Deferasirox shows inhibition activity against cervical cancer in vitro and in vivo.

OBJECTIVE: Iron depletion may be a novel therapeutic strategy for cancer. This study aimed to assess the inhibition effects of deferasirox (DFX), an oral iron chelator, on cervical cancer. METHODS: In this study, we performed immunohistochemical analysis, enzyme-linked immunoassay, cell viability and invasive ability assay, cell cycle and apoptosis analysis, protein expression investigation, molecular mechanism investigation, and in vivo murine xenograft model to evaluate the impact of DFX on cervical cancer. RESULTS: The cervical cancer cell lines viability decreased and cell apoptosis was induced after DFX incubation. Additionally, DFX promoted cell cycle arrest by regulating the expression of cell cycle regulators cyclin D1, cyclin E and proliferating cell nuclear antigen (PCNA) in cervical cancer cell lines. DFX also decreased cell invasion by upregulating the expression of NDRG1 and downregulating c-Myc. The activation of Akt and the MEK/ERK signaling pathway was inhibited by DFX. DFX also significantly suppressed xenograft tumor growth, decreased the levels of ferritin in serum and tumor tissue, reduced iron deposits and reactive oxygen species (ROS) levels in xenografts of DFX-treated group compared with the control group, with no serious side effects. CONCLUSION: Present study demonstrated the inhibitory effect of DFX against cervical cancer, and provided a potential therapeutic agent for cervical cancer.

Clioquinol Attenuates Pulmonary Fibrosis through Inactivation of Fibroblasts via Iron Chelation.

Strict control of iron homeostasis is critical for the maintenance of normal lung function. Iron accumulates in the lungs of patients with idiopathic pulmonary fibrosis (PF), but the characteristics of iron metabolism in the pathogenesis of PF and related targeting therapeutics are not well studied. In this study, we investigated the cellular and molecular characteristics of iron metabolism in fibrotic lungs and further explored the efficacy of clioquinol (CQ) for the treatment of PF as well as its functional mechanism. Iron aggregates accumulated in the lungs of patients with idiopathic PF, and FTL (ferritin light chain) transcripts were increased in their pulmonary fibroblasts. In the bleomycin (BLM)-induced PF (BLM-PF) mouse model, pulmonary iron accumulation is a very early and concomitant event of PF. Labile iron pool levels in both fibroblasts and macrophages from the BLM-PF model were elevated, and iron metabolism was dysregulated. CQ attenuated PF induced by BLM and FITC, and iron-saturated CQ did not alleviate BLM-PF. Furthermore, CQ inhibited the activation of fibroblasts, including proliferation, fibrotic differentiation, proinflammatory cytokine secretion, and migration. In conclusion, our study demonstrated that CQ, acting as an iron chelator, attenuates experimental PF through inactivation of fibroblasts, providing support for targeting iron metabolism as a basis for PF treatment.

Deferasirox protects against hydrogen peroxide-induced cell apoptosis by inhibiting ubiquitination and degradation of p21WAF1/CIP1.

Deferasirox (DFX) is an iron chelator approved for the treatment of iron overload diseases. However, the role of DFX in oxidative stress-induced cell apoptosis and the exact molecular mechanisms underlying these processes remain poorly understood and require further investigation. In this study, we found that DFX rendered resistant to H2O2-induced apoptosis in HEK293T cells, reduced the intracellular levels of the labile iron pool (LIP) and oxidative stress induced by H2O2. Furthermore, DFX inhibited the ubiquitination and degradation of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21) via modulation of the interaction of p21 with SCF-Skp2. DFX also showed the inhibition effect on the activation of c-Jun N-terminal kinase (JNK), pro-caspase-3 and related mitochondrial apoptosis pathway induced by H2O2. These results provide novel insights into the molecular mechanism underpinning iron-mediated oxidative stress and apoptosis, and they may represent a promising target for therapeutic interventions in related pathological conditions.

Comparative Analysis of 95 Patients with Different Severity in the Early Outbreak of COVID-19 in Wuhan, China.

OBJECTIVE: To explore the clinical characteristics of patients with different severity in the early outbreak of COVID-19, hoping to provide reference for clinical diagnosis and treatment. METHODS: We retrospectively analyzed the clinical data of 95 COVID-19 patients in Wuhan Red Cross Hospital of China from January 17 to February 13, 2020. All patients were investigated with epidemiological questionnaires. Outcomes were followed up until April 1, 2020. RESULTS: There were 53 males and 42 females, aged 22-84 years (mean 57.3 years). Clinical classification included 54 cases of common type, 27 cases of severe type, and 14 cases of critical type. Six patients had been exposed to the local Huanan seafood market. There were 38 clusters of COVID-19, including 27 family clusters and 11 work unit clusters. Common symptoms included fever (86 (90.5%) of 95), cough (73 (76.8%)), and fatigue (50 (52.6%)). Laboratory findings showed that the most common abnormalities were lymphopenia (75 (78.9%)), elevated D-dimer (60 (63.2%)), and elevated C-reactive protein (56 (58.9%)) on admission. All patients had abnormal chest computed tomography, showing patchy shadows or ground-glass opacities. Severe and critical cases were older, more likely to have shortness of breath, more likely to have underlying comorbidities, and more likely to have abnormal laboratory findings than common cases. The prognosis of patients with different degrees of severity was significantly different. All common and severe patients (100%) were cured and discharged from the hospital, while 10 (71.4%) of 14 critical patients died. CONCLUSIONS: COVID-19 has fast transmission speed and high pathogenicity. We must assess the severity of the disease and take corresponding treatment measures as early as possible.

Mitochondrial ferritin, a new target for inhibiting neuronal tumor cell proliferation.

Mitochondrial ferritin (FtMt) has a significant effect on the regulation of cytosolic and mitochondrial iron levels. However, because of the deficiency of iron regulatory elements (IRE) in FtMt's gene sequence, the exact function of FtMt remains unclear. In the present study, we found that FtMt dramatically inhibited SH-SY5Y cell proliferation and tumor growth in nude mice. Interestingly, excess FtMt did not adversely affect the development of drosophila. Additionally, we found that the expression of FtMt in human normal brain tissue was significantly higher than that of neuroblastoma, but not higher than that of neurospongioma. However, the expression of transferrin receptor 1 is completely opposite. We therefore hypothesized that increased expression of FtMt may negatively affect the vitality of neuronal tumor cells. Therefore, we further investigated the underlying mechanisms of FtMt's inhibitory effects on neuronal tumor cell proliferation. As expected, FtMt overexpression disturbed the iron homeostasis of tumor cells and significantly downregulated the expression of proliferating cell nuclear antigen. Moreover, FtMt affected cell cycle, causing G1/S arrest by modifying the expression of cyclinD1, cyclinE, Cdk2, Cdk4 and p21. Remarkably, FtMt strongly upregulated the expression of the tumor suppressors, p53 and N-myc downstream-regulated gene-1 (NDRG1), but dramatically decreased C-myc, N-myc and p-Rb levels. This study demonstrates for the first time a new role and mechanism for FtMt in the regulation of cell cycle. We thus propose FtMt as a new candidate target for inhibiting neuronal tumor cell proliferation. Appropriate regulation of FtMt expression may prevent tumor cell growth. Our study may provide a new strategy for neuronal cancer therapy.

Quantum dots-hemin: Preparation and application in the absorption of heme iron.

The absorption mechanism of heme iron remains unclear due to the limit of labeling techniques. Quantum dots (QDs) are powerful fluorescent probes resistant to photobleaching, however, there is no data about the application of QDs in heme iron absorption. Herein, we prepared hemin-coated CdSe/ZnS (QDs-hemin), and studied their absorption in vitro and in vivo. Results showed that QDs-hemin had uniform particle sizes, physiological stability and high joint efficiency. Moreover, QDs-hemin could be successfully absorbed gradually into the duodenum with the time using synchrotron radiation micro X-ray fluorescence and confocal laser scanning microscopy. Furthermore, QDs-hemin were observed to degrade in lysosomes, and their absorption was blocked by Heme Carrier Protein 1 (HCP1) antibody and HCP1 siRNA. All the results demonstrate that QDs can be a good tracer for heme iron and that HCP1 pathway is critical and predominant over the endocytosis pathway in the absorption mechanism.

The effect of anti-inflammatory properties of ferritin light chain on lipopolysaccharide-induced inflammatory response in murine macrophages.

Ferritin light chain (FTL) reduces the free iron concentration by forming ferritin complexes with ferritin heavy chain (FTH). Thus, FTL competes with the Fenton reaction by acting as an antioxidant. In the present study, we determined that FTL influences the lipopolysaccharide (LPS)-induced inflammatory response. FTL protein expression was regulated by LPS stimulation in RAW264.7 cells. To investigate the role of FTL in LPS-activated murine macrophages, we established stable FTL-expressing cells and used shRNA to silence FTL expression in RAW264.7 cells. Overexpression of FTL significantly decreased the LPS-induced production of tumor necrosis factor alpha (TNF-α), interleukin 1ß (IL-1ß), nitric oxide (NO) and prostaglandin E2 (PGE2). Additionally, overexpression of FTL decreased the LPS-induced increase of the intracellular labile iron pool (LIP) and reactive oxygen species (ROS). Moreover, FTL overexpression suppressed the LPS-induced activation of MAPKs and nuclear factor-κB (NF-κB). In contrast, knockdown of FTL by shRNA showed the reverse effects. Therefore, our results indicate that FTL plays an anti-inflammatory role in response to LPS in murine macrophages and may have therapeutic potential for treating inflammatory diseases.

Deferoxamine attenuates lipopolysaccharide-induced inflammatory responses and protects against endotoxic shock in mice.

To examine the role of the intracellular labile iron pool (LIP) in the induction of inflammatory responses, we investigated the anti-inflammatory effect of the iron chelator deferoxamine (DFO) on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 macrophage cells and endotoxic shock in mice in the present study. Our data showed that DFO significantly decreased LPS-induced LIP and ROS upregulation. We then found that DFO inhibited phosphorylation of MAP kinases such as ERK and p38 and also inhibited the activation of NF-κB induced by LPS. Furthermore, the production of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), nitric oxide (NO) and prostaglandin E2 (PGE2) induced by LPS was inhibited by DFO in RAW264.7 macrophages. Administration of DFO significantly decreased the mortality and improved the survival of septic mice with lethal endotoxemia in LPS-injected mice. These results demonstrate that iron plays a pivotal role in the induction of inflammatory responses and against septic shock. DFO has effective inhibitory effect on the production of inflammatory mediators via suppressing activation of MAPKs and NF-κB signaling pathways; it also has a protective effect on LPS-induced endotoxic shock in mice. Our findings open doors to further studies directed at exploring a new class of drugs against septic shock or other inflammatory diseases by modulating cellular chelatable iron.

Age-dependent expression of duodenal cytochrome b, divalent metal transporter 1, ferroportin 1, and hephaestin in the duodenum of rats.

BACKGROUND AND AIM: The body's requirement for iron is different at different developmental stages. However, the molecular mechanisms of age-dependent iron metabolism are poorly understood. In the present study, we investigated the expression of iron transport proteins in the duodenum of Sprague-Dawley rats at five different age stages. METHODS: Male Sprague-Dawley rats at postnatal week (PNW) 1, 3, 12, 44, and 88 were employed in the study. Serum iron status and tissue non-heme iron concentrations in the spleen, liver, bone marrow, heart, kidney, duodenal epithelium, and gastrocnemius were examined at each age stage. The expression of duodenal cytochrome b (DcytB), divalent metal transporter 1 (DMT1), ferroportin 1 (FPN1), hephaestin, and hepcidin were measured by real-time polymerase chain reaction or Western blot. RESULTS: The levels of serum iron and transferrin saturation were higher in the rats at PNW1 and 3 than in those at PNW12, 44, and 88. Non-heme iron contents decreased from PNW1 to PNW3 and then increased thereafter. Duodenal DcytB, DMT1, and FPN1 increased to the highest level at PNW3 and then decreased from PNW12 to 88. The hepatic hepcidin mRNA level decreased to the lowest level at PNW3 and then increased with age. CONCLUSION: Our findings showed that age had a significant effect on body iron status. The increased duodenal DcytB, DMT1, and FPN1 expression can enhance intestinal iron absorption to meet the high iron requirements in infants. Hepcidin or enterocyte iron levels may be involved in the regulation of age-dependent FPN1, DMT1, and DcytB expression in the duodenum.

Regulation of histone demethylase KDM6B by hypoxia-inducible factor-2α.

Lysine (K)-specific demethylase 6B (KDM6B) is a histone H3K27 demethylase, which specifically catalyzes the demethylation of H3 lysine-27 tri/dimethylation (H3K27me3/2). KDM6B can activate gene transcription by promoting transcriptional elongation which is associated with RNA polymerase II and related elongation factors. So KDM6B is important for the regulation of gene expression. Previous studies have indicated that several histone demethylases such as KDM3A, KDM4B, and KDM4C are regulated by hypoxia-inducible factor (HIF). But, the effect of hypoxia on KDM6B is not fully understood. In this study, we found that the expression levels of KDM6B mRNA and protein are modestly up-regulated under hypoxia (1% O2) or mimic hypoxia (desferrioxamine mesylate or CoCl2 treatment) (P<0.05). The result of RNAi shows that the up-regulation of KDM6B is dependent on HIF-2α, but not on HIF-1α. The result of chromatin immunoprecipitation assay indicates that there is a hypoxia response element in KDM6B promoter (-4041 to -4037). The result of Co-IP assay indicates that KDM6B can form complex with HIF-2α or HIF-1α. The knockdown experiment implies that KDM6B is a potential regulator for HIF-2α target genes. These data demonstrate that KDM6B is a new hypoxia response gene regulated by HIF-2α. Our results also show that KDM6B is a potential co-activator of HIF-α, which is important for the activation of hypoxia response genes.

Gene expression profiles of sodium-dependent vitamin C transporters in mice after alcohol consumption.

Alcoholic liver disease (ALD) is a serious liver problem in western countries. Our previous study has demonstrated that vitamin C plays a protective role in ALD. The vitamin C homeostasis is tightly regulated by sodium-dependent vitamin C transporters (SVCTs) 1 and 2. But the role of two SVCTs in ALD is less understood. In this study, we examined the expression patterns of two SVCTs in mice after alcohol consumption. Our results suggested that alcohol consumption obviously increased the expression of two SVCTs in liver and SVCT1 in kidney and intestine, which is important for vitamin C absorption. Vitamin C supplement increased the sera vitamin C content and ameliorated the symptom of ALD. Intestinal absorption and renal re-absorption mediated by SVCT1 are key factors to increase the sera vitamin C content after alcohol consumption. We proposed that both reactive oxygen species and low vitamin C concentration regulate the expression of SVCTs, and the protective role of vitamin C is mediated by suppressing the stability of hypoxia-inducible factor-1α. Thus, our study is significant for the understanding of vitamin C homeostasis in ALD and for better use of other antioxidants in ALD therapy.

[Tumor suppressor role of chromatin-remodeling factor ARID1A].

The mammalian SWI/SNF complex is one of ATP-dependent chromatin-remodeling complexes, which plays important roles in cell proliferation, differentiation, development and tumor suppression. ARID1A (AT-rich interactive domain-containing protein 1A) is a large subunit of SWI/SNF complex, and also an ARID family member with non- sequence-specific DNA binding activity. ARID1A is a tumor suppressor gene which is frequently mutated in many cancers, such as ovarian, bladder and gastric cancers. ARID1A can suppress cell proliferation through the up-regulation of p21 and the down-regulation of E2F-responsive genes. These findings on ARID1A and its role of tumor suppression contribute to understanding the mechanism of cancer development and developing new therapy for cancer.It is introduced in the review that ARID1A basic characteristic, related to cancer development, and biological role for full understanding of ARID1A.

Expression and significance of histone H3K27 demethylases in renal cell carcinoma.

BACKGROUND: The histone H3K27 demethylases UTX and JMJD3 are important regulatory factors that modulate gene expression by altering the physical state of chromatin. Previous studies have indicated an abnormal H3K27 methylation status in carcinogenesis. We therefore investigated the expression patterns of UTX and JMJD3 in renal cell carcinoma (RCC) and their roles in cancer development. METHODS: The mRNA expression levels of the UTX and JMJD3 genes were determined in cancer tissues and adjacent normal tissues in 36 patients with primary RCC, using quantitative real-time-polymerase chain reaction. The UTX and JMJD3 protein contents were measured by western blotting and immunohistochemical analysis. RESULTS: UTX and JMJD3 transcripts were significantly increased in cancer tissues compared to normal tissues (P < 0.05). mRNA levels of the inhibitor of cyclin-dependent kinases 4 and 6 p16INK4a were also increased in cancer tissues (P < 0.001). Western blotting indicated that levels of both demethylases were increased in cancer tissues. The level of tri-methylated H3K27 (H3K27me3) was lower in cancer tissues compared to normal tissues, but expression of the H3K27 methyltransferase EZH2 was increased (P < 0.05). These results suggest that the two H3K27 demethylases may play critical roles in the regulation of H3K27 methylation status in RCC. Immunohistochemical analysis confirmed that UTX and JMJD3 expression were upregulated in cancer tissues compared to adjacent tissues. CONCLUSIONS: This study demonstrated that UTX and JMJD3 were upregulated in cancer tissues, suggesting that they may be involved in the development of primary RCC. The potential roles of H3K27 demethylases as biomarkers in the early diagnosis of RCC need to be further explored.

Ascorbate antagonizes nickel ion to regulate JMJD1A expression in kidney cancer cells.

Abnormal expression of histone demethylase Jumonji domain-containing protein 1A (JMJD1A) is associated with many kinds of cancers. JMJD1A is also a hypoxic response gene and its expression is regulated by hypoxia-inducible factor-1α (HIF-1α). In this study, we determined the role of JMJD1A in development and hypoxia pathway. We also measured the expression of JMJD1A and two hypoxia factors glucose transporter 1 (GLUT1) and vascular endothelial growth factor (VEGF) in 786-0 and HEK293 cells treated with different concentrations of NiCl(2) (2.5-100 µM) for 24 h, and found that JMJD1A mRNA and protein were up-regulated with increased concentrations of NiCl(2). We then observed that ascorbate could retard the up-regulated effect of NiCl(2)-induced JMJD1A expression in a dose-dependent manner through decreasing the stability of HIF-1α protein. Immunohistochemical analysis further demonstrated ascorbate antagonized Ni(2+)-induced up-regulation of JMJD1A expression in 786-0, HEK293, and OS-RC-2 cells. These findings suggest that both Ni(2+) and ascorbate can regulate the expression of histone demethylase JMJD1A, which is important for cancer development or inhibition.

JNK/Itch Axis Mediates the Lipopolysaccharide-Induced Ubiquitin-Proteasome-Dependent Degradation of Ferritin Light Chain in Murine Macrophage Cells.

Ferritin, which is composed of a heavy chain and a light chain, plays a critical role in maintaining iron homeostasis by sequestering iron. The ferritin light chain (FTL) is responsible for the stability of the ferritin complex. We have previously shown that overexpression of FTL decreases the levels of the labile iron pool (LIP) and reactive oxygen species (ROS) in lipopolysaccharide (LPS)-treated murine macrophage cells. The protein level of FTL was downregulated by LPS within a short treatment period. However, the mechanism underlying the LPS-induced changes in the FTL levels is not known. In the present study, we report that LPS induces the ubiquitin-proteasome-dependent degradation of FTL and that the mechanism of LPS-induced FTL degradation involves the JNK/Itch axis. We found that LPS downregulates the protein and mRNA levels of FTL in a time-dependent manner. The proteasome inhibitor MG-132 significantly reverses the LPS-induced decrease in FTL. Furthermore, we observed that LPS treatment cannot cause ubiquitination of the lysine site (K105 and K144) mutant of FTL. Interestingly, LPS-mediated ubiquitin-dependent degradation of FTL is significantly inhibited by the JNK-specific inhibitor SP600125. Moreover, LPS could upregulate the protein level of E3 ubiquitin ligase Itch, a substrate of JNK kinases. Immunoprecipitation analyses revealed an increase in the association of FTL with Itch, a substrate of JNK kinases, in response to LPS stimulation. SP600125 decreased LPS-induced Itch upregulation. Taken together, these results suggest that LPS stimulation leads to the degradation of FTL through the ubiquitin-proteasome proteolytic pathway, and this FTL degradation is mediated by the JNK/Itch axis in murine macrophage cells.

Vitamin C protective role for alcoholic liver disease in mice through regulating iron metabolism.

Alcoholic liver disease (ALD) is a major medical complication of drinking alcohol, and commonly accompanied with hepatic iron overload and liver injuries. Oxidative stress plays an important role in pathogenesis of ALD and also leads to iron-metabolic disorders. In this study, the effects of vitamin C (Vc) on iron metabolism-related genes expression and liver protection from drinking in mice were investigated. Twenty-four male kunming mice were divided into four groups (six mice per group): control (water drinking); alcohol group (20% alcohol drinking), alcohol + low Vc group (adding 50 mg/kg Vc daily) and alcohol + high Vc group (adding 100 mg/kg Vc daily). All these mice were sacrificed after 7 days. Vc can ameliorate the increase of sera alanine aminotransferase (ALT) activity and hepatic iron overload of drinking alcohol in mice. Vc increases the expression of the iron-regulated hormone hepcidin and decreases transferrin receptor 1 (TfR1) expression in liver. Vc also down-regulates the expression of ferroportin 1 (Fpn1) in the intestine and decreases the iron release to blood. In conclusion, Vc ameliorated the alcoholic liver injuries through regulating the iron metabolism-related genes expression.

Calcitonin increases hepatic hepcidin expression through the BMP6 of kidney in mice.

BACKGROUND: Osteoporosis is frequently accompanied by iron disorders. Calcitonin (CT) was approved as a clinical drug to treat osteoporosis. Hepcidin is a peptide hormone that is secreted by the liver and controls body iron homeostasis. Hepcidin deficiency leads to iron overload diseases. This study was aimed at investigating the effect of CT on hepatic hepcidin and the mechanism by which CT modulates hepatic hepcidin pathways and iron metabolism. METHOD: RT-PCR, Western blot, ELISA and siRNA were used to detect the effect of CT on iron metabolism in vivo and in vitro. In addition, the regulatory signal molecules of hepcidin were measured to explore the molecular mechanism of its regulation. RESULTS: The results showed that CT strongly increased hepcidin expression and altered iron homeostasis, after mice were intraperitoneal injection of CT. In response to CT administration, BMP6 level in kidney and the serum BMP6 was increased significantly. The phosphorylation of Smad1/5/8 proteins in liver was increased at 3 h and 6 h. Moreover, the Bmp inhibitor LDN-193,189 pretreatment significantly attenuated the CT-mediated increases in phosphorylated Smad1/5/8 and Hamp1 mRNA levels. Calcitonin receptor (CTR) siRNA transfection significant suppressed the role of CT on BMP6 expression in Caki-1 cells. CONCLUSION: Our results suggest that CT strongly induces hepcidin expression and affected iron metabolism. It will provide a new strategy for the treatment of calcium iron related diseases.

Nuciferine protects against folic acid-induced acute kidney injury by inhibiting ferroptosis.

BACKGROUND AND PURPOSE: Acute kidney injury is a common clinical problem with no definitive or specific treatment. Therefore, the molecular mechanisms of acute kidney injury must be fully understood to develop novel treatments. Nuciferine, a major bioactive compound isolated from the lotus leaf, possesses extensive pharmacological activities. Its effect on folic acid-induced acute kidney injury, however, remains unknown. Here, we aimed to clarify the pharmacological effects of nuciferine and its mechanisms of action in acute kidney injury. EXPERIMENTAL APPROACH: The effects of nuciferine on folic acid-induced acute kidney injury in mice were investigated. HK-2 human proximal tubular epithelial cells and HEK293T HEK cells were used to evaluate the protective effect of nuciferine on RSL3-induced ferroptosis. KEY RESULTS: Nuciferine treatment mitigated the pathological alterations, ameliorated inflammatory cell infiltration and improved kidney dysfunction in mice with folic acid-induced acute kidney injury. In HK-2 and HEK293T cells, nuciferine significantly prevented RSL3-induced ferroptotic cell death. Mechanistically, nuciferine significantly inhibited ferroptosis by preventing iron accumulation and lipid peroxidation in vitro and in vivo. Moreover, knockdown of glutathione (GSH) peroxidase 4 (GPX4) abolished the protective effect of nuciferine against ferroptosis. CONCLUSION AND IMPLICATIONS: Nuciferine ameliorated renal injury in mice with acute kidney injury, perhaps by inhibiting the ferroptosis. Nuciferine may represent a novel treatment that improves recovery from acute kidney injury by targeting ferroptosis.

Nitric Oxide contributes to the regulation of iron metabolism in skeletal muscle in vivo and in vitro.

Nitric Oxide (NO) plays an important role in iron redistribution during exercise, while its molecular regulatory mechanism is still not clear. Our present studies were to investigate the effects of NO on iron metabolism and to elucidate the regulatory mechanism of iron transport in skeletal muscle both in vivo and in vitro. One group of male Wistar rats (300 +/- 10 g) were subjected to an exercise of 30 min on a treadmill for 5 weeks (exercise group, EG, 6 rats) and the other one was placed on the treadmill without running (control group, CG, 6 rats). The cultured L6 rat skeletal muscle cells were treated with either 0.5 mM SNAP (NO donor) or not for 24 h, and their iron release and intake amount were examined by measuring radiolabelled (55)Fe. The results showed: (1) The NO content (CG, 1.09 +/- 0.18 micromol/g vs. EG, 1.49 +/- 0.17 micromol/g) and non-heme iron in gastrocnemius (CG, 118.35 +/- 11.41 microg/g vs. EG, 216.65 +/- 11.10 microg/g) of EG were significantly increased compared with CG. (2) The expression of DMT1 (IRE) and TfR1 of EG was increased. (3) The iron intake was increased in L6 cells treated with SNAP (P < 0.01). (4) Western blot results showed the protein level of both TfR1 and DMT1 (IRE) in SNAP cells were up-regulated, while the expression of FPN1 was down-regulated (P < 0.05). The data suggested that the induced elevation of NO level by exercise lead to the up-regulation of both TfR1 and DMT1 (IRE), which in turn increasing the iron absorption in skeletal muscle.

[A case report on treatment of compartment syndrome with novel coronavirus pneumonia].

A 49-year-old male patient with compartment syndrome of the right leg caused by acute carbon monoxide poisoning was admitted on December 30, 2019. The patient had a 10-year history of chronic nephritis and began dialysis treatment due to renal failure 1 month ago. Emergency surgical decompression for compartment syndrome was performed after admission. Two weeks later, the patient was diagnosed as the novel coronavirus pneumonia caused by 2019 novel coronavirus (2019-nCoV) infection. Then, the patient was transferred to the isolation ward, where he was given anti-infection, anti-virus, expectorant, heat-clearing and detoxifying drugs, bedside dialysis, and nutrition support symptomatic treatment. After 2 weeks of treatment, the patient is getting better, with no fever, cough, wheezing, and other discomfort. Meanwhile, the sensory and motor functions of right lower limb recovered gradually. This case is rare, severe, and difficult to diagnose and treat. It is the first reported case of novel coronavirus pneumonia after orthopedic surgery.