Effects of dietary omega-3 and omega-6 lipids and vitamin E on serum cytokines, lipid mediators and anti-DNA antibodies in a mouse model for rheumatoid arthritis

OBJECTIVE: Omega-3 (omega-3) fatty acid rich-fish oil (FO) and vitamin E (vit-E) may delay the progress of certain autoimmune diseases. The present study examined the mechanism of action of omega-3 and omega-6 lipids and vit-E on the serum cytokines and lipid mediators in autoimmune-prone MRL/lpr mice (a model for rheumatoid arthritis, RA). The lpr (lymphoproliferative) gene is overexpressed in these mice causing extensive lymphoproliferation, lupus-like symptoms and accelerated aging. METHODS: Weanling female MRL/lpr and congenic control MRL/++ mice were fed 10% corn oil (CO, omega6) or FO-based semipurified diets containing two levels of vitamin E (vit-E-75, I.U. and vit-E-500 I.U./Kg diet) for four months. At the end of the experiment, serum anti-DNA antibodies, cytokines and lipid mediators levels were determined. RESULTS: The appearance of enlarged lymph nodes was delayed in the mice fed FO, and the FO-500 IU vit-E diet offered further protection against enlargement of lymph nodes. The MRL/lpr mice exhibited significantly higher levels of serum anti-dsDNA antibodies. The FO-fed mice had significantly lower serum IL-6, IL-10, IL-12, TNF-alpha, PGE2, TXB2 and LTB4 levels compared with CO-fed mice. In mice fed 500 IU vit-E diets, the serum IL-6, IL-10, IL-12 and TNF-alpha levels were significantly lower and serum IL-1beta was significantly higher compared to 75 IU-vit-E-fed mice in CO/FO or both. The levels of anti-DNA antibodies, IL-4, IL-6, TNF-alpha, IL-10 and IL-12 were higher in the sera of MRL/lpr mice. The FO diet lowered the levels of these cytokines (except IL-4) and lipid mediators. Adding 500 IU of vit-E to the FO diet further lowered the levels of IL-6, IL-10, IL-12, and TNF-alpha. CONCLUSION: It is clear from our observations that the beneficial effects of FO can be enhanced by the addition of 500 IU of vit-E in the diet. The FO diet containing 500 IU of vit-E may specifically modulate the levels of IL-6, IL-10, IL-12 and TNF-alpha and thereby may delay the onset of autoimmunity in the MRL/lpr mouse model. The observations from this study may form a basis for selective nutrition intervention based on specific fatty acids and antioxidants in delaying the progress of RA.     

Effect of dietary legumes on bone-specific gene expression in ovariectomized rats

In previous studies, we found that the consumption of legumes decreased bone turnover in ovariectomized rats. The purpose of the present study is to determine whether the protective effects on bone mineral density (BMD) and the microarchitecture of a diet containing legumes are comparable. In addition, we aim to determine their protective actions in bones by studying bone specific gene expression. Forty-two Sprague-Dawley rats are being divided into six groups during the 12 week study: 1) rats that underwent sham operations (Sham), 2) ovariectomized rats fed an AIN-93M diet (OVX), 3) ovariectomized rats fed an AIN-93M diet with soybeans (OVX-S), 4) ovariectomized rats fed an AIN-93M diet with mung beans (OVX-M), 5) ovariectomized rats fed an AIN-93M diet with cowpeas (OVX-C), and 6) ovariectomized rats fed an AIN-93M diet with azuki beans (OVX-A). Consumption of legumes significantly increased BMD of the spine and femur and bone volume of the femur compared to the OVX. Serum calcium and phosphate ratio, osteocalcin, expression of osteoprotegerin (OPG), and the receptor activator of nuclear factor κB ligand (RANKL) ratio increased significantly, while urinary excretion of calcium and deoxypyridinoline and expression of TNF-α and IL-6 were significantly reduced in OVX rats fed legumes, compared to OVX rats that were not fed legumes. This study demonstrates that consumption of legumes has a beneficial effect on bone through modulation of OPG and RANKL expression in ovariectomized rats and that legume consumption can help compensate for an estrogen-deficiency by preventing bone loss induced by ovarian hormone deficiency.     

DcR3、EMMPRIN、RANKL与绝经后类风湿关节炎患者骨密度的相关性分析

目的分析诱骗受体3(DcR3)、细胞外基质金属蛋白酶诱导因子(EMMPRIN)、核因子-кB受体活化因子配体(RANKL)与绝经后类风湿关节炎患者骨密度(BMD)的相关性。方法选取2018年1月-2019年1月该院收治的绝经后类风湿关节炎患者80例作为类风湿关节炎组,另外选取同期在该院行健康体检的80例健康绝经后女性作为健康对照组。检测所有研究对象DcR3表达水平、RANKL表达水平、EMMPRIN蛋白表达量及BMD,分析DcR3、EMMPRIN、RANKL与BMD之间的相关性。结果类风湿关节炎组DcR3、EMMPRIN、RANKL水平均高于健康对照组,BMD低于健康对照组,差异有统计学意义(P<0.05)。高度活动组、中度活动组DcR3、EMMPRIN、RANKL水平均高于低缓组,BMD低于低缓组,差异有统计学意义(P<0.05);高度活动组DcR3、EMMPRIN、RANKL水平均高于中度活动组,BMD低于中度活动组,差异有统计学意义(P<0.05)。DcR3、EMMPRIN之间呈正相关(r=0.426,P=0.001);DcR3、RANKL之间呈正相关(r=0.391,P=0.001);EMMPRIN、RANKL之间呈正相关(r=0.385,P=0.001)。DcR3与BMD之间呈负相关(r=-0.392,P=0.001);EMMPRIN与BMD之间呈负相关(r=-0.375,P=0.001);RANKL与BMD之间呈负相关(r=-0.222,P=0.048)。结论DcR3、EMMPRIN、RANKL在绝经后类风湿关节炎患者中高表达,疾病越严重其表达越加剧,且与患者BMD相关,参与疾病的发生发展。     

l-Cysteine and Vitamin D Co-Supplementation Alleviates Markers of Musculoskeletal Disorders in Vitamin D-Deficient High-Fat Diet-Fed Mice

Vitamin D (VD) deficiency is associated with musculoskeletal disorders. This study examines whether co-supplementation of l-cysteine (LC) and VD is better than monotherapy with LC or VD at alleviating musculoskeletal dyshomeostasis in the skeletal muscle of VD-deficient high-fat diet (HFD-VD-) fed mice. Mice were fed a healthy diet or an HFD; for VD-deficient animals, the mice were maintained on a HFD-VD-diet (16 weeks); after the first 8 weeks, the HFD-VD-diet-fed mice were supplemented for another 8 weeks with LC, VD-alone, or the same doses of LC + VD by oral gavage. Saline and olive oil served as controls. Myotubes were exposed with high-glucose, palmitate, Monocyte Chemoattractant Protein 1 (MCP-1), and Tumor Necrosis Factor (TNF), to mimic the in vivo microenvironment. In vitro deficiencies of glutathione and hydrogen sulfide were induced by knockdown of GCLC and CSE genes. Relative gene expression of biomarkers (myogenic: MyoD, Mef2c, Csrp3; muscle dystrophy: Atrogin1, Murf1, and Myostatin; bone modeling and remodeling: RANK, RANKL, OPG) were analyzed using qRT-PCR. Co-supplementatoin with LC + VD showed beneficial effects on gene expression of myogenic markers and OPG but reduced markers of dystrophy, RANK/RANKL in comparison to LC or VD alone-supplementation. In vitro myotubes treated with glutathione (GSH) precursors also showed a positive effect on OPG and the myogenesis genes, and inhibited RANK/RANKL and muscle-dystrophy markers. This study reveals that the co-supplementation of LC with VD significantly alleviates the markers of musculoskeletal disorders in the skeletal muscle better than monotherapy with LC or VD in HFD-VD-fed mice.     

Effect of dietary n-3 and n-6 oils with and without food restriction on activity of antioxidant enzymes and lipid peroxidation in livers of cyclophosphamide treated autoimmune-prone NZB/W female mice

OBJECTIVE: Cyclophosphamide (CTX), an alkylating agent, is extensively used in the treatment of lupus nephritis, but its administration has been associated with free radical mediated oxidative stress. The present study was designed to investigate the effect of dietary corn oil (CO), fish oil (FO) and food restriction (FR) on the activities of hepatic antioxidant enzymes, fatty acid composition and lipid peroxidation following CTX administration in autoimmune-prone NZB/W female mice. METHODS: Autoimmune-prone NZB/W female mice were fed either ad libitum (AL) or food restricted (60% of AL intake), semipurified diets containing 5% CO or 5% FO supplemented with equal levels of antioxidants and injected with either phosphate buffered saline (PBS), or CTX (50 mg/kg body weight) every 10 days. Proteinuria was measured biweekly. The treatment was stopped at 10 months and diets were continued until the mice were killed at 12 months. Fatty acid composition, activity of antioxidant enzymes and lipid peroxidation were analyzed in liver homogenates, and anti-DNA antibodies were analyzed in the serum. RESULTS: Mice in the FO/AL dietary group exhibited significantly higher liver catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities compared to the CO/AL dietary group. CTX significantly decreased SOD and GSH-Px activity in the FO/AL group and CAT and GSH-Px in the CO/AL group. In AL fed mice given CTX, activities of CAT, GSH-Px and GST were significantly higher in mice fed FO diets than in mice fed CO diets. FR increased the activity of enzymes in both the CO and FO diet groups. In FR mice, CTX decreased CAT and GSH-Px activity in both the CO and FO dietary groups, but glutathione S-transferase (GST) only in the CO group. The decrease in SOD activity was not significant in either of the restricted groups. CTX significantly increased generation of thiobarbituric acid reactive substances (TBARS) in both AL groups. FR significantly decreased lipid peroxidation in both the CO and FO groups, with or without CTX. CTX decreased serum anti-DNA antibody levels in both the CO and FO dietary groups. FR also decreased antibody titer in both the CO and FO dietary groups, and it was decreased further with CTX treatment. FO fed animals had higher levels of n-3 fatty acids, whereas CO fed animals had high levels of n-6 fatty acids. CTX significantly increased 20:4 and decreased 18:1 in CO/AL fed animals, whereas it increased 18:1 and decreased 22:6 in FO/AL fed animals. CONCLUSIONS: Results obtained in the present study suggests that FO and, more significantly, FO combined with FR can have a beneficial effect in hepatic tissues subjected to CTX induced oxidative stress by regulating the activity of antioxidant enzymes. In addition, the study also indicates that n-3 and n-6 dietary lipids are susceptible to lipid peroxidation, particularly in the presence of a prooxidant like CTX, and that FR is beneficial in decreasing lipid peroxidation. The study also suggests that FO and CTX can have additive effects in preventing kidney disease in NZB/W mice.     

Receptor activator of NF(Kappa)B ligand/osteoprotegerin (RANKL/OPG) system and osteopontin (OPN) serum levels in a population of apulian postmenopausal women

AIM: Osteoporosis is a bone disease, characterized by a reduction of bone resistance; in postmenopausal period bone metabolism is imbalanced. Several parameters have been proposed as markers of bone metabolism; the attention have been recently placed on the receptor of activator of NF(Kappa)B ligand receptor (RANKL) and osteoprotegerin (OPG), namely RANKL/OPG system. The aim of this paper is to evaluate changes in postmenopausal women in serum concentration of OPG, RANKL, and their ratio (i.e. RANKL/OPG ratio), osteopontin (OPN), bone-type alcaline phosphatase (BAP), serum-N-Telopeptide of type I collagen (serum-NTX); and their correlations with bone mineral density (BMD). METHODS: An Apulian population group of 163 native postmenopausal women were followed at the Osteoporosis Centre of Policlinico of Bari (Southenrn Italy). Patients were classified into 3 separate groups, according to T-score: osteoporotic, osteopenic and control group. Serum concentrations of OPG, RANKL, RANKL/OPG ratio, BAP and NTX have been calculated. RESULTS: No differences were found in OPG and BAP values. Significant correlations were found in the osteopenic group between OPG and RANKL (negative), and between RANKL and OPN or serum-NTX, OPN and serum-NTX or RANKL/OPG ratio, BAP and serum-NTX, serum-NTX and RANKL/OPG ratio (positive). In the other groups a significant correlation was observed between BAP and NTX. CONCLUSIONS: In postmenopausal women, important modifications of bone metabolism markers (i.e. RANKL, OPG and OPN) could be due to serious engagement of bone turnover, especially in the pre-osteoporotic phase. Low bone density in postmenopausal women should be identified as soon as possible, and urgent measures are needed to reverse the process. Parameters namely RANKL e OPG may become an important index for the evaluation of the activity of drugs against osteoporosis, old and new like AMG 162 (anti-RANKL action).     

Serum osteoprotegerin and RANKL levels in chronic alcoholic liver disease

OBJECTIVES: Osteoprotegerin (OPG) is a decoy receptor that binds RANK-ligand (RANKL) and prevents osteoclast activation. Oestrogens, androgens, corticosteroids, parathyroid hormone (PTH), vitamin D, and several cytokines exert their effects on bone modulating the OPG/RANKL system. Since these substances become altered in chronic alcoholic liver disease, we investigated the OPG/RANKL system in alcoholic liver disease, its relation with bone mineral density (BMD) and with several hormones and cytokines. METHODS: Serum OPG, RANKL, C-terminal cross-linking telopeptide of type 1 collagen, osteocalcin, insulin-like growth factor 1 (IGF-1), 1,25 dihydroxyvitamin D, IL-6, tumour necrosis factor (TNF)-alpha, PTH, estradiol, free testosterone and corticosterone were measured in 77 male alcoholic patients, 25 of them cirrhotics. All these patients underwent assessment of BMD at lumbar spine and left hip by a Hologic QDR-2000 (Waltham, MA) bone densitometer. Nineteen non-drinkers male sanitary workers of similar age served as controls. RESULTS: Serum OPG levels were higher in patients (12.66 +/- 6.44 pmol/l) than in controls (6.59 +/- 1.58 pml/l, P < 0.005), especially in cirrhotics (15.97 +/- 7.03 pmol/l) vs non-cirrhotics (10.96 +/- 5.45 pmol/l, P < 0.001). Patients also showed higher telopeptide levels (0.60 +/- 0.36 vs 0.20 +/- 0.10 nmol/100 ml, P < 0.001), less IGF-1 [median = 192, interquartile range (IQR) = 46.7-175.99 ng/ml vs 150, IQR = 118.8-239.4 ng/ml, P < 0.001], vitamin D (25.5, IQR = 18.25-35 pg/ml vs 77.89, IQR = 57.48-98.53 pg/ml, P < 0.001) and osteocalcin (1.8, IQR = 1-3.6 ng/ml vs 6.04, IQR = 4.63-8.20 ng/ml, P < 0.001) than controls, but no differences in PTH and RANKL. Patients also showed lower Z-scores than controls at trochanter (-0.36 +/- 1.10 vs 0.26 +/- 0.87 in controls, P = 0.026), intertrochantereal area (-0.56 +/- 1.16 vs 0.46 +/- 1.01, P = 0.001), and total hip (-0.44 +/- 1.12 vs 0.42 +/- 1, P = 0.003). TNF-alpha levels were higher in patients (7.40, IQR = 4.30-17.80 pg/ml) than in controls (5.10, IQR = 4.40-8 pg/ml, P = 0.009), especially in cirrhotics (median = 13.90, IR = 6.10-21.10 pg/ml). OPG levels showed strong correlations with TNF-alpha (rho = 0.57, P < 0.001) and IL-6 (r = 0.62, P < 0.001), but not with BMD. Estradiol levels (31.83 +/- 13.11 pg/ml) were higher and free testosterone lower (13.62 +/- 11.96 pg/ml) in patients than in controls (20.36 +/- 3.08 and 18.19 +/- 4.68 pg/ml, respectively, P < 0.001 in both cases). CONCLUSION: OPG is raised in alcoholics, especially in cirrhotics, showing no relationship with decreased BMD. Also, raised TNF and IL-6 were observed, and were strongly, directly related with OPG levels. Since TNF and IL-6 enhance bone resorption, their relation with OPG suggests a protective effect of raised OPG on bone loss.     

1α,25(OH)_2D_3对大鼠成骨细胞КB受体活化因子配体及骨保护素蛋白表达的影响

目的研究1α,25-二羟维生素D3(1α,25(OH)2D3)对体外培养3～4d的SD大鼠成骨细胞(OB)核因子κB受体活化因子配体(RANKL)及骨保护素(OPG)蛋白和mRNA表达的影响。方法1α,25(OH)2D3作用24、48、72h,分别采用ELISA及FQ-PCR法测定。结果10、100nmol/L1α,25(OH)2D3较对照及1nmol/L显著或极显著促进RANKL蛋白及mRNA表达;1、10nmol/L1α,25(OH)2D3较对照显著或极显著促进OPG蛋白及mRNA表达,而100nmol/L则极显著抑制OPGmRNA表达;RANKLmRNA/OPGmRNA及RANKL/OPG显示,1nmol/L组与对照组差异不显著,10、100nmol/L组RANKLmRNA/OPGmRNA及RANKL/OPG极显著高于对照组和1nmol/L组。结论低浓度1α,25(OH)2D3(1nmol/L)对骨更新作用不明显,而中、高浓度1α,25(OH)2D(310、100nmol/L)能通过上调RANKLmRNA/OPGmRNA及RANKL/OPG比例,促进OC的生成及骨吸收功能,增强骨更新。     

1α,25(OH)_2D_3对大鼠成骨细胞κB受体活化因子配体及骨保护素蛋白表达的影响

目的 研究1α,25-二羟维生素D_3(1α,25(OH)_2D_3)对体外培养3～4 d的SD大鼠成骨细胞(OB)核因子κ B受体活化因子配体(RANKL)及骨保护素(OPG)蛋白和mRNA表达的影响.方法 1α,25(OH)_2D_3作用24、48、72 h,分别采用ELISA及FQ-PCR法测定.结果 10、100 nmol/L 1α,25(OH)_2D_3较对照及1 nmol/L显著或极显著促进RANKL蛋白及mRNA表达;1、10 nmol/L 1α,25(OH)_2D_3较对照显著或极显著促进OPG蛋白及mRNA表达,而100 nmol/L则极显著抑制OPG mRNA表达;RANKL mRNA/OPG mRNA及RANKL/OPG显示,1 nmol/L组与对照组差异不显著,10、100 nmol/L组RANKL mRNA/OPG mRNA及RANKL/OPG板显著高于对照组和1 nmol/L组.结论 低浓度1α,25(OH)_2D_3(1 nmol/L)对骨更新作用不明显,而中、高浓度1α,25(OH)_2D_3(10、100 nmol/L)能通过上调RANKL mRNA/OPG mRNA及RANKL/OPG比例,促进OC的生成及骨吸收功能,增强骨更新.     

Opposite effects of low and high dose supplementation of vitamin E on survival of MRL/lpr mice

OBJECTIVE: The purpose of this study is to investigate the effects of vitamin E supplementation on the autoimmune disease course in MRL/lymphoproliferative mice. METHODS: Three-month-old MRL/lymphoproliferative lpr female mice were fed an AIN-76 diet containing 50 mg/kg (control), 250 mg/kg (E5), 375 mg/kg (E7.5), or 500 mg/kg (E10) all-rac-alpha-tocopheryl acetate. Eight mice per group were killed for analysis after two months of experimental diets, and the rest of the mice were followed up to observe their proteinuria levels and life span. RESULTS: The data suggest that the life span of the E5 group was longer than the E10 group. Though alpha-tocopherol content in the plasma, liver, and kidneys increased in the mice fed the diet supplemented with vitamin E, the thiobarbituric acid reactive substance values in the liver and kidneys among these groups were not significantly different. IgM anti-ds-DNA and anticardiolipin antibodies were significantly higher in the E10 group than in those of the other groups. Phytohemagglutinin-stimulated interleukin (IL)-2 secretion was significantly lower, but concanavalinA-stimulated IL-4 and IL-10 production was significantly higher in the E10 group compared with the control group. The in vitro study also showed decreased IL-2 secretion and messenger RNA expression in phytohemagglutinin-stimulated splenocytes cultured in medium supplemented with high doses of vitamin E, but increased IL-2 with low doses of vitamin E. CONCLUSIONS: Our data suggest that low and high dose supplementation of vitamin E has the opposite effect on the survival of MRL/lpr mice. The inhibitory effect of Th1 from high vitamin E content may not be beneficial for those suffering from Th2 prone autoimmune diseases, such as systemic lupus erythematosus.     

Clinical implications of new insights into the regulation of bone resorption

It has recently been discovered that the receptor activator of nuclear kappaB-ligand (RANKL) plays a key role in the activation, differentiation and proliferation ofosteoblasts. The effects of RANKL are counteracted by the decoy receptor osteoprotegerin (OPG), which protects against bone resorption by preventing RANKL from coupling to its receptor RANK. An increase in the balance between RANKL and OPG leads to increased bone resorption (both locally and generalised), e.g. in patients with postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, multiple myeloma, other malignancies with skeletal metastases, or rheumatoid arthritis. The development of new anti-osteoporotic drugs, based on the restoration of the imbalance between RANKL and OPG, may be a breakthrough in optimising the treatment of patients with bone diseases. However, the results of studies on fracture reduction, the safety profile, the costs of the new drugs and their comparison with bisphosphonates, currently the gold standard in osteoporosis treatment, must be awaited.     

Dietary fish oil decreases the proportion of classical monocytes in blood in healthy mice but increases their proportion upon induction of inflammation

Fish oil can have beneficial effects in health and disease. In healthy individuals, reduction of the inflammatory status may be of benefit, whereas in patients with systemic inflammation, such as sepsis, it is important to diminish the immunosuppression that is thought to contribute to poor outcome. The objective of this study was to determine the effects of dietary fish oil on monocytes/macrophages in blood, bone marrow, spleen, and peritoneum and chemokine concentrations in blood and peritoneum in healthy mice and mice with endotoxin-induced inflammation. Mice were fed a Western-type diet without fish oil (C) or with 2.8% fish oil (FO) for 6 wk and then either killed (healthy mice) or injected i.p. with endotoxin (LPS) and killed after 3, 8, 12, 24, or 48 h. Blood, bone marrow, spleen, and peritoneal lavage were collected. Expression of cell surface molecules and chemokine receptors was analyzed by flow cytometry and chemokine concentrations measured by ELISA. Healthy mice in the FO group had lower proportions of classical monocytes in blood than healthy mice in the C group. LPS administration increased the proportion of classical monocytes in blood in mice in the FO group but not in those in the C group. Healthy mice in the FO group had lower serum concentrations of CCL2 than mice in the C group, but in inflamed mice, CCL2 concentrations were higher in the FO group than in the C group. These results indicate that dietary fish oil can attenuate the inflammatory status in homeostasis but intensify the immune response upon inflammation.     

Dietary fish oil suppresses experimental immunoglobulin a nephropathy in mice

Dietary fish oil (FO) supplementation reportedly retards the progression of renal disease in patients with immunoglobulin (Ig)A nephropathy (IgAN), the most common glomerulonephritis worldwide. Using an experimental mouse model in which early immunopathological hallmarks of IgAN are induced by the mycotoxin vomitoxin (VT), the ameliorative effects of FO ingestion on this disease were evaluated in two studies. In Study 1, the capacity of VT to induce IgAN was evaluated in mice fed for 12 wk AIN-76A diets containing 50 g/kg corn oil (CO), 50 g/kg CO plus 9 mg/kg tert butylhydroquinone (TBHQ), or 5 g/kg CO plus 45 g/kg menhaden FO that contained 200 mg/kg TBHQ. Serum IgA, serum IgA immune complexes and kidney mesangial IgA deposition were greater in mice fed VT + CO compared with the CO control group, whereas all three variables were significantly attenuated in mice fed VT + FO. Although TBHQ also had attenuating effects, these were significantly less than those for the VT + FO group. In Study 2, the effects of feeding modified AIN 93G diets containing either 70 g/kg CO or 10 g/kg CO plus 60 g/kg FO for 20 wk on VT-induced IgAN were compared. Again, consumption of FO attenuated all three immunopathological variables. In addition, spleen cell cultures from the VT + FO group produced markedly less IgA than those cultures from mice fed VT + CO. Taken together, the results suggested that diets containing FO may impair early immunopathogenesis in VT-induced IgAN and that this was not totally dependent on the presence of the antioxidant TBHQ.     

IRP1 activity and expression are increased in the liver and the spleen of rats fed fish oil-rich diets and are related to oxidative stress

Many clinical studies have indicated that diets rich in fish oil (FO) reduce the risk of cardiovascular disease and have anti-inflammatory and antithrombotic properties. Although the therapeutic effects of FO have been well described, their impact on iron metabolism remains unclear. The aim of this work was to study the activity and expression of IRP1 in the liver and the spleen of rats fed FO-rich diets with 0 (FO-0) or 100 (FO-1) mg/kg of all-rac-alpha-tocopherol acetate. We also measured nonheme iron, alpha-tocopherol and retinol concentrations, and superoxide (SOD) and catalase activity in these organs. Rats fed FO were compared to rats fed a corn oil (CO)-rich diet with 100 mg/kg all-rac-alpha-tocopherol acetate. The activity and expression of IRP1 in both the liver and the spleen of rats fed FO diets were greater than in those fed the CO diet. FO-fed rats also had lower nonheme iron concentrations in these organs. Hepatic alpha-tocopherol and retinol concentrations and SOD activity were lower in FO-0-fed rats compared to those fed the CO diet. In the spleen, alpha-tocopherol and retinal concentrations were not altered but SOD activity was lower in FO-0- fed rats, whereas catalase activity was greater than in rats fed CO. The results indicate that there is an increase in oxidative stress in the liver and in the spleen of rats fed FO diets. These changes, together with the reduction of nonheme iron concentrations in both FO-0- and FO-1-fed rats, may explain the increase in activity and expression of IRP1. Therefore, the ingestion of FO-rich diets should be monitored under close supervision.     

2型糖尿病患者骨保护素与骨质疏松的关系

目的 探讨2型糖尿病患者骨保护素与骨量变化之间的关系。方法 选择2型糖尿病患者60例,均行双能X线骨密度（BMD）测定和骨保护素测定,并进行各项生化指标检测。结果 2型糖尿病骨密度和骨保护素之间有明显相关性,有统计学意义。结论 测定2型糖尿病患者的骨保护素水平能反映其骨密度变化。     

Inhibition of autoimmune deterioration in MRL/lpr mice by vitamin E.

The potential of the antioxidant vitamin E to modulate the progress of the SLE-like (systemic lupus erythematosus) autoimmune disease in MRL/MP-lpr/lpr (MRL/lpr) mice is described. Mice were orally supplemented with 0.4 mg vitamin E per day 5 times per week from week 8 of age onwards and compared with mice on a commercial or a vitamin E-deficient diet. Supplementation with vitamin E extended the mean survival time from 157 to 196 days; the massive spleen and lymph node enlargements were reduced; mitogenic responses of B and T cells were normalized; the abnormal differentiation patterns of thymic and splenic cell sub-populations were changed; titers of anti-double stranded DNA antibodies, concentrations of serum amyloid P component (SAP, an acute phase protein), and proteinuria were reduced. The results indicate that vitamin E beneficially affects the development of the SLE-like disease in MRL/lpr mice suggesting a possible measure to reduce human SLE and probably various other autoimmune diseases in humans as well.     

Decreases in bone mineral content by dietary all-trans retinoic acid precede decreases in bone mineral density in a weanling rat model of cigarette smoke-induced lung injuries

Research has indicated that excessive vitamin A can have deleterious impacts on bone. Retinoic acid (RA), the most active metabolite of vitamin A, has been tested in clinical trials for treatment of lung cancer and emphysema. These trials are not measuring Bone Mineral Content (BMC) or Bone Mineral Density (BMD). In this study, we used an animal model to determine potential deleterious effects of all-trans RA on bone mass when used as a means to protect against or treat cigarette smoke-induced lung injuries, and also to evaluate BMC as a potential early indicator of osteoporosis risk. Twenty-four male weanling rats were fed either a control diet or a RA-supplemented diet. Half of each group was exposed to 40 cigarettes per day, 5 days per week, for 4 weeks. BMC and BMD were measured at weeks 2 and 4. RA supplementation in all groups significantly decreased (p < 0.05) only BMC at week 2 and both BMC and BMD (both p < 0.05) at week 4. The same results were observed when BMC was expressed relative to body weight. These data suggest that caution should be used when RA is used to treat smoke-related lung injuries.     

类风湿性关节炎患者anti-Sa、anti-CCP抗体浓度检测及其与炎症及骨关节损伤严重程度的相关关系

目的检测类风湿性关节炎(RA)患者血清中抗环状瓜氨酸(anti-CCP)抗体、抗Sa(anti-Sa)抗体浓度,探讨其与机体炎症及骨关节损伤程度的内在联系。方法选择2014年1月-2018年5月首次确诊并接受治疗的RA患者129例作为RA组,同期进行体检的健康志愿者100例作为对照组。检测2组血清anti-Sa、anti-CCP抗体浓度以及血清炎症因子含量、骨关节损伤评分及相关指标含量,采用Pearson检验评估RA患者血清anti-Sa、anti-CCP抗体浓度与机体病情严重程度的相关关系。结果RA组患者血清anti-Sa、anti-CCP抗体浓度高于对照组(P<0.05)。RA组患者血清炎症因子肿瘤坏死因子-α(TNF-α)、白介素-17(IL-17)、白介素-22(IL-22)、白介素-37(IL-37)的含量高于对照组,Lysholm评分、HSS评分值低于对照组,血清中骨关节损伤相关指标护骨素(OPG)、核因子-κB受体活化因子配体(RANKL)、基质金属蛋白酶3(MMP3)的含量高于对照组(P<0.05)。相关性分析显示,RA患者血清anti-Sa、anti-CCP抗体浓度与血清炎症因子及骨关节损伤相关指标含量呈正相关(P<0.05),与膝关节Lysholm评分、HSS评分值呈负相关(P<0.05)。结论RA患者血清anti-Sa、anti-CCP抗体浓度异常升高,且具体水平与机体炎症反应程度、骨关节损伤程度密切相关,对RA病情严重程度评估具有重要意义。     

Influence of chronic energy intake restriction on intestinal alkaline phosphatase in C3H/Bi mice and autoimmune-prone MRL/lpr,lpr mice

The influence of chronic energy intake restriction (CEIR) on the level and activity of intestinal alkaline phosphatase was investigated in mice of the autoimmune-prone MRL/lpr,lpr strain and in mice of the autoimmune-resistant C3H/Bi strain. In both strains of mice, CEIR of 40% resulted in a significant increase in intestinal alkaline phosphatase (IAP) specific activity in MRL/lpr,lpr mice after 10 wk of feeding, and in C3H/Bi mice after 6 wk of feeding. An increase in the amount of immunoreactive alkaline phosphatase antigen was also found to be associated with the increased enzyme activity in CEIR mice. These results suggest that a specific induction of an intestinal enzyme occurs or, alternatively, that there is a specific relative decrease in synthesis of intestinal proteins other than IAP as a function of CEIR. Thus, CEIR appears to regulate the expression of proteins in the small intestine in a specific manner.     

Effect of dietary alpha-linolenic acid on growth, metastasis, fatty acid profile and prostaglandin production of two murine mammary adenocarcinomas

The purpose of this study was to determine whether dietary (n-3) fatty acids would affect mammary tumor growth and metastasis. Weanling female BALB/c mice were fed diets that contained 10% corn oil (CO), linseed oil (LO) or a fish oil-corn oil mix (FO) for 3-8 wk prior to receiving subcutaneous injections of one of two syngeneic mammary tumor cell types (410 and 410.4). Tumor growth was assessed by monitoring mean tumor diameter and tumor weight upon removal. Feeding LO, but not FO, reduced the growth (p less than 0.05) of 410.4 mammary tumors compared with growth in those fed CO. Metastasis data paralleled the tumor growth rate. Feeding LO and FO enhanced (p less than 0.005) incorporation of (n-3) fatty acids into tumors. Tumor prostaglandin E (PGE) production was reduced (p less than 0.005) by LO and FO, compared with CO. FO feeding reduced 410.4 tumor PGE synthesis more (p less than 0.05) than LO feeding, yet tumor growth was only inhibited by LO. These data suggest an inhibitory effect of dietary linolenic acid [i.e., 18:3 (n-3)] on mammary tumor growth and metastasis. However, this effect did not directly correlate with diet-induced changes in PGE synthesis.