Erchen decoction alleviates the progression of NAFLD by inhibiting lipid accumulation and iron overload through Caveolin-1 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: A combination of 6 different Chinese herbs known as Erchen decoction (ECD) has been traditionally used to treat digestive tract diseases and found to have a protective effect against nonalcoholic fatty liver disease (NAFLD). Despite its efficacy in treating NAFLD, the precise molecular mechanism by which Erchen Decoction regulated iron ion metabolism to prevent disease progression remained poorly understood. AIM OF STUDY: Our study attempted to confirm the specific mechanism of ECD in reducing lipid and iron in NAFLD from the perspective of regulating the expression of Caveolin-1 (Cav-1). STUDY DESIGN: In our study, the protective effect of ECD was investigated in Palmitic Acid + Oleic Acid-induced hepatocyte NAFLD model and high-fat diet-induced mice NAFLD model. To investigate the impact of Erchen Decoction (ECD) on lipid metabolism and iron metabolism via mediating Cav-1 in vitro, Cav-1 knockdown cell lines were established using lentivirus-mediated transfection techniques. MATERIALS AND METHODS: We constructed NAFLD model by feeding with high-fat diet for 12 weeks in vivo and Palmitic Acid + Oleic Acid treatment for 24 h in vitro. The regulation of Lipid and iron metabolism results by ECD were detected by serological diagnosis, immunofluorescent and immunohistochemical staining, and western blotting. The binding ability of 6 small molecules of ECD to Cav-1 was analyzed by molecular docking. RESULTS: We demonstrated that ECD alleviated the progression of NAFLD by inhibiting lipid accumulation, nitrogen oxygen stress, and iron accumulation in vivo and in vitro experiments. Furthermore, ECD inhibited lipid and iron accumulation in liver by up-regulating the expression of Cav-1, which indicated that Cav-1 was an important target for ECD to exert its curative effect. CONCLUSIONS: In summary, our study demonstrated that ECD alleviated the accumulation of lipid and iron in NAFLD through promoting the expression of Cav-1, and ECD might serve as a novel Cav-1 agonist to treat NAFLD.

Regulating effects of phytosterol esters-loaded emulsions stabilized with green tea polysaccharide conjugates and Tween on lipids in KKAy mice.

Phytosterol esters (PSE) have been shown to have cholesterol-lowering effects, but their insolubility in water limits their applications. Green tea polysaccharide conjugates (gTPC) have hypoglycemic and emulsifying effects. To address lipid dysregulation in diabetic patients, we developed PSE-loaded emulsions stabilized with gTPC and Tween-20 (gTPC-PSE emulsions) and evaluated their physicochemical properties. We subsequently investigated the lipid-regulating potential of these emulsions to in KKAy mice. The KKAy mice were randomly assigned to eight groups: the model group, the Lipitor (10 mg·kg-1)-acarbose (30 mg·kg-1) combination group, two gTPC groups, two PSE groups, and two gTPC-PSE groups with a 1:2 mass ratio of gTPC to PSE. The administered doses were 90 and 270 mg kg-1, respectively. Administration of a 270 mg·kg-1 dose of gTPC-PSE emulsions led to the most significant effects including increased levels of liver and serum high-density lipoprotein cholesterol (HDL-CH), reduced serum leptin and insulin, and improved liver superoxide dismutase (SOD) and reduced malondialdehyde (MDA). In general, gTPC and PSE demonstrated a synergistic effect on lipid regulation in mice. Our results indicate that gTPC-PSE emulsions hold potential as a nutritional intervention for diabetes by modulating lipid levels.

Metabolic disturbance in lettuce (Lactuca sativa) plants triggered by imidacloprid and fenvalerate.

Intensive and indiscriminate use of insecticides in agroecosystems causes phytotoxic disturbances in non-target crops. However, the mechanisms by which plants reprogram cellular metabolites to resist and tolerate such agrochemicals remain unclear. Here, the interaction between lettuce plants with imidacloprid and fenvalerate was investigated by the complementary use of physiological and metabolomic analyses. Neither imidacloprid nor fenvalerate induced overt phytotoxicity in lettuce seedlings. The plant biomass, chlorophyll fluorescence, lipid peroxidation, and membrane integrity were not significantly affected by the selected insecticides. Flavonoid content decreased by 25% in lettuce leaves under fenvalerate exposure, whereas polyphenol and flavonoid contents were not significantly altered by imidacloprid. Although the content of most of the nutrient element in the leaves remained the same following pesticide treatment, iron content decreased by 28.1% under imidacloprid exposure but increased by 22.8% under fenvalerate exposure. Metabolomic analysis revealed that the selected insecticides induced extensive metabolic reprogramming in lettuce roots and shoots. Imidacloprid dramatically increased the metabolism of several amino acids (arginine, cysteine, homoserine, and 4-hydroxyisoleucine), whereas markedly decreased the metabolism of various carbohydrates (glucose, raffinose, maltotetraose, maltopentaose, and stachyose). Fenvalerate did not significantly alter amino acid metabolism but decreased carbohydrate metabolism. Additionally, the relative abundance of most organic acids and polyphenolic compounds decreased significantly after pesticide exposure. These results suggest that plants might program their primary and secondary metabolism to resist and tolerate insecticides. The findings of this study provide important information on how neonicotinoid and pyrethroid insecticides affect the health and physiological state of plants, which are ultimately associated with crop yield and quality.

Inhibition of intestinal lipases alleviates the adverse effects caused by high-fat diet in Nile tilapia.

Intestinal lipases are fat-digesting enzymes, which play vital roles in lipid absorption in the intestine. To study the regulation of intestinal lipase activity in systemic lipid metabolism in fish, especially in the metabolic diseases caused by high-fat diet (HFD) feeding, we inhibited intestinal lipases in Nile tilapia to investigate the physiological consequences. In the present study, Nile tilapia were firstly fed with HFD (12% fat) for 6 weeks to establish a fatty fish model. Afterwards, Orlistat as a potent intestinal lipase inhibitor was added into the HFD for the following 5-week feeding trial, with two dietary doses (Orlistat16 group, 16 mg/kg body weight; Orlistat32 group, 32 mg/kg body weight). After the trial, both doses of Orlistat treatment significantly reduced intestinal lipase activity, fat absorption, hepatic lipid accumulation, and gene expression of lipogenesis, whereas increased gene expression of lipid catabolism. Moreover, intestinal lipase inhibition increased immune enzyme activities, antioxidant capacity, and gene expression of anti-inflammatory cytokines, whereas lowered gene expression of pro-inflammatory cytokines. Besides, Orlistat could also improve the structure of the intestine and increase expression of intestinal tight-coupling protein. Taken together, intestinal lipase inhibition alleviated the adverse effects caused by HFD in Nile tilapia. Thus, intestinal lipases played key roles in absorbing dietary lipid and could be a promising target in regulating systemic lipid metabolism in fish.

Near-Infrared II Phototherapy Induces Deep Tissue Immunogenic Cell Death and Potentiates Cancer Immunotherapy.

The deep and inner beds of solid tumors lack lymphocytic infiltration and are subjected to various immune escape mechanisms. Reversing immunosuppression deep within the tumor is vital in clinical cancer therapy, however it remains a huge challenge. In this work, we have demonstrated the use of a second window near-infrared (NIR(II)) photothermal treatment to trigger more homogeneous and deeper immunogenic cancer cell death in solid tumors, thereby eliciting both innate and adaptive immune responses for tumor control and metastasis prevention. Specifically, photothermal transducers with similar components, structures, and photothermal conversion efficiencies, but different absorptions in red light, NIR(I), and NIR(II) biowindows, were constructed by controlling the self-assembly of gold nanoparticles on fluidic liposomes. In vitro, photothermal treatments induced immunogenic cell death (ICD) that were accompanied by the release of damage-associated molecular patterns (DAMPs) regardless of the wavelength of incident lasers. In vivo, NIR(II) light resulted in a more homogeneous release and distribution of DAMPs in the deeper parts of the tumors. With the induction of ICD, NIR(II) photothermal therapy simultaneously triggered both innate and adaptive immune responses and enabled efficient tumor control with 5/8 of the mice remaining tumor-free in the cancer vaccination assay. Additionally, the NIR(II) photothermal treatment in combination with checkpoint blockade therapy exerted long-term tumor control over both primary and distant tumors. Finally, using systemically administered two-dimensional polypyrrole nanosheets as a NIR(II) transducer, we achieved striking therapeutic effects against whole-body tumor metastasis via a synergistic photothermal-immunological response.

Alteration of Phenolic Composition in Lettuce (Lactuca sativa L.) by Reducing Nitrogen Supply Enhances its Anti-Proliferative Effects on Colorectal Cancer Cells.

Consumption of vegetables rich in phenolic compounds has become a useful method to reduce the risk of developing several types of cancer. This study investigated the potential relationship between the alteration of phenolic compounds in lettuce induced by reduced nitrogen supply and its anti-proliferative effects on Caco-2 colorectal cancer cells. Our results showed that phenolic extracts from lettuce grown under low nitrogen conditions (LP) exhibited better anti-proliferative effects against Caco-2 cells, in part, by interfering with the cell cycle and inducing apoptosis, compared with those from lettuce supplied with adequate nitrogen. High performance liquid chromatography (HPLC) analysis and correlation analysis indicated that the better anticancer activity of LP may be not only related to the increased phenolic content, but also associated with the increased percentage contribution of quercetin to total phenolics. Taken together, alteration of phenolic composition by reduced nitrogen supply can be an effectively strategy for the development of healthy vegetables as anticancer products.

Inhibited autophagy impairs systemic nutrient metabolism in Nile tilapia.

Autophagy is a conserved cellular degradation process through which intracellular components are degraded by the lysosome, but its roles in fish metabolism have not been studied in depth. Therefore, the present study aimed to investigate whether autophagy plays a key role in maintaining metabolic homeostasis in fish. In an 8-week feeding trial, Nile tilapia were fed either a control diet with medium fat and medium carbohydrate (Control), or a control diet supplemented with a classic autophagy inhibitor (chloroquine, CQ). CQ supplementation significantly inhibited autophagy and impaired fish growth and protein synthesis, and the glycolysis was stimulated, accompanied by fat accumulation, high oxidative stress and inflammation. Physiological status and gene expressions suggested that impaired autophagy might be at least one cause of the metabolic diseases which has been commonly seen in aquaculture. These results indicate that inhibition of autophagy could significantly affect the metabolism of lipid, carbohydrate and protein in fish; hence, autophagy could play important roles in maintaining homeostasis of nutrient metabolism in cultured fish.

Luteolin alleviates alcoholic liver disease induced by chronic and binge ethanol feeding in mice.

Ethanol consumption can lead to hepatic steatosis that contributes to late-stage liver diseases such as cirrhosis and hepatocellular carcinoma. In this study, we investigated the potential protective effect of a flavonoid, luteolin, on ethanol-induced fatty liver development and liver injury. Six-wk-old male C57BL/6 mice were divided into 3 groups: a control group; a group exposed to alcohol by using a chronic and binge ethanol feeding protocol (EtOH); and a group that was administered daily 50 mg/kg of luteolin in addition to ethanol exposure (EtOH + Lut). A chronic and binge ethanol feeding protocol was used, including chronic ethanol consumption (1%, 2%, and 4% for 3 d, and 5% for 9 d) and a binge (30% ethanol) on the last day. Compared with the control group, the EtOH group had a significant elevation in serum concentrations of alanine aminotransferase (ALT) (561%), triglyceride (TG) (47%), and LDL cholesterol (95%), together with lipid accumulation in the liver. Compared with the EtOH group, the EtOH + Lut group had significant reductions in serum concentrations of ALT (43%), TG (22%), LDL cholesterol (52%), and lipid accumulation in the liver. Ethanol elevated liver expression of lipogenic genes including sterol regulatory element-binding protein 1c (Srebp1c) (560%), fatty acid synthase (Fasn) (190%), acetyl-CoA carboxylase (Acc) (48%), and stearoyl-CoA desaturase 1 (Scd1) (286%). Luteolin reduced ethanol-induced expression of these genes in the liver: Srebp1c (79%), Fasn (80%), Acc (60%), and Scd1 (89%). In cultured hepatocytes, luteolin prevented alcohol-induced lipid accumulation and increase in the expression of lipogenic genes. The transcriptional activity of the master regulator of lipid synthesis, sterol regulatory element-binding protein (SREBP), was enhanced by ethanol treatment (160%) and reduced by luteolin administration (67%). In addition, ethanol-induced reduction of AMP-activated protein kinase and SREBP-1c phosphorylation was abrogated by luteolin. Collectively, our study indicates that luteolin is effective in ameliorating ethanol-induced hepatic steatosis and injury.

[Spinal balancing intervention in the treatment of tinnitus: a randomized controlled study].

OBJECTIVE: To compare the differences in the clinical efficacy on tinnitus between the spinal balancing intervention and the conventional acupuncture. METHODS: The randomized controlled trial were adopted. One hundred and twenty cases of tinnitus were randomized into a spinal balancing group and a conventional acupuncture group, 60 cases in each one. In the spinal balancing group, the comprehensive therapy of acu-puncture and Tuina was applied to the spine, the Back-shu points, Jiaji (EX-B 2), Tinggong (SI 19), Yifeng (TE 17), Fengchi (GB 20), Yuzhen (BL 9), Tianzhu (BL 10), etc. for the balancing intervention. In the conventional acupuncture group, acupuncture was applied to the local points and the points along the affected meridians. In each group, after 3 sessions of treatment, the degree of tinnitus and the accompanied symptoms were scored and compared before and after treatment. The comprehensive efficacy was assessed. RESULTS: In the spinal balancing group, the clinical curative rate was 70.0% (42/60) and the total effective rate was 98.3% (59/60), which were significantly better than 45.0% (27/60) and 86.7% (52/60) in the conventional acupuncture group separately (P < 0.01, P < 0.05). After treatment, the degree of tinnitus and the accompanied symptom scores were all reduced in both groups (all P < 0.05), but the improvements in the spinal balancing group were better than those in the conventional acupuncture group (all P < 0.05). In 3-month follow-up visit after treatment, the recurrence rate in the spinal balancing group was lower than that in the conventional acupuncture group [5.1% (3/59) vs 13.5% (7/52)] (P < 0.05). CONCLUSION: The spinal balancing intervention therapy relieves the symptoms of the patients with tinnitus remarkably. Its clinical efficacy is superior significantly to that of the conventional acupuncture and the recurrence rate is lower.

[Treatment of herpes zoster with cotton sheet moxibustion: multicentral randomized controlled trial].

OBJECTIVE: To compare the therapeutic effects and safety of herpes zoster treated by the cotton sheet moxibustion combined with the plum-blossom-needle tapping therapy to western medicine. METHODS: The multicentral random controlled method was adopted, 120 cases of herpes zoster were randomly divided into a comprehensive treatment group and a western medication group, 60 cases in each one. In the comprehensive treatment group, the tapping therapy of plum blossom needle was applied to the foci, corresponding Jiaji (EX-B 2), Quchi (LI 11), Waiguan (TE 5), Zusanli (ST 36), Taichong (LR 3), etc. Afterward, the cotton sheet moxibustion was given. In western medication group, Acyclovir ointment for external application, Valaciclovir Hydrochloride tablets and Vitamin B1 for oral administration were prescribed. In 7 days of treatment, the clinical symptom score, effect time, efficacy and safety were observed before and after treatment between two groups. The recurrence of disease was followed up for 1 month. RESULTS: In the comprehensive treatment group, the cured rate and the total effective rate were 80.0% (48/60) and 98.3% (59/60) separately, which were significantly better than 45.0% (27/60) and 71.7% (43/60) in western medication group separately (P < 0.01, P < 0.05). After treatment, in either group, the scores of clinical symptoms such as pain rating index (PRI), Visual Analogue Scale (VAS), present pain intensity (PPI), skin lesion and sleeping score, etc. were all reduced significantly (P < 0.01, P < 0.05). The score reducing was much more obvious in the comprehensive treatment group (P < 0.01, P < 0.05). In the comprehensive treatment group, the time of pain stopping, the time of blister stopping, the time of scarring and the time of healing were all shorter tha tn those in western medication group (P < 0.01, P < 0.05). In the follow-up observation, 1 case (1.6%) was recurred in the comprehensive treatment group and 8 cases (13.3%) were in western medication group. In western medication group, 6 cases presented mild adverse reactions. CONCLUSION: The cotton sheet moxibustion combined with the plum-blossom-needle tapping therapy is advantageous at good efficacy, quick effect and short-time treatment for herpes zoster, which is apparently superior to the treatment with Acyclovir ointment for external application, Valaciclovir Hydrochloride tablets and Vitamin B1 for oral administration. It is the safe and effective therapy.