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1.
Metal often causes delayed-type hypersensitivity reactions, which are possibly mediated by accumulating T cells in the inflamed skin, called irritant or allergic contact dermatitis. However, accumulating T cells during development of a metal allergy are poorly characterized because a suitable animal model is unavailable. We have previously established novel murine models of metal allergy and found accumulation of both metal-specific T cells and natural killer (NK) T cells in the inflamed skin. In our novel models of metal allergy, skin hypersensitivity responses were induced through repeated sensitizations by administration of metal chloride and lipopolysaccharide into the mouse groin followed by metal chloride challenge in the footpad. These models enabled us to investigate the precise mechanisms of the immune responses of metal allergy in the inflamed skin. In this review, we summarize the immune responses in several murine models of metal allergy and describe which antigen-specific responses occur in the inflamed skin during allergic contact dermatitis in terms of the T cell receptor. In addition, we consider the immune regulation of accumulated NK T cells in metal ion–induced allergic contact dermatitis.  相似文献   

2.
Anti-Müllerian hormone (AMH) is secreted by Sertoli or granulosa cells. Recent evidence suggests that AMH may play a role in the pathogenesis of hypogonadotropic hypogonadism (HH) and that its serum levels could help to discriminate HH from delayed puberty. Moreover, the growth hormone (GH)/insulin-like growth factor 1 (IGF1) system may be involved in the function of gonadotropin-releasing hormone (GnRH) neurons, as delayed puberty is commonly found in patients with GH deficiency (GHD) or with Laron syndrome, a genetic form of GH resistance. The comprehension of the stimuli enhancing the migration and secretory activity of GnRH neurons might shed light on the causes of delay of puberty or HH. With these premises, we aimed to better clarify the role of the AMH, GH, and IGF1 on GnRH neuron migration and GnRH secretion, by taking advantage of previously established models of immature (GN11 cell line) and mature (GT1-7 cell line) GnRH neurons. Expression of Amhr, Ghr, and Igf1r genes was confirmed in both cell lines. Cells were then incubated with increasing concentrations of AMH (1.5–150 ng/mL), GH (3–1000 ng/mL), or IGF1 (1.5–150 ng/mL). All hormones were able to support GN11 cell chemomigration. AMH, GH, and IGF1 significantly stimulated GnRH secretion by GT1-7 cells after a 90-min incubation. To the best of our knowledge, this is the first study investigating the direct effects of GH and IGF1 in GnRH neuron migration and of GH in the GnRH secreting pattern. Taken together with previous basic and clinical studies, these findings may provide explanatory mechanisms for data, suggesting that AMH and the GH-IGF1 system play a role in HH or the onset of puberty.  相似文献   

3.
The growth hormone (GH)/insulin-like growth factor I (IGF-I) axis is involved in metabolic control. Malnutrition reduces IGF-I and modifies the thermogenic capacity of brown adipose tissue (BAT). Leptin has effects on the GH/IGF-I axis and the function of BAT, but its interaction with IGF-I and the mechanisms involved in the regulation of thermogenesis remains unknown. We studied the GH/IGF-I axis and activation of IGF-I-related signaling and metabolism related to BAT thermogenesis in chronic central leptin infused (L), pair-fed (PF), and control rats. Hypothalamic somatostatin mRNA levels were increased in PF and decreased in L, while pituitary GH mRNA was reduced in PF. Serum GH and IGF-I concentrations were decreased only in PF. In BAT, the association between suppressor of cytokine signaling 3 and the IGF-I receptor was reduced, and phosphorylation of the IGF-I receptor increased in the L group. Phosphorylation of Akt and cyclic AMP response element binding protein and glucose transporter 4 mRNA levels were increased in L and mRNA levels of uncoupling protein-1 (UCP-1) and enzymes involved in lipid anabolism reduced in PF. These results suggest that modifications in UCP-1 in BAT and changes in the GH/IGF-I axis induced by negative energy balance are dependent upon leptin levels.  相似文献   

4.
Inflammation induces a wide response of the neuroendocrine system, which leads to modifications in all the endocrine axes. The hypothalamic–growth hormone (GH)–insulin-like growth factor-1 (IGF-1) axis is deeply affected by inflammation, its response being characterized by GH resistance and a decrease in circulating levels of IGF-1. The endocrine and metabolic responses to inflammation allow the organism to survive. However, in chronic inflammatory conditions, the inhibition of the hypothalamic–GH–IGF-1 axis contributes to the catabolic process, with skeletal muscle atrophy and cachexia. Here, we review the changes in pituitary GH secretion, IGF-1, and IGF-1 binding protein-3 (IGFBP-3), as well as the mechanism that mediated those responses. The contribution of GH and IGF-1 to muscle wasting during inflammation has also been analyzed.  相似文献   

5.
The aim of this study is to describe the results obtained after growth hormone (GH) treatment and neurorehabilitation in a young man that suffered a very grave traumatic brain injury (TBI) after a plane crash. Methods: Fifteen months after the accident, the patient was treated with GH, 1 mg/day, at three-month intervals, followed by one-month resting, together with daily neurorehabilitation. Blood analysis at admission showed that no pituitary deficits existed. At admission, the patient presented: spastic tetraplegia, dysarthria, dysphagia, very severe cognitive deficits and joint deformities. Computerized tomography scanners (CT-Scans) revealed the practical loss of the right brain hemisphere and important injuries in the left one. Clinical and blood analysis assessments were performed every three months for three years. Feet surgery was needed because of irreducible equinovarus. Results: Clinical and kinesitherapy assessments revealed a prompt improvement in cognitive functions, dysarthria and dysphagia disappeared and three years later the patient was able to live a practically normal life, walking alone and coming back to his studies. No adverse effects were observed during and after GH administration. Conclusions: These results, together with previous results from our group, indicate that GH treatment is safe and effective for helping neurorehabilitation in TBI patients, once the acute phase is resolved, regardless of whether or not they have GH-deficiency (GHD).  相似文献   

6.
(1) Background: As a novel type of non-coding RNA with a stable closed-loop structure, circular RNA (circRNA) can interact with microRNA (miRNA) and influence the expression of miRNA target genes. However, circRNA involved in pituitary growth hormone (GH) regulation is poorly understood. Our previous study revealed protein kinase C alpha (PRKCA) as the target gene of miR-709. Currently, the expression and function of rno_circRNA_0001004 in the rat pituitary gland is not clarified; (2) Methods: In this study, both bioinformatics analysis and dual-luciferase report assays showed a target relationship between rno_circRNA_0001004 and miR-709. Furthermore, the rno_circRNA_0001004 overexpression vector and si-circ_0001004 were constructed and transfected into GH3 cells; (3) Results: We found that rno_circRNA_0001004 expression was positively correlated with the PRKCA gene and GH expression levels, while it was negatively correlated with miR-709. In addition, overexpression of rno-circ_0001004 also promoted proliferation and relieved the inhibition of miR-709 in GH3 cells; (4) Conclusions: Our findings show that rno_circ_0001004 acts as a novel sponge for miR-709 to regulate GH synthesis and cell proliferation, and are the first case of discovery of the regulatory role of circRNA_0001004 in pituitary GH.  相似文献   

7.
The electronic properties of Ni and Pt nanoparticles deposited on CeO2(111) have been examined using core and valence photoemission. The results of valence photoemission point to a new type of metal–support interaction which produces large electronic perturbations for small Ni and Pt particles in contact with ceria. The Ni/CeO2(111) and Pt/CeO2(111) systems exhibited a density of metal d states near the Fermi level that was much smaller than that expected for bulk metallic Ni or Pt. The electronic perturbations induced by ceria on Ni made this metal a very poor catalyst for CO methanation, but transformed Ni into an excellent catalyst for the production of hydrogen through the water-gas shift and the steam reforming of ethanol. Furthermore, the large electronic perturbations seen for small Pt particles in contact with ceria significantly enhanced the ability of the admetal to adsorb and dissociate water made it a highly active catalyst for the water-gas shift. The behaviour seen for the Ni/CeO2(111) and Pt/CeO2(111) systems illustrates the positive effects derived from electronic metal–support interactions and points to a promising approach for improving or optimizing the performance of metal/oxide catalysts.  相似文献   

8.
Retinoic acid (RA), the principal active metabolite of vitamin A, is known to be involved in stress-related disorders. However, its mechanism of action in this regard remains unclear. This study reports that, in mice, endogenous cellular RA binding protein 1 (Crabp1) is highly expressed in the hypothalamus and pituitary glands. Crabp1 knockout (CKO) mice exhibit reduced anxiety-like behaviors accompanied by a lowered stress induced-corticosterone level. Furthermore, CRH/DEX tests show an increased sensitivity (hypersensitivity) of their feedback inhibition in the hypothalamic–pituitary–adrenal (HPA) axis. Gene expression studies show reduced FKBP5 expression in CKO mice; this would decrease the suppression of glucocorticoid receptor (GR) signaling thereby enhancing their feedback inhibition, consistent with their dampened corticosterone level and anxiety-like behaviors upon stress induction. In AtT20, a pituitary gland adenoma cell line elevating or reducing Crabp1 level correspondingly increases or decreases FKBP5 expression, and its endogenous Crabp1 level is elevated by GR agonist dexamethasone or RA treatment. This study shows, for the first time, that Crabp1 regulates feedback inhibition of the the HPA axis by modulating FKBP5 expression. Furthermore, RA and stress can increase Crabp1 level, which would up-regulate FKBP5 thereby de-sensitizing feedback inhibition of HPA axis (by decreasing GR signaling) and increasing the risk of stress-related disorders.  相似文献   

9.
The serine/threonine kinase mechanistic target of rapamycin (mTOR) plays a pivotal role in the regulation of cell proliferation, survival, and motility in response to availability of energy and nutrients as well as mitogens. The mTOR signaling axis regulates important biological processes, including cellular growth, metabolism, and survival in many tissues. In the skin, dysregulation of PI3K/AKT/mTOR pathway may lead to severe pathological conditions characterized by uncontrolled proliferation and inflammation, including skin hyperproliferative as well as malignant diseases. Herein, we provide an update on the current knowledge regarding the pathogenic implication of the mTOR pathway in skin diseases with inflammatory features (such as psoriasis, atopic dermatitis, pemphigus, and acne) and malignant characteristics (such as cutaneous T cell lymphoma and melanoma) while we critically discuss current and future perspectives for therapeutic targeting of mTOR axis in clinical practice.  相似文献   

10.
Melatonin and resistance exercise alone have been shown to increase the levels of growth hormone (GH). The purpose of this study was to determine the effects of ingestion of a single dose of melatonin and heavy resistance exercise on serum GH, somatostatin (SST), and other hormones of the GH/insulin-like growth factor 1 (IGF-1) axis. Physically active males (n = 30) and females (n = 30) were randomly assigned to ingest either a melatonin supplement at 0.5 mg or 5.0 mg, or 1.0 mg of dextrose placebo. After a baseline blood sample, participants ingested the supplement and underwent blood sampling every 15 min for 60 min, at which point they underwent a single bout of resistance exercise with the leg press for 7 sets of 7 reps at 85% 1-RM. After exercise, participants provided additional blood samples every 15 min for a total of 120 min. Serum free GH, SST, IGF-1, IGFBP-1, and IGFBP-3 were determined with ELISA. Data were evaluated as the peak pre- and post-exercise values subtracted from baseline and the delta values analyzed with separate three-way ANOVA (p < 0.05). In males, when compared to placebo, 5.0 mg melatonin caused GH to increase (p = 0.017) and SST to decrease prior to exercise (p = 0.031), whereas both 0.5 and 5.0 mg melatonin were greater than placebo after exercise (p = 0.045) and less than placebo for SST. No significant differences occurred for IGF-1; however, males were shown to have higher levels of IGFBP-1 independent of supplementation (p = 0.004). The 5.0 mg melatonin dose resulted in higher IGFBP-3 in males (p = 0.017). In conclusion, for males 5.0 mg melatonin appears to increase serum GH while concomitantly lowering SST levels; however, when combined with resistance exercise both melatonin doses positively impacts GH levels in a manner not entirely dependent on SST.  相似文献   

11.
Atopic dermatitis (AD) is a chronic pruritic skin disease with a complex pathogenesis underlying its heterogeneous clinical phenotypes and endotypes. The skin manifestation of AD reflects the cytokine milieu of a type-2-dominant immunity axis induced by genetic predisposition, innate immunity dysregulation, epidermal barrier defects, and allergic inflammation. However, the detailed pathomechanism of eczematous dermatitis, which is the principal characteristic of AD, remains unclear. This review examines previous studies demonstrating research progress in this area and considers the immunological pathomechanism of “spongiotic dermatitis”, which is the histopathological hallmark of eczematous dermatitis. Studies in this field have revealed the importance of IgE-mediated delayed-type hypersensitivity, the Fas/Fas-ligand system, and cell-mediated cytotoxicity in inducing the apoptosis of keratinocytes in spongiotic dermatitis. Recent studies have demonstrated that, together with infiltrating CD4 T cells, IgE-expressing dendritic cells (i.e., inflammatory dendritic epidermal cells and Langerhans cells) that capture specific allergens (i.e., house dust mites) are present in the spongiotic epidermis of lichenified eczema in patients with IgE-allergic AD. These findings suggest that IgE-mediated delayed-type hypersensitivity plays a pivotal role in the pathogenesis of spongiotic dermatitis in the skin lesions of AD.  相似文献   

12.
Little is known about the interactions of single nucleotide polymorphisms (SNPs) and overweight/obesity on blood pressure levels. The present study was undertaken to detect 10 lipid-related gene SNPs and their interactions with overweight/obesity on blood pressure levels. Genotyping of ATP-binding cassette transporter A1 (ABCA-1) V825I, acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) rs1044925, low density lipoprotein receptor (LDL-R) AvaII hepatic lipase gene (LIPC) −250G > A, endothelial lipase gene (LIPG) 584C > T, methylenetetrahydrofolate reductase (MTHFR) 677C > T, the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP) rs3757354, proprotein convertase subtilisin-like kexin type 9 (PCSK9) E670G, peroxisome proliferator-activated receptor delta (PPARD) +294T > C, and Scavenger receptor class B type 1 (SCARB1) rs5888 was performed in 978 normal weight and 751 overweight/obese subjects. The interactions were detected by factorial regression analysis. The genotypes of ACAT-1 AC, LIPC GA and AA, and SCARB1 TT; LDL-R A-A- and LIPC GA; and SCARB1 TT were interacted with overweight/obesity to increase systolic, diastolic blood pressure (SBP, DBP) and pulse pressure (PP) levels; respectively. The genotypes of ACAT-1 CC; ACAT-1 AA and CC were interacted with overweight/obesity to decrease SBP, PP levels (p < 0.01–0.001); respectively. The differences in blood pressure levels between normal weight and overweight/obese subjects might partly result from different interactions of several SNPs and overweight/obesity.  相似文献   

13.
14.
采用国外先进的in silico技术,应用QSAR(Quantitative structure activity relationship)测试模块,对防晒剂成分的皮肤接触过敏性、人体感觉刺激性以及眼刺激性分别进行了预测和评价,并针对其人体感觉刺激性预测结果,计算了防晒剂成分的职业暴露限量OEL(occupational exposure limit)值.结果表明,防晒剂成分表现出不同的皮肤接触过敏性、人体感觉刺激性以及眼刺激性可能性,尤其是二苯甲酮-3和苯基苯并咪唑磺酸的过敏性和刺激性可能性较高,而4-二甲氨基苯甲酸2-乙基己酯相对较低.针对感觉刺激性作用,防晒剂成分的OEL值在0.03 cm3/m3~1.85 cm3/m3,尤其是二苯酮-3的OEL值最低,为0.03 cm3/m3左右.说明防晒剂成分应用于化妆品产品中时,对人体可能有一定的皮肤接触过敏性、人体感觉刺激性以及眼刺激性作用,具有一定的人体暴露风险,需要引起注意.  相似文献   

15.

Background

Hormones, which influence satiety and hunger, play a significant role in body energy balance regulation. Ghrelin is a peptide that plays an important role in short-term appetite regulation, whereas leptin is a factor that controls long-term energy balance and is considered as a satiety hormone. The aim of this study was to evaluate the leptin/ghrelin ratio in a fasting state and after the intake of meals with varying macronutrient contents and to assess the possible differences between normal body weight and overweight/obese men.

Methods

We examined 46 healthy adult men (23 with normal body weight and 23 overweight/obese) aged 21–58, who were divided into two groups. In the crossover study, participants received isocaloric (450?kcal) meals with different macronutrient contents: men from the first group received high-carbohydrate (HC) and normo-carbohydrate (NC) meals, and in the second group, participants received high-carbohydrate and high-fat (HF) meals. The ratio of leptin/ghrelin levels was calculated from leptin and total ghrelin serum concentrations in a fasting state and 30, 60, 120, 180 and 240?min after meal intake. One-way ANOVA and Wilcoxon signed-rank tests were carried out. The normality of the variable distribution was checked with the Shapiro–Wilk test, the homogeneity of variances was verified with the Levene test, and the false discovery rate p-value adjustment method was used.

Results

The leptin/ghrelin ratio was significantly higher in overweight/obese men than individuals with normal body weight in a fasting state, as well as postprandially. We observed trends towards a higher leptin/ghrelin ratio values from the 60?min after HC-meal intake compared to the NC- and HF-meals in normal body weight participants, while in overweight/obese men, we did not note any significant differences dependent on the meal type.

Conclusions

We have observed a significantly different postprandial leptin/ghrelin ratio in normal body weight and overweight/obese men, and our results suggest that in men with normal body weight, a greater feeling of satiety may occur after high-carbohydrate meal intake, which was not noted in the overweight/obese individuals.
  相似文献   

16.

Background

This study aimed to investigate the relationship of anemia and body mass index among adult women in Jiangsu Province, China. Data were collected in a sub-national cross-sectional survey, and 1,537 women aged 20 years and above were included in the analyses. Subjects were classified by body mass index (BMI) categories as underweight, normal weight, overweight and obese according to the Chinese standard. Central obesity was defined as a waist circumference?≥?80 cm. Anemia was defined as hemoglobin concentration?<?12 g/dl. Prevalence ratios (PRs) of the relationship between anemia and BMI or waist circumference were calculated using Poisson regression.

Findings

Overall, 31.1% of the Chinese women were anemic. The prevalence of overweight, obesity and central obesity was 34.2%, 5.8% and 36.2%, respectively. The obese group had the highest concentrations of hemoglobin compared with other BMI groups. After adjustment for confounders, overweight and obese women had a lower PR for anemia (PR: 0.72, 95% CI: 0.62-0.89; PR: 0.59, 95% CI: 0.43-0.79). Central obesity was inversely associated with anemia.

Conclusion

In this Chinese population, women with overweight/obesity or central obesity were less likely to be anemic as compared to normal weight women. No measures are required currently to target anemia specifically for overweight and obese people in China.  相似文献   

17.
采用成核/晶化隔离法制备出一系列Ni2+-Co2+-Fe2+-Fe3+-SO42--LDHs层状前驱体,焙烧后得到尖晶石型铁氧体Ni1-xCoxFe2O4。对样品的晶体结构及元素组成进行分析,结果表明,制得的尖晶石型铁氧体Ni1-xCoxFe2O4 晶体结构优良, 元素组成可控性强。分别将Ni1-xCoxFe2O4、NiFe2O4和CoFe2O4的磁学性能参数的理论混合值和机械混合值随x[x=nCo)∶n(Ni)]的变化情况进行比较,发现Ni1-xCoxFe2O4的磁学性能并不是简单的NiFe2O4和CoFe2O4磁学性能的加合,Co和Ni原子之间存在着一定的协同效应,且当x为0.2时,Ni1-xCoxFe2O4的磁学性能最佳。  相似文献   

18.
Carbon deposition is sensitive to the metal particle sizes of supported Ni catalysts in CH4/CO2 reforming.To explore the reason of this phenomenon,Ni4,Ni8,and Ni12 which reflect the different cluster thicknesses supported on the MgO(100) slabs,have been employed to simulate Ni/MgO catalysts,and the reaction pathways of CH4/CO2 reforming on Nix/MgO(100) models are investigated by density functional theory.The reforming mechanisms of CH4/CO2 on different Nix/MgO(100) indicate the energy barriers of CH4 dissociated adsorption,CH dissociation,and C oxidation three factors are all declining with the decrease of the Ni cluster sizes.The Hirshfeld charges analyses of three steps as described above show only Ni atoms in bottom two layers can obtain electrons from the MgO supporters,and the main electron transfer occurs between adsorbed species and their directly contacted Ni atoms.Due to more electron-rich Ni atoms in contact with the MgO supporters,the Ni/MgO catalysts with small Ni particles have a strong metal particle size effect and lead to its better catalytic activity.  相似文献   

19.
The potentials of silty clay(SC), acquired from Chaman, Balochistan, were investigated as adsorbent for Ni(Ⅱ)and Cd(Ⅱ) removal from contaminated media. The influence of different operating factors like dose, pH, temperature, and time of contact was explored, and optimum values were noted under batch adsorption method. Isothermal study was conducted with varying concentrations of solutions on optimized conditions and different adsorption models i.e., Langmuir, Freundlich, Temkin and Dubinin–Radushkevich(D–R) isotherm, which were employed to interpret the process. The isothermal data of both Ni(Ⅱ) and Cd(Ⅱ) were well fitted to Langmuir isotherm suggesting the formation of monolayer of metal ions on silty clay. The values of adsorption capacity noted for Ni(Ⅱ) and Cd(Ⅱ) were 3.603 mg·g~(-1) and 5.480 mg·g~(-)1, respectively. Kinetic studies affirmed that pseudo second order(PSO) kinetics was being obeyed by the removal of Ni(Ⅱ) and Cd(Ⅱ). Thermodynamic variables like free energy change(ΔG°), enthalpy change(ΔH°) and entropy change(ΔS°) were calculated. The negative value of ΔG° and the positive values of ΔH° and ΔS° unfolded that the removal process of both metal ions of by SC was spontaneous, endothermic and feasible.  相似文献   

20.
A direct current (DC)-driven transient liquid phase bonding strategy was proposed for joining 3 mol% Y2O3-stabilized ZrO2 (3YSZ) and GH3128 superalloy with a Ni interlayer. The DC application triggered the rapid formation and diffusion of metallic Zr in 3YSZ and chemical reactions at the 3YSZ/Ni interface. The formed Ni–Zr eutectic liquid well wetted 3YSZ and hence completely filled the bonding gap in seconds. Eutectic structures in the joints were eventually transformed into Ni–Zr intermetallic compounds or a Ni-based solid solution. The remaining Ni interlayer effectively alleviated residual stress through plastic deformation during cooling stage, and thereby contributed substantially to the high joint strength. Under the joining conditions of a current density of 30 mA/mm2, an energization time of 30 s, and a joining temperature of 1100°C, the obtained joints exhibited a maximum shear strength of 188 ± 8 MPa. This paper proposes an economical and reliable method for the rapid preparation of YSZ/metal joints for high-temperature applications.  相似文献   

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