Mechanisms of norcantharidin against renal tubulointerstitial fibrosis.

Renal tubulointerstitial fibrosis (RTIF) is a common feature and inevitable consequence of all progressive chronic kidney diseases, leading to end-stage renal failure regardless of the initial cause. Although research over the past few decades has greatly improved our understanding of the pathophysiology of RTIF, until now there has been no specific treatment available that can halt the progression of RTIF. Norcantharidin (NCTD) is a demethylated analogue of cantharidin, a natural compound isolated from 1500 species of medicinal insect, the blister beetle (Mylabris phalerata Pallas), traditionally used for medicinal purposes.

Pharmacological mechanisms of norcantharidin against hepatocellular carcinoma.

Norcantharidin (NCTD) is a water-soluble synthetic small molecule drug that has been approved by the Chinese FDA for the treatment of cancer in China. Among these NCTD-treated cancers, hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide and one of the most extensively studied. Research over the past few decades has made great strides in understanding how NCTD induces mitotic arrest, anti-proliferation, anti-metastasis, apoptosis and cytotoxic autophagy or autophagic cell death in HCC.

Downregulation of hepcidin by norcantharidin in macrophage.

Norcantharidin (NCTD) is a demethylated analogue of cantharidin. It was recently demonstrated that NCTD reduces iron contents in the liver and spleen of mice , indicating that NCTD can affect iron metabolism hepcidin. Here, we investigated the effects of NCTD on expression of iron storage protein ferritin-light chain (Ft-L), transferrin receptor 1 (TfR1), divalent metal transporter 1 (DMT1), ferroportin 1 (Fpn1), hepcidin, iron regulatory protein 1 (IRP1), IL-6, p-JAK2 and p-STAT3 in lipopolysaccharides (LPS)-treated RAW264.

Norcantharidin down-regulates iron contents in the liver and spleen of lipopolysaccharide-treated mice.

Objective: The inhibiting effect of Norcantharidin (NCTD) on IL-6 (interleukin-6) and STAT3 and the involvement of the IL-6/STAT3 pathway in hepcidin expression prompted us to speculate that NCTD could affect iron metabolism.

Unlabelled: We examined the effects of NCTD on serum iron (SI) and transferrin (Tf) saturation, iron and ferritin light chain (FTL), transferrin receptor 1 (TfR1), divalent metal transporter 1 (DMT1), ferroportin 1 (Fpn1), iron regulatory protein 1 (IRP1) and hepcidin, as well as IL-6 and STAT3 in the liver, spleen and duodenum of mice treated with lipopolysaccharide (LPS) in vivo, using RT-PCR, Western blotting and immunofluorescence analysis.

Unlabelled: NCTD could increase SI and Tf saturation and reduce tissue iron and FTL content by affecting expression of cell-iron transport proteins TfR1, DMT1 and Fpn1.

The Role of Iron in Atherosclerosis in Apolipoprotein E Deficient Mice.

The role of iron in atherosclerosis is still a controversial and unsolved issue. Here, we investigated serum iron, expression of iron regulatory, transport and storage proteins, pro-inflammatory chemokines and cytokines in ApoE mice. We demonstrated that ApoE induced atherosclerosis and an increase in iron contents, expression of transferrin receptor 1 (TfR1), iron regulatory proteins (IRPs), heme oxygenase 1 (HO1), cellular adhesion molecules and pro-inflammatory cytokines, production of reactive oxygen species (ROS), and a reduction in expression of superoxide dismutase and glutathione peroxidase enzyme in aortic tissues.

Verapamil downregulates iron uptake and upregulates divalent metal transporter 1 expression in H9C2 cardiomyocytes.

Belgrade rats have a defect in divalent metal transport 1 (DMT1) with a reduced heart iron, indicating that DMT1 plays a physiological role in non-transferrin-bound iron (NTBI) uptake by cardiomyocytes. However, L-type voltage-dependent Ca channel (LVDCC) blockers were recently demonstrated to significantly reduce NTBI uptake by cardiomyocytes, implying that LVDCC plays a dominant role in NTBI uptake by cardiomyocytes under iron-overloaded conditions. These findings led us to hypothesize that the LVDCC blocker-induced reduction in NTBI uptake might result not only from the inhibition of LVDCC-mediated NTBI uptake but also from the suppression of DMT1-mediated NTBI uptake.

Apolipoprotein E deficiency induces a progressive increase in tissue iron contents with age in mice.

Association of both iron/hepcidin and apolipoprotein E (ApoE) with development of Alzheimer disease (AD) and atherosclerosis led us to hypothesize that ApoE might be required for body iron homeostasis. Here, we demonstrated that ApoE knock-out (KO) induced a progressive accumulation of iron with age in the liver and spleen of mice. Subsequent investigations showed that the increased iron in the liver and spleen was due to phosphorylated extracellular regulated protein kinases (pERK) mediated up-regulation of transferrin receptor 1 (TfR1), and nuclear factor erythroid 2-related factor-2 (Nrf2)-dependent down-regulation of ferroportin 1.

The involvement of nuclear factor-κB in astroprotection against ischemia-reperfusion injury by ischemia-preconditioned neurons.

Ischemic preconditioned (IP) neurons protect astrocytes against ischemia/reperfusion (I/R)-induced injury by inhibiting oxidative stress. However, the relevant mechanisms are unknown. Based on the role of nuclear factor-κB (NF-κB) in cell survival and adaption to oxidative stress, we hypothesized that NF-κB might be associated with astroprotection induced by IP neurons via upregulation of antioxidant enzymes.

Hepcidin inhibits autophagy in intracerebral hemorrhage models in vitro and in vivo.

Iron has a key role in the activation of the autophagic pathway in rats with intracerebral hemorrhage (ICH), and hepcidin has the ability to reduce brain iron in ICH-rats. We therefore hypothesized that hepcidin might be able to inhibit autophagy by reducing iron in an ICH brain. Here, we investigated the effects of Ad-hepcidin and/or hepcidin peptide on autophagic activities in ICH models in vitro and in vivo.

Kocuria soli sp. nov., an actinobacterium isolated from soil.

A Gram-stain-positive, aerobic, coccoid-shaped, non-spore-forming actinobacterial strain, designated M5W7-7, was isolated from a hot spring soil sample collected from Anshan, Liaoning province, PR China. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain M5W7-7 clustered closely with species of the genus Kocuria, and showed the highest sequence similarity of 97.1 % to Kocuria subflava YIM 13062.

Brachybacterium endophyticum sp. nov., a novel endophytic actinobacterium isolated from bark of Scutellaria baicalensis Georgi.

A Gram-positive, aerobic, coccus-shaped, non-spore-forming actinobacterium, designated strain M1HQ-2, was isolated from a surface-sterilized bark of Scutellaria baicalensis Georgi collected from Guizhou, China and tested using a polyphasic approach to determine its taxonomic position. Strain M1HQ-2 grew at 4-37 °C (optimum, 30 °C), pH 5.0-11.

Different Characteristics of Hepcidin Expression in IL-6+/+ and IL-6-/- Neurons and Astrocytes Treated with Lipopolysaccharides.

A region-specific regulation of inflammation on the expression hepcidin in the brain has been demonstrated, however, it remains unknown whether there is also a cell-specific regulation of inflammation on hepcidin in the brain. Here, we investigated the effects of lipopolysaccharides (LPS) on the expression of hepcidin mRNA and also the expression of IL-6 mRNA, the phosphorylation of STAT3 and the expression of ferroportin 1 (Fpn1) and ferritin light chain (Ft-L) proteins in neurons and astrocytes obtained from wild type (IL-6+/+) and IL-6 knockout (IL-6-/-) mice. We demonstrated that the responses of the expression of hepcidin and IL-6 mRNAs, the phosphorylation of STAT3, and the expression of Fpn1 protein to LPS in IL-6+/+ astrocytes and also the responses of the expression of hepcidin mRNA, the phosphorylation of STAT3 and the expression of Fpn1 protein to IL-6 in IL-6-/- astrocytes were much stronger than those in IL-6+/+ and IL-6-/- neurons.

[Consumptions of Meat, Dietary Fat, and Fatty-acids and Prevalence of Overweight/Obesity in Children and Adolescents-a Cross-sectional Survey in Chengdu].

Objectives: To determine the prevalence of overweight and obesity in children and adolescents aged 7-15 years in Longquanyi District of Chengdu and its association with consumptions of meat, dietary fat and fatty-acids.

Methods: A total of 1 811 children and adolescents aged 7-15 years in Longquanyi District were selected using stratified cluster sampling strategy. Their body mass, height and waist circumference were measured.

[Dietary Fiber and Pubertal Development among Children and Adolescents--a Cross-sectional Study in Chengdu, Sichuan].

Objective: To determine the association between intake of dietary fiber and pubertal development among children and adolescents in Chengdu.

Methods: A cross-sectional survey was undertaken in 1 340 children and adolescents aged 9-15 years. Data about dietary intake were collected through 24-h dietary self-recall.

[Consumptions of Meat and Dairy Products, Zinc Intake and Pubertal Development in Adolescents in Chengdu].

Objective: To determine the associations between meat, dairy and zinc intake and pubertal development in adolescents in Chengdu.

Methods: A total of 1320 children and adolescents aged 9-15 years in Chengdu were recruited using a stratified cluster sampling strategy. Dietary intake was assessed by the food frequency questionnaire (FFQ) and 3-day 24-hour dietary recall.