Comparative efficacy of nine exercise methods on the prognosis in chronic kidney disease patients with hemodialysis: a systematic review and network meta-analysis.

BACKGROUND: Several kinds of physical activities have been applied to improve the prognosis of patients with hemodialysis (HD). However, the comparative efficacy of physical activities on the outcomes in HD patients is still unknown. This study explored the effectiveness and safety of all exercise types in HD patients. METHODS: We searched randomized clinical trials from the PubMed, EMBASE, and Cochrane Library databases. Physical exercises interventions included resistance exercise (RE), aerobic exercise (AE), electrical muscle stimulation (EMS), range of motion (ROM), resistance exercise + aerobic exercise (RE + AE), stretching exercise (STE), respiratory muscle training (RMT), peripheral muscle training (PMT), walking exercise (WE), or usual care/sham exercise (UC/SE). Primary outcomes were six-minute walk test (6-mwt) and quality of life (QOL). Secondary outcomes were Kt/V, VO2max, hemoglobin (Hb), C-reactive protein (CRP), interleukin-6 (IL-6), and systolic and diastolic blood pressure (sbp and dbp). Frequentist network meta-analysis with multivariate random effects models provided mean with 95% confidence intervals (95%CI). RESULTS: A total of 58 eligible studies were included. AE, RMT, and RE + AE significantly improved 6-mwt compared with UC/SE. SE was the worst intervention and reduced QOL much more than the UC/SE and other exercise types. AE and RE + AE were associated with higher VO2max, while ROM and RE + AE induced higher Hb levels. All physical activities did not elevate blood pressure, CRP and IL-6. Only ROM decreased sbp/dbp. CRP is significantly lower in RE. CONCLUSION: Physical activities play a crucial role in the different outcomes of HD patients. They can be applied to specific area for their specific efficacy.

Efficacy and safety of trastuzumab deruxtecan in patients with solid tumors: a systematic review and meta-analysis of 3 randomized controlled trials.

Trastuzumab deruxtecan (T-DXd, DS-8201) is a targeted antibody-drug conjugate that specifically targets human epidermal growth factor receptor 2 (HER2). In 2019, it was approved by the US Food and Drug Administration for the treatment of HER2-positive breast cancer. However, ongoing research is exploring its potential efficacy in other solid tumors, such as non-small-cell lung cancer and colorectal cancer, as well as in tumors with low HER2 levels. It is important to examine the safety and effectiveness of trastuzumab deruxtecan in these various types of solid tumors, as some studies have raised concerns about potential serious adverse events associated with its use. In this meta-analysis, we conducted a comprehensive search of PubMed, EMBASE, Cochrane Library, and Web of Science to identify randomized controlled trials (RCTs) that evaluated the efficacy and safety of trastuzumab deruxtecan in solid tumors. We used RevMan 5.4 software to perform a meta-analysis, calculating odds ratios (OR), risk ratios (RR), and weighted mean differences (WMD) with 95% confidence intervals (CIs). After an exhaustive search, we identified three articles that met our inclusion criteria, which included a total of 1268 patients. The results of the meta-analysis showed that the treatment group had significantly higher overall survival (WMD=5.12, 95% CI (2.79, 7.44), P<0.0001), progression-free survival (WMD=3.45, 95% CI (0.8, 6.1), P=0.01), overall response rate (OR=6.49, 95% CI (4.90, 8.58), P<0.00001), and disease control rate (OR=4.68, 95% CI (2.78, 7.89), P<0.00001), TRAEs (RR=6.93, 95% CI (2.06, 23.25), P=0.002). However, there was no significant difference in TRAEs≥3 (RR=1.08, 95% CI (0.75, 1.56), P=0.68) between the trials. Based on the available evidence, trastuzumab deruxtecan appears to be an effective and safe treatment option for HER2-positive solid tumors. Although the number of studies included in this analysis is limited, ongoing trials are being conducted, further evaluating its potential in various solid tumors. The results of these trials will enhance our understanding of trastuzumab deruxtecan and potentially expand its applications, bringing hope to more patients with solid tumors.

Determination of D-serine and D-alanine Tissue Levels in the Prefrontal Cortex and Hippocampus of Rats After a Single Dose of Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, with Potential Antipsychotic and Antidepressant Properties.

The effects of the N-methyl-D-aspartate receptor activators D-serine, D-alanine, and sarcosine against schizophrenia and depression are promising. Nevertheless, high doses of D-serine and sarcosine are associated with undesirable nephrotoxicity or worsened prostatic cancer. Thus, alternatives are needed. DAAO inhibition can increase D-serine as well as D-alanine and protect against D-serine-induced nephrotoxicity. Although several DAAO inhibitors improve the symptoms of schizophrenia and depression, they can increase the plasma levels but not brain levels of D-serine. The mechanism of action of DAAO inhibitors remains unclear. We investigated the effects of the DAAO inhibitor sodium benzoate on the prefrontal cortex and hippocampal level of D-alanine as known another substrate with antipsychotic and antidepressant properties and other NMDAR-related amino acids, such as, L-alanine, D-serine, L-serine, D-glutamate, L-glutamate, and glycine levels. Our results indicate that sodium benzoate exerts antipsychotic and antidepressant-like effects without changing the D-serine levels in the brain prefrontal cortex (PFC) and hippocampus. Moreover, D-alanine levels in the PFC and hippocampus did not change. Despite these negative findings regarding the effects of D-amino acids in the PFC and hippocampus, sodium benzoate exhibited antipsychotic and antidepressant-like effects. Thus, the therapeutic effects of sodium benzoate are independent of D-serine or D-alanine levels. In conclusion, sodium benzoate may be effective among patients with schizophrenia or depression; however, the mechanisms of actions remain to be elucidated.

A Light-Driven Molecular Machine Controls K+ Channel Transport and Induces Cancer Cell Apoptosis.

The design of artificial ion channels with high activity, selectivity and gating function is challenging. Herein, we designed the light-driven motor molecule MC2, which provides new design criteria to overcome these challenges. MC2 forms a selective K+ channel through a single molecular transmembrane mechanism, and the light-driven rotary motion significantly accelerates ion transport, which endows the irradiated motor molecule with excellent cytotoxicity and cancer cell selectivity. Mechanistic studies reveal that the rotary motion of MC2 promotes K+ efflux, generates reactive oxygen species and eventually activates caspase-3-dependent apoptosis in cancer cells. Combined with the spatiotemporally controllable advantages of light, we believe this strategy can be exploited in the structural design and application of next-generation synthetic cation transporters for the treatment of cancer and other diseases.

Acetic acid transporter-mediated, oral, multifunctional polymer liposomes for oral delivery of docetaxel.

Nanoparticle-structuring aimed at the acetic acid (A) transporter on intestinal epithelial cells and tumor cells is a new potential strategy to enhance oral bioavailability and anti-tumor efficacy. In this study, chitosan (CS) was modified with hydrophilic A and hydrophobic lipoic acid (L), to produce ACSL. A novel ACSL-modified multifunctional liposomes (Lip) loaded with docetaxel (DTX; DTX-ACSL-Lip) was then prepared and characterized. DTX-ACSL-Lip recorded higher pH sensitivity and slower release than DTX-Lip and showed dithiothreitol (DTT) response release. DTX-ACSL-Lip uptake by Caco-2 cells was also significantly enhanced mainly viaA transporters compared with DTX-Lip. ACSL modification of DTX-Lip also improved oral bioavailability by 10.70-folds, with a 3.45-fold increase in Cmax and a 1.19-fold prolongation in retention time of DTX in the blood. Moreover, the grafting degree of A significantly affected cell uptake and oral bioavailability. They also showed a significant (1.33-fold) increase in drug intratumoral distribution, as well as an increase in tumor growth inhibition rate from 54.34% to 87.51% without weight loss, compared with DTX-Lip. Therefore, modification of DTX-Lip with ACSL can significantly enhance the oral bioavailability and anti-tumor efficacy of DTX without obvious toxicity, confirming the potential of the dual strategy of targeting A transporter and controlled drug release in tumor cells in oral therapy of tumor.

[Assessing fractional vegetation cover changes and ecological quality of the Wuyi Mountain National Nature Reserve based on remote sensing spatial information]. / 基于遥感空间信息的武夷山国家级自然保护区植被覆盖度变化与生态质量评估.

The Wuyi Mountain National Nature Reserve (WYS), established in 1979, is the largest and most intact subtropical forest ecosystem in southeastern China. No study has assessed the vegetation coverage change along with its ecological effect after the protection of the reserve for almost 40 years. In this study, the NDVI data of Landsat Image was corrected using the NDVI data of MODIS, the fractional vegetation cover (FVC) and the remote sensing based ecological index (RSEI) were calculated to assess the change of FVC and ecological quality in WYS with five Landsat images representing a period from 1979 to 2017. The results showed that after protection for nearly 40 years the FVC of the reserve had been significantly increased from 73.6% in 1979 to 89.5% in 2017, which consequently improved ecological quality from 0.801 in 1988 to 0.823 in 2017. In 2017, the area with the good and excellent ecological quality grades accounted for 98.7% of the total. Spatially, the ecologically-improved areas mainly distributed in the northeast core area and the center of the southwest core area. The ecologically-declined areas mostly occurred along roadsides and peaks. Vertically, the highest FVC and ecological quality areas distributed in the elevations between 1300-1900 m. In general, the improvement of FVC and ecological quality in the Wuyi Mountain National Nature Reserve was due largely to the effective policies and the successful protection by local government and people, except for some special year that may be affected mainly by climate conditions.

Light-responsive polymersomes with a charge-switch for targeted drug delivery.

Unlike the traditional block amphiphilic polymersomes, we herein report a lipid-like amphiphilic polymer that self-assembles into photo-responsive polymersomes for drug delivery. The introduction of a quaternary ammonium moiety not only provides a hydrophilic segment of the polymersomes, but also enables electrostatic adsorption with folic acid, thus achieving the targeting of cancer cells with overexpression of folate receptor. Upon light irradiation, the photocleavage reaction of the o-nitrobenzyl moiety disintegrates polymersomes by changing the polymer structure from cationic amphiphilic state to zwitterionic hydrophilic state, thus realizing photo-triggered drug release. The data showed that anticancer drugs (doxorubicin hydrochloride, DOX·HCl) can be loaded into the hydrophilic cavity of polymersomes and controllably released by photo-induced disintegration of polymersomes. Cellular assay showed that the active targeting of folic acid and photo-triggered release endowed the DOX-loaded polymersomes with a higher cytotoxicity to HeLa cells. Such cationic polymersomes provide a novel strategy for designing effective and intelligent drug carriers, and have potential application as a novel integrated platform for targeted drug delivery.

Association between Interleukin-6 Levels and Perioperative Fatigue in Gastric Adenocarcinoma Patients.

BACKGROUND: Gastric adenocarcinoma (GA), one of the most common gastrointestinal cancers worldwide, is often accompanied by cancer cachexia in the advanced stage owing to malnutrition and cancer-related symptoms. Although resection is the most effective curative procedure for GA patients, it may cause perioperative fatigue, worsening the extent of cancer cachexia. Although the relationship between cytokines and cancer fatigue has been evaluated, it is unclear which cytokines are associated with fatigue in GA patients. Therefore, this study aimed to investigate whether the changes in cytokine levels were associated with the perioperative changes in fatigue amongst GA patients. METHODS: We included GA patients undergoing gastric surgery in a single academic medical center between June 2017 and December 2018. Fatigue-related questionnaires, serum cytokine levels (interferon-gamma, interleukin (IL)-1, IL-2, IL-5, IL-6, IL-12 p70, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor), and biochemistry profiles (albumin, prealbumin, C-reactive protein, and white blood cell counts) were assessed at three time points (preoperative day 0 (POD 0), post-operative day 1 (POD 1), and postoperative day 7 (POD 7)). We used the Brief Fatigue Inventory-Taiwan Form to assess the extent of fatigue. The change in fatigue scores among the three time points, as an independent variable, was adjusted for clinicopathologic characteristics, malnutrition risk, and cancer stages. RESULTS: A total of 34 patients were included for analysis, including 12 female and 22 male patients. The mean age was 68.9 years. The mean score for fatigue on POD 0, POD 1, and POD 7 was 1.7, 6.2, and 3.6, respectively, with significant differences among the three time points (P < 0.001). Among the cytokines, only IL-6 was significantly elevated from POD 0 to POD 1. In the regression model, the change in IL-6 levels between POD 0 and POD 1 (coefficients = 0.01 for every 1 pg/mL increment; 95% confidence interval: 0.01-0.02; P = 0.037) and high malnutrition risk (coefficients = 2.80; 95% confidence interval: 1.45-3.52; P = 0.041) were significantly associated with changes in fatigue scores. CONCLUSIONS: The perioperative changes in plasma IL-6 levels are positively associated with changes in the fatigue scores of GA patients undergoing gastric surgery. Targeting the IL-6 signaling cascade or new fatigue-targeting medications may attenuate perioperative fatigue, and further clinical studies should be designed to validate this hypothesis.

Is frying oil a dietary source of an endocrine disruptor? Anti-estrogenic effects of polar compounds from frying oil in rats.

The objective was to investigate endocrine-disrupting effects of polar compounds from oxidized frying oil. Estrogenicity of polar compounds was tested with a rat uterotrophic bioassay. Dietary oxidized frying oil (containing 51% polar compounds) or polar compounds isolated from it were incorporated into feed (in lieu of fresh soybean oil) and fed to ovariectomized rats, with or without treatment with exogenous ethynyl estradiol. Exogenous estrogen restored uterine weight, and caused histological abnormalities (stratified epithelia and conglomerate glands) as well as proliferation of uterine epithelial cells. However, tamoxifen or polar compounds reduced these effects. Furthermore, tamoxifen or polar compounds down-regulated uterine mRNA expression of estrogen receptor (ER)-target genes, implicating reduced ER activity in this hypo-uterotrophic effect. Inhibition of ER signaling and mitosis by polar compounds were attributed to reduced MAPK and AKT activation, as well as a reduced ligand binding domain-transactivity of ERα/ß. We concluded polar compounds from frying oil are potential endocrine-disrupting chemicals, with implications for food and environmental safety.

Quinazolin-2,4-dione-Based Hydroxamic Acids as Selective Histone Deacetylase-6 Inhibitors for Treatment of Non-Small Cell Lung Cancer.

We designed and synthesized quinazolin-2,4-dione-based hydroxamic acids to serve as selective competitive inhibitors of histone deacetylase-6 (HDAC6). The most potent and selective compound, 3d (IC50, 4 nM, HDAC6; IC50 > 10 µM, HDAC1), substantially increased acetylation of α-tubulin instead of histones in the lung cancer cell line, LL2. Paclitaxel in combination with 3d had a synergistic anticancer effect on reduction of programmed death-ligand 1 expression in LL/2 cells. When given orally, 3d was mainly found to locate in the liver and lungs, at a concentration 18- to 70-fold greater, respectively, than in plasma. As an orally active HDAC6 inhibitor, 3d (20 mg/kg) potentiated paclitaxel antitumor activity (percentage tumor growth inhibition, 67.5%) in a xenograft syngeneic non-small cell lung cancer mouse model.

[Care Plan for Resuming the Physical Activity of Patients With Pancreatic Cancer and Diabetes After Surgery].

Many barriers influence the ability of postoperative cancer patients to reengage in normal physical activities. Training programs have been shown to be effective in helping restore physical activity in patients and in reducing the care burdens of family members. Nurses cannot use physical activity guidelines in their care plan to assess individual needs. The clinical practice guidelines for physical activity in survivorship were published by the National Comprehensive Cancer Network (NCCN) in 2016. These guidelines are used to assess patients' physical status, curable factors, physical barriers, and risk of postoperative pancreatic cancer and diabetes. In line with this assessment tool, the physical activity guidelines, and the recommendations for cancer patients, the authors planned a physical activity training program that addressed the actual needs of patients under their care. Further, the authors provided special notes for a diabetic diet that helped reduce the barriers to resuming physical activity and enhanced independent care efficacy. Meanwhile, the authors encouraged family members to participate in patient-care activities and family mental-health support and to promote patient participation in the training program in order to increase quality of life. The present project demonstrates that this care plan may provide an effective guide for nurses to help other cancer patients resume physical activity.

Genetic polymorphisms of FADS1, FADS2, and FADS3 and fatty acid profiles in subjects received methadone maintenance therapy.

Abnormal fatty acid metabolism and the related enzymes had been observed to be associated with psychiatric disorders. We investigated FADS gene family genetic polymorphisms and variations of lipid profiles in patients with heroin dependence receiving 6-month methadone maintenance therapy (MMT). We recruited 89 MMT drug abusers and analyzed 3 tag single nucleotide polymorphisms (SNPs) from Fatty acid desaturases (FADS), FADS1, FADS2 and FADS3. The fatty acid profiles of erythrocyte membranes were analyzed based on genetic variations. Six-month MMT therapy were significantly associated with decreased C20: 5n3 and C22:4n6 levels in the whole group of drug abusers. The decreases of C22: 6n3 after MMT therapy were associated with specific genetic variations, including FADS1 C/C, FADS2 T/T and FADS3 C/C genotypes. The variations on n3 and n6 PUFA composition were significantly shown in different alleles of FADS in MMT drug abusers. Further studies are needed to elucidate the role of fatty acid metabolism on rehabilitation by MMT.

Polyunsaturated fatty acids and inflammatory markers in major depressive episodes during pregnancy.

INTRODUCTION: Prenatal depression (PND) is a common psychiatric disorder in pregnant women and leads to psychosocial dysfunction, high suicidal rate, and adverse childcare. Patients with PND have omega-3 polyunsaturated fatty acid (omega-3 or n-3 PUFAs) deficits, which might link to chronic low-grade inflammatory process and the pathophysiological mechanisms of depression. In this case-control study, we examined the levels of PUFAs and inflammatory cytokines in PND. METHOD: Blood samples were obtained and analyzed from 16 healthy controls and 17 depressed cases (PND group) diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Independent sample t-test and correlation analysis were performed with Statistical Package for the Social Sciences (SPSS) logistics correlation analysis. RESULTS: PND group had significantly lower levels of total n-3 (p=0.026), docosahexaenoic acid (DHA) (p=0.020) and eicosapentaenoic (EPA) (p=0.019) but a higher omega-6 (n-6)/n-3 PUFAs ratio (p=0.007) and tumor necrosis factor alpha (TNF-α) (p=0.016) level. Moreover, the duration of current PND episodes were also significantly correlated with DHA, EPA, n-3 PUFAs, n-6/n-3 ratio and TNF-α. In terms of PUFAs and cytokine levels, only DHA was inversely correlated with TNF-α. CONCLUSION: PND is significantly associated with lower DHA, EPA, and total n-3 PUFAs levels and an increased n-6/n-3 PUFAs ratio, while the duration of PND is associated with lower levels of n-3 PUFAs, including DHA and EPA. The correlation of PUFAs levels with depression and TNF-α level grant further investigation into the inflammatory process underlying PND, mediated by PUFAs.

Houttuynia cordata aqueous extract attenuated glycative and oxidative stress in heart and kidney of diabetic mice.

PURPOSE: The anti-glycative and anti-oxidative effects from Houttuynia cordata leaves aqueous extract (HCAE) in heart and kidney of diabetic mice were examined. METHODS: HCAE, at 1 or 2 %, was supplied in drinking water for 8 weeks. Plasma glucose and blood urea nitrogen (BUN) levels and creatine phosphokinase (CPK) activity were measured. The production of oxidative and inflammatory factors was determined. Activity and protein expression of associated enzymes or regulators were analyzed. RESULTS: HCAE intake at both doses lowered plasma glucose and BUN levels, and CPK activity and also restored creatinine clearance rate in diabetic mice. HCAE intake, only at 2 %, retained plasma insulin levels (P < 0.05). HCAE reduced reactive oxygen species, protein carbonyl, interleukin-6, tumor necrosis factor-alpha, N (ε) -(carboxymethyl)-lysine, pentosidine and fructose levels, and reserved glutathione content in heart and kidney of diabetic mice (P < 0.05). Diabetes enhanced aldose reductase (AR) activity and protein expression in heart and kidney (P < 0.05). HCAE intake at both doses decreased renal AR activity and protein expression, but only at 2 % lowered cardiac AR activity and protein expression (P < 0.05). Diabetes increased protein expression of RAGE, p47(phox) and gp91(phox), nuclear factor kappa-B (NF-κB) p50, NF-κB p65 and mitogen-activated protein kinase in heart and kidney (P < 0.05). HCAE intake only at 2 % limited RAGE expression, but at 1 and 2 % downregulated p47(phox), NF-κB p65 and p-p38 expression in these organs (P < 0.05). CONCLUSIONS: These findings suggest that Houttuynia cordata leaves aqueous extract could ameliorate cardiac and renal injury under diabetic condition.

Asiatic acid and maslinic acid protected heart via anti-glycative and anti-coagulatory activities in diabetic mice.

The cardiac protective effects of asiatic acid (AA) and maslinic acid (MA) in diabetic mice were examined. These triterpenoids at 0.1 or 0.2% of the diet were supplied to diabetic mice for 12 weeks. The AA or MA treatments decreased plasma glucose and HbA1c levels, and creatine phosphokinase and lactate dehydrogenase activities in diabetic mice (p < 0.05). AA or MA intake increased the amount deposited in the heart which retained the cardiac glutathione content and reduced the production of reactive oxygen species, N(ε)-(carboxymethyl)-lysine, pentosidine, methylglyoxal, interleukin-6, tumor necrosis factor-alpha and monocyte chemoattractant protein-1 in the hearts of diabetic mice (p < 0.05). AA or MA intake lowered plasma von Willebrand factor and fibrinogen levels, and factor VII activity (p < 0.05), also AA or MA intake maintained circulating antithrombin-III and protein C activities (p < 0.05). AA or MA treatments down-regulated cardiac expression of NADPH oxidase, aldose reductase, nuclear factor kappa B (NF-κB) p65 and p-p38; as well as reserving glyoxalase 1 expression (p < 0.05). These two compounds at only 0.2% lowered cardiac expression of NF-κB p50, p-ERK1/2 and the receptor of the advanced glycation endproduct (p < 0.05). These findings support the conclusion that the supplement of these triterpenoids could protect the heart under diabetic conditions via attenuating glycative injury and coagulatory disorders.

Auricularia polytricha aqueous extract supplementation decreases hepatic lipid accumulation and improves antioxidative status in animal model of nonalcoholic fatty liver.

Background: Amelioration effect of Auricularia polytricha water extract (AP) on hepatic injury in an animal model of NAFLD was investigated. Methods: Forty six-week-old Wistar rats were housed and thirty-two fed ten percent lard high-fat diet to induce NAFLD. After eight weeks of induction, animals were divided into five groups of eight rats each: normal control, high-fat diet, RN (reversion to a normal diet), 1× AP (normal diet plus 0.75% AP, w/w), and 2×AP (normal diet plus 1.5% AP). Animals were sacrificed four weeks later. Results: Rats receiving either 0.75% or 1.5% AP exhibited effective interruption of NAFLD progression, as evidenced by decreased lipid accumulation and elevated antioxidative status. Histological examination proved AP anti-inflammatory function and lower level of related markers for tumor necrosis factor-α and interleukin-6. Besides abundant polysaccharides against lipid accumulation, AP had a specific high level of phenolic compounds and tannins thus may be a potent anti-inflammatory and antioxidative agent. Conclusion: Findings suggest that under normal diet recovery, AP supplement may represent novel, protective material against NAFLD by attenuating inflammatory response, oxidative stress and lipid deposition.

Protective effects of maslinic acid against alcohol-induced acute liver injury in mice.

Protective effects of maslinic acid (MA) at 10, 15 or 20 mg/kg body weight/day against alcohol-induced acute hepatotoxicity in mice were examined. Mice were administrated by MA for 3 weeks, and followed by alcohol treatment. Results showed that MA pre-intake at three doses resulted in its accumulation in the liver; and dose-dependently lowered cytochrome P450 2E1 activity and protein expression at 23.5-51.2% and 21.4-62.3%, respectively (P <0.05). MA pre-intake decreased subsequent alcohol-induced reactive oxygen species, interleukin-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, nitric oxide and prostaglandin E2 production; retained glutathione content; maintained catalase and glutathione peroxidase activities; and declined cyclooxygenase-2 and total nitric oxide synthase activities in the liver (P <0.05). Furthermore, MA pre-intake suppressed 17.3-51.7% nuclear factor kappa (NF-κ)B p50, 23.5-58.8% NF-κB p65, 25.6-62.4% p-p38 and 24.1-63.0% p-JNK expression in the liver (P <0.05). Histological data indicated that MA intake at test doses attenuated hepatic inflammatory infiltrate. These findings support that maslinic acid is a potent preventive agent against acute alcoholic liver disease.

Asiatic acid ameliorates hepatic lipid accumulation and insulin resistance in mice consuming a high-fat diet.

Effects of asiatic acid (AA) at 10 or 20 mg/kg/day upon hepatic steatosis in mice consuming a high-fat diet (HFD) were examined. AA intake decreased body weight, water intake, feed intake, epididymal fat, and plasma and hepatic triglyceride levels in HFD-treated mice (P < 0.05). HFD enhanced 2.85-fold acetyl coenzyme A carboxylase (ACC1), 3.34-fold fatty acid synthase (FAS), 3.71-fold stearoyl CoA desaturase (SCD)-1, 3.62-fold 3-hydroxy-3-methylglutaryl coenzyme A reductase, 2.91-fold sterol regulatory element-binding protein (SREBP)-1c, and 2.75-fold SREBP-2 expression in liver (P < 0.05). Compared with HFD groups, AA intake at two doses reduced 18.9-45.7% ACC1, 25.1-49.8% FAS, 24.7-57.1% SCD-1, and 21.8-53.3% SREBP-1c protein expression (P < 0.05). Histological results indicated AA intake at two doses reduced hepatic lipid accumulation and inflammatory infiltrate. HFD increased hepatic production of reactive oxygen species, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α, as well as decreased hepatic glutathione content and glutathione peroxidase and catalase activities (P < 0.05). AA intake at two doses reversed these alterations (P < 0.05). AA intake suppressed 32.4-58.8% nuclear factor kappa (NF-κ)B p65 and 24.2-56.7% p-p38 expression (P < 0.05) and at high dose down-regulated 29.1% NF-κB p50 and 40.7% p-JNK expression in livers from HFD-treated mice. AA intake at two doses lowered plasma insulin secretion and HOMR-IR (P < 0.05). These results suggest that AA is a potent hepatic protective agent against HFD-induced hepatic injury.

Effect of commercially available green and black tea beverages on drug-metabolizing enzymes and oxidative stress in Wistar rats.

The effect of commercially available green tea (GT) and black tea (BT) drinks on drug metabolizing enzymes (DME) and oxidative stress in rats was investigated. Male Wistar rats were fed a laboratory chow diet and GT or BT drink for 5 weeks. Control rats received de-ionized water instead of the tea drinks. Rats received the GT and BT drinks treatment for 5 weeks showed a significant increase in hepatic microsomal cytochrome P450 (CYP) 1A1 and CYP1A2, and a significant decrease in CYP2C, CYP2E1 and CYP3A enzyme activities. Results of immunoblot analyses of enzyme protein contents showed the same trend with enzyme activity. Significant increase in UDP-glucuronosyltransferase activity and reduced glutathione content in liver and lungs were observed in rats treated with both tea drinks. A lower lipid peroxide level in lungs was observed in rats treated with GT drink. Electrophoretic mobility shift assay revealed that both tea drinks decreased pregnane X receptor binding to DNA and increased nuclear factor-erythroid 2 p45-related factor 2 binding to DNA. These results suggest that feeding of both tea drinks to rats modulated DME activities and reduced oxidative stress in liver and lungs. GT drink is more effective on reducing oxidative stress than BT drink.

Dietary fish oil reduces systemic inflammation and ameliorates sepsis-induced liver injury by up-regulating the peroxisome proliferator-activated receptor gamma-mediated pathway in septic mice.

This study investigated the effect of dietary fish oil on systemic inflammation and hepatic injury in mice with polymicrobial sepsis. Male ICR mice were assigned to a control group (C, n=30) and a fish oil group (FO, n=30). Mice in the C group were fed a semi-purified diet with 10% soybean oil, and those in the FO group were fed a fish oil diet (2.5% fish oil+7.5% soybean oil; w/w). Three weeks later, sepsis was induced by cecal ligation and puncture (CLP), and mice were sacrificed at 0, 6 and 24 h after CLP, respectively. Results showed that compared with C group, the FO group had lower plasma levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and nitrite at 6 and 24 h after CLP. Also, peritoneal lavage fluid concentrations of TNF-α and prostaglandin (PG) E2 were significantly lower at 24 h in the FO than in the C group. The FO group had lower myeloperoxidase activities at 6 h after CLP in various organs. Plasma aminotransferase and alanine aminotransferase activities revealed significantly decreased in the FO group. The DNA-binding activity of peroxisome proliferators-activated receptor gamma (PPARγ) and mRNA expression of I kappaB alpha (IκBα) were up-regulated while nuclear factor (NF)-κB p65 DNA-binding activity, inducible nitric oxide synthase protein expression and the concentration of nitrotyrosine were significantly decreased in the FO group in liver after CLP. These results indicate that dietary fish oil administration may attenuate systemic inflammation and up-regulate hepatic PPARγ DNA-binding activity, which may consequently have ameliorated liver injury in these septic mice.