Potential signal pathway of all-trans retinoic acid for MMP-2 and MMP-9 expression in injury podocyte induced by adriamycin

Abstract

All-trans-retinoic acid (ATRA) can regulate some specific genes expression in various tissue and cells via nuclear retinoic acid receptors (RARs), including three subtypes: retinoic acid receptor-alpha (RAR-α), retinoic acid receptor-beta (RAR-β) and retinoic acid receptor-gamma (RAR-γ). Podocyte injury plays a pivotal role in the progression of glomerulosclerosis (GS). This study was performed to study the potential signal pathway of ATRA in the expression of matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9) in injury podocyte. Cells were divided into three groups: group of negative control (NC), group of injury podocyte induced by adriamycin (ADR) (AI) and group of ADR inducing podocyte injury model treated with ATRA (AA). The cells morphology changes were detected using microscope and scanning electron microscopy. MMP-2 and MMP-9 enzymic activity was detected using the gelatin zymography method. Protein and mRNA expressions of MMP-2, MMP-9, RAR-α, RAR-β and RAR-γ were measured by western-blot and real-time RT-PCR. Enzymatic activity of MMP-2 and MMP-9 in group AA was significantly enhanced compared to AI group after ATRA-treated 24?h (p?<?0.05). The protein and mRNA expressions of MMP-2/MMP-9 in group AA were significantly increased than those in group AI at both 12 and 24?h time points (p?<?0.05). Compared to group AI, RAR-α and RAR-γ protein/mRNA expressions of group AA were significantly increased at both 12 and 24?h time points (p?<?0.05). There was no difference for the expression of RAR-β between group AI and group AA (p?>?0.05). RAR-α protein level was positively correlated with MMP-2 or MMP-9 protein expression (p?<?0.05), and RAR-γ protein level was also positively correlated with MMP-2 or MMP-9 protein expression (p?<?0.05). In conclusion, ATRA may increase expression of MMP-2 and MMP-9 by the potential signal pathway of RAR-α and RAR-γ in injury podocyte induced by adriamycin, but not RAR-β.     

Polymorphism identification in GDF9 gene and its association analysis with reproduction traits in Jinghai Yellow chicken

Abstract

GDF9 (growth differentiation factor 9) belongs to the transforming growth factor-β (TGF-β) superfamily and plays an irreplaceable role in female fertility. To reveal its genetic effects on productivity performance in chickens, 373 Jinghai Yellow chickens were chosen randomly to detect SNPs in GDF9 by PCR-SSCP and DNA sequencing methods. Eventually, four SNPs (g.2053G?>?A, g.2275T?>?C, g.2338C?>?T, g.2420T?>?C) in total had been detected. Amongst them, g.2420T?>?C was first found significantly associated with reproduction trait in chickens and heterozygous type C₂T₂ had higher average egg weight at 300?days of age (AEWD300) than T₂T₂ (p?<?0.01). Least squares analysis showed that age at first laying (AFE) of H1 and H1H1 chickens were significantly earlier than that of H7 and H7H7 ones, respectively (p?<?0.05). H1H5 hens showed higher AEWD300 than H4H7 ones (p?<?0.05). For total egg number at 300?days of age (END300), mean of H5H5 was significantly higher than that of H4H4 (p?<?0.05). Hence, the study suggested that hybrid vigor at g.2420T?>?C could be utilized in practice. H1H1, H1H5 and H5H5 could be the dominant diplotypes for chicken breeding. The study may contribute to the breeding progress of productive chickens and supply reference for oviparous animal production practice.     

Effects of Selenium Supplementation on Expression of Endothelin-1 and Its Receptors in Pulmonary Microvascular Endothelial Cells from Chick Embryos

The objective of this study was to evaluate the effects of supplemental selenium (Se) on expression of endothelin-1 (ET-1) and its receptors in cultured chick embryos pulmonary microvascular endothelial cells (PMVECs). To accomplish this, PMVECs were treated in Se-deficient or Se-supplement (12, 24, 50, 100?ng/ml) culture medium for 48?h. Low Se medium was achieved by reducing serum concentrations and the essential growth factors were added. After the incubation, the effects of supplemental Se on ET-1 and its receptors gene expression were assessed by quantitative real-time PCR (qRT-PCR). Compared with the control group, our results showed that among the different concentrations of Se supplement, the levels of ET-1 gene expression treated with both the moderate Se doses (24, 50?ng/ml, P?<?0.01, P?<?0.01, respectively) and the high doses (100?ng/ml, P?<?0.05) were noticeably decreased, the low-dose group (12?ng/ml), which showed no changes. Meanwhile, Se supplement (24, 50, 100?ng/ml) was found to be effective in reducing the expression levels of ETA (P?<?0.01, P?<?0.05, P?<?0.05, respectively) in cultured PMVECs grown in low Se medium. However, there were no significant changes (P?>?0.05) in ETB mRNA levels during the cell proliferation. These observations indicated that Se may play both direct and indirect role in the regulation of ET-1 and its receptors gene expression and their production in avian PMVECs. Se supplement decreases in ET-1 and ETA production in Se-deficient PMVECs may partly explain the mechanism of the protective effects of the Se on the cardiovascular system.     

Role of ascitic endocan levels in the diagnosis of spontaneous bacterial peritonitis in decompensated cirrhosis

Abstract

Objective: To assess the role of ascitic endocan levels in the diagnosis of spontaneous bacterial peritonitis (SBP) in decompensated cirrhosis.

Methods: Ascites samples, as well as demographic and laboratory data, were collected at admission from patients with decompensated cirrhosis. Ascitic endocan, tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were measured by ELISA. The influencing factors of SBP, the correlation of ascitic endocan with other inflammatory indicators, and the diagnostic value of ascitic endocan for SBP were analyzed.

Results: A total of 167 patients were enrolled, 39 with the SBP group and 128 in the non-SBP group. Ascitic endocan, TNF-α, and IL-6 levels were significantly higher in the SBP group than in the non-SBP group (p?<?0.001). Multivariate analysis demonstrated that ascitic endocan was an independent risk factor for SBP [OR = 1.006 (95% CI: 1.002–1.011); p?<?0.001]. Endocan was positively correlated with ascites polymorphonuclear leukocytes, TNF-α, and IL-6. ROC curve analysis showed that ascitic endocan had an AUC of 0.805 for the diagnosis of SBP (p?<?0.001) and had a sensitivity of 82.1% and specificity of 73.4% when the cut-off value was 295.011?pg/ml.

Conclusions: Ascitic endocan level is an independent risk factor and a valuable diagnostic indicator for SBP in decompensated cirrhosis.     

Productivity and Selenium Concentrations in Egg and Tissue of Laying Quails Fed Selenium from Hydroponically Produced Selenium-Enriched Kale Sprout (Brassica oleracea var. alboglabra L.)

This study aimed to determine the effectiveness of Se from hydroponically produced Se-enriched kale sprout (HPSeKS) on productive performance, egg quality, and Se concentrations in egg and tissue of laying quails. Two-hundred quails, 63 days of age, were divided into four groups. Each group consisted of five replicates and each replicate had ten birds, according to a completely randomized design. The experiment lasted for 6 weeks. The dietary treatments were T1 (control diet), T2 (control diet plus 0.2 mg Se/kg from sodium selenite), T3 (control diet plus 0.2 mg Se/kg from Se-enriched yeast), T4 (control diet plus 0.2 mg Se/kg from HPSeKS). The findings revealed that productive performance and egg quality of quails were not altered (p?>?0.05) by Se sources. Whole egg Se concentrations of quails fed Se from HPSeKS and Se-enriched yeast were higher (p?<?0.05) than that of quails fed the control diet. Breast muscle Se concentrations in quails fed Se from HPSeKS were higher (p?<?0.05) than that of quails fed Se from sodium selenite and Se-enriched yeast. Heart tissue Se concentrations of quails fed Se from Se-enriched yeast and HPSeKS were similar (p?>?0.05), but higher (p?<?0.05) than that of quails fed Se from sodium selenite. The results reveal that Se from HPSeKS did not change the performance and egg quality of quails. The effectiveness of Se from HPSeKS was comparable to that of Se-enriched yeast, which was higher than that of Se from sodium selenite.     

Effects of High Zinc Levels on the Lipid Synthesis in Rat Hepatocytes

Zinc deficiency impairs the hepatic lipid metabolism. Previous studies were focused on the negative effects of zinc deficiency on the hepatic lipid metabolism. A few studies investigated the effects of high zinc levels on the lipid metabolism in hepatocytes. In this study, rat hepatocytes were cultured and treated with different and high concentrations of zinc to investigate the effects of high zinc levels on the lipid synthesis in hepatocytes in vitro. The levels of hepatocytes functional markers, including alkaline phosphatase, lactate dehydrogenase, and albumin, were significantly higher in the zinc treatment groups than in the control group (p?<?0.05, p?<?0.01). The mRNA and protein levels of sterol regulatory element-binding protein 1c (SREBP-1c) were significantly higher in the zinc treatment groups than in the control group (p?<?0.05, p?<?0.01). Furthermore, the mRNA expression levels of acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FAS) were significantly higher in the medium- and high-dose zinc treatment groups than in the control group (p?<?0.01). The mRNA levels of stearoyl-CoA desaturase-1 (SCD-1) were significantly higher in the high-dose group (p?<?0.01). These results indicate that high levels of zinc increase hepatocytes activity and SREBP-1c expression, which upregulate the expression of ACC1, FAS, and SCD-1, thereby improving the lipid metabolism in the hepatocytes.     

Expression of Duffy antigen receptor for chemokines (DARC) is down-regulated in colorectal cancer

Abstract

Duffy antigen receptor for chemokines (DARC) is a silent chemokine receptor which selectively binds angiogenic chemokines without inducing conventional signaling responses. DARC has been reported to inhibit the development of multiple cancers through clearance of angiogenic chemokines. However, its role in colorectal cancer (CRC) remains unclear. We investigated the expression of DARC in CRC and explored correlation of DARC expression with clinical pathological features and microvessel density (MVD). The protein expression levels of DARC were detected by immunohistochemistry in 90 CRC and 64 paired unaffected tissues. The mRNA levels of DARC were detected by quantitative real-time PCR in 15 CRC and paired unaffected tissues. MVD in CRC was also assessed by immunohistochemistry of CD34. We found that the mRNA and protein expression levels of DARC were significantly lower in CRC than in the unaffected tissues (p?<?0.05). The DARC protein expression levels were positively correlated with DARC mRNA expression levels in both CRC (p?<?0.001) and unaffected tissues (p?<?0.001). We also found that DARC expression was significantly correlated with tumor differentiation (p?<?0.001), lymph node metastasis (p?<?0.01) and TNM stage (p?<?0.05). Moreover, we observed a strong negative relationship between DARC expression and MVD in CRC (p?<?0.001). We showed that DARC expression is down-regulated in CRC and associated with clinical pathological features and MVD of CRC. DARC might be involved in tumorigenesis, progression, angiogenesis, and metastasis of CRC.     

THERMOREGULATORY EFFECT IN HUMANS OF SUPPRESSED ENDOGENOUS MELATONIN BY PRE-SLEEP BRIGHT-LIGHT EXPOSURE IN A COLD ENVIRONMENT

This study investigated the physiological function of suppressed melatonin through thermoregulation in a cold environment. Interactions between thermoregulation directly affected by exposure to a cold environment and indirectly affected by endogenous melatonin suppression by bright-light exposure were examined. Ten male subjects were exposed to two different illumination intensities (30 and 5000 lux) for 4.5?h, and two different ambient temperatures (15 and 27°C) for 2?h before sleep under dark and thermoneutral conditions. Salivary melatonin level was suppressed by bright light (p?<?0.001), although the ambient temperature condition had no significant effect on melatonin. During sleep, significant effects of pre-sleep exposure to a cold ambient temperature (p?<?0.001) and bright light (p?<?0.01) on rectal temperature (T_re) were observed. Pre-sleep, bright-light exposure led to an attenuated fall in T_re during sleep. Moreover, T_re dropped more precipitously after cold exposure than thermoneutral conditions (cold: ?0.54?±?0.07°C/h; thermoneutral: ?0.16?±?0.03°C/h; p?<?0.001). Pre-sleep, bright-light exposure delayed the nadir time of T_re under thermoneutral conditions (p?<?0.05), while cold exposure masked the circadian rhythm with a precipitous decrease in T_re. A significant correlation between the T_re nadir and melatonin level (r?=??0.774, p?<?0.05) indicated that inter-individual differences with higher melatonin levels lead to a reduction in T_re after cold exposure. These results suggest that suppressed endogenous melatonin inhibits the downregulation of the body temperature set-point during sleep. (Author correspondence: ishibasi@design.kyushu-u.ac.jp)     

The potential signaling pathway between peroxisome proliferator-activated receptor gamma and retinoic acid receptor alpha in renal interstitial fibrosis disease

Abstract

Peroxisome proliferator-activated receptorγ (PPARγ) can regulate the process of cell apoptosis and is related to the progression of renal disorders. Retinoic acid receptor alpha (RARα) is one of the nuclear receptors involved in a variety of kidney diseases. Renal interstitial fibrosis (RIF) is a common denominator of chronic kidney disease (CKD). This study investigated whether a potential signaling pathway existed between PPARγ and RARα in RIF rats with unilateral ureteral obstruction (UUO). The rats were randomly divided into four groups: a model group subjected to UUO (GU), and three other groups treated with rosiglitazone sodium (GRS), GW9662 and dimethyl sulfoxide (DMSO), n?=?40, respectively. Renal tissues were collected two and four weeks after post-surgery. The relevant indicators were detected. In comparison with the GU group, the expressions of PPARγ and RARα (protein and mRNA) were increased in the GRS group, and decreased in the GW9662 group (all p?<?0.01). The RIF index, mRNA and protein expression of transforming growth factor-β1 (TGF-β1), and the protein expressions of collagen-IV (Col-IV) and fibronectin (FN) in the GRS group were more markedly reduced than those in the GU group; their levels in the GW9662 group were elevated (all p?<?0.01). PPARγ or RARα was negatively correlated to the RIF index, TGF-β1, Col-IV and FN. PPARγ was positively correlated with RARα (all p?<?0.01). In conclusion, PPARγ agonist can elevate the expression of PPARγ or RARα in RIF rats. There might be a potential signaling pathway between PPARγ and RARα in RIF disease.     

TGFβ (transforming growth factor β) and keratocyte motility in 24 h zebrafish explant cultures

Fish keratocytes are used as a model system for the study of the mechanics of cell motility because of their characteristic rapid, smooth gliding motion, but little work has been done on the regulation of fish keratocyte movement. As TGFβ (transforming growth factor β) plays multiple roles in primary human keratinocyte cell migration, we investigated the possible involvement of TGFβ in fish keratocyte migration. Studying the involvement of TGFβ1 in 24 h keratocyte explant allows the examination of the cells before alterations in cellular physiology occur due to extended culture times. During this initial period, TGFβ levels increase 6.2‐fold in SFM (serum‐free medium) and 2.4‐fold in SFM+2% FBS (fetal bovine serum), while TGFβ1 and TGFβRII (TGFβ receptor II) mRNA levels increase ～3‐ and ～5‐fold respectively in each culture condition. Two measures of motility, cell sheet area and migration distance, vary with the amount of exogenous TGFβ1 and culture media. The addition of 100 ng/ml exogenous TGFβ1 in SFM increases both measures [3.3‐fold (P=4.5 × 10^?5) and 26% (P=2.1 × 10^?2) respectively]. In contrast, 100 ng/ml of exogenous TGFβ1 in medium containing 2% FBS decreases migration distance by 2.1‐fold (P=1.7 × 10^?7), but does not affect sheet area. TGFβ1 (10 ng/ml) has little effect on cell sheet area in SFM cultures, but leads to a 1.8‐fold increase (P=1.5 × 10^?2) with 2% FBS. The variable response to TGFβ1 may be, at least in part, explained by the effect of 2% FBS on cell morphology, mode of motility and expression of endogenous TGFβ1 and TGFβRII. Together, these results suggest that expression of TGFβ and its receptor are up‐regulated during zebrafish keratocyte explant culture and that TGFβ promotes fish keratocyte migration.     

Tobacco Smoke Exposure During Pregnancy Increases Maternal Blood Lead Levels Affecting Neonate Birth Weight

To assess the effect of lead exposure from cigarette smoke on fetal growth, blood lead concentrations were measured using inductively coupled plasma mass spectrometry in 150 healthy pregnant women. Mean lead concentrations in plasma and whole blood were significantly higher in the smoking group compared with the nonsmoking group in each trimester of pregnancy (p?<?0.001). Logistic regression analysis showed the highest impact of the number of cigarettes smoked per day for serum lead concentration (β?=?0.238; p?<?0.05), while in whole blood, it was duration of smoking before conception (β?=?0.297; p?<?0.001). Birth weight of the smoking mothers' infants was significantly lower (mean?±?SEM, 3,192?±?50.8 and 3,569?±?49.6 g, respectively; p?<?0.001) and negatively correlated with lead levels in plasma (r?=??0.38; p?<?0.001) and in whole blood (r?=??0.27; p?<?0.001). Therefore, it is suggested that smoking during pregnancy increases lead concentrations in maternal blood. Fetal exposure to low doses of lead in utero may be a serious risk factor causing lower birth weight.     

The evaluation of protective and mitigating effects of vitamin C against side effects induced by radioiodine therapy

The goal of this study was to evaluate the protective and mitigative effect of vitamin C on oxidative stress in differentiated thyroid cancer (DTC) patients ablated with radioiodine. 58 DTC patients selected for radioactive iodine therapy (RAIT) with 5550 MBq ¹³¹Iodine were divided into four groups. Group 1 (control group) consisted of patients who underwent RAIT routinely. Other patients received 1500 mg vitamin C daily 2 days after (group 2), 2 days before to 2 days after (group 3) and 2 days before RAIT (group 4). Serum oxidative stress markers including malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) were measured immediately before and 2 days after RAIT. A significant increase in MDA after RAIT was observed in all groups (p?<?0.05). The concentrations of MDA were significantly higher in the control group compared to the intervention groups (p?<?0.05). A significant decrease in the control group (p?<?0.05) and increase in group 4 (p?<?0.05) were observed in GSH level after RAIT (p?<?0.05). Mean variation of GSH was significant between control group with groups 3 (p?<?0.01) and 4 (p?<?0.01). The results indicate that activity of SOD remained unchanged in all groups (p?>?0.05). A significant increase was observed in CAT activity after RAIT in all groups (p?<?0.05), which was higher in control group than intervention groups. In groups 3 (p?<?0.05) and 4 (p?<?0.05), this increase in CAT activity was significantly lower than the control group. RAIT causes serum oxidative stress, which can be ameliorated using vitamin C as an antioxidant. These results indicate that radioprotective effect of vitamin C is preferable to its mitigative effect.     

Research on association between variants and haplotypes of TRPV1 and TRPA1 genes with growth traits in three cattle breeds

The objective of this study was to examine the association of transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) genes polymorphisms with growth traits in three Chinese cattle breeds (Jiaxian red cattle, Qinchuan cattle and Luxi cattle). Through experiments we identified three single nucleotide polymorphisms (SNPs) in these three cattle breeds TRPV1 and TRPA1 genes using PCR-SSCP, (forced) PCR-RFLP methods. Three of these polymorphisms are all synonymous mutation which includes (NW_003104493.1: 30327 C?>?T), (NW_003104493.1: 33394 A?>?G) and (NW_003104493.1: 38471?G?>?A) are in exons. The other three polymorphisms are located at 3'UTR. Furthermore, we evaluated the haplotype frequency and the statistical analyses indicated that these SNPs of TRPV1 and TRPA1 genes were associated with bovine body height, body length, waist angle width, hucklebone width, cross ministry height, chest qingwidth (p?<?0.05) and recommendation height, cannon circumference (p?<?0.01) of Qingchuan cattle; body length, waist angle width (p?<?0.05) of Jiaxian red cattle; body weight, Body length, cannon circumference, chest circumference (p?<?0.05) and body height (p?<?0.01) of Luxi cattle. Our result confirms the polymorphisms in the TRPV1 and TRPA1 genes are associated with growth traits that may be used for marker-assisted selection (MAS) in three beef breeds programs.     

Biomarker-specific differences between transpulmonary and peripheral arterial–venous blood sampling in patients with pulmonary hypertension

Abstract

Purpose: Transpulmonary biomarkers may provide insight into pulmonary hypertension (PH) pathophysiology, but require cardiac catheterization. We investigated whether the peripheral arterial–venous ratio (PR) could substitute for the transpulmonary ratio (TPR).

Materials and methods: Blood from the pulmonary artery (PA), pulmonary arterial wedge (PAW), peripheral venous, and peripheral arterial positions was analysed for ET-1, NT-pro-BNP and cAMP levels in subjects with no PH (n?=?18) and PH due to left heart disease (PH-LHD), which included combined pre- and post-capillary PH (Cpc-PH; n?=?7) and isolated post-capillary PH (Ipc-PH; n?=?9). Bland–Altman comparisons were made between peripheral venous and PA samples and between peripheral arterial and PAW samples. TPR was defined as [PAW]/[PA].

Results: For ET-1, Bland–Altman analysis indicated negative bias (?24%) in peripheral arterial compared to PAW concentration and positive bias (23%) in peripheral venous compared to PA concentration. There was <10% absolute bias for NT-pro-BNP and cAMP. For ET-1, there was no difference in PR between Cpc-PH and Ipc-PH (0.87?±?0.4 vs. 0.94?±?0.6, p?=?0.8), whereas there was a difference in TPR (2.2?±?1.1 vs. 1.1?±?0.2, p?<?0.05).

Conclusions: In PH-LHD, peripheral samples may be inadequate surrogates for transpulmonary samples, particularly when measuring mediators with prominent pulmonary secretion or clearance, such as ET-1.     

Lipoprotein subfraction oxidation in acute exercise and ageing

Exercise and ageing can independently increase free radical production that may enhance the susceptibility of LDL to oxidation and create a more atherogenic LDL particle. This investigation was designed to examine exercise and ageing on the susceptibility of LDL subfractions to oxidation. Eleven aged (55?± 4 years) and twelve young (21?± 2 years) participants completed a progressive exercise test to exhaustion and within one week performed a 1?h bout of moderate intensity (65% VO_2max) exercise. Blood was assayed for metabolites associated with lipid composition (total cholesterol, free cholesterol, triglycerides) and lipoprotein susceptibility to oxidation. Exercise increased small density (sdLDL) oxidation, independently of age (p?<?0.05). However, sdLDL oxidation further increased 24?h post exercise in the aged group (p?<?0.05). With regards to the changes in lipid components within LDL, free and total cholesterol and triglycerides in large buoyant (lbLDL) were all elevated 24?h post exercise in aged compared with young (p?<?0.05 for all comparisons). There was a decrease in triglycerides in medium density (mdLDL) 24?h post exercise in the aged group (p?<?0.05). The lipid composition of sdLDL, VLDL, HDL₂, HDL₃ and serum lipid hydroperoxides remained unchanged as a function of exercise and ageing (p?>?0.05). Although regular exercise training is known to be protective against cardiovascular disease (CVD) onset, our data demonstrates that acute exercise can increase sdLDL oxidative susceptibility, and this is independent of age and regardless of a change in LDL lipid composition. However, age seems to be a determining factor with regards the susceptibility of sdLDL to oxidation 24?h following exercise.     

Leptin restores markers of female fertility in lipodystrophy

Objectives

Female reproductive dysfunction occurs in patients with pathological loss of adipose tissue, i.e. lipodystrophy (LD). However, mechanisms remain largely unclear and treatment effects of adipocyte-derived leptin have not been assessed in LD animals.

Stability and Fragmentation of the Activity Rhythm Across the Sleep-Wake Cycle: The Importance of Age,Lifestyle, and Mental Health

The rhythms of activity across the 24-h sleep-wake cycle, determined in part by the circadian clock, change with aging. Few large-scale studies measured the activity rhythm objectively in the general population. The present population-based study in middle-aged and elderly persons evaluated how activity rhythms change with age, and additionally investigated sociodemographics, mental health, lifestyle, and sleep characteristics as determinants of rhythms of activity. Activity rhythms were measured objectively with actigraphy. Recordings of at least 96?h (138?±?14?h, mean?±?SD) were collected from 1734 people (age: 62?±?9.4?yrs) participating in the Rotterdam Study. Activity rhythms were quantified by calculating interdaily stability, i.e., the stability of the rhythm over days, and intradaily variability, i.e., the fragmentation of the rhythm relative to its 24-h amplitude. We assessed age, gender, presence of a partner, employment, cognitive functioning, depressive symptoms, body mass index (BMI), coffee use, alcohol use, and smoking as determinants. The results indicate that older age is associated with a more stable 24-h activity profile (β?=?0.07, p?=?0.02), but also with a more fragmented distribution of periods of activity and inactivity (β?=?0.20, p?<?0.001). Having more depressive symptoms was related to less stable (β?=??0.07, p?=?0.005) and more fragmented (β?=?0.10, p?<?0.001) rhythms. A high BMI and smoking were also associated with less stable rhythms (BMI: β?=??0.11, p?<?0.001; smoking: β?=??0.11, p?<?0.001) and more fragmented rhythms (BMI: β?=?0.09, p?<?0.001; smoking: β?=?0.11, p?<?0.001). We conclude that with older age the 24-h activity rhythm becomes more rigid, whereas the ability to maintain either an active or inactive state for a longer period of time is compromised. Both characteristics appear to be important for major health issues in old age.     

Interleukin-6 and Lipopolysaccharide Modulate Hepcidin mRNA Expression by Hepg2 Cells

Iron homeostasis is controlled by hepcidin (Hpc) as well as other ways. Hpc expression is regulated by iron (Fe) storage and by inflammation, but the joint effect of both stimuli remains unclear. We studied the modulatory role of inflammatory agents (IL6 and LPS) over Hpc and DMT1 mRNA expression in HepG2 cells preloaded with Fe. HepG2 cells were preloaded with different Fe concentrations (holo-Tf or Fe-NTA) and then incubated with IL6 or LPS. We measured intracellular Fe levels by AAS with graphite furnace, transferrin receptor (TfR) by ELISA and mRNA relative abundance of Hpc and DMT1 by qRT-PCR. The maximum effect on Fe uptake was observed in cells incubated with 30?ng/ml IL6 (p?<?0.01) and 500?ng/ml LPS (p?<?0.05). In HepG2 cells preloaded with holo-Tf or Fe-NTA and challenged with IL6 and LPS, we observed a decreased: (a) Hpc mRNA relative abundance (two-way ANOVA: p?<?0.05 and p?<?0.001, respectively), (b) DMT1 mRNA relative abundance and TfR1 protein levels (two-way ANOVA: p?<?0.001), and (c) intracellular Fe concentration (two-way ANOVA: p?<?0.001 and p?<?0.01, respectively) compared to control cells incubated only with Fe (holo-Tf or Fe-NTA). Our results support the idea that Fe storage and inflammation act together to regulate Fe homeostasis and suggest a negative regulation in this hepatic cellular model to prevent excessive increases in Hpc.     

Serum Trace Element Levels in Tuberculous Pleurisy

In this study, copper, zinc, magnesium, manganese, selenium, and iron were measured by inductively coupled plasma atomic emission spectrophotometry in patients with tuberculous (TB) pleurisy (n?=?24) and in the control group (n?=?20). Selenium, magnesium, and zinc were found to be significantly lower in TB pleurisy cases than those in the control group (p?<?0.01, p?<?0.001, and p?<?0.001, respectively). There was no significant difference in the value of manganese and iron between TB pleurisy and the control group (p?>?0.05). Copper levels were significantly increased in the serum of the patients (p?<?0.0001). These results may provide an additional disease correlate for assessing TB pleurisy risk.