A facile boronophenylalanine modified polydopamine dual drug-loaded nanoparticles for enhanced anti-tumor immune response in hepatocellular carcinoma comprehensive treatment.

Hepatocellular carcinoma (HCC) has an insidious onset and high malignancy. Most patients have progressed to intermediate and advanced stages by the time of diagnosis, and the long-term efficacy of traditional treatments is not satisfactory. Immunotherapy has shown great promise in the treatment of HCC in recent years; however, the low immunogenicity and severe immunosuppressive tumor microenvironment result in a low response rate to immunotherapy in HCC patients. Therefore, it is of great significance to improve the immunogenicity of HCC and thus enhance its sensitivity to immunotherapy. Here, we prepared the boronophenylalanine-modified dual drug-loaded polydopamine nanoparticles by a facile method. This system used boronophenylalanine-modified polydopamine nanoparticles as a delivery vehicle and photothermal material for the chemotherapeutic drug doxorubicin and the immune agonist CpG oligodeoxynucleotides (CpG-ODN), with both active targeting and lysosomal escape functions. The cancer cells are rapidly killed by photothermal treatment, and then chemotherapy is used to further kill cancer cells that are inadequately treated by photothermal treatment. The combination of photothermal-chemotherapy synergistically induces the release of relevant antigens from tumor cells, thus initiating anti-tumor immunity; and then cooperates with CpG-ODN to trigger a powerful anti-tumor immune memory effect, potently and durably inhibiting HCC recurrence.

Replication of a Gene-Diet Interaction at CD36, NOS3 and PPARG in Response to Omega-3 Fatty Acid Supplements on Blood Lipids: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Modulation of genetic variants on the effect of omega-3 fatty acid supplements on blood lipids is still unclear. METHODS: In a double-blind randomized controlled trial, 150 patients with type 2 diabetes (T2D) were randomized into omega-3 fatty acid group (n = 56 for fish oil and 44 for flaxseed oil) and control group (n = 50) for 180 days. All patients were genotyped for genetic variants at CD36 (rs1527483), NOS3 (rs1799983) and PPARG (rs1801282). Linear regression was used to examine the interaction between omega-3 fatty acid intervention and CD36, NOS3 or PPARG variants for blood lipids. FINDINGS: Significant interaction with omega-3 fatty acid supplements was observed for CD36 on triglycerides (p-interaction = 0.042) and PPAGR on low-density lipoprotein-cholesterol (p-interaction = 0.02). We also found a significant interaction between change in erythrocyte phospholipid omega-3 fatty acid composition and NOS3 genotype on triglycerides (p-interaction = 0.042), total cholesterol (p-interaction = 0.013) and ratio of total cholesterol to high-density lipoprotein cholesterol (p-interaction = 0.015). The T2D patients of CD36-G allele, PPARG-G allele and NOS3-A allele tended to respond better to omega-3 fatty acids in improving lipid profiles. The interaction results of the omega-3 fatty acid group were mainly attributed to the fish oil supplements. INTERPRETATION: This study suggests that T2D patients with different genotypes at CD36, NOS3 and PPARG respond differentially to intervention of omega-3 supplements in blood lipid profiles.

Effects of n-3 fatty acid supplements on glycemic traits in Chinese type 2 diabetic patients: A double-blind randomized controlled trial.

SCOPE: To investigate the effects of n-3 fatty acid supplements, both marine and plant-based, on glycemic traits in Chinese type 2 diabetes patients. METHOD AND RESULTS: In a double-blind randomized controlled trial, 185 recruited Chinese type 2 diabetes patients were randomized to either fish oil (FO, n = 63), flaxseed oil (FSO, n = 61), or corn oil group (served as control group, n = 61) for 180 days. The patients were asked to take corresponding oil capsules (four capsules/day), which totally provided 2 g/day of eicosapentaenoic acid + docosahexaenoic acid in FO group and 2.5 g/day of alpha-linolenic acid in FSO group. No group × time interaction was observed for homeostatic model assessment of insulin resistance, fasting insulin, or glucose. Significant group × time interaction (P = 0.035) was observed for glycated hemoglobin A1c (HbA1c), with HbA1c decreased in FO group compared with corn oil group (P = 0.037). We also found significant group × time interactions for lipid traits, including LDL cholesterol (P = 0.043), total cholesterol (P = 0.021), total cholesterol/HDL cholesterol (P = 0.009), and triacylglycerol (P = 0.003), with the lipid profiles improved in FO group. No significant effects of FSO on glycemic traits or blood lipids were observed. CONCLUSIONS: Marine n-3 PUFA supplements may improve glycemic control and lipid profiles among Chinese type 2 diabetic patients.

[Protective Effect of Total Flavones of Bidens pilosa L. on IgA1 Induced Injury of HUVECs in Henoch-Schönlein Purpura Children Patients].

OBJECTIVE: To explore the protective effect and mechanism of total flavones of Bidens pilosa L. (TFB) on IgA1 induced injury of venous endothelial cells in Henoch-Schönlein purpura (HSP) children patients. METHODS Human umbilical venous endothelial cells (HUVECs) were taken as subject. They were intervened by normal IgA1 and HSP children patients' serum IgA1, and added with different concentrations TFB at the same time. Then they were divided into the blank control group, the normal control group, the HSP IgA1 group, and HSP IgA1 plus TFB (1.0, 0.5, 0.25 mg/mL) groups. Levels of TNF-α and IL-8 in supernate were detected by ELISA. The NO level was detected by nitrate reductase method. mRNA and protein expressions of NF-κB and ICAM-1 in HUVECs were detected by fluorescent quantitative PCR and Western blot respectively. RESULTS: Compared with the normal control group and the blank control group, levels of IL-8, TNF-α, and NO all significantly increased in the HSP group (P < 0.05). Compared with the HSP group, levels of IL-8, TNF-α, and NO significantly decreased after intervention of TFB (1.0 and 0.5 mg/mL; P < 0.05, P < 0.01). Results of fluorescent quantitative PCR and Western blot showed, as compared with the blank control group and the normal control group, mRNA and protein expressions of NF-κB and ICAM-1 in HSP children patients' serum IgA1 induced venous endothelial cells significantly increased with statistical difference (P < 0.05, P < 0.01). Compared with the HSP group, mRNA and protein expressions of NF-KB and ICAM-1 were obviously down-regulated after intervention of TFB (1.0, 0.5, 0.25 mg/mL), with statistical difference (P < 0.05, P < 0.01). CONCLUSION: TFB could protect vascular damage by inhibiting in vivo high expression of NF-κB, reducing the production of IL-8, TNF-α, and NO in vascular endothelial cells of HSP children patients.

Total flavonoids of Bidens bipinnata L. a traditional Chinese medicine inhibits the production of inflammatory cytokines of vessel endothelial cells stimulated by sera from Henoch-Schönlein purpura patients.

OBJECTIVES: Bidens bipinnata L. is well known as a traditional antipyretic, anti-inflammatory and anti-rheumatic medicine in China. This study was designed to evaluate the role of total extracted flavonoids from B. bipinnata (TFB) in inhibiting the production of inflammatory cytokines. METHODS: Human umbilical vein endothelial cells (HUVEC) were used to examine the effect of TFB on the production of inflammatory cytokines. The supernatant interleukin (IL)-8, tumour necrosis factor (TNF)-α and nitric oxide (NO) levels of HUVEC were measured with ELISA methods. Nuclear factor-kappaB (NF-κB) and fractalkine expression was evaluated by RT-PCR and Western blot methods, respectively. KEY FINDINGS: We observed that IL-8, TNF-α and NO release of HUVEC incubated with sera from active Henoch-Schönlein purpura (HSP) was significantly increased. TFB intervention may significantly suppressed the supernatant IL-8, TNF-α and NO levels of HUVEC. Similarly, TFB obviously suppressed the NF-κB and fractalkine mRNA and protein expression. CONCLUSIONS: These results suggested that TFB may be useful for improving microvascular inflammation in HSP patients.

Protective effects of total flavonoids of Bidens bipinnata L. against carbon tetrachloride-induced liver fibrosis in rats.

Bidens bipinnata L. is well known in China as a traditional Chinese medicine and has been used to treat hepatitis in clinics for many years. In a previous study we found that total flavonoids of Bidens bipinnata L. (TFB) had a protective effect against carbon tetrachloride (CCl4)-induced acute liver injury in mice. Now this study was designed to investigate its therapeutic effect against CCl4-induced liver fibrosis in rats and to determine, in part, its mechanism of action. The liver fibrosis model was established by subcutaneous injection of 50% CCl4 twice a week for 18 weeks. TFB (40, 80 and 160 mg kg(-1)) was administered by gastrogavage daily from the 9th week. The results showed that TFB (80 and 160 mg kg(-1)) treatment for 10 weeks significantly reduced the elevated liver index (liver weight/body weight) and spleen index (spleen weight/body weight), elevated levels of serum transaminases (alanine aminotransferase and aspartate aminotransferase), hyaluronic acid, type III procollagen and hepatic hydroxyproline. In addition, TFB markedly inhibited CCl4-induced lipid peroxidation and enhanced the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase. Moreover, TFB (80 and 160 mg kg(-1)) treatment improved the morphologic changes of hepatic fibrosis induced by CCl4 and suppressed nuclear factor (NF)-kappaB, alpha-smooth muscle actin (SMA) protein expression and transforming growth factor (TGF)-beta1 gene expression in the liver of liver fibrosis of rats. In conclusion, TFB was able to ameliorate liver injury and protect rats from CCl4-induced liver fibrosis by suppressing oxidative stress. This process may be related to inhibiting the induction of NF-kappaB on hepatic stellate cell activation and the expression of TGF-beta1.

Protective effects of total flavonoids of Bidens pilosa L. (TFB) on animal liver injury and liver fibrosis.

The hepatoprotective effects of total flavonoids of Bidens pilosa L. (TFB), a traditional Chinese medicine were evaluated in carbon tetrachloride (CCl(4))-induced liver injury in mice and rats. Total flavonoids of Bidens pilosa L. (25, 50 and 100mg/kg) were administered via gavage daily for 10 days to CCl(4)-treated mice as well as TFB (30, 60 and 90mg/kg) administered for 6 weeks to CCl(4)-treated rats. Liver index (liver weight/body weight), serum levels of transaminases (alanine aminotransferase, ALT and aspartate aminotransferase, AST), hepatic malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were evaluated following the 10 days treatment in mice. In addition histopathologic changes and nuclear factor-kappaB (NF-kappaB) expression of the liver were detected with hematoxylin-eosin (HE) and immunohistochemistry methods, respectively. The results showed that TFB (50 and 100mg/kg) effectively reduced the CCl(4)-induced elevated liver index, serum ALT, AST levels, hepatic MDA content, and restored hepatic SOD, GSH-Px activities in acute liver injury mice. TFB (60 and 90mg/kg) treatment significantly inhibited NF-kappaB activation in liver fibrosis of rats. The histopathological analysis suggested that TFB reduced the degree of liver injury in mice and severity of liver fibrosis in rats. These results suggested that TFB had a protective and therapeutic effect on animal liver injury, which might be associated with its antioxidant properties and inhibition of NF-kappaB activation.

Protective effect of total flavonoids from Bidens bipinnata L. against carbon tetrachloride-induced liver injury in mice.

Bidens bipinnata L. is well known in China as a traditional Chinese medicine. This study was designed to evaluate the hepatoprotective activity of the total flavonoids of B. bipinnata L. (TFB) against carbon tetrachloride (CCl4)-induced acute liver injury in mice and to determine its mechanism of action. Oral administration of TFB at doses of 50, 100 and 200 mg kg(-1) for 7 days significantly reduced the elevated relative values of liver weight, serum transaminases (alanine aminotransferase and aspartate aminotransferase) and the hepatic morphologic changes induced by CCl4 in mice. In addition, TFB markedly inhibited CCl4-induced lipid peroxidation and enhanced the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase. Moreover, pretreatment with TFB suppressed nitric oxide production and nuclear factor-kappaB activation in CCl4-treated mice. The results suggest that TFB has significant hepatoprotective activity and its mechanism is related, at least in part, to its antioxidant properties. Further research is required to investigate the detailed mechanism of the protective effect of TFB on acute liver injury.

[Study on the property of adsorption and separation of the macroporous resins for total flavonoids of Bidens bipinnata L].

OBJECTIVE: To screen macroporous resins for isolation and purification of total flavonoids of Bidens bipinnata L. (TFB) through investigating the property of adsorption and desorption of 7 kinds of macroporous adsorption resins for TFB. METHODS: The content of total flavonoids was used as the evaluating criteria, and the static and dynamic adsorption-desorption methods were adopted to compare the adsorption quantity, the rate of desorption and adsorption kinetics of different macroporous adsorption resins. RESULTS: Among 7 kinds of macroporous adsorption resins, the HPD 100 resin was the best for isolating and purifying TFB. CONCLUSION: HPD 100 possess a better adsorbability and separating property, and its property is obviously higher than any other resins.

Protective effect of total flavones of rhododendra on ischemic myocardial injury in rabbits.

This study was to investigate the effect of total flavones of rhododendra (TFR) on ischemic myocardial injury in rabbits. Rabbit ischemic myocardial injury was induced by occluding the anterior descent of the left artery (LAD). The ECG was recorded; the plasma creatine kinase (CK), nitric oxide (NO) and endothelin-1 (ET-1) levels were measured using spectrophotometry, Griess method and radioimmunoassay, respectively. The myocardial ischemic size and infarction size were determined by dual staining with Evan's blue and Nitroblue tetrazolium reductionest (N-BT). A typical ECG S-T segment elevation and an increase of plasma CK activity were observed 6 and 24 hours after the induction of ischemia. These changes were inhibited in rabbits treated with either TFR (30, 60 mg/kg) or ginkgo biloba extract (EGB) for 7 days, indicating a protective effect of TFR on ischemic myocardial injury. The myocardial ischemic size and infarction size were 40.7 +/- 3.6% and 36.8 +/- 3.6% respectively in the control group, while TFR (60 mg/kg) pretreatment for 7 days significantly reduced both myocardial ischemic size (32.40 +/- 5.38%, p < 0.05) and infarction size (28.7 +/- 5.8%, p < 0.05). In addition, the occlusion of LAD resulted in an increase of ET-1 and a decrease of NO levels in the plasma, effects that were inhibited by TFR treatment, suggesting a possible mechanism for the protective effect of TFR against myocardial ischemic injury.