentration in different tissues and determining its cardiac metabolism. A novel HPLC tandem mass spectrometry assay was developed, allowing detection of T1AM, thyronamine, 3-iodothyroacetic acid, and thyroacetic acid. T1AM was detected in rat serum, at the concentration of 0.3±0.03 pmol/ml, and in all tested organs (heart, liver, kidney, skeletal muscle, stomach, lung, and brain), at concentrations significantly higher than the serum concentration, ranging from 5.6±1.5 pmol/g in lung to 92.9±28.5 pmol/g in liver. T1AM was also identified for the first time in human blood. In H9c2 cardiomyocytes and isolated perfused rat hearts, significant Na+-dependent uptake of exogenous T1AM was observed, and at the steady state total cellular or tissue T1AM concentration exceeded extracellular concentration by more than 20-fold. In both preparations T1AM underwent oxidative deamination to 3-iodothyroacetic acid. T1AM deamination was inhibited by iproniazid but not pargyline or semicarbazide, suggesting the involvement of both monoamine oxidase and semicarbazide-sensitive amine oxidase. Thyronamine and thyroacetic acid were not detected in heart. Finally, evidence of T1AM production was observed in cardiomyocytes exposed to exogenous thyroid hormone, although the activity of this pathway was very low.

Similarities in cardiac gene expression in hypothyroidism and left ventricular (LV) pathological remodeling after myocardial infarction (MI) suggest a role for impaired cardiac thyroid hormone (TH) signaling in the development of heart failure. Increased ventricular activity of the TH-degrading enzyme type 3 deiodinase (D3) is recognized as a potential cause. In the present study, we investigated the cardiac expression and activity of D3 over an 8-wk period after MI in C57Bl/6J mice. Pathological remodeling of the noninfarcted part of the LV was evident from cardiomyocyte hypertrophy, interstitial fibrosis, and impairment of contractility. These changes were maximal and stable from the first week onward, as was the degree of LV dilation. A strong induction of D3 activity was found, which was similarly stable for the period examined. Plasma T(4) levels were transiently decreased at 1 wk after MI, but T(3) levels remained normal. The high D3 activity was associated with increased D3 mRNA expression at 1 but not at 4 and 8 wk after MI. Immunohistochemistry localized D3 protein to cardiomyocytes. In vivo measurement of TH-dependent transcription activity in cardiomyocytes using a luciferase reporter assay indicated a 48% decrease in post-MI mice relative to sham-operated animals, and this was associated with a 50% decrease in LV tissue T(3) concentration. In conclusion, pathological ventricular remodeling after MI in the mouse leads to high and stable induction of D3 activity in cardiomyocytes and a local hypothyroid condition.

Heavy metal (HM) pollution, specifically cadmium (Cd) contamination, is a worldwide concern for its consequences for plant health and ecosystem stability. This review sheds light on the intricate mechanisms underlying Cd toxicity in plants and the various strategies employed by these organisms to mitigate its adverse effects. From molecular responses to physiological adaptations, plants have evolved sophisticated defense mechanisms to counteract Cd stress. We highlighted the role of phytochelatins (PC_n) in plant detoxification, which chelate and sequester Cd ions to prevent their accumulation and minimize toxicity. Additionally, we explored the involvement of glutathione (GSH) in mitigating oxidative damage caused by Cd exposure and discussed the regulatory mechanisms governing GSH biosynthesis. We highlighted the role of transporter proteins, such as ATP-binding cassette transporters (ABCs) and heavy metal ATPases (HMAs), in mediating the uptake, sequestration, and detoxification of Cd in plants. Overall, this work offered valuable insights into the physiological, molecular, and biochemical mechanisms underlying plant responses to Cd stress, providing a basis for strategies to alleviate the unfavorable effects of HM pollution on plant health and ecosystem resilience.