Genistein prevents bone loss in type 2 diabetic rats induced by streptozotocin.

BACKGROUND: Diabetic osteoporosis has become a severe public health problem in the aging societies. Genistein has been reported to play an important role in preventing and treating metabolic diseases via its anti-inflammatory, antioxidant, anti-estrogenic, and estrogen-like functions. OBJECTIVE: We aimed to investigate whether genistein exerts bone-protective effect on diabetic rats induced by 35 mg/kg streptozotocin (STZ) plus a 4-week high-fat diet. DESIGN: Sprague-Dawley rats were randomly divided into four groups: (1) control group, (2) type 2 diabetes mellitus (T2DM) model group, (3) T2DM with 10 mg/kg genistein, and (4) T2DM with 30 mg/kg genistein. After an 8-week treatment with genistein, the femurs, tibias, and blood were collected from all rats for further analysis. RESULTS: Genistein at 10 mg/kg showed little effect on diabetic osteoporosis, whereas genistein at 30 mg/kg significantly improved glucose and bone metabolisms compared with diabetic rats. Our results showed that 30 mg/kg genistein significantly increased bone mineral density, serum osteocalcin, and bone alkaline phosphatase. Genistein also effectively lowered fasting blood glucose, tartrate-resistant acid phosphatase 5b, tumor necrosis factor-α, interleukin-6, and numbers of adipocytes and osteoclasts. Compared with the T2DM group, protein levels of receptor activator of nuclear factor κB ligand (RANKL) and peroxisome proliferator-activated receptor-γ (PPAR-γ) were decreased, while protein levels of osteoprotegerin (OPG), ß-catenin, and runt-related transcription factor 2 (Runx-2) were increased after genistein intervention. CONCLUSION: Genistein could effectively improve abnormal bone metabolism in STZ-induced diabetic rats; the underlying molecular mechanisms might be related to OPG/RANKL, PPAR-γ, and ß-catenin/Runx-2 pathways.

Effect of Genistein on Cholesterol Metabolism-Related Genes in HepG2 Cell.

It has been reported that genistein could improve metabolic syndromes. Our study aimed to investigate the effects and potential mechanisms of genistein on improving cholesterol metabolism in HepG2 cell. HepG2 cells were cultured with 0, 0.01, 1.00, 10.00, and 50.00 µM genistein for 24 hr. The current results showed a dose-dependent manner between genistein and intracellular contents of total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and cellular apolipoprotein A1 (Apo-A1) secretion. TC was increased by 25.69%, meanwhile HDL-C and Apo-A1 were decreased by 56.00% and 25.93%, respectively, when the dosage of genistein was 1.00 µM. Genistein dose-dependently upregulated the protein and mRNA levels of sterol regulatory element binding proteins-2 (SREBP-2), as well as the mRNA levels of low-density lipoprotein receptor (LDLR) and 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR), by 145.91%, 72.29%, 310.23%, and 123.08%, respectively, when we gave 1.00 µM genistein, indicating that intracellular cholesterol synthesis and absorption of exogenous cholesterol were increased. In addition, the mRNA levels of peroxisome proliferator-activated receptor-γ (PPARγ) and liver X receptor (LXRα), lowered by 58.23% and 34.86% at 0.01 µM genistein, were reduced in a dose-dependent manner. LXRα and ATP-binding cassette transporter A1 (ABCA1) protein levels were significantly (P < 0.05) decreased by 50.35% and 11.60% at 1.00 µM genistein, which indicated that cellular cholesterol efflux was inhibited. Taken together, our results suggested that genistein at dosage of more than 1.00 µM was able to increase the intracellular cholesterol levels by up regulating SREBP-2/LDLR/HMGCR pathway and suppressing PPARγ/LXRα/ABCA1 pathway. PRACTICAL APPLICATION: In this study, genistein appeared to be effective in reducing plasma cholesterol levels due to increase the intracellular cholesterol levels by upregulating cholesterol absorption through SREBP-2/LDLR/HMGCR pathway, and also downregulating cholesterol efflux via PPARγ/LXRα/ABCA1 pathway in vitro. In addition, plasma cholesterol is regarded as the key indicator of atherosclerosis; therefore, we believe that our findings could be used for further exploration on a possible therapeutic application of genistein for atherosclerosis.

Lycopene Ameliorated Oxidative Stress and Inflammation in Type 2 Diabetic Rats.

We aim to study the antioxidative and anti-inflammatory effects of lycopene on type 2 diabetes mellitus (T2DM) rats, anticipating a complementary strategy for the prevention of long-term complications of T2DM. In this study, rats with streptozotocin-induced diabetes were divided into four groups, receiving a 10-week lycopene intervention: DM, DM + low dose of lycopene (L), DM + medium dose of lycopene (M), and DM + high dose of lycopene (H) group with 0, 5, 10, and 15 mg/kg BW lycopene, respectively. At the end of intervention, fasted blood glucose (FBG) level, oxidative stress indicators, including glycosylated hemoglobin (GHb), glycosylated low-density lipoprotein, oxidized low-density lipoprotein (ox-LDL). and malondialdehyde (MDA), as well as antioxidants, that is, catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), and inflammatory factors like tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were determined. The results indicated that oxidative stress and inflammatory factors were elevated in DM rats. Lycopene intervention decreased the FBG level in DM rats compared with the untreated ones. It revealed a dose-dependent effect on decreasing serum oxidative stress biomarkers, including GHb, ox-LDL, and MDA. Inflammatory factors (TNF-α and CRP) in DM rats were also decreased by lycopene intervention. Total antioxidative capacity as well as the activities of antioxidants in DM rats including CAT, SOD, and GPx were increased after lycopene intervention. We conclude that lycopene protects against diabetic progression and prevents further complications of diabetic rats through ameliorating oxidative stress and inflammation, as well as improving the systemic antioxidative capacity. PRACTICAL APPLICATION: According to our study, lycopene intakes at experimental dosages appear to have beneficial effects on ameliorating oxidative stress and inflammation in type 2 diabetes mellitus (T2DM) rats, suggesting that lycopene might help improving T2DM progression when its daily intake is up to about 0.79 mg/kg BW in humans, which approximately equals to 5 mg/kg BW in rats. However, more clinical trials are needed to provide a more reliable and convincing conclusion in humans.

Genistein can ameliorate hepatic inflammatory reaction in nonalcoholic steatohepatitis rats.

Genistein plays an active role in improving nonalcoholic fatty liver disease (NAFLD). This study is designed to investigate the effect of genistein on liver inflammation in rats with nonalcoholic steatohepatitis (NASH). Forty SPF male SD rats were randomly divided into normal group, model group, genistein low-dose group (0.1% wt/wt) and high-dose group (0.2% wt/wt) with 10 rats in each group. After 12 weeks' feeding, liver tissues and serum samples of rats were taken, and HE staining was used to perform pathological examination of liver tissues, then the degree of inflammatory infiltration was observed and NAFLD activity score(NAS) was calculated. With corresponding kits, several indicators were detected, namely, serum triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), liver TC and TG, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood glucose and serum endotoxin. The levels of tumor necrosis factor (TNFα) in liver and insulin in blood of rats were detected by enzyme linked immunosorbent assay (ELISA), then the HOMA-IR index was calculated. Immunohistochemistry staining was used to observe the expression level of TLR4 protein and the RT-PCR was used to detect Tlr4 mRNA expression in liver tissue. The results showed that genistein could reduce TLR4 protein and gene expression, decrease the endotoxin and TNFα, alleviate the inflammatory reaction and make the indicators detected in blood and liver stay near normal in NASH rats. In conclusion, genistein can ameliorate hepatic inflammatory reaction in nonalcoholic steatohepatitis rats.

Effects of lycopene on metabolism of glycolipid in type 2 diabetic rats.

Diabetes is a series of metabolic diseases, which characteristics is hyperglycemia caused by the interruption of insulin action. Lycopene is an antioxidant which has potential anti-diabetic activity but the correlative reports are rare. This study was designed to explore the influence of lycopene on metabolism of glycolipid in type 2 diabetes. The model of type2 diabetes was induced in adult male albino Sprague Dawley rats, weighing 180-220 g, feeding high fat diet for 4 weeks, then streptozotocin (25 mg/kg) was intraperitoneally injected. 1 week after, rats in diabetic group showed increasing in fasting blood glucose, lipid in blood and liver, glycosylated hemoglobin, HOMA-IR and decreasing in plasma insulin comparing with the normal control group after modeling. Oral administration of lycopene oil solution (10 mg/kg or 20 mg/kg body weight) once a day for 10 weeks can improve the above changes and make them toward to normality. The activities of oxidative enzymes SOD and GSH-Px increased and MDA decreased in pancreatic tissue of rats after the intervention of lycopene. In addition, it can also observe that lycopene can protect body weight loss from diabetic rats. These results showed that lycopene has potential effect on anti-diabetes and it can regulate the metabolism of glycolipid in diabetic rats.

Genistein Ameliorates Fat Accumulation Through AMPK Activation in Fatty Acid-Induced BRL Cells.

Genstein is the most abundant phytoestrogen in soybean that was reported to play positive roles in menopausal syndrome and metabolic syndrome. In the present study, we investigated the effects and potential mechanisms of genistein against progression of nonalcoholic fatty liver disease (NAFLD) in BRL cells treated with fatty acid mixture (oleate/palmitate, 2:1 ratio). Our data demonstrated that genistein remarkably improved fatty acid mixture-induced hepatocelluler fat accumulation, inhibited upregulation of genes expression related to fatty acid synthesis, and derepressed those associated with fatty acid oxidation. In addition, the results displayed that genistein promoted the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) suppressed by fatty acid, which were significantly weakened by compound C, an AMPK inhibitor. Taken all together, genistein is capable to ameliorate fat accumulation through regulation of fatty acid metabolism mediated by AMPK activation in BRL cells. Further investigations are needed to verify the protective effects of genistein on NAFLD model in in vivo animal study or in vitro human cell lines along with absorption, distribution, metabolism, and excretion studies of genistein. PRACTICAL APPLICATION: Genistein is able to ameliorate fat accumulation through regulation of fatty acid metabolism mediated by AMPK activation in vitro.

Effects of soy isoflavone on hepatic steatosis in high fat-induced rats.

Soy isoflavone has benefits for metabolic syndrome but the mechanism is not completely understood. This study was designed to determine the effects of soy isoflavone on hepatic fat accumulation in non-alcoholic fatty liver disease (NAFLD) rats induced by high fat diet (HFD). Sprague-Dawley rats were administrated with a normal fat diet (control), HFD (NAFLD model), HFD with 10 or 20 mg/kg soy isoflavone daily for 12 weeks. Hepatic and serum lipid contents, liver histopathological examination, serum alanine transaminase (ALT), protein and mRNA expression of sterol regulatory element binding protein (SREBP)-1c, fatty acid synthase (FAS), peroxisome proliferator-activated receptor (PPAR) α were assayed respectively. Our study found that soy isoflavone reduced HFD-induced lipid accumulation in liver, serum ALT and improved liver lobule structure. In addition, the expression of SREBP-1c and FAS was lower, whereas protein level of PPARα was higher in two soy isoflavone groups than that of the HFD group. Collectively, these results demonstrate that soy isoflavone is capable of alleviating hepatic steatosis and delaying the progression of NAFLD via inhibiting lipogenesis and promoting fatty acid oxidation in liver.

Beneficial Effect of Educational and Nutritional Intervention on the Nutritional Status and Compliance of Gastric Cancer Patients Undergoing Chemotherapy: A Randomized Trial.

Surgery combined with chemotherapy is the standard treatment for gastric cancer (GC); however, chemotherapy-relative adverse effects are common and result in malnutrition and a poor prognosis. In addition, compliance to postoperative chemotherapy remains a problem. This study aimed to prospectively investigate the effect of educational and nutritional interventions on the nutritional status and compliance of GC patients undergoing postoperative chemotherapy. A total of 144 GC patients were randomized into an intervention group that received intensive individualized nutritional and educational interventions during the entire course of chemotherapy and control group that received basic nutrition care and health education during hospitalization. The nutritional status and compliance between the two groups were compared. The interventions significantly improved calorie and iron intake within 24 h after the first chemotherapy session, and improved patients' weight, hemoglobin, total serum protein, and albumin levels during the entire course of chemotherapy. The compliance rate with chemotherapy was significantly higher in the intervention group than in the control group (73.61% vs. 55.56%, P = 0.024). A combination of nutritional and educational interventions provided beneficial effect on the nutrition status and compliance of gastric patients undergoing postoperative chemotherapy, which is worthy of clinical application.

Genistein has beneficial effects on hepatic steatosis in high fat-high sucrose diet-treated rats.

Genistein, a kind of phytoestrogen abundant in soybeans, is beneficial for alleviating non-alcoholic fatty liver disease (NAFLD), but the specific mechanism was not clearly understood. This study was designed to determine the effect of genistein on NAFLD and explore the possible mechanism. 36 male Sprague-Dawley rats were divided into 4 groups: the control group, high fat-high sucrose diet (HFS) group, HFS with 4mg/kg body weight genistein, and HFS with 8mg/kg body weight genistein. 12 weeks later, serum and hepatic lipid profiles, liver histopathological examination were characterized. The protein levels of liver AMP-activated protein kinase (AMPK), phosphorylation of AMPK (p-AMPK), acetyl-CoA carboxylase (ACC), phosphorylation of ACC (p-ACC) and sterol regulatory element binding protein 1 (SREBP-1) were determined by western blot. mRNA expressions of fatty acid synthase gene (FAS) and glycerol-3-phosphate acyltransferase (GPAT), peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyl transfer enzyme-1 (CPT-1) and acyl-CoA oxidase (ACO) were measured by reverse transcription polymerase chain reaction (RT-PCR). Results showed that genistein effectively improved serum and hepatic lipid metabolism and diminished fat accumulation in liver. And the protein level of hepatic p-AMPK and p-ACC were increased, but SREBP-1 was decreased by genistein. Meanwhile, the mRNA levels of FAS and GPAT were lower, but PPARα, CPT-1, ACO were higher in rats treated with genistein compared with HFS group. Collectively, genistein can improve hepatic steatosis via activating AMPK, thus promoting fatty acid oxidation and inhibiting lipid synthesis in liver.

Resveratrol ameliorates hepatic steatosis and inflammation in methionine/choline-deficient diet-induced steatohepatitis through regulating autophagy.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is one of the leading causes of chronic liver disease that can progress to liver fibrosis, cirrhosis and eventually hepatocellular carcinoma. Resveratrol, a naturally occurring phytoalexin, is believed to have therapeutic effects on hepatic steatosis. However, the effect of resveratrol on NASH and the underlying mechanism is not fully illustrated. In the present study, we aimed to exam the effect of resveratrol on methionine/choline-deficient (MCD) diet or medium-induced hepatic steatosis, oxidation and inflammation, and to explore the possible mechanism. METHODS: C57BL/6 mice and AML12 cells were treated with MCD alone or in combination with different concentrations of resveratrol (100 mg/kg/day or 250 mg/kg/day for mice and 25 µmol/L, 50 µmol/L, or 100 µmol/L for cells). Levels of aminotransferases (ALT), interleukin 1ß (IL-1ß), IL-6, and tumor necrosis factor alpha (TNF-α) were measured, concentrations of triglyceride (TG) and thiobarbituric acid reactive substances (TBARs) were determined, and expressions of proteins involved in autophagy were analyzed. RESULTS: The results indicate that MCD diet or medium induced NASH in mouse and AML12 cell, which was confirmed by the elevated levels of TG, TNF-α, IL-1ß, IL-6, ALT and TBARS in mice serum or cell culture medium. Resveratrol administration slowed down NASH progression, decreased the levels of ALT, TG, TBARS, IL-1ß, IL-6, downregulated mRNA expressions of TNF-α, IL-1ß, IL-6, and regulated the expressions of proteins involved in autophagy, both in vitro and in vivo. However, an autophagical inhibitor significantly impaired the protective role of resveratrol on liver injury and inflammation. CONCLUSIONS: Resveratrol can attenuate hepatic steatosis and inflammation in MCD-induced NASH by regulating autophagy. Thus, resveratrol may be a promising agent for inhibiting lipid accumulation and inflammatory processes associated with NASH.

[Effects of multi-nutrients supplementation on the nutritional status and antioxidant capability of healthy adults].

OBJECTIVE: To determine whether daily multivitamins/minerals supplement can improve nutrient status, plasma, antioxidant enzymes activity and total antioxidant capacity in healthy adults. METHODS: One hundred and fifty-one healthy adults living in a normal lifestyle with a mean age of 28 (20 - 50) years were recruited from Guangzhou. The subjects were divided into the supplement group and the control ineral supplements. METHODS: One hundred and fifty-one healthy adults living in a normal lifestyle with a mean age of 28 (20 - 50) years were recruited from Guangzhou. The subjects were divided into the supplement group and the control group carefully matched with age and gender. Supplement pellets (consisted of multivitamins/minerals, including VitA, VitC, VitE,Ca, Zn, Fe, Se, etc.) and placebo pellets (consisted of only dextrin with the same color, shape and size as the supplement pellets) were administrated in a double-blinded manner for 8 week. The nutrients intake data of the research subjects were collected daily by a 24-hour dietary recall method. Blood samples were collected at the beginning and the end of the intervention period for determining the nutritional status, the activities of antioxidant enzymes and the products of oxidative damage. RESULTS: The dietary intake of nutrients was insufficient in these subjects. The levels of plasma VitC, alpha-tocopherol, beta-carotene, Zn, Fe and Se in the supplement group were increased in comparison with the control group by 46%, 28%, 116%, 7%, 30% and 28% respectively (P < 0.05), indicating that the nutritional status regarding antioxidant nutrients had largely been improved. But levels of plasma gamma-tocopherol were decreased by 25% in comparison with the control group (P < 0.05). The activities of GPX, CAT and T-AOC were increased in comparison with the control group and before the supplementation (P < 0.05), while the activities of SOD and the level of 8-isoprostanes remained steady. CONCLUSION: Supplementation of multiple micronutrients could effectively increase the levels of plasma VitC, alpha-tocopherol, beta-carotene, Zn, Fe and Se and the activities of GPX, CAT and T-AOC.

[Effect of soy protein on expression of SREBP-1 in rats].

OBJECTIVE: To explore the effects of soy protein on the expression of SREBP-1,2 in rats feeding normal and high-fat diet. METHODS: Forty eight Sprague-Dawley SPF class rats were randomly divided into 4 groups matched by body weight, soy protein group, casein group, soy protein-high fat group, casein-high fat group. The experiment diets were fed for 28 d. Then the rats were sacrificed off cervical, determined serum levels of homone and the level of gene expression. RESULTS: The concentration of serum insulin and the ratio of insulin/glucagon in the soy protein group were significantly lower than that of the casein group ((54.1 +/- 10.7) vs (63.5 +/- 16.9) pmol/L, P < 0.05, (2.33 +/- 0.75) vs (3.21 +/- 1.41), P < 0.05), the concentration of serum insulin and the ratio of insulin/glucagon in the soy protein high-fat group were significantly lower than that of the casein high-fat group ((46.3 +/- 9.6) vs (50.4 +/- 10.1) pmol/L, P < 0.05, (1.53 +/- 0.72) vs (2.92 +/-1.23), P < 0.05). The expression of SREBP-1,2 in soy protein group and soy protein high-fat group were significantly lower than that in casein group and casein high-fat group. The protein expression of SREBP-1 in soy protein group and soy protein high-fat group were significantly lower than that in casein group and casein high-fat group. CONCLUSION: Dietary soy protein intake may modulate serum lipid levels through influence the insulin level then infulence the expression of SREBP-1,2 mRNA.

Genistein suppresses LPS-induced inflammatory response through inhibiting NF-κB following AMP kinase activation in RAW 264.7 macrophages.

Genistein, the major isoflavone in soybean, was recently reported to exert beneficial effects in metabolic disorders and inflammatory diseases. In the present study, we investigated the effects and mechanisms of a dietary concentration of genistein on the inflammatory response in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Our results demonstrated that genistein effectively inhibited the LPS-induced overproduction of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6), as well as LPS-induced nuclear factor kappa B (NF-κB) activation. In addition, the data also showed that genistein prevented LPS-induced decrease in adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. These effects were obviously attenuated by an AMPK inhibitor. Taken together, our results suggest that the dietary concentration of genistein is able to attenuate inflammatory responses via inhibition of NF-κB activation following AMPK stimulation. The data provide direct evidence for the potential application of low concentrations of genistein in the prevention and treatment of inflammatory diseases.

[Effect of dietary protein on serum lipid profile in hypercholesterolemic people].

OBJECTIVE: To observe the effect of soy protein on the concentration of serum lipids in hypercholesterolemic people and the correlation between dietary protein and serum lipids. METHODS: Ninety healthy hypercholesterolemic volunteers were given beverages contained either 24 g of casein or 18 g of soy protein plus 6 g of casein by random daily for 8 weeks without change of their habitual life. Body height, body weight, waist and hip circumference and serum lipids were measured before and after the study. RESULT: (1) The body weight and body mass index of subjects in the soy group were decreased slightly but significantly (P < 0.05), while the waist-to-hip circumference of subjects in casein group was decreased (P < 0.05). (2) ApoB and TC/HDL-C ratio were significantly reduced after consuming soy protein beverages for 8 weeks (P < 0.05), while in casein group, TC, LDL-C and ApoB were reduced significantly (P < 0.05). (3) The reduction in TC concentration was negatively correlated with the quantity of dietary protein intake (r = - 0.419, P < 0.01), whereas it was positively correlated with the quantity of vegetable protein intake (r = 0.521, P < 0.01). CONCLUSION: The effect of soy protein on serum lipids could be influenced by the source and quantity of dietary protein.

[Effect of early vitamin D supplementation on lung inflammatory factors in baby rat with asthma].

OBJECTIVE: To explore the effect of different doses of 1,25-(OH)(2)VitD(3) early supplementation on airway inflammation and lung inflammatory factors in baby rats with asthma. METHODS: Forty male weaned Wistar rats were divided into normal group, model group, low 1,25-(OH)(2)VitD(3) group, middle 1,25-(OH)(2)VitD(3) group, high 1,25-(OH)(2)VitD(3) group using random number table (8 rats each group). The rats in low, middle and high 1,25-(OH)(2)VitD(3) groups were given 1, 4, 10 µg/kg of 1,25-(OH)(2)VitD(3) every other day by intraperitoneal injection respectively for 25 days. Except normal group, the rats in other groups were challenged with ovalbumin to establish the asthma model. The pathologic changes of lung tissue, the total white blood cell and classified cell counts in bronchoalveolar lavage fluid (BALF) were measured. The concentrations of IL-4, IL-5 and IFN-γ in serum and BALF were measured by ELISA method. RESULTS: The level of total white blood cell counts in BALF were (5.98 ± 1.67)×10(5)/ml, (25.34 ± 4.28)×10(5)/ml, (17.24 ± 3.3)×10(5)/ml, (9.31 ± 3.37)×10(5)/ml, (45.1 ± 15.75)×10(5)/ml, respectively (F = 33.453, P < 0.01). The percent ratio of EOS in BALF were (1.44 ± 0.78)%, (17.81 ± 6.88)%, (15.00 ± 5.70)%, (8.89 ± 3.66)%, (25.88 ± 5.57)%, respectively (F = 27.299, P < 0.01). The level of IL-4 in serum of normal, model, low, middle and high-1,25-(OH)(2)VitD(3) groups were (0.62 ± 0.54), (7.57 ± 1.04), (3.58 ± 0.56), (2.70 ± 0.78) and (5.27 ± 0.30) pg/ml, respectively (F = 116.287, P < 0.01); IL-5 in resume were (32.20 ± 4.23), (67.14 ± 18.14), (37.51 ± 0.47), (40.69 ± 2.47) and (124.60 ± 36.19) pg/ml, respectively (F = 23.902, P < 0.01); IFN-γ in serum were (79.71 ± 10.08), (49.06 ± 4.46), (59.15 ± 2.51), (59.27 ± 2.33) and (53.85 ± 1.97) pg/ml, respectively (F = 39.954, P < 0.01). Also in BLAF, the IL-4 of all groups were (0.51 ± 0.30), (102.92 ± 54.61), (8.64 ± 4.07), (3.10 ± 1.28) and (33.67 ± 8.1) pg/ml, respectively (F = 24.062, P < 0.01); the IFN-γ were (247.37 ± 189.18), (43.82 ± 13.76), (81.32 ± 17.07), (86.50 ± 14.26) and (59.89 ± 34.17) pg/ml, respectively (F = 7.157, P < 0.01); the IL-5 in BALF were (38.81 ± 0.60), (80.48 ± 17.90), (45.11 ± 1.33), (43.39 ± 1.11) and (149.60 ± 45.87) pg/ml, respectively (F = 35.978, P < 0.01). Pathologic changes in lung of asthma rat groups were obvious. The lung pathologic changes in low and middle dose groups showed a significant improvement compared to the asthma group and high dosage group showed more serious pathologic changes compared to the low and middle dose groups. CONCLUSION: Intervention with appropriate dose of 1,25-(OH)(2)VitD(3) in the early life could improve lung pathologic changes and reduce the effect of inflammatory factors in air way of baby rat asthma model. However, overdose might play detrimental effect.

A pilot study to evaluate the effect of soy isolate protein on the serum lipid profile and other potential cardiovascular risk markers in moderately hypercholesterolemic Chinese adults.

This article examines the effect of soy isolate protein on the serum lipids and other potential cardiovascular risk markers in 90 moderately hypercholesterolemic Chinese adults (64 women and 26 men, aged 25 to 70 years). Fasting blood samples were taken before and after consuming 24 g of protein supplied by soy isolate protein supplement (including 18 g soy protein and 6 g milk protein) or milk protein supplement daily for 8 weeks. Dietary intake was assessed by a 3-day record collected at baseline, week 4, and week 8 of the study. The results indicate that the two kinds of protein can modestly improve serum lipids and markers associated with obesity and inflammation.

Environmental tobacco smoke exposure and Chinese schoolchildren's respiratory health: a prospective cohort study.

BACKGROUND: Although China is the most coveted cigarette market worldwide, few studies have examined the longitudinal effects of environmental tobacco smoke (ETS) on health. PURPOSE: To examine the relationship between exposure to ETS and respiratory health in Chinese schoolchildren. METHODS: The study subjects included 1718 children, who were never-smokers, aged 10.05±0.86 years and asthma-free at baseline. The children performed spirometric tests in 2006 and 18 months later. Parents reported the children's respiratory symptoms and illnesses, ETS exposure, and other related information by self-administered survey at both assessment points. The data were analyzed in 2010. RESULTS: Significant exposure-response relationships were found between ETS exposure and coughing at night (p for trend<0.001); sneezing (p for trend=0.031); and sneezing with itchy, watery eyes (p for trend=0.006) in the first survey, and coughing at night (p for trend=0.019); phlegm without a cold (p for trend<0.001); and sneezing (p for trend=0.036) in the second survey. Compared with those who reported no ETS exposure in either survey, children who had a high ETS exposure level (>5 cigarettes/day) in either survey had lower growth rates in forced expiratory flow between 25% and 75% of forced vital capacity (FEF(25-75); ß= -0.104, p=0.020) and forced expiratory flow at 25% of forced vital capacity (FEF(25); ß= -0.077, p=0.027). A monotonic exposure-response effect was observed between ETS exposure and the deficits in the growth rate of FEF(25) and FEF(25-75.) CONCLUSIONS: Exposure to ETS increased the risks of respiratory symptoms in Chinese school-aged children and was associated with impaired lung function growth. A dose-response relationship was observed for the latter effect.

[Effects of soybean isoflavone on liver lipid metabolism in nonalcoholic fatty liver rats].

OBJECTIVE: To study the effects of soybean isoflavone on liver lipid, serum lipid, antioxidant index and hepatic lipid metabolism associated factors in nonalcoholic fatty liver rats. METHODS: Thirty-six male rats (SD) were randomly divided into four groups by weight: normal control group, nonalcoholic fatty liver disease (NAFLD) model control group, low-dose isoflavone treatment group (10 mg/kg) and high-dose isoflavone group (20 mg/kg), 9 rats in each group. Normal control rats were fed with D12450B (10% fat energy), model control and isoflavone intervention rats were fed with D12492 (60% fat energy). Twelve weeks later, liver lipid, serum lipid and antioxidant index were observed. Liver sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS) and peroxisome proliferators activated receptor alpha (PPAR alpha) were detected by western blotting. RESULTS: Liver triglyceride (TG) in normal control group, NAFLD model control group, low-dose isoflavone group and high-dose isoflavone group were (8.11 ± 4.13), (57.06 ± 16.95), (31.26 ± 10.48), (31.38 ± 13.25) mmol/mg protein, respectively (F = 22.569, P < 0.01); liver free fatty acid (FFA) were (0.030 ± 0.007), (0.042 ± 0.009), (0.038 ± 0.009), (0.032 ± 0.005) µmol/mg protein, respectively (F = 4.857, P < 0.01); liver superoxide dismutase (SOD) activity were (502.29 ± 23.71), (201.83 ± 16.99), (228.93 ± 21.71), (238.08 ± 15.96) U/mg protein, respectively (F = 9.555, P < 0.01); liver malondialdehyde (MDA) were (1.29 ± 0.29), (2.85 ± 0.73), (2.07 ± 0.49), (2.03 ± 0.37) nmol/mg protein, respectively (F = 13.449, P < 0.01); SREBP-1c protein expression were 0.45 ± 0.16, 1.42 ± 0.30, 1.02 ± 0.31, 0.47 ± 0.27, respectively (F = 24.515, P < 0.01); FAS protein expression were 0.27 ± 0.08, 1.97 ± 0.47, 1.35 ± 0.30, 0.49 ± 0.12, respectively (F = 60.361, P < 0.01); PPARα protein expression were 2.03 ± 0.56, 0.41 ± 0.17, 0.81 ± 0.27, 0.66 ± 0.16, respectively (F = 37.97, P < 0.01). CONCLUSION: Soy isoflavone can reduce the hepatic lipid deposition and increase antioxidant capacity, the mechanism may be related to inhibition of SREBP-1c and activation of PPARα expression in liver.

Anti-inflammatory effect of genistein on non-alcoholic steatohepatitis rats induced by high fat diet and its potential mechanisms.

Genistein is a naturally occurring plant-derived phytoestrogen present in the human diet, and is known to possess anti-cancer, anti-oxidant and anti-osteoporosis effects. Anti-inflammatory activity of genistein has been revealed in animal studies. In this paper, we investigated the anti-inflammatory effect of genistein on non-alcoholic steatohepatitis (NASH) rats induced by high fat diet (HFD), and explored its potential mechanisms. Rats were fed with normal chow diet or HFD for 12 weeks with or without low (4 mg/kg/day body weight) or high (8 mg/kg/day body weight) dose of genistein. Serum levels of aminotransferases, thiobarbituric acid-reactive substances (TBARS), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and transforming growth factor beta (TGF-ß(1)) were measured, hepatic inflammation, liver TBARS, IL-6, TNF-α and TGF-ß(1) levels were determined, and proteins involved in mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) pathways were assayed. The results showed that the NASH model rats reproduced typical pathogenetic and histopathological features of NASH in human, and genistein administration improved liver function, slowed down NASH progression, decreased the levels of TBARS, TNF-α and IL-6 in serum and liver, as well as inhibited IκB-α phosphorylation, nuclear translocation of NF-κB p65 subunit, and activation of c-Jun N-terminal kinase (JNK). In conclusion, genistein may be a promising drug to inhibit the inflammatory process and prevent liver damage in patients with NASH.

Comparison of dietary control and atorvastatin on high fat diet induced hepatic steatosis and hyperlipidemia in rats.

BACKGROUND: Treatment with atorvastatin (ATO) or dietary control has been demonstrated to benefit patients with non-alcoholic fatty liver disease (NAFLD) and hyperlipidemia. However, little is known on whether combination of dietary control and ATO treatment could enhance the therapeutic effect. METHODS: We employed a rat model of NAFLD to examine the therapeutic efficacy of dietary control and/or ATO treatment. Sprague-Dawley rats were fed with normal chow diet as normal controls or with high fat diet (HFD) for 12 weeks to establish NAFLD. The NAFLD rats were randomized and continually fed with HFD, with normal chow diet, with HFD and treated with 30 mg/kg of ATO or with normal chow diet and treated with the same dose of ATO for 8 weeks. Subsequently, the rats were sacrificed and the serum lipids, aminotransferase, hepatic lipids, and liver pathology were characterized. The relative levels of fatty acid synthesis and ß-oxidation gene expression in hepatic tissues were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Hepatic expression of hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was determined by Western blot assay. RESULTS: While continual feeding with HFD deteriorated NAFLD and hyperlipidemia, treatment with dietary control, ATO or ATO with dietary control effectively improved serum and liver lipid metabolism and liver function. In comparison with ATO treatment, dietary control or combined with ATO treatment significantly reduced the liver weight and attenuated the HFD-induced hyperlipidemia and liver steatosis in rats. Compared to ATO treatment or dietary control, combination of ATO and dietary control significantly reduced the levels of serum total cholesterol and low density lipoprotein cholesterol (LDL-C). However, the combination therapy did not significantly improve triglyceride and free fatty acid metabolism, hepatic steatosis, and liver function, as compared with dietary control alone. CONCLUSIONS: ATO treatment effectively improved NAFLD-related hyperlipidemia and inhibited liver steatosis, accompanied by modulating the expression of genes for regulating lipid metabolism. ATO enhanced the effect of dietary control on reducing the levels of serum total cholesterol and LDL-C, but not triglyceride, free fatty acid and hepatic steatosis in HFD-induced fatty liver and hyperlipidemia in rats.