MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

Arsenic (As) and cadmium (Cd) are elements arousing major public health concerns associated with environmental pollution, high toxicity potential, and carcinogenic nature. However, selenium (Se) at low doses and incorporated into enzymes and proteins has antioxidant properties and protects animals and humans from the risk of various diseases. It also has an exceptionally narrow range between necessary and toxic concentrations, which is a well-known hindrance in its use as a dietary supplement. The present article aims to update and expand the role of Se in As and Cd toxicity discussed in our earlier paper. In general, recent reports show that Se, regardless of its form (as selenite, selenomethionine, nanoSe, or Se from lentils), can reduce As- or Cd-mediated toxicity in the liver, kidney, spleen, brain, or heart in animal models and in cell culture studies. As was suggested in our earlier review, Se antagonizes the toxicity of As and Cd mainly through sequestration of these elements into biologically inert complexes and/or through the action of Se-dependent antioxidant enzymes. An increase in the As methylation efficiency is proposed as a possible mechanism by which Se can reduce As toxicity. However, new studies indicate that Se may also diminish As or Cd toxicity by activation of the Nrf2 pathway. In addition, this paper discusses possible signs of Se toxic effects, which may be a challenge for its future use in the therapy of As and Cd poisoning and provide future directions to address this issue.

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The Role of Selenium in Arsenic and Cadmium Toxicity: an Updated Review of Scientific Literature

Immunosuppression, oxidative stress, and glycometabolism disorder caused by cadmium in common carp (Cyprinus carpio L.): Application of transcriptome analysis in risk assessment of environmental contaminant cadmium.

Inflammation is a potential crucial factor in the pathogenesis of subarachnoid hemorrhage (SAH). Circulating microRNAs (miRNAs) are involved in the regulation of diverse aspects of neuronal dysfunction. The therapeutic potential of miRNAs has been demonstrated in several CNS disorders and is thought to involve modulation of neuroinflammation. Here, we found that peripherally injected modified exosomes (Exos) delivered miRNAs to the brains of mice with SAH and that the potential mechanism was regulated by regulation of neuroinflammation. Next-generation sequencing (NGS) and qRT-PCR were used to define the global miRNA profile of plasma exosomes in aSAH patients and healthy controls. We peripherally injected RVG/Exos/miR-193b-3p to achieve delivery of miR-193b-3p to the brain of mice with SAH. The effects of miR-193b-3p on SAH were assayed using a neurological score, brain water content, blood-brain barrier (BBB) injury, and Fluoro-Jade C (FJC) staining. Western blotting analysis, enzyme-linked immunosorbent assay (ELISA), and qRT-PCR were used to measure various proteins and mRNA levels. NGS and qRT-PCR revealed that four circulating exosomal miRNAs were differentially expressed. RVG/Exos exhibited improved targeting to the brains of SAH mice. MiR-193b-3p suppressed the expression and activity of HDAC3, upregulating the acetylation of NF-κB p65. Finally, miR-193b-3p treatment mitigated the neurological behavioral impairment, brain edema, BBB injury, and neurodegeneration induced by SAH, and reduced inflammatory cytokine expression in the brains of mice after SAH. Exos/miR-193b-3p treatment attenuated the inflammatory response by acetylation of the NF-κB p65 via suppressed expression and activity of HDAC3. These effects alleviated neurobehavioral impairments and neuroinflammation following SAH.

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Systemic exosomal miR-193b-3p delivery attenuates neuroinflammation in early brain injury after subarachnoid hemorrhage in mice

H2S induces Th1/Th2 imbalance with triggered NF-κB pathway to exacerbate LPS-induce chicken pneumonia response.

Necroptosis has been discovered as a new paradigm of cell death and may play a key role in heart disease and selenium (Se) deficiency. Hence, we detected the specific microRNA (miRNA) in response to Se-deficient heart using microRNAome analysis. For high-throughput sequencing using Se-deficient chicken cardiac tissue, we selected miR-200a-5p and its target gene ring finger protein 11 (RNF11) based on differential expression in cardiac tissue and confirmed the relationship between miR-200a-5p and RNF11 by dual luciferase reporter assay and real-time quantitative PCR (qRT-PCR) in cardiomyocytes. We further explored the function of miR-200a-5p and observed that overexpression of miR-200a-5p spark the receptor interacting serine/threonine kinase 3 (RIP3)-dependent necroptosis in vivo and in vitro. To understand whether miR-200a-5p and RNF11 are involved in the RIP3-dependent necroptosis pathway, we presumed that oxidative stress, inflammation response and the mitogen-activated protein kinase (MAPK) pathway might trigger necroptosis. Interestingly, necroptosis trigger, z-VAD-fmk, failed to induce necroptosis but enhanced cell survival against necrosis in cardiomyocytes with knockdown of miR-200a-5p. Our present study provides a new insight that the modulation of miR-200a-5p and its target gene might block necroptosis in the heart, revealing a novel myocardial necrosis regulation model in heart disease.

miR-200a-5p regulates myocardial necroptosis induced by Se deficiency via targeting RNF11

Despite the well-established toxicity of cadmium (Cd) to animals and the ameliorative effects of selenium (Se), some specific mechanisms in the chicken ovary are not yet clarified. To explore the mechanism by which the toxicity effect of Cd is induced and explore the effect of supranutritional Se on Cd toxicity in female bird reproduction, forty-eight 50-day-old Isa Brown female chickens were divided randomly into four groups. Group I (control group) was fed the basic diet containing 0.2 mg/kg Se. Group II (Se-treated group) was fed the basic diet supplemented with sodium selenite (Na2SeO3), and the total Se content was 2 mg/kg. Group III (Se + Cd-treated group) was fed the basic diet supplemented with Na2SeO3; the total Se content was 2 mg/kg, and it was supplemented with 150 mg/kg cadmium chloride (CdCl2). Group IV (Cd-treated group) was with the basic diet supplemented with 150 mg/kg CdCl2. The Cd, estradiol (E2), and progestogen (P4) contents changed after subchronic Cd exposure in chicken ovarian tissue; subsequently, oxidative stress occurred and activated the endoplasmic reticulum (ER) pathway to induce apoptosis. Further, Se decreased the accumulation of Cd in ovarian tissue, increased the E2 and P4 contents, alleviated oxidative stress, and reduced apoptosis via the ER stress pathway. The present results demonstrated that Cd could induce apoptosis via the ER stress pathway in chicken ovarian tissue and that Se had a significant antagonistic effect. These results are potentially valuable for finding a strategy to prevent Cd poisoning.

Ameliorative Effects of Selenium on Cadmium-Induced Injury in the Chicken Ovary: Mechanisms of Oxidative Stress and Endoplasmic Reticulum Stress in Cadmium-Induced Apoptosis.

MicroRNA-193b-3p regulates hepatocyte apoptosis in selenium-deficient broilers by targeting MAML1

// Tianshu Yang 1, * , Zeping Zhao 2, * , Tianqi Liu 1 , Ziwei Zhang 1 , Pengzu Wang 1 , Shiwen Xu 1, 3 , Xin Gen Lei 2 , Anshan Shan 1 1 Northeast Agricultural University, Harbin, P. R. China 2 Department of Animal Science, Cornell University, Ithaca, NY, USA 3 Key Laboratory of Animal Cellular and Genetic Engineering of Heilongjiang Province, Northeast Agricultural University, Harbin, China * These authors are contributed equally to this work Correspondence to: Shiwen Xu, email: shiwenxu@neau.edu.cn Xin Gen Lei, email: xl20@cornell.edu Anshan Shan, email: asshan@neau.edu.cn Keywords: high-energy, se deficiency, neutrophils, oxidative stress, Nrf2 Received: November 09, 2016      Accepted: December 27, 2016      Published: January 07, 2017 ABSTRACT The mechanism of the interaction between Se deficiency and high energy remains limited. The aim of the current study was to identify whether Se-deficient, high-energy diet can induce oxidative stress, and downregulate the Nrf2 pathway and phagocytic dysfunction of neutrophils. We detected the phagocytic activity, ROS production, protein levels of Nrf2 and Nrf2 downstream target genes, and the mRNA levels of 25 selenoproteins, heat shock proteins, and cytokines in neutrophils. Cytokine ELISA kits were used to measure the serum cytokines. The concentration of ROS was elevated ( P < 0.05) in obese swine fed on a low Se diet (less than 0.03 mg/kg Se) compared to control swine. The protein levels of Nrf2 and its downstream target genes were depressed during Se deficiency and high-energy intake. The mRNA levels of 16 selenoproteins were significantly decreased ( P < 0.05) in the Se-deficient group and Se-deficient, high-energy group compared to the control group. However, the mRNA levels of 13 selenoproteins in peripheral blood neutrophils were upregulated in high energy group, except TrxR1, SelI and SepW. In summary, these data indicated that a Se-deficient, high-energy diet inhibits the Nrf2 pathway and its regulation of oxidative stress, and prompted a pleiotropic mechanism that suppresses phagocytosis.

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Oxidative stress induced by Se-deficient high-energy diet implicates neutrophil dysfunction via Nrf2 pathway suppression in swine.

// Zhe Xu 1 , Xi Jin 1 , Tingru Pan 1 , Tianqi Liu 1 , Na Wan 1 and Shu Li 1 1 College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, P. R. China Correspondence to: Shu Li, email: lishu@neau.edu.cn Keywords: cadmium, selenium, spleens, mitochondrial dynamics, apoptosis Received: January 28, 2017      Accepted: April 12, 2017      Published: April 30, 2017 ABSTRACT The aim of this study was to investigate the mechanism of cadmium-induced apoptosis in chicken spleens and the antagonistic effects of selenium. We duplicated the selenium-cadmium interaction model and examined the expression of apoptosis-, immune-, mitochondrial dynamics- and energy metabolism-related genes. The results demonstrated that after treatment with cadmium, the frequency of apoptosis was significantly increased, and the morphological characteristics of apoptosis were observed. The expression of pro-apoptotic genes was increased, and that of anti-apoptotic genes was decreased. The mRNA levels of tumor necrosis factor-α and interlenkin-1β were observably increased, but the interlenkin-2 and interferon-γ levels were markedly decreased. Furthermore, the mRNA and protein levels of dynamin-related protein 1 and mitochondrial fission factor were significantly enhanced, whereas mitofusin 1, mitofusin 2, and optic atrophy 1 were markedly decreased. The expression of hexokinase 1, hexokinase 2, aconitase 2, lactate dehydrogenase A, lactate dehydrogenase B, succinatedehydrogenase B, pyruvate kinase and phosphofructokinase were also reduced. Selenium supplements remarkably attenuated cadmium-induced effects ( p < 0.05). Based on the above results, conclude that the cadmium treatment promoted a mitochondrial dynamic imbalance and reduced energy metabolism, leading to apoptosis and immune dysfunction in chicken spleens, and selenium had an antagonistic effect on Cd-induced apoptosis.

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Antagonistic effects of selenium on cadmium-induced apoptosis by restoring the mitochondrial dynamic equilibrium and energy metabolism in chicken spleens.

Tianqi Liu

Papers

miR-200a-5p regulates myocardial necroptosis induced by Se deficiency via targeting RNF11

Ameliorative Effects of Selenium on Cadmium-Induced Injury in the Chicken Ovary: Mechanisms of Oxidative Stress and Endoplasmic Reticulum Stress in Cadmium-Induced Apoptosis.

MicroRNA-193b-3p regulates hepatocyte apoptosis in selenium-deficient broilers by targeting MAML1

Oxidative stress induced by Se-deficient high-energy diet implicates neutrophil dysfunction via Nrf2 pathway suppression in swine.

Antagonistic effects of selenium on cadmium-induced apoptosis by restoring the mitochondrial dynamic equilibrium and energy metabolism in chicken spleens.