It is reported that iron metabolism and ferroptosis can influence the occurrence and development of myeloid tumors, which can serve as therapeutic targets. Dysregulation of iron metabolism is present in a variety of myeloid neoplasms. The prognosis of acute myeloid leukemia is related to differential expression of molecules related to iron metabolism. The prognosis of myelodysplastic syndrome patients with iron overload is poor. Myeloproliferative neoplasms are often characterized by the coexistence of iron deficiency and erythrocytosis, which can be treated by targeting hepcidin. Myeloid tumor cells are susceptible to oxidative damage caused by the accumulation of reactive oxygen species and are sensitive to ferroptosis. Ferroptosis has anti-tumor effect in acute myeloid leukemia and myelodysplastic syndrome. Targeting ferroptosis can reverse imatinib resistance in chronic myeloid leukemia. This article reviews the characteristics of iron metabolism in the development and progression of myeloid neoplasms, as well as the mechanism of ferroptosis, to provide a basis for the development of new therapeutic strategies.
Ferroptosis ; Humans ; Iron/metabolism* ; Myelodysplastic Syndromes/pathology* ; Reactive Oxygen Species/metabolism* ; Leukemia, Myeloid, Acute/pathology* ; Hepcidins/metabolism* ; Iron Overload/metabolism* ; Myeloproliferative Disorders/metabolism* ; Prognosis

As the central organ of metabolism, the liver plays a pivotal role in the regulation of the synthesis and metabolism of various nutrients within the body. Ferroptosis, as a newly discovered type of programmed cell death caused by the accumulation of iron-dependent lipid peroxides, is involved in the physiological and pathological processes of a variety of acute and chronic liver diseases. Ferroptosis can accelerate the pathogenetic process of acute liver injury, metabolic associated fatty liver disease, alcoholic liver disease, viral hepatitis, and autoimmune hepatitis; while it can slower disease progression in advanced liver fibrosis and hepatocellular carcinoma. This suggests that targeted regulation of ferroptosis may impact the occurrence and development of various liver diseases. This article reviews the latest research progress of ferroptosis in various liver diseases, including acute liver injury, metabolic associated fatty liver disease, alcoholic liver disease, viral hepatitis, autoimmune hepatitis, liver fibrosis and hepatocellular carcinoma. It aims to provide insights for the prevention and treatment of acute and chronic liver diseases through targeting ferroptosis.
Humans ; Liver Diseases/etiology* ; Ferroptosis/physiology* ; Liver Neoplasms/pathology* ; Carcinoma, Hepatocellular/pathology* ; Liver Cirrhosis/etiology* ; Liver/pathology* ; Hepatitis, Autoimmune/metabolism* ; Liver Diseases, Alcoholic/metabolism*

Ferroptosis is defined as an iron-dependent regulated form of cell death driven by lipid peroxidation. In the past decade, it has been implicated in the pathogenesis of various diseases that together involve almost every organ of the body, including various cancers, neurodegenerative diseases, cardiovascular diseases, lung diseases, liver diseases, kidney diseases, endocrine metabolic diseases, iron-overload-related diseases, orthopedic diseases and autoimmune diseases. Understanding the underlying molecular mechanisms of ferroptosis and its regulatory pathways could provide additional strategies for the management of these disease conditions. Indeed, there are an expanding number of studies suggesting that ferroptosis serves as a bona-fide target for the prevention and treatment of these diseases in relevant pre-clinical models. In this review, we summarize the progress in the research into ferroptosis and its regulatory mechanisms in human disease, while providing evidence in support of ferroptosis as a target for the treatment of these diseases. We also discuss our perspectives on the future directions in the targeting of ferroptosis in human disease.
Humans ; Ferroptosis ; Autoimmune Diseases ; Cardiovascular Diseases ; Iron ; Musculoskeletal Diseases

Amino Acid Substitution ; Antineoplastic Agents/pharmacology* ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; Gastrointestinal Neoplasms/pathology* ; Humans ; MAP Kinase Signaling System/genetics* ; Mutation, Missense ; Receptor, ErbB-3/metabolism* ; Receptor, Fibroblast Growth Factor, Type 1/metabolism*

Recently, ferroptosis, an iron-dependent novel type of cell death, has been characterized as an excessive accumulation of lipid peroxides and reactive oxygen species. Emerging studies demonstrate that ferroptosis not only plays an important role in the pathogenesis and progression of chronic diseases, but also functions differently in the different disease context. Notably, it is shown that activation of ferroptosis could potently inhibit tumor growth and increase sensitivity to chemotherapy and immunotherapy in various cancer settings. As a result, the development of more efficacious ferroptosis agonists remains the mainstay of ferroptosis-targeting strategy for cancer therapeutics. By contrast, in non-cancerous chronic diseases, including cardiovascular & cerebrovascular diseases and neurodegenerative diseases, ferroptosis functions as a risk factor to promote these diseases progression through triggering or accelerating tissue injury. As a matter of fact, blocking ferroptosis has been demonstrated to effectively prevent ischemia-reperfusion heart disease in preclinical animal models. Therefore, it is a promising field to develope potent ferroptosis inhibitors for preventing and treating cardiovascular & cerebrovascular diseases and neurodegenerative diseases. In this article, we summarize the most recent progress on ferroptosis in chronic diseases, and draw attention to the possible clinical impact of this recently emerged ferroptosis modalities.
Animals ; Chronic Disease ; Ferroptosis ; physiology ; Iron ; metabolism ; Reactive Oxygen Species

Iron homeostasis plays an important role for the maintenance of human health. It is known that iron metabolism is tightly regulated by several key genes, including divalent metal transport-1(), transferrin receptor 1(), transferrin receptor 2(), ferroportin(), hepcidin(), hemojuvelin() and . Recently, it is reported that DNA methylation, histone acetylation, and microRNA (miRNA) epigenetically regulated iron homeostasis. Among these epigenetic regulators, DNA hypermethylation of the promoter region of , and bone morphogenetic protein 6 () genes result in inhibitory effect on the expression of these iron-related gene. In addition, histone deacetylase (HADC) suppresses gene expression. On the contrary, HADC inhibitor upregulates gene expression. Additional reports showed that miRNA can also modulate iron absorption, transport, storage and utilization via downregulation of and other genes. It is noteworthy that some key epigenetic regulatory enzymes, such as DNA demethylase TET2 and histone lysine demethylase JmjC KDMs, require iron for the enzymatic activities. In this review, we summarize the recent progress of DNA methylation, histone acetylation and miRNA in regulating iron metabolism and also discuss the future research directions.
Epigenesis, Genetic ; Gene Expression Regulation ; genetics ; Homeostasis ; Humans ; Iron ; metabolism ; Receptors, Transferrin

Zinc levels are high in pancreatic β-cells, and zinc is involved in the synthesis, processing and secretion of insulin in these cells. However, precisely how cellular zinc homeostasis is regulated in pancreatic β-cells is poorly understood. By screening the expression of 14 Slc39a metal importer family member genes, we found that the zinc transporter Slc39a5 is significantly down-regulated in pancreatic β-cells in diabetic db/db mice, obese ob/ob mice and high-fat diet-fed mice. Moreover, β-cell-specific Slc39a5 knockout mice have impaired insulin secretion. In addition, Slc39a5-deficient pancreatic islets have reduced glucose tolerance accompanied by reduced expression of Pgc-1α and its downstream target gene Glut2. The down-regulation of Glut2 in Slc39a5-deficient islets was rescued using agonists of Sirt1, Pgc-1α and Ppar-γ. At the mechanistic level, we found that Slc39a5-mediated zinc influx induces Glut2 expression via Sirt1-mediated Pgc-1α activation. These findings suggest that Slc39a5 may serve as a possible therapeutic target for diabetes-related conditions.

Objective To evaluate the effect of wireless wearable intelligent body temperature monitoring system on temperature monitoring of perioperative patients. Method The body temprature of 572 patients with abdoiminal surgery who hospitalized in our hospital from June 2017 to Juanuary 2018 was measured by mercury thermometers and wireless intelligent body temprature monitoring system four times a day for three days with toally 6864 times after surgery.The measured time and data by both ways were compared and its relativity were analyzed. Results The measured data by mercury thermometers and wireless intelligent body temprature monitoring system was compared with no statistical significance (P>0.05), but the time measured by wireless intelligent body temprature monitoring system was shorter (P＜0.05). The measured data of two ways was postively related (r=0.962,P＜0.05). Conclusions The measurement results by the wireless wearable intelligent body temperature monitoring system are the same as by mercury thermometers. The accuracy of the system is well validated, and it can improve the working efficiency of nurses.

BACKGROUND: Decreasing of absorption of zinc from small intestine can induce dermatitis, alopecia, growth and developmental disorder and so on. It is not very clear that how to keep homeostasis when there is low zinc concentration. The discoveries of zinc transporters and relative researches provide new study direction.OBJECTIVE: To study the effect of different zinc concentration on the expressions of divalent metal transporter 1 (DMT1) and human zinc-regulated transporter (ZRT), iron-regulated transporter (IRT)-like protein (ZIP) 4mRNA, and analyze the potential pathway of absorption of zinc from small intestine in low zinc concentration.DESIGN: Blank-controlled experiment.SETTING: Department of Military Hygiene, Navy Faculty, Second Military Medical University of Chinese PLA.MATERIALS: The experiment was accomplished in Department of Military Hygiene, Navy Faculty of Second Military Medical University of Chinese PLA between October 2004 and May 2005. Materials were human colon adenocarcinoma cells Caco2 that were purchased from Shanghai Institute of Cell of Chinese Academy of Sciences.Time-dependent effect: The expression of DMT1 and ZIP4 mRNA was detected with reverse transcription-polymerase chain reaction (RT-PCR) at 0,dependent effect: The expression of DMT1 and ZIP4 mRNA were measured after the 0, 2.5, 5, 7.5 and 10 μmol/L TPEN exposure, respectively, by RT-PCR.MAIN OUTCOME MEASURES: Time-and dose-dependent effect of zinc on the expression of DMT1 and ZIP4 mRNA in Caco2 cells.RESULTS: ①Time-dependent effect: Compared with 0 hour, the expression of DMT1 mRNA obviously increased at 6, 8 and 10 hours (P ＜ 0.05 ), but there was no significant change at 2 and 4 hours. The expression of ZIP4 mRNA markedly increased in all timing, and ZIP4 mRNA level at the 6th hour reached the peak with the prolongation of low zinc duration,which was 2.1 times ofthat at 0 hour. ②Dose-dependent effect: The expression of DMT1 mRNA distinctly increased at the concentration of 7.5 and 10 μmol/L TPEN exposure as compared with that of the control group (P ＜ 0.05), but there was no significant change at 2.5 and 5 μmol/L. The ZIP4 mRNA expression increased with the increasing of the concentration of TPEN, the expression of ZIP4 mRNA was 2.7 times of that at 0 μmol/L. CONCLUSION: Zinc can regulate the expression of DMT1 and ZIP4 mRNA in Caco2 cells, and there is time-and dose-dependent effect. But the mRNA expression of ZIP4 is more sensitive and prompt than DMT1. Cells can upregulate the expression of DMT1 and ZIP4 mRNA to keep the homeostasis in low zinc condition.

Objective To investigate the role of 15 kinds of growth regulatory factors in the pathogenesis of benign prostatic hyperplasia (BPH). Methods 15 kinds of growth regulatory factors involving cell proliferation and apoptosis were studied by immunohistochemistry with computer assisted quantitative image analysis.The mean percent area densities of stroma,epithelium and glandular lumen in BPH were examined by quantitative image analysis. Results Positive relations were found bewteen expressions of basic fibroblast growth factor (bFGF),transforming growth factor ?, fibronectin, type Ⅳ collagen and proportions of stroma (r=0.323?0.278?0.235?0.241,P