Thioredoxin reductase 3 (Txnrd3) plays a crucial role in antioxidant and anti-cancer activities, and sperm maturation. The damage of heavy metals, including Nickel (Ni), is the most prominent harm in social development, and hampering Txnrd3 might exacerbate Ni-induced cardiac damage. In this study, a total of 160 8-week-old C57BL/N male mice with 25-30 g weight of Txnrd3+/+ wild-type and Txnrd3À/À homozygote-type were randomly divided into eight groups. The mice in the control and Ni groups were gavaged with distilled water and a freshly prepared 10 mg/kg NiCl 2 solution. Melatonin (Mel) groups were administered at a concentration of 2 mg/kg for 21 days at the mice's 0.1 ml/10 g body weight. Ni exposure up-regulated the messenger RNA (mRNA) levels of mitochondrial apoptosis (caspase-3, caspase-9, cytochrome c, p53, and BAX), autophagy (LC3, ATG 1, ATG 7, and Beclin-1), and inflammation (TNF-α, COX 2, IL-1β, IL-2, IL-6, and IL-7)-related markers, but downregulated the mRNA levels of BCL-2, p62 and mTOR (p < .05). Ni exposure decreased the expression of BCL-2 and p62 protein but increased the expression levels of caspase-3, caspase-9, cytochrome c, p53, BAX, ATG 7, Beclin-1, TNF-α, COX 2, IL-1β and IL-2 protein (p < .05). Ni increased the contents of glutathione disulfide (GSSG) and malondialdehyde (MDA) and decreased the activities of catalase (CAT) and total superoxide dismutase (T-SOD) (p < .05). Decreased Txnrd3 expression significantly exacerbated changes compared to the Ni exposure (p < .05). Mel significantly attenuated these changes, but the effect decreased when Txnrd3 was inhibited (p < .05). In conclusion, decreased Txnrd3 expression promoted Ni-induced mitochondrial apoptosis and inflammation via oxidative stress and aggravated heart damage in mice. Decreased Txnrd3 expression significantly reduced the protective effect of Mel to Ni exposure.

Homeobox (HOX) transcript antisense RNA (Hotair) is elevated in many cancers significantly. However, the oncogenic role of Hotair in human laryngeal squamous cell carcinoma (LSCC) is still unknown. Thus, we explored the expression profile of Hotair and its function in LSCC. We observed high expression levels of Hotair in six LSCC cell lines compared to the human nasopharyngeal epithelial cell line. Knockdown of Hotair inhibited proliferation and enhanced apoptosis of Tu212 and Hep-2 cell lines in vitro. Moreover, the overexpression of hsa-miR-30a-5p inhibited the expression of GRP78 and PD-L1, but Hotair overexpression in LSCC cells rescues both proteins. Furthermore, the impacts of hsa-miR-30a-5p upregulation on the apoptosis and proliferation of LSCC cells were rescued by overexpression of Hotair. Finally, we combined si-Hotair and a VEGF inhibitor to treat LSCC cells in vitro or in vivo and surprisingly observed a significant inhibition of LSCC growth. In summary, these results indicate that Hotair displays an oncogenic role in both malignancy and immune escape in LSCC related to hsa-miR-30a-5p/GRP78/PD-L1 signaling. Therefore, Hotair may be a potential target for treating LSCC.

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Editorial on the Research TopicThe mechanism of trace elements on regulating immunity in prevention and control of human and animal diseases Nickel is a hard, malleable, silver-white transition metal that is widely used in metallurgical processes such as alloy manufacturing, nickel cadmium battery manufacturing, and food industries (1). Nickel can be enriched in humans and animals through the food chain and direct contact, and when it accumulates to a certain level in the body without proper treatment, it can be harmful to living organisms as a toxic metal ion (2-4). Human exposure to excessive nickel can cause toxic side effects such as allergies, cardiovascular disease, kidney disease, pulmonary fibrosis, and cancers (5). It has been shown that nickel nanoparticles can cause reproductive toxicity in mice (6). Melatonin (MT) is an indole hormone secreted primarily by the pineal gland in mammals and humans (7). It is used for the treatment of hypertension, hyperlipidemia, myocardial injury, and myocardial ischemia reperfusion injury (8). Previous experiments by Cai et al. showed that MT ameliorates trimethyltin chloride-induced cardiotoxicity through the nuclear xenobiotic metabolism and Keap1-Nrf2/ARE axis-mediated pyroptosis.Selenium is an essential trace element for the human body, which exists in selenoproteins in the form of selenocysteine and selenomethionine, and exerts its biological functions through 25 selenoproteins. Selenoprotein M (SelM) is one of the executive factors of selenium in vivo and may be involved in antioxidant, neuroprotection and the regulation of intracellular calcium (9). Existing studies have shown that the overexpression of human SelM in rats increases the activity of antioxidant enzymes such as glutathione peroxidase (GPX) and superoxide dismutase (SOD) (10). In addition, SelM has Frontiers in Immunology frontiersin.org 01